U.S. patent application number 17/491687 was filed with the patent office on 2022-01-27 for peroxide-less biophotonic compositions and methods.
This patent application is currently assigned to KLOX TECHNOLOGIES LIMITED. The applicant listed for this patent is KLOX TECHNOLOGIES LIMITED. Invention is credited to Francesco BELLINI, William CURTIS, Nikolaos LOUPIS, David OHAYON, Remigio PIERGALLINI.
Application Number | 20220023181 17/491687 |
Document ID | / |
Family ID | |
Filed Date | 2022-01-27 |
United States Patent
Application |
20220023181 |
Kind Code |
A1 |
BELLINI; Francesco ; et
al. |
January 27, 2022 |
PEROXIDE-LESS BIOPHOTONIC COMPOSITIONS AND METHODS
Abstract
The present disclosure provides biophotonic topical
compositions, kits and their uses. In some aspects, the biophotonic
topical compositions of the present disclosure comprise a first
chromophore, a salt selected from one or more bicarbonate or
carbonate salts or a combination of the foregoing salts, and one or
more gelling agents. In some aspects, the biophotonic topical
compositions of the present disclosure comprise a first
chromophore, one or more polyols, and one or more gelling agents.
The biophotonic compositions of the present disclosure do not
include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate. The biophotonic compositions
are useful for promoting wound healing and skin rejuvenation, as
well as treating acne and various skin disorders.
Inventors: |
BELLINI; Francesco;
(Calgary, CA) ; OHAYON; David;
(Dollard-des-Ormeaux, CA) ; PIERGALLINI; Remigio;
(Grottammare, IT) ; LOUPIS; Nikolaos; (Athens,
GR) ; CURTIS; William; (Montreal, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
KLOX TECHNOLOGIES LIMITED |
Dublin |
|
IE |
|
|
Assignee: |
KLOX TECHNOLOGIES LIMITED
|
Appl. No.: |
17/491687 |
Filed: |
October 1, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16066487 |
Jun 27, 2018 |
11135146 |
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PCT/CA2016/051544 |
Dec 28, 2016 |
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17491687 |
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62271593 |
Dec 28, 2015 |
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International
Class: |
A61K 8/49 20060101
A61K008/49; A61Q 19/08 20060101 A61Q019/08; A61K 47/10 20060101
A61K047/10; A61K 33/00 20060101 A61K033/00; A61K 9/00 20060101
A61K009/00; A61K 41/00 20060101 A61K041/00; A61K 47/02 20060101
A61K047/02; A61K 9/06 20060101 A61K009/06; A61K 47/32 20060101
A61K047/32; A61K 8/34 20060101 A61K008/34; A61K 8/81 20060101
A61K008/81; A61K 8/19 20060101 A61K008/19; C09K 11/06 20060101
C09K011/06; A61Q 19/00 20060101 A61Q019/00; A61K 8/14 20060101
A61K008/14; A61N 5/06 20060101 A61N005/06; A61K 31/728 20060101
A61K031/728; A61K 31/4166 20060101 A61K031/4166; A61K 31/7008
20060101 A61K031/7008; A61P 17/10 20060101 A61P017/10; A61P 1/02
20060101 A61P001/02; A61P 17/02 20060101 A61P017/02; A61P 29/00
20060101 A61P029/00; A61K 31/35 20060101 A61K031/35 |
Claims
1. A biophotonic composition comprising: a first chromophore; one
or more gelling agents; and one or more salts selected from one or
more bicarbonate salts, one or more carbonate salts, or a
combination of the foregoing salts; wherein said composition does
not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate.
2. The biophotonic composition of claiml, wherein the salt is one
or more bicarbonate salts.
3. The biophotonic composition of claim 2, wherein the one or more
bicarbonate salts are selected from ammonium bicarbonate, caesium
bicarbonate, potassium bicarbonate, sodium bicarbonate, choline
bicarbonate, aminoguanidine bicarbonate, or tetraethylammonium
bicarbonate.
4. The biophotonic composition of claim 3, wherein the bicarbonate
salt is sodium bicarbonate.
5. The biophotonic composition of claim 3, wherein the bicarbonate
salt is potassium bicarbonate.
6. The biophotonic composition of claim 1, wherein the salt is one
or more carbonate salts.
7. The biophotonic composition of claim 6, wherein the one or more
carbonate salts are selected from barium carbonate, beryllium
carbonate, caesium carbonate, calcium carbonate, cobalt (II)
carbonate, copper (II) carbonate, lithium carbonate, magnesium
carbonate, nickel (II) carbonate, potassium carbonate, sodium
carbonate, or zinc carbonate.
8. The biophotonic composition of claim 7, wherein the carbonate
salt is calcium carbonate.
9. The biophotonic composition of claim 7, wherein the carbonate
salt is sodium carbonate.
10. The biophotonic composition of claim 7, wherein the carbonate
salt is potassium carbonate.
11. The biophotonic composition of any one of claims 1 to 10,
further comprising at least one polyol.
12. The biophotonic composition of claim 11, wherein the polyol is
glycerine.
13. The biophotonic composition of claim 11, wherein the polyol is
at least one glycol.
14. The biophotonic composition of claim 13, wherein the glycol is
selected from ethylene glycol and propylene glycol.
15. The biophotonic composition of claim 14, wherein the glycol is
propylene glycol.
16. A biophotonic composition comprising: a first chromophore; one
or more gelling agents; and one or more polyols; wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate.
17. The biophotonic composition of claim 16, wherein the polyol is
glycerine.
18. The biophotonic composition of claim 16, wherein the polyol is
at least one glycol.
19. The biophotonic composition of claim 18, wherein the glycol is
selected from the group consisting of ethylene glycol and propylene
glycol.
20. The biophotonic composition of claim 19, wherein the glycol is
propylene glycol.
21. The biophotonic composition of any one of claims 1 to 20,
wherein the first chromophore is present in an amount of from about
0.001% to about 40% by weight of the total composition.
22. The biophotonic composition of claim 21, wherein the first
chromophore is present in an amount of from about 0.005% to about
2% by weight of the total composition.
23. The biophotonic composition of any one of claims 1 to 20,
wherein the first chromophore is present in an amount of at least
about 0.2% by weight of the total composition.
24. The biophotonic composition of any one of claims 1-23, wherein
the gelling agent is a carbomer comprising a polymer of acrylic
acid.
25. The biophotonic composition of claim 24, wherein the carbomer
is crosslinked.
26. The biophotonic composition of any one of claims 1 to 25,
wherein the first chromophore is in solution in a medium of the
composition.
27. The biophotonic composition of claim 26, wherein the medium is
an aqueous substance or an alcohol.
28. The biophotonic composition of claim 27, wherein the medium is
an aqueous substance.
29. The biophotonic composition of any one of claims 1-28, wherein
the first chromophore is a fluorescent chromophore.
30. The biophotonic composition of any one of claims 1-28, wherein
the first chromophore is a xanthene dye.
31. The biophotonic composition of claim 30, wherein the first
chromophore is selected from the group consisting of Eosin Y, Eosin
B, Erythrosin B, Fluorescein, Rose Bengal, and Phloxin B.
32. The biophotonic composition of claim 31, wherein the first
chromophore is Eosin Y.
33. The biophotonic composition of any one of claims 1 to 32,
wherein the composition further comprises a second chromophore.
34. The biophotonic composition of claim 33, wherein the first
chromophore has an emission spectrum that overlaps at least 20%
with an absorption spectrum of the second chromophore.
35. The biophotonic composition of claim 33 or 34, wherein the
first chromophore transfers energy to the second chromophore upon
illumination with a light.
36. The biophotonic composition of any one of claims 33 to 35,
wherein the first chromophore is Eosin Y, and the second
chromophore is one or more selected from Fluorescein, Phloxine B
and Erythrosine B.
37. The biophotonic composition of any one of claims 33 to 36,
wherein the first chromophore is Fluorescein, and the second
chromophore is Eosin Y.
38. The biophotonic composition of any one of claims 33 to 37,
wherein the second chromophore is present in an amount of from
about 0.0001% to about 40% by weight of the total composition.
39. The biophotonic composition of claim 38, wherein the second
chromophore is present in an amount of from about 0.0001% to about
2% by weight of the total composition.
40. The biophotonic composition of any one of claims 33 to 39,
further comprising a third chromophore, wherein the third
chromophore is a chlorophyll or saffron.
41. The biophotonic composition of any one of claims 1 to 40,
wherein the pH of the composition is within the range of from about
4.0 to about 7.0, from about 4.0 to about 6.5, or from about 4.0 to
about 5.0.
42. The biophotonic composition of any one of claims 1 to 40,
wherein the pH of the composition is within the range of from about
6.0 to about 8.0 or about 6.5 to about 7.5.
43. The biophotonic composition of any one of claims 1 to 42,
wherein the composition further comprises one or more healing
factors selected from the group consisting of glucosamine,
hyaluronic acid, and allantoin.
44. A method for promoting skin rejuvenation, comprising: applying
topically to a skin a biophotonic composition according to any one
of claims 1 to 43; and illuminating said biophotonic composition
with light having a wavelength that overlaps with an absorption
spectrum of the first chromophore.
45. A method of promoting wound healing, comprising: applying
topically to a wound a biophotonic composition according to any one
of claims 1 to 43; and illuminating said biophotonic composition
with light having a wavelength that overlaps with an absorption
spectrum of the first chromophore.
46. A method for biophotonic treatment of a skin disorder,
comprising: applying topically to a target skin tissue afflicted
with the skin disorder a biophotonic composition, according to any
one of claims 1 to 43; and illuminating said biophotonic
composition with light having a wavelength that overlaps with an
absorption spectrum of the first chromophore.
47. A method for biophotonic treatment of acne, comprising:
applying topically to a target tissue a biophotonic composition,
according to any one of claims 1 to 43; and illuminating said
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the first chromophore.
48. A method for biophotonic treatment of acne scar, comprising:
applying topically to a target tissue a biophotonic composition,
according to any one of claims 1 to 43; and illuminating said
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the first chromophore.
49. A method of biophotonic treatment of an oral disease,
comprising: applying topically to a target site a biophotonic
composition, according to any one of claims 1 to 43; and
illuminating said biophotonic composition with light having a
wavelength that overlaps with an absorption spectrum of the first
chromophore.
50. A method of biophotonic treatment of acute or chronic
inflammation, comprising: applying topically to a target site a
biophotonic composition, according to any one of claims 1 to 43;
and illuminating said biophotonic composition with light having a
wavelength that overlaps with an absorption spectrum of the first
chromophore.
51. The method of any one of claims 44 to 50, further comprising
removing the biophotonic composition after illumination.
52. The method of any one of claims 44 to 51, wherein the
biophotonic composition is illuminated for about 1 minute to about
30 minutes.
53. The method of any one of claims 44 to 51, wherein the
biophotonic composition is illuminated for less than about 20
minutes, about 15 minutes, about 10 minutes or about 5 minutes.
54. The method of any one of claims 44 to 53, wherein the
biophotonic composition is illuminated with actinic light.
55. The method of any one of claims 44 to 54, wherein the
biophotonic composition is illuminated with violet and/or blue
light.
56. A composition according to any one of claims 1 to 43 for use in
the treatment of wounds.
57. A composition according to any one of claims 1 to 43 for use in
the treatment or prevention of skin disorders.
58. A composition according to any one of claims 1 to 43 for use in
the treatment of acne.
59. A composition according to any one of claims 1 to 43 for use in
the treatment of acne scars.
60. A composition according to any one of claims 1 to 43 for use in
the treatment or prevention of an oral disease.
61. A composition according to any one of claims 1 to 43 for use in
the treatment of acute or chronic inflammation.
62. A kit comprising: a composition according to any one of claims
1 to 43 and one or more of a light source for activating the first
chromophore, instructions for use of the composition and/or the
light source, a dressing, and a device for applying and/or removing
the composition from a treatment area.
63. Use of a composition according to any one of claims 1 to 43 in
the manufacture of a medicament for the treatment of wounds.
64. Use of a composition according to any one of claims 1 to 43 in
the manufacture of a medicament for the treatment or prevention of
skin disorders.
65. Use of a composition according to any one of claims 1 to 43 in
the manufacture of a medicament for the treatment of acne.
66. Use of a composition according to any one of claims 1 to 43 in
the manufacture of a medicament for the treatment of acne
scars.
67. Use of a composition according to any one of claims 1 to 43 in
the manufacture of a medicament for the treatment or prevention of
an oral disease.
68. Use of a composition according to any one of claims 1 to 43 in
the manufacture of a medicament for the treatment of acute or
chronic inflammation.
Description
RELATED APPLICATIONS
[0001] This application claims priority to and benefit from U.S.
Provisional Patent Application No. 62/271,593, filed Dec. 28, 2015,
the disclosure of which is incorporated herein by reference in its
entirety.
BACKGROUND OF THE DISCLOSURE
[0002] Phototherapy has recently been recognized as having a wide
range of applications in both the medical, cosmetic and dental
fields for use in surgeries, therapies and examinations. For
example, phototherapy has been developed to treat cancers and
tumors with lessened invasiveness. Phototherapy has also been used
to disinfect target sites as an antimicrobial treatment.
Phototherapy has also been found to promote wound healing.
[0003] Photodynamic therapy is a type of phototherapy which
involves a step of systemic administration or uptake of a
photosensitive agent into the diseased or injured tissue, which
step is followed by site-specific application of activating light
(photodynamic therapy). Such regimens, however, are often
associated with undesired side-effects, including irritation due to
the presence of peroxides in the compositions used in therapy.
Therefore, it is an object of the present disclosure to provide new
and improved compositions and methods useful in phototherapy.
SUMMARY OF THE DISCLOSURE
[0004] The present disclosure provides biophotonic compositions and
methods useful in phototherapy. In some aspects, the biophotonic
compositions of the present disclosure comprise one or more
chromophores; one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts; and one or
more gelling agents, but do not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate. In some aspects, the biophotonic compositions of the
present disclosure comprise one or more chromophores; one or more
salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts; one or more polyols; and one or
more gelling agents, but do not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate. In some aspects, the biophotonic compositions of the
present disclosure comprise a first chromophore, one or more
polyols, and one or more gelling agents, but do not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate. Such biophotonic compositions are useful
for decreasing undesired side effects associated with oxidants,
e.g., peroxides, in phototherapy.
[0005] In some aspects, there is provided a biophotonic composition
comprising a first chromophore; one or more gelling agents; and one
or more salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts, wherein said composition does
not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate.
[0006] In some embodiments, there is provided a biophotonic
composition comprising a first chromophore; one or more gelling
agents; and one or more bicarbonate salts, wherein said composition
does not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate. In some embodiments, the one
or more bicarbonate salts are selected from ammonium bicarbonate,
caesium bicarbonate, potassium bicarbonate, sodium bicarbonate,
choline bicarbonate, aminoguanidine bicarbonate, or
tetraethylammonium bicarbonate. In some embodiments, the
bicarbonate salt is sodium bicarbonate. In some embodiments, the
bicarbonate salt is potassium bicarbonate.
[0007] In some embodiments, there is provided a biophotonic
composition comprising a first chromophore; one or more gelling
agents; and sodium bicarbonate, wherein said composition does not
include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate.
[0008] In some embodiments, there is provided a biophotonic
composition comprising a first chromophore; one or more gelling
agents; and one or more carbonate salts, wherein said composition
does not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate. In some embodiments, the one
or more carbonate salts are selected from barium carbonate,
beryllium carbonate, caesium carbonate, calcium carbonate, cobalt
(II) carbonate, copper (II) carbonate, lithium carbonate, magnesium
carbonate, nickel (II) carbonate, potassium carbonate, sodium
carbonate, or zinc carbonate. In some embodiments, the carbonate
salt is calcium carbonate. In some embodiments, the carbonate salt
is sodium carbonate. In some embodiments, the carbonate salt is
potassium carbonate.
[0009] In some embodiments, there is provided a biophotonic
composition comprising a first chromophore, one or more gelling
agents, and calcium carbonate, wherein said composition does not
include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate.
[0010] In certain embodiments of any of the foregoing or following,
the composition further comprises at least one polyol. In some
embodiments, the polyol is glycerine. In some embodiments, the
polyol is at least one glycol, such as ethylene glycol and
propylene glycol. In some embodiments, the glycol is propylene
glycol. In some embodiments, there is provided a biophotonic
composition comprising a first chromophore; one or more gelling
agents; glycerine; and one or more salts selected from bicarbonate
salts, carbonate salts or a combination of the foregoing salts,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate. In some embodiments, there is provided a biophotonic
composition comprising a first chromophore; one or more gelling
agents; glycerine; and sodium bicarbonate, wherein said composition
does not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate.
[0011] In certain embodiments, the first chromophore is present in
an amount of from about 0.001% to about 40% by weight of the total
composition, such as from about 0.005% to about 30% by weight of
the total composition, from about 0.005% to about 20% by weight of
the total composition, from about 0.005% to about 10% by weight of
the total composition, from about 0.005% to about 8% by weight of
the total composition, from about 0.005% to about 6% by weight of
the total composition, from about 0.005% to about 4% by weight of
the total composition, about 0.005% to about 2% by weight of the
total composition; such as about 0.2 by weight of the total
composition, about 0.4% by weight of the total composition, about
0.6% by weight of the total composition, about 0.8% by weight of
the total composition, about 1% by weight of the total composition,
about 1.2% by weight of the total composition, about 1.4% by weight
of the total composition, about 1.6% by weight of the total
composition, or about 1.8% by weight of the total composition.
[0012] In some aspects, there is provided a biophotonic composition
comprising a first chromophore, one or more gelling agents, and one
or more polyols, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate. In some embodiments, the polyol is
glycerine. In some embodiments, the polyol is at least one glycol.
In some embodiments, the glycol is selected from ethylene glycol
and propylene glycol. In some embodiments, the glycol is propylene
glycol.
[0013] In some embodiments, there is provided a biophotonic
composition comprising a first chromophore, one or more gelling
agents, and glycerine, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate.
[0014] In certain embodiments, wherein the biophotonic composition
comprises one or more gelling agents, the gelling agent is a
carbomer comprising a polymer of acrylic acid. In some embodiments,
the carbomer is crosslinked.
[0015] In certain embodiments, the first chromophore is in solution
in a medium of the biophotonic composition. In certain such
embodiments, the medium is an aqueous substance or an alcohol, such
as an aqueous substance.
[0016] In certain embodiments, the first chromophore of the
biophotonic composition is a fluorescent chromophore. In certain
embodiments, the first chromophore of the biophotonic composition
is a xanthene dye. In some embodiments, the first chromophore is
selected from Eosin Y, Eosin B, Erythrosin B, Fluorescein, Rose
Bengal and Phloxin B. In some embodiments, the first chromophore is
Eosin Y.
[0017] In some embodiments, the biophotonic composition further
comprises a second chromophore. In certain such embodiments, the
first chromophore has an emission spectrum that overlaps at least
20% with an absorption spectrum of the second chromophore. In some
embodiments, the first chromophore transfers energy to the second
chromophore upon illumination with a light. In some embodiments,
the first chromophore is Eosin Y, and the second chromophore is one
or more of Fluorescein, Phloxine B and Erythrosine B. In some
embodiments, the first chromophore is Fluorescein, and the second
chromophore is Eosin Y. In some embodiments, the second chromophore
is present in an amount of from about 0.0001% to about 40% by
weight of the total composition, such as about from about 0.0001%
to about 2% by weight of the total composition.
[0018] In some embodiments, the biophotonic composition further
comprises a third chromophore. In certain such embodiments, the
third chromophore is a chlorophyll or saffron.
[0019] In some embodiments, the pH of the biophotonic composition
is within the range of from about 4.0 to about 7.0, from about 4.0
to about 6.5, or from about 4.0 to about 5.0. In some embodiments,
the pH of the biophotonic composition is within the range of from
about 6.0 to about 8.0 or from about 6.5 to about 7.5.
[0020] In some embodiments, the biophotonic composition further
comprises one or more healing factors selected from the group
consisting of glucosamine, hyaluronic acid, and allantoin.
[0021] In some aspects, the disclosure of this application provides
a method for promoting skin rejuvenation, comprising applying
topically to a skin a biophotonic composition comprising a first
chromophore; one or more gelling agents; and one or more salts
selected from bicarbonate salts, carbonate salts or a combination
of the foregoing salts, wherein said composition does not include
an oxidant selected from the group consisting of a peroxide, a
peroxy acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate; and illuminating said biophotonic
composition with light having a wavelength that overlaps with an
absorption spectrum of the first chromophore.
[0022] In some aspects, the disclosure of this application provides
a method for promoting skin rejuvenation, comprising applying
topically to a skin a biophotonic composition comprising a first
chromophore, one or more gelling agents, and one or more polyols,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate; and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore.
[0023] In some aspects, the disclosure of this application provides
a method of promoting wound healing, comprising: applying topically
to a wound a biophotonic composition comprising a first
chromophore; one or more gelling agents; and one or more salts
selected from bicarbonate salts, carbonate salts or a combination
of the foregoing salts, wherein said composition does not include
an oxidant selected from the group consisting of a peroxide, a
peroxy acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate; and illuminating said biophotonic
composition with light having a wavelength that overlaps with an
absorption spectrum of the first chromophore.
[0024] In some aspects, the disclosure of this application provides
a method of promoting wound healing, comprising: applying topically
to a wound a biophotonic composition comprising a first
chromophore, one or more gelling agents, and one or more polyols,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate; and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore.
[0025] In some aspects, the disclosure of this application provides
a method for biophotonic treatment of a skin disorder, comprising:
applying topically to a target skin tissue afflicted with the skin
disorder a biophotonic composition comprising a first chromophore;
one or more gelling agents; and one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate; and illuminating said biophotonic
composition with light having a wavelength that overlaps with an
absorption spectrum of the first chromophore.
[0026] In some aspects, the disclosure of this application provides
a method for biophotonic treatment of a skin disorder, comprising:
applying topically to a target skin tissue afflicted with the skin
disorder a biophotonic composition comprising a first chromophore,
one or more gelling agents, and one or more polyols, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate; and
illuminating said biophotonic composition with light having a
wavelength that overlaps with an absorption spectrum of the first
chromophore.
[0027] In some aspects, the disclosure of this application provides
a method for biophotonic treatment of acne, comprising: applying
topically to a target tissue a biophotonic composition comprising a
first chromophore one or more gelling agents; and one or more salts
selected from bicarbonate salts, carbonate salts or a combination
of the foregoing salts, wherein said composition does not include
an oxidant selected from the group consisting of a peroxide, a
peroxy acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate; and illuminating said biophotonic
composition with light having a wavelength that overlaps with an
absorption spectrum of the first chromophore.
[0028] In some aspects, the disclosure of this application provides
a method for biophotonic treatment of acne, comprising: applying
topically to a target tissue a biophotonic composition comprising a
first chromophore, one or more gelling agents, and one or more
polyols, wherein said composition does not include an oxidant
selected from the group consisting of a peroxide, a peroxy acid,
hydrogen peroxide, carbamide peroxide, an alkali metal peroxide, an
alkali metal percarbonate, peroxyacetic acid, and an alkali metal
perborate; and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore.
[0029] In some aspects, the disclosure of this application provides
a method for biophotonic treatment of acne scars, comprising:
applying topically to a target tissue a biophotonic composition
comprising a first chromophore; one or more gelling agents; and one
or more salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts, wherein said composition does
not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate; and illuminating said
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the first chromophore.
[0030] In some aspects, the disclosure of this application provides
a method for biophotonic treatment of acne scars, comprising:
applying topically to a target tissue a biophotonic composition
comprising a first chromophore, one or more gelling agents, and one
or more polyols, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate; and illuminating said biophotonic
composition with light having a wavelength that overlaps with an
absorption spectrum of the first chromophore.
[0031] In some aspects, the disclosure of this application provides
a method of biophotonic treatment of on oral disease, comprising:
applying topically to a target site a biophotonic composition
comprising a first chromophore; one or more gelling agents; and one
or more salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts, wherein said composition does
not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate; and illuminating said
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the first chromophore. In
certain such embodiments, said oral disease is chosen from
gingivitis, periodontitis, periodontal disease, oral thrush, lichen
planus, stomatitis, herpes simplex lesion, oral mucositis, oral
ulcers, oral submucous fibrosis, and glossitis.
[0032] In some aspects, the disclosure of this application provides
a method of biophotonic treatment of an oral disease, comprising:
applying topically to a target site a biophotonic composition
comprising a first chromophore, one or more gelling agents, and one
or more polyols, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate; and illuminating said biophotonic
composition with light having a wavelength that overlaps with an
absorption spectrum of the first chromophore. In certain such
embodiments, said oral disease is chosen from gingivitis,
periodontitis, periodontal disease, oral thrush, lichen planus,
stomatitis, herpes simplex lesion, oral mucositis, oral ulcers,
oral submucous fibrosis, and glossitis.
[0033] In some embodiments, the method further comprises removing
the biophotonic composition after illumination.
[0034] In some embodiments, the biophotonic composition is
illuminated for about 1 minute to about 30 minutes. In certain
embodiments of any of the foregoing or following, the biophotonic
composition is illuminated for less than about 20 minutes, about 15
minutes, about 10 minutes, or about 5 minutes.
[0035] In some embodiments, the biophotonic composition is
illuminated with actinic light.
[0036] In some embodiments, the biophotonic composition is
illuminated with violet and/or blue light.
[0037] In some aspects, the disclosure of this application provides
a biophotonic composition comprising a first chromophore; one or
more gelling agents; and one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate for use in the treatment of wounds.
[0038] In some aspects, the disclosure of this application provides
a biophotonic composition comprising a first chromophore, one or
more gelling agents, and one or more polyols, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate for
use in the treatment of wounds.
[0039] In some aspects, the disclosure of this application provides
a biophotonic composition comprising a first chromophore; one or
more gelling agents; and one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate for use in the treatment or prevention of
skin disorders.
[0040] In some aspects, the disclosure of this application provides
a biophotonic composition comprising a first chromophore, one or
more gelling agents, and one or more polyols, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate for
use in the treatment or prevention of skin disorders.
[0041] In some aspects, the disclosure of this application provides
a biophotonic composition comprising a first chromophore; one or
more gelling agents; and one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate for use in the treatment of acne.
[0042] In some aspects, the disclosure of this application provides
a biophotonic composition comprising a first chromophore, one or
more gelling agents, and one or more polyols, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate for
use in the treatment of acne.
[0043] In some aspects, the disclosure of this application provides
a biophotonic composition comprising a first chromophore; one or
more gelling agents; and one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate for use in the treatment of acne scars.
[0044] In some aspects, the disclosure of this application provides
a biophotonic composition comprising a first chromophore, one or
more gelling agents, and one or more polyols, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate for
use in the treatment of acne scars.
[0045] In some aspects, the disclosure of this application provides
a biophotonic composition comprising a first chromophore; one or
more gelling agents; and one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate for use in the treatment or prevention of an
oral disease. In certain such embodiments, said oral disease is
chosen from gingivitis, periodontitis, periodontal disease, oral
thrush, lichen planus, stomatitis, herpes simplex lesion, oral
mucositis, oral ulcers, oral submucous fibrosis, and glossitis.
[0046] In some aspects, the disclosure of this application provides
a biophotonic composition comprising a first chromophore, one or
more gelling agents, and one or more polyols, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate for
use in the treatment or prevention of an oral disease. In certain
such embodiments, said oral disease is chosen from gingivitis,
periodontitis, periodontal disease, oral thrush, lichen planus,
stomatitis, herpes simplex lesion, oral mucositis, oral ulcers,
oral submucous fibrosis, and glossitis.
[0047] In some aspects, the disclosure of this application provides
a biophotonic composition comprising a first chromophore; one or
more gelling agents; and one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate for use in the treatment of acute or chronic
inflammation.
[0048] In some aspects, the disclosure of this application provides
a biophotonic composition comprising a first chromophore, one or
more gelling agents, and one or more polyols, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate for
use in the treatment of acute or chronic inflammation.
[0049] In some aspects, the disclosure of this application provides
a kit comprising:
[0050] a) a biophotonic composition comprising: a first
chromophore; one or more gelling agents; and one or more salts
selected from bicarbonate salts, carbonate salts or a combination
of the foregoing salts, wherein said composition does not include
an oxidant selected from the group consisting of a peroxide, a
peroxy acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate; and
[0051] b) one or more of a light source for activating the first
chromophore; instructions for use of the composition and/or the
light source; a dressing; and a device for applying and/or removing
the composition from a treatment area.
[0052] In some aspects, the disclosure of this application provides
a kit comprising a biophotonic composition comprising a first
chromophore, one or more gelling agents, and one or more polyols,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate and one or more of a light source for activating the
first chromophore, instructions for use of the composition and/or
the light source, a dressing, and a device for applying and/or
removing the composition from a treatment area.
[0053] In some aspects, the disclosure of this application provides
use of a biophotonic composition comprising a first chromophore;
one or more gelling agents; and one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate in the manufacture of a medicament for the
treatment of wounds.
[0054] In some aspects, the disclosure of this application provides
use of a biophotonic composition comprising a first chromophore,
one or more gelling agents, and one or more polyols, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate in
the manufacture of a medicament for the treatment of wounds.
[0055] In some aspects, the disclosure of this application provides
use of a biophotonic composition comprising a first chromophore;
one or more gelling agents; and one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate in the manufacture of a medicament for the
treatment or prevention of skin disorders.
[0056] In some aspects, the disclosure of this application provides
use of a biophotonic composition comprising a first chromophore,
one or more gelling agents, and one or more polyols, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate in
the manufacture of a medicament for the treatment or prevention of
skin disorders.
[0057] In some aspects, the disclosure of this application provides
use of a biophotonic composition comprising a first chromophore;
one or more gelling agents; and one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate in the manufacture of a medicament for the
treatment of acne.
[0058] In some aspects, the disclosure of this application provides
use of biophotonic composition comprising a first chromophore, one
or more gelling agents, and one or more polyols, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate in
the manufacture of a medicament for the treatment of acne.
[0059] In some aspects, the disclosure of this application provides
use of a biophotonic composition comprising a first chromophore;
one or more gelling agents; and one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate in the manufacture of a medicament for the
treatment of acne scars.
[0060] In some aspects, the disclosure of this application provides
use of biophotonic composition comprising a first chromophore, one
or more gelling agents, and one or more polyols, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate in
the manufacture of a medicament for the treatment of acne
scars.
[0061] In some aspects, the disclosure of this application provides
use of a biophotonic composition comprising a first chromophore;
one or more gelling agents; and one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate in the manufacture of a medicament for the
treatment or prevention of an oral disease. In certain such
embodiments, said oral disease is chosen from gingivitis,
periodontitis, periodontal disease, oral thrush, lichen planus,
stomatitis, herpes simplex lesion, oral mucositis, oral ulcers,
oral submucous fibrosis, and glossitis.
[0062] In some aspects, the disclosure of this application provides
use of a biophotonic composition comprising a first chromophore,
one or more gelling agents, and one or more polyols, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate in
the manufacture of a medicament for the treatment or prevention of
an oral disease. In certain such embodiments, said oral disease is
chosen from gingivitis, periodontitis, periodontal disease, oral
thrush, lichen planus, stomatitis, herpes simplex lesion, oral
mucositis, oral ulcers, oral submucous fibrosis, and glossitis.
[0063] In some aspects, the disclosure of this application provides
use of a biophotonic composition comprising a first chromophore;
one or more gelling agents; and one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate in the manufacture of a medicament for the
treatment of acute or chronic inflammation.
[0064] In some aspects, the disclosure of this application provides
use of a biophotonic composition comprising a first chromophore,
one or more gelling agents, and one or more polyols, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate in
the manufacture of a medicament for the treatment of acute or
chronic inflammation.
BRIEF DESCRIPTION OF THE DRAWINGS
[0065] FIG. 1 illustrates the Stokes' shift.
[0066] FIG. 2 illustrates the absorption and emission spectra of
donor and acceptor chromophores. The spectral overlap between the
absorption spectrum of the acceptor chromophore and the emission
spectrum of the donor chromophore is also shown.
[0067] FIG. 3 is a schematic of a Jablonski diagram that
illustrates the coupled transitions involved between a donor
emission and acceptor absorbance.
[0068] FIGS. 4A and 4B depict reactive oxygen species (ROS)
production in a urea peroxide (UP) dilution assay with gel A3 (FIG.
4A) and gel A (FIG. 4B) (Example 2).
[0069] FIGS. 5A, 5B and 5C depict changes in fluorescence with
decreasing concentration of Eosin Y in gel A3 (FIGS. 5A and 5B) and
the effect of Eosin Y concentration (20.times.=2,180 .mu.g/g Eosin
Y, 10.times.=1,090 .mu.g/g Eosin Y, and 5.times.=545 .mu.g/g Eosin
Y) on ROS production (FIG. 5C) (Example 3).
[0070] FIGS. 6A and 6B depict the production of hydrogen peroxide
in gel D1 in the presence of varying concentrations of sodium
bicarbonate (Example 6). 109, 327, 545, and 763 .mu.g/g of Eosin Y
(labelled as 1.times., 3.times., 5.times., and 7.times.
respectively)
[0071] FIG. 7 depicts a comparison of the fluorescence of gel C (no
glycerin) with the fluorescence of gel D (with glycerin) in the
presence of 1% sodium bicarbonate (Example 7).
[0072] FIG. 8 depicts the effect of the presence of varying
concentrations of sodium bicarbonate on the fluorescence of gel D1
(Example 8).
[0073] FIGS. 9A, 9B and 9C depict the effects of low glycerin (218
mg/g), medium glycerin 436 mg/g), and high glycerin (654 mg/g) on
the fluorescence colors output of gel D1 (Example 9).
[0074] FIGS. 10A, 10B and 10C depict the effect of increased
amounts of eosin Y (109, 327, 545, and 763 .mu.g/g of Eosin Y
(labelled as 1.times., 3.times., 5.times., and 7.times.
respectively)) on the fluorescence colors output of gel D1 (Example
10).
[0075] FIGS. 11A, 11B and 11C depict the impact of various salts,
such as sodium bicarbonate (SB), calcium carbonate (Calcium Carb.),
potassium bicarbonate (Potassium Bicarb.), sodium acetate (Sod.
Acetate), sodium biphosphate (Sod. Biphosphate) on the fluorescence
of gel D1 with 327 .mu.g/g (3.times.E) Eosin Y (Example 11).
[0076] FIGS. 12A, 12B, 12C, 12D and 12E depict the impact of
varying concentrations of superoxide dismutase (SOD) on the
fluorescence and ROS production of gel D1 in the absence of sodium
bicarbonate (FIGS. 12A, 12B, and 12) and in the presence of sodium
bicarbonate (FIGS. 12D and 12E) (Example 12).
[0077] FIGS. 13A and 13B depict the impact of varying
concentrations of sodium bicarbonate (SB) on the fluorescence of
gel D1 with 327 .mu.g/g (3.times.E) Eosin Y (Example 13).
[0078] FIG. 14 depicts the impact of glycerin, propylene glycol,
and the combination of glycerin and propylene glycol on the
fluorescence of gel D1 (Example 14).
[0079] FIGS. 15A, 15B, 15C, 15D, 15E and 15F depicts the impact of
glycerin, propylene glycol, and the combination of glycerin and
propylene glycol on the fluorescence color output of gel D2
(Example 15).
[0080] FIG. 16 depicts the impact of varying concentrations of
sodium bicarbonate on the fluorescence of gel D2 with 327 .mu.g/g
Eosin Y (Example 16).
[0081] FIGS. 17A, 17B and 17C depict the impact of varying
concentrations of propylene glycol and glycerin on the fluorescence
of gel D2 and of varying concentrations of propylene glycol,
glycerin, and parabens on the fluorescence of gel E. Both gels have
327 .mu.g/g Eosin Y (Example 17).
[0082] FIGS. 18A, 18B and 18C depict the impact of methyl and
propyl parabens on the fluorescence of gel E in the presence and
absence of sodium bicarbonate (SB). Gel D2 lacks parabens, but gel
E contains parabens. Both gels have 327 .mu.g/g Eosin Y (Example
18).
[0083] FIGS. 19A, 19B, 19C and 19D depict the impact of varying
concentrations of Eosin Y on the fluorescence of gel E. Gel E
contains parabens (Example 19).
[0084] FIGS. 20A and 20B illustrate the impact of various
components on the photobleaching of Eosin Y (327 .mu.g/g
(3.times.E)). The gel used is the D1 gel. Tested components
include: urea peroxide (UP), sodium bicarbonate (SB), propylene
glycol (PG), and EDTA. The D1 gel contains glycerin (Example
20).
[0085] FIG. 21 illustrates the impact of changes in pH on the
fluorescence of the D1 gel in the presence and absence of sodium
bicarbonate (Example 21).
[0086] FIG. 22 illustrates the impact of adding sodium bicarbonate
in a gel, solid sodium bicarbonate, sodium carbonate in a gel, or
solid sodium carbonate on the fluorescence of the D1 gel. Sodium
bicarbonate in a gel, solid sodium bicarbonate, sodium carbonate in
a gel, or solid sodium carbonate was added at various times to the
D1 gel and the fluorescence was analyzed to determine the stability
of the gel (Example 22).
DETAILED DESCRIPTION
(1) Overview
[0087] Photodynamic therapy regimens have been developed to promote
wound healing, rejuvenate facial skins and treat various skin
disorders. However, these methods tend to require the presence of
oxidants, such as peroxides (e.g., hydrogen peroxide and carbamide
peroxide). The presence of peroxides in the composition can lead to
undesired side-effects, including skin irritation and bleaching,
redness and stinging, and blisters or ulcers to the patient.
[0088] Phototherapy on the other hand utilizes the therapeutic
effect of light. However, expensive and sophisticated light sources
are often required to provide therapeutic wavelengths and
intensities of light.
[0089] The present disclosure provides biophotonic compositions
which are useful in phototherapy and which include photoactive
exogenous chromophores which can emit a therapeutic light or which
can promote a therapeutic effect on a treatment site by activating
other components of the biophotonic composition. The present
disclosure also provides methods useful for promoting wound
healing, cosmetic treatment of skin such as skin rejuvenation,
treating acne and treating other skin disorders, treating acute or
chronic inflammation, which are distinguished from conventional
photodynamic therapy.
[0090] Biophotonic therapy using these compositions does not rely
on the presence of an oxidant selected from the group consisting of
a peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide,
an alkali metal peroxide, an alkali metal percarbonate,
peroxyacetic acid, and an alkali metal perborate. Therefore, the
undesired side effects caused by such oxidants may be reduced,
minimized, or prevented.
[0091] (2) Definitions
[0092] Before continuing to describe the present disclosure in
further detail, it is to be understood that this disclosure is not
limited to specific compositions or process steps, as such may
vary. It must be noted that, as used in this specification and the
appended claims, the singular form "a", "an" and "the" include
plural referents unless the context clearly dictates otherwise.
[0093] It is convenient to point out here that "and/or" where used
herein is to be taken as specific disclosure of each of the two
specified features or components with or without the other. For
example "A and/or B" is to be taken as specific disclosure of each
of (i) A, (ii) B and (iii) A and B, just as if each is set out
individually herein.
[0094] "Biophotonic" means the generation, manipulation, detection
and application of photons in a biologically relevant context. In
other words, biophotonic compositions exert their physiological
effects primarily due to the generation and manipulation of
photons. "Biophotonic composition" is a composition as described
herein that may be activated by light to produce photons for
biologically relevant applications.
[0095] "Gels" are defined as substantially dilute cross-linked
systems. Gels may be semi-solids and exhibit substantially no flow
when in the steady state at room temperature (e.g. about
20-25.degree. C.). By steady state is meant herein during a
treatment time and under treatment conditions. Gels, as defined
herein, may be physically or chemically cross-linked. As defined
herein, gels also include gel-like compositions such as viscous
liquids.
[0096] "Topical" means as applied to body surfaces, such as the
skin, mucous membranes, vagina, oral cavity, internal surgical
wound sites, and the like.
[0097] Terms "chromophore", "photoactivating agent" and
"photoactivator" are used herein interchangeably. A chromophore
means a chemical compound, moiety, or complex, when contacted by
light irradiation, is capable of absorbing the light. The
chromophore readily undergoes photoexcitation and can then transfer
its energy to other molecules or emit it as light.
[0098] The "initial level of fluorescence" is the level of
fluorescence exhibited by a biophotonic composition of the
disclosure immediately upon application of or activation with
light.
[0099] "Photobleaching" means the photochemical destruction of a
chromophore.
[0100] The term "actinic light" is intended to mean light energy
emitted from a specific light source (e.g., lamp, LED, or laser)
and capable of being absorbed by matter (e.g. the chromophore or
photoactivator defined above). In some embodiments, the actinic
light is visible light.
[0101] As used herein, a "hygroscopic" substance is a substance
capable of taking up water, for example, by absorption or
adsorption even at relative humidity as low as 50%, at room
temperature (e.g. about 20-25.degree. C.).
[0102] "Impermeable membrane" means that the material contained
within the membrane is sufficiently or substantially impermeable to
the surrounding environment such that the migration of such
material out of the membrane, and/or the migration of the
environmental components (such as water) into the membrane, is so
low as to having substantially no adverse impact on the function or
activity of the materials retained within the membrane. The
impermeable membrane may be `breathable` in that gas flow through
the membrane is permitted whilst the flow of liquid is not
permitted. The impermeable membrane may also selectively allow the
migration of some of the materials through the membrane but not
others.
[0103] "Wound" means an injury to any tissue, including for
example, acute, subacute, delayed or difficult to heal wounds, and
chronic wounds. Examples of wounds include both open and closed
wounds. Wounds include, for example, burns, incisions, excisions,
lesions, lacerations, abrasions, puncture or penetrating wounds,
gunshot wounds, surgical wounds, contusions, hematomas, crushing
injuries, ulcers (such as for example pressure, venous, pressure or
diabetic), wounds caused by periodontitis (inflammation of the
periodontium), or other soft tissue disorders.
[0104] "Skin rejuvenation" means a process of reducing,
diminishing, retarding or reversing one or more signs of skin
aging. For instance, common signs of skin aging include, but are
not limited to, appearance of fine lines or wrinkles, thin and
transparent skin, loss of underlying fat (leading to hollowed
cheeks and eye sockets as well as noticeable loss of firmness on
the hands and neck), bone loss (such that bones shrink away from
the skin due to bone loss, which causes sagging skin), dry skin
(which might itch), inability to sweat sufficiently to cool the
skin, unwanted facial hair, freckles, age spots, spider veins,
rough and leathery skin, fine wrinkles that disappear when
stretched, loose skin, or a blotchy complexion. According to the
present disclosure, one or more of the above signs of aging may be
reduced, diminished, retarded or even reversed by the compositions
and methods of the present disclosure.
(3) Biophotonic Topical Compositions
[0105] The present disclosure provides biophotonic compositions.
Biophotonic compositions are compositions that are, in a broad
sense, activated by light (e.g., photons) of specific wavelength.
These compositions contain at least one exogenous chromophore which
is activated by light and accelerates the dispersion of light
energy, which leads to light carrying on a therapeutic effect on
its own, and/or to the photochemical activation of other agents
contained in the composition. The composition may comprise an agent
which, when mixed with the first chromophore and subsequently
activated by light, can be photochemically activated which may lead
to the formation of oxygen radicals, such as singlet oxygen.
[0106] In some aspects, the present disclosure provides biophotonic
compositions comprising at least a first chromophore; one or more
gelling agents; and one or more salts selected from bicarbonate
salts, carbonate salts or a combination of the foregoing salts,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate.
[0107] In some aspects, the present disclosure provides biophotonic
compositions comprising at least a first chromophore; one or more
salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts; one or more polyols; and one or
more gelling agents, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate.
[0108] In some aspects, the biophotonic compositions of the present
disclosure comprise a first chromophore, one or more polyols, and
one or more gelling agents, wherein said composition does not
include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate. In certain such aspects, said
biophotonic compositions maintain, within a first minute of
illumination, at least 80% of their initial levels of
fluorescence.
[0109] In some aspects, the present disclosure provides a first
composition and a second composition that are mixed together before
use to generate a biophotonic composition, wherein the first
composition comprises at least a first chromophore and one or more
gelling agents and the second composition comprises one or more
salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts, wherein said first and second
compositions do not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate.
[0110] In some aspects, the present disclosure provides a first
composition and a second composition, wherein the first composition
comprises at least a first chromophore and the second composition
comprises one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts and one or
more gelling agents, wherein said first and second compositions do
not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate.
[0111] In some aspects, the present disclosure provides a first
composition and a second composition, wherein the first composition
comprises at least a first chromophore and one or more gelling
agents and the second composition comprises one or more salts
selected from bicarbonate salts, carbonate salts or a combination
of the foregoing salts and one or more gelling agents, wherein said
first and second compositions do not include an oxidant selected
from the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate.
[0112] In some aspects, the present disclosure provides a first
composition and a second composition that are mixed together before
use to generate a biophotonic composition, wherein the first
composition comprises at least a first chromophore, and the second
composition comprises one or more gelling agents and one or more
polyols, which, when mixed with the first composition and
subsequently activated by light, disperses the light energy,
leading to the photochemical activation of the combined
compositions, which may lead to the formation of oxygen radicals,
such as singlet oxygen. In certain such embodiments, said first and
second compositions do not include an oxidant selected from the
group consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate.
[0113] In some aspects, the present disclosure provides a first
composition and a second composition, wherein the first composition
comprises at least a first chromophore, and one or more gelling
agents and the second composition comprises one or more polyols,
wherein said first and second compositions do not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate.
[0114] In some aspects, the present disclosure provides a first
composition and a second composition, wherein the first composition
comprises at least a first chromophore, and one or more polyols and
the second composition comprises one or more gelling agents,
wherein said first and second compositions do not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate.
[0115] In some aspects, the present disclosure provides a first
composition and a second composition, wherein the first composition
comprises at least a first chromophore, and one or more gelling
agents and the second composition comprises one or more polyols and
one or more gelling agents, wherein said first and second
compositions do not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate.
[0116] In some aspects, the present disclosure provides a first
composition and a second composition, wherein the first composition
comprises at least a first chromophore, and one or more polyols and
the second composition comprises one or more polyols and one or
more gelling agents, wherein said first and second compositions do
not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate.
[0117] In some aspects, the present disclosure provides a first
composition and a second composition, wherein the first composition
comprises at least a first chromophore and the second composition
comprises one or more bicarbonate salts or carbonate salts or a
combination of the foregoing salts; one or more gelling agents; and
one or more polyols, which, when mixed with the first composition
and subsequently activated by light, disperses the light energy,
leading to the photochemical activation of the combined
compositions, which may lead to the formation of oxygen radicals,
such as singlet oxygen. In certain such embodiments, said first and
second compositions do not include an oxidant selected from the
group consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate.
[0118] In some aspects, the present disclosure provides a first
composition and a second composition, wherein the first composition
comprises at least a first chromophore and one or more gelling
agents and the second composition comprises one or more polyols and
one or more bicarbonate salts or carbonate salts or a combination
of the foregoing salts, wherein said first and second compositions
do not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate.
[0119] In some aspects, the present disclosure provides a first
composition and a second composition, wherein the first composition
comprises at least a first chromophore and one or more polyols and
the second composition comprises one or more gelling agents and one
or more bicarbonate salts or carbonate salts or a combination of
the foregoing salts, wherein said first and second compositions do
not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate.
[0120] In some aspects, the present disclosure provides a first
composition and a second composition, wherein the first composition
comprises at least a first chromophore and one or more gelling
agents and the second composition comprises one or more bicarbonate
salts or carbonate salts or a combination of the foregoing salts;
one or more polyols; and one or more gelling agents, wherein said
first and second compositions do not include an oxidant selected
from the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate.
[0121] In some aspects, the present disclosure provides a first
composition and a second composition, wherein the first composition
comprises at least a first chromophore and one or more polyols and
the second composition comprises one or more bicarbonate salts or
carbonate salts or a combination of the foregoing salts; one or
more polyols; and one or more gelling agents, wherein said first
and second compositions do not include an oxidant selected from the
group consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate.
[0122] In some aspects, the present disclosure provides a first
composition and a second composition, wherein the first composition
comprises at least a first chromophore, one or more gelling agents,
and one or more polyols and the second composition comprises one or
more bicarbonate salts or carbonate salts or a combination of the
foregoing salts; one or more polyols; and one or more gelling
agents, wherein said first and second compositions do not include
an oxidant selected from the group consisting of a peroxide, a
peroxy acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate.
[0123] In some aspects, the present disclosure provides a first
composition and a second composition, wherein the first composition
comprises at least a first chromophore, one or more gelling agents,
and one or more polyols and the second composition comprises one or
more bicarbonate salts or carbonate salts or a combination of the
foregoing salts, wherein said first and second compositions do not
include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate.
[0124] When a chromophore absorbs a photon of a certain wavelength,
it becomes excited. This is an unstable condition and the molecule
tries to return to the ground state, giving away the excess energy.
For some chromophores, it is favorable to emit the excess energy as
light when transforming back to the ground state. This process is
called fluorescence. The peak wavelength of the emitted
fluorescence is shifted towards longer wavelengths compared to the
absorption wavelengths (`Stokes' shift`). The emitted fluorescent
energy can then be transferred to the other components of the
composition or to a treatment site on to which the biophotonic
composition is topically applied. Differing wavelengths of light
may have different and complementary therapeutic effects on tissue.
Stokes' shift is illustrated in FIG. 1.
[0125] Without being bound to theory, it is thought that
fluorescent light emitted by photoactivated chromophores may have
therapeutic properties due to its femto-, pico- or nano-second
emission properties which may be recognized by biological cells and
tissues, leading to favorable biomodulation. Furthermore, the
emitted fluorescent light has a longer wavelength and hence a
deeper penetration into the tissue than the activating light.
Irradiating tissue with such a broad range of wavelengths,
including in some embodiments the activating light which passes
through the composition, may have different and complementary
effects on the cells and tissues. Moreover, in embodiments of the
composition containing bicarbonate or carbonate salts,
micro-bubbling within the composition has been observed by the
inventor which may be associated with the generation of oxygen
species by the photoactivated chromophores. This may have a
physical impact on the tissue to which it is applied, for example
by dislodging biofilm and debridement of necrotic tissue or
providing a pressure stimulation. The biofilm can also be
pre-treated with an oxygen-releasing agent to weaken the biofilm
before treating with the composition of the present disclosure.
[0126] In certain embodiments, the biophotonic compositions of the
present disclosure are substantially transparent/translucent and/or
have high light transmittance in order to permit light dissipation
into and through the composition. In this way, the area of tissue
under the composition can be treated both with the fluorescent
light emitted by the composition and the light irradiating the
composition to activate it, which may benefit from the different
therapeutic effects of light having different wavelengths.
[0127] The % transmittance of the biophotonic composition can be
measured in the range of wavelengths from 250 nm to 800 nm using,
for example, a Perkin-Elmer Lambda 9500 series UV-visible
spectrophotometer. Alternatively, a Synergy HT spectrophotometer
(BioTek Instrument, Inc.) can be used in the range of wavelengths
from 380 nm to 900 nm.
[0128] Transmittance is calculated according to the following
equation:
A .lamda. = log 10 .times. I 0 I = log 10 .times. 1 T .
##EQU00001##
where A is absorbance, T is transmittance, I.sub.0 is intensity of
radiation before passing through material, I is intensity of light
passing through material.
[0129] The values can be normalized for thickness. As stated
herein, % transmittance (translucency) is as measured for a 2 mm
thick sample at a wavelength of 526 nm. It will be clear that other
wavelengths can be used.
[0130] The biophotonic compositions of the present disclosure are
for topical uses. The biophotonic compositions can be in the form
of a semi-solid or viscous liquid, such as a gel, or are gel-like,
and which have a spreadable consistency at room temperature (e.g.
about 20-25.degree. C.), prior to illumination. By spreadable is
meant that the composition can be topically applied to a treatment
site at a thickness of about 0.5 mm to about 3.0 mm, about 0.5 mm
to about 2.5 mm, about 1.0 mm to about 2.0 mm. In some embodiments,
the composition can be topically applied to a treatment site at a
thickness of about 2.0 mm or about 1.0 mm. Spreadable compositions
can conform to a topography of a treatment site, e.g. a wound. This
can have advantages over a non-conforming material in that a better
and/or more complete illumination of the treatment site can be
achieved and the compositions are easy to apply and remove.
[0131] These compositions may be described based on the components
making up the composition. Additionally or alternatively, the
compositions of the present disclosure have functional and
structural properties and these properties may also be used to
define and describe the compositions. Individual components of the
composition of the present disclosure are detailed as below.
(a) Chromophores
[0132] The biophotonic topical compositions of the present
disclosure comprise one or more chromophores, which can be
considered exogenous, e.g., are not naturally present in skin or
tissue. When a biophotonic composition of the present disclosure is
illuminated with light, the chromophore(s) are excited to a higher
energy state. When the chromophore(s)' electrons return to a lower
energy state, they emit photons with a lower energy level, thus
causing the emission of light of a longer wavelength (Stokes'
shift). In the proper environment, some of this energy release is
transferred to oxygen and causes the formation of oxygen radicals,
such as singlet oxygen.
[0133] Suitable chromophores for the biophotonic compositions of
the disclosure can be fluorescent dyes (or stains), although other
dye groups or dyes (biological and histological dyes, food
colorings, carotenoids, naturally occurring fluorescent and other
dyes) can also be used.
[0134] In some embodiments, the biophotonic topical composition of
the present disclosure comprises a first chromophore which
undergoes partial or complete photobleaching upon application of
light. By photobleaching is meant a photochemical destruction of
the chromophore which can generally be visualized as a loss of
color. Without wishing to be bound by theory, the biophotonic
compositions of the present disclosure may take longer to
photobleach upon application of light than compositions comprising
one or more chromophores and one or more oxidants selected from the
group consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate. In
some embodiments, the biophotonic compositions of the disclosure
maintain, within a first minute of illumination, at least 80% of
their initial level of fluorescence.
[0135] In some embodiments, the first chromophore absorbs at a
wavelength in the range of the visible spectrum, such as at a
wavelength of about 380-800 nm, about 380-700 nm, or about 380-600
nm. In some embodiments, the first chromophore absorbs at a
wavelength of about 200-800 nm, about 200-700 nm, about 200-600 nm
or about 200-500 nm. In some embodiments, the first chromophore
absorbs at a wavelength of about 200-600 nm. In some embodiments,
the first chromophore absorbs light at a wavelength of about
200-300 nm, about 250-350 nm, about 300-400 nm, about 350-450 nm,
about 400-500 nm, about 400-600 nm, about 450-650 nm, about 600-700
nm, about 650-750 nm or about 700-800 nm.
[0136] In some embodiments, the first chromophore is present in an
amount of about 0.001-40% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of about
0.005-2%, about 0.01-1%, about 0.01-2%, about 0.05-1%, about
0.05-2%, about 0.1-1%, about 0.1-2%, about 1-5%, about 2.5-7.5%,
about 5-10%, about 7.5-12.5%, about 10-15%, about 12.5-17.5%, about
15-20%, about 17.5-22.5%, about 20-25%, about 22.5-27.5%, about
25-30%, about 27.5-32.5%, about 30-35%, about 32.5-37.5%, or about
35-40% by weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.2% by
weight of the composition.
[0137] In some embodiments, the first chromophore is present in an
amount of 0.001-40% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of
0.005-2%, 0.01-1%, 0.01-2%, 0.05-1%, 0.05-2%, 0.1-1%, 0.1-2%, 1-5%,
2.5-7.5%, 5-10%, 7.5-12.5%, 10-15%, 12.5-17.5%, 15-20%, 17.5-22.5%,
20-25%, 22.5-27.5%, 25-30%, 27.5-32.5%, 30-35%, 32.5-37.5%, or
35-40% by weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least 0.2% by weight of
the composition.
[0138] In some embodiments, the first chromophore is present in an
amount of about 0.05% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of about
0.1% by weight of the composition. In some embodiments, the first
chromophore is present in an amount of about 0.15% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of about 0.2% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of about
0.25% by weight of the composition. In some embodiments, the first
chromophore is present in an amount of about 0.3% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of about 0.35% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of about
0.4% by weight of the composition. In some embodiments, the first
chromophore is present in an amount of about 0.45% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of about 0.5% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of about
0.55% by weight of the composition. In some embodiments, the first
chromophore is present in an amount of about 0.6% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of about 0.65% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of about
0.7% by weight of the composition. In some embodiments, the first
chromophore is present in an amount of about 0.75% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of about 0.8% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of about
0.85% by weight of the composition. In some embodiments, the first
chromophore is present in an amount of about 0.9% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of about 0.95% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of about
1% by weight of the composition.
[0139] In some embodiments, the first chromophore is present in an
amount of 0.05% by weight of the composition. In some embodiments,
the first chromophore is present in an amount of 0.1% by weight of
the composition. In some embodiments, the first chromophore is
present in an amount of 0.15% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of 0.2%
by weight of the composition. In some embodiments, the first
chromophore is present in an amount of 0.25% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of 0.3% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of 0.35%
by weight of the composition. In some embodiments, the first
chromophore is present in an amount of 0.4% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of 0.45% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of 0.5%
by weight of the composition. In some embodiments, the first
chromophore is present in an amount of 0.55% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of 0.6% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of 0.65%
by weight of the composition. In some embodiments, the first
chromophore is present in an amount of 0.7% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of 0.75% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of 0.8%
by weight of the composition. In some embodiments, the first
chromophore is present in an amount of 0.85% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of 0.9% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of 0.95%
by weight of the composition. In some embodiments, the first
chromophore is present in an amount of 1% by weight of the
composition.
[0140] In some embodiments, the first chromophore is present in an
amount of at least about 0.05% by weight of the composition. In
some embodiments, the first chromophore is present in an amount of
at least about 0.1% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of at
least about 0.15% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of at
least about 0.2% by weight of the composition. In some embodiments,
the first chromophore is present in an amount of at least about
0.25% by weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.3% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.35% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.4% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.45% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.5% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.55% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.6% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.65% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.7% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.75% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.8% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.85% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.9% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.95% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 1% by weight
of the composition.
[0141] In some embodiments, the first chromophore is present in an
amount of at least 0.05% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of at
least 0.1% by weight of the composition. In some embodiments, the
first chromophore is present in an amount of at least 0.15% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least 0.2% by weight of
the composition. In some embodiments, the first chromophore is
present in an amount of at least 0.25% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of at least 0.3% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of at
least 0.35% by weight of the composition. In some embodiments, the
first chromophore is present in an amount of at least 0.4% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least 0.45% by weight of
the composition. In some embodiments, the first chromophore is
present in an amount of at least 0.5% by weight of the composition.
In some embodiments, the first chromophore is present in an amount
of at least 0.55% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of at
least 0.6% by weight of the composition. In some embodiments, the
first chromophore is present in an amount of at least 0.65% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least 0.7% by weight of
the composition. In some embodiments, the first chromophore is
present in an amount of at least 0.75% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of at least 0.8% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of at
least 0.85% by weight of the composition. In some embodiments, the
first chromophore is present in an amount of at least 0.9% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least 0.95% by weight of
the composition. In some embodiments, the first chromophore is
present in an amount of at least 1% by weight of the
composition.
[0142] It will be appreciated to those skilled in the art that
optical properties of a particular chromophore may vary depending
on the chromophore's surrounding medium. Therefore, as used herein,
a particular chromophore's absorption and/or emission wavelength
(or spectrum) corresponds to the wavelengths (or spectrum) measured
in a biophotonic composition of the present disclosure.
[0143] The biophotonic compositions disclosed herein may include at
least one additional chromophore (e.g., a second or third
chromophore). Combining chromophores may increase photo-absorption
by the combined dye molecules and enhance absorption and
photo-biomodulation selectivity. This creates multiple
possibilities of generating new photosensitive, and/or selective
chromophores mixtures.
[0144] When such multi-chromophore compositions are illuminated
with light, energy transfer can occur between the chromophores.
This process, known as resonance energy transfer, is a
photophysical process through which an excited `donor` chromophore
(also referred to herein as first chromophore) transfers its
excitation energy to an `acceptor` chromophore (also referred to
herein as second chromophore). The efficiency and directedness of
resonance energy transfer depends on the spectral features of donor
and acceptor chromophores. In particular, the flow of energy
between chromophores is dependent on a spectral overlap reflecting
the relative positioning and shapes of the absorption and emission
spectra. For energy transfer to occur the emission spectrum of the
donor chromophore overlap with the absorption spectrum of the
acceptor chromophore (FIG. 2).
[0145] Energy transfer manifests itself through decrease or
quenching of the donor emission and a reduction of excited state
lifetime accompanied also by an increase in acceptor emission
intensity. FIG. 3 is a Jablonski diagram that illustrates the
coupled transitions involved between a donor emission and acceptor
absorbance.
[0146] To enhance the energy transfer efficiency, the donor
chromophore should have good abilities to absorb photons and emit
photons. Furthermore, it is thought that the more overlap there is
between the donor chromophore's emission spectra and the acceptor
chromophore's absorption spectra, the better a donor chromophore
can transfer energy to the acceptor chromophore.
[0147] In some embodiments, the biophotonic topical composition of
the present disclosure further comprises a second chromophore. In
some embodiments, the first chromophore has an emission spectrum
that overlaps at least about 80%, about 70%, about 60%, about 50%,
about 40%, about 30%, about 20%, or about 10% with an absorption
spectrum of the second chromophore. In some embodiments, the first
chromophore has an emission spectrum that overlaps at least about
20% with an absorption spectrum of the second chromophore. In some
embodiments, the first chromophore has an emission spectrum that
overlaps at least 1-10%, 5-15%, 10-20%, 15-25%, 20-30%, 25-35%,
30-40%, 35-45%, 50-60%, 55-65% or 60-70% with an absorption
spectrum of the second chromophore.
[0148] Percentage (%) spectral overlap, as used herein, means the %
overlap of a donor chromophore's emission wavelength range with an
acceptor chromophore's absorption wavelength range, measured at
spectral full width quarter maximum (FWQM). For example, FIG. 2
shows the normalized absorption and emission spectra of donor and
acceptor chromophores. The spectral FWQM of the acceptor
chromophore's absorption spectrum is from about 60 nm (about 515 nm
to about 575 nm). The overlap of the donor chromophore's spectrum
with the absorption spectrum of the acceptor chromophore is about
40 nm (from 515 nm to about 555 nm). Thus, the % overlap can be
calculated as 40 nm / 60 nm x 100 =66.6%.
[0149] In some embodiments, the second chromophore absorbs at a
wavelength in the range of the visible spectrum. In some
embodiments, the second chromophore has an absorption wavelength
that is relatively longer than that of the first chromophore within
the range of about 50-250 nm, about 25-150 nm or about 10-100
nm.
[0150] As discussed above, the application of light to the
compositions of the present disclosure can result in a cascade of
energy transfer between the chromophores. In some embodiments, such
a cascade of energy transfer provides photons that penetrate the
epidermis, dermis and/or mucosa at the target tissue, including,
such as, a site of wound, or a tissue afflicted with acne or a skin
disorder. In some embodiments, such a cascade of energy transfer is
not accompanied by concomitant generation of heat. In some other
embodiments, the cascade of energy transfer does not result in
tissue damage.
[0151] Optionally, in embodiments wherein the biophotonic topical
composition comprises a first and a second chromophore, the first
chromophore is present in an amount of about 0.005-40% by weight of
the composition, and the second chromophore is present in an amount
of about 0.0001-40% by weight of the composition. In some
embodiments, the total weight by weight of the first chromophore or
combination of chromophores may be in the amount of about 0.005-40%
by weight of the composition. In some embodiments, the first
chromophore is present in an amount of about 0.005-1%, about
0.005-2%, about 0.01-2%, about 0.02-1%, about 0.02-2%, about
0.05-1%, about 0.05-2%, about 0.05-1%, about 0.05-2%, about 0.1-1%,
about 0.1-2%, about 1-5%, about 2.5-7.5%, about 5-10%, about
7.5-12.5%, about 10-15%, about 12.5-17.5%, about 15-20%, about
17.5-22.5%, about 20-25%, about 22.5-27.5%, about 25-30%, about
27.5-32.5%, about 30-35%, about 32.5-37.5%, or about 35-40% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.2% by
weight of the composition. In some embodiments, the second
chromophore is present in an amount of about 0.0001-2%, about
0.001-1%, about 0.001-2%, about 0.001-0.01%, about 0.01-0.1%, about
0.1-1%, about 0.1-2%, about 1-2%, about 1-5%, about 2.5-7.5%, about
5-10%, about 7.5-12.5%, about 10-15%, about 12.5-17.5%, about
15-20%, about 17.5-22.5%, about 20-25%, about 22.5-27.5%, about
25-30%, about 27.5-32.5%, about 30-35%, about 32.5-37.5%, or about
35-40% by weight of the composition. In some embodiments, the total
weight by weight of the first chromophore or combination of
chromophores may be in the amount of about 0.005-1%, about
0.005-2%, about 0.01-2%, about 0.05-2%, about 0.1-1%, about 0.1-2%,
about 0.5-1%, about 0.5-2%, about 1-5%, about 2.5-7.5%, about
5-10%, about 7.5-12.5%, about 10-15%, about 12.5-17.5%, about
15-20%, about 17.5-22.5%, about 20-25%, about 22.5-27.5%, about
25-30%, about 27.5-32.5%, about 30-35%, about 32.5-37.5%, or about
35-40% by weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.2% by
weight of the composition.
[0152] In some embodiments, when the biophotonic topical
composition comprises a first and a second chromophore, the first
chromophore is present in an amount of 0.005-40% by weight of the
composition, and the second chromophore is present in an amount of
0.0001-40% by weight of the composition. In some embodiments, the
total weight by weight of the first chromophore or combination of
chromophores may be in the amount of 0.005-40% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of 0.005-1%, 0.005-2%, 0.01-2%, 0.02-1%, 0.02-2%,
0.05-1%, 0.05-2%, 0.05-1%, 0.05-2%, 0.1-1%, 0.1-2%, 1-5%, 2.5-7.5%,
5-10%, 7.5-12.5%, 10-15%, 12.5-17.5%, 15-20%, 17.5-22.5%, 20-25%,
22.5-27.5%, 25-30%, 27.5-32.5%, 30-35%, 32.5-37.5%, or 35-40% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least 0.2% by weight of
the composition. In some embodiments, the second chromophore is
present in an amount of 0.0001-2%, 0.001-1%, 0.001-2%, 0.001-0.01%,
0.01-0.1%, 0.1-1%, 0.1-2%, 1-2%, 1-5%, 2.5-7.5%, 5-10%, 7.5-12.5%,
10-15%, 12.5-17.5%, 15-20%, 17.5-22.5%, 20-25%, 22.5-27.5%, 25-30%,
27.5-32.5%, 30-35%, 32.5-37.5%, or 35-40% by weight of the
composition. In some embodiments, the total weight by weight of the
first chromophore or combination of chromophores may be in the
amount of 0.005-1%, 0.005-2%, 0.01-2%, 0.05-2%, 0.1-1%, 0.1-2%,
0.5-1%, 0.5-2%, 1-5%, 2.5-7.5%, 5-10%, 7.5-12.5%, 10-15%,
12.5-17.5%, 15-20%, 17.5-22.5%, 20-25%, 22.5-27.5%, 25-30%,
27.5-32.5%, 30-35%, 32.5-37.5%, or 35-40% by weight of the
composition. In some embodiments, the first chromophore or
combination of chromophores is present in an amount of at least
0.2% by weight of the composition.
[0153] In some embodiments, when the biophotonic topical
composition comprises a first, a second chromophore, and a third
chromophore, the first chromophore is present in an amount of about
0.005-40% by weight of the composition, the second chromophore is
present in an amount of about 0.0001-40% by weight of the
composition, and the third chromophore is present in an amount of
about 0.0001-40% by weight of the composition. In some embodiments,
the total weight by weight of the first chromophore or combination
of chromophores may be in the amount of 0.005-40% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of about 0.005-1%, about 0.005-2%, about 0.01-2%,
about 0.02-1%, about 0.02-2%, about 0.05-1%, about 0.05-2%, about
0.05-1%, about 0.1-1%, about 0.1-2%, about 0.05-2%, about 1-5%,
about 2.5-7.5%, about 5-10%, about 7.5-12.5%, about 10-15%, about
12.5-17.5%, about 15-20%, about 17.5-22.5%, about 20-25%, about
22.5-27.5%, about 25-30%, about 27.5-32.5%, about 30-35%, about
32.5-37.5%, or about 35-40% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of at
least about 0.2% by weight of the composition. In some embodiments,
the second chromophore is present in an amount of about 0.0001-2%,
about 0.001-1%, about 0.001-2%, about 0.001-0.01%, about 0.01-0.1%,
about 0.1-1%, about 0.1-2%, about 1-2%, about 1-5%, about 2.5-7.5%,
about 5-10%, about 7.5-12.5%, about 10-15%, about 12.5-17.5%, about
15-20%, about 17.5-22.5%, about 20-25%, about 22.5-27.5%, about
25-30%, about 27.5-32.5%, about 30-35%, about 32.5-37.5%, or about
35-40% by weight of the composition. In some embodiments, the third
chromophore is present in an amount of about 0.0001-2%, about
0.001-1%, about 0.001-2%, about 0.001-0.01%, about 0.01-0.1%, about
0.1-1%, about 0.1-2%, about 1-2%, about 1-5%, about 2.5-7.5%, about
5-10%, about 7.5-12.5%, about 10-15%, about 12.5-17.5%, about
15-20%, about 17.5-22.5%, about 20-25%, about 22.5-27.5%, about
25-30%, about 27.5-32.5%, about 30-35%, about 32.5-37.5%, or about
35-40% by weight of the composition. In some embodiments, the total
weight by weight of the first chromophore or combination of
chromophores may be in the amount of about 0.005-1%, about
0.005-2%, about 0.01-2%, about 0.05-2%, about 0.1-1%, about 0.1-2%,
about 0.5-1%, about 0.5-2%, about 1-5%, about 2.5-7.5%, about
5-10%, about 7.5-12.5%, about 10-15%, about 12.5-17.5%, about
15-20%, about 17.5-22.5%, about 20-25%, about 22.5-27.5%, about
25-30%, about 27.5-32.5%, about 30-35%, about 32.5-37.5%, or about
35-40% by weight of the composition. In some embodiments, the first
chromophore or combination of chromophores is present in an amount
of at least about 0.2% by weight of the composition.
[0154] In some embodiments, when the biophotonic topical
composition comprises a first, a second chromophore, and a third
chromophore, the first chromophore is present in an amount of
0.005-40% by weight of the composition, the second chromophore is
present in an amount of 0.0001-40% by weight of the composition,
and the third chromophore is present in an amount of 0.0001-40% by
weight of the composition. In some embodiments, the total weight by
weight of chromophore or combination of chromophores may be in the
amount of 0.005-40% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of
0.005-1%, 0.005-2%, 0.01-2%, 0.02-1%, 0.02-2%, 0.05-1%, 0.05-2%,
0.05-1%, 0.1-1%, 0.1-2%, 0.05-2%, 1-5%, 2.5-7.5%, 5-10%, 7.5-12.5%,
10-15%, 12.5-17.5%, 15-20%, 17.5-22.5%, 20-25%, 22.5-27.5%, 25-30%,
27.5-32.5%, 30-35%, 32.5-37.5%, or 35-40% by weight of the
composition. In some embodiments, the second chromophore is present
in an amount of 0.0001-2%, 0.001-1%, 0.001-2%, 0.001-0.01%,
0.01-0.1%, 0.1-1%, 0.1-2%, 1-2%, 1-5%, 2.5-7.5%, 5-10%, 7.5-12.5%,
10-15%, 12.5-17.5%, 15-20%, 17.5-22.5%, 20-25%, 22.5-27.5%, 25-30%,
27.5-32.5%, 30-35%, 32.5-37.5%, or 35-40% by weight of the
composition. In some embodiments, the third chromophore is present
in an amount of 0.0001-2%, 0.001-1%, 0.001-2%, 0.001-0.01%,
0.01-0.1%, 0.1-1%, 0.1-2%, 1-2%, 1-5%, 2.5-7.5%, 5-10%, 7.5-12.5%,
10-15%, 12.5-17.5%, 15-20%, 17.5-22.5%, 20-25%, 22.5-27.5%, 25-30%,
27.5-32.5%, 30-35%, 32.5-37.5%, or 35-40% by weight of the
composition. In some embodiments, the total weight by weight of
chromophore or combination of chromophores may be in the amount of
0.005-1%, 0.005-2%, 0.01-2%, 0.05-2%, 0.1-1%, 0.1-2%, 0.5-1%,
0.5-2%, 1-5%, 2.5-7.5%, 5-10%, 7.5-12.5%, 10-15%, 12.5-17.5%,
15-20%, 17.5-22.5%, 20-25%, 22.5-27.5%, 25-30%, 27.5-32.5%, 30-35%,
32.5-37.5%, or 35-40% by weight of the composition.
[0155] In some embodiments, the chromophore or chromophores are
selected such that their emitted fluorescent light, upon
photoactivation, is within one or more of the green, yellow,
orange, red and infrared portions of the electromagnetic spectrum,
for example having a peak wavelength within the range of about 490
nm to about 800 nm. In some embodiments, the emitted fluorescent
light has a power density of between 0.005 to about 10 mW/cm.sup.2,
about 0.5 to about 5 mW/cm.sup.2.
[0156] Suitable chromophores useful in the biophotonic topical
compositions of the present disclosure include, but are not limited
to the following:
Chlorophyll dyes
[0157] Exemplary chlorophyll dyes include but are not limited to
chlorophyll a; chlorophyll b; oil soluble chlorophyll;
bacteriochlorophyll a; bacteriochlorophyll b; bacteriochlorophyll
c; bacteriochlorophyll d; protochlorophyll; protochlorophyll a;
amphiphilic chlorophyll derivative 1; and amphiphilic chlorophyll
derivative 2.
Xanthene derivatives
[0158] Exemplary xanthene dyes include but are not limited to Eosin
B (4',5'-dibromo,2',7'-dinitr- o-fluorescein, dianion); eosin Y;
eosin Y (2',4',5',7'-tetrabromo-fluorescein, dianion); eosin
(2',4',5',7'-tetrabromo-fluorescein, dianion); eosin
(2',4',5',7'-tetrabromo-fluorescein, dianion) methyl ester; eosin
(2',4',5',7'-tetrabromo-fluorescein, monoanion) p-isopropylbenzyl
ester; eosin derivative (2',7'-dibromo-fluorescein, dianion); eosin
derivative (4',5'-dibromo-fluorescein, dianion); eosin derivative
(2',7'-dichloro-fluorescein, dianion); eosin derivative
(4',5'-dichloro-fluorescein, dianion); eosin derivative
(2',7'-diiodo-fluorescein, dianion); eosin derivative
(4',5'-diiodo-fluorescein, dianion); eosin derivative
(tribromo-fluorescein, dianion); eosin derivative
(2',4',5',7'-tetrachloro-fluorescein, dianion); eosin; eosin
dicetylpyridinium chloride ion pair; erythrosin B
(2',4',5',7'-tetraiodo-fluorescein, dianion); erythrosin;
erythrosin dianion; erythiosin B; fluorescein; fluorescein dianion;
phloxin B (2',4',5',7'-tetrabromo-3,4,5,6-tetrachloro-fluorescein,
dianion); phloxin B (tetrachloro-tetrabromo-fluorescein); phloxine
B; rose bengal
(3,4,5,6-tetrachloro-2',4',5',7'-tetraiodofluorescein, dianion);
pyronin G, pyronin J, pyronin Y; Rhodamine dyes such as rhodamines
include 4,5-dibromo-rhodamine methyl ester; 4,5-dibromo-rhodamine
n-butyl ester; rhodamine 101 methyl ester; rhodamine 123; rhodamine
6G; rhodamine 6G hexyl ester; tetrabromo-rhodamine 123; and
tetramethyl-rhodamine ethyl ester.
Methylene Blue Dyes
[0159] Exemplary methylene blue derivatives include but are not
limited to 1-methyl methylene blue; 1,9-dimethyl methylene blue;
methylene blue; methylene blue (16 .mu.M); methylene blue (14
.mu.M); methylene violet; bromomethylene violet; 4-iodomethylene
violet;
1,9-dimethyl-3-dimethyl-amino-7-diethyl-amino-phenothiazine; and
1,9-dimethyl-3-diethylamino-7-dibutyl-amino-phenothiazine.
Azo Dyes
[0160] Exemplary azo (or diazo-) dyes include but are not limited
to methyl violet, neutral red, para red (pigment red 1), amaranth
(Azorubine S), Carmoisine (azorubine, food red 3, acid red 14),
allura red AC (FD&C 40), tartrazine (FD&C Yellow 5), orange
G (acid orange 10), Ponceau 4R (food red 7), methyl red (acid red
2), and murexide-ammonium purpurate.
[0161] In some aspects of the disclosure, the one or more
chromophores of the biophotonic composition disclosed herein can be
independently selected from any of Acid black 1, Acid blue 22, Acid
blue 93, Acid fuchsin, Acid green, Acid green 1, Acid green 5, Acid
magenta,
[0162] Acid orange 10, Acid red 26, Acid red 29, Acid red 44, Acid
red 51, Acid red 66, Acid red 87, Acid red 91, Acid red 92, Acid
red 94, Acid red 101, Acid red 103, Acid roseine, Acid rubin, Acid
violet 19, Acid yellow 1, Acid yellow 9, Acid yellow 23, Acid
yellow 24, Acid yellow 36, Acid yellow 73, Acid yellow S, Acridine
orange, Acriflavine, Alcian blue, Alcian yellow, Alcohol soluble
eosin, Alizarin, Alizarin blue 2RC, Alizarin carmine, Alizarin
cyanin BBS, Alizarol cyanin R, Alizarin red S, Alizarin purpurin,
Aluminon, Amido black 10B, Amidoschwarz, Aniline blue WS,
Anthracene blue SWR, Auramine 0, Azocannine B, Azocarmine G, Azoic
diazo 5, Azoic diazo 48, Azure A, Azure B, Azure C, Basic blue 8,
Basic blue 9, Basic blue 12, Basic blue 15, Basic blue 17, Basic
blue 20, Basic blue 26, Basic brown 1, Basic fuchsin, Basic green
4, Basic orange 14, Basic red 2 (Saffranin 0), Basic red 5, Basic
red 9, Basic violet 2, Basic violet 3, Basic violet 4, Basic violet
10, Basic violet 14, Basic yellow 1, Basic yellow 2, Biebrich
scarlet, Bismarck brown Y, Brilliant crystal scarlet 6R, Calcium
red, Carmine, Carminic acid (acid red 4), Celestine blue B, China
blue, Cochineal, Coelestine blue, Chrome violet CG, Chromotrope 2R,
Chromoxane cyanin R, Congo corinth, Congo red, Cotton blue, Cotton
red, Croceine scarlet, Crocin, Crystal ponceau 6R, Crystal violet,
Dahlia, Diamond green B, Di0C6, Direct blue 14, Direct blue 58,
Direct red, Direct red 10, Direct red 28, Direct red 80, Direct
yellow 7, Eosin B, Eosin Bluish, Eosin, Eosin Y, Eosin yellowish,
Eosinol, Erie garnet B, Eriochrome cyanin R, Erythrosin B, Ethyl
eosin, Ethyl green, Ethyl violet, Evans blue, Fast blue B, Fast
green FCF, Fast red B, Fast yellow, Fluorescein, Food green 3,
Gallein, Gallamine blue, Gallocyanin, Gentian violet,
[0163] Haematein, Haematine, Haematoxylin, Helio fast rubin BBL,
Helvetia blue, Hematein, Hematine, Hematoxylin, Hoffman's violet,
Imperial red, Indocyanin green, Ingrain blue, Ingrain blue 1,
Ingrain yellow 1, INT, Kermes, Kermesic acid, Kernechtrot, Lac,
Laccaic acid, Lauth's violet, Light green, Lissamine green SF,
Luxol fast blue, Magenta 0, Magenta I, Magenta II, Magenta III,
Malachite green, Manchester brown, Martius yellow, Merbromin,
Mercurochrome, Metanil yellow, Methylene azure A, Methylene azure
B, Methylene azure C, Methylene blue, Methyl blue, Methyl green,
Methyl violet, Methyl violet 2B, Methyl violet 10B, Mordant blue 3,
Mordant blue 10, Mordant blue 14, Mordant blue 23, Mordant blue 32,
Mordant blue 45, Mordant red 3, Mordant red 11, Mordant violet 25,
Mordant violet 39 Naphthol blue black, Naphthol green B, Naphthol
yellow S, Natural black 1, Natural red, Natural red 3, Natural red
4, Natural red 8, Natural red 16, Natural red 25, Natural red 28,
Natural yellow 6, NBT, Neutral red, New fuchsin, Niagara blue 3B,
Night blue, Nile blue, Nile blue A, Nile blue oxazone, Nile blue
sulphate, Nile red, Nitro BT, Nitro blue tetrazolium, Nuclear fast
red, Oil red 0, Orange G, Orcein, Pararosanilin, Phloxine B,
phycobilins, Phycocyanins, Phycoerythrins. Phycoerythrincyanin
(PEC), Phthalocyanines, Picric acid, Ponceau 2R, Ponceau 6R,
Ponceau B, Ponceau de Xylidine, Ponceau S, Primula, Purpurin,
Pyronin B, Pyronin G, Pyronin Y, Rhodamine B, Rosanilin, Rose
bengal, Saffron, Safranin O, Scarlet R, Scarlet red, Scharlach R,
Shellac, Sirius red F3B, Solochrome cyanin R, Soluble blue, Solvent
black 3, Solvent blue 38, Solvent red 23, Solvent red 24, Solvent
red 27, Solvent red 45, Solvent yellow 94, Spirit soluble eosin,
Sudan III, Sudan IV, Sudan black B, Sulfur yellow S, Swiss blue,
Tartrazine, Thioflavine S, Thioflavine T, Thionin, Toluidine blue,
Toluyline red, Tropaeolin G, Trypaflavine, Trypan blue, Uranin,
Victoria blue 4R, Victoria blue B, Victoria green B, Water blue I,
Water soluble eosin, Xylidine ponceau, or Yellowish eosin.
[0164] In some embodiments, the composition of the present
disclosure includes any of the chromophores listed above, or a
combination thereof, so as to provide a biophotonic impact at the
application site. This is a distinct application of these agents
and differs from the use of chromophores as simple stains or as a
catalyst for photo-polymerization.
[0165] Chromophores can be selected, for example, on their emission
wavelength properties in the case of fluorophores, on the basis of
their energy transfer potential, their ability to generate reactive
oxygen species, or their antimicrobial effect. These needs may vary
depending on the condition requiring treatment. For example,
chlorophylls may have an antimicrobial effect on bacteria found on
the face.
[0166] In some embodiments, the composition includes Eosin Y as a
first chromophore. In some embodiments, the composition includes
Eosin Y as a first chromophore and any one or more of Rose Bengal,
Erythrosin, Phloxine B as a second chromophore. It is believed that
these combinations have a synergistic effect as Eosin Y can
transfer energy to Rose Bengal, Erythrosin or Phloxine B when
activated. This transferred energy is then emitted as fluorescence
or by production of reactive oxygen species. This absorbed and
re-emitted light is thought to be transmitted throughout the
composition, and also to be transmitted into the site of
treatment.
[0167] In some embodiments, the composition includes the following
synergistic combinations: Eosin Y and Fluorescein; Fluorescein and
Rose Bengal; Erythrosine in combination with Eosin Y, Rose Bengal
or Fluorescein; Phloxine B in combination with one or more of Eosin
Y, Rose Bengal, Fluorescein and Erythrosine. Other synergistic
chromophore combinations are also possible.
[0168] By means of synergistic effects of the chromophore
combinations in the composition, chromophores which cannot normally
be activated by an activating light (such as a blue light from an
LED) can be activated through energy transfer from chromophores
which are activated by the activating light. In this way, the
different properties of photoactivated chromophores can be
harnessed and tailored according to the cosmetic or the medical
therapy required.
[0169] For example, Rose Bengal can generate a high yield of
singlet oxygen when photoactivated in the presence of molecular
oxygen, however it has a low quantum yield in terms of emitted
fluorescent light. Rose Bengal has a peak absorption around 540 nm
and so is normally activated by green light. Eosin Y has a high
quantum yield and can be activated by blue light. By combining Rose
Bengal with Eosin Y, one obtains a composition which can emit
therapeutic fluorescent light and generate singlet oxygen when
activated by blue light. In this case, the blue light
photoactivates Eosin Y which transfers some of its energy to Rose
Bengal as well as emitting some energy as fluorescence.
[0170] Chromophore combinations can also have a synergistic effect
in terms of their photoactivated state. For example, two
chromophores may be used, one of which emits fluorescent light when
activated in the blue and green range, and the other which emits
fluorescent light in the red, orange and yellow range, thereby
complementing each other and irradiating the target tissue with a
broad wavelength of light having different depths of penetration
into target tissue and different therapeutic effects.
(b) Gelling Agent
[0171] The biophotonic topical compositions of the present
disclosure comprise one or more gelling agents. In some
embodiments, the disclosure provides biophotonic compositions that
comprise at least a first chromophore; one or more salts selected
from bicarbonate salts, carbonate salts or a combination of the
foregoing salts; and one or more gelling agents. In some
embodiments the disclosure provides biophotonic compositions that
comprise at least a first chromophore; one or more salts selected
from bicarbonate salts, carbonate salts or a combination of the
foregoing salts; one or more polyols, and one or more gelling
agents. In some embodiments the disclosure provides biophotonic
compositions that comprise at least a first chromophore, one or
more polyols, and one or more gelling agents.
[0172] A gelling agent for use according to the present disclosure
may comprise any ingredient suitable for use in a topical
biophotonic formulation as described herein. The gelling agent may
be an agent capable of forming a cross-linked matrix, including
physical and/or chemical cross-links. The gelling agent can be
biocompatible, and may be biodegradable. In some embodiments, the
gelling agent is able to form a hydrogel or a hydrocolloid. An
appropriate gelling agent is one that can form a viscous liquid or
a semisolid. In some embodiments, the gelling agent and/or the
composition has appropriate light transmission properties. It is
also important to select a gelling agent which will allow
biophotonic activity of the chromophore(s). For example, some
chromophores require a hydrated environment in order to fluoresce.
The gelling agent may be able to form a gel by itself or in
combination with other ingredients such as water or another gelling
agent, or when applied to a treatment site, or when illuminated
with light.
[0173] The gelling agent of the present disclosure may include, but
not be limited to, polyalkylene oxides, particularly polyethylene
glycol and poly(ethylene oxide)-poly(propylene oxide) copolymers,
including block and random copolymers; polyols such as glycerol,
polyglycerol (particularly highly branched polyglycerol), propylene
glycol and trimethylene glycol substituted with one or more
polyalkylene oxides, e.g., mono-, di- and tri-polyoxyethylated
glycerol, mono- and di-polyoxy-ethylated propylene glycol, and
mono- and di-polyoxyethylated trimethylene glycol; polyoxyethylated
sorbitol, polyoxyethylated glucose; acrylic acid polymers and
analogs and copolymers thereof, such as polyacrylic acid per se,
polymethacrylic acid, poly(hydroxyethylmethacrylate),
poly(hydroxyethylacrylate), poly(methylalkylsulfoxide
methacrylate), poly(methylalkylsulfoxide acrylate) and copolymers
of any of the foregoing, and/or with additional acrylate species
such as aminoethyl acrylate and mono-2-(acryloxy)-ethyl succinate;
polymaleic acid; poly(acrylamides) such as polyacrylamide per se,
poly(methacrylamide), poly(dimethylacrylamide), and
poly(N-isopropyl-acrylamide); poly(olefinic alcohol)s such as
poly(vinyl alcohol); poly(N-vinyl lactams) such as poly(vinyl
pyrrolidone), poly(N-vinyl caprolactam), and copolymers thereof,
polyoxazolines, including poly(methyloxazoline) and
poly(ethyloxazoline); silicones, polyvinyl silicates,
tetramethoxyorthosilicates, methyltrimethoxyorthosilicates,
tetraalkoxyorthosilicates, trialkoxyorthosilicates, pressure
sensitive silicone adhesives (such as BioPSA from Dow-Corning), and
polyvinylamines.
[0174] The gelling agent of the present disclosure may include a
polymer selected from any of synthetic or semi-synthetic polymeric
materials, polyacrylate copolymers, cellulose derivatives and
polymethyl vinyl ether/maleic anhydride copolymers. In some
embodiments, the hydrophilic polymer comprises a polymer that is a
high molecular weight (i.e., molar masses of more than about 5,000,
and in some instances, more than about 10,000, or about 100,000, or
about 1,000,000) and/or cross-linked polyacrylic acid polymer.
[0175] In some embodiments, the one or more gelling agents comprise
about 0.01-20% by weight of the biophotonic composition. In some
embodiments, the one or more gelling agents are present in an
amount of about 0.01-10% by weight of the biophotonic composition.
In some embodiments, the one or more gelling agents are present in
an amount of about 0.01-5% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of about 0.01-2% by weight of the
biophotonic composition. In some embodiments, the one or more
gelling agents are present in an amount of about 0.01-1% by weight
of the biophotonic composition. In some embodiments, the one or
more gelling agents are present in an amount of about 0.05-20% by
weight of the biophotonic composition. In some embodiments, the one
or more gelling agents are present in an amount of about 0.05-10%
by weight of the biophotonic composition. In some embodiments, the
one or more gelling agents are present in an amount of about
0.05-5% by weight of the biophotonic composition. In some
embodiments, the one or more gelling agents are present in an
amount of about 0.05-2% by weight of the biophotonic composition.
In some embodiments, the one or more gelling agents are present in
an amount of about 0.05-1% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of about 0.1-20% by weight of the
biophotonic composition. In some embodiments, the one or more
gelling agents are present in an amount of about 0.1-10% by weight
of the biophotonic composition. In some embodiments, the one or
more gelling agents are present in an amount of about 0.1-5% by
weight of the biophotonic composition. In some embodiments, the one
or more gelling agents are present in an amount of about 0.1-2% by
weight of the biophotonic composition. In some embodiments, the one
or more gelling agents comprise are present in an amount of 0.5-20%
by weight of the biophotonic composition. In some embodiments, the
one or more gelling agents are present in an amount of about
0.5-10% by weight of the biophotonic composition. In some
embodiments, the one or more gelling agents are present in an
amount of about 0.5-5% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 0.5-2% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 0.5-1% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 1-20% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 1-10% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 1-5% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 1-4% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 1-3% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 1-2% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 1.5-2% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 5-20% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 10-20% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 15-20% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 5-10% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 1% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 1.25% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 1.5% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 1.75% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 2% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 2.5% by weight of the biophotonic composition. In
some embodiments, the one or more gelling agents are present in an
amount of about 3% by weight of the biophotonic composition.
[0176] In some embodiments, the one or more gelling agents are
present in an amount of 0.01-20% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.01-10% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.01-5% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.01-2% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.01-1% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.05-20% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.05-10% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.05-5% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.05-2% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.05-1% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.1-20% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.1-10% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.1-5% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.1-2% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.5-20% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.5-10% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.5-5% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.5-2% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 0.5-1% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 1-20% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 1-10% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 1-5% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 1-4% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 1-3% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 1-2% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 1.5-2% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 5-20% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
are present in an amount of 10-20% by weight of the biophotonic
composition. In some embodiments, the one or more gelling agents
comprise are present in an amount of 15-20% by weight of the
biophotonic composition. In some embodiments, the one or more
gelling agents are present in an amount of 5-10% by weight of the
biophotonic composition. In some embodiments, the one or more
gelling agents are present in an amount of 1% by weight of the
biophotonic composition. In some embodiments, the one or more
gelling agents are present in an amount of 1.25% by weight of the
biophotonic composition. In some embodiments, the one or more
gelling agents are present in an amount of 1.5% by weight of the
biophotonic composition. In some embodiments, the one or more
gelling agents are present in an amount of 1.75% by weight of the
biophotonic composition. In some embodiments, the one or more
gelling agents are present in an amount of 2% by weight of the
biophotonic composition. In some embodiments, the one or more
gelling agents are present in an amount of 2.5% by weight of the
biophotonic composition. In some embodiments, the one or more
gelling agents are present in an amount of 3% by weight of the
biophotonic composition.
[0177] In some embodiments, the gelling agent comprises a carbomer.
Carbomers are synthetic high molecular weight polymer of acrylic
acid that are cross-linked with either allylsucrose or allylethers
of pentaerythritol having a molecular weight of about
3.times.10.sup.6. The gelation mechanism depends on neutralization
of the carboxylic acid moiety to form a soluble salt. The polymer
is hydrophilic and produces sparkling clear gels when neutralized.
Carbomer gels possess good thermal stability in that gel viscosity
and yield value are essentially unaffected by temperature. As a
topical product, carbomer gels possess optimum rheological
properties. The inherent pseudoplastic flow permits immediate
recovery of viscosity when shear is terminated and the high yield
value and quick break make it ideal for dispensing. Aqueous
solution of Carbopol.RTM. is acidic in nature due to the presence
of free carboxylic acid residues. Neutralization of this solution
cross-links and gelatinizes the polymer to form a viscous integral
structure of desired viscosity.
[0178] In some embodiments, the carbomer is present in an amount of
about 0.01-10% by weight of the biophotonic composition. In some
embodiments, the carbomer is present in an amount of about 0.01-5%
by weight of the biophotonic composition. In some embodiments, the
carbomer is present in an amount of about 0.01-2% by weight of the
biophotonic composition. In some embodiments, the carbomer is
present in an amount of about 0.01-1% by weight of the biophotonic
composition. In some embodiments, the carbomer is present in an
amount of about 0.05-10% by weight of the biophotonic composition.
In some embodiments, the carbomer is present in an amount of about
0.05-5% by weight of the biophotonic composition. In some
embodiments, the carbomer is present in an amount of about 0.05-2%
by weight of the biophotonic composition. In some embodiments, the
carbomer is present in an amount of about 0.05-1% by weight of the
biophotonic composition. In some embodiments, the carbomer is
present in an amount of about 0.1-10% by weight of the biophotonic
composition. In some embodiments, the carbomer is present in an
amount of about 0.1-5% by weight of the biophotonic composition. In
some embodiments, the carbomer is present in an amount of about
0.1-2% by weight of the biophotonic composition. In some
embodiments, the carbomer is present in an amount of about 0.1-1%
by weight of the biophotonic composition. In some embodiments, the
carbomer is present in an amount of about 0.5-10% by weight of the
biophotonic composition. In some embodiments, the carbomer is
present in an amount of about 0.5-5% by weight of the biophotonic
composition. In some embodiments, the carbomer is present in an
amount of about 0.5-2% by weight of the biophotonic composition. In
some embodiments, the carbomer is present in an amount of about
0.5-1% by weight of the biophotonic composition. In some
embodiments, the carbomer is present in an amount of about 1-5% by
weight of the biophotonic composition. In some embodiments, the
carbomer is present in an amount of about 1-4% by weight of the
biophotonic composition. In some embodiments, the carbomer is
present in an amount of about 1-3% by weight of the biophotonic
composition. In some embodiments, the carbomer is present in an
amount of about 1-2% by weight of the biophotonic composition. In
some embodiments, the carbomer is present in an amount of about
1.5-2% by weight of the biophotonic composition. In some
embodiments, the carbomer is present in an amount of about 1% by
weight of the biophotonic composition. In some embodiments, the
carbomer is present in an amount of about 1.25% by weight of the
biophotonic composition. In some embodiments, the carbomer is
present in an amount of about 1.5% by weight of the biophotonic
composition. In some embodiments, the carbomer is present in an
amount of about 1.75% by weight of the biophotonic composition. In
some embodiments, the carbomer is present in an amount of about 2%
by weight of the biophotonic composition. In some embodiments, the
carbomer is present in an amount of about 2.5% by weight of the
biophotonic composition. In some embodiments, the carbomer is
present in an amount of about 3% by weight of the biophotonic
composition.
[0179] In some embodiments, the carbomer is present in an amount of
0.01-10% by weight of the biophotonic composition. In some
embodiments, the carbomer is present in an amount of 0.01-5% by
weight of the biophotonic composition. In some embodiments, the
carbomer is present in an amount of 0.01-2% by weight of the
biophotonic composition. In some embodiments, the carbomer is
present in an amount of 0.01-1% by weight of the biophotonic
composition. In some embodiments, the carbomer is present in an
amount of 0.05-10% by weight of the biophotonic composition. In
some embodiments, the carbomer is present in an amount of 0.05-5%
by weight of the biophotonic composition. In some embodiments, the
carbomer is present in an amount of 0.05-2% by weight of the
biophotonic composition. In some embodiments, the carbomer is
present in an amount of 0.05-1% by weight of the biophotonic
composition. In some embodiments, the carbomer is present in an
amount of 0.1-10% by weight of the biophotonic composition. In some
embodiments, the carbomer is present in an amount of 0.1-5% by
weight of the biophotonic composition. In some embodiments, the
carbomer is present in an amount of 0.1-2% by weight of the
biophotonic composition. In some embodiments, the carbomer is
present in an amount of 0.1-1% by weight of the biophotonic
composition. In some embodiments, the carbomer is present in an
amount of 0.5-10% by weight of the biophotonic composition. In some
embodiments, the carbomer is present in an amount of 0.5-5% by
weight of the biophotonic composition. In some embodiments, the
carbomer is present in an amount of 0.5-2% by weight of the
biophotonic composition. In some embodiments, the carbomer is
present in an amount of 0.5-1% by weight of the biophotonic
composition. In some embodiments, the carbomer is present in an
amount of 1-5% by weight of the biophotonic composition. In some
embodiments, the carbomer is present in an amount of 1-4% by weight
of the biophotonic composition. In some embodiments, the carbomer
is present in an amount of 1-3% by weight of the biophotonic
composition. In some embodiments, the carbomer is present in an
amount of 1-2% by weight of the biophotonic composition. In some
embodiments, the carbomer is present in an amount of 1.5-2% by
weight of the biophotonic composition. In some embodiments, the
carbomer is present in an amount of 1% by weight of the biophotonic
composition. In some embodiments, the carbomer is present in an
amount of 1.25% by weight of the biophotonic composition. In some
embodiments, the carbomer is present in an amount of 1.5% by weight
of the biophotonic composition. In some embodiments, the carbomer
is present in an amount of 1.75% by weight of the biophotonic
composition. In some embodiments, the carbomer is present in an
amount of 2% by weight of the biophotonic composition. In some
embodiments, the carbomer is present in an amount of 2.5% by weight
of the biophotonic composition. In some embodiments, the carbomer
is present in an amount of 3% by weight of the biophotonic
composition.
[0180] Carbomers are available as fine white powders which disperse
in water to form acidic colloidal suspensions (a 1% dispersion has
approx. pH 3) of low viscosity. Neutralization of these suspensions
using a base, for example sodium, potassium or ammonium hydroxides,
low molecular weight amines and alkanolamines, results in the
formation of translucent gels. Nicotine salts such as nicotine
chloride form stable water-soluble complexes with carbomers at
about pH 3.5 and are stabilized at an optimal pH of about 5.6.
[0181] In some embodiments, the carbomer is Carbopol. Such polymers
are commercially available from B.F. Goodrich or Lubrizol under the
designation Carbopol.RTM. 71G NF, 420, 430, 475, 488, 493, 910,
934, 934P, 940, 971PNF, 974P NF, 980 NF, 981 NF and the like.
Carbopols are versatile controlled-release polymers, as described
by Brock (Pharmacotherapy, 14:430-7 (1994)) and Durrani
(Pharmaceutical Res. (Supp.) 8:S-135 (1991)), and belong to a
family of carbomers which are synthetic, high molecular weight,
non-linear polymers of acrylic acid, crosslinked with polyalkenyl
polyether. In some embodiments, the carbomer is Carbopol.RTM. 974P
NF, 980 NF, 5984 EP, ETD 2020NF, Ultrez 10 NF, 934 NF, 934P NF or
940 NF. In some embodiments, the carbomer is Carbopol.RTM. 980 NF,
ETD 2020 NF, Ultrez 10 NF, Ultrez 21 or 1382 Polymer, 1342 NF, 940
NF. For example, about 0.05 to 10%, about 0.5 to 5%, or about 1 to
3% by weight of the final composition of a high molecular weight
carbopol can be present as the gelling agent. In some embodiments,
the biophotonic composition of the disclosure comprises 0.05 to
10%, about 0.5 to 5%, or about 1 to 3% by weight of the final
composition of a high molecular weight carbopol.
[0182] In some embodiments, the high molecular weight carbopol is
present in an amount of less than about 1.5% by weight of the total
composition. In some embodiments, the high molecular weight
carbopol is present in an amount of about 1.5-3% by weight of the
total composition. In some embodiments, the high molecular weight
carbopol is present in an amount of about 1.5-2.5% by weight of the
total composition. In some embodiments, the high molecular weight
carbopol is present in an amount of about 1.5-2% by weight of the
total composition. In some embodiments, the high molecular weight
carbopol is present in an amount of about 1% by weight of the total
composition. In some embodiments, the high molecular weight
carbopol is present in an amount of about 1.25% by weight of the
total composition. In some embodiments, the high molecular weight
carbopol is present in an amount of about 1.5% by weight of the
total composition. In some embodiments, the high molecular weight
carbopol is present in an amount of about 1.75% by weight of the
total composition. In some embodiments, the high molecular weight
carbopol is present in an amount of about 2% by weight of the total
composition. In some embodiments, the high molecular weight
carbopol is present in an amount of about 2.5% by weight of the
total composition. In some embodiments, the high molecular weight
carbopol is present in an amount of about 3% by weight of the total
composition.
[0183] In some embodiments, the high molecular weight carbopol is
present in an amount of less than 1.5% by weight of the total
composition. In some embodiments, the high molecular weight
carbopol is present in an amount of 1.5-3% by weight of the total
composition. In some embodiments, the high molecular weight
carbopol is present in an amount of 1.5-2.5% by weight of the total
composition. In some embodiments, the high molecular weight
carbopol is present in an amount of 1.5-2% by weight of the total
composition. In some embodiments, the high molecular weight
carbopol is present in an amount of 1% by weight of the total
composition. In some embodiments, the high molecular weight
carbopol is present in an amount of 1.25% by weight of the total
composition. In some embodiments, the high molecular weight
carbopol is present in an amount of 1.5% by weight of the total
composition. In some embodiments, the high molecular weight
carbopol is present in an amount of 1.75% by weight of the total
composition. In some embodiments, the high molecular weight
carbopol is present in an amount of 2% by weight of the total
composition.
[0184] In some embodiments, the high molecular weight carbopol is
present in an amount of 2.5% by weight of the total composition. In
some embodiments, the high molecular weight carbopol is present in
an amount of 3% by weight of the total composition.
[0185] In some embodiments, the gelling agent comprises a
hygroscopic and/or a hydrophilic material useful for their water
attracting properties. The hygroscopic or hydrophilic material may
include, but is not limited to, glucosamine, glucosamine sulfate,
polysaccharides, cellulose derivatives (hydroxypropyl
methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose,
methylcellulose and the like), noncellulose polysaccharides
(galactomannans, guar gum, carob gum, gum arabic, sterculia gum,
agar, alginates and the like), glycosaminoglycan, poly(vinyl
alcohol), poly(2-hydroxyethylmethylacrylate), polyethylene oxide,
collagen, chitosan, alginate, a poly(acrylonitrile)-based hydrogel,
poly(ethylene glycol)/poly(acrylic acid) interpenetrating polymer
network hydrogel, polyethylene oxide-polybutylene terephthalate,
hyaluronic acid, high-molecular-weight polyacrylic acid,
poly(hydroxy ethylmethacrylate), poly(ethylene glycol),
tetraethylene glycol diacrylate, polyethylene glycol methacrylate,
and poly(methyl acrylate-co-hydroxyethyl acrylate).
[0186] The gelling agent may be protein-based/naturally derived
material such as sodium hyaluronate, gelatin or collagen, lipids,
or the like. The gelling agent may be a polysaccharide such as
starch, chitosan, chitin, agarose, agar, locust bean gum,
carrageenan, gellan gum, pectin, alginate, xanthan, guar gum, and
the like.
[0187] In some embodiments, the composition can include up to about
2% by weight of the final composition of sodium hyaluronate as the
single gelling agent. In some embodiments, the composition can
include more than about 4%, more than about 5%, by weight of the
final composition of gelatin as the single gelling agent. In some
embodiments, the composition can include up to about 10%, up to
about 8%, starch as the single gelling agent. In some embodiments,
the composition can include more than about 5%, more than about
10%, by weight of the final composition of collagen as the gelling
agent. In some embodiments, about 0.1 to about 10%, or about 0.5 to
about 3%, by weight of the final composition of chitin can be used
as the gelling agent. In some embodiments, about 0.5% to about 5%
by weight of the final composition of corn starch, or about 5 to
about 10% by weight of the final composition of starch can be used
as the gelling agent. In some embodiments, more than about 2.5wt%
by weight of the final composition of alginate can be used in the
composition as the gelling agent. In some embodiments, the
percentages by weight percent of the final composition of the
gelling agents can be as follows: cellulose gel (about 0.3 to about
2.0%), konjac gum (about 0.5 to about 0.7%), carrageenan gum (about
0.02 to about 2.0%), xanthan gum (about 0.01 to about 2.0%), acacia
gum (about 3 to about 30%), agar (about 0.04 to about 1.2%), guar
gum (about 0.1 to about 1%), locust bean gum (about 0.15 to about
0.75%), pectin (about 0.1 to about 0.6%), tara gum (about 0.1 to
about 1.0%), polyvinylypyrrolidone (about 1 to about 5%), sodium
polyacrylate (about 1 to about 10%). Other gelling agents can be
used in amounts sufficient to gel the composition or to
sufficiently thicken the composition. It will be appreciated that
lower amounts of the above gelling agents may be used in the
presence of another gelling agent or a thickener.
[0188] The biophotonic composition of the present disclosure may be
further encapsulated, e.g., in a membrane. Such a membrane may be
transparent, and/or substantially, or fully impermeable. The
membrane may be impermeable to liquid but permeable to gases such
as air. In some embodiments, the composition may form a membrane
that encapsulates the chromophore(s) of the biophotonic topical
composition, where the membrane may be substantially impermeable to
liquid and/or gas. The membrane may be formed of one or more
lipidic agents, polymers, gelatin, cellulose or cyclodextrins, or
the like. In some embodiments, the membrane is translucent or
transparent to allow light to infiltrate to and from the
chromophore(s). In some embodiments, the composition is a dendrimer
with an outer membrane comprising poly(propylene amine). In some
embodiments, the outer membrane comprises gelatin.
(c) Carbonate and Bicarbonate Salts
[0189] In some embodiments, the compositions of the present
disclosure may optionally further comprise one or more carbonate or
bicarbonate salts.
[0190] Suitable carbonate or bicarbonate salts that may be present
in the composition include, but are not limited to: ammonium
bicarbonate, caesium bicarbonate, potassium bicarbonate, sodium
bicarbonate, choline bicarbonate, aminoguanidine bicarbonate,
tetraethylammonium bicarbonate, barium carbonate, beryllium
carbonate, caesium carbonate, calcium carbonate, cobalt (II)
carbonate, copper (II) carbonate, lithium carbonate, magnesium
carbonate, nickel (II) carbonate, potassium carbonate, sodium
carbonate, or zinc carbonate.
[0191] In some embodiments, the biophotonic composition of the
disclosure comprises one or more salts selected from bicarbonate
salts, carbonate salts or a combination of the foregoing salts. In
some embodiments, the biophotonic composition of the disclosure
comprises one or more bicarbonate salts. In some embodiments when
the biophotonic composition comprises one or more bicarbonate
salts, the bicarbonate salt is sodium bicarbonate. In some
embodiments when the biophotonic composition comprises one or more
bicarbonate salts, the bicarbonate salt is potassium bicarbonate.
In some embodiments, the biophotonic composition of the disclosure
comprises one or more carbonate salts. In some embodiments when the
biophotonic composition comprises one or more carbonate salts, the
carbonate salt is sodium carbonate. In some embodiments when the
biophotonic composition comprises one or more carbonate salts, the
carbonate salt is potassium carbonate. In some embodiments when the
biophotonic composition comprises one or more carbonate salts, the
carbonate salt is calcium carbonate.
[0192] In some embodiments, the one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts are present in an amount of about 0.01-30% by
weight of the total composition. In some embodiments, the one or
more salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts are present in an amount of
about 0.01-20% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of about 0.01-10% by weight of the total composition.
In some embodiments, the one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts are present in an amount of about 0.01-5% by weight
of the total composition. In some embodiments, the one or more
salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts are present in an amount of
about 0.05-30% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of about 0.05-20% by weight of the total composition.
In some embodiments, the one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts are present in an amount of about 0.05-10% by
weight of the total composition. In some embodiments, the one or
more salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts are present in an amount of
about 0.05-5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of about 0.1-30% by weight of the total composition.
In some embodiments, the one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts are present in an amount of about 0.1-20% by weight
of the total composition. In some embodiments, the one or more
salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts are present in an amount of
about 0.1-10% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of about 0.1-5% by weight of the total composition. In
some embodiments, the one or more salts selected from bicarbonate
salts, carbonate salts or a combination of the foregoing salts are
present in an amount of about 0.5-30% by weight of the total
composition. In some embodiments, the one or more salts selected
from bicarbonate salts, carbonate salts or a combination of the
foregoing salts are present in an amount of about 0.5-20% by weight
of the total composition. In some embodiments, the one or more
salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts are present in an amount of
about 0.5-10% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of about 0.5-5% by weight of the total composition. In
some embodiments, the one or more salts selected from bicarbonate
salts, carbonate salts or a combination of the foregoing salts are
present in an amount of about 1-30% by weight of the total
composition. In some embodiments, the one or more salts selected
from bicarbonate salts, carbonate salts or a combination of the
foregoing salts are present in an amount of about 1-20% by weight
of the total composition. In some embodiments, the one or more
salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts are present in an amount of
about 1-10% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of about 5-30% by weight of the total composition. In
some embodiments, the one or more salts selected from bicarbonate
salts, carbonate salts or a combination of the foregoing salts are
present in an amount of about 5-20% by weight of the total
composition. In some embodiments, the one or more salts selected
from bicarbonate salts, carbonate salts or a combination of the
foregoing salts are present in an amount of about 5-10% by weight
of the total composition. In some embodiments, the one or more
salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts are present in an amount of
about 10-30% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of about 10-20% by weight of the total composition. In
some embodiments, the one or more salts selected from bicarbonate
salts, carbonate salts or a combination of the foregoing salts are
present in an amount of about 20-30% by weight of the total
composition. In some embodiments, the one or more salts selected
from bicarbonate salts, carbonate salts or a combination of the
foregoing salts are present in an amount of about 1-5% by weight of
the total composition. In some embodiments, the one or more salts
selected from bicarbonate salts, carbonate salts or a combination
of the foregoing salts are present in an amount of about 0.1% by
weight of the total composition. In some embodiments, the one or
more salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts are present in an amount of
about 0.2% by weight of the total composition. In some embodiments,
the one or more salts selected from bicarbonate salts, carbonate
salts or a combination of the foregoing salts are present in an
amount of about 0.3% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of about 0.4% by weight of the total composition. In
some embodiments, the one or more salts selected from bicarbonate
salts, carbonate salts or a combination of the foregoing salts are
present in an amount of about 0.5% by weight of the total
composition. In some embodiments, the one or more salts selected
from bicarbonate salts, carbonate salts or a combination of the
foregoing salts are present in an amount of about 1% by weight of
the total composition. In some embodiments, the one or more salts
selected from bicarbonate salts, carbonate salts or a combination
of the foregoing salts are present in an amount of about 1.5% by
weight of the total composition. In some embodiments, the one or
more salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts are present in an amount of
about 2% by weight of the total composition. In some embodiments,
the one or more salts selected from bicarbonate salts, carbonate
salts or a combination of the foregoing salts are present in an
amount of about 2.5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of about 3% by weight of the total composition. In
some embodiments, the one or more salts selected from bicarbonate
salts, carbonate salts or a combination of the foregoing salts are
present in an amount of about 3.5% by weight of the total
composition. In some embodiments, the one or more salts selected
from bicarbonate salts, carbonate salts or a combination of the
foregoing salts are present in an amount of about 4% by weight of
the total composition. In some embodiments, the one or more salts
selected from bicarbonate salts, carbonate salts or a combination
of the foregoing salts are present in an amount of about 4.5% by
weight of the total composition. In some embodiments, the one or
more salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts are present in an amount of
about 5% by weight of the total composition. In some embodiments,
the one or more salts selected from bicarbonate salts, carbonate
salts or a combination of the foregoing salts are present in an
amount of about 5.5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of about 6% by weight of the total composition. In
some embodiments, the one or more salts selected from bicarbonate
salts, carbonate salts or a combination of the foregoing salts are
present in an amount of about 6.5% by weight of the total
composition. In some embodiments, the one or more salts selected
from bicarbonate salts, carbonate salts or a combination of the
foregoing salts are present in an amount of about 7% by weight of
the total composition. In some embodiments, the one or more salts
selected from bicarbonate salts, carbonate salts or a combination
of the foregoing salts are present in an amount of about 7.5% by
weight of the total composition. In some embodiments, the one or
more salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts are present in an amount of
about 8% by weight of the total composition. In some embodiments,
the one or more salts selected from bicarbonate salts, carbonate
salts or a combination of the foregoing salts are present in an
amount of about 8.5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of about 9% by weight of the total composition. In
some embodiments, the one or more salts selected from bicarbonate
salts, carbonate salts or a combination of the foregoing salts are
present in an amount of about 9.5% by weight of the total
composition. In some embodiments, the one or more salts selected
from bicarbonate salts, carbonate salts or a combination of the
foregoing salts are present in an amount of about 10% by weight of
the total composition. In some embodiments, the one or more salts
selected from bicarbonate salts, carbonate salts or a combination
of the foregoing salts are present in an amount of about 12.5% by
weight of the total composition. In some embodiments, the one or
more salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts are present in an amount of
about 15% by weight of the total composition. In some embodiments,
the one or more salts selected from bicarbonate salts, carbonate
salts or a combination of the foregoing salts are present in an
amount of about 17.5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of about 20% by weight of the total composition.
[0193] In some embodiments, the one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts are present in an amount of 0.01-30% by weight of
the total composition. In some embodiments, the one or more salts
selected from bicarbonate salts, carbonate salts or a combination
of the foregoing salts are present in an amount of 0.01-20% by
weight of the total composition. In some embodiments, the one or
more salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts are present in an amount of
0.01-10% by weight of the total composition. In some embodiments,
the one or more salts selected from bicarbonate salts, carbonate
salts or a combination of the foregoing salts are present in an
amount of 0.01-5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 0.05-30% by weight of the total composition. In
some embodiments, the one or more salts selected from bicarbonate
salts, carbonate salts or a combination of the foregoing salts are
present in an amount of 0.05-20% by weight of the total
composition. In some embodiments, the one or more salts selected
from bicarbonate salts, carbonate salts or a combination of the
foregoing salts are present in an amount of 0.05-10% by weight of
the total composition. In some embodiments, the one or more salts
selected from bicarbonate salts, carbonate salts or a combination
of the foregoing salts are present in an amount of 0.05-5% by
weight of the total composition. In some embodiments, the one or
more salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts are present in an amount of
0.1-30% by weight of the total composition. In some embodiments,
the one or more salts selected from bicarbonate salts, carbonate
salts or a combination of the foregoing salts are present in an
amount of 0.1-20% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 0.1-10% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 0.1-5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 0.5-30% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 0.5-20% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 0.5-10% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 0.5-5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 1-30% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 1-20% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 1-10% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 5-30% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 5-20% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 5-10% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 10-30% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 10-20% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 20-30% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 1-5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 0.1% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 0.2% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 0.3% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 0.4% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 0.5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 1% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 1.5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 2% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 2.5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 3% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 3.5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 4% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 4.5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 5.5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 6% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 6.5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 7% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 7.5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 8% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 8.5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 9% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 9.5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 10% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 12.5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 15% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 17.5% by weight of the total composition. In some
embodiments, the one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts are present
in an amount of 20% by weight of the total composition.
[0194] In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.01-30% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.01-20% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.01-10% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.01-5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.05-30% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.05-20% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.05-10% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.05-5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.1-30% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.1-20% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.1-10% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.1-5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.5-30% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.5-20% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.5-10% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.5-5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 1-30% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 1-20% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 1-10% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 5-30% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 5-20% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 5-10% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 10-30% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 10-20% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 20-30% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 1-5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.1% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.2% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.3% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.4% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 0.5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 1% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 1.5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 2% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 2.5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 3% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 3.5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 4% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 4.5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 5.5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 6% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 6.5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 7% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 7.5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 8% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 8.5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 9% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 9.5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 10% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 12.5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 15% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 17.5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of about 20% by weight of the total
composition.
[0195] In some embodiments, one or more bicarbonate salts are
present in an amount of 0.01-30% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of 0.01-20% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of 0.01-10% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of 0.01-5% by weight of the total composition.
In some embodiments, one or more bicarbonate salts are present in
an amount of 0.05-30% by weight of the total composition. In some
embodiments, one or more bicarbonate salts are present in an amount
of 0.05-20% by weight of the total composition. In some
embodiments, one or more bicarbonate salts are present in an amount
of 0.05-10% by weight of the total composition. In some
embodiments, one or more bicarbonate salts are present in an amount
of 0.05-5% by weight of the total composition. In some embodiments,
one or more bicarbonate salts are present in an amount of 0.1-30%
by weight of the total composition. In some embodiments, one or
more bicarbonate salts are present in an amount of 0.1-20% by
weight of the total composition. In some embodiments, one or more
bicarbonate salts are present in an amount of 0.1-10% by weight of
the total composition. In some embodiments, one or more bicarbonate
salts are present in an amount of 0.1-5% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of 0.5-30% by weight of the total composition.
In some embodiments, one or more bicarbonate salts are present in
an amount of 0.5-20% by weight of the total composition. In some
embodiments, one or more bicarbonate salts are present in an amount
of 0.5-10% by weight of the total composition. In some embodiments,
one or more bicarbonate salts are present in an amount of 0.5-5% by
weight of the total composition. In some embodiments, one or more
bicarbonate salts are present in an amount of 1-30% by weight of
the total composition. In some embodiments, one or more bicarbonate
salts are present in an amount of 1-20% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of 1-10% by weight of the total composition.
In some embodiments, one or more bicarbonate salts are present in
an amount of 5-30% by weight of the total composition. In some
embodiments, one or more bicarbonate salts are present in an amount
of 5-20% by weight of the total composition. In some embodiments,
one or more bicarbonate salts are present in an amount of 5-10% by
weight of the total composition. In some embodiments, one or more
bicarbonate salts are present in an amount of 10-30% by weight of
the total composition. In some embodiments, one or more bicarbonate
salts are present in an amount of 10-20% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of 20-30% by weight of the total composition.
In some embodiments, one or more bicarbonate salts are present in
an amount of 1-5% by weight of the total composition. In some
embodiments, one or more bicarbonate salts are present in an amount
of 0.1% by weight of the total composition. In some embodiments,
one or more bicarbonate salts are present in an amount of 0.2% by
weight of the total composition. In some embodiments, one or more
bicarbonate salts are present in an amount of 0.3% by weight of the
total composition. In some embodiments, one or more bicarbonate
salts are present in an amount of 0.4% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of 0.5% by weight of the total composition. In
some embodiments, one or more bicarbonate salts are present in an
amount of 1% by weight of the total composition. In some
embodiments, one or more bicarbonate salts are present in an amount
of 1.5% by weight of the total composition. In some embodiments,
one or more bicarbonate salts are present in an amount of 2% by
weight of the total composition. In some embodiments, one or more
bicarbonate salts are present in an amount of 2.5% by weight of the
total composition. In some embodiments, one or more bicarbonate
salts are present in an amount of 3% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of 3.5% by weight of the total composition. In
some embodiments, one or more bicarbonate salts are present in an
amount of 4% by weight of the total composition. In some
embodiments, one or more bicarbonate salts are present in an amount
of 4.5% by weight of the total composition. In some embodiments,
one or more bicarbonate salts are present in an amount of 5% by
weight of the total composition. In some embodiments, one or more
bicarbonate salts are present in an amount of 5.5% by weight of the
total composition. In some embodiments, one or more bicarbonate
salts are present in an amount of 6% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of 6.5% by weight of the total composition. In
some embodiments, one or more bicarbonate salts are present in an
amount of 7% by weight of the total composition. In some
embodiments, one or more bicarbonate salts are present in an amount
of 7.5% by weight of the total composition. In some embodiments,
one or more bicarbonate salts are present in an amount of 8% by
weight of the total composition. In some embodiments, one or more
bicarbonate salts are present in an amount of 8.5% by weight of the
total composition. In some embodiments, one or more bicarbonate
salts are present in an amount of 9% by weight of the total
composition. In some embodiments, one or more bicarbonate salts are
present in an amount of 9.5% by weight of the total composition. In
some embodiments, one or more bicarbonate salts are present in an
amount of 10% by weight of the total composition. In some
embodiments, one or more bicarbonate salts are present in an amount
of 12.5% by weight of the total composition. In some embodiments,
one or more bicarbonate salts are present in an amount of 15% by
weight of the total composition. In some embodiments, one or more
bicarbonate salts are present in an amount of 17.5% by weight of
the total composition. In some embodiments, one or more bicarbonate
salts are present in an amount of 20% by weight of the total
composition.
[0196] In some embodiments, one or more carbonate salts are present
in an amount of about 0.01-30% by weight of the total composition.
In some embodiments, one or more carbonate salts are present in an
amount of about 0.01-20% by weight of the total composition. In
some embodiments, one or more carbonate salts are present in an
amount of about 0.01-10% by weight of the total composition. In
some embodiments, one or more carbonate salts are present in an
amount of about 0.01-5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.05-30% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.05-20% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.05-10% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.05-5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.1-30% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.1-20% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.1-10% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.1-5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.5-30% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.5-20% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.5-10% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.5-5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 1-30% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 1-20% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 1-10% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 5-30% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 5-20% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 5-10% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 10-30% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 10-20% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 20-30% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 1-5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.1% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.2% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.3% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.4% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 0.5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 1% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 1.5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 2% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 2.5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 3% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 3.5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 4% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 4.5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 5.5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 6% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 6.5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 7% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 7.5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 8% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 8.5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 9% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 9.5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 10% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 12.5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 15% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 17.5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of about 20% by weight of the total composition.
[0197] In some embodiments, one or more carbonate salts are present
in an amount of 0.01-30% by weight of the total composition. In
some embodiments, one or more carbonate salts are present in an
amount of 0.01-20% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of 0.01-10% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of 0.01-5% by weight of the total composition. In some embodiments,
one or more carbonate salts are present in an amount of 0.05-30% by
weight of the total composition. In some embodiments, one or more
carbonate salts are present in an amount of 0.05-20% by weight of
the total composition. In some embodiments, one or more carbonate
salts are present in an amount of 0.05-10% by weight of the total
composition. In some embodiments, one or more carbonate salts are
present in an amount of 0.05-5% by weight of the total composition.
In some embodiments, one or more carbonate salts are present in an
amount of 0.1-30% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of 0.1-20% by weight of the total composition. In some embodiments,
one or more carbonate salts are present in an amount of 0.1-10% by
weight of the total composition. In some embodiments, one or more
carbonate salts are present in an amount of 0.1-5% by weight of the
total composition. In some embodiments, one or more carbonate salts
are present in an amount of 0.5-30% by weight of the total
composition. In some embodiments, one or more carbonate salts are
present in an amount of 0.5-20% by weight of the total composition.
In some embodiments, one or more carbonate salts are present in an
amount of 0.5-10% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of 0.5-5% by weight of the total composition. In some embodiments,
one or more carbonate salts are present in an amount of 1-30% by
weight of the total composition. In some embodiments, one or more
carbonate salts are present in an amount of 1-20% by weight of the
total composition. In some embodiments, one or more carbonate salts
are present in an amount of 1-10% by weight of the total
composition. In some embodiments, one or more carbonate salts are
present in an amount of 5-30% by weight of the total composition.
In some embodiments, one or more carbonate salts are present in an
amount of 5-20% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of 5-10% by weight of the total composition. In some embodiments,
one or more carbonate salts are present in an amount of 10-30% by
weight of the total composition. In some embodiments, one or more
carbonate salts are present in an amount of 10-20% by weight of the
total composition. In some embodiments, one or more carbonate salts
are present in an amount of 20-30% by weight of the total
composition. In some embodiments, one or more carbonate salts are
present in an amount of 1-5% by weight of the total composition. In
some embodiments, one or more carbonate salts are present in an
amount of 0.1% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of 0.2% by weight of the total composition. In some embodiments,
one or more carbonate salts are present in an amount of 0.3% by
weight of the total composition. In some embodiments, one or more
carbonate salts are present in an amount of 0.4% by weight of the
total composition. In some embodiments, one or more carbonate salts
are present in an amount of 0.5% by weight of the total
composition. In some embodiments, one or more carbonate salts are
present in an amount of 1% by weight of the total composition. In
some embodiments, one or more carbonate salts are present in an
amount of 1.5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of 2% by weight of the total composition. In some embodiments, one
or more carbonate salts are present in an amount of 2.5% by weight
of the total composition. In some embodiments, one or more
carbonate salts are present in an amount of 3% by weight of the
total composition. In some embodiments, one or more carbonate salts
are present in an amount of 3.5% by weight of the total
composition. In some embodiments, one or more carbonate salts are
present in an amount of 4% by weight of the total composition. In
some embodiments, one or more carbonate salts are present in an
amount of 4.5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of 5% by weight of the total composition. In some embodiments, one
or more carbonate salts are present in an amount of 5.5% by weight
of the total composition. In some embodiments, one or more
carbonate salts are present in an amount of 6% by weight of the
total composition. In some embodiments, one or more carbonate salts
are present in an amount of 6.5% by weight of the total
composition. In some embodiments, one or more carbonate salts are
present in an amount of 7% by weight of the total composition. In
some embodiments, one or more carbonate salts are present in an
amount of 7.5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of 8% by weight of the total composition. In some embodiments, one
or more carbonate salts are present in an amount of 8.5% by weight
of the total composition. In some embodiments, one or more
carbonate salts are present in an amount of 9% by weight of the
total composition. In some embodiments, one or more carbonate salts
are present in an amount of 9.5% by weight of the total
composition. In some embodiments, one or more carbonate salts are
present in an amount of 10% by weight of the total composition. In
some embodiments, one or more carbonate salts are present in an
amount of 12.5% by weight of the total composition. In some
embodiments, one or more carbonate salts are present in an amount
of 15% by weight of the total composition. In some embodiments, one
or more carbonate salts are present in an amount of 17.5% by weight
of the total composition. In some embodiments, one or more
carbonate salts are present in an amount of 20% by weight of the
total composition.
(d) Polyols
[0198] In some embodiments, the compositions of the present
disclosure may optionally further comprise one or more polyols.
Suitable polyols that may be included in the composition include,
but are not limited to a diol, a triol, a saccharide, glycerine,
butane-1,2,3-triol, butane-1,2,4-triol, hexane-1,2,6-triol,
propylene glycol, butanediol, butenediol, butynediol, pentanediol,
hexanediol, octanediol, neopentyl glycol, 2-methyl-1,3-propanediol,
diethylene glycol, triethylene glycol, tetraethylene glycol,
dipropylene glycol and dibutylene glycol. In some embodiments when
the biophotonic composition of the disclosure includes one or more
polyols, the polyol is glycerine. In some embodiments when the
biophotonic composition of the disclosure includes one or more
polyols, the polyol is propylene glycol. In some embodiments when
the biophotonic composition of the disclosure includes one or more
polyols, the polyol is a combination of glycerine and propylene
glycol.
[0199] In some embodiments, one or more polyols are present in an
amount of about 5-75% by weight of the total composition. In some
embodiments, one or more polyols are present in an amount of about
10-75% by weight of the total composition. In some embodiments, one
or more polyols are present in an amount of about 15-75% by weight
of the total composition. In some embodiments, one or more polyols
are present in an amount of about 20-75% by weight of the total
composition. In some embodiments, one or more polyols are present
in an amount of about 10% by weight of the total composition. In
some embodiments, one or more polyols are present in an amount of
about 15% by weight of the total composition. In some embodiments,
one or more polyols are present in an amount of about 20% by weight
of the total composition. In some embodiments, one or more polyols
are present in an amount of about 25% by weight of the total
composition. In some embodiments, one or more polyols are present
in an amount of about 30% by weight of the total composition. In
some embodiments, one or more polyols are present in an amount of
about 35% by weight of the total composition. In some embodiments,
one or more polyols are present in an amount of about 40% by weight
of the total composition. In some embodiments, one or more polyols
are present in an amount of about 45% by weight of the total
composition. In some embodiments, one or more polyols are present
in an amount of about 50% by weight of the total composition. In
some embodiments, one or more polyols are present in an amount of
about 55% by weight of the total composition. In some embodiments,
one or more polyols are present in an amount of about 60% by weight
of the total composition. In some embodiments, one or more polyols
are present in an amount of about 65% by weight of the total
composition. In some embodiments, one or more polyols are present
in an amount of about 70% by weight of the total composition. In
some embodiments, one or more polyols are present in an amount of
about 75% by weight of the total composition.
[0200] In some embodiments, one or more polyols are present in an
amount of 5-75% by weight of the total composition. In some
embodiments, one or more polyols are present in an amount of 10-75%
by weight of the total composition. In some embodiments, one or
more polyols are present in an amount of 15-75% by weight of the
total composition. In some embodiments, one or more polyols are
present in an amount of 20-75% by weight of the total composition.
In some embodiments, one or more polyols are present in an amount
of 10% by weight of the total composition. In some embodiments, one
or more polyols are present in an amount of 15% by weight of the
total composition. In some embodiments, one or more polyols are
present in an amount of 20% by weight of the total composition. In
some embodiments, one or more polyols are present in an amount of
25% by weight of the total composition. In some embodiments, one or
more polyols are present in an amount of 30% by weight of the total
composition. In some embodiments, one or more polyols are present
in an amount of 35% by weight of the total composition. In some
embodiments, one or more polyols are present in an amount of 40% by
weight of the total composition. In some embodiments, one or more
polyols are present in an amount of 45% by weight of the total
composition. In some embodiments, one or more polyols are present
in an amount of 50% by weight of the total composition. In some
embodiments, one or more polyols are present in an amount of 55% by
weight of the total composition. In some embodiments, one or more
polyols are present in an amount of 60% by weight of the total
composition. In some embodiments, one or more polyols are present
in an amount of 65% by weight of the total composition. In some
embodiments, one or more polyols are present in an amount of 70% by
weight of the total composition. In some embodiments, one or more
polyols are present in an amount of 75% by weight of the total
composition.
[0201] In the compositions and methods of the present disclosure,
additional components may optionally be included, or used in
combination with the biophotonic compositions as described herein.
Such additional components include, but are not limited to, healing
factors, growth factors, antimicrobials, wrinkle fillers (e.g.
botox, hyaluronic acid or polylactic acid), collagens, anti-virals,
anti-fungals, antibiotics, drugs, and/or agents that promote
collagen synthesis. These additional components may be applied to
the wound, skin or soft tissues including mucosa in a topical
fashion, prior to, at the same time of, and/or after topical
application of the biophotonic composition of the present
disclosure, and may also be systemically administered. Suitable
healing factors, antimicrobials, collagens, and/or agents that
promote collagen synthesis are discussed below:
(e) Healing Factors
[0202] In some embodiments, the compositions of the present
disclosure may optionally further comprise one or more healing
factors. Healing factors comprise compounds that promote or enhance
the healing or regenerative process of the tissues on the
application site of the composition. During the photoactivation of
the composition of the present disclosure, there is an increase of
the absorption of molecules at the treatment site by the skin,
wound or the mucosa. An augmentation in the blood flow at the site
of treatment is observed for an extent period of time. An increase
in the lymphatic drainage and a possible change in the osmotic
equilibrium due to the dynamic interaction of the free radical
cascades can be enhanced or even fortified with the inclusion of
healing factors. Suitable healing factors include, but are not
limited to:
[0203] Hyaluronic acid (Hyaluronan, hyaluronate): is a non-sulfated
glycosaminoglycan, distributed widely throughout connective,
epithelial and neural tissues. It is one of the primary components
of the extracellular matrix, and contributes significantly to cell
proliferation and migration. Hyaluronan is a major component of the
skin, where it is involved in tissue repair. While it is abundant
in extracellular matrices, it contributes to tissues hydrodynamics,
movement and proliferation of cells and participates in a wide
number of cell surface receptor interactions, notably those
including primary receptor CD44. The hyaluronidases enzymes degrade
hyaluronan. There are at least seven types of hyaluronidase-like
enzymes in humans, several of which are tumor suppressors. The
degradation products of hyaluronic acid, the oligosaccharides and
the very-low molecular weight hyaluronic acid, exhibit
pro-angiogenic properties. In addition, recent studies show that
hyaluronan fragments, but not the native high molecular mass of
hyaluronan, can induce inflammatory responses in macrophages and
dendritic cells in tissue injury. Hyaluronic acid is well suited to
biological applications targeting the skin. Due to its high
biocompatibility, it is used to stimulate tissue regeneration.
Studies have shown hyaluronic acid appearing in the early stages of
healing to physically create room for white blood cells that
mediate the immune response. It is used in the synthesis of
biological scaffolds for wound healing applications and in wrinkle
treatment. A suitable range of concentration over which hyaluronic
acid can be used in the present composition is from about 0.001% to
about 3% by weight of the total composition.
[0204] Glucosamine: is one of the most abundant monosaccharides in
human tissues and a precursor in the biological synthesis of
glycosylated proteins and lipids. It is commonly used in the
treatment of osteoarthritis. The common form of glucosamine used is
its sulfate salt and including glucosamine sulfate sodium chloride.
Glucosamine shows a number of effects including an
anti-inflammatory activity, stimulation of the synthesis of
proteoglycans and the synthesis of proteolytic enzymes. A suitable
range of concentration over which glucosamine can be used in the
present composition is from about 0.01% to about 3% by weight of
the total composition.
[0205] Allantoin: is a diureide of glyosilic acid. It has
keratolytic effect, increases the water content of the
extracellular matrix, enhances the desquamation of the upper layers
of dead (apoptotic) skin cells, and promotes skin proliferation and
wound healing.
[0206] Also, saffron can act as both a chromophore and a healing
factor, and as a potentiator. Other healing agents can also be
included such as growth factors.
(f) Antimicrobials
[0207] In some embodiments, the compositions of the present
disclosure may optionally further comprise one or more
antimicrobials. Antimicrobials kill microbes or inhibit their
growth or accumulation. Exemplary antimicrobials (or antimicrobial
agent) are recited in U.S. Patent Application Publications
20040009227 and 20110081530. Suitable antimicrobials for use in the
methods of the present disclosure include, but not limited to,
phenolic and chlorinated phenolic and chlorinated phenolic
compounds, resorcinol and its derivatives, bisphenolic compounds,
benzoic esters (parabens), halogenated carbonilides, polymeric
antimicrobial agents, thazolines, trichloromethylthioimides,
natural antimicrobial agents (also referred to as "natural
essential oils"), metal salts, and broad-spectrum antibiotics.
[0208] Specific phenolic and chlorinated phenolic antimicrobial
agents that can be used in the disclosure include, but are not
limited to: phenol; 2-methyl phenol; 3-methyl phenol; 4-methyl
phenol; 4-ethyl phenol; 2,4-dimethyl phenol; 2,5-dimethyl phenol;
3,4-dimethyl phenol; 2,6-dimethyl phenol; 4-n-propyl phenol;
4-n-butyl phenol; 4-n-amyl phenol; 4-tert-amyl phenol; 4-n-hexyl
phenol; 4-n-heptyl phenol; mono- and poly-alkyl and aromatic
halophenols; p-chlorophenyl; methyl p-chlorophenol; ethyl
p-chlorophenol; n-propyl p-chlorophenol; n-butyl p-chlorophenol;
n-amyl p-chlorophenol; sec-amyl p-chlorophenol; n-hexyl
p-chlorophenol; cyclohexyl p-chlorophenol; n-heptyl p-chlorophenol;
n-octyl; p-chlorophenol; o-chlorophenol; methyl o-chlorophenol;
ethyl o-chlorophenol; n-propyl o-chlorophenol; n-butyl
o-chlorophenol; n-amyl o-chlorophenol; tert-amyl o-chlorophenol;
n-hexyl o-chlorophenol; n-heptyl o-chlorophenol; o-benzyl
p-chlorophenol; o-benxyl-m-methyl p-chlorophenol;
o-benzyl-m,m-dimethyl p-chlorophenol; o-phenylethyl p-chlorophenol;
o-phenylethyl-m-methyl p-chlorophenol; 3-methyl p-chlorophenol
3,5-dimethyl p-chlorophenol, 6-ethyl-3-methyl p-chlorophenol,
6-n-propyl-3-methyl p-chlorophenol; 6-iso-propyl-3-methyl
p-chlorophenol; 2-ethyl-3,5-dimethyl p-chlorophenol;
6-sec-butyl-3-methyl p-chlorophenol; 2-iso-propyl-3,5-dimethyl
p-chlorophenol; 6-diethylmethyl-3-methyl p-chlorophenol;
6-iso-propyl-2-ethyl-3-methyl p-chlorophenol;
2-sec-amyl-3,5-dimethyl p-chlorophenol;
2-diethylmethyl-3,5-dimethyl p-chlorophenol; 6-sec-octyl-3-methyl
p-chlorophenol; p-chloro-m-cresol p-bromophenol; methyl
p-bromophenol; ethyl p-bromophenol; n-propyl p-bromophenol; n-butyl
p-bromophenol; n-amyl p-bromophenol; sec-amyl p-bromophenol;
n-hexyl p-bromophenol; cyclohexyl p-bromophenol; o-bromophenol;
tert-amyl o-bromophenol; n-hexyl o-bromophenol;
n-propyl-m,m-dimethyl o-bromophenol; 2-phenyl phenol;
4-chloro-2-methyl phenol; 4-chloro-3-methyl phenol;
4-chloro-3,5-dimethyl phenol; 2,4-dichloro-3,5-dimethylphenol;
3,4,5,6-tetabromo-2-methylphenol; 5-methyl-2-pentylphenol;
4-isopropyl-3-methylphenol; para-chloro-metaxylenol (PCMX);
chlorothymol; phenoxyethanol; phenoxyisopropanol; and
5-chloro-2-hydroxydiphenylmethane.
[0209] Resorcinol and its derivatives can also be used as
antimicrobial agents. Specific resorcinol derivatives include, but
are not limited to: methyl resorcinol; ethyl resorcinol; n-propyl
resorcinol; n-butyl resorcinol; n-amyl resorcinol; n-hexyl
resorcinol; n-heptyl resorcinol; n-octyl resorcinol; n-nonyl
resorcinol; phenyl resorcinol; benzyl resorcinol; phenylethyl
resorcinol; phenylpropyl resorcinol; p-chlorobenzyl resorcinol;
5-chloro-2,4-dihydroxydiphenyl methane;
4'-chloro-2,4-dihydroxydiphenyl methane;
5-bromo-2,4-dihydroxydiphenyl methane; and
4'-bromo-2,4-dihydroxydiphenyl methane.
[0210] Specific bisphenolic antimicrobial agents that can be used
in the disclosure include, but are not limited to: 2,2'-methylene
bis-(4-chlorophenol); 2,4,4'trichloro-2'-hydroxy-diphenyl ether,
which is sold by Ciba Geigy, Florham Park, N.J. under the trade
name Triclosan.RTM.; 2,2'-methylene bis-(3,4,6-trichlorophenol);
2,2'-methylene bis-(4-chloro-6-bromophenol);
bis-(2-hydroxy-3,5-dichlorophenyl) sulphide; and
bis-(2-hydroxy-5-chlorobenzyl)sulphide.
[0211] Specific benzoic esters (parabens) that can be used in the
disclosure include, but are not limited to: methylparaben;
propylparaben; butylparaben; ethylparaben; isopropylparaben;
isobutylparaben; benzylparaben; sodium methylparaben; and sodium
propylparaben.
[0212] Specific halogenated carbanilides that can be used in the
disclosure include, but are not limited to:
3,4,4'-trichlorocarbanilides, such as
3-(4-chlorophenyl)-1-(3,4-dichlorphenyl)urea sold under the
tradename Triclocarban.RTM. by Ciba-Geigy, Florham Park, N.J.;
3-trifluoromethyl-4,4'-dichlorocarbanilide; and
3,3',4-trichlorocarbanilide.
[0213] Specific polymeric antimicrobial agents that can be used in
the disclosure include, but are not limited to: polyhexamethylene
biguanide hydrochloride; and poly(iminoimidocarbonyl
iminoimidocarbonyl iminohexamethylene hydrochloride), which is sold
under the tradename Vantocil.RTM. IB.
[0214] Specific thazolines that can be used in the disclosure
include, but are not limited to that sold under the tradename
Micro-Check.RTM.; and 2-n-octyl-4-isothiazolin-3-one, which is sold
under the tradename Vinyzene.RTM. IT-3000 DIDP.
[0215] Specific trichloromethylthioimides that can be used in the
disclosure include, but are not limited to:
N-(trichloromethylthio)phthalimide, which is sold under the
tradename Fungitrol.RTM.; and
N-trichloromethylthio-4-cyclohexene-1,2-dicarboximide, which is
sold under the tradename Vancide.RTM..
[0216] Specific natural antimicrobial agents that can be used in
the disclosure include, but are not limited to, oils of: anise;
lemon; orange; rosemary; wintergreen; thyme; lavender; cloves;
hops; tea tree; citronella; wheat; barley; lemongrass; cedar leaf;
cedarwood; cinnamon; fleagrass; geranium; sandalwood; violet;
cranberry; eucalyptus; vervain; peppermint; gum benzoin; basil;
fennel; fir; balsam; menthol; ocmea origanuin; hydastis;
carradensis; Berberidaceac daceae; Ratanhiae longa; and Curcuma
longa. Also included in this class of natural antimicrobial agents
are the key chemical components of the plant oils which have been
found to provide antimicrobial benefit. These chemicals include,
but are not limited to: anethol; catechole; camphene; thymol;
eugenol; eucalyptol; ferulic acid; farnesol; hinokitiol; tropolone;
limonene; menthol; methyl salicylate; carvacol; terpineol;
verbenone; berberine; ratanhiae extract; caryophellene oxide;
citronellic acid; curcumin; nerolidol; and geraniol.
[0217] Specific metal salts that can be used in the disclosure
include, but are not limited to, salts of metals in Groups 3a-5a,
3b-7b, and 8 of the periodic table. Specific examples of metal
salts include, but are not limited to, salts of: aluminum;
zirconium; zinc; silver; gold; copper; lanthanum; tin; mercury;
bismuth; selenium; strontium; scandium; yttrium; cerium;
praseodymiun; neodymium; promethum; samarium; europium; gadolinium;
terbium;
[0218] dysprosium; holmium; erbium; thalium; ytterbium; lutetium;
and mixtures thereof An example of the metal-ion based
antimicrobial agent is sold under the tradename HealthShield.RTM.,
and is manufactured by HealthShield Technology, Wakefield,
Mass.
[0219] Specific broad-spectrum antimicrobial agents that can be
used in the disclosure include, but are not limited to, those that
are recited in other categories of antimicrobial agents herein.
[0220] Additional antimicrobial agents that can be used in the
methods of the disclosure include, but are not limited to:
pyrithiones, and in particular pyrithione-including zinc complexes
such as that sold under the tradename Octopirox.RTM.;
dimethyidimethylol hydantoin, which is sold under the tradename
Glydant.RTM.; methylchloroisothiazolinone/methylisothiazolinone,
which is sold under the tradename Kathon CG.RTM.; sodium sulfite;
sodium bisulfite; imidazolidinyl urea, which is sold under the
tradename Germall 1150; diazolidinyl urea, which is sold under the
tradename Germall 11CD; benzyl alcohol
v2-bromo-2-nitropropane-1,3-diol, which is sold under the tradename
Bronopol.RTM.; formalin or formaldehyde; iodopropenyl
butylcarbamate, which is sold under the tradename Polyphase
P100.RTM.; chloroacetamide; methanamine; methyldibromonitrile
glutaronitrile (1,2-dibromo-2,4-dicyanobutane), which is sold under
the tradename Tektamer.RTM.; glutaraldehyde;
5-bromo-5-nitro-1,3-dioxane, which is sold under the tradename
Bronidox.RTM.; phenethyl alcohol; o-phenylphenol/sodium
o-phenylphenol sodium hydroxymethylglycinate, which is sold under
the tradename Suttocide A.RTM.; polymethoxy bicyclic oxazolidine;
which is sold under the tradename Nuosept C.RTM.; dimethoxane;
thimersal; dichlorobenzyl alcohol; captan; chlorphenenesin;
dichlorophene; chlorbutanol; glyceryl laurate; halogenated diphenyl
ethers; 2,4,4'-trichloro-2'-hydroxy-diphenyl ether, which is sold
under the tradename Triclosan.RTM. and is available from
Ciba-Geigy, Florham Park, N.J.; and
2,2'-dihydroxy-5,5'-dibromo-diphenyl ether.
[0221] Additional antimicrobial agents that can be used in the
methods of the disclosure include those disclosed by U.S. Pat. Nos.
3,141,321; 4,402,959; 4,430,381; 4,533,435; 4,625,026; 4,736,467;
4,855,139; 5,069,907; 5,091,102; 5,639,464; 5,853,883; 5,854,147;
5,894,042; and 5,919,554, and U.S. Pat. Appl. Publ. Nos.
20040009227 and 20110081530, the contents of all of which are
incorporated herein by reference.
(g) Collagens and Agents that Promote Collagen Synthesis
[0222] In some embodiments, the compositions of the present
disclosure may optionally further comprise one or more collagens or
agents that promote collagen synthesis. Collagen is a fibrous
protein produced in dermal fibroblast cells and forming 70% of the
dermis. Collagen is responsible for the smoothing and firming of
the skin. Therefore, when the synthesis of collagen is reduced,
skin aging will occur, and so the firming and smoothing of the skin
will be rapidly reduced. As a result, the skin will be flaccid and
wrinkled. On the other hand, when metabolism of collagen is
activated by the stimulation of collagen synthesis in the skin, the
components of dermal matrices will be increased, leading to
effects, such as wrinkle improvement, firmness improvement and skin
strengthening. Thus, collagens and agents that promote collagen
synthesis may also be useful in the present disclosure. Agents that
promote collagen synthesis (i.e., pro-collagen synthesis agents)
include amino acids, peptides, proteins, lipids, small chemical
molecules, natural products and extracts from natural products.
[0223] For instance, it was discovered that intake of vitamin C,
iron, and collagen can effectively increase the amount of collagen
in skin or bone. See, e.g., U.S. Patent Application Publication
20090069217, the contents of which are all incorporated herein by
reference. Examples of the vitamin C include an ascorbic acid
derivative such as L-ascorbic acid or sodium L-ascorbate, an
ascorbic acid preparation obtained by coating ascorbic acid with an
emulsifier or the like, and a mixture containing two or more of
those vitamin Cs at an arbitrary rate. In addition, natural
products containing vitamin C such as acerola and lemon may also be
used. Examples of the iron preparation include: an inorganic iron
such as ferrous sulfate, sodium ferrous citrate, or ferric
pyrophosphate; an organic iron such as heme iron, ferritin iron, or
lactoferrin iron; and a mixture containing two or more of those
irons at an arbitrary rate. In addition, natural products
containing iron such as spinach or liver may also be used.
Moreover, examples of the collagen include: an extract obtained by
treating bone, skin, or the like of a mammal such as bovine or
swine with an acid or alkaline; a peptide obtained by hydrolyzing
the extract with a protease such as pepsine, trypsin, or
chymotrypsin; and a mixture containing two or more of those
collagens at an arbitrary rate.
Collagens extracted from plant sources may also be used.
[0224] Additional pro-collagen synthesis agents are described, for
example, in U.S. Patent Patents 7598291, 7722904, 6203805, 5529769,
etc, and U.S. Patent Application Publications 20060247313,
20080108681, 20110130459, 20090325885, and 20110086060, the
contents of all of which are incorporated herein by reference.
[0225] The compositions of the disclosure can also include other
ingredients such as humectants (e.g. glycerine, ethylene glycol,
and propylene glycol), preservatives such as parabens, and pH
adjusters such as sodium hydroxide and HC1. In some embodiments,
the pH of the composition is in or adjusted to the range of about 4
to about 10. In some embodiments, the pH of the composition is in
or adjusted to the range of about 4 to about 9. In some
embodiments, the pH of the composition is in or adjusted to the
range of about 4 to about 8. In some embodiments, the pH of the
composition is within the range of about 4 to about 7. In some
embodiments, the pH of the composition is within the range of about
4 to about 6.5. In some embodiments, the pH of the composition is
within the range of about 4 to about 6. In some embodiments, the pH
of the composition is within the range of about 4 to about 5.5. In
some embodiments, the pH of the composition is within the range of
about 4 to about 5. In some embodiments, the pH of the composition
is within the range of about 5.0 to about 8.0. In some embodiments,
the pH of the composition is within the range of about 6.0 to about
8.0. In some embodiments, the pH of the composition is within the
range of about 6.5 to about 7.5. In some embodiments, the pH of the
composition is within the range of about 5.5 to about 7.5.
[0226] In some embodiments, the pH of the composition is in or
adjusted to the range of 4 to 10. In some embodiments, the pH of
the composition is in or adjusted to the range of 4 to 9. In some
embodiments, the pH of the composition is in or adjusted to the
range of 4 to 8. In some embodiments, the pH of the composition is
within the range of 4 to 7. In some embodiments, the pH of the
composition is within the range of 4 to 6.5. In some embodiments,
the pH of the composition is within the range of 4 to 6. In some
embodiments, the pH of the composition is within the range of 4 to
5.5. In some embodiments, the pH of the composition is within the
range of 4 to 5. In some embodiments, the pH of the composition is
within the range of 5.0 to 8.0. In some embodiments, the pH of the
composition is within the range of 6.0 to 8.0. In some embodiments,
the pH of the composition is within the range of 6.5 to 7.5. In
some embodiments, the pH of the composition is within the range of
5.5 to 7.5.
[0227] In some embodiments, the compositions of the disclosure also
include an aqueous substance (water) or an alcohol. Alcohols
include, but are not limited to, ethanol, propanol, isopropanol,
butanol, iso-butanol, t-butanol or pentanol. In some embodiments,
the first chromophore is in solution in a medium of the biophotonic
composition. In some embodiments wherein the first chromophore is
in solution in a medium of the biophotonic composition, the medium
is an aqueous substance. In some embodiments, the first and second
chromophores are in solution in a medium of the biophotonic
composition. In some embodiments wherein the first and second
chromophores are in solution in a medium of the biophotonic
composition, the medium is an aqueous substance. In some
embodiments, the first, second, and third chromophores are in
solution in a medium of the biophotonic composition. In some
embodiments wherein the first, second, and third chromophores are
in solution in a medium of the biophotonic composition, the medium
is an aqueous substance.
(4) Methods of Use
[0228] The biophotonic compositions of the present disclosure have
numerous uses. Without being bound by theory, the biophotonic
compositions of the present disclosure are useful in promoting
wound healing or tissue repair. The biophotonic compositions of the
present disclosure are useful for treating or preventing a skin
disorder. The biophotonic compositions of the present disclosure
are useful in treating acne. The biophotonic compositions of the
present disclosure are useful in treating acne scars. The
biophotonic compositions of the present disclosure are useful for
skin rejuvenation. The biophotonic compositions of the present
disclosure are useful for treating acute or chronic inflammation.
The biophotonic compositions of the present disclosure are useful
for treating or preventing an oral disease. Therefore, it is an
objective of the present disclosure to provide a method of
providing biophotonic therapy to a wound, wherein the method
promotes wound healing. It is also an objective of the present
disclosure to provide a method of providing biophotonic therapy to
a skin tissue afflicted with acne, wherein the method is used to
treat acne. It is an objective of the present disclosure to provide
a method of providing biophotonic therapy to a skin tissue
afflicted with acne scars, wherein the method is used to treat acne
scars. It is also an objective of the present disclosure to provide
a method of providing biophotonic therapy to a skin tissue
afflicted with a skin disorder, wherein the method is used to treat
or prevent the skin disorder. It is an objective of the present
disclosure to provide a method of providing biophotonic therapy to
skin tissue, wherein the method is used for promoting skin
rejuvenation. It is also an objective of the present disclosure to
provide a method of providing biophotonic therapy to a subject's
mouth, wherein the method is used to treat or prevent an oral
disease.
[0229] A "patient," "subject," or "host" to be treated by the
disclosed compositions and methods may mean either a human or
non-human animal, such as a mammal, a fish, a bird, a reptile, or
an amphibian. Thus, the subject of the herein disclosed methods can
be a human, non-human primate, horse, pig, rabbit, dog, sheep,
goat, cow, cat, guinea pig, or rodent. The term does not denote a
particular age or sex. Thus, adult and newborn subjects, as well as
fetuses, whether male or female, are intended to be covered. In
some embodiments, the subject is a mammal In some embodiments, the
subject is a human. A patient refers to a subject afflicted with a
disease or disorder.
[0230] The term "therapeutic" treatment is art-recognized and
includes administration to the host of one or more of the subject
compositions. If treatment is administered after manifestation of
the unwanted condition, the treatment is therapeutic (i.e., it is
intended to diminish, ameliorate, or stabilize the existing
unwanted condition or side effects thereof).
[0231] The present disclosure provides a method for providing a
biophotonic therapy to a wound, the method comprising: applying
(e.g., by topical application) to a site of a wound a biophotonic
composition of the present disclosure, and illuminating the
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the chromophore(s) of the
biophotonic composition.
[0232] In some aspects, the present disclosure provides a method
for providing biophotonic therapy to a wound, comprising: topically
applying to a wound a biophotonic composition comprising a first
chromophore; one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts; and one or
more gelling agents, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate; and illuminating said biophotonic
composition with light having a wavelength that overlaps with an
absorption spectrum of the first chromophore. In some embodiments,
the composition further comprises one or more polyols.
[0233] In some aspects, the present disclosure provides a method
for providing biophotonic therapy to a wound, comprising: topically
applying to a wound a biophotonic composition comprising a first
chromophore, one or more polyols, and one or more gelling agents,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate; and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore.
[0234] The present disclosure provides a method for treating a
wound, the method comprising: topically applying to a site of a
wound a biophotonic composition of the present disclosure, and
illuminating the biophotonic composition with light having a
wavelength that overlaps with an absorption spectrum of the
chromophore(s) of the biophotonic composition.
[0235] In another aspect, the present disclosure provides a method
of treating a wound, comprising: topically applying to a site of a
wound a biophotonic composition comprising a first chromophore; one
or more salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts; and one or more gelling agents,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate; and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore. In some embodiments, the composition further
comprises one or more polyols.
[0236] In some aspects, the present disclosure provides a method of
treating a wound, comprising: topically to a site of a wound
applying a biophotonic composition comprising a first chromophore,
one or more polyols, and one or more gelling agents, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate; and
illuminating said biophotonic composition with light having a
wavelength that overlaps with an absorption spectrum of the first
chromophore.
[0237] The present disclosure provides a method for providing a
biophotonic therapy for skin rejuvenation, the method comprising:
applying (e.g., by topical application) to the skin a biophotonic
composition of the present disclosure, and illuminating the
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the chromophore(s) of the
biophotonic composition.
[0238] In some aspects, the present disclosure provides a method
for providing biophotonic therapy for skin rejuvenation,
comprising: topically applying to the skin a biophotonic
composition comprising a first chromophore; one or more salts
selected from bicarbonate salts, carbonate salts or a combination
of the foregoing salts; and one or more gelling agents, wherein
said composition does not include an oxidant selected from the
group consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate; and
illuminating said biophotonic composition with light having a
wavelength that overlaps with an absorption spectrum of the first
chromophore. In some embodiments, the composition further comprises
one or more polyols.
[0239] In some aspects, the present disclosure provides a method
for providing biophotonic therapy for skin rejuvenation,
comprising: topically applying to the skin a biophotonic
composition comprising a first chromophore, one or more polyols,
and one or more gelling agents, wherein said composition does not
include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate; and illuminating said
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the first chromophore.
[0240] In some aspects, the present disclosure provides a method
for providing skin rejuvenation, the method comprising: applying
(e.g., by topical application) to the skin a biophotonic
composition of the present disclosure, and illuminating the
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the chromophore(s) of the
biophotonic composition.
[0241] The present disclosure provides a method for promoting skin
rejuvenation comprising: topically applying to the skin a
biophotonic composition comprising a first chromophore; one or more
salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts; and one or more gelling agents,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate; and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore. In some embodiments, the composition further
comprises one or more polyols.
[0242] In some embodiments, the present disclosure provides a
method for promoting skin rejuvenation comprising: topically
applying to the skin a biophotonic composition comprising a first
chromophore, one or more polyols, and one or more gelling agents,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate; and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore.
[0243] The present disclosure provides a method for providing a
biophotonic therapy to a target skin tissue, the method comprising:
applying (e.g., by topical application) to a target skin tissue a
biophotonic composition of the present disclosure, and illuminating
the biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the chromophore(s) of the
biophotonic composition.
[0244] In some aspects, the present disclosure provides a method
for providing biophotonic therapy to a target skin tissue afflicted
with a skin disorder, comprising: topically applying to a target
skin tissue a biophotonic composition comprising a first
chromophore; one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts; and one or
more gelling agents, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate; and illuminating said biophotonic
composition with light having a wavelength that overlaps with an
absorption spectrum of the first chromophore. In some embodiments,
the composition further comprises one or more polyols.
[0245] In some aspects, the present disclosure provides a method
for providing biophotonic therapy to a target skin tissue afflicted
with a skin disorder, comprising: topically applying to a target
skin tissue a biophotonic composition comprising a first
chromophore, one or more polyols, and one or more gelling agents,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate; and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore.
[0246] The present disclosure provides a method for treating or
preventing a skin disorder, the method comprising: topically
applying to a target skin tissue afflicted with the skin disorder a
biophotonic composition of the present disclosure, and illuminating
the biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the chromophore(s) of the
biophotonic composition.
[0247] The present disclosure provides a method for treating or
preventing a skin disorder, comprising: topically applying to a
target skin tissue afflicted with the skin disorder a biophotonic
composition, wherein the biophotonic composition comprises a first
chromophore; one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts; and one or
more gelling agents, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate; and illuminating said biophotonic
composition with light having a wavelength that overlaps with an
absorption spectrum of the first chromophore. In some embodiments,
the composition further comprises one or more polyols.
[0248] In some embodiments, the present disclosure provides a
method for treating or preventing a skin disorder, comprising:
topically applying to a target skin tissue afflicted with the skin
disorder a biophotonic composition, wherein the biophotonic
composition comprises a first chromophore, one or more polyols, and
one or more gelling agents, wherein said composition does not
include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate; and illuminating said
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the first chromophore.
[0249] The present disclosure provides a method for providing a
biophotonic therapy to a target skin tissue afflicted with acne,
the method comprising: applying (e.g., by topical application) to a
target skin tissue a biophotonic composition of the present
disclosure, and illuminating the biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the chromophore(s) of the biophotonic composition.
[0250] In some aspects, the present disclosure provides a method
for providing biophotonic therapy to a target skin tissue afflicted
with acne, comprising: topically applying to a target skin tissue a
biophotonic composition comprising a first chromophore; one or more
salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts; and one or more gelling agents,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate; and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore. In some embodiments, the composition further
comprises one or more polyols.
[0251] In some aspects, the present disclosure provides a method
for providing biophotonic therapy to a target skin tissue afflicted
with acne, comprising: topically applying to a target skin tissue a
biophotonic composition comprising a first chromophore, one or more
polyols, and one or more gelling agents, wherein said composition
does not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate; and illuminating said
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the first chromophore.
[0252] The present disclosure provides a method for treating acne,
the method comprising: topically applying to a target skin tissue a
biophotonic composition of the present disclosure, and illuminating
the biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the chromophore(s) of the
biophotonic composition.
[0253] The present disclosure provides a method for treating acne,
comprising: topically applying to a target skin tissue a
biophotonic composition, wherein the biophotonic composition
comprises a first chromophore; one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts; and one or more gelling agents, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate; and
illuminating said biophotonic composition with light having a
wavelength that overlaps with an absorption spectrum of the first
chromophore. In some embodiments, the composition further comprises
one or more polyols.
[0254] The present disclosure further provides a method for
treating acne, comprising:
[0255] topically applying to a target skin tissue a biophotonic
composition, wherein the biophotonic composition comprises a first
chromophore, one or more polyols, and one or more gelling agents,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate; and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore.
[0256] The present disclosure provides a method for providing a
biophotonic therapy to a target skin tissue afflicted with acne
scars, the method comprising: applying (e.g., by topical
application) to a target skin tissue a biophotonic composition of
the present disclosure, and illuminating the biophotonic
composition with light having a wavelength that overlaps with an
absorption spectrum of the chromophore(s) of the biophotonic
composition.
[0257] In some aspects, the present disclosure provides a method
for providing biophotonic therapy to a target skin tissue afflicted
with acne scars, comprising: topically applying to a target skin
tissue a biophotonic composition comprising a first chromophore;
one or more salts selected from bicarbonate salts, carbonate salts
or a combination of the foregoing salts; and one or more gelling
agents, wherein said composition does not include an oxidant
selected from the group consisting of a peroxide, a peroxy acid,
hydrogen peroxide, carbamide peroxide, an alkali metal peroxide, an
alkali metal percarbonate, peroxyacetic acid, and an alkali metal
perborate; and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore. In some embodiments, the composition further
comprises one or more polyols.
[0258] In some aspects, the present disclosure provides a method
for providing biophotonic therapy to a target skin tissue afflicted
with acne scars, comprising: topically applying to a target skin
tissue a biophotonic composition comprising a first chromophore,
one or more polyols, and one or more gelling agents, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate; and
illuminating said biophotonic composition with light having a
wavelength that overlaps with an absorption spectrum of the first
chromophore.
[0259] The present disclosure provides a method for treating acne
scars, comprising: topically applying to a target skin a
biophotonic composition comprising a first chromophore;
[0260] and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore.
[0261] The present disclosure provides a method for treating acne
scars, comprising: topically applying to a target skin a
biophotonic composition, wherein the biophotonic composition
comprises a first chromophore; one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts; and one or more gelling agents, wherein said
composition does not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate; and
illuminating said biophotonic composition with light having a
wavelength that overlaps with an absorption spectrum of the first
chromophore. In some embodiments, the composition further comprises
one or more polyols.
[0262] The present disclosure further provides a method for
treating acne scars, comprising: topically applying to a target
skin afflicted a biophotonic composition, wherein the biophotonic
composition comprises a first chromophore, one or more polyols, and
one or more gelling agents, wherein said composition does not
include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate; and illuminating said
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the first chromophore.
[0263] The present disclosure provides a method for providing a
biophotonic therapy to a target tissue afflicted with acute or
chronic inflammation, the method comprising: applying (e.g., by
topical application) to a target skin tissue a biophotonic
composition of the present disclosure, and illuminating the
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the chromophore(s) of the
biophotonic composition.
[0264] In some aspects, the present disclosure provides a method
for providing biophotonic therapy to a target tissue afflicted with
acute or chronic inflammation, comprising: topically applying to a
target skin tissue a biophotonic composition comprising a first
chromophore; one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts; and one or
more gelling agents, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate; and illuminating said biophotonic
composition with light having a wavelength that overlaps with an
absorption spectrum of the first chromophore. In some embodiments,
the composition further comprises one or more polyols.
[0265] In some aspects, the present disclosure provides a method
for providing biophotonic therapy to a target tissue afflicted with
acute or chronic inflammation, comprising: topically applying to a
target skin tissue a biophotonic composition comprising a first
chromophore, one or more polyols, and one or more gelling agents,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate; and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore.
[0266] In another aspect, the present disclosure provides a method
for treating acute or chronic inflammation, comprising: topically
applying to a target tissue with acute or chronic inflammation a
biophotonic composition comprising a first chromophore; and
illuminating said biophotonic composition with light having a
wavelength that overlaps with an absorption spectrum of the first
chromophore.
[0267] The present disclosure provides a method for treating acute
or chronic inflammation, comprising: topically applying to a target
tissue with acute or chronic inflammation a biophotonic
composition, wherein the biophotonic composition comprises a first
chromophore; one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts; and one or
more gelling agents, wherein said composition does not include an
oxidant selected from the group consisting of a peroxide, a peroxy
acid, hydrogen peroxide, carbamide peroxide, an alkali metal
peroxide, an alkali metal percarbonate, peroxyacetic acid, and an
alkali metal perborate; and illuminating said biophotonic
composition with light having a wavelength that overlaps with an
absorption spectrum of the first chromophore. In some embodiments,
the composition further comprises one or more polyols.
[0268] The present disclosure also provides a method for treating
acute or chronic inflammation, comprising: topically applying to a
target tissue with acute or chronic inflammation a biophotonic
composition, wherein the biophotonic composition comprises a first
chromophore, one or more polyols, and one or more gelling agents,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate; and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore.
[0269] The present disclosure provides a method for providing a
biophotonic therapy to a target tissue afflicted with acute or
chronic inflammation, the method comprising: applying (e.g., by
topical application) to a target skin tissue a biophotonic
composition of the present disclosure, and illuminating the
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the chromophore(s) of the
biophotonic composition. In some embodiments, the target site may
be skin or nails.
[0270] In some aspects, the present disclosure provides a method
for providing biophotonic therapy to a target site afflicted with
fungal infection, comprising: topically applying to a target site a
biophotonic composition comprising a first chromophore; one or more
salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts; and one or more gelling agents,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate; and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore. In some embodiments, the target site may be
skin or nails. In some embodiments, the composition further
comprises one or more polyols.
[0271] In some aspects, the present disclosure provides a method
for providing biophotonic therapy to a target site afflicted with
fungal infection, comprising: topically applying to a target site a
biophotonic composition comprising a first chromophore, one or more
polyols, and one or more gelling agents, wherein said composition
does not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate; and illuminating said
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the first chromophore. In
some embodiments, the target site may be skin or nails.
[0272] In another aspect, the present disclosure provides a method
for treating a fungal infection, comprising: topically applying to
a target site afflicted with fungal infection a biophotonic
composition comprising a first chromophore; and illuminating said
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the first chromophore. In
some embodiments, the target site may be skin or nails.
[0273] In another aspect, the present disclosure provides a method
for treating a fungal infection, comprising: topically applying to
a target site afflicted with fungal infection a biophotonic
composition comprising a first chromophore; one or more salts
selected from bicarbonate salts, carbonate salts or a combination
of the foregoing salts; and one or more gelling agents, wherein
said composition does not include an oxidant selected from the
group consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate; and
illuminating said biophotonic composition with light having a
wavelength that overlaps with an absorption spectrum of the first
chromophore. In some embodiments, the target site may be skin or
nails. In some embodiments, the composition further comprises one
or more polyols.
[0274] In another aspect, the present disclosure provides a method
for a treating fungal infection, comprising: topically applying to
a target site afflicted with fungal infection a biophotonic
composition comprising a first chromophore, one or more polyols,
and one or more gelling agents, wherein said composition does not
include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate; and illuminating said
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the first chromophore. In
some embodiments, the target site may be skin or nails.
[0275] The present disclosure provides a method for providing a
biophotonic therapy to a target mouth afflicted with an oral
disease, the method comprising: applying (e.g., by topical
application) to a target site a biophotonic composition of the
present disclosure, and illuminating the biophotonic composition
with light having a wavelength that overlaps with an absorption
spectrum of the chromophore(s) of the biophotonic composition. In
certain such embodiments, said oral disease is chosen from
gingivitis, periodontitis, periodontal disease, oral thrush, lichen
planus, stomatitis, herpes simplex lesion, oral mucositis, oral
ulcers, oral submucous fibrosis, and glossitis.
[0276] In some aspects, the present disclosure provides a method
for providing biophotonic therapy to a target mouth afflicted with
an oral disease, comprising: topically applying to a target site a
biophotonic composition comprising a first chromophore; one or more
salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts; and one or more gelling agents,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate; and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore. In some embodiments, the composition further
comprises one or more polyols. In certain such embodiments, said
oral disease is chosen from gingivitis, periodontitis, periodontal
disease, oral thrush, lichen planus, stomatitis, herpes simplex
lesion, oral mucositis, oral ulcers, oral submucous fibrosis, and
glossitis.
[0277] In some aspects, the present disclosure provides a method
for providing biophotonic therapy to a target mouth afflicted with
an oral disease, comprising: topically applying to a target site a
biophotonic composition comprising a first chromophore, one or more
polyols, and one or more gelling agents, wherein said composition
does not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate; and illuminating said
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the first chromophore. In
certain such embodiments, said oral disease is chosen from
gingivitis, periodontitis, periodontal disease, oral thrush, lichen
planus, stomatitis, herpes simplex lesion, oral mucositis, oral
ulcers, oral submucous fibrosis, and glossitis.
[0278] In some aspects, the present disclosure provides a method
for treating or preventing an oral disease, comprising: topically
applying to the mouth of a subject a biophotonic composition
comprising a first chromophore; and illuminating said biophotonic
composition with light having a wavelength that overlaps with an
absorption spectrum of the first chromophore. In certain such
embodiments, said oral disease is chosen from gingivitis,
periodontitis, periodontal disease, oral thrush, lichen planus,
stomatitis, herpes simplex lesion, oral mucositis, oral ulcers,
oral submucous fibrosis, and glossitis.
[0279] The present disclosure provides a method for treating or
preventing an oral disease, comprising: topically applying to the
mouth of a subject a biophotonic composition, wherein the
biophotonic composition comprises a first chromophore; one or more
salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts; and one or more gelling agents,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate; and illuminating said biophotonic composition with light
having a wavelength that overlaps with an absorption spectrum of
the first chromophore. In some embodiments, the composition further
comprises one or more polyols. In certain such embodiments, said
oral disease is chosen from gingivitis, periodontitis, periodontal
disease, oral thrush, lichen planus, stomatitis, herpes simplex
lesion, oral mucositis, oral ulcers, oral submucous fibrosis, and
glossitis.
[0280] The present disclosure also provides a method for treating
or preventing an oral disease, comprising: topically applying to
the mouth of a subject a biophotonic composition, wherein the
biophotonic composition comprises a first chromophore, one or more
polyols, and one or more gelling agents, wherein said composition
does not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate; and illuminating said
biophotonic composition with light having a wavelength that
overlaps with an absorption spectrum of the first chromophore. In
certain such embodiments, said oral disease is chosen from
gingivitis, periodontitis, periodontal disease, oral thrush, lichen
planus, stomatitis, herpes simplex lesion, oral mucositis, oral
ulcers, oral submucous fibrosis, and glossitis.
[0281] The biophotonic compositions suitable for use in the methods
of the present disclosure may be selected from any of the
embodiments of the biophotonic compositions described above. For
instance, the biophotonic compositions useful in the method of the
present disclosure may comprise a first chromophore that undergoes
at least partial photobleaching upon application of light. In some
embodiments, the biophotonic compositions of the disclosure
maintain, within a first minute of illumination, at least 80% of
their initial level of fluorescence. The first chromophore may
absorb at a wavelength of about 200 to about 800 nm, about 200 to
about 700 nm, about 200 to about 600 nm or about 200 to about 500
nm. In some embodiments, the first chromophore absorbs at a
wavelength of about 200 to about 600 nm. In some embodiments, the
first chromophore absorbs light at a wavelength of about 200 to
about 300 nm, about 250 to about 350 nm, about 300 to about 400 nm,
about 350 to about 450 nm, about 400 to about 500 nm, about 450 to
about 650 nm, about 600 to about 700 nm, about 650 to about 750 nm
or about 700 to about 800 nm. In other examples, suitable
biophotonic compositions for the methods of the present disclosure
may further comprise at least one additional chromophore (e.g., a
second chromophore). The absorption spectrum of the second
chromophore overlaps at least about 80%, about 70%, about 60%,
about 50%, about 40%, about 30%, or about 20% with the emission
spectrum of the first chromophore. In some embodiments, the first
chromophore has an emission spectrum that overlaps at least 1-10%,
5-15%, 10-20%, 15-25%, 20-30%, 25-35%, 30-40%, 35-45%, 50-60%,
55-65% or 60-70% with an absorption spectrum of the second
chromophore.
[0282] Illumination of the biophotonic composition with light may
cause a transfer of energy from the first chromophore to the second
chromophore. Subsequently, the second chromophore may emit energy
as fluorescence and/or generate reactive oxygen species. In some
embodiments of the methods the present disclosure, energy transfer
caused by the application of light is not accompanied by
concomitant generation of heat, or does not result in tissue
damage.
[0283] When the method involves a biophotonic composition having at
least two chromophores, the first chromophore is present in an
amount of about 0.005-40% by weight of the composition, and the
second chromophore is present in an amount of about 0.0001-40% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of about 0.005-2%, about
0.01-1%, about 0.1-1%, about 0.1-2%, about 0.5-2%, about 1-5%,
about 2.5-7.5%, about 5-10%, about 7.5-12.5%, about 10-15%, about
12.5-17.5%, about 15-20%, about 17.5-22.5%, about 20-25%, about
22.5-27.5%, about 25-30%, about 27.5-32.5%, about 30-35%, about
32.5-37.5%, or about 35-40% by weight of the composition. In some
embodiments, the first chromophore is present in an amount of at
least about 0.2% by weight of the composition. In some embodiments,
the second chromophore is present in an amount of about 0.0001-2%,
about 0.001-1%, about 0.1-1%, about 0.1-2%, about 0.5-2%, about
1-5%, about 2.5-7.5%, about 5-10%, about 7.5-12.5%, about 10-15%,
about 12.5-17.5%, about 15-20%, about 17.5-22.5%, about 20-25%,
about 22.5-27.5%, about 25-30%, about 27.5-32.5%, about 30-35%,
about 32.5-37.5%, or about 35-40% by weight of the composition. In
some embodiments, the total weight by weight of the first
chromophore or combination of chromophores may be in the amount of
about 0.005-1%, about 0.1-1%, about 0.1-2%, about 0.5-2%, about
1-5%, about 2.5-7.5%, about 5-10%, about 7.5-12.5%, about 10-15%,
about 12.5-17.5%, about 15-20%, about 17.5-22.5%, about 20-25%,
about 22.5-27.5%, about 25-30%, about 27.5-32.5%, about 30-35%,
about 32.5-37.5%, or about 35-40% by weight of the composition. In
some embodiments, the first chromophore or combination of
chromophores is present in an amount of at least about 0.2% by
weight of the composition.
[0284] In some embodiments when the method involves a biophotonic
composition having at least two chromophores, the first chromophore
is present in an amount of 0.005-40% by weight of the composition,
and the second chromophore is present in an amount of 0.0001-40% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of 0.005-2%, 0.01-1%, 0.1-1%,
0.1-2%, 0.5-2%, 1-5%, 2.5-7.5%, 5-10%, 7.5-12.5%, 10-15%,
12.5-17.5%, 15-20%, 17.5-22.5%, 20-25%, 22.5-27.5%, 25-30%,
27.5-32.5%, 30-35%, 32.5-37.5%, or 35-40% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of at least 0.2% by weight of the composition. In some
embodiments, the second chromophore is present in an amount of
0.0001-2%, 0.001-1%, 0.1-1%, 0.1-2%, 0.5-2%, 1-5%, 2.5-7.5%, 5-10%,
7.5-12.5%, 10-15%, 12.5-17.5%, 15-20%, 17.5-22.5%, 20-25%,
22.5-27.5%, 25-30%, 27.5-32.5%, 30-35%, 32.5-37.5%, or 35-40% by
weight of the composition. In some embodiments, the total weight by
weight of the first chromophore or combination of chromophores may
be in the amount of 0.005-1%, 0.1-1%, 0.1-2%, 0.5-2%, 1-5%,
2.5-7.5%, 5-10%, 7.5-12.5%, 10-15%, 12.5-17.5%, 15-20%, 17.5-22.5%,
20-25%, 22.5-27.5%, 25-30%, 27.5-32.5%, 30-35%, 32.5-37.5%, or
35-40% by weight of the composition. In some embodiments, the first
chromophore or combination of chromophores is present in an amount
of at least 0.2% by weight of the composition.
[0285] In the methods of the present disclosure, any source of
actinic light can be used to illuminate the biophotonic
compositions. Any type of halogen, LED or plasma arc lamp or laser
may be suitable. The primary characteristic of suitable sources of
actinic light will be that they emit light in a wavelength (or
wavelengths) appropriate for activating the one or more
photoactivators present in the composition. In some embodiments, an
argon laser is used. In some embodiments, a potassium-titanyl
phosphate (KTP) laser (e.g. a GreenLight.TM. laser) is used. In
another embodiment, sunlight may be used. In some embodiments, a
LED photocuring device is the source of the actinic light. In some
embodiments, the source of the actinic light is a source of light
having a wavelength between about 200 nm to about 800 nm. In some
embodiments, the source of the actinic light is a source of visible
light having a wavelength between about 400 nm and about 700 nm. In
some embodiments, the source of the actinic light is a source of
visible light having a wavelength between about 400 nm and about
600 nm. In some embodiments, the source of the actinic light is a
source of visible light having a wavelength between about 400 nm
and about 550 nm. In some embodiments, the source of the actinic
light is a source of visible light having a wavelength between
about 380 nm and about 700 nm. In some embodiments, the source of
the actinic light is a source of visible light having a wavelength
between about 380 nm and about 600 nm. In some embodiments, the
source of the actinic light is a source of visible light having a
wavelength between about 380 nm and about 550 nm. In some
embodiments, the source of the actinic light is a source of light
having a wavelength between 200 nm to 800 nm. In some embodiments,
the source of the actinic light is a source of visible light having
a wavelength between 400 nm and 700 nm. In some embodiments, the
source of the actinic light is a source of visible light having a
wavelength between 400 nm and 600 nm. In some embodiments, the
source of the actinic light is a source of visible light having a
wavelength between 400 nm and 550 nm. In some embodiments, the
source of the actinic light is a source of visible light having a
wavelength between 380 nm and 700 nm. In some embodiments, the
source of the actinic light is a source of visible light having a
wavelength between 380 nm and 600 nm. In some embodiments, the
source of the actinic light is a source of visible light having a
wavelength between 380 nm and 550 nm. In some embodiments, the
biophotonic composition of the disclosure is illuminated with
violet and/or blue light. Furthermore, the source of actinic light
should have a suitable power density. Suitable power density for
non-collimated light sources (LED, halogen or plasma lamps) are in
the range from about 1 mW/cm.sup.2 to about 200 mW/cm.sup.2.
Suitable power density for laser light sources are in the range
from about 0.5 mW/cm.sup.2 to about 0.8 mW/cm.sup.2.
[0286] In some embodiments of the methods of the present
disclosure, the light has an energy at the subject's skin, wound or
mucosa surface of between about 1 mW/cm.sup.2 and about 500
mW/cm.sup.2, about 1-300 mW/cm.sup.2, or about 1-200 mW/cm.sup.2,
wherein the energy applied depends at least on the condition being
treated, the wavelength of the light, the distance of the subject's
skin from the light source, and the thickness of the biophotonic
composition. In some embodiments, the light at the subject's skin
is between about 1-40 mW/cm.sup.2, or about 20-60 mW/cm.sup.2, or
about 40-80 mW/cm.sup.2, or about 60-100 mW/cm.sup.2, or about
80-120 mW/cm.sup.2, or about 100-140 mW/cm.sup.2, or about 120-160
mW/cm.sup.2, or about 140-180 mW/cm.sup.2, or about 160-200
mW/cm.sup.2, or about 110-240 mW/cm.sup.2, or about 110-150
mW/cm.sup.2, or about 190-240 mW/cm.sup.2.
[0287] In some embodiments, a mobile device can be used to activate
embodiments of the biophotonic composition of the present
disclosure, wherein the mobile device can emit light having an
emission spectrum which overlaps an absorption spectrum of the
chromophore in the biophotonic composition. The mobile device can
have a display screen through which the light is emitted and/or the
mobile device can emit light from a flashlight which photoactivates
the biophotonic composition.
[0288] In some embodiments, a display screen on a television or a
computer monitor can be used to activate the biophotonic
composition, wherein the display screen can emit light having an
emission spectrum which overlaps an absorption spectrum of a
photoactive agent in the photoactivatable composition.
[0289] In some embodiments, the first and/or the second chromophore
(when present) can be photoactivated by ambient light which may
originate from the sun or other light sources. Ambient light can be
considered to be a general illumination that comes from all
directions in a room that has no visible source. In some
embodiments, the first and/or the second chromophore (when present)
can be photoactivated by light in the visible range of the
electromagnetic spectrum. Exposure times to ambient light may be
longer than that to direct light.
[0290] In some embodiments, different sources of light can be used
to activate the biophotonic compositions, such as a combination of
ambient light and direct LED light.
[0291] The duration of the exposure to actinic light required will
be dependent on the surface of the treated area, the type of
lesion, trauma or injury that is being treated, the power density,
wavelength and bandwidth of the light source, the thickness of the
biophotonic composition, and the treatment distance from the light
source. The illumination of the treated area by fluorescence may
take place within seconds or even fragment of seconds, but a
prolonged exposure period is beneficial to exploit the synergistic
effects of the absorbed, reflected and reemitted light on the
composition of the present disclosure and its interaction with the
tissue being treated. In some embodiments, the time of exposure to
actinic light of the tissue, skin or wound on which the biophotonic
composition has been applied is a period between 1 minute and 30
minutes. In some embodiments, the time of exposure to actinic light
of the tissue, skin or wound on which the biophotonic composition
has been applied is a period between 1 minute and 5 minutes. In
some embodiments, the time of exposure to actinic light of the
tissue, skin or wound on which the biophotonic composition has been
applied is a period between 1 minute and 5 minutes. In some
embodiments, the biophotonic composition is illuminated for a
period between 1 minute and 3 minutes. In some embodiments, light
is applied for a period of 1-30 seconds, 1-60 seconds, 15-45
seconds, 30-60 seconds, 0.75-1.5 minutes, 1-2 minutes, 1.5-2.5
minutes, 2-3 minutes, 2.5-3.5 minutes, 3-4 minutes, 3.5-4.5
minutes, 4-5 minutes, 5-10 minutes, 10-15 minutes, 15-20 minutes,
20-25 minutes, or 20-30 minutes. In some embodiments, light is
applied for a period of 1 second. In some embodiments, the
biophotonic composition is illuminated for a period less than 30
minutes. In some embodiments, the biophotonic composition is
illuminated for a period less than 20 minutes. In some embodiments,
the biophotonic composition is illuminated for a period less than
15 minutes. In some embodiments, the biophotonic composition is
illuminated for a period less than 10 minutes. In some embodiments,
the biophotonic composition is illuminated for a period less than 5
minutes. In some embodiments, the biophotonic composition is
illuminated for a period less than 1 minute. In some embodiments,
the biophotonic composition is illuminated for a period less than
30 seconds. In some embodiments, the biophotonic composition is
illuminated for a period less than 20 seconds.
[0292] In some embodiments, the biophotonic composition is
illuminated for a period less than 10 seconds. In some embodiments,
the biophotonic composition is illuminated for a period less than 5
seconds. In some embodiments, the biophotonic composition is
illuminated for a period less than 1 second. In some embodiments,
the source of actinic light is in continuous motion over the
treated area for the appropriate time of exposure. In some
embodiments, multiple applications of the biophotonic composition
and actinic light are performed. In some embodiments, the tissue,
skin or wound is exposed to actinic light at least two, three,
four, five or six times. In some embodiments, a fresh application
of the biophotonic composition is applied before exposure to
actinic light.
[0293] In the methods of the present disclosure, the biophotonic
composition may be optionally removed from the site of treatment
following application of light. In some embodiments, the
biophotonic composition is left on the treatment site for more than
30 minutes, more than one hour, more than 2 hours, more than 3
hours. It can be illuminated with ambient light. To prevent drying,
the composition can be covered with a transparent or translucent
cover such as a polymer film, or an opaque cover which can be
removed before illumination.
[0294] For any of the methods described herein, the embodiments of
this disclosure contemplate the use of any of the compositions, or
mixtures of them, described throughout the application. In
addition, in various embodiments of any of the methods described
herein, combinations of any step or steps of one method with any
step or steps from another method may be employed.
(5) Wounds and Wound Healing
[0295] The biophotonic compositions and methods of the present
disclosure are useful to treat wounds and promote wound healing.
Wounds that may be treated by the biophotonic compositions and
methods of the present disclosure include, for example, injuries to
the skin and subcutaneous tissue initiated in different ways (e.g.,
pressure ulcers from extended bed rest, wounds induced by trauma,
wounds induced by conditions such as periodontitis) and with
varying characteristics. In some embodiments, the present
disclosure provides biophotonic compositions and methods for
treating and/or promoting the healing of, for example, burns,
incisions, excisions, lacerations, abrasions, puncture or
penetrating wounds, surgical wounds, contusions, hematomas,
crushing injuries, sores and ulcers. Wounds that may be treated by
the biophotonic compositions and methods of the present disclosure
also include wounds of the skin and soft tissues. The biophotonic
compositions and methods of the present disclosure are also useful
for cosmesis.
[0296] Biophotonic compositions and methods of the present
disclosure are useful to treat and/or promote the healing of
chronic cutaneous ulcers or wounds, which are wounds that have
failed to proceed through an orderly and timely series of events to
produce a durable structural, functional, and cosmetic closure. The
vast majority of chronic wounds can be classified into three
categories based on their etiology: pressure ulcers, neuropathic
(diabetic foot) ulcers and vascular (venous or arterial)
ulcers.
[0297] The present disclosure provides biophotonic compositions and
methods for treating and/or promoting healing, Grade I-IV ulcers.
In some embodiments, the application provides compositions suitable
for use with Grade II ulcers in particular. Ulcers may be
classified into one of four grades depending on the depth of the
wound: i) Grade I: wounds limited to the epithelium; ii) Grade II:
wounds extending into the dermis; iii) Grade III: wounds extending
into the subcutaneous tissue; and iv) Grade IV (or full-thickness
wounds): wounds wherein bones are exposed (e.g., a bony pressure
point such as the greater trochanter or the sacrum).
[0298] For example, the present disclosure provides biophotonic
compositions and methods for treating and/or promoting healing of a
diabetic ulcer. Diabetic patients are prone to foot and other
ulcerations due to both neurologic and vascular complications.
Peripheral neuropathy can cause altered or complete loss of
sensation in the foot and/or leg. Diabetic patients with advanced
neuropathy lose all ability for sharp-dull discrimination. Any cuts
or trauma to the foot may go completely unnoticed for days or weeks
in a patient with neuropathy. A patient with advanced neuropathy
loses the ability to sense a sustained pressure insult, as a
result, tissue ischemia and necrosis may occur leading to for
example, plantar ulcerations. Microvascular disease is one of the
significant complications for diabetics which may also lead to
ulcerations. In some embodiments, compositions and methods of
treating a chronic wound are provided here in, where the chronic
wound is characterized by diabetic foot ulcers and/or ulcerations
due to neurologic and/or vascular complications of diabetes.
[0299] In other examples, the present disclosure provides
biophotonic compositions and methods for treating and/or promoting
healing of a pressure ulcer. Pressure ulcer includes bed sores,
decubitus ulcers and ischial tuberosity ulcers and can cause
considerable pain and discomfort to a patient. A pressure ulcer can
occur as a result of a prolonged pressure applied to the skin.
Thus, pressure can be exerted on the skin of a patient due to the
weight or mass of an individual. A pressure ulcer can develop when
blood supply to an area of the skin is obstructed or cut off for
more than two or three hours. The affected skin area can turns red,
becomes painful and can become necrotic. If untreated, the skin
breaks open and can become infected. An ulcer sore is therefore a
skin ulcer that occurs in an area of the skin that is under
pressure from e.g. lying in bed, sitting in a wheelchair, and/or
wearing a cast for a prolonged period of time. Pressure ulcer can
occur when a person is bedridden, unconscious, unable to sense
pain, or immobile. Pressure ulcer often occur in boney prominences
of the body such as the buttocks area (on the sacrum or iliac
crest), or on the heels of foot.
[0300] In other examples, the present disclosure provides
biophotonic compositions and methods for treating and/or promoting
healing of acute wounds.
[0301] Additional types of wound that can be treated by the
biophotonic compositions and methods of the present disclosure
include those disclosed by U.S. Pat. Appl. Publ. No. 20090220450,
which is incorporated herein by reference.
[0302] Wound healing in adult tissues is a complicated reparative
process. For example, the healing process for skin involves the
recruitment of a variety of specialized cells to the site of the
wound, extracellular matrix and basement membrane deposition,
angiogenesis, selective protease activity and
re-epithelialization.
[0303] There are three distinct phases in the wound healing
process. First, in the inflammatory phase, which typically occurs
from the moment a wound occurs until the first two to five days,
platelets aggregate to deposit granules, promoting the deposit of
fibrin and stimulating the release of growth factors. Leukocytes
migrate to the wound site and begin to digest and transport debris
away from the wound. During this inflammatory phase, monocytes are
also converted to macrophages, which release growth factors for
stimulating angiogenesis and the production of fibroblasts.
[0304] Second, in the proliferative phase, which typically occurs
from two days to three weeks, granulation tissue forms, and
epithelialization and contraction begin. Fibroblasts, which are key
cell types in this phase, proliferate and synthesize collagen to
fill the wound and provide a strong matrix on which epithelial
cells grow. As fibroblasts produce collagen, vascularization
extends from nearby vessels, resulting in granulation tissue.
Granulation tissue typically grows from the base of the wound.
Epithelialization involves the migration of epithelial cells from
the wound surfaces to seal the wound. Epithelial cells are driven
by the need to contact cells of like type and are guided by a
network of fibrin strands that function as a grid over which these
cells migrate. Contractile cells called myofibroblasts appear in
wounds, and aid in wound closure. These cells exhibit collagen
synthesis and contractility, and are common in granulating
wounds.
[0305] Third, in the remodeling phase, the final phase of wound
healing which can take place from three weeks up to several years,
collagen in the scar undergoes repeated degradation and
re-synthesis. During this phase, the tensile strength of the newly
formed skin increases.
[0306] However, as the rate of wound healing increases, there is
often an associated increase in scar formation. Scarring is a
consequence of the healing process in most adult animal and human
tissues. Scar tissue is not identical to the tissue which it
replaces, as it is usually of inferior functional quality. The
types of scars include, but are not limited to, atrophic,
hypertrophic and keloidal scars, as well as scar contractures.
Atrophic scars are flat and depressed below the surrounding skin as
a valley or hole. Hypertrophic scars are elevated scars that remain
within the boundaries of the original lesion, and often contain
excessive collagen arranged in an abnormal pattern. Keloidal scars
are elevated scars that spread beyond the margins of the original
wound and invade the surrounding normal skin in a way that is site
specific, and often contain whorls of collagen arranged in an
abnormal fashion.
[0307] In contrast, normal skin consists of collagen fibers
arranged in a basket-weave pattern, which contributes to both the
strength and elasticity of the dermis. Thus, to achieve a smoother
wound healing process, an approach is needed that not only
stimulates collagen production, but also does so in a way that
reduces scar formation.
[0308] The biophotonic compositions and methods of the present
disclosure promote the wound healing by promoting the formation of
substantially uniform epithelialization; promoting collagen
synthesis; promoting controlled contraction; and/or by reducing the
formation of scar tissue. In some embodiments, the biophotonic
compositions and methods of the present disclosure are useful in
promoting wound healing by promoting the formation of substantially
uniform epithelialization. In some embodiments, the biophotonic
compositions and methods of the present disclosure promote collagen
synthesis. In some embodiments, the biophotonic compositions and
methods of the present disclosure promote controlled contraction.
In some embodiments, the biophotonic compositions and methods of
the present disclosure promote wound healing, for example, by
reducing the formation of scar tissue or by speeding up the wound
closure process. In some embodiments, the biophotonic compositions
and methods of the present disclosure promote wound healing, for
example, by reducing inflammation. In some embodiments, the
biophotonic composition can be used following wound closure to
optimize scar revision. In this case, the biophotonic composition
may be applied at regular intervals such as once a week, or at an
interval deemed appropriate by the physician.
[0309] The biophotonic composition may be soaked into a woven or
non-woven material or a sponge and applied as a wound dressing. A
light source, such as LEDs or waveguides, may be provided within or
adjacent the wound dressing or the composition to illuminate the
composition. The waveguides can be optical fibers which can
transmit light, not only from their ends, but also from their body.
In some embodiments, the waveguides are made of polycarbonate or
polymethylmethacrylate.
[0310] Adjunct therapies which may be topical or systemic such as
antibiotic treatment may also be used. Negative pressure assisted
wound closure can also be used to assist wound closure and/or to
remove the composition.
(6) Acne and Acne Scars
[0311] The biophotonic compositions and methods of the present
disclosure are useful to treat acne. As used herein, "acne" means a
disorder of the skin caused by inflammation of skin glands or hair
follicles. The biophotonic compositions and methods of the
disclosure can be used to treat acne at early pre-emergent stages
or later stages where lesions from acne are visible. Mild, moderate
and severe acne can be treated with embodiments of the biophotonic
compositions and methods. Early pre-emergent stages of acne usually
begin with an excessive secretion of sebum or dermal oil from the
sebaceous glands located in the pilosebaceous apparatus. Sebum
reaches the skin surface through the duct of the hair follicle. The
presence of excessive amounts of sebum in the duct and on the skin
tends to obstruct or stagnate the normal flow of sebum from the
follicular duct, thus producing a thickening and solidification of
the sebum to create a solid plug known as a comedone. In the normal
sequence of developing acne, hyperkeratinazation of the follicular
opening is stimulated, thus completing blocking of the duct. The
usual results are papules, pustules, or cysts, often contaminated
with bacteria, which cause secondary infections. Acne is
characterized particularly by the presence of comedones,
inflammatory papules, or cysts. The appearance of acne may range
from slight skin irritation to pitting and even the development of
disfiguring scars. Accordingly, the biophotonic compositions and
methods of the present disclosure can be used to treat one or more
of skin irritation, pitting, development of scars, acne scars,
comedones, inflammatory papules, cysts, hyperkeratinazation, and
thickening and hardening of sebum associated with acne.
[0312] The composition may be soaked into or applied to a woven or
non-woven material or a sponge and applied as a mask to body parts
such as the face, body, arms, legs, etc. A light source, such as
LEDs or waveguides, may be provided within or adjacent the mask or
the composition to illuminate the composition. The waveguides can
be optical fibers which can transmit light, not only from their
ends, but also from their body. In some embodiments, the waveguides
are made of polycarbonate or polymethylmethacrylate.
[0313] The biophotonic compositions and methods of the present
disclosure are useful in the treatment of various types of acne.
Some types of acne include, for example, acne vulgaris, cystic
acne, acne atrophica, bromide acne, chlorine acne, acne conglobata,
acne cosmetica, acne detergicans, epidemic acne, acne estivalis,
acne fulminans, halogen acne, acne indurata, iodide acne, acne
keloid, acne mechanica, acne papulosa, pomade acne, premenstral
acne, acne pustulosa, acne scorbutica, acne scrofulosorum, acne
urticata, acne varioliformis, acne venenata, propionic acne, acne
excoriee, gram negative acne, steroid acne, and nodulocystic
acne.
(7) Skin Aging and Rejuvenation
[0314] The dermis is the second layer of skin, containing the
structural elements of the skin, the connective tissue. There are
various types of connective tissue with different functions.
Elastin fibers give the skin its elasticity, and collagen gives the
skin its strength.
[0315] The junction between the dermis and the epidermis is an
important structure. The dermal-epidermal junction interlocks
forming finger-like epidermal ridges. The cells of the epidermis
receive their nutrients from the blood vessels in the dermis. The
epidermal ridges increase the surface area of the epidermis that is
exposed to these blood vessels and the needed nutrients.
[0316] The aging of skin comes with significant physiological
changes to the skin. The generation of new skin cells slows down,
and the epidermal ridges of the dermal-epidermal junction flatten
out. While the number of elastin fibers increases, their structure
and coherence decrease. Also, the amount of collagen and the
thickness of the dermis decrease with the aging of the skin.
[0317] Collagen is a major component of the skin's extracellular
matrix, providing a structural framework. During the aging process,
the decrease of collagen synthesis and insolubilization of collagen
fibers contribute to a thinning of the dermis and loss of the
skin's biomechanical properties.
[0318] The physiological changes to the skin result in noticeable
aging symptoms often referred to as chronological-, intrinsic- and
photo-ageing. The skin becomes drier, roughness and scaling
increase, the appearance becomes duller, and most obviously fine
lines and wrinkles appear. Other symptoms or signs of skin aging
include, but are not limited to, thinning and transparent skin,
loss of underlying fat (leading to hollowed cheeks and eye sockets
as well as noticeable loss of firmness on the hands and neck), bone
loss (such that bones shrink away from the skin due to bone loss,
which causes sagging skin), dry skin (which might itch), inability
to sweat sufficiently to cool the skin, unwanted facial hair,
freckles, age spots, spider veins, rough and leathery skin, fine
wrinkles that disappear when stretched, loose skin, a blotchy
complexion.
[0319] The dermal-epidermal junction is a basement membrane that
separates the keratinocytes in the epidermis from the extracellular
matrix, which lies below in the dermis. This membrane consists of
two layers: the basal lamina in contact with the keratinocytes, and
the underlying reticular lamina in contact with the extracellular
matrix. The basal lamina is rich in collagen type IV and laminin,
molecules that play a role in providing a structural network and
bioadhesive properties for cell attachment.
[0320] Laminin is a glycoprotein that only exists in basement
membranes. It is composed of three polypeptide chains (alpha, beta
and gamma) arranged in the shape of an asymmetric cross and held
together by disulfide bonds. The three chains exist as different
subtypes which result in twelve different isoforms for laminin,
including Laminin-1 and Laminin-5.
[0321] The dermis is anchored to hemidesmosomes, specific junction
points located on the keratinocytes, which consist of a-integrins
and other proteins, at the basal membrane keratinocytes by type VII
collagen fibrils. Laminins, and particularly Laminin-5, constitute
the real anchor point between hemidesmosomal transmembrane proteins
in basal keratinocytes and type VII collagen.
[0322] Laminin-5 synthesis and type VII collagen expression have
been proven to decrease in aged skin. This causes a loss of contact
between dermis and epidermis, and results in the skin losing
elasticity and becoming saggy.
[0323] Recently another type of wrinkles generally referred to as
expression wrinkles, got general recognition. These wrinkles
require loss of resilience, particularly in the dermis, because of
which the skin is no longer able to resume its original state when
facial muscles which produce facial expressions exert stress on the
skin, resulting in expression wrinkles.
[0324] The compositions and methods of the present disclosure
promote skin rejuvenation. In some embodiments, the compositions
and methods of the present disclosure promote collagen synthesis.
The compositions and methods of the present disclosure may reduce,
diminish, retard or even reverse one or more signs of skin aging
including, but not limited to, appearance of fine lines or
wrinkles, thin and transparent skin, loss of underlying fat
(leading to hollowed cheeks and eye sockets as well as noticeable
loss of firmness on the hands and neck), bone loss (such that bones
shrink away from the skin due to bone loss, which causes sagging
skin), dry skin (which might itch), inability to sweat sufficiently
to cool the skin, unwanted facial hair, freckles, age spots, spider
veins, rough and leathery skin, fine wrinkles that disappear when
stretched, loose skin, or a blotchy complexion. In some
embodiments, the compositions and methods of the present disclosure
may induce a reduction in pore size, enhance sculpturing of skin
subsections, and/or enhance skin translucence.
(8) Skin Disorders
[0325] The biophotonic compositions and methods of the present
disclosure are useful to treat skin disorders that include, but are
not limited to, erythema, telangiectasia, actinic telangiectasia,
psoriasis, skin cancer, pemphigus, sunburn, dermatitis, eczema,
rashes, impetigo, lichen simplex chronicus, rhinophyma, perioral
dermatitis, pseudofolliculitis barbae, drug eruptions, erythema
multiforme, erythema nodosum, granuloma annulare, actinic
keratosis, purpura, alopecia areata, aphthous stomatitis, drug
eruptions, dry skin, chapping, xerosis, ichthyosis vulgaris, fungal
infections, parasitic infection, herpes simplex, intertrigo,
keloids, keratoses, milia, moluscum contagiosum, pityriasis rosea,
pruritus, urticaria, and vascular tumors and malformations.
Dermatitis includes contact dermatitis, atopic dermatitis,
seborrheic dermatitis, nummular dermatitis, generalized exfoliative
dermatitis, and statis dermatitis. Skin cancers include melanoma,
basal cell carcinoma, and squamous cell carcinoma.
[0326] Some skin disorders present various symptoms including
redness, flushing, burning, scaling, pimples, papules, pustules,
comedones, macules, nodules, vesicles, blisters, telangiectasia,
spider veins, sores, surface irritations or pain, itching,
inflammation, red, purple, or blue patches or discolorations,
moles, and/or tumors. Accordingly, the biophotonic compositions and
methods of the present disclosure can be used to treat redness,
flushing, burning, scaling, pimples, papules, pustules, comedones,
macules, nodules, vesicles, blisters, telangiectasia, spider veins,
sores, surface irritations or pain, itching, inflammation, red,
purple, or blue patches or discolorations, moles, and/or
tumors.
[0327] The composition may be soaked into or applied to a woven or
non-woven material or a sponge and applied as a mask to body parts
to treat skin disorders. A light source, such as
[0328] LEDs or waveguides, may be provided within or adjacent the
mask or the composition to illuminate the composition. The
waveguides can be optical fibres which can transmit light, not only
from their ends, but also from their body. In some embodiments, the
waveguides are made of polycarbonate or polymethylmethacrylate.
(9) Acute and Chronic Inflammation
[0329] Acute inflammation can present itself as pain, heat,
redness, swelling and loss of function. It includes conditions seen
in allergic reactions e.g.; such as insect bites (mosquito, bees,
wasps, ants, spiders etc), reaction to poison ivy or stinging
nettle or the like, post-ablative treatment.
[0330] Chronic inflammation can be caused by conditions including,
but not limited to, persistent injuries or infections, such as
ulcers or tuberculosis; prolonged exposure to a toxic agent;
cancer, diabetes, or autoimmune diseases such as rheumatoid
arthritis, systemic lupus erythematosus, and multiple
sclerosis.
[0331] The composition may be soaked into or applied to a woven or
non-woven material or a sponge and applied as a mask to body parts
to treat skin disorders. A light source, such as
[0332] LEDs or waveguides, may be provided within or adjacent the
mask or the composition to illuminate the composition. The
waveguides can be optical fibres which can transmit light, not only
from their ends, but also from their body. In some embodiments, the
waveguides are made of polycarbonate or polymethylmethacrylate.
(10) Oral Diseases
[0333] The biophotonic compositions and methods of the present
disclosure are useful to treat oral diseases. The oral disease may
be chosen from, but is not limited to, gingivitis, periodontitis,
periodontal disease, oral thrush, lichen planus, and
stomatitis.
Gingivitis
[0334] Gingivitis is a disorder that is defined by the inflammation
of the gums, and is characterized as a periodontal disease, which
are characterized by the destruction of the gums, tissue, tooth
sockets, and ligaments which create the structure that holds the
teeth in place. Gingivitis is one of the first stages of serious
periodontal disease.
[0335] The symptoms of gingivitis include swollen gums, mouth
sores, a bright red or purple appearance to the gums, shiny gums,
gums that are painless except when touched, and bleeding gums.
Often the first signs of gingivitis have no symptoms except for
visual symptoms and is likely only to be diagnosed by a dental
professional.
Periodontal Disease
[0336] Periodontal disease is more prevalent in developing nations
and in most cases, a professional cleaning and antibiotics can
clear up most cases of periodontal disease. However, if left
untreated the infection can spread throughout the body and can lead
to serious health complications.
[0337] Symptoms of periodontal disease include painful gums, bad
breath, a foul taste to the mouth, fever, gums that bleed with only
mild amounts of pressure, crater sized canker sores between the
teeth and gums, swollen lymph nodes around the head, neck, or jaw,
a gray film on the gums, red gums, swollen gums, and pain when
eating and swallowing.
[0338] Periodontitis
[0339] Periodontitis or Pyorrhea alveolaris is the inflammation of
the periodontium which comprises tissues supporting the teeth in
the oral cavity. Parts included in the periodontium are the gingiva
(gum tissue), the alveolar bone which are sockets where teeth are
attached, the cementum or outer layer of teeth roots and the
periodontal ligaments or PDL composed of connective tissue fibers
linking the gingival and cementum to the alveolar bone. The
condition is described as the progressive loss of bone around teeth
leading to loose teeth or loss of teeth if left unattended. There
are different causes for the disease in which bacteria is the most
common. Periodontitis is considered as an advanced phase of gum
disease since it already involves bone loss in the area. It is the
effect of mild gingivitis being left untreated. Due to the presence
of bacterial infection, the body can also respond negatively to it
leading to further complications. The condition is one of the
leading causes of tooth loss among adults, affecting around 50% of
everyone over the age of 30.
[0340] Signs and symptoms arise due to the unstable anchoring of
teeth as well as the presence of microorganisms. Gums occasionally
or frequently bleed or turn red while brushing teeth, using dental
floss, biting into food, chewing or touching with fingers. Gums
swell or develop pus occasionally as well. The affected individual
likely has halitosis or bad breath and have a lingering metallic or
tinny taste inside the mouth. Teeth seem longer and sharper due to
gingival recession which partly may also be caused by hard
brushing. If enzymes called collagenases have begun destroying
collagen, the person will have deep pockets between the teeth and
gums. In some embodiments, biophotonic compositions of the present
disclosure are applied to the periodontal pockets of a subject.
[0341] During the early stages of periodontal disease, only a few
signs and symptoms may be noticeable. Aggressive periodontitis may
affect younger individuals and can occur in episodes. Some episodes
may present very mild symptoms while others may be very severe. The
signs and symptoms especially in the case of chronic periodontitis
are usually progressive in nature.
Oral Thrush
[0342] Oral thrush is the condition where the fungus Candida
albicans grows rapidly and uncontrollably in the mouth. The
bacterium known as flora keeps the growth of Candida albicans under
control in a healthy body. Oral thrush presents with creamy white
paste that covers the tongue, and can spread rapidly to the roof of
the mouth, gums, back of the throat, tonsils, and the inside of the
cheeks. Babies, toddlers, older adults, and patients whose immune
systems have been somehow compromised are most likely to come down
with oral thrush.
[0343] Symptoms of oral thrush begin with a white pasty covering
over the tongue and inside of the cheeks. As the oral thrush
continues to develop, it can cause a mild amount of bleeding if the
tongue is scraped or when the patient brushes their teeth. These
symptoms may develop very quickly, but thrush can last for months.
If the lesions of oral thrush spread down the esophagus, the
patient may develop addition symptoms such as difficulty
swallowing, the sensation of food being caught in the throat or the
middle of the chest, and a fever should the infection continue to
spread past the esophagus.
Lichen Planus
[0344] Lichen planus is most often defined as an oral disease that
affects the lining of the mouth with inflammation. Lichen planus is
most often recognized as a rash that irritates the tissue of the
oral cavity. Most patients come down with their first case between
the age of 45 and 60, although a slowly increasing number of
reports dealing with younger patients have trickled in. While
lichen planus is most often associated with the interior of the
cheeks, many cases will find the entire mouth is affected,
including the gums, the tongue, the lips, and in rare cases, the
throat or esophagus. Lichen planus also occurs on the skin, as a
skin disease, and often must be referred to specifically as skin
lichen planus to differentiate between the oral type.
[0345] Lichen planus is a self-contained disease that can last for
weeks, months, and in some cases, years. It is not contagious. It
is often mistaken for genital diseases, as the genitalia are often
the most noticeably affected during the early development stage.
Because the symptoms and outbreaks occur rapidly and then
disappear, often for weeks, treatment is difficult. While some
patients find great relief in cool compresses or tub soaks and cool
baths, most patients require medical treatment in order to relieve
their symptoms.
Stomatitis
[0346] Stomatitis basically means inflammation of the mouth, but
more specifically, stomatitis is the inflammation of the mucous
lining of the mouth which may include the gums, tongue, cheeks,
lips and the floor or roof of the mouth. There are different types
of stomatitis and classification is based on how the disease was
acquired by a person. The two types of stomatitis are contact
stomatitis and aphthous stomatitis. Contact stomatitis is an
inflammation of the oral mucosa caused by coming in contact with
allergens or irritants. It is classified by its pattern of
distribution, etiologic factors, and clinical features. There some
cases of contact stomatitis that are left undetected because of the
lack of clinical signs. Anybody can have contact stomatitis
regardless of race, age and sex. Although it has been observed that
it is more common in the elders.
[0347] Aphthous stomatitis, also known as canker sore or aphthous
ulcers, has an unknown etiology. Just like contact stomatitis,
canker sore affects the oral mucosa. An aphthous ulcer is a type of
oral ulcer, which presents as a painful open sore inside the mouth
or upper throat (including the uvula) caused by a break in the
mucous membrane. The condition is also known as Sutton's Disease,
especially in the case of major, multiple, or recurring ulcers. The
ulcers can be described as shallow, discrete, and painful and are
usually visible on the mucous membranes that are unattached. This
type of stomatitis, just like contact stomatitis, is self limited
and do not usually cause complications. The normal size of ulcers
may last for 1 to 2 weeks but larger ulcers may last for
months.
Herpes Simplex Lesions
[0348] Herpes simplex is a viral disease caused by herpes simplex
viruses; both herpes simplex virus 1 (HSV-1) and herpes simplex
virus 2 (HSV-2) cause herpes simplex. Infection with the herpes
virus is categorized into one of several distinct disorders based
on the site of infection. Oral Herpes, the visible symptoms of
which are colloquially called cold sores, and infects the face and
mouth. Oral herpes is the most common form of herpes simplex
viruses infection.
Other Oral Inflammatory Lesions
[0349] The subject matters of the present disclosure may be used to
treat other types of oral inflammation, including but not limited
to oral mucositis, oral ulcers caused by viral, bacterial, fungal
or protozoan infections, or caused by disorders of the immune
system (immunodeficiency, autoimmunity, or allergy). Also included
is Oral Submucous Fibrosis, a chronic debilitating disease of the
oral cavity characterized by inflammation and progressive fibrosis
of the submucosal tissues. Also included is Glossitis, an
inflammation or infection of the tongue. It causes the tongue to
swell and change color.
(11) Kits
[0350] The present disclosure also provides kits for preparing
and/or applying any of the compositions of the present disclosure.
The kit may include a biophotonic topical composition, as defined
above, together with one or more of a light source, devices for
applying or removing the composition, instructions of use for the
composition and/or light source. In some embodiments, the
composition comprises at least a first chromophore; one or more
salts selected from bicarbonate salts, carbonate salts or a
combination of the foregoing salts; and one or more gelling agents,
wherein said composition does not include an oxidant selected from
the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate. In some embodiments, the composition further comprises
one or more polyols.
[0351] In some embodiments, the composition comprises at least a
first chromophore, one or more gelling agents, and one or more
polyols, wherein said composition does not include an oxidant
selected from the group consisting of a peroxide, a peroxy acid,
hydrogen peroxide, carbamide peroxide, an alkali metal peroxide, an
alkali metal percarbonate, peroxyacetic acid, and an alkali metal
perborate.
[0352] The first chromophore may be present in an amount of about
0.005-0.1%, about 0.05-1%, about 0.1-1%, about 0.1-2%, about
0.5-2%, about 1-5%, about 2.5-7.5%, about 5-10%, about 7.5-12.5%,
about 10-15%, about 12.5-17.5%, about 15-20%, about 17.5-22.5%,
about 20-25%, about 22.5-27.5%, about 25-30%, about 27.5-32.5%,
about 30-35%, about 32.5-37.5%, or about 35-40% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of at least about 0.2% by weight of the composition.
The first chromophore may be present in an amount of 0.005-0.1%,
0.05-1%, 0.1-1%, 0.1-2%, 0.5-2%, 1-5%, 2.5-7.5%, 5-10%, 7.5-12.5%,
10-15%, 12.5-17.5%, 15-20%, 17.5-22.5%, 20-25%, 22.5-27.5%, 25-30%,
27.5-32.5%, 30-35%, 32.5-37.5%, or 35-40% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of at least 0.2% by weight of the composition.
[0353] In embodiments where the composition comprises more than one
chromophore, the first chromophore may be present in an amount of
about 0.005-40% by weight of the composition, and a second
chromophore may be present in an amount of about 0.0001-40% by
weight of the composition. In some embodiments, the first
chromophore is present in an amount of about 0.005-2%, about
0.01-0.1%, about 0.05-1%, about 0.1-1%, about 0.1-2%, about 0.5-2%,
about 1-5%, about 2.5-7.5%, about 5-10%, about 7.5-12.5%, about
10-15%, about 12.5-17.5%, about 15-20%, about 17.5-22.5%, about
20-25%, about 22.5-27.5%, about 25-30%, about 27.5-32.5%, about
30-35%, about 32.5-37.5%, or about 35-40% by weight of the
composition. In some embodiments, the first chromophore is present
in an amount of at least about 0.2% by weight of the composition.
In some embodiments, the second chromophore is present in an amount
of about 0.0001-2%, about 0.001-0.1%, about 0.05-1%, about 0.1-1%,
about 0.1-2%, about 0.5-2%, about 1-5%, about 2.5-7.5%, about
5-10%, about 7.5-12.5%, about 10-15%, about 12.5-17.5%, about
15-20%, about 17.5-22.5%, about 20-25%, about 22.5-27.5%, about
25-30%, about 27.5-32.5%, about 30-35%, about 2.5-37.5%, or about
35-40% by weight of the composition. In some embodiments, the
amount of the first chromophore or combination of chromophores may
be in the amount of about 0.05-40% by weight of the composition. In
some embodiments, the amount of the first chromophore or
combination of chromophores may be in the amount of about
0.005-0.1%, about 0.05-1%, about 0.1-1%, about 0.1-2%, about
0.5-2%, about 1-5%, about 2.5-7.5%, about 5-10%, about 7.5-12.5%,
about 10-15%, about 12.5-17.5%, about 15-20%, about 17.5-22.5%,
about 20-25%, about 22.5-27.5%, about 25-30%, about 27.5-32.5%,
about 30-35%, about 32.5-37.5%, or about 35-40% by weight of the
composition. In some embodiments, the first chromophore or
combination of chromophores is present in an amount of at least
about 0.2% by weight of the composition. In embodiments where the
composition comprises more than one chromophore, the first
chromophore may be present in an amount of about 0.005-40% by
weight of the composition, and a second chromophore may be present
in an amount of about 0.0001-40% by weight of the composition. In
some embodiments, the first chromophore is present in an amount of
0.005-2%, 0.01-0.1%, 0.05-1%, 0.1-1%, 0.1-2%, 0.5-2%, 1-5%,
2.5-7.5%, 5-10%, 7.5-12.5%, 10-15%, 12.5-17.5%, 15-20%, 17.5-22.5%,
20-25%, 22.5-27.5%, 25-30%, 27.5-32.5%, 30-35%, 32.5-37.5%, or
35-40% by weight of the composition. In some embodiments, the first
chromophore is present in an amount of at least 0.2% by weight of
the composition. In some embodiments, the second chromophore is
present in an amount of 0.0001-2%, 0.001-0.1%, 0.05-1%, 0.1-1%,
0.1-2%, 0.5-2%, 1-5%, 2.5-7.5%, 5-10%, 7.5-12.5%, 10-15%,
12.5-17.5%, 15-20%, 17.5-22.5%, 20-25%, 22.5-27.5%, 25-30%,
27.5-32.5%, 30-35%, 32.5-37.5%, or 35-40% by weight of the
composition. In some embodiments, the amount of the first
chromophore or combination of chromophores may be in the amount of
about 0.05-40% by weight of the composition. In some embodiments,
the amount of the first chromophore or combination of chromophores
may be in the amount of 0.005-0.1%, 0.05-1%, 0.1-1%, 0.1-2%,
0.5-2%, 1-5%, 2.5-7.5%, 5-10%, 7.5-12.5%, 10-15%, 12.5-17.5%,
15-20%, 17.5-22.5%, 20-25%, 22.5-27.5%, 25-30%, 27.5-32.5%, 30-35%,
32.5-37.5%, or 35-40% by weight of the composition. In some
embodiments, the first chromophore or combination of chromophores
is present in an amount of at least 0.2% by weight of the
composition.
[0354] In some embodiments, the kit includes more than one
composition, for example, a first and a second composition. The
first composition may include one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts and the second composition may include the first
chromophore in the one or more gelling agents, wherein said first
and second compositions do not include an oxidant selected from the
group consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate. In
some embodiments, the first composition, the second composition, or
both further comprise one or more polyols.
[0355] In some embodiments, the first composition may include one
or more polyols and the second composition may include the first
chromophore, and one or more gelling agents, wherein said first and
second compositions do not include an oxidant selected from the
group consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate.
[0356] The first chromophore may have an emission wavelength
between about 400 nm and about 570 nm. The first chromophore may be
present in the second composition in an amount of about 0.005-0.1%,
about 0.05-1%, about 0.1-1%, about 0.1-2%, about 0.5-2%, about
1-5%, about 2.5-7.5%, about 5-10%, about 7.5-12.5%, about 10-15%,
about 12.5-17.5%, about 15-20%, about 17.5-22.5%, about 20-25%,
about 22.5-27.5%, about 25-30%, about 27.5-32.5%, about 30-35%,
about 32.5-37.5%, or about 35-40% by weight of the second
composition. In some embodiments, the first chromophore is present
in an amount of at least about 0.2% by weight of the second
composition. In embodiments where the second composition comprises
more than one chromophore, the first chromophore may be present in
an amount of about 0.005-40% by weight of the second composition,
and a second chromophore may be present in an amount of about
0.0001-40% by weight of the second composition. In some
embodiments, the first chromophore is present in an amount of about
0.005-2%, about 0.001-0.1%, about 0.05-1%, about 0.1-1%, about
0.1-2%, about 0.5-2%, about 1-5%, about 2.5-7.5%, about 5-10%,
about 7.5-12.5%, about 10-15%, about 12.5-17.5%, about 15-20%,
about 17.5-22.5%, about 20-25%, about 22.5-27.5%, about 25-30%,
about 27.5-32.5%, about 30-35%, about 32.5-37.5%, or about 35-40%
by weight of the second composition. In some embodiments, the first
chromophore is present in an amount of at least about 0.2% by
weight of the second composition. In some embodiments, the second
chromophore is present in an amount of about 0.0001-2%, about
0.001-0.1%, about 0.05-1%, about 0.5-2%, about 1-5%, about
2.5-7.5%, about 5-10%, about 7.5-12.5%, about 10-15%, about
12.5-17.5%, about 15-20%, about 17.5-22.5%, about 20-25%, about
22.5-27.5%, about 25-30%, about 27.5-32.5%, about 30-35%, about
32.5-37.5%, or about 35-40% by weight of the second composition. In
some embodiments, the amount of the first chromophore or
combination of chromophores may be in the amount of about 0.005-40%
by weight of the second composition. In some embodiments, the
amount of the first chromophore or combination of chromophores may
be in the amount of about 0.005-0.1%, about 0.1-1%, about 0.1-2%,
about 0.05-1%, about 0.5-2%, about 1-5%, about 2.5-7.5%, about
5-10%, about 7.5-12.5%, about 10-15%, about 12.5-17.5%, about
15-20%, about 17.5-22.5%, about 20-25%, about 22.5-27.5%, about
25-30%, about 27.5-32.5%, about 30-35%, about 32.5-37.5%, or about
35-40% by weight of the second composition. In some embodiments,
the first chromophore or combination of chromophores is present in
an amount of at least about 0.2% by weight of the second
composition. The first chromophore may be present in the second
composition in an amount of 0.005-0.1%, 0.05-1%, 0.1-1%, 0.1-2%,
0.5-2%, 1-5%, 2.5-7.5%, 5-10%, 7.5-12.5%, 10-15%, 12.5-17.5%,
15-20%, 17.5-22.5%, 20-25%, 22.5-27.5%, 25-30%, 27.5-32.5%, 30-35%,
32.5-37.5%, or 35-40% by weight of the second composition. In some
embodiments, the first chromophore is present in an amount of at
least 0.2% by weight of the second composition. In embodiments
where the second composition comprises more than one chromophore,
the first chromophore may be present in an amount of 0.005-40% by
weight of the second composition, and a second chromophore may be
present in an amount of 0.0001-40% by weight of the second
composition. In some embodiments, the first chromophore is present
in an amount of 0.005-2%, 0.001-0.1%, 0.05-1%, 0.1-1%, 0.1-2%,
0.5-2%, 1-5%, 2.5-7.5%, 5-10%, 7.5-12.5%, 10-15%, 12.5-17.5%,
15-20%, 17.5-22.5%, 20-25%, 22.5-27.5%, 25-30%, 27.5-32.5%, 30-35%,
32.5-37.5%, or 35-40% by weight of the second composition. In some
embodiments, the first chromophore is present in an amount of at
least 0.2% by weight of the second composition. In some
embodiments, the second chromophore is present in an amount of
0.0001-2%, 0.001-0.1%, 0.05-1%, 0.5-2%, 1-5%, 2.5-7.5%, 5-10%,
7.5-12.5%, 10-15%, 12.5-17.5%, 15-20%, 17.5-22.5%, 20-25%,
22.5-27.5%, 25-30%, 27.5-32.5%, 30-35%, 32.5-37.5%, or 35-40% by
weight of the second composition. In some embodiments, the amount
of the first chromophore or combination of chromophores may be in
the amount of 0.005-40% by weight of the second composition. In
some embodiments, the amount of the first chromophore or
combination of chromophores may be in the amount of 0.005-0.1%,
0.1-1%, 0.1-2%, 0.05-1%, 0.5-2%, 1-5%, 2.5-7.5%, 5-10%, 7.5-12.5%,
10-15%, 12.5-17.5%, 15-20%, 17.5-22.5%, 20-25%, 22.5-27.5%, 25-30%,
27.5-32.5%, 30-35%, 32.5-37.5%, or 35-40% by weight of the second
composition. In some embodiments, the first chromophore is present
in an amount of at least 0.2% by weight of the second
composition.
[0357] In some embodiments, the first composition may comprise the
first chromophore in a liquid or as a powder, and the second
composition may comprise one or more gelling agents for thickening
the first composition, wherein said first and second compositions
do not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate. The salt selected from one or
more bicarbonate salts or carbonate salts or a combination of the
foregoing salts may be contained in the second composition or in a
third composition in the kit, wherein said first, second, and third
compositions do not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate. In
some embodiments, the first composition, the second composition,
the third composition or all three compositions further comprise
one or more polyols.
[0358] In some embodiments, the first composition may comprise the
first chromophore in a liquid or as a powder, and the second
composition may comprise one or more gelling agents for thickening
the first composition, wherein said first and second compositions
do not include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate. The one or more polyols may be
contained in the second composition or in a third composition in
the kit, wherein said first, second, and third compositions do not
include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate.
[0359] In some embodiments, the first composition may comprise the
first chromophore in a liquid or as a powder, and the second
composition may comprise one or more gelling agents for thickening
the first composition and one or more salts selected from
bicarbonate salts, carbonate salts or a combination of the
foregoing salts, wherein said first and second compositions do not
include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate. In some embodiments, the first
composition, the second composition, or both further comprise one
or more polyols.
[0360] In some embodiments, the first composition may comprise the
first chromophore in a liquid or as a powder, and the second
composition may comprise one or more gelling agents for thickening
the first composition and a polyol, wherein said first and second
compositions do not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate.
[0361] In some embodiments, the first composition may comprise the
first chromophore and a polyol, and the second composition may
comprise one or more gelling agents for thickening the first
composition, wherein said first and second compositions do not
include an oxidant selected from the group consisting of a
peroxide, a peroxy acid, hydrogen peroxide, carbamide peroxide, an
alkali metal peroxide, an alkali metal percarbonate, peroxyacetic
acid, and an alkali metal perborate.
[0362] In some embodiments, the kit includes containers comprising
the compositions of the present disclosure. In some embodiments,
the kit includes a first container comprising a first composition
that includes one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts, and a
second container comprising a second composition that includes at
least one chromophore and one or more gelling agents, wherein said
first and second compositions do not include an oxidant selected
from the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate. In some embodiments, the first composition further
comprises one or more gelling agents. In some embodiments, the
first composition, the second composition, or both further comprise
one or more polyols.
[0363] In some embodiments, the kit includes containers comprising
the compositions of the present disclosure. In some embodiments,
the kit includes a first container comprising a first composition
that includes one or more salts selected from bicarbonate salts,
carbonate salts or a combination of the foregoing salts and one or
more gelling agents, and a second container comprising a second
composition that includes at least one chromophore, wherein said
first and second compositions do not include an oxidant selected
from the group consisting of a peroxide, a peroxy acid, hydrogen
peroxide, carbamide peroxide, an alkali metal peroxide, an alkali
metal percarbonate, peroxyacetic acid, and an alkali metal
perborate. In some embodiments, the second composition further
comprises one or more gelling agents. In some embodiments, the
first composition, the second composition, or both further comprise
one or more polyols.
[0364] In some embodiments, the kit includes containers comprising
the compositions of the present disclosure. In some embodiments,
the kit includes a first container comprising a first composition
that includes one or more polyols and a second container comprising
a second composition that includes at least the first chromophore
and one or more gelling agents, wherein said first and second
compositions do not include an oxidant selected from the group
consisting of a peroxide, a peroxy acid, hydrogen peroxide,
carbamide peroxide, an alkali metal peroxide, an alkali metal
percarbonate, peroxyacetic acid, and an alkali metal perborate. In
some embodiments, the first composition further comprises one or
more gelling agents. In some embodiments, the second composition
further comprises one or more polyols.
[0365] The containers may be light impermeable, air-tight and/or
leak resistant. Exemplary containers include, but are not limited
to, syringes, vials, or pouches. The first and second compositions
may be included within the same container but separated from one
another until a user mixes the compositions. For example, the
container may be a dual-chamber syringe where the contents of the
chambers mix on expulsion of the compositions from the chambers. In
another example, the pouch may include two chambers separated by a
frangible membrane. In another example, one component may be
contained in a syringe and injectable into a container comprising
the second component.
[0366] The biophotonic composition may also be provided in a
container comprising one or more chambers for holding one or more
components of the biophotonic composition, and an outlet in
communication with the one or more chambers for discharging the
biophotonic composition from the container.
[0367] In some embodiments, the kit comprises a systemic or topical
drug for augmenting the treatment of the composition. For example,
the kit may include a systemic or topical antibiotic or hormone
treatment for acne treatment or wound healing.
[0368] Written instructions on how to use the biophotonic
composition in accordance with the present disclosure may be
included in the kit, or may be included on or associated with the
containers comprising the compositions of the present
disclosure.
[0369] In some embodiments, the kit may comprise a further
component which is a dressing. The dressing may be a porous or
semi-porous structure for receiving the biophotonic composition.
The dressing may comprise woven or non-woven fibrous materials.
[0370] In some embodiments of the kit, the kit may further comprise
a light source such as a portable light with a wavelength
appropriate to activate the chromophore in the biophotonic
composition. The portable light may be battery operated or
re-chargeable.
[0371] In some embodiments, the kit may further comprise one or
more waveguides.
[0372] Identification of equivalent compositions, methods and kits
are well within the skill of the ordinary practitioner and would
require no more than routine experimentation, in light of the
teachings of the present disclosure. Practice of the disclosure
will be still more fully understood from the following examples,
which are presented herein for illustration only and should not be
construed as limiting the disclosure in any way.
EXAMPLES
[0373] The examples below are given so as to illustrate the
practice of various embodiments of the present disclosure. They are
not intended to limit or define the entire scope of this
disclosure.
[0374] It should be appreciated that the subject matters of this
disclosure are not limited to the particular embodiments described
and illustrated herein but includes all modifications and
variations falling within the scope of the subject matters of this
disclosure as defined in the appended claims.
Part A. Oxygen/Oxygen-species Production
Example 1. Brief Description of Gel Compositions and Assays for
Oxygen/Oxygen-Species (ROS) Production
[0375] The Examples of the present disclosure recite a number of
differing gel compositions utilized in the course of various
experimental protocols. For convenience and reference, a summary
table (Table 1 below) is presented listing the various gel
compositions along with a cross-reference to the particular Example
of the present disclosure wherein the particular gel composition is
mentioned. It is to be noted that for the Examples of the present
disclosure, if a particular component were added to a given gel
composition for testing of that particular component, the given
component is identified as being added to the given gel
composition.
TABLE-US-00001 TABLE 1 Gel compositions referred to Examples of the
description First Gel Referred to Name--Letter in Example
Abbreviation Components Number A Gel composition comprising gels A1
+ A2 2 mixed together A1 Gel composition having urea peroxide 2
(UP) + other components (but lacks having a chromophore) (% amount
of UP may vary) A2 Gel composition containing a chromophore (Eosin
Y @ 109 .mu.g/g) + other components 2 (but lacks UP). A3 A1 gel
composition, lacking the UP 2 A4 A2 gel composition, lacking the 4
chromophore B Carbopol + H.sub.2O 4 C Carbopol + H.sub.2O +
(sodium) bicarbonate + 5 chromophore D1 Carbopol + H.sub.2O +
glycerin + chromophore 5 D2 Carbopol + H.sub.2O + glycerin +
propylene 15 glycol (PG) + chromophore E Carbopol + H.sub.2O +
glycerin + PG + 17 parabens + chromophore
[0376] A concentration of the chromophore such as Eosin Y (which
may be abbreviated herein as EY or E) of 109 .mu.g/g (per 100 grams
of gel) is noted throughout the present disclosure to be 1.times.,
and would translate into a chromophore concentration of 0.109% per
100 gram weight of a gel composition. In Examples wherein the
amount of chromophore was altered, such levels are stated, as being
2.times. for twice the amount, 3.times. for three times the amount,
etc., based on the noted 1.times. concentration.
[0377] Assays
[0378] (i) The In Vitro Release Assay:
[0379] In an initial experiment, an in vitro release test was
employed, the general procedure for which is described in "Topical
and Transdermal Drug Products" (Dissolution Technologies, November
2010, at pages 17-18), incorporated herein by reference, and which
consists of a placing a test sample (e.g., a gel or ointment or
cream) onto a 3 cm diameter polycarbonate (PC) membrane having a
pore size of 3 .mu.m. The membrane is secured in a polycarbonate
holder device, which is placed into a well of a 6 well plate such
that the membrane is in direct contact (but not submerged) with a
phosphate buffer saline (PBS) solution situated in the well. A
typical form of the apparatus is a Thermo Scientific.TM.
GENESYS.TM. 10S UV-Vis spectrophotometer, which is commercially
available from Thermo Fisher Scientific Inc. In the case of the
present disclosure, in order to assay for the production of ROS,
the PBS solution also contained a quantity of liposomes (0.77 mg/mL
of liposome are loaded into the well with the total sample), and
the total volume of the PBS-liposome mixture in the well is 11 mL.
A volume of 1.4 mL of the given gel sample, which equates to an
approximately 2 mm thick layer of gel that would be typically
applied in vivo, is placed onto the membrane and the gel is
illuminated for 5 minutes using the KLOX multi-LED blue light
(THERA.TM.) at a distance of 5 cm from the gel surface. Upon
completion of the illumination period, a 100 .mu.L to 300 .mu.L
aliquot of the PBS-liposome solution is transferred from the test
apparatus to a 96-well microtiter plate for performance of the ROS
test (as further described below at (iii)).
[0380] (ii) The Dilution Assay:
[0381] For the dilution assay, an amount of a given gel composition
is taken and mixed into a volume of PBS in order to dilute the gel.
For example, to make a 10 mL solution ten times diluted, a 1 gram
sample of the particular gel is mixed into 9 mL of PBS. Thereafter,
depending on the make-up of the sample to be tested, an amount of a
particular compound, for example urea peroxide (UP) or a particular
salt, could be added in order to either boost an amount of the
particular compound that was already in the sample to be tested or
to test the effect of adding that given compound per se. With
respect to adding UP in order to make test samples with various
concentrations to be tested in a concomitant series of tests, an
initial sample with a high concentration would be prepared from
which aliquots would be taken and diluted down with PBS in order to
the test samples with the various concentration of UP. In a
multi-well plate, the given diluted sample are mixed with 19.1
.mu.L of the liposome solution (to give a final liposome
concentration of 15.4 mg/mL in the test sample) in order to provide
a 2 mm thickness of the resulting paste-like mixture, this
thickness being equivalent to a thickness of gel that would be
spread on a patient or used in an in vitro assay. Also present in
the sample-liposome mixture is a quantity of the chemical probe
that is used in the reactive oxygen species (ROS) test assay (362.9
.mu.L of the of the diluted gel (i.e., the given gel sample that is
to be tested) is mixed with 19.1 .mu.L of liposome-probe, as
including the chemical probe in the sample-liposome mixture is to
ensure that any ROS species will be afforded a maximal opportunity
to interact with the probe and thus be detectable as having been
generated as a result of any interaction that may occur in the gel
composition upon it becoming activated. The prepared
sample-liposome mixture is then illuminated under the THERA light
that is placed at a distance of 5 cm from the sample, with the
illumination time being 5 minutes. After the illumination is
completed, a 100 .mu.L to 300 .mu.L aliquot of the sample-liposome
transferred to a 96-well plate for conducting the ROS test (as
further described in (iii) below). For the test samples, stock
solutions of the samples were made and diluted such that direct
comparisons could be made between the samples (e.g., for the
measurement of reactive oxygen species).
[0382] (iii) The ROS Test Assay
[0383] The ROS test assay utilized in the experimental protocols of
the Examples of the present disclosure is that which is described
in Krumova et al. "How Lipid Unsaturation, Peroxyl Radical
Partitioning, and Chromanol Lipophilic Tail Affect the Antioxidant
Activity of a-Tocopherol: direct Visualization via High-Throughput
Fluorescence Studies Conducted with Fluorogenic a-Tocopherol
Analogues" (J. Am. Chem. Soc. 2012, vol. 134, pages 10102-10113).
The assay utilizes highly sensitive fluorogenic .alpha.-tocopherol
(TOH) analogues that undergo a 30-fold fluorescence intensity
enhancement upon their reaction with peroxyl radicals that are
generated due to the oxidation of the liposome membrane with ROS
species that may be present in the reaction mixture. The assay
utilizes a high-throughput microplate reader that relies on the
high sensitivity of the TOH probes and provides a quantitative
treatment of the temporal evolution of the fluorescence intensity
thereby allowing for kinetic information to be obtained under the
conditions being analyzed. The TOH analogues are two-segment
receptor-reporter probes that consist of a chromanol moiety coupled
to the meso position of a BODIPY fluorophore, either by an ester
linker (the probe being called H.sub.2B-TOH) or via a methylene
linker (the probe being called H.sub.2B-PMHC). The chromanol moiety
quenches the emission of the fluorophore until it is oxidized
following reaction with peroxyl radicals. The reporter segment for
both probes is an improved BODIPY dye having improved redox
potential; the favorable photoinduced electron transfer from the
chromanol to the BODIPY group allows for an excellent contrast
between the dark (reduced) and emissive (oxidized) states, thereby
allowing for the high-throughput fluorescence method to be
practiced. Both probes have been designed to ensure the efficient
photoinduced electron transfer from the chromanol to the BODIPY
segment, thereby ensuring an overall sensitivity to the "off-on"
probe.
Example 2. ROS Level Establishment
[0384] A series of experiments were performed to allow for an
assessment as to what degree the presence of a peroxide may
contribute to the formation of oxygen/oxygen-species in a
particular gel, and to test the for sensitivity of the in vitro
release test and the dilution assay.
[0385] In a first set of tests to establish the sensitivity of the
in vitro release test, samples of the gel A compositions were
prepared in which either no oxidant or an oxidant (a peroxide, in
the form of UP) was present in an amount as indicated in Table 2
below. The gel samples were placed on the membranes as described in
Example 1, and the samples illuminated for a period of 5 minutes,
after which an aliquot of the well-solution was taken and analyzed
for the amount of ROS present utilizing the ROS test described
above. The results are presented in Table 2 below.
TABLE-US-00002 TABLE 2 Testing for ROS production using the in
vitro release test Average Fluorescence Total ROS Samples With
Probe Without Prob Fluorescence .mu.M Gel A 16000 5800 10200 1.10
(4.6% UP) Gel A 16600 5790 10810 1.17 (1% UP) Gel A 15800 5400
10400 1.12 (0% UP)
[0386] From the results presented in Table 1, it was a determined
that while both of the chromophore-containing gel samples that were
tested produced ROS, distinguishing between the sample gel having
4.6% UP versus the sample gel containing 1% UP could not be made
despite the more than four-fold difference in the amount of UP
between the two samples, and furthermore, that the presence of the
chromophore may be a substantial contributing factor for the
generation of ROS in the gel composition. As such, a second round
of testing was performed utilizing the dilution assay methodology
(as described above in Example 1) to test for the generation of ROS
in illuminated gel samples.
[0387] For the second round of testing, a series of gel samples
were prepared as listed in Table 3 below; in order to first
establish the sensitivity of the assay, the samples comprised the
A3 gel (i.e., the Al gel, but lacking UP unless such was
specifically added) alone (lacking the presence of any chromophore)
to which the indicated amount of urea peroxide was added (on a %
weight basis) or not. Samples of the prepared gel were diluted
1000-fold, and the samples were illuminated for a period of 5
minutes each using the KLOX blue lamp (THERA.TM.) at a distance of
5 cm from the sample, after which the samples (300 .mu.L each) were
tested for the presence of ROS. The results are presented below in
Table 3 and FIG. 4.
TABLE-US-00003 TABLE 3 Testing for ROS production using the
dilution assay Average Fluorescence Total ROS Samples With Probe
Without Probe Fluorescence .mu.m Gel A3 17346 5.4 16280.6 1.26
(4.6% UP) Gel A3 16562 7.2 15494.8 1.20 (3% UP) Gel A3 13953 8.4
12884.6 0.99 (2% UP) Gel A3 12325 10 11255 0.87 (1% UP) Gel A3 4026
10.8 2955.2 0.23 (0% UP)
[0388] As can be seen from Table 3, the sensitivity of the dilution
assay enabled a clear distinction to be made as to the level of ROS
being produced in the tested gel samples, with a level of ROS being
produced progressively increasing with the increase in amount of UP
added to the samples of gel A3. As well, as can be seen from FIG.
4A, the impact of adding UP on the amount of ROS produced was
evident, and even without the presence of a chromophore in the gel
sample, there was still ROS generated upon the gel sample being
illuminated.
[0389] In a further round of testing, gel A3 samples were prepared
as per the second round of testing, however, in this third round of
testing, after the liposomes were added to the samples, the samples
were left to stand for a period of 5 minutes without being
illuminated. Upon completion of the 5 minute incubation period,
each of the samples was measured for the amount of ROS produced,
and the results and the results are presented below in Table 4.
TABLE-US-00004 TABLE 4 Testing for ROS production with dilution
assay--no illumination Samples Assay Gel A3 Gel A3 Gel A3 Gel A3
Gel A3 Result 0% UP 1% UP 2% UP 3% UP 4.6% UP Liposome + 1775.6
2301.6 2457.2 2723.1 2496 Probe Liposome 15.8 17.4 18.2 19.5 19.4
Total 119.8 644.2 799 1063.6 836.6 Fluorescence ROS 0.008 0.044
0.055 0.073 0.057 (.mu.M)
[0390] The results from the third round of testing indicated that
increasing the amount of UP in the sample gel resulted in an
increase yield of ROS despite the lack of illumination of the gel
samples; however, the yield of ROS in the non-illuminated gel
samples was considerably less than that which occurred when the gel
samples were subject to illumination.
[0391] In a fourth round of testing, samples of gel A bearing
various amounts of UP were prepared as listed in Table 5 below.
Samples were diluted 1000-fold, and after being illuminated for a
period of 5 minutes with the KLOX Thera.TM. light, a 300 .mu.L
aliquot of the test gel sample was assayed for the presence of ROS.
The results of the testing are presented below in Table 5, and
graphically represented in FIG. 4B.
TABLE-US-00005 TABLE 5 Testing for ROS production in Gel A Assay
Gel A (with % UP) Result 6% UP 4.66% UP 3% UP 2% UP 1% UP 0% UP
Liposome + 17621 17995.2 17735.9 16896.1 15414.5 10404.9 Probe
Liposome 353.8 461.8 475.1 517 579.8 644 Total 15867.2 15593.4
15320.8 14439.1 12894.7 7820.9 Fluorescence ROS 1.23 1.21 1.19 1.12
1.00 0.61 (.mu.M)
[0392] As can be seen from the results of the fourth round of
testing, in comparison to the second round of testing wherein the
gel samples lacked the presence of the chromophore, for the fourth
round testing sample that had no (0%) UP, there was a substantial
difference in the amount of ROS produced compared to the similar
sample of the second round testing. The result indicates that
having the chromophore present in the gel could affect the amount
of ROS that the gel would be capable of producing, and thus, the
amount of chromophore would be a factor to be considered in further
developing a oxidant-less gel that would be capable of producing a
level of ROS at least comparable to that of gel A. Furthermore, it
was apparent that there was a plateau effect with respect to the
amount of ROS generated versus the concentration of UP in the gel
samples tested; for those in this fourth round of testing the
plateau level was reached with a range of about 3% to about 6% UP
(weight concentration in the gel).
Example 3. Chromophore Concentration for ROS
[0393] A series of experiments were performed in order to evaluate
the effect of altering the amount of a chromophore in a gel
composition would have on the ability of the given gel to produce
ROS upon being illuminated with the KLOX blue light (THERA.TM.) for
a 5 minute illumination time. In a first round of testing, the
dilution assay method as described in Example 1 was utilized to
assess the level of ROS production: a sample of gel A3 was diluted
10-fold in a PBS solution containing 6% UP, following which,
various amounts of a chromophore (either Eosin Y or a combination
of Eosin Y and Fluorescein in a 3:1 ratio) ranging from 0 to 400
.mu.g/mL were added. After addition of the chromophore, the gel
sample was illuminated with the KLOX blue light (THERA.TM.) at a
distance of 5 cm and for a period of 5 minutes. The results are
presented below in Table 6 and in FIG. 5.
TABLE-US-00006 TABLE 6 Chromophore concentration for ROS production
in 10 .times. diluted gel A3 + 6% UP Liposome + Total [Eosin Y]
Probe Liposome Fluorescence ROS .mu.M 400 22706.3 24030.5 neg
3264.2 BDL .mu.g/mL 350 24076.9 24402.3 neg 2265.4 BDL .mu.g/mL 300
24797.3 24438.5 neg 1041.2 BDL .mu.g/mL 250 24594 24127.5 neg 933.5
BDL .mu.g/mL 200 24609 21986.7 1222.3 0.10 .mu.g/mL 150 20113.5
17059.2 1654.3 0.13 .mu.g/mL 100 18311.7 15123 1788.7 0.14 .mu.g/mL
50 19562.5 14873.5 2749 0.21 .mu.g/mL 25 21444.1 13195.4 6308.7
0.49 .mu.g/mL 0.5 33375.4 3758 27677.4 2.15 .mu.g/mL 0.25 35622
2138 31544 2.45 .mu.g/mL 0.08 29150.6 250.3 27500.3 2.14 .mu.g/mL
0.06 27610.6 193.7 26016.9 2.02 .mu.g/mL 0.04 26605.2 140.3 25064.9
1.95 .mu.g/mL 0.02 25254.3 77.9 23776.4 1.85 .mu.g/mL 0 23161 15.5
21745.5 1.69 .mu.g/mL BDL = Below Detection Limit (0.01 .mu.M) of
the instrument
[0394] From the results presented in Table 6, it was apparent that
at a concentration of chromophore above 0.5 .mu.g/mL, diminishing
amounts of ROS were being produced in the illuminated gel samples.
The diminished output of ROS at the higher concentration levels of
the chromophore were indicative of a fluorescence quenching (due to
the elevated level of the chromophore). Furthermore, from a range
of 50 .mu.g/mL to 0.25 .mu.g/mL of the chromophore, the
fluorescence increased with the decreasing the concentration of
chromophore, and thereafter decreased with a decreasing chromophore
concentration from 0.08 .mu.g/mL to the no chromophore containing
test sample. The results are also represented graphically in FIG.
5A, and also in FIG. 5B where a linear relationship can be observed
between 0.08 .mu.g/mL and 0 .mu.g/mL. The results from this first
round of testing thus indicated that while adding a chromophore to
the gel mixture could aid in increasing the level of ROS
production, only a limited amount of a chromophore could be added
before a negative impact on ROS production would occur.
[0395] Further testing, again utilizing the dilution assay
methodology, of the chromophore concentration for ROS production
was done utilizing a series of PBS-diluted gels (diluted over a
range of concentrations as seen in Table 7 below) bearing various
amounts of either a single chromophore (Eosin Y) or a mixture of
chromophores (a 3:1 mixture of Eosin Y and Fluorescein). The
results are presented below in Table 7, and also in FIG. 5C.
TABLE-US-00007 TABLE 7 ROS production with varying the level of
chromophore in a gel A composition Dilution Liposome + Total ROS
Sample Factor Probe Liposome Fluorescence (.mu.M) Gel A--20 .times.
EY 1600.times. 41254.3 3510.8 35743.5 2.10 Gel A--10 .times. EY
1600.times. 43321 1962.8 41358.2 2.43 Gel A--20 .times. EY
2400.times. 42197.8 2685 39512.8 2.32 Gel A--10 .times. EY
2400.times. 43109.5 1387.5 41722 2.45 Gel A--20 .times. EY
4000.times. 44248.6 1921.2 42327.4 2.49 Gel A--10 .times. EY
4000.times. 41332.6 941.2 40391.4 2.38 Gel A--5 .times. EY
4000.times. 37090.4 606.3 36484.1 2.15 Gel A 4000.times. 28989.5
279.8 28709.7 1.69 Gel A--20 .times. EY/F 4000.times. 42967.3
1304.1 41663.2 2.45 Gel A--10 .times. EY/F 4000.times. 40325 788.8
39536.2 2.33 Gel A--5 .times. EY/F 4000.times. 36902.6 491.1
36411.5 2.14 Gel A--1 .times. EY/F 4000.times. 30355.6 281.6 30074
1.77
[0396] As observed from the results, while a greater amount of ROS
was generated at chromophore concentrations of over 5-times the
chromophore concentration present in gel A, it was unnecessary to
go beyond 5-times the chromophore concentration, in either the
single chromophore sample gel or in the chromophore mixture sample
gel, in order to obtain a comparable level of ROS production to gel
A.
Example 4. Illumination Effect on ROS Production
[0397] To test the effect that altering the length of the
illumination period may have on the production of ROS in a given
gel composition, a sample of gel B having 18.1 mg/g of carbopol in
the mixture was prepared. For comparative testing to evaluate the
effect of having a chromophore present in the gel mixture along
with altering the illumination period, a chromophore (Eosin Y) was
also added to the sample gel to be tested, as listed below: [0398]
Sample 1: Gel B, 2 cm high, 2 minutes illumination, no UP [0399]
Sample 2: Gel B, 2 cm high, 5 minutes illumination, no UP [0400]
Sample 3: Gel B, 2 cm high, 10 minutes illumination, no UP [0401]
Sample 4: Gel B +EY @ 20 .mu.g/mL, 2 cm high, 2 minutes
illumination, no UP [0402] Sample 5: Gel B +EY @ 20 .mu.g /mL, 2 cm
high, 5 minutes illumination, no UP [0403] Sample 6: Gel B +EY @ 20
.mu.g /mL, 2 cm high, 10 minutes illumination, no UP The samples
were tested using the dilution assay described in Example 1.
Results from the testing of the gel samples are presented in Table
8 below.
TABLE-US-00008 [0403] TABLE 8 ROS production in Gel B--varying
illumination time Liposome + Total ROS Sample Probe Liposome
Fluorescence (.mu.M) S1 2542.7 40.2 1302.5 0.08 S2 7634.6 22.7
6411.9 0.39 S3 10153.3 15.8 8937.5 0.54 S4 17625.7 3393 13032.7
0.79 S5 39817.8 2344 36273.8 2.20 S6 40285.6 1272.2 37813.4
2.29
[0404] As can be seen in comparing sample 1 to sample 6, the
production of ROS was proportional to the illumination time, and
could be enhanced by having a chromophore present in the gel
mixture.
[0405] In a second round of testing, again using the dilution assay
described in Example 1, the following samples were evaluated for
their ability to produce ROS upon being illuminated for the noted
time period with the light source place consistently at 5 cm
distance from the tested sample to be illuminated. Samples were
prepared as listed below, and those samples denoted with an "n1"
and "n2" are replicate samples, and the gel sample numbered 5 to 11
were diluted 1000-fold in PBS prior to testing: [0406] Sample 1:
Gel A, 12% UP, 5 minutes illumination [0407] Sample 2: Light alone,
9 minutes illumination (n1) [0408] Sample 3: Light alone, 9 minutes
illumination (n 2) [0409] Sample 4: Mix of Gel A3+Gel A4, 9 minutes
illumination (n1) [0410] Sample 5: Mix of Gel A3+Gel A4, 9 minutes
illumination (n2) [0411] Sample 6: Mix of Gel A2+Gel A3, 9 minutes
illumination (n1) [0412] Sample 7: Mix of Gel A2+Gel A3, 9 minutes
illumination (n2) [0413] Sample 8: Gel A4, 9 minutes illumination
(n1) [0414] Sample 9: Gel A4, 9 minutes illumination (n2) [0415]
Sample 10: Gel A2 (12% UP), 9 minutes illumination (n1) [0416]
Sample 11: Gel A2 (12% UP), 9 minutes illumination (n2) Results
from the testing of the gel samples are presented below in Table
9.
TABLE-US-00009 [0416] TABLE 9 Illumination of various gel
compositions--ROS yield Liposome + Total ROS Sample Probe Liposome
Fluorescence (.mu.M) S 1 28118.6 951.5 26197.1 1.52 S 2 7529.6 10.3
6549.3 0.38 S 3 7203.2 11.8 6221.4 0.36 S 4 8022.3 15.5 7036.8 0.41
S 5 7836.6 14.5 6852.1 0.40 S 6 25668.1 871 23827.1 1.38 S 7
24538.9 838.1 22730.8 1.32 S 8 21582 9 20603 1.19 S 9 20864.2 32.9
19861.3 1.15 S 10 31774.4 290.7 30513.7 1.77 S 11 30539.7 314.5
29255.2 1.70
[0417] Regarding samples 2 and 3, illumination of the
liposome-containing solution alone (without any gel added) provided
a base number of ROS production, and addition of gel lacking any
added chromophore or UP only resulted in a marginal increase in the
amount of ROS generated (see samples 4 and 5). Addition of
chromophore to the gel composition (having other components added
as well) resulted in an increase in ROS production (see samples 6
and 7) when compared to an equivalent gel composition lacking the
chromophores (see samples 8 and 9), and this effect was magnified
with the addition of the oxidant to the gel composition (see
samples 10 and 11), such levels of ROS production being comparable
to the level of ROS production of gel A.
Example 5. Component Testing
[0418] In a next phase of testing, a series of experiments were
performed, utilizing the dilution assay described in Example 1, to
evaluate whether various components of a gel A composition (as
described in Example 1), or other various possible chemical
additives, may affect the ability of a gel composition to produce
ROS and to what level, upon the given gel composition being
illuminated for a specific period of time (e.g. either 5 or 9
minutes). Given that gel B, comprising water plus 18.1 mg/g of
carbopol had the fewest constituent components, gel B was utilized
as the denominator gel to which various chemical compounds were
added (e.g., gel B+chemical compound A (plus, optionally, chemical
compound "a", "b", "c", etc.)) in order to individually evaluate
the particular candidate chemical. For the addition of glycerin,
when added, the amount was 44.2 g (for a 100 g weight of gel) and
for propylene glycol (PG), the amount added was 15.4 g (for a 100 g
weight of gel). As well, for comparative purposes, the tested
samples also included those to which various amounts of UP and/or a
chromophore were added either as a single chromophore or in
combination with another chromophore. For most gel samples, testing
was performed in replicate for the given sample.
[0419] In a first round of testing, the following gel samples with
the noted additional chemical compound or compounds tested for the
ability of the given gel composition to produce ROS: [0420] Sample
1: Gel B+5% Sodium Bicarbonate (SB), 5 minutes illumination
(20.times. dilution) [0421] Sample 2: Gel A2 +5% Sodium
Bicarbonate, 5 minutes illumination (20.times. dilution) [0422]
Sample 3: Gel A2, 5 minutes illumination (20.times. dilution)
[0423] Sample 4: Gel B+1.times. Eosin Y, 5 minutes illumination
(1000.times. dilution) [0424] Sample 5: Gel B+Glycerin+1.times.
Eosin Y, 5 minutes illumination (1000.times. dilution) [0425]
Sample 6: Gel B+Propylene Glycol (PG)+1.times. Eosin Y, 5 minutes
illumination [0426] Sample 7: Gel B+Glycerin+PG+1.times. Eosin Y, 5
minutes illumination [0427] Sample 8: Gel A3+A4+1% UP, 9 minutes
illumination [0428] Sample 9: Gel A3+A4+3% UP 9 minutes
illumination [0429] Sample 10: Gel A3+A4+6% UP, 9 minutes
illumination [0430] Sample 11: Gel A3+A4+12% UP, 9 minutes
illumination [0431] Sample 12: Gel A3+A4, 2.times. Eosin Y, 9
minutes illumination (n1) [0432] Sample 13: Gel A3+A4, 2.times.
Eosin Y, 9 minutes illumination (n2) [0433] Sample 14: Gel
A3+A4+12% UP) 2.times. Eosin Y, 9 minutes illumination (n1) [0434]
Sample 15: Gel A3+A4+12% UP) 2.times. Eosin Y, 9 minutes
illumination (n2) [0435] Sample 16: Gel A3+A4+1% UP) 2.times. Eosin
Y, 9 minutes illumination (n1) [0436] Sample 17: Gel A3+A4+3% UP)
2.times. Eosin Y, 9 minutes illumination (n1) [0437] Sample 18: Gel
A3+A4+6% UP) 2.times. Eosin Y, 9 minutes illumination (n1) [0438]
Sample 19: Gel A3+A4+9% UP, 2.times. Eosin Y, 9 minutes
illumination (n1) [0439] Sample 20: Light+1% UP, 9 minutes
illumination (n1) [0440] Sample 21: Light+1% UP, 9 minutes
illumination (n2) [0441] Sample 22: Light+3% UP, 9 minutes
illumination (n1) [0442] Sample 23: Light+3% UP, 9 minutes
illumination (n2) [0443] Sample 24: Light+6% UP, 9 minutes
illumination (n1) [0444] Sample 25: Light+6% UP, 9 minutes
illumination (n2) [0445] Sample 26: Light+8% UP, 9 minutes
illumination (n1) [0446] Sample 27: Light+8% UP, 9 minutes
illumination (n2) [0447] Sample 28: Light+12% UP, 9 minutes
illumination (n1) [0448] Sample 29: Light+12% UP, 9 minutes
illumination (n2) Results from the aforementioned round of testing
are presented below in Table 10.
TABLE-US-00010 [0448] TABLE 10 ROS production--testing of gel
samples having added components Liposome + Total ROS Sample Probe
Liposome Fluorescence (.mu.M) S 1 3538.2 69 1069.2 0.06 S 2 14121.1
48 11673.1 0.61 S 3 7091.7 41.4 4650.3 0.25 S 4 10471.2 1185.3
6885.9 0.36 S 5 11295.1 1248.8 7646.3 0.40 S 6 10547.9 1237.8
6910.1 0.36 S 7 9992.2 1200.1 6392.1 0.34 S 8 11497.3 13 9084.3
0.48 S 9 17668.3 11.2 15257.1 0.80 S 10 25620.6 7.2 23213.4 1.22 S
11 28344.2 9.3 25934.9 1.37 S 12 31459 2442.6 26616.4 1.40 S 13
32793.1 2274.9 28118.2 1.48 S 14 24402.1 1289.2 20712.9 1.09 S 15
23484.9 1309.4 19775.5 1.04 S 16 31638.6 1757.5 27481.1 1.45 S 17
29763.1 1707.7 25655.4 1.35 S 18 25703.2 1583.3 21719.9 1.14 S 19
27288.9 701.7 24187.2 1.27 S 20 9492.6 654.5 6438.1 0.34 S 21
9806.6 9.8 7396.8 0.39 S 22 11624.4 8.2 9216.2 0.49 S 23 11137.3
10.1 8727.2 0.46 S 24 12036.9 9 9627.9 0.51 S 25 12976.1 7.1 10569
0.56 S 26 16170.2 8.5 13761.7 0.72 S 27 16654.8 8.3 14246.5 0.75 S
28 18911.1 8.7 16502.4 0.87 S 29 18668.3 10.2 16258.1 0.86
[0449] The results from the first round of testing were
inconclusive, though with respect to an addition of 5% sodium
bicarbonate (SB) (and an illumination time of 5 minutes), comparing
the result for samples 1, 2 and 4, there was a difference between
the samples that may have been due to having additional factors
other than the presence of having a chromophore in the gel
composition when the sodium bicarbonate was present in the
composition. When added alone or in combination to gel B, glycerin
and PG did not appear to have any effect (see samples 4 to 7) even
though the chromophore was added to the gel as well. When increased
amounts of UP alone were added to gel B, the yield of ROS also
increased (see samples 8 to 11 and samples 20 to 29), with a
similar effect occurring when a greater amount of chromophore was
also present in the gel B (see samples 14 to 19).
[0450] In a second round of testing, the following samples tested
for the ability of the given gel composition to produce ROS: [0451]
Sample 1: Gel B+5.times. Eosin Y, 10 minutes illumination [0452]
Sample 2: Gel B, 10 minutes illumination [0453] Sample 3: Gel B+10%
Sodium Bicarbonate, 10 minutes illumination (i.e. a Gel C). [0454]
Sample 4: Gel B+Glucosamine, 10 minutes illumination [0455] Sample
5: Gel B+Propyl paraben, 10 minutes illumination [0456] Sample 6:
Gel A, 2.times. Eosin Y, 9 minutes illumination (n1) (2000.times.
dilution) [0457] Sample 7: Gel A, 2.times. Eosin Y, 9 minutes
illumination (n2) (2000.times. dilution) [0458] Sample 8: Gel A,
2.times. Eosin Y, 9 minutes illumination (2000.times. dilution)
[0459] Sample 9: Gel A, 6% UP), 2.times. Eosin Y, 9 minutes
illumination (2000.times. dilution) [0460] Sample 10: Gel A, 1%UP,
2.times. Eosin Y, 9 minutes illumination (2000.times. dilution)
[0461] Sample 11: Gel A1+A4, 12% UP, 9 minutes illumination [0462]
Sample 12: Gel Ab1+A4, 12% UP, 9 minutes illumination [0463] Sample
13: PBS +Liposome-Probe standing for 9 minutes, no illumination
(n1) [0464] Sample 14 : PBS +Liposome-Probe standing for 9 minutes,
no illumination (n2) Results from the testing of this second round
of gel samples are presented below in Table 11.
TABLE-US-00011 [0464] TABLE 11 ROS production testing of gel
samples having added components Liposome + Total ROS Sample Probe
Liposome Fluorescence (.mu.M) S 1 17150.2 245.8 15204.4 0.94 S 2
7229.9 17.2 5512.7 0.34 S 3 29272.3 20.7 27551.6 1.70 S 4 7758.5
15.7 6042.8 0.37 S 5 10776.8 16.2 9060.6 0.56 S 6 24989.2 145.5
23143.7 1.42 S 7 24463.2 143.7 22619.5 1.39 S 8 24028.6 181.6 22147
1.36 S 9 20629.6 218 18711.6 1.15 S 10 16597.5 432.4 14465.1 0.89 S
11 27567 11.3 25855.7 1.59 S 12 25200.5 13.4 23487.1 1.45 S 13
1915.8 31.1 184.7 0.01 S 14 1999.1 34.5 264.6 0.02
[0465] From the second round of testing, wherein a longer
illumination period was utilized than in the first round of
testing, adding 5.times. extra chromophore to the gel B composition
resulted, not unsurprisingly, to a yield of ROS that was higher
than with only 1.times. chromophore (see samples 1 and 2, and
compare to the round 1 testing). Quite surprising, however, was the
amount of ROS produced when the 10% sodium bicarbonate alone was
added to the gel B composition and the composition (gel C)
thereafter illuminated for the 10 minute period (see sample 3).
Addition of glucosamine or propyl parabens alone did not have an
effect (see samples 6 and 7, compared to sample 2). The result
obtained with the addition of the 10% sodium bicarbonate was even
greater than that obtained when the gel A was tested with twice the
amount of chromophore present in the gel A composition (see sample
3 compared to samples 6 to 8 (and 9 and 10 with lower levels of
UP)) or a composition comprising gels A1+A4 with 12% UP in the
mixture.
[0466] In a third round of testing, an effect of having several
components concomitantly in a gel B composition was tested, in
comparison to a diluted gel A composition and a gel composition
comprising gel A2 +A3 to which a chromophore was added. The gels
tested are noted below: [0467] Sample 1: Gel A, 1000 time dilution,
5 minutes illumination [0468] Sample 2: Gel A2+A3, 1000 times
diluted, 5 minutes illumination [0469] Sample 3: Gel B+Glycerin,
3.times. Eosin Y+1% Sodium Bicarbonate, 10 minutes illumination
[0470] Results from the testing of this third round of gel samples
are presented below in Table 12.
TABLE-US-00012 TABLE 12 ROS production testing of gel samples
having added components Liposome + Total ROS Sample Probe Liposome
Fluorescence (.mu.M) S 1 20315 557.8 16757.2 1.22 S 2 17439 1253.2
12185.8 0.86 S 3 25330.4 1303.4 20227 1.42
[0471] As observed from the results, the ROS produced by the 10
minute-illuminated gel composition of sample 3, was greater than
that of the gel A, although the sample 3 gel was illuminated for a
longer period of time than the sample 1 gel.
[0472] In a fourth round of testing, similar to the third round of
testing, an effect of having several components concomitantly in a
gel B composition was tested, in comparison to a diluted gel A
composition or gel composition similar to gel A but lacking UP. The
tested gel compositions are noted below: [0473] Sample 1: Gel
A2+A3, 1000.times.dilution, 5 minutes illumination [0474] Sample 2:
Gel A (12% UP), 1000.times.dilution, 5 minutes illumination [0475]
Sample 3: Gel A3+A4, 1.times.Fluorescein, 5 minutes illumination
[0476] Sample 4: Gel B+Glycerin+3.times.Eosin Y, 10 minutes
illumination [0477] Sample 5: Gel B+Glycerin+SOD
(1mg/ml)+3.times.Eosin Y, 10 minutes illumination [0478] Sample 6:
Gel B+Glycerin (which thus forms a Gel DO+1% Sodium
Bicarbonate+3.times.Eosin Y, 10 minutes illumination [0479] Sample
7: Gel A3+SOD (1mg/ml)+3.times.Eosin Y, 10 minutes illumination
[0480] Sample 8: Gel A3+1% Sodium Bicarbonate+3.times.Eosin Y, 10
minutes illumination [0481] Sample 9: Gel A3+3% Sodium
Bicarbonate+3.times.Eosin Y, 10 minutes illumination [0482] Sample
10: Gel A4+SOD (1mg/ml)+3.times.Eosin Y, 10 minutes illumination
[0483] Sample 11: Gel A4+1% Sodium Bicarbonate+3.times.Eosin Y, 10
minutes illumination Results from the testing of this fourth round
of gel samples are presented below in Table 13.
TABLE-US-00013 [0483] TABLE 13 ROS production testing of gel
samples having added components Liposome + Total ROS Sample Probe
Liposome Fluorescence (.mu.M) S 1 18848.7 2017.2 14611.5 0.94 S 2
26492.8 443 23829.8 1.54 S 3 17067 1048.3 13798.7 0.89 S 4 26795.3
1317.4 23257.9 1.50 S 5 24534.5 572.5 21742 1.40 S 6 29503.6 1610
25673.6 1.66 S 7 17158.1 492.8 14445.3 0.93 S 8 34519.1 3273.9
29025.2 1.87 S 9 33136.5 3371.7 27544.8 1.78 S 10 14407.2 738.7
11448.5 0.74 S 11 33464.1 2869.1 28375 1.83
[0484] As observed from the result with respect to sample 4, an
addition of glycerin along with having an elevated amount of
chromophore in the gel B composition yielded an ROS production
level similar to that of the gel A composition that contained
chromophore plus the oxidant; this comparative difference was also
observed in the third round of sample testing. As well, with the
presence of an amount of sodium bicarbonate in the gel B
composition along with the glycerin and elevated chromophore
amount, a greater ROS production level was reached (see sample 6).
Regarding samples 8 and 9, a higher ROS level was also achieved
with these gels compositions in comparison to the gel composition
of sample 2. Addition of an O.sub.2.sup.- metabolizing enzyme,
superoxide dismutase (SOD), in the gel compositions tested in this
fourth round of testing, did not appear to have an impact on an
amount of ROS that the given gel sample could produce.
Example 6. Scaling of Bicarbonate
[0485] As the results indicated that addition of bicarbonate to gel
composition could positively impact an amount of ROS produced by an
illuminated gel, a further set of experiments were carried out in
order to evaluate concentrations of sodium bicarbonate added in the
D1 gel that would result in a creation of hydrogen peroxide in the
gel over the 10 minute course of the gel being illuminated. The
objective was that of determining the range of bicarbonate
concentrations that could be used in order to minimize hydrogen
peroxide production while providing for an adequate level of
production of oxygen/oxygen-species from the illuminated gel. Gel
compositions akin to those of Example 5, third round sample gel 3
and fourth round 6, were evaluated when having an added sodium
bicarbonate amount that ranged from 1% to 20% (per weight of the
gel composition).
[0486] Gel D1 samples were prepared having 3.times. chromophore,
and after being illuminated for the above-noted time period,
aliquots of the test gel sample were assayed for their hydrogen
peroxide content using a Pierce Quantitative Peroxide Assay Kit
(Product No. 23280, Pierce Biotechnology, Rockford, Ill., USA).
Briefly, the methodology for the Pierce assay kit allows for a
detection of peroxide based on oxidation of ferrous to ferric ion
in the presence of xylenol orange; the sensitivity of the detection
procedure is enhanced through the use of an aqueous-compatible
formulation that includes sorbitol. In the assay, hydroperoxides
convert the Fe.sup.2+ to Fe.sup.3+ at acidic pH, and with the
aqueous-compatible formulation, peroxide first reacts with
sorbitol, converting it to a peroxyl radical, which in turn
initiates Fe.sup.2+ oxidation to Fe.sup.3+. In a sulfuric acid
solution (supplied as part of the kit), the Fe.sup.3+ complexes
with the xylenol orange dye to yield a purple product with a
maximum absorbance at 560 nm. Based on a standard curve from the
absorbance measurement of a standardized reaction utilizing a
dilution series from a 1000 .mu.M H.sub.2O.sub.2 solution, the
amount of hydrogen peroxide in a test solution(s) can be plotted
utilizing the absorbance readings from the test samples, and the
amount of H.sub.2O.sub.2 in the test sample quantitatively
determined.
[0487] To perform the Pierce assay, a working reagent (WR) is
prepared by mixing 1 volume of the kit-supplied Reagent A (a 1 mL
composition: 25 mM ammonium ferrous (II) sulfate, 2.5 M
H.sub.2SO.sub.4) with 100 volumes of the kit-supplied Reagent B
(2.times.50 mL composition: 100 mM sorbitol, 125 .mu.M xylenol
orange in water). At least 1 mL of WR is prepared for each sample
to be tested. For preparation of the peroxide standard, a 30% (8.8
M) hydrogen peroxide stock solution is serially diluted in
ultrapure water to obtain 8-10 standards in a concentration range
of 1-1000 .mu.M. Upon completion of the test sample's treatment
procedure (this being the illumination of the given gel sample), 10
volumes of WR are added to 1 volume of the sample, and the assay
sample contents are mixed and incubated for 15-20 minutes at room
temperature (the incubation step is necessary for the reaction to
reach an endpoint and form a stable complex). The absorbance of
assay samples were taken at 560 nm in a spectrophotometer, and the
concentration of peroxide in each of the assay samples was
calculated by reference to its assay absorbance compared to the
standard curve from the peroxide standard. The results from the
experiment are described below.
[0488] The tested samples were first evaluated visually, and for
the test sample gels having the 1% to 4% sodium bicarbonate range,
upon mixing with the WR, the respective solutions changed color
either not at all to only very slightly, to a yellowish-to-brownish
color. The test sample gel having a 5% sodium bicarbonate the
solution turned a deep blue, while the test sample gel having the
7.5% sodium bicarbonate was violet, and the for test gel samples
that were in the 10% to 20% sodium bicarbonate amount range, these
turned a deep purple color on being mixed with the WR solution.
Given that the indicator dye is supposed to change from a yellow
color to a purple color in the presence of hydrogen peroxide it was
clear that 7.5% (and higher) sodium bicarbonate test samples had
hydrogen peroxide present in them.
[0489] Upon completion of the visual inspection, the test sample
solutions were then measured for their absorbance at 560 nm (see
FIG. 6A) and the absorbance reading converted into a concentration
value (see FIG. 6B and Table 14). From this data, it was evident
that an addition of an amount of sodium bicarbonate in the range of
about 1% to about 4% resulted in less than 20 .mu.M hydrogen
peroxide production in the illuminated gel. At 5% sodium
bicarbonate, there was about 36 .mu.M hydrogen peroxide produced,
and at 7.5% sodium bicarbonate resulted in a 52 .mu.M amount of
hydrogen peroxide. With 10% sodium bicarbonate or more, the
hydrogen peroxide level values exceeded the standard curve,
however, by using the scan data to extrapolate an approximate
amount of hydrogen peroxide production (at 10% sodium bicarbonate
addition) a value of about 90 .mu.M hydrogen peroxide resulted.
TABLE-US-00014 TABLE 14 Scaling of Bicarbonate to detect
H.sub.2O.sub.2 presence % Sodium Absorb- Absorbance
[H.sub.2O.sub.2] Bicarbonate ance Dilution [H.sub.2O.sub.2] @560 nm
(.mu.M) in D1 gel @560 nm factor (.mu.M) Recalculated Recalculated
1% 0.4753 9.12 2% 0.5604 11.83 3% 0.8054 19.63 4% 0.7776 18.75 5%
1.3208 36.04 7.50% 1.8241 52.07 10% 3.0845 92.21 15% 3.0675 91.67
20% 2.9518 87.98 7.5% 0.129 5 1.8241 52.07 (diluted) 10% 0.3732 5
5.277163721 162.04 (diluted) 15% 0.4097 5 5.793285039 178.48
(diluted) 20% 0.3826 5 5.410082636 166.28 (diluted)
[0490] To conclude, until at least an amount about 5% sodium
bicarbonate (w/w) was added, an addition of sodium bicarbonate did
not result in any significant production of hydrogen peroxide from
the illuminated D1 gel. Moving up to an amount of 10% sodium
bicarbonate greatly increased the amount of hydrogen peroxide.
Part B. Fluorescence Determination
Example 7. Bicarbonate and Glycerin (Glycerol) Effect
[0491] Results from the experiments directed towards evaluating the
effect that individual ingredients, when added alone or in
combination, may have on the ability of the gel to produce ROS when
illuminated with an actinic light source (the KLOX multi-LED lamp
emitting blue light) indicated that the addition of sodium
bicarbonate, and glycerin in the presence of an elevated amount of
chromophore, could result in an ROS level comparable or above an
oxidant-containing biophotonic gel composition such as that of gel
A.
[0492] To evaluate the effect of particular components on the
ability of the oxidant-less gel composition to yield an adequate
fluorescence spectrum production (both in terms of an overall
amount of fluorescence and a spectrum of colors in the visible
light range), when the given oxidant-less gel either has or lacked
a bicarbonate (such as sodium bicarbonate), further tests were
conducted in solution to see if ingredients would have a amplifying
or synergistic effect to the added sodium bicarbonate.
[0493] Using gel B with 3.times. eosin Y and 1% sodium bicarbonate
(i.e. gel C), having either a blank (no glycerin added) versus a
glycerin-added (i.e. to form a gel DO aliquot samples were tested
for their fluorescence. To test the samples for their fluorescence
yield, an aliquot of the given gel sample was taken (approximately
2 mL) and placed in a circular well device that has a 2 mm depth
inscribed thereupon (the gel is loaded into the well in order to
completely fill (with no air pockets remaining) the well up to the
2 mm depth line) and the device is placed upon a glass slide
mounted above a SP-100 photodetector (CSA Group/ORB Optronix
(Washington state, USA, Kirkland, 98033); once prepared, the gel
was illuminated using the KLOX multi-LED blue light (THERA.TM.),
positioned at 5 cm from the gel sample, for a pre-set time
(typically either 5 or 10 minutes). Light passing through and being
emitted from the gel was captured by the photodetector.
[0494] The results from this initial test are presented in FIG. 7;
while the gel C sample had an adequate level of fluorescence yield,
being in the range of about 0.75 to 1 mW/cm.sup.2 over the course
of the illumination period (which is a yield level that is
comparable to or greater than that of gel A), the gel D1 sample had
a comparably significantly greater fluorescence yield from the
outset of the illumination period. Also, after about 30 seconds of
being illuminated, the fluorescence yield of the gel D1 sample rose
steeply over the course of the following 30 seconds and plateaued
at level that was about 2.times. greater than its yield level at
the commencement of the illumination period (and about 4.times.
greater than that of the gel C sample). As a result from this
preliminary round of in-solution testing, it was determined that
glycerin (glycerol) could be a candidate compound for addition to a
gel along with a bicarbonate so as to provide for a gel that would
have an adequate or even enhanced level of fluorescence.
Example 8. Initial Scaling of Bicarbonate
[0495] As addition of glycerin (in order to produce a gel DO had a
positive impact on the amount of fluorescence that a gel
composition could yield, a subsequent test, was performed utilizing
a % range of sodium bicarbonate added to a D1 gel to test whether
increasing the sodium bicarbonate would affect fluorescence of the
D1 gel. To prepare the D1 gel samples, all of the ingredients
(along with 3.times. of the chromophore Eosin Y) were combined and
mixed together. Thereafter, the given amount of sodium bicarbonate
(SB) powder (based on a % weight for a 100 gram amount of gel) was
added to the mixed gel. The SB levels that were tested from 0.1% to
10%.
[0496] Referring to FIG. 8, the results indicated that addition of
sodium bicarbonate could, depending on the percent amount added and
after having a post-addition incubation period run its course,
could have a positive influence on the fluorescence yield of D1
gel. With the addition of the sodium bicarbonate, upon the gel
being illuminated with the multi-LED blue light, the tested D1 gels
changed their physical texture, becoming less gel-like and
noticeably more swollen.
Example 9. Scaling of Glycerol
[0497] In a further series of experiments, samples of the D1 gel
having various amounts of 0glycerin were tested for their
fluorescence yield capacity and, also, to evaluate the contribution
that the added glycerin may make to changing the texture of the gel
during the illumination period given that the inclusion of glycerin
in the gel was observed as being required in order to have the gel
swell and become less viscous (which would facilitate its removal
from a patient after completion of a round of treatment). Prior
observations made in Example 7 indicated that in an absence of
glycerin, the gel did not undergo a textural change upon the gel
being illuminated. As such, D1 gel samples were prepared having
either a lowered glycerin content (218 mg/g), a medium glycerin
content (436 mg/g) or a high glycerin content (654 mg/g), and
subsequently tested for their fluorescence capacity.
[0498] To test the samples for their fluorescence yield, an 0.63 mL
aliquot of the given gel sample is placed in a circular well device
that has a 2 mm depth inscribed thereupon (the gel is loaded into
the well in order to completely fill (with no air pockets
remaining) the well up to the 2 mm depth line, a cover slip/slide
is placed on top the ensure that the 2 mm depth of gel is
maintained) and the device is placed upon a glass slide mounted
above a SP-100 photodetector (CSA Group/ORB Optronix (Washington
state, USA, Kirkland, 98033)); once readied, the gel is illuminated
using the KLOX multi-LED blue light (THERA.TM.) for a pre-set time
(typically either 5 or 10 minutes, in the present Example 8, this
time being a 5 minute illumination period for the high and medium
glycerin content D1 gel samples, and 10 minutes for the lower
glycerin content D1 gel sample), while the light passing through
and being emitted from the gel is captured by the
photodetector.
[0499] The results of the fluorescence testing are presented in
FIGS. 9A-9C and Table 15 below. Visual observations were also made
of the D1 gel samples during the preparation process and while
being illuminated; the high glycerin content D1 gel mixture was
very sticky, and the low glycerin content D1 gel mixture was only
slightly sticky, and while being illuminated (along with having
sodium bicarbonate is added to the mixtures) there was a much
greater degree of swelling and reduction of the viscous nature of
the high glycerin content D1 gel. As shown in FIG. 9A, the
fluorescence yield from both the high and medium glycerin content
gels was significantly elevated over that of the lower glycerin
amount D1 gel test sample (which itself was higher than that of a
gel A). With respect to the fluorescence color spectrum emitted
from the illuminated gels, as can be seen from the results shown in
FIG. 9B and FIG. 9C, both the high and medium glycerin content gels
emitted elevated levels of green and yellow fluorescence, along
with greater amounts of orange and red.
TABLE-US-00015 TABLE 15 Gel D1 fluorescence colors output--scalling
of glycerol Color Low Glycerin Med Glycerin High Glycerin Violet
5.82 4.08 4.02 Blue 2.21 1.56 1.45 Green 0.26 0.49 0.47 Yellow 0.16
0.32 0.41 Orange 0.07 0.17 0.23 Red 0.01 0.16 0.20
[0500] As a result of the Example 9 experiments, for utilization of
the D1 gel in further testing, samples having the medium amount of
glycerin added to them (436 mg/g) were utilised, given the high
level of fluorescence output and the ability of such a gel to have
a change in its physical texture occur during the illumination
period.
Example 10. Scaling of Chromophore with Bicarbonate Added
[0501] As addition of sodium bicarbonate (to form a gel C
composition) and glycerin (to form a D1 gel composition) gave
positive results, further series of experiments were conducted in
order to evaluate a range of chromophore (in present disclosure,
this being Eosin Y) concentrations that would result in a gel
composition with adequate fluorescence. For these Example 10
experiments, samples of the D1 gel with 5% sodium bicarbonate was
used, with the amounts of chromophore added as 109, 327, 545, and
763 .mu.g/g of Eosin Y (labelled as 1.times., 3.times., 5.times.,
and 7.times. respectively). Sample placement, lamp distance and
illumination times were as per those described in Example 9 of the
present disclosure.
[0502] Results from the experiment are presented in FIGS. 10A-10C
and Table 16 below. As can be seen from FIG. 10A, the D1 gel
samples that had the elevated amount of the chromophore beyond
1.times. yielded an elevated level of fluorescence, with the
3.times. and 5.times. chromophore D1 gels having the greatest
fluorescence but with the 7.times. chromophore D1 gel having less
(compared to the 3.times. and 5.times. chromophore D1 gels) overall
fluorescence and significantly less blue and green emitted
wavelengths, suggesting that a level above 5.times. chromophore,
the D1 gel did not function as well.
TABLE-US-00016 TABLE 16 Gel D1 fluorescene colors output-scaling of
chromophore Color 1 .times. Eosin Y 3 .times. Eosin Y 5 .times.
Eosin Y 7 .times. Eosin Violet 7.06 3.48 2.29 1.75 Blue 3.11 1.08
0.51 0.32 Green 0.31 0.42 0.34 0.23 Yellow 0.17 0.33 0.37 0.32
Orange 0.07 0.18 0.21 0.20 Red 0.01 0.17 0.20 0.19
[0503] The results from the Example 10 experiments indicated that
elevating the chromophore (Eosin Y) content, but not over-elevating
it, would produce a D1 gel with an enhanced fluorescence profile,
and thus, for further experiments levels of either 3.times. or
5.times. Eosin Y contents for D1 gel testing were to be used in
further rounds of testing.
Example 11. Bicarbonate alternative salts
[0504] As the addition of bicarbonate, in the form of sodium
bicarbonate, to form gel C, and additionally as an additive to the
D1 gel, could positively influence the fluorescence output from a
gel composition, other salts of a similar nature to sodium
bicarbonate were evaluated, by adding them in powder form to a
given gel composition. In a first round of experiments, tests were
performed with potassium bicarbonate, calcium carbonate, sodium
acetate and sodium biphosphate to test their on the fluorescence
output from a D1 gel having a 3.times. level of chromophore Eosin
Y. Test samples comprising the various salts were evaluated in
comparison to the D1 gel (with 3.times. Eosin Y) containing 1%
sodium bicarbonate and to the D1 gel (with 3.times. Eosin Y)
lacking any added salt. Gels were prepared as per the procedure
described in Example 9, with the illumination time being 10
minutes. Results from the first round of testing the alternative
salts are presented in FIGS. 11A and 11B, and in Table 17
below.
[0505] As can be seen from FIG. 11A, while the sodium acetate and
sodium biphosphate salts did not appear to cause any enhancement of
the D1 gel fluorescence given that these gel samples yielded the
same fluorescence profile as the D1 gel itself, addition of the
potassium bicarbonate and calcium carbonate salts, respectively, to
the D1 gel resulted in an enhanced fluorescence level after several
minutes of the gels being illuminated, and the fluorescence level
output from the D1 gels bearing either of these two salts was
similar to the sodium bicarbonate salt by the end of the
illumination period. The D1 gel bearing each of these salts
potassium bicarbonate give a close result to we had with the sodium
bicarbonate, but it seems that the reaction occur is slower with
those two new powders. With respect to the fluorescence color
profile, referring to FIG. 11B and Table 17, the D1 gel containing
the 1% potassium bicarbonate was most similar (albeit with lower
output levels) to the D1 gel bearing the sodium bicarbonate both
from a color emission profile and a textural perspective.
Similarly, the D1 gel having the 1% calcium carbonate added had
color emission profile similar to the two bicarbonate salt D1 gels
(elevated output of green, yellow, orange and red light), however,
its texture remained unchanged over the course of the illumination
period.
TABLE-US-00017 TABLE 17 Gel D1 Fluoresence output and structure
with various salts added Gel Gel D1 Gel acidity structure
Fluorescence color output type (pH) (Bubble) Purple Blue Green
Yellow Orange Red Gel D1 4.8 N/A N/A N/A N/A N/A N/A N/A Gel D1 +
4.8 Low 5.54 1.51 0.13 0.11 0.06 0.01 3XE Gel D1 + 5.65 High 3.41
0.93 0.44 0.38 0.22 0.2 3XE +1% NaBicarb Gel D1 + 4.86 N/A 3.32
0.97 0.3 0.28 0.16 0.15 3XE + 1% CalCarb Gel D1 + 5.8 High 2.84
0.78 0.32 0.3 0.17 0.16 3XE + 1% PotBicarb. Gel D1 + 5.02 Low 6.24
1.68 0.13 0.11 0.05 0.01 3XE + 1% SodAcetate Gel D1 + 5.5 N/A 6.43
1.8 0.14 0.11 0.05 0.01 3XE + 1% NaBiphosphate
[0506] A further round of experiments was conducted to determine
what, if any, difference would occur when different sources of
bicarbonate (or carbonate) were used in conjunction with the D1
gel.
[0507] To perform this experiment, a D1 gel composition with 327
.mu.of Eosin Y was prepared. Thereafter, an amount (in powder form)
of each respective bicarbonate (or carbonate) salt was added to the
given D1 gel sample. The bicarbonate and carbonate salts that were
tested, denoted in the final weight percentage that was added to
the given D1 gel composition, included: sodium bicarbonate (1% and
5%); potassium bicarbonate (1% and 5%), ammonium bicarbonate (1%);
calcium carbonate (1% and 5%); and magnesium carbonate (1% and 5%).
Each gel with its respective added salt powder was then mixed for 1
minute, and then measured for its fluorescent properties in
accordance with the procedure described in Example 9. The results
from this round of testing are presented in FIG. 11C.
[0508] As can be seen from FIG. 11C, all of the bicarbonate and
carbonate salts that were tested resulted in a D1 gel compositions
that yielded elevated levels of fluorescence, and although the D1
gel comprising the 1% calcium carbonate salt had the lowest
fluorescence level of the group, its level of fluorescence was
still well beyond that of a gel A composition. As such, it would be
possible to use any of these tested bicarbonate or carbonate salts
in a gel composition for enhancing a level of fluorescence output
from the given gel.
Example 12. Superoxide Dismutase (SOD) with/without Bicarbonate
SOD--Fluorescence
[0509] In a first set of experiments to test the effect of adding
super oxide dismutase (SOD) to the gel composition, an experiment
was conducted to determine whether an addition of SOD to a D1 gel
composition could have an impact on a fluorescence output of the D1
gel. As such, 0.1%, 0.2%, 0.5%, and 1% SOD were added to a 1 gram
mixture of a D1 gel, followed by an addition of 327 .mu.g/g of the
chromophore Eosin Y, and the resulting mixture was analyzed
spectrophotometrically for fluorescence in accordance with the
procedure described in Example 9.
[0510] Referring to FIG. 12A and FIG. 12B, the results indicated
that with these percentages of added SOD, there was only a minor
effect on a fluorescence output from the given D1 gels. While the
D1 gels that contained the relatively higher amounts of SOD had
relatively higher levels of fluorescence output to those D1 gels
with lower amounts of SOD, no direct correlation was observed as
between the presence of SOD in the gel and the gel's fluorescence
output. In addition, without sodium bicarbonate the gel will not
"transform", and thus its fluorescence is reduced.
SOD--ROS Production
[0511] This experiment was conducted to determine how SOD at
various concentrations affects the fluorescence output from a D1
gel. An evaluation was also performed as to whether the addition of
SOD to a D1 gel composition may affect the D1 gel vis-a-vis its ROS
production capacity. To measure for such an effect, the total
hydrogen peroxide content in a D1 gel comprising an addition of SOD
ranging from concentration of 0.1%, 0.2%, 0.5% to 1% SOD were
tested to establish an amount of SOD that could be added to a D1
gel to maximize hydrogen peroxide content.
[0512] To perform the experiment, 0.1 grams of D1 gel were mixed
with various SOD concentrations, with 1 mL of working reagent. The
solution was mixed, and allowed to sit at room temperature for 30
minutes, after which time, the absorbance was measured for each
solution at 560 nm using the Pierce assay described in Example
6.
[0513] One result, not from the spectrophotometer, to be assayed
for by visual inspection was the color of the solutions. A high
concentration of hydrogen peroxide should turn the yellow solution
to a purple solution. All 4 solutions tested turned the solution to
a brown.
[0514] At the completion of the 30 minute incubation period, all
four D1 gel test solutions were analyzed, first of all, visually,
and all 4 solutions were observed to have turned the test solution
brown, indicating a level of hydrogen peroxide production in each
of test solutions. With reference to FIG. 12C, the
spectrophotometric measurements indicated that with increasing the
amount of SOD added to the D1 gel composition, an increase in the
hydrogen peroxide content was observed.
[0515] From the above-noted data, it was concluded that increasing
SOD content could result in an increase hydrogen peroxide content
in the D1 gel, with very little difference between adding SOD to a
final amount 0.5% versus 1% per weight of gel, with the 0.5% SOD
being the more effective amount.
SOD--with Glycerine and Bicarbonate--Fluorescence Effect
[0516] As the prior experiments described above indicated the
addition of SOD to a D1 gel could stimulate ROS production in the
D1 with the addition of 0.5% SOD (per weight of gel), tests were
thus performed to assess whether a combined addition of SOD and
sodium bicarbonate might result in a D1 gel with an elevated
fluorescence profile of a D1 gel.
[0517] D1 gel samples were prepared with 0.1% SOD and 0.5% SOD (as
these SOD concentrations were the lowest and highest concentrations
that had previous effects on the gel) to which 1% sodium
bicarbonate and 7.5% sodium bicarbonate were added (likewise, these
% concentrations were chosen for the same reasons). As such, using
these ingredients, the following four D1 gels were made:
[0518] 0.1% SOD with 1% sodium bicarbonate
[0519] 0.5% SOD with 1% sodium bicarbonate
[0520] 0.1% SOD with 7.5% sodium bicarbonate
[0521] 0.5% SOD with 7.5% sodium bicarbonate
[0522] The gels were measured for their fluorescence output in
accordance with the procedure described in Example 9, and the
results of this experiment are presented in FIG. 12D. Looking at
the results presented in FIG. 12D, an addition of SOD may have had
an effect on fluorescence when added at the lower concentration
amounts in combination with an addition of sodium bicarbonate.
[0523] With respect to an addition of glycerin having an effect on
the amount of ROS being produced in a D1 gel composition that also
had SOD and sodium bicarbonate added, the protocol described above
regarding the preparation of the gel compositions was utilized, and
the amount of ROS generated from each of the gels was assayed using
the Pierce assay methodology.
[0524] The results of ROS measurement experiment are shown in FIG.
12E. Firstly, the results indicated that the presence of the sodium
bicarbonate has a larger impact than SOD alone on generation of ROS
production (at the concentrations used). Secondly, the results also
indicated that the two ingredients could be used in combination to
increase ROS production even further than either ingredient
alone.
Example 13. Optimizing the Bicarbonate Concentration
[0525] A further experiment was conducted in order to investigate a
more refined percentage gradient of bicarbonate (in the form of
sodium bicarbonate) that could be added to a D1 gel composition in
order to generate a maximal amount of fluorescence while
concomitantly maintaining at least a neutral pH and a ROS output of
between 1.5-2.0 .mu.M (based on prior experimental results--see
Part A of the Examples). As such D1 gel compositions were prepared,
to which were added various amounts of sodium bicarbonate powder in
order to provide D1 gel samples with the following % sodium
bicarbonate: 0.1%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, and 5%. Gel
samples were tested for their overall fluorescence output and with
respect to their fluorescence output for colors in the visible
range; the set-up, illumination and analysis was that as described
in Example 9. The results from the experiment are presented in FIG.
13A regarding the overall fluorescence output and FIG. 13B and
Table 18 with respect to the fluorescence of the individual colors
in the visible range.
[0526] Looking at FIG. 13A, it can be observed that with the
exception of the lowest and highest salt % concentrations, all of
the % sodium bicarbonate concentrations incorporated into a D1 gel
resulted in a gel having elevated fluorescence output. For the 2%
sodium bicarbonate test gel, this gel appeared to have a minor lag
time before its fluorescence level increased, however, its overall
level ultimately was like the other % concentrations tested (with
the exception of the 0.1% and the 5% test sample gels). Regarding
the individual fluorescence color profiles for each of the sample
D1 gels tested, looking at FIG. 13B and Table 18, it is clear that,
with the exception of the 0.1% and 5% sodium bicarbonate sample D1
gels, the test gels with the added bicarbonate salt % yielded
fluorescence evenly across the entire range of visible colors.
TABLE-US-00018 TABLE 18 Gel D1 fluorescence-scaling of bicarbonate
(SB) Gel D1 Gel Acidity structure Fluorescence color output type
(pH) (Bubble) Purple Blue Green Yellow Orange Red 3XE + 0.1% SB
5.38 Low 6.61 1.92 0.16 0.13 0.06 0.01 3XE + 0.4% SB 5.61
Low-Average 3.38 0.89 0.36 0.31 0.18 0.15 3XE + 0.5% SB 5.7 Average
3.39 0.92 0.39 0.33 0.19 0.17 3XE + 0.75% SB 5.95 High 2.97 0.78
0.42 0.36 0.2 0.19 3XE + 1% SB 6.15 High 3.41 0.93 0.44 0.38 0.22
0.2 3XE + 2% SB 6.38 High 2.7 0.76 0.42 0.35 0.2 0.18 3XE + 3% SB
6.69 High 2.45 1.52 0.41 0.27 0.16 0.17 3XE + 4% SB 7.3 High 3.18
1.05 0.42 0.33 0.19 0.17 3XE + 5% SB 7.6 High 8.92 5.26 0.19 0.11
0.06 0.02
Example 14. Propylene Glycol (Separately or in Combination with
Glycerol)
[0527] Further testing was performed in order to evaluate whether
an addition of propylene glycol (PG) along with the presence of
glycerin in a D1 gel could alterthe fluorescence output of such a
gel.
[0528] Firstly, the effect of combining PG and glycerol was
evaluated in solution; an aqueous solution was prepared containing
3.times. Eosin Y, to which only glycerin, or only PG, or both
glycerin and PG were added. The water-only solution served as the
control. Each solution was then measured for its fluorescence using
the KLOX multi-LED blue lamp with an illumination period for 5
minutes to determine their fluorescence properties of the given
solutions. The results are presented in FIG. 14 along with Table 19
and Table 20.
TABLE-US-00019 TABLE 19 Glycerin and propylene glycol fluoresence
Time (min) - Fluorescence Sample 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5
AVG Glycerin 1.62 1.57 1.54 1.50 1.47 1.44 1.39 1.36 1.32 1.29 1.24
1.43 Propylene 2.19 2.14 2.12 2.10 2.08 2.06 2.05 2.02 1.99 1.98
1.96 2.06 Glycol Both 2.17 2.06 2.04 2.00 1.99 1.99 1.96 1.95 1.94
1.91 1.91 1.99 Water 0.87 0.84 0.81 0.81 0.80 0.80 0.79 0.78 0.78
0.78 0.77 0.80
TABLE-US-00020 TABLE 20 Glycerin and propylene glycol
fluorescence--color output Color Water Glycerin Both PG Violet 6.80
7.56 7.88 9.41 Blue 2.06 2.65 2.75 3.59 Green 0.12 0.16 0.22 0.24
Yellow 0.07 0.16 0.22 0.23 Orange 0.04 0.09 0.13 0.12 Red 0.01 0.03
0.04 0.03
[0529] As can be seen from FIG. 14 and Table 19, adding both
glycerin and PG had a very significant effect on the fluorescence
of chromophore solutions. While the solution of 3.times. Eosin Y
only had a fluorescence level of 0.8, with an addition of glycerin
the fluorescence increased by 79% (to 1.4). When the 3.times. Eosin
Y was placed in solution with both glycerin and PG, the
fluorescence increased by 149% (to 2.0), and a similar effect was
observed with adding PG itself--the fluorescence increased 158% (to
2.1). In addition to this, the blue light from the KLOX lamp also
increased in this same manner, though not as significant as for
fluorescence. Regarding the color spectrum of emitted fluorescence,
as shown in Table 20, it was evident that the addition of glycerin
resulted in an increase output of the green to red color range, and
this effect was increased with the addition of the glycerin-PG
combination. As such, it was concluded that the fluorescence level
could be modulated by adding either a single additive such as the
glycerin, or a combination such as the glycerin with PG.
Example 15. Scaling of Propylene Glycol
[0530] As an addition of PG to a glycerin-containing chromophore
solution resulted in a positive impact on the fluorescence
generating properties of the solution, a further evaluation was
performed with respect to adding PG to a D1 gel formulation;
aspects that were considered included an impact on fluorescence
output from the D1 gel and whether a D1 gel with PG added to it
could transmit/emit light, and also the physical characteristics of
the D1 gel with the PG added; if the gel with the PG were to have
an increased viscosity and tackiness (or stickiness) to it upon
being illuminated with the KLOX multi-LED blue light, such would be
considered as a detrimental additional quality as it would make the
gel more difficult to remove.
[0531] In a first round of testing in order to establish a scale of
mg/g PG that could possibly be added to a D1 gel, testing was
performed on aqueous solutions with combinations of propylene
glycol, glycerin and water. Ratios of these ingredients were tested
to see how much of each component may be required to maximize
fluorescence. Test solutions were made as follows: 1) 0 mg/g
Propylene Glycol and 0 mg/g Glycerin, 2) 600 mg/g Propylene Glycol
and 200 mg/g Glycerin, 3) 400 mg/g Propylene Glycol and 100 mg/g
Glycerin, and 4) 400 mg/g Propylene Glycol and 400 mg/g Glycerin.
To each solution, 327 .mu.g/g Eosin Y was added. Each solution was
then illuminated with the KLOX multi-LED blue light (THERA.TM.) for
a period of 5 minutes, and the fluorescence data captured as
described in Example 9.
[0532] The results from the in-solution testing are presented in
FIG. 15A and Table 21 with respect to the overall fluorescence
output of the illuminated test solutions, while the color output
information from the illuminated test solutions is presented in
FIG. 15B and FIG. 15C together with Table 22.
TABLE-US-00021 TABLE 21 Fluorescence of Gel D2 - scaling of
propylene glycol (PG) and glycerin - in solution Gel D2
Time/Fluorescence Sample 0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50
4.00 4.50 5.00 Avg 0 mg/g PG 0.92 0.92 0.89 0.88 0.88 0.86 0.83
0.82 0.78 0.76 0.73 0.84 0 mg/g Glycerin 600 mg/g PG 2.16 2.13 2.10
2.08 2.06 2.04 2.03 2.00 1.98 1.98 1.92 2.04 200 mg/g Glycerin 400
mg/g PG 1.86 1.82 1.80 1.78 1.76 1.74 1.74 1.71 1.66 1.64 1.60 1.74
100 mg/g Glycerin 400 mg/g PG 2.17 2.11 2.07 2.04 2.00 1.95 1.90
1.86 1.85 1.80 1.75 1.96 400 mg/g Glycerin
TABLE-US-00022 TABLE 22 Fluorescence of Gel D2--scaling, in
solution, of propylene glycol (PG) and glycerin--color output 0
mg/g PG 600 mg/g PG 400 mg/g PG 400 mg/g PG 0 mg/g 200 mg/g 100
mg/g 400 mg/g Color Glycerin Glycerin Glycerin Glycerin violet 8.21
9.78 9.16 9.30 blue 3.02 3.54 3.35 3.51 green 0.14 0.25 0.23 0.22
yellow 0.08 0.22 0.18 0.22 orange 0.04 0.12 0.09 0.12 red 0.01 0.03
0.02 0.04
[0533] The results from the in-solution PG scaling indicated that
with adding an increased level of PG (600 mg versus 400 mg), an
increase in the overall fluorescence could be obtained, and a
similar effect could also be achieved with adding an increased
level of glycerin (although the effect was not a dramatic).
Regarding the color output from the illuminated PG-glycerin
chromophore-contain solutions, each solution produced a significant
larger amount of green, yellow, orange and red fluorescence
compared to the solution lacking any added PG or glycerin.
Differences, however, in the fluorescence color output profile as
between the test solutions was noticeable, for example, the test
solution containing the 400 mg/g PG:100 mg/g glycerin added
combination produced a lower amount of yellow, orange and red
relative to the other additive-containing test solutions.
[0534] Given the results from the first round of PG scaling
in-solution testing, testing for scaling of PG in a gel composition
was undertaken. First, a gel B was prepared by mixing 18.1 mg/g
carbopol into water for 3 hours, and adding base to the solution
(to pH 5.0). A sample of D1 gel was also prepared using the same
procedure and adding 436 mg/g glycerin as well. The remaining three
gels, A) 600 mg/g Propylene Glycol and 200 mg/g Glycerin, B) 400
mg/g Propylene Glycol and 100 mg/g Glycerin, and C) 400 mg/g
Propylene Glycol and 400 mg/g Glycerin were prepared by adding the
appropriate amounts of glycerin and PG to the gel B and mixing
thoroughly. To each of gel sample, 327 .mu.g/g of Eosin Y was
added, and prior to the gels being illuminated, 1% sodium
bicarbonate was added to the gel mixture.
[0535] Each of the gel samples were illuminated as per the
procedure described in Example 9, with the illumination period
lasting for 5 minutes for each sample. The results from the in-gel
testing are presented in FIG. 15D and Table 23 with respect to the
overall fluorescence output of the illuminated test gels, while the
color output information from the illuminated test gels is
presented in FIG. 15E and FIG. 15F together with Table 24.
TABLE-US-00023 TABLE 23 Fluorescence of Gel D2 - scaling of
propylene glycol (PG) and glycerin - in gel Gel D2
Time/Fluorescence Sample 0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50
4.00 4.50 5.00 Avg 0 mg/g PG 0.79 0.84 0.86 0.88 0.92 0.94 0.95
0.97 0.98 0.99 1.00 0.92 0 mg/g Glycerin 0 mg/g PG 3.57 3.76 3.83
3.83 3.79 3.75 3.72 3.68 3.64 3.57 3.54 3.70 436 mg/g Glycerin 600
mg/g PG 1.98 1.96 1.94 1.95 1.94 1.95 1.94 1.96 1.97 1.99 2.01 1.96
200 mg/g Glycerin 400 mg/g PG 4.79 5.40 5.69 5.68 5.55 5.34 5.11
4.89 4.67 4.51 4.35 5.09 100 mg/g Glycerin 400 mg/g PG 2.02 1.98
1.97 2.00 2.04 2.05 2.08 2.11 2.12 2.13 2.12 2.06 400 mg/g
Glycerin
TABLE-US-00024 TABLE 24 Fluorescence of Gel D2--scaling, in gel, of
propylene glycol (PG) and glycerin--color output 0 mg/g 0 mg/g 600
mg/g 400 mg/g 400 mg/g PG PG PG PG PG 0 mg/g 436 mg/g 200 mg/g 100
mg/g 400 mg/g Color Glycerin Glycerin Glycerin Glycerin Glycerin
violet 3.39 2.47 8.44 3.67 7.29 blue 1.00 0.65 2.90 1.21 2.47 green
0.11 0.38 0.24 0.56 0.25 yellow 0.10 0.35 0.21 0.48 0.22 orange
0.06 0.20 0.11 0.27 0.12 red 0.02 0.19 0.03 0.25 0.03
[0536] The results from the in-gel testing indicated that the
sample (B) having 400 mg/g Propylene Glycol and 100 mg/g Glycerin
performed the best with respect to an amount of overall
fluorescence output (see FIG. 15D) as well as the amount of
fluorescence for each of the green, yellow, orange and red colors.
Interestingly, the gels that had the increased levels of PG, their
output of fluorescence was not as great as the sample (B), even
though the results from the in-solution testing implied that the
opposite should be the case. Noteworthy was the fact that gel
samples with the higher levels of PG content became very
liquid-like upon being illuminated, and it was concluded that these
high-PG content gels would have too high a PG in order to function
effectively as a gel that would retain some degree of its physical
stickiness during a treatment process.
[0537] In a further experiment to evaluate the physical
characteristics of the test gels (A) to (C) described above, a
consistent size aliquot of each gel was applied onto a hand and
held upside down for 1 minute. Observations of each gel were done
to determine their consistency. All of the test gels were found to
be easy to spread, and would stick to the hand when held upside
down. The gel B had a firm feel, and could be removed with paper
towel easily, while the D1 gel was sticky and was harder to remove
with a paper towel. Test gels (A) and (C) were both liquid-like,
whereas test gel (B) was found to behave similar to the gel B
sample and was very easy to remove despite its having a definite
gel consistency.
Example 16. Scaling of Bicarbonate in Presence of Glycerol and
Propylene Glycol
[0538] In a further round of testing, an evaluation was performed
with respect to determining an amount of sodium bicarbonate that
could be added to a D2 gel that containing 654 mg/g glycerin and
234 mg/g propylene glycol (roughly equivalent to the sample (A) gel
test in Example 15, second round).
[0539] To perform the experiment, a series of D2 gel samples were
prepared, each having a 3.times. amount of Eosin Y chromophore. To
each gel sample, just prior to being illuminated, an amount of
sodium bicarbonate was added. The values of sodium bicarbonate were
0%, 0.1%, 0.5%, 1.0%, 2.0%, 5.0%, and 10.0%. The contents of the
given gel were mixed for about 1 minute just before illumination
began. The gel was then illuminated under the KLOX blue lamp for 5
minutes, and the fluorescence of the gel was measured in accordance
with the procedure detailed in Example 9. The results for the
overall fluorescence output of the tested gel samples are presented
in FIG. 16 and Table 25.
TABLE-US-00025 TABLE 25 Scaling of Sodium Bicarbonate (NaBicarb) in
Gel D2 - Fluorescence output Sample/ Time/Fluorescence % NaBicarb 0
0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 AVERAGE 0% 2.28 2.24 2.16 2.10 2.05
2.03 1.99 1.96 1.92 1.89 1.84 2.04 0.10% 2.28 2.18 2.12 2.07 2.02
2.00 1.96 1.93 1.88 1.85 1.82 2.01 0.50% 2.42 2.39 2.38 2.39 2.44
4.37 4.52 4.78 5.00 5.22 5.37 3.75 1% 2.64 2.76 5.08 5.62 6.04 6.20
6.09 5.90 5.63 5.51 5.33 5.16 2% 5.29 5.94 6.63 6.87 6.72 6.37 6.03
5.77 5.60 5.49 5.45 6.01 5% 7.13 6.59 6.03 5.67 5.64 5.67 5.70 5.87
5.91 5.92 5.88 6.00 10% 7.11 6.17 5.79 5.75 5.85 5.98 6.02 6.11
5.99 6.00 5.88 6.06
[0540] As can be seen from FIG. 16, addition of the low amounts
(0.1% and 0.5%) of sodium bicarbonate either had no or a delayed
effect on increasing the level of fluorescence of the D2 gel
sample. Overall, as can be seen in Table 25, the results indicated
that the more sodium bicarbonate added, the faster the increase in
fluorescence occurred, along with the achieving a higher level per
se. For increasing the fluorescence level of a D2 gel, without
delay, using a bicarbonate salt such as 2% sodium bicarbonate
served such a purpose, as adding a higher amount of such a
bicarbonate would yield an equivalent result.
Example 17. Ratio of Glycerol:Propylene Glycol, and Addition of
Parabens to Increase Fluorescence
[0541] In a further round of experiments, alterations were
introduced into D2 gel compositions with respect to adding
different ratios of PG to glycerin and, as well, adding further
components to the gel mixture in order to sustain the fluorescence
output of the gel at an elevated level. Previously, in the
preparation of gel B, an amount (about 2 mL) of 10 N NaOH would be
added in order to basify the gel composition, however, doing so
often resulted in a lack of gel formation. As such, attempts were
made at adding various components of a gel together, ultimately to
form a D2 gel composition, followed thereafter by basification. The
gel samples that were prepared for testing in this Example all had
a 3.times. amount of Eosin Y added as the chromophore. The gels
made, based on previous successful results were as described in
Table 26 below.
TABLE-US-00026 TABLE 26 Gel D2 mixtures--alternative ratios of PEG
to glycerol--parabens D2 D2 with Methyl Paraben and Propyl Paraben
(Gel E) D2 with D2 with 600 mg/g PG 500 mg/g PG D2 with 500 mg/g PG
D2 with 300 mg/g PG 150 mg/g Glycerin 50 mg/g Glycerin D2 with 400
mg/g PG D2 with 200 mg/g PG 200 mg/g Glycerin 200 mg/g Glycerin
[0542] After the D2 gel samples were prepared, 1% sodium
bicarbonate was added (in powder form) and mixed for 1 minute with
each gel sample before being illuminated with the KLOX blue lamp
for 10 minutes with 5 cm distance between the gel and the lamp (in
accordance with the procedure detailed in Example 9).
[0543] The results from the gel testing are presented in FIG. 17A
and Table 27 with respect to the overall fluorescence output of the
illuminated test gels, while the color output information from the
illuminated test gels is presented in FIG. 17B and FIG. 17C
together with Table 28.
TABLE-US-00027 TABLE 27 Gel D2 - Fluorescence output - variable
ratio of PG to glycerin - parabens D2 gel Time/Fluorescence sample
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 400 mg/g PG 4.61 5.13 5.45 5.48
5.41 5.21 5.01 4.77 4.42 4.23 4.07 100 mg/g Glycerin Methyl Paraben
4.98 5.22 5.41 5.44 5.51 5.55 5.54 5.55 5.57 5.54 5.52 5.51 Propyl
Paraben (Gel E) 500 mg/g PG 2.30 2.52 4.81 5.21 5.43 5.42 5.28 5.11
4.98 4.79 4.64 4.51 600 mg/g PG 2.03 2.00 2.01 2.00 2.03 2.04 2.05
2.06 2.07 2.08 2.08 2.07 500 mg/g PG 2.03 2.01 2.12 2.28 2.49 4.65
4.96 5.19 5.22 5.11 5.05 4.96 150 mg/g Glycerin 300 mg/g PG 4.09
4.37 4.54 4.59 4.58 4.54 4.46 4.34 4.27 4.16 4.06 3.96 50 mg/g
Glycerin 400 mg/g PG 2.36 2.56 4.92 5.21 5.31 5.17 4.89 4.68 4.46
4.24 4.03 3.83 200 mg/g Glycerin 200 mg/g PG 4.31 4.78 4.84 4.82
4.73 4.66 4.52 4.40 4.28 4.18 4.07 3.97 200 mg/g Glycerin D2 gel
Time/Fluorescence sample 6 6.5 7 7.5 8 8.5 9 9.5 10 AVG 400 mg/g PG
4.89 100 mg/g Glycerin Methyl Paraben 5.55 5.55 5.55 5.54 5.52 5.52
5.51 5.52 5.53 5.48 Propyl Paraben (Gel E) 500 mg/g PG 4.36 4.28
4.20 4.15 4.03 3.96 3.92 3.87 2.14 4.28 600 mg/g PG 2.06 2.05 2.04
2.03 2.05 2.05 2.08 2.08 2.11 2.05 500 mg/g PG 4.89 4.73 4.68 4.64
4.62 4.62 4.60 4.57 4.57 4.19 150 mg/g Glycerin 300 mg/g PG 3.86
3.81 3.76 3.68 3.61 3.55 3.48 3.43 3.39 4.03 50 mg/g Glycerin 400
mg/g PG 3.72 2.02 1.98 1.92 1.87 1.82 1.79 1.75 1.70 3.34 200 mg/g
Glycerin 200 mg/g PG 3.86 3.79 3.70 3.62 3.56 3.51 3.43 3.38 3.32
4.08 200 mg/g Glycerin
TABLE-US-00028 TABLE 28 Gel D2 - Fluorescence color output -
variable ratio of PG to glycerin - parabens D2 Gel type D2 with D2
with D2 with D2 with D2 with Methyl D2 500 300 400 200 Paraben,
with D2 with mg/g mg/g mg/g mg/g Propyl 500 600 PG, 150 PG, 50 PG,
200 PG, 200 Paraben mg/g mg/g mg/g mg/g mg/g mg/g Color D2 (Gel E)
PG PG Glycerin Glycerin Glycerin Glycerin violet 4.08 3.83 4.76
7.25 6.00 3.48 4.82 2.84 blue 1.31 1.10 1.48 2.39 1.91 1.07 1.72
0.83 green 0.56 0.63 0.52 0.25 0.40 0.50 0.49 0.49 yellow 0.45 0.49
0.43 0.22 0.35 0.40 0.41 0.43 orange 0.25 0.27 0.24 0.11 0.20 0.22
0.23 0.24 red 0.23 0.25 0.20 0.03 0.14 0.20 0.19 0.22
[0544] The results indicated that with an insufficient gel amount
due to too much PG being added (e.g., 600 mg/g) the gel
fluorescence decreased, or would not react with sodium bicarbonate
effectively. Additionally, the results also indicated an amount of
glycerin was required as opposed to pure propylene glycol, in order
to maximize fluorescence. Also, the ratio of gel to additive is
very important and it seems that 400-500 mg/g of the PG added to
the D2 gel composition provided a better performing D2 gel in terms
of overall fluorescence output as well as across the range of the
color spectrum. Furthermore, adding a small amount of parabens to
the D2 gel allowed the gel to reach the same maximum fluorescence
of the other gels, but the gel would not degrade (i.e., lose its
structural characteristics), even after 10 minutes of
illumination.
Example 18. Further Testing of Parabens
[0545] As the addition of parabens to the D2 gel provided an
improved and prolonged performance of the gel with respect to the
gel's fluorescence output, a further set of tests were performed to
evaluate whether an addition of methyl and propyl parabens, either
with or without sodium bicarbonate being added to the gel mixture,
would have on the D2 gel.
[0546] To perform the experiment, 10 grams of D2 gel was made with
3.times. Eosin Y added. This gel was then divided into two equal
batches, one with no further components being added, and the other
had 1.01 mg/g methyl paraben and 0.54 mg/g propyl paraben in
combination. The first and second batches containing either no
parabens or the parabens were then further subdivided into two
groups (i.e., a total of four gels) with one member of each group
being kept as is, while the other member of the group having 1%
sodium bicarbonate added to it. If sodium bicarbonate were added,
then the gel was mixed with the sodium bicarbonate for 1 minute
before starting the illumination period.
[0547] The gels were illuminated for a period of 5 minutes and at a
distance of 5 cm from the gel surface and the fluorescence results
were captured on a spectrophotometer as per Example 9.
[0548] The results from the parabens-containing D2 gel (designated
as Gel E) testing are presented in FIG. 18A and Table 29 with
respect to the overall fluorescence output of the illuminated test
gels, while the color output information from the illuminated test
gels is presented in FIG. 18B and FIG. 18C toether with Table
30.
TABLE-US-00029 TABLE 29 Fluorescence output of gels D2 and E, with
or without sodium bicarbonate (SB) Time/Fluorescence Gel type 0 0.5
1 1.5 2 2.5 3 3.5 4 4.5 5 AVG D2 1.58 1.54 1.53 1.52 1.50 1.49 1.46
1.43 1.40 1.37 1.36 1.47 no SB E 1.51 1.53 1.48 1.46 1.42 1.40 1.37
1.36 1.34 1.32 1.32 1.41 no SB D2 + 4.61 5.13 5.45 5.48 5.41 5.21
5.01 4.77 4.42 4.23 4.07 4.89 SB E + 4.48 4.56 4.93 5.23 5.48 5.54
5.62 5.67 5.68 5.72 5.76 5.33 SB
TABLE-US-00030 TABLE 30 Fluorescence color output of gels D2 and E,
+/- sodium bicarbonate (SB) Gel type Gel D2 Gel E Gel D2 Gel E
Color No SB No SB Yes SB Yes SB violet 8.00 8.06 4.08 4.01 blue
2.60 2.68 1.31 1.12 green 0.20 0.19 0.56 0.60 yellow 0.16 0.15 0.45
0.48 orange 0.08 0.07 0.25 0.26 red 0.02 0.02 0.23 0.25
[0549] The results, as indicated in FIG. 18A and Table 29,
regarding the overall fluorescence output of the tested gels
indicated that regardless of the presence of parabens in the gels,
the fluorescence output level is increased with the addition of the
sodium bicarbonate; the parabens had no apparent effect on the
level of fluorescence of the D2 gel or the Gel E compositions.
Furthermore, comparing the results for the D2 gel versus gel E when
both gels either had or lacked an addition of the 1% sodium
bicarbonate, parabens did not appear to have any effect on the
fluorescence color output spectrum or on the amount of any of the
green, yellow, orange or red fluorescence emitted from the
illuminated gels. The fluorescence of the gel E samples, containing
the parabens, did not, however, degrade over the illumination
period, indicating that a prolonged fluorescence exposure could be
obtained by utilizing a parabens-containing gel composition such as
gel E.
Example 19. Scaling of Chromophore Concentration in Presence of
Bicarbonate, Glyercol, Propylene Glycol and Parabens
[0550] A further evaluation was performed with respect to the
performance of the parabens-containing gel E with respect to
addressing what amount of chromophore might be added in order to
induce a maximum yield of fluorescence from an illuminated gel
E.
[0551] To perform the experiment, a batch of gel E was prepared,
and after mixing, an amount of the chromophore Eosin Y was added,
in solution, to each aliquot of the gel E batch so as to result in
gel E samples having a final Eosin Y concentration being 2.times.,
3.times., 4.times., 5.times., and 6.times. Eosin Y. Each of the gel
samples was mixed well, and thereafter 2% sodium bicarbonate was
added to the gels approximately 1 minute before the samples were
illuminated for 10 minutes using the KLOX multi-LED blue light.
Illumination and fluorescence analysis were performed as described
in Example 9. The results from the experiment are presented in FIG.
19A with respect to the fluorescence output per gel over the
illumination time period, while FIG. 19B shows the amount of blue
light that is transmitted through the illuminated gel sample at
time points over the course of the illumination period.
[0552] As can been seen from FIG. 19A, the results indicated that
altering the Eosin Y concentration in the gel E composition may
only have a minor effect on the fluorescence output of the gel E
composition given that all of the tested gel samples had a
fluorescence yield that stabilized between 4.5 and 5 mW/cm.sup.2,
in no particular order of concentration. Looking at FIG. 19B, blue
light passing through the gel could serve as an indicator of how
much of the illuminating light was converted into fluorescence due
to the activity of the chromophore in the gel. At added chromophore
concentrations of 3.times. and above, less blue light was
transmitted through the given sample gel. However, the degree to
which the lack of blue light transmittance at the 4.times.,
5.times. and 6.times. Eosin Y concentrations was simply due to a
quenching effect of the chromophore presence was not
determined.
[0553] A further experimental round was conducted to further
determine an appropriate amount of chromophore to add to gel E in
order to maximize fluorescence.
[0554] To perform the experiment, a gel E mixture was prepared as
per the first round experiment, however, for this second round of
testing additional Eosin Y chromophore concentrations were also
tested, which included 0.5.times. and 1.times. Eosin Y. The gels
were illuminated and data captured as per the first round
experiment, and the results are presented in FIG. 19C with respect
to the fluorescence output per gel over the illumination time
period, while FIG. 19D shows the amount of blue light that is
transmitted through the illuminated gel sample at time points over
the course of the illumination period.
[0555] Referring to FIG. 19C, it can be seen that the adjusting the
chromophore concentration to below 2.times. Eosin Y in the gel E
resulted in a comparatively significant lower level of fluorescence
yield and a higher level of transmittance of the blue light through
the illuminated gel E samples. The blue light passing through
however is greatly increased by lower Eosin Y concentrations.
Example 20. Components that may Affect Photobleaching Rate
[0556] As results from prior experimental rounds, whether in
relation to ROS production or in relation to fluorescence
generating capacity, indicated that some components may have a
beneficial impact, a round of further testing was conducted in
order to evaluate the effect that certain added components may have
on a rate of photobleaching of the chromophore Eosin Y and
fluorescence output in the context of the given gel mixture and
illumination time period. The purpose of this experiment was to
find out the ingredients responsible for increasing the bleaching
time and the components that boost the fluorescence.
[0557] To perform the experiment, a gel D1 composition was prepared
by mixing 18.1 grams of carbopol, 43.6 grams of glycerin and 54.59
grams of water, mixing and then adding a 3.times. amount of the
Eosin Y chromophore followed by further mixing to form a uniform
composition. Optionally, further components were mixed into the D1
gel, such as either PG or an amount of the divalent ion chelator
EDTA. For comparative purposes, a gel mixture was also prepared,
but having an amount of chromophore added (2.times. Eosin Y). To
each prepared gel sample, an amount of sodium bicarbonate was added
to provide for a final concentration of either 1% or 0.2% sodium
bicarbonate in the gel mixture, and after mixing and incubation for
approximately 1 minute, the given prepared gel sample was
illuminated as described in Example 9 for a period of 10
minutes.
[0558] The results are presented in FIG. 20A and Table 31 with
respect to the fluorescence output per gel over the illumination
time period, while FIG. 20B and Table 32 provide the data with
respect to the fluorescence color output across the visual spectrum
range for each of the illuminated gel samples.
[0559] As can be seen from FIG. 20A and Table 31, the better
perfoming gel compositions on a comparative basis were the D1 gels
having the 1% sodium bicarbonate and, additionally, the PG added to
the gel. Regarding the fluorescence color output, these two gels
also show more green, yellow, orange and red fluorescence spectrum
output. Regarding the gel A composition, which already contained
EDTA, while its initial level of fluorescence could be elevated
with an addition of the 1% sodium bicarbonate, its fluorescence
output decreased rapidly to a level of those other gels to which
EDTA was also added (see FIG. 20A). According to the result, an
addition of glycerin and the PG resulted in an increase the
fluorescence, while a presence of EDTA altered the performance of
the gel composition by affecting the rate of photobleaching of the
chromophore.
TABLE-US-00031 TABLE 31 Fluoresecence output of gels A and D1, with
various additives Gel + Time/Fluorescence output additive 0 0.5 1
1.5 2 2.5 3 3.5 4 4.5 5 D1 + 4.07 4.07 4.15 4.20 4.20 4.18 4.13
4.05 3.97 3.89 3.77 3X YE + 1% SB A 5.29 4.94 4.52 4.10 3.30 2.84
2.30 1.92 1.68 1.51 1.30 0% UP + 3X EY + 1% SB D1 + 5.60 5.60 5.51
5.35 5.17 4.98 4.81 4.64 4.50 4.35 4.26 PEG + 3X EY + 1% SB D1 +
4.00 3.03 5.08 3.42 2.11 1.64 1.32 1.07 0.95 0.83 0.80 EDTA + 3X EY
+ 1% SB TG + PEG + 5.48 3.11 4.80 3.03 2.31 1.76 1.55 1.42 1.28
1.19 1.14 EDTA + 3XE + 1% SB D1 + 1.48 1.51 1.50 1.50 1.50 1.49
1.49 1.47 1.48 1.48 1.47 3X EY + 0.2% SB A 2.28 2.07 1.81 1.56 1.10
0.69 0.87 0.67 0.62 0.53 0.51 0% UP + 3X EY + 0.2% SB Gel +
Time/Fluorescence output additive 5.5 6 6.5 7 7.5 8 8.5 9 9.5 10 D1
+ 3.69 3.62 3.51 3.46 3.37 3.30 3.25 3.17 3.12 3.08 3X YE + 1% SB A
1.26 1.22 1.18 1.16 1.14 1.10 1.07 1.03 1.02 1.01 0% UP + 3X EY +
1% SB D1 + 4.13 4.05 3.98 3.91 3.83 3.75 3.69 3.62 3.55 3.48 PEG +
3X EY + 1% SB D1 + 0.71 0.66 0.63 0.60 0.57 0.54 0.53 0.52 0.48
0.47 EDTA + 3X EY + 1% SB TG + PEG + 1.08 1.02 0.97 0.93 0.87 0.86
0.80 0.75 0.73 0.70 EDTA + 3XE + 1% SB D1 + 1.47 1.48 1.47 1.47
1.47 1.47 1.46 1.47 1.47 1.47 3X EY + 0.2% SB A 0.512 0.47 0.441
0.401 0.4 0.406 0.385 0.399 0.364 0.328 0% UP + 3X EY + 0.2% SB
TABLE-US-00032 TABLE 32 Fluoresecence color output of gels A and
D1, with various additives Gel Gel + texture Fluorescence color
output additive pH (bubbles) Purple Blue Green Yellow Orange Red D1
+ 5.65 High 3.41 0.93 0.44 0.38 0.22 0.2 3X YE + 1% SB A 5.05
Average 2.45 1.52 0.41 0.27 0.16 0.17 0% UP + 3X EY + 1% SB D1 +
5.61 High 1.73 0.39 0.45 0.51 0.29 0.28 PG + 3X EY + 1% SB D1 +
5.78 High 6.24 4.36 0.5 0.14 0.08 0.07 EDTA + 3X EY + 1% SB D1 +
5.6 High 5.6 3.92 0.49 0.18 0.1 0.09 PG + EDTA + 3XE + 1% SB D1 +
5.04 Low 5.99 1.79 0.19 0.16 0.08 0.02 3X EY + 0.2% SB A 4.7 Low
8.92 5.26 0.19 0.11 0.06 0.02 0% UP + 3X EY + 0.2% SB
Example 21. Altering pH with or without the Presence of
Bicarbonate
[0560] An experiment was conducted to determine the fluorescence of
the D1 gel under various pH conditions, with the gel either
containing or lacking sodium bicarbonate.
[0561] To perform the experiment, three sample D1 gels were
prepared with each having 3.times. Eosin Y and were measured for
fluorescence (as per the procedure detailed in Example 9) under
three conditions: two of the gels had their pH adjusted to pH 5,
which is a standard pH setting for the Dlgel, and one of these two
gels sodium bicarbonate in powder form was added, just prior to
illumination of the gel, to provide a final concentration of 1%
sodium bicarbonate in the gel sample. A third gel was also prepared
that had its pH adjusted to pH 3, and this gel had no sodium
bicarbonate added. The three test gels were thus those noted as: D1
gel at pH 5 with sodium bicarbonate; D1 gel at pH 5; and D1 gel at
pH 3. Note that increasing the pH of the D1 gel to above a neutral
level was not tested, as the chromophore becomes degraded at pH
>7, and thus the gel will not fluoresce at all.
[0562] Each of the gels was illuminated for a period of 10 minutes
at a distance of 5 cm between the lamp and the gel, and the
fluorescence data were recorded using a spectrophotometer. The
results from the experiment are presented in FIG. 21 and Table
32.
TABLE-US-00033 TABLE 33 Gel D1 fluorescence with scaling of pH
Fluorescence/Sample Time Gel D1, pH 5 + (minutes) 1% NaBicarb Gel
D1, pH 5 Gel D1, pH 3 0 4.15 1.30 0.36 0.5 3.99 1.27 0.37 1 3.93
1.25 0.38 1.5 3.89 1.24 0.36 2 3.87 1.23 0.36 2.5 3.83 1.21 0.36 3
3.78 1.20 0.36 3.5 3.72 1.18 0.35 4 3.66 1.19 0.34 4.5 3.60 1.17
0.34 5 3.54 1.17 0.34 5.5 3.47 1.16 0.34 6 3.39 1.16 0.35 6.5 3.38
1.15 0.33 7 3.33 1.15 0.34 7.5 3.28 1.13 0.33 8 3.22 1.13 0.33 8.5
3.18 1.13 0.33 9 3.15 1.12 0.33 9.5 3.09 1.11 0.32 10 3.05 1.11
0.32 AVG 3.55 1.18 0.35
[0563] Referring to Table 32 and FIG. 21, it is clearly evident
that the D1 gel with sodium bicarbonate had a substantially greater
amount of fluorescence yield compared to an equivalent gel that
lacked the added bicarbonate. Furthermore, lowering the pH of the
D1 gel had a negative effect on the amount of fluorescence that the
gel could produce, and was even far below the level of fluorescence
that a gel A would typically produce under the same illumination
conditions.
Example 22. Stability of Pre-Mixed Bicarbonate (Non-Powder)
[0564] As addition of bicarbonate to a gel composition of the
present disclosure occurs by an addition of the salt in a powder
form, an experiment was conducted to determine if having sodium
bicarbonate stored in a separate gel could still have the same
effect as when mixed with the D1 gel as sodium bicarbonate in
powder form.
[0565] To perform the experiment, a gel B was basified to a very
high pH (13). Then separately sodium carbonate and sodium
bicarbonate were added to the gel B in excess (200 milligrams per 1
gram of gel) and mixed well so as to form a carbonate-gel B and a
bicarbonate-gel B. A separate gel B was then made using an
unbasified gel B (acidic) and adding glycerin (330 milligrams per 1
gram of gel) and Eosin Y (6.times.) to the separate gel, this
prepared gel referred to as the glycerin gel for this experiment.
The prepared gels were either tested on the day of preparation, or
the following or kept for a one week period of time and then
tested.
[0566] The spectrophotometer was prepared for taking fluorescence
measurements as described in Example 9, and thereafter the glycerin
gel was mixed with either the bicarbonate-gel B or the
carbonate-gel B at a 10 to 1 ratio to provide a resulting gel
mixture having a pH of approximately 8. After mixing for one
minute, the fluorescence of the glycerin/carbonate-gel B mixture
and the glycerin/bicarbonate-gel B mixtures was measured over the
course of a 10 minute illumination period using the KLOX multi-LED
blue light.
[0567] The results from the experiment are presented in FIG. 22 and
show the same day and next day results, along with the fluorescence
measurements taken when the sodium bicarbonate is added in a powder
form. The results indicate that at least for the gels stored
overnight prior to mixing, an enhanced level of fluorescence
comparable to that obtained when adding the sodium bicarbonate
powder form could be obtained, thereby indicating that the highly
basified gel B containing the sodium bicarbonate could be stable
for a period of time.
INCORPORATION BY REFERENCE
[0568] All references cited in this specification, and their
references, are incorporated by reference herein in their entirety
where appropriate for teachings of additional or alternative
details, features, and/or technical background.
EQUIVALENTS
[0569] While the subject matters of this disclosure has been
particularly shown and described with reference to particular
embodiments, it will be appreciated that variations of the
above-disclosed and other features and functions, or alternatives
thereof, may be desirably combined into many other different
systems or applications. Also, that various presently unforeseen or
unanticipated alternatives, modifications, variations or
improvements therein may be subsequently made by those skilled in
the art which are also intended to be encompassed by the following
claims.
* * * * *