U.S. patent application number 13/911470 was filed with the patent office on 2013-11-07 for moisturizing foam containing lanolin.
The applicant listed for this patent is Foamix Ltd.. Invention is credited to Alex Besonov, Meir Eini, Doron Friedman, Dov Tamarkin.
Application Number | 20130295022 13/911470 |
Document ID | / |
Family ID | 34864843 |
Filed Date | 2013-11-07 |
United States Patent
Application |
20130295022 |
Kind Code |
A1 |
Friedman; Doron ; et
al. |
November 7, 2013 |
Moisturizing Foam Containing Lanolin
Abstract
The present invention provides a highly tolerable, hydrating
lanolin containing foamable composition for administration to the
skin, body surface, body cavity or mucosal surface, e.g., the
mucosa of the nose, mouth, eye, ear, respiratory system, vagina or
rectum. The foamable composition includes lanolin, a surface-active
agent, about 0.01% to about 5% by weight of at least one polymeric
additive selected from the group consisting of a bioadhesive agent,
a gelling agent, a film forming agent and a phase change agent,
water, and a liquefied or compressed gas propellant at a
concentration of about 3% to about 25% by weight of the total
composition.
Inventors: |
Friedman; Doron; (Karmei
Yosef, IL) ; Besonov; Alex; (Rehovot, IL) ;
Tamarkin; Dov; (Macabim, IL) ; Eini; Meir;
(Ness Ziona, IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Foamix Ltd. |
Rehovot |
IL |
US |
|
|
Family ID: |
34864843 |
Appl. No.: |
13/911470 |
Filed: |
June 6, 2013 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
11099942 |
Apr 6, 2005 |
8486376 |
|
|
13911470 |
|
|
|
|
PCT/IB0300/005527 |
Oct 24, 2003 |
|
|
|
11099942 |
|
|
|
|
10911367 |
Aug 4, 2004 |
|
|
|
11099942 |
|
|
|
|
60492546 |
Aug 4, 2003 |
|
|
|
60492385 |
Aug 4, 2003 |
|
|
|
Current U.S.
Class: |
424/43 ; 424/617;
424/62; 424/642; 424/646; 424/665; 424/683; 514/1.1; 514/170 |
Current CPC
Class: |
A61K 8/31 20130101; A61K
8/062 20130101; A61K 45/06 20130101; A61K 9/0014 20130101; A61K
31/575 20130101; A61K 9/122 20130101; A61K 9/107 20130101; A61K
8/046 20130101; A61Q 19/00 20130101 |
Class at
Publication: |
424/43 ; 514/170;
424/62; 514/1.1; 424/617; 424/642; 424/646; 424/683; 424/665 |
International
Class: |
A61K 9/12 20060101
A61K009/12; A61K 45/06 20060101 A61K045/06; A61K 31/575 20060101
A61K031/575 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 25, 2002 |
IL |
152486 |
Claims
1.-20. (canceled)
21. A hydrating foamable composition comprising an emulsion, the
emulsion comprising: i) a hydrating component comprising an
emollient, a humectant, or a mixture thereof; ii) about 0.1% to
about 5% of a surface-active agent by weight of the emulsion; iii)
about 0.01% to about 5% by weight of the emulsion of at least one
polymeric additive selected from the group consisting of a
bioadhesive agent, a gelling agent, a film forming agent, a phase
change agent, a water-soluble cellulose ether, a
naturally-occurring polymeric material, and mixtures of two or more
thereof; iv) water; and v) optionally at least one therapeutic
agent; and a liquefied or compressed gas propellant at a
concentration of about 3% to about 25% by weight of the hydrating
foamable composition; wherein upon release from a pressurized
container the composition expands to form a foam that collapses
upon application of shear force but does not immediately collapse
upon exposure to skin temperature.
22. The foamable composition of claim 21, further comprising at
least one organic carrier selected from the group consisting of a
hydrophobic organic carrier, a polar solvent, and mixtures of two
or more thereof, wherein the at least one organic carrier is
present in an amount selected from the group consisting of (i)
about 2% to about 5% by weight of the emulsion; (ii) about 5% to
about 10% by weight of the emulsion; (iii) about 10% to about 20%
by weight of the emulsion; and (iv) about 20% to about 50% by
weight of the emulsion.
23. The foamable composition of claim 21, further comprising about
0.1% to about 5% by weight of the emulsion of a foam adjuvant
selected from the group consisting of a fatty alcohol having 15 or
more carbons in its carbon chain; a fatty acid having 16 or more
carbons in its carbon chain; fatty alcohols derived from beeswax
and including a mixture of alcohols, a majority of which has at
least 20 carbon atoms in their carbon chain; a fatty alcohol having
at least one double bond; a fatty acid having at least one double
bond; a branched fatty alcohol; a branched fatty acid; and a fatty
acid substituted with a hydroxyl group; and mixtures of any two or
more thereof.
24. The foamable composition of claim 21, wherein the foamable
composition is substantially free of short chain alcohols.
25. The foamable composition of claim 21, wherein the hydrating
component comprises a lanolin selected from the group consisting
of: i) lanolin, wool fat, lanolin wax, and a synthetic lanolin; ii)
a synthetic lanolin comprising at least one of cholesterol,
isocholesterol, and analogs, derivatives, salts, and esters
thereof; iii) an oil-soluble hydrophobic derivative of lanolin; iv)
a synthetic lanolin comprising at least one of cholesterol and
isocholesterol covalently linked with an organic moiety; v) a
synthetic lanolin comprising at least one of cholesterol and
isocholesterol covalently linked with an aliphatic acid; vi) a
lanolin acid; vii) an ester of lanolin acid with an aliphatic
alcohol; viii) a compound selected from the group consisting of
acetylated lanolin, isopropyl lanolate, and cetyl lanolate; and ix)
mixtures of any two or more thereof.
26. The foamable composition of claim 25, wherein the concentration
range of lanolin is selected from the group of (i) between about 5%
and about 12% by weight of the emulsion; and (ii) between about 12%
and about 24% by weight of the emulsion.
27. The foamable composition of claim 21, wherein the surface
active agent is non ionic and the concentration of the non-ionic
surface active agent is less than about 2% by weight of the
emulsion.
28. The foamable composition of claim 21, wherein the
surface-active agent comprises a combination of at least one
non-ionic surfactant having HLB of less than 9 and at least one
non-ionic surfactant having HLB of equal or more than 9, wherein
the ratio between the at least one non-ionic surfactant having HLB
of less than 9 and the at least one non-ionic surfactant having HLB
of equal or more than 9, is between 1:8 and 8:1.
29. The foamable composition of claim 21, wherein the polymeric
agent is selected from the group consisting of methylcellulose,
hydroxypropyl cellulose, hydroxypropyl methylcellulose,
hydroxyethyl cellulose, methylhydroxyethylcellulose,
methylhydroxypropylcellulose, hydroxyethylcarboxymethylcellulose,
carboxymethylcellulose, carboxymethylhydroxyethylcellulose, xanthan
gum, guar gum, carrageenan gum, locust bean gum, tragacanth gum,
and mixtures of any two or more thereof.
30. The foamable composition of claim 21, comprising a therapeutic
agent selected from the group consisting of an anti-infective, an
antibiotic, an antibacterial agent, an antifungal agent, an
antiviral agent, an antiparasitic agent, a steroidal
antiinflammatory agent, an immunosuppressive agent, an
immunomodulator, an immunoregulating agent, a hormonal agent, a
vitamin A, a vitamin A derivative, a vitamin B, a vitamin B
derivative, a vitamin C, a vitamin C derivative, a vitamin D, a
vitamin D derivative, a vitamin E, a vitamin E derivative, a
vitamin F, a vitamin F derivative, a vitamin K, a vitamin K
derivative, a wound healing agent, a disinfectant, an anesthetic,
an antiallergic agent, an alpha hydroxyl acid, lactic acid,
glycolic acid, a beta-hydroxy acid, a protein, a peptide, a
neuropeptide, a allergen, an immunogenic substance, a haptene, an
oxidizing agent, an antioxidant, a dicarboxylic acid, azelaic acid,
sebacic acid, adipic acid, fumaric acid, a retinoid, an
antiproliferative agent, an anticancer agent, a photodynamic
therapy agent, benzoyl chloride, calcium hypochlorite, magnesium
hypochlorite, an anti-wrinkle agent, a radical scavenger, a metal,
silver, a metal oxide, titanium dioxide, zinc oxide, zirconium
oxide, iron oxide, silicone oxide, talc, carbon, a skin whitening
agent, a skin protective agent, a masking agent, an anti-wart
agent, a refatting agent, a lubricating agent, and mixtures of any
two or more thereof.
31. The composition of claim 21, wherein the hydrating component is
selected from the group consisting of a lanolin, a beeswax, a
mineral oil, a MCT oil, isopropyl myristate (IPM), and isopropyl
palmitate (IPP).
32. The composition of claim 25, wherein the hydrating component is
at least about 5% by weight of the emulsion and comprises a
combination of a lanolin and a component selected from the group
consisting of a beeswax, a mineral oil, a MCT oil, isopropyl
myristate (IPM) isopropyl palmitate (IPP), and mixtures of any two
or more thereof.
33. A hydrating foamable composition comprising an emulsion, the
emulsion comprising: i) a hydrating component comprising a
humectant; ii) about 0.1% to about 5% of a surface-active agent by
weight of the emulsion; iii) about 0.01% to about 5% by weight of
the emulsion of at least one polymeric additive selected from the
group consisting of a bioadhesive agent, a gelling agent, a film
forming agent, a phase change agent, a water-soluble cellulose
ether, a naturally-occurring polymeric material, and mixtures of
two or more thereof; iv) water; and v) optionally at least one
therapeutic agent; and a liquefied or compressed gas propellant at
a concentration of about 3% to about 25% by weight of the hydrating
foamable composition; wherein upon release from a pressurized
container the composition expands to form a foam that collapses
upon application of shear force but does not immediately collapse
upon exposure to skin temperature.
34. The foamable composition of claim 33, further comprising at
least one organic carrier selected from the group consisting of a
hydrophobic organic carrier, a polar solvent, an emollient, and
mixtures of two or more thereof, wherein the at least one organic
carrier is present in an amount selected from the group consisting
of (i) about 2% to about 5% by weight of the emulsion; (ii) about
5% to about 10% by weight of the emulsion; (iii) about 10% to about
20% by weight of the emulsion; and (iv) about 20% to about 50% by
weight of the emulsion.
35. A method of treating or alleviating insufficient hydration of
skin, a body cavity or a mucosal surface, comprising: administering
topically to skin, a body cavity or a mucosal surface a foam that
collapses upon application of shear force but does not immediately
collapse upon exposure to skin temperature, wherein the foam is
obtained by releasing from a pressurized container a foamable
composition comprising an emulsion comprising: i) a hydrating
component comprising an emollient, a humectant, or mixture thereof;
ii) about 0.1% to about 5% of a non-ionic surface-active agent by
weight of the emulsion; iii) about 0.01% to about 5% by weight of
the emulsion of at least one polymeric additive selected from the
group consisting of a bioadhesive agent, a gelling agent, a film
forming agent, a phase change agent, a water-soluble cellulose
ether, a naturally-occurring polymeric material, and mixtures of
two or more thereof; and iv) water; and a liquefied or compressed
gas propellant at a concentration of about 3% to about 25% by
weight of the hydrating foamable composition; wherein the non-ionic
surface-active agent comprises a combination of at least one
non-ionic surfactant having HLB of less than 9 and at least one
non-ionic surfactant having HLB of equal or more than 9, wherein
the ratio between the at least one non-ionic surfactant having HLB
of less than 9 and the at least one non-ionic surfactant having HLB
of equal or more than 9, is between 1:8 and 8:1.
36. The method of claim 35, wherein the hydrating component
comprises a lanolin selected from the group consisting of: i)
lanolin, wool fat, lanolin wax, and a synthetic lanolin; ii) a
synthetic lanolin comprising at least one of cholesterol,
isocholesterol, and analogs, derivatives, salts, and esters
thereof; iii) an oil-soluble hydrophobic derivative of lanolin; iv)
a synthetic lanolin comprising at least one of cholesterol and
isocholesterol covalently linked with an organic moiety; v) a
synthetic lanolin comprising at least one of cholesterol and
isocholesterol covalently linked with an aliphatic acid; vi) a
lanolin acid; vii) an ester of lanolin acid with an aliphatic
alcohol; viii) a compound selected from the group consisting of
acetylated lanolin, isopropyl lanolate, and cetyl lanolate; and ix)
mixtures of any two or more thereof.
37. The method of claim 35, wherein the composition further
comprises at least about 5% by weight of the emulsion of a lanolin
and about 0.1% to about 5% by weight of the emulsion of a foam
adjuvant selected from the group consisting of a fatty alcohol
having 15 or more carbons in its carbon chain; a fatty acid having
16 or more carbons in its carbon chain; fatty alcohols, derived
from beeswax and including a mixture of alcohols, a majority of
which has at least 20 carbon atoms in their carbon chain; a fatty
alcohol having at least one double bond; a fatty acid having at
least one double bond; a branched fatty alcohol; a branched fatty
acid; a fatty acid substituted with a hydroxyl group; and mixtures
of any two or more thereof.
38. The method of claim 35, wherein the composition further
comprises an additional active agent effective to treat a disorder
of skin, a body cavity or a mucosal surface.
39. The method of claim 35, wherein the foamable composition
further comprises an organic carrier consisting of at least one
therapeutically active oil.
40. The method of claim 38, wherein the additional active agent is
selected from the group consisting of an anti-infective, an
antibiotic, an antibacterial agent, an antifungal agent, an
antiviral agent, an antiparasitic agent, an steroidal
antiinflammatory agent, an immunosuppressive agent, an
immunomodulator, an immunoregulating agent, a hormonal agent, a
vitamin A, a vitamin A derivative, a vitamin B, a vitamin B
derivative, a vitamin C, a vitamin C derivative, a vitamin D, a
vitamin D derivative, a vitamin E, a vitamin E derivative, a
vitamin F, a vitamin F derivative, a vitamin K, a vitamin K
derivative, a wound healing agent, a disinfectant, an anesthetic,
an antiallergic agent, an alpha hydroxyl acid, lactic acid,
glycolic acid, a beta-hydroxy acid, a protein, a peptide, a
neuropeptide, a allergen, an immunogenic substance, a haptene, an
oxidizing agent, an antioxidant, a dicarboxylic acid, azelaic acid,
sebacic acid, adipic acid, fumaric acid, a retinoid, an
antiproliferative agent, an anticancer agent, a photodynamic
therapy agent, benzoyl chloride, calcium hypochlorite, magnesium
hypochlorite, an anti-wrinkle agent, a radical scavenger, a metal,
silver, a metal oxide, titanium dioxide, zinc oxide, zirconium
oxide, iron oxide, silicone oxide, talc, carbon, a skin whitening
agent, a skin protective agent, a masking agent, an anti-wart
agent, a refatting agent, a lubricating agent, and mixtures of any
two or more thereof.
41. The method of claim 35, wherein the surface active agent is non
ionic and the concentration of the nonionic surface active agent is
less than about 2% by weight of the emulsion.
42. The method of claim 35, wherein the hydrating component is
selected from the group consisting of a lanolin, beeswax, mineral
oil, MCT oil, isopropyl myristate (IPM) isopropyl palmitate (IPP),
and mixtures of any two or more thereof.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part application of
co-pending International Patent Application No. IB03/005527
designating the United States and filed on Oct. 24, 2003, which
claims the benefit of priority under 35 U.S.C. .sctn.119(e) to U.S.
Patent Application Ser. No. 60/492,546, filed on Nov. 29, 2002,
both entitled "Cosmetic and Pharmaceutical Foam," and which also
claims the benefit of priority under 35 USC.sctn.119(a) to Israeli
Patent Appl. No. 152486, filed Oct. 25, 2002, all of which are
hereby incorporated in their entirety by reference.
[0002] This application is a continuation-in-part application of
co-pending U.S. patent application Ser. No. 10/911,367, filed on
Aug. 4, 2004, which claims the benefit of priority under 35 U.S.C.
.sctn.119(e) to U.S. Patent Application Ser. No. 60/492,385, filed
on Aug. 4, 2003, both entitled "Foam Carrier Containing Amphiphilic
Copolymer Gelling Agent" and both hereby incorporated in their
entirety by reference.
BACKGROUND OF THE INVENTION
[0003] Foams and, in particular, foam emulsions are complex
dispersion systems which do not form under all circumstances.
Slight shifts in foam emulsion composition, such as by the addition
of active ingredients, may destabilize the foam.
[0004] There have been a few attempts to create foams containing
lanolin.
[0005] U.S. Pat. No. 5,679,324 pertains to an aerosol foamable
fragrance composition, translucent in its pre-dispensed state,
which forms a fast-breaking foam. The composition contains a
surfactant selected from the group consisting of ethoxylated
lanolin oil derivatives, propoxylated lanolin oil derivatives, and
mixtures thereof, a propellant, a fragrance, a thickener, and a
cosmetic vehicle (preferably water). Emollients may be included,
however, being translucent, the composition cannot comprise
significant oil concentrations (which would make it opaque).
Apparently the foam breaks spontaneously upon discharging from an
aerosol container (with no need of any rubbing or sheer force
application), thus making it impractical for certain applications
such as intravaginal applications.
SUMMARY OF THE INVENTION
[0006] The present invention provides a highly tolerable, hydrating
lanolin containing foamable composition product for administration
to the skin, a body surface, a body cavity or mucosal surface,
e.g., the mucosa of the nose, mouth, eye, ear, respiratory system,
vagina or rectum (the "target site"). The foamable composition
includes lanolin, a surface-active agent, about 0.01% to about 5%
by weight of at least one polymeric additive selected from the
group consisting of a bioadhesive agent, a gelling agent, a film
forming agent and a phase change agent, water, and a liquefied or
compressed gas propellant at a concentration of about 3% to about
25% by weight of the total composition. The hydrating lanolin foam
composition absorbs and stores water from the environment to
thereby hydrate\ the target site.
[0007] According to further embodiments of the present invention,
the foamable composition further contains at least one organic
carrier selected from the group consisting of a hydrophobic organic
carrier, a polar solvent, an emollient and mixtures thereof,
wherein the at least one organic carrier is present in an amount
selected from the group consisting of about 2% to about 5%, about
5% to about 10%, about 10% to about 20%, and about 20% to about
50%.
[0008] According to further embodiments of the present invention,
lanolin is selected from the group consisting of lanolin, wool fat,
lanolin wax and hydrophobic derivatives thereof.
[0009] According to further embodiments of the present invention,
there is provided a method of treating, alleviating or preventing a
disorders of the skin, a body cavity or mucosal surface, wherein
the disorder involves insufficient hydration as one of its
etiological factors. The method includes administering topically to
a subject having the disorder, a foamed composition including
lanolin, about 0.1% to about 5% by weight of a surface-active
agent, about 0.01% to about 5% by weight of a polymeric additive
selected from a bioadhesive agent, a gelling agent, a film forming
agent and a phase change agent, and water.
[0010] According to still further embodiments of method according
to the present invention, the composition further includes at least
one additional therapeutic agent.
[0011] According to yet further embodiments of method according to
the present invention, the organic carrier includes at least one
therapeutically active oil.
BRIEF DESCRIPTION OF THE DRAWING
[0012] The invention is described with reference to the figures,
which are presented for the purpose of illustration and are not
intended to be limiting of the invention.
[0013] FIG. 1 is a plot of hydration value vs. time for two foamed
lanolin compositions, illustrating the skin hydrating effect of two
lanolin--containing foams.
[0014] FIG. 2 is a bar graph illustrating the difference in skin
hydration between two lanolin--containing foams and "no
treatment".
DETAILED DESCRIPTION OF THE INVENTION
[0015] The present invention provides a highly tolerable, hydrating
lanolin-containing foamable composition product.
[0016] All % values are provided on a weight (w/w) basis.
[0017] According to one or more embodiments of the present
invention, the foamable lanolin containing composition for
administration to the skin, a body surface, a body cavity or
mucosal surface, e.g., the mucosa of the nose, mouth, eye, ear,
respiratory system, vagina or rectum (severally and interchangeably
termed herein "target site") includes:
[0018] (1) lanolin;
[0019] (2) about 0.1% to about 5% by weight of a surface-active
agent;
[0020] (3) about 0.01% to about 5% by weight of at least one
polymeric agent selected from a bioadhesive agent, a gelling agent,
a film forming agent and a phase change agent; and
[0021] (4) a liquefied or compressed gas propellant at a
concentration of about 3% to about 25% by weight of the total
composition.
[0022] Water and optional ingredients are added to complete the
total mass to 100%. Upon release from an aerosol container, the
foamable composition forms an expanded foam suitable for topical
administration.
[0023] Lanolin, also termed "wool fat" and "wool fat alcohols" is a
hydrophobic greasy, substance extracted from wool, produced from
the oil glands of sheep. Lanolin wax is a high melting wax fraction
separated from lanolin, and white lanolin is obtained by further
purifications to obtain desired lanolin fractions or
derivatives.
[0024] Natural lanolin is produced, among other methods, by
extraction from the wool by kneading with water, with which it
readily forms an emulsion. On heating, it separates as a distinct
layer at the surface of the liquid. Purification is effected by
repeated treatment with water in a centrifugal machine, or by some
other suitable process.
[0025] The constituents of lanolin include cholesterol and
isocholesterol, together with various esters of cholesterol and/or
isocholesterol with one or more fatty acids, including, but not
limited to lanoceric acid, lanopalmitic acid, carnaubic acid,
myristic acid, oleic acid, cerotic acid and palmitic acid.
[0026] In one or more embodiments of the present invention, lanolin
is a synthetic lanolin or a synthetic lanolin derivative. In the
context of the present invention, a synthetic lanolin or a
synthetic lanolin derivative is a hydrophobic derivative of
lanolin, which is the result of a chemical or biochemical
modification of natural lanolin. Synthetic lanolin or a synthetic
lanolin derivative may consist of cholesterol or isocholesterol
covalently linked with an organic moiety. By way of non-limiting
examples, synthetic lanolin derivatives include organic alcohols
derived from the hydrolysis of lanolin, esters of lanolin with an
aliphatic acid (e.g., acetylated lanolin), lanolin acid (a mixture
of organic acids obtained from the hydrolysis of lanolin), esters
of lanolin acid with aliphatic alcohols (e.g., isopropyl lanolate
and cetyl lanolate).
[0027] The presence of lanolin may be determined by detection of
cholesterol, a compound making up lanolin. To test, one gram of a
fat is dissolved in 3 or 4 mL of acetic anhydride and 0.3 mL of
sulfuric acid, resulting in a pink coloration, further changing to
green and blue.
[0028] Optionally, the composition further contains at least one
organic carrier selected from a hydrophobic organic carrier, a
polar solvent, an emollient and mixtures thereof, at a
concentration of about 2% to about 5%, or about 5% to about 10%, or
about 10% to about 20%, or about 20% to about 50% by weight.
[0029] A "hydrophobic organic carrier" as used herein refers to a
material having solubility in distilled water at ambient
temperature of less than about 1 gm per 100 mL, more preferable
less than about 0.5 gm per 100 mL, and most preferably less than
about 0.1 gm per 100 mL. It is liquid at ambient temperature. The
identification of a hydrophobic organic carrier or "hydrophobic
solvent", as used herein, is not intended to characterize the
solubilization capabilities of the solvent for any specific active
agent or any other component of the foamable composition. Rather,
such information is provided to aid in the identification of
materials suitable for use as a hydrophobic carrier in the foamable
compositions described herein.
[0030] In one or more embodiments, the hydrophobic organic carrier
is an oil, such as mineral oil. Mineral oil (Chemical Abstracts
Service Registry number 8012-95-1) is a mixture of aliphatic,
naphthalenic, and aromatic liquid hydrocarbons that derive from
petroleum. It is typically liquid; its viscosity is in the range of
between about 35 CST and about 100 CST (at 40.degree. C.), and its
pour point (the lowest temperature at which an oil can be handled
without excessive amounts of wax crystals forming so preventing
flow) is below 0.degree. C. In one or more embodiments, the term
hydrophobic organic carrier does not include thick or semi-solid
materials, such as white petrolatum, also termed "Vaseline", which,
in certain compositions is disadvantageous due to its waxy nature
and semi-solid texture.
[0031] According to one or more embodiments, hydrophobic solvents
are liquid oils originating from vegetable, marine or animal
sources. Suitable liquid oil includes saturated, unsaturated or
polyunsaturated oils. By way of example, the unsaturated oil may be
olive oil, corn oil, soybean oil, canola oil, cottonseed oil,
coconut oil, sesame oil, sunflower oil, borage seed oil, syzigium
aromaticum oil, hempseed oil, herring oil, cod-liver oil, salmon
oil, flaxseed oil, wheat germ oil, evening primrose oils or
mixtures thereof, in any proportion.
[0032] Suitable hydrophobic solvents also include polyunsaturated
oils containing poly-unsaturated fatty acids. In one or more
embodiments, said unsaturated fatty acids are selected from the
group of omega-3 and omega-6 fatty acids. Examples of such
polyunsaturated fatty acids are linoleic and linolenic acid,
gamma-linoleic acid (GLA), eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA). Such unsaturated fatty acids are known
for their skin-conditioning effect, which contribute to the
therapeutic benefit of the present foamable composition. Thus, the
hydrophobic solvent can include at least 6% of an oil selected from
omega-3 oil, omega-6 oil, and mixtures thereof. In the context of
the present invention, oils that possess therapeutically beneficial
properties are termed "therapeutically active oil".
[0033] Another class of hydrophobic solvents is the essential oils,
which are also considered therapeutically active oil, which contain
active biologically occurring molecules and, upon topical
application, exert a therapeutic effect, which is conceivably
synergistic to the beneficial effect of the NSAID in the
composition.
[0034] Another class of therapeutically active oils includes liquid
hydrophobic plant-derived oils, which are known to possess
therapeutic benefits when applied topically.
[0035] Silicone oils also may be used and are desirable due to
their known skin protective and occlusive properties. Suitable
silicone oils include non-volatile silicones, such as polyalkyl
siloxanes, polyaryl siloxanes, polyalkylaryl siloxanes and
polyether siloxane copolymers, polydimethylsiloxanes (dimethicones)
and poly(dimethylsiloxane)-(diphenyl-siloxane) copolymers. These
are chosen from cyclic or linear polydimethylsiloxanes containing
from about 3 to about 9, preferably from about 4 to about 5,
silicon atoms. Volatile silicones such as cyclomethicones can also
be used. Silicone oils are also considered therapeutically active
oil, due to their barrier retaining and protective properties.
[0036] In one or more embodiments, the hydrophobic carrier includes
at least 2% by weight silicone oil or at least 5% by weight.
[0037] The solvent may be a mixture of two or more of the above
hydrophobic solvents in any proportion.
[0038] A further class of solvents includes "emollients" that have
a softening or soothing effect, especially when applied to body
areas, such as the skin and mucosal surfaces. Emollients are not
necessarily hydrophobic. Examples of suitable emollients include
hexyleneglycol, propylene glycol, isostearic acid derivatives,
isopropyl palmitate, isopropyl isostearate, diisopropyl adipate,
diisopropyl dimerate, maleated soybean oil, octyl palmitate, cetyl
lactate, cetyl ricinoleate, tocopheryl acetate, acetylated lanolin
alcohol, cetyl acetate, phenyl trimethicone, glyceryl oleate,
tocopheryl linoleate, wheat germ glycerides, arachidyl propionate,
myristyl lactate, decyl oleate, propylene glycol ricinoleate,
isopropyl lanolate, pentaerythrityl tetrastearate, neopentylglycol
dicaprylate/dicaprate, isononyl isononanoate, isotridecyl
isononanoate, myristyl myristate, triisocetyl citrate, octyl
dodecanol, sucrose esters of fatty acids, octyl hydroxystearate and
mixtures thereof.
[0039] According to one or more embodiments of the present
invention, the hydrophobic organic carrier includes a mixture of a
hydrophobic solvent and an emollient. According to one or more
embodiments, the foamable composition is a mixture of mineral oil
and an emollient in a ratio between 2:8 and 8:2 on a weight
basis.
[0040] A "polar solvent" is an organic solvent, typically soluble
in both water and oil. Examples of polar solvents include polyols,
such as glycerol (glycerin), propylene glycol, hexylene glycol,
diethylene glycol, propylene glycol n-alkanols, terpenes,
di-terpenes, tri-terpenes, terpen-ols, limonene, terpene-ol,
1-menthol, dioxolane, ethylene glycol, other glycols, sulfoxides,
such as dimethylsulfoxide (DMSO), dimethylformanide, methyl dodecyl
sulfoxide, dimethylacetamide, monooleate of ethoxylated glycerides
(with 8 to 10 ethylene oxide units), azone
(1-dodecylazacycloheptan-2-one), 2-(n-nonyl)-1,3-dioxolane, esters,
such as isopropyl myristate/palmitate, ethyl acetate, butyl
acetate, methyl proprionate, capric/caprylic triglycerides,
octylmyristate, dodecyl-myristate; myristyl alcohol, lauryl
alcohol, lauric acid, lauryl lactate ketones; amides, such as
acetamide oleates such as triolein; various alkanoic acids such as
caprylic acid; lactam compounds, such as azone; alkanols, such as
dialkylamino acetates, and admixtures thereof.
[0041] According to one or more embodiments, the polar solvent is a
polyethylene glycol (PEG) or PEG derivative that is liquid at
ambient temperature, including PEG200 (MW (molecular weight) about
190-210 kD), PEG300 (MW about 285-315 kD), PEG400 (MW about 380-420
kD), PEG600 (MW about 570-630 kD) and higher MW PEGs such as PEG
4000, PEG 6000 and PEG 10000 and mixtures thereof.
[0042] According to one or more embodiments, the foamable
composition is substantially alcohol-free, i.e., free of short
chain alcohols. Short chain alcohols, having up to 5 carbon atoms
in their carbon chain skeleton and one hydroxyl group, such as
ethanol, propanol, isopropanol, butanol, iso-butanol, t-butanol and
pentanol, are considered less desirable solvents or polar solvents
due to their skin-irritating effect. Thus, the composition is
substantially alcohol-free and includes less than about 5% final
concentration of lower alcohols, preferably less than about 2%,
more preferably less than about 1%.
[0043] The polymeric agent serves to stabilize the foam composition
and to control drug residence in the target organ. Exemplary
polymeric agents, are classified below in a non-limiting manner. In
certain cases, a given polymer can belong to more than one of the
classes provided below.
[0044] In one or more embodiments, the composition of the present
invention includes at least one gelling agent. A gelling agent
controls the residence of a therapeutic composition in the target
site of treatment by increasing the viscosity of the composition,
thereby limiting the rate of its clearance from the site. Many
gelling agents are known in the art to possess mucoadhesive
properties.
[0045] The gelling agent can be a natural gelling agent, a
synthetic gelling agent and an inorganic gelling agent. Exemplary
gelling agents that can be used in accordance with one or more
embodiments of the present invention include, for example,
naturally-occurring polymeric materials, such as locust bean gum,
sodium alginate, sodium caseinate, egg albumin, gelatin agar,
carrageenin gum, sodium alginate, xanthan gum, quince seed extract,
tragacanth gum, guar gum, starch, chemically modified starches and
the like, semi-synthetic polymeric materials such as cellulose
ethers (e.g. hydroxyethyl cellulose, methyl cellulose,
carboxymethyl cellulose, hydroxy propylmethyl cellulose), guar gum,
hydroxypropyl guar gum, soluble starch, cationic celluloses,
cationic guars, and the like, and synthetic polymeric materials,
such as carboxyvinyl polymers, polyvinylpyrrolidone, polyvinyl
alcohol, polyacrylic acid polymers, polymethacrylic acid polymers,
polyvinyl acetate polymers, polyvinyl chloride polymers,
polyvinylidene chloride polymers and the like. Mixtures of the
above compounds are contemplated.
[0046] Further exemplary gelling agents include the acrylic
acid/ethyl acrylate copolymers and the carboxyvinyl polymers sold,
for example, by the B.F. Goodrich Company under the trademark of
Carbopol.RTM. resins. These resins consist essentially of a
colloidal water-soluble polyalkenyl polyether crosslinked polymer
of acrylic acid crosslinked with from 0.75% to 2% of a crosslinking
agent such as polyallyl sucrose or polyallyl pentaerythritol.
Examples include Carbopol.RTM. 934, Carbopol.RTM. 940,
Carbopol.RTM. 950, Carbopol.RTM. 980, Carbopol.RTM. 951 and
Carbopol.RTM. 981. Carbopol.RTM. 934 is a water-soluble polymer of
acrylic acid crosslinked with about 1% of a polyallyl ether of
sucrose having an average of about 5.8 allyl groups for each
sucrose molecule.
[0047] In one or more embodiment, the composition of the present
invention includes at least one polymeric agent, which is a
water-soluble cellulose ether. Preferably, the water-soluble
cellulose ether is selected from the group consisting of
methylcellulose, hydroxypropyl cellulose, hydroxypropyl
methylcellulose (Methocel), hydroxyethyl cellulose,
methylhydroxyethylcellulose, methylhydroxypropylcellulose,
hydroxyethylcarboxymethylcellulose, carboxymethylcellulose and
carboxymethylhydroxyethylcellulose. More preferably, the
water-soluble cellulose ether is selected from the group consisting
of methylcellulose, hydroxypropyl cellulose and hydroxypropyl
methylcellulose (Methocel). In one or more embodiments, the
composition includes a combination of a water-soluble cellulose
ether; and a naturally-occurring polymeric materials, selected from
the group including xanthan gum, guar gum, carrageenan gum, locust
bean gum and tragacanth gum.
[0048] Yet, in other embodiments, the gelling agent includes
inorganic gelling agents, such as silicone dioxide (fumed
silica).
[0049] Mucoadhesion/bioadhesion is defined as the attachment of
synthetic or biological macromolecules to a biological tissue.
Mucoadhesive agents are a class of polymeric biomaterials that
exhibit the basic characteristic of a hydrogel, i.e. swell by
absorbing water and interacting by means of adhesion with the
mucous that covers epithelia. Compositions of the present invention
may contain a mucoadhesive macromolecule or polymer in an amount
sufficient to confer bioadhesive properties. The bioadhesive
macromolecule enhances the delivery of biologically active agents
on or through the target surface. The mucoadhesive macromolecule
may be selected from acidic synthetic polymers, preferably having
at least one acidic group per four repeating or monomeric subunit
moieties, such as poly(acrylic)- and/or poly(methacrylic) acid
(e.g., Carbopol.RTM., Carbomer.RTM.), poly(methylvinyl ether/maleic
anhydride) copolymer, and their mixtures and copolymers; acidic
synthetically modified natural polymers, such as
carboxymethylcellulose (CMC); neutral synthetically modified
natural polymers, such as (hydroxypropyl)methylcellulose; basic
amine-bearing polymers such as chitosan; acidic polymers obtainable
from natural sources, such as alginic acid, hyaluronic acid,
pectin, gum tragacanth, and karaya gum; and neutral synthetic
polymers, such as polyvinyl alcohol or their mixtures. An
additional group of mucoadhesive polymers includes natural and
chemically modified cyclodextrin, especially
hydroxypropyl-.beta.-cyclodextrin. Such polymers may be present as
free acids, bases, or salts, usually in a final concentration of
about 0.01% to about 0.5% by weight.
[0050] A suitable bioadhesive macromolecule is the family of
acrylic acid polymers and copolymers, (e.g., Carbopol.RTM.). These
polymers contain the general structure
--[CH.sub.2--CH(COOH)--].sub.n. Hyaluronic acid and other
biologically-derived polymers may be used.
[0051] Exemplary bioadhesive or mucoadhesive macromolecules have a
molecular weight of at least 50 kDa, or at least 300 kDa, or at
least 1,000 kDa. Favored polymeric ionizable macromolecules have
not less than 2 mole percent acidic groups (e.g., COOH, SO3H) or
basic groups (NH2, NRH, NR2), relative to the number of monomeric
units. The acidic or basic groups can constitute at least 5 mole
percent, or at least 10 mole percent, or at least 25, at least 50
more percent, or even up to 100 mole percent relative to the number
of monomeric units of the macromolecule.
[0052] Yet, another group of mucoadhesive agent includes inorganic
gelling agents such as silicon dioxide (fumed silica), including
but not limited to, AEROSIL 200 (DEGUSSA).
[0053] Many mucoadhesive agents are known in the art to also
possess gelling properties.
[0054] The foam composition may contain a film forming component.
The film forming component may include at least one water-insoluble
alkyl cellulose or hydroxyalkyl cellulose. Exemplary alkyl
cellulose or hydroxyalkyl cellulose polymers include ethyl
cellulose, propyl cellulose, butyl cellulose, cellulose acetate,
hydroxypropyl cellulose, hydroxybutyl cellulose, and
ethylhydroxyethyl cellulose, alone or in combination. In addition,
a plasticizer or a cross linking agent may be used to modify the
polymer's characteristics. For example, esters such as dibutyl or
diethyl phthalate, amides such as diethyldiphenyl urea, vegetable
oils, fatty acids and alcohols such as oleic and myristyl acid may
be used in combination with the cellulose derivative.
[0055] In one or more embodiments, the composition of the present
invention includes a phase change polymer, which alters the
composition behavior from fluid-like prior to administration to
solid-like upon contact with the target mucosal surface. Such phase
change results from external stimuli, such as changes in
temperature or pH and exposure to specific ions (e.g.,
Ca.sup.2+).
[0056] Non-limiting examples of phase change polymers include
poly(N-isopropylamide), Poloxamer 407.RTM. and Smart-Gel.RTM.
(Poloxamer PAA)
[0057] The polymeric agent is present in an amount in the range of
about 0.01% to about 5.0% by weight of the foam composition. In one
or more embodiments, it is typically less than about 1 wt % of the
foamable composition.
[0058] Surface-active agents (also termed "surfactants") include
any agent linking oil and water in the composition, in the form of
emulsion. A surfactant's hydrophilic/lipophilic balance (HLB)
describes the emulsifier's affinity toward water or oil. The HLB
scale ranges from 1 (totally lipophilic) to 20 (totally
hydrophilic), with 10 representing an equal balance of both
characteristics. Lipophilic emulsifiers form water-in-oil (w/o)
emulsions; hydrophilic surfactants form oil-in-water (o/w)
emulsions. The HLB of a blend of two emulsifiers equals the weight
fraction of emulsifier A times its HLB value plus the weight
fraction of emulsifier B times its HLB value (weighted
average).
[0059] According to one or more embodiments of the present
invention, the surface-active agent has a hydrophilic lipophilic
balance (HLB) between about 9 and about 14, which is the required
HLB (the HLB required to stabilize an O/W emulsion of a given oil)
of most oils and hydrophobic solvents. Thus, in one or more
embodiments, the composition contains a single surface active agent
having an HLB value between about 9 and 14, and in one or more
embodiments, the composition contains more than one surface active
agent and the weighted average of their HLB values is between about
9 and about 14. Yet, in other embodiments, when a water in oil
emulsion is desirable, the composition contains one or more surface
active agents, having an HLB value between about 2 and about 9.
[0060] The surface-active agent is selected from anionic, cationic,
nonionic, zwitterionic, amphoteric and ampholytic surfactants, as
well as mixtures of these surfactants. Such surfactants are well
known to those skilled in the therapeutic and cosmetic formulation
art. Nonlimiting examples of possible surfactants include
polysorbates, such as polyoxyethylene (20) sorbitan monostearate
(Tween 60) and poly(oxyethylene) (20) sorbitan monooleate (Tween
80); poly(oxyethylene) (POE) fatty acid esters, such as Myrj 45,
Myrj 49, Myrj 52 and Myrj 59; poly(oxyethylene)alkylyl ethers, such
as poly(oxyethylene)cetyl ether, poly(oxyethylene)palmityl ether,
polyethylene oxide hexadecyl ether, polyethylene glycol cetyl
ether, brij 38, brij 52, brij 56 and brij W1; sucrose esters,
partial esters of sorbitol and its anhydrides, such as sorbitan
monolaurate and sorbitan monolaurate; mono or diglycerides,
isoceteth-20, sodium methyl cocoyl taurate, sodium methyl oleoyl
taurate, sodium lauryl sulfate, triethanolamine lauryl sulfate and
betaines.
[0061] In one or more embodiments of the present invention, the
surface-active agent includes at least one non-ionic surfactant.
Ionic surfactants are known to be irritants. Therefore, non-ionic
surfactants are preferred in applications including sensitive
tissue such as found in most mucosal tissues, especially when they
are infected or inflamed. We have surprisingly found that non-ionic
surfactants alone provide foams of excellent quality, i.e. a score
of "E" according to the grading scale discussed herein below.
[0062] In one or more embodiments, the surface active agent
includes a mixture of at least one non-ionic surfactant and at
least one ionic surfactant in a ratio in the range of about 100:1
to 6:1. In one or more embodiments, the non-ionic to ionic
surfactant ratio is greater than about 6:1, or greater than about
8:1; or greater than about 14:1, or greater than about 16:1, or
greater than about 20:1.
[0063] In one or more embodiments of the present invention, a
combination of a non-ionic surfactant and an ionic surfactant (such
as sodium lauryl sulphate and cocamidopropylbetaine) is employed,
at a ratio of between 1:1 and 20:1, or at a ratio of 4:1 to 10:1.
The resultant foam has a low specific gravity, e.g., less than 0.1
g/ml.
[0064] It has been surprisingly discovered that the stability of
the composition is especially pronounced when a combination of at
least one non-ionic surfactant having HLB of less than 9 and at
least one non-ionic surfactant having HLB of equal or more than 9
is employed. The ratio between the at least one non-ionic
surfactant having HLB of less than 9 and the at least one non-ionic
surfactant having HLB of equal or more than 9, is between 1:8 and
8:1, or at a ratio of 4:1 to 1:4. The resultant HLB of such a blend
of at least two emulsifiers is between about 9 and about 14.
[0065] Thus, in an exemplary embodiment, a combination of at least
one non-ionic surfactant having HLB of less than 9 and at least one
non-ionic surfactant having HLB of equal or more than 9 is
employed, at a ratio of between 1:8 and 8:1, or at a ratio of 4:1
to 1:4, wherein the HLB of the combination of emulsifiers is
between about 9 and about 14.
[0066] In one or more embodiments of the present invention, the
surface-active agent includes mono-, di- and tri-esters of sucrose
with fatty acids (sucrose esters), prepared from sucrose and esters
of fatty acids or by extraction from sucro-glycerides. Suitable
sucrose esters include those having high monoester content, which
have higher HLB values.
[0067] The total surface active agent is in the range of about 0.1
to about 5% of the foamable composition, and is typically less than
about 2% or less than about 1%.
[0068] Preferably, a therapeutically effective foam adjuvant is
included in the foamable compositions of the present invention to
increase the foaming capacity of surfactants and/or to stabilize
the foam. In one or more embodiments of the present invention, the
foam adjuvant agent includes fatty alcohols having 15 or more
carbons in their carbon chain, such as cetyl alcohol and stearyl
alcohol (or mixtures thereof). Other examples of fatty alcohols are
arachidyl alcohol (C20), behenyl alcohol (C22), 1-triacontanol
(C30), as well as alcohols with longer carbon chains (up to C50).
Fatty alcohols, derived from beeswax and including a mixture of
alcohols, a majority of which has at least 20 carbon atoms in their
carbon chain, are especially well suited as foam adjuvant agents.
The amount of the fatty alcohol required to support the foam system
is inversely related to the length of its carbon chains. Foam
adjuvants, as defined herein are also useful in facilitating
improved spreadability and absorption of the composition.
[0069] In one or more embodiments of the present invention, the
foam adjuvant agent includes fatty acids having 16 or more carbons
in their carbon chain, such as hexadecanoic acid (C16) stearic acid
(C18), arachidic acid (C20), behenic acid (C22), octacosanoic acid
(C28), as well as fatty acids with longer carbon chains (up to
C50), or mixtures thereof. As for fatty alcohols, the amount of
fatty acids required to support the foam system is inversely
related to the length of its carbon chain.
[0070] Optionally, the carbon atom chain of the fatty alcohol or
the fatty acid may have at least one double bond. A further class
of foam adjuvant agent includes a branched fatty alcohol or fatty
acid. The carbon chain of the fatty acid or fatty alcohol also can
be substituted with a hydroxyl group, such as 12-hydroxy stearic
acid.
[0071] An important property of the fatty alcohols and fatty acids
used in context of the composition of the present invention is
related to their therapeutic properties per se. Long chain
saturated and mono unsaturated fatty alcohols, e.g., stearyl
alcohol, erucyl alcohol, arachidyl alcohol and behenyl alcohol
(docosanol) have been reported to possess antiviral, antiinfective,
antiproliferative and antiinflammatory properties (see, for
example, U.S. Pat. No. 4,874,794). Longer chain fatty alcohols,
e.g., tetracosanol, hexacosanol, heptacosanol, octacosanol,
triacontanol, etc., are also known for their metabolism modifying
properties and tissue energizing properties. Long chain fatty acids
have also been reported to possess anti-infective
characteristics.
[0072] Thus, in preferred embodiments of the present invention, a
combined and enhanced therapeutic effect is attained by including
both a nonsteroidal immunomodulating agent and a therapeutically
effective foam adjuvant in the same composition, thus providing a
simultaneous anti-inflammatory and antiinfective effect from both
components. Furthermore, in a further preferred embodiment, the
composition concurrently comprises a nonsteroidal immunomodulating
agent, a therapeutically effective foam adjuvant and a
therapeutically active oil, as detailed above. Such combination
provides an even more enhanced therapeutic benefit. Thus, the
foamable carrier, containing the foam adjuvant provides an extra
therapeutic benefit in comparison with currently used vehicles,
which are inert and non-active.
[0073] The foam adjuvant according to preferred embodiments of the
present invention includes a mixture of fatty alcohols, fatty acids
and hydroxy fatty acids and derivatives thereof in any proportion,
providing that the total amount is 0.1% to 5% (w/w) of the carrier
mass. More preferably, the total amount is 0.4%-2.5% (w/w) of the
carrier mass.
[0074] The therapeutic foam of the present invention may further
optionally include a variety of formulation excipients, which are
added in order to fine-tune the consistency of the formulation,
protect the formulation components from degradation and oxidation
and modify their consistency. Such excipients may be selected, for
example, from stabilizing agents, antioxidants, humectants,
preservatives, colorant and odorant agents and other formulation
components, used in the art of formulation.
[0075] Aerosol propellants are used to generate and administer the
foamable composition as a foam. The total composition including
propellant, foamable compositions and optional ingredients is
referred to as the foamable carrier. The propellant makes up about
3% to about 25 wt % of the foamable carrier. Examples of suitable
propellants include volatile hydrocarbons such as butane, propane,
isobutane or mixtures thereof, and fluorocarbon gases.
[0076] Several disorders of the skin, body cavity or mucosal
surface (e.g., the mucosa of the nose, mouth, eye, ear, vagina or
rectum), involve a combination of dry and scaly skin, which can be
treated with lanolin as the hydrating component of the composition
and additional therapeutic modalities that address other
etiological factors of the disorder. For example, psoriasis
involves dry and scaly skin, as well as inflammation, excessive
cell proliferation and inadequate cell differentiation, which can
be alleviated by treatment with lanolin and an additional active
agent, such as a steroid, a retinoid or an alpha or beta hydroxy
acid. Likewise, atopic dermatitis involves skin dryness and
inflammation, which may be treated with lanolin and a steroid or an
immunomodulating agent.
[0077] Thus, in one or more embodiments, the composition of the
present invention is a carrier of a cosmetically or
pharmaceutically active agents. Exemplary, non binding and
cosmetically or pharmaceutically active agents include, but are not
limited to an anti-infective, an antibiotic, an antibacterial
agent, an antifungal agent, an antiviral agent, an antiparasitic
agent, an steroidal antiinflammatory agent, an immunosuppressive
agent, an immunomodulator, an immunoregulating agent, a hormonal
agent, vitamin A, a vitamin A derivative, vitamin B, a vitamin B
derivative, vitamin C, a vitamin C derivative, vitamin D, a vitamin
D derivative, vitamin E, a vitamin E derivative, vitamin F, a
vitamin F derivative, vitamin K, a vitamin K derivative, a wound
healing agent, a disinfectant, an anesthetic, an antiallergic
agent, an alpha hydroxyl acid, lactic acid, glycolic acid, a
beta-hydroxy acid, a protein, a peptide, a neuropeptide, a
allergen, an immunogenic substance, a haptene, an oxidizing agent,
an antioxidant, a dicarboxylic acid, azelaic acid, sebacic acid,
adipic acid, fumaric acid, a retinoid, an antiproliferative agent,
an anticancer agent, a photodynamic therapy agent, an anti-wrinkle
agent, a radical scavenger, a metal oxide (e.g., titanium dioxide,
zinc oxide, zirconium oxide, iron oxide), silicone oxide, an anti
wrinkle agent, a skin whitening agent, a skin protective agent, a
masking agent, an anti-wart agent, a refatting agent, a lubricating
agent and mixtures thereof.
Composition and Foam Physical Characteristics
[0078] A pharmaceutical or cosmetic composition manufactured using
the foam carrier according to one or more embodiments of the
present invention is very easy to use. When applied onto the
afflicted body surface of mammals, i.e., humans or animals, it is
in a foam state, allowing free application without spillage. Upon
further application of a mechanical force, e.g., by rubbing the
composition onto the body surface, it freely spreads on the surface
and is rapidly absorbed.
[0079] The foam composition of the present invention creates a
stable emulsion having an acceptable shelf-life of at least one
year, or at least two years at ambient temperature. A feature of a
product for cosmetic or medical use is long term stability.
Propellants, which are a mixture of low molecular weight
hydrocarbons, tend to impair the stability of emulsions. It has
been observed, however, that foam compositions according to the
present invention are surprisingly stable. Following accelerated
stability studies, they demonstrate desirable texture; they form
fine bubble structures that do not break immediately upon contact
with a surface, spread easily on the treated area and absorb
quickly.
[0080] The composition should also be free flowing, to allow it to
flow through the aperture of the container, e.g., and aerosol
container, and create an acceptable foam. Compositions containing
semi-solid hydrophobic solvents, e.g., white petrolatum, as the
main ingredients of the oil phase of the emulsion, exhibit high
viscosity and poor flowability and are inappropriate candidates for
a foamable composition.
[0081] Foam quality can be graded as follows:
[0082] Grade E (excellent): very rich and creamy in appearance,
does not show any bubble structure or shows a very fine (small)
bubble structure; does not rapidly become dull; upon spreading on
the skin, the foam retains the creaminess property and does not
appear watery.
[0083] Grade G (good): rich and creamy in appearance, very small
bubble size, "dulls" more rapidly than an excellent foam, retains
creaminess upon spreading on the skin, and does not become
watery.
[0084] Grade FG (fairly good): a moderate amount of creaminess
noticeable, bubble structure is noticeable; upon spreading on the
skin the product dulls rapidly and becomes somewhat lower in
apparent viscosity.
[0085] Grade F (fair): very little creaminess noticeable, larger
bubble structure than a "fairly good" foam, upon spreading on the
skin it becomes thin in appearance and watery.
[0086] Grade P (poor): no creaminess noticeable, large bubble
structure, and when spread on the skin it becomes very thin and
watery in appearance.
[0087] Grade VP (very poor): dry foam, large very dull bubbles,
difficult to spread on the skin.
[0088] Topically administratable foams are typically of quality
grade E or G, when released from the aerosol container. Smaller
bubbles are indicative of more stable foam, which does not collapse
spontaneously immediately upon discharge from the container. The
finer foam structure looks and feels smoother, thus increasing its
usability and appeal.
[0089] As further aspect of the foam is breakability. The breakable
foam is thermally stable, yet breaks under sheer force. Sheer-force
breakability of the foam is clearly advantageous over
thermally-induced breakability. Thermally sensitive foams
immediately collapse upon exposure to skin temperature and,
therefore, cannot be applied on the hand and afterwards delivered
to the afflicted area.
[0090] Another property of the foam is specific gravity, as
measured upon release from the aerosol can. Typically, foams have
specific gravity of less than 0.1 g/mL or less than 0.05 g/mL.
Fields of Pharmaceutical Applications
[0091] By including lanolin and optional active agents in the
compositions of the present invention, the composition are useful
in treating an animal or a human patient having any one of a
variety of dermatological disorders that include dry and/or scaly
skin as one or their etiological factors (also termed
"dermatoses"), such as classified in a non-limiting exemplary
manner according to the following groups:
[0092] Dermatitis including contact dermatitis, atopic dermatitis,
seborrheic dermatitis, nummular dermatitis, chronic dermatitis of
the hands and feet, generalized exfoliative dermatitis, stasis
dermatitis; lichen simplex chronicus; diaper rash;
[0093] Bacterial infections including cellulitis, acute
lymphangitis, lymphadenitis, erysipelas, cutaneous abscesses,
necrotizing subcutaneous infections, staphylococcal scalded skin
syndrome, folliculitis, furuncles, hidradenitis suppurativa,
carbuncles, paronychial infections, erythrasma;
[0094] Fungal Infections including dermatophyte infections, yeast
Infections; parasitic Infections including scabies, pediculosis,
creeping eruption;
[0095] Viral Infections;
[0096] Disorders of hair follicles and sebaceous glands including
acne, rosacea, perioral dermatitis, hypertrichosis (hirsutism),
alopecia, including male pattern baldness, alopecia greata,
alopecia universalis and alopecia totalis; pseudofolliculitis
barbae, keratinous cyst;
[0097] Scaling papular diseases including psoriasis, pityriasis
rosea, lichen planus, pityriasis rubra pilaris;
[0098] Benign tumors including moles, dysplastic nevi, skin tags,
lipomas, angiomas, pyogenic granuloma, seborrheic keratoses,
dermatofibroma, keratoacanthoma, keloid;
[0099] Malignant tumors including basal cell carcinoma, squamous
cell carcinoma, malignant melanoma, paget's disease of the nipples,
kaposi's sarcoma;
[0100] Reactions to sunlight including sunburn, chronic effects of
sunlight, photosensitivity;
[0101] Bullous diseases including pemphigus, bullous pemphigoid,
dermatitis herpetiformis, linear immunoglobulin A disease;
[0102] Pigmentation disorders including hypopigmentation such as
vitiligo, albinism and postinflammatory hypopigmentation and
hyperpigmentation such as melasma (chloasma), drug-induced
hyperpigmentation, postinflammatory hyperpigmentation;
[0103] Disorders of comification including ichthyosis, keratosis
pilaris, calluses and corns, actinic keratosis;
[0104] Pressure sores;
[0105] Disorders of sweating; and
[0106] Inflammatory reactions including drug eruptions, toxic
epidermal necrolysis; erythema multiforme, erythema nodosum,
granuloma annulare.
[0107] According to one or more embodiments of the present
invention, the compositions are also useful in the therapy of
non-dermatological disorders by providing transdermal delivery of
an active nonsteroidal immunomodulating agent that is effective
against non-dermatological disorders.
[0108] The same advantage is expected when the composition is
topically applied to a body cavity or mucosal surface (e.g., the
mucosa of the nose, mouth, eye, ear, vagina or rectum) to treat
conditions such as chlamydia infection, gonorrhea infection,
hepatitis B, herpes, HIV/AIDS, human papillomavirus (HPV), genital
warts, bacterial vaginosis, candidiasis, chancroid, granuloma
Inguinale, lymphogranloma venereum, mucopurulent cervicitis (MPC),
molluscum contagiosum, nongonococcal urethritis (NGU),
trichomoniasis, vulvar disorders, vulvodynia, vulvar pain, yeast
infection, vulvar dystrophy, vulvar intraepithelial neoplasia
(VIN), contact dermatitis, pelvic inflammation, endometritis,
salpingitis, oophoritis, genital cancer, cancer of the cervix,
cancer of the vulva, cancer of the vagina, vaginal dryness,
dyspareunia, anal and rectal disease, cnal abscess/fistula, anal
cancer, anal fissure, anal warts, Crohn's disease, hemorrhoids,
anal itch, pruritus ani, fecal incontinence, constipation, polyps
of the colon and rectum.
[0109] The following examples exemplify the therapeutic kits and
pharmacological compositions and methods described herein. The
examples are for the purposes of illustration only and are not
intended to be limiting of the invention.
Example 1
Lanolin Based Foamable Compositions
TABLE-US-00001 [0110] Composition No: LAN1 LAN2 LAN3 LAN4
Ingredient % Lanolin 5.00 15.00 30.00 40.00 Mineral oil light 20.00
-- -- -- MCT oil -- 10.00 -- -- Glyceryl monostearate 0.45 0.45
0.45 1.00 Stearyl alcohol 0.95 -- -- -- Xanthan gum 0.28 -- -- --
Methocel K100M 0.28 -- -- -- Polysorbate 80 0.95 0.95 0.95 0.95
PEG-40 Stearate 2.80 2.80 2.80 2.80 Preservative 0.25 0.25 0.25
0.25 Propellant 8.00 8.00 8.00 8.00 Water To 100 To 100 To 100 To
100 Composition Properties Emulsion color White White White White
Foam Density 0.06 0.06 0.08 0.08
Example 2
Additional Lanolin Based Foamable Compositions
TABLE-US-00002 [0111] Composition No: LAN5 LAN6 LAN7 LAN8
Ingredient % Lanolin 5.00 5.00 5.00 5.00 Mineral oil 20.00 20.00
20.00 -- IPP 10.00 -- -- -- IPM -- 10.00 10.00 -- Beeswax 2.00 2.00
2.00 2.00 Glyceryl oleate 0.80 0.80 0.80 0.80 Glyceryl monostearate
SE 0.80 0.80 0.80 0.80 Arlacel P135 0.40 0.40 0.40 0.40 Ceteth-2
(Lipocol C2) 6.00 5.00 5.00 5.00 Arlatone 2121 0.50 0.50 0.50 0.50
Sucrose ester SP30 0.80 0.80 0.80 0.80 Sucrose ester SP10 0.80 0.80
0.80 0.80 Aloe vera extract 0.10 0.10 0.10 0.10 Xanthan gum 0.40
0.40 0.40 0.40 Magnesium sulfate -- 0.20 0.20 0.20 D-Pantenol 4.00
4.00 4.00 4.00 Disodium EDTA 0.20 0.40 0.40 0.40 Alpha Bisabolol --
0.20 0.20 0.20 Benzalkonium chloride (50% sol) 0.20 0.20 0.20 0.20
Zinc oxide 10.00 10.00 -- -- Water To 100 To 100 To 100 To 100
Composition Properties Emulsion color White White White White Foam
Density 0.072 0.086 0.088 0.070
Example 6
Controlled Study, to Assess the Skin Hydration of Two Lanolin Based
Foam Compositions
[0112] Six subjects were treated with foam compositions LAN1 and
LAN2, on their arm. Skin hydration was measured using Corneometer
CM825 for 240 minutes (6 hours) at the treatment sites and at an
untreated site. The skin hydration values for the two lanolin based
foams vs. "no treatment" is presented in Table 1 below and is shown
in FIG. 1. Table 2 provides the "delta" values, i.e., the
difference between the hydration effect of LAN1 and LAN2, and the
hydration value of the non-treated sites, which is illustrated in
FIG. 2. As demonstrated in Tables 1 and 2, LAN1 and LAN2 foams
provided significant hydration for at least 6 hours. The
improvement rendered by LAN1 was in the range of 16.7%-22.4%, and
for LAN2, there was a 24.9%-19.6% improvement. For comparison
purposes, in a parallel group, which was treated with a commercial
12% ammonium lactate lotion, the skin moisture was improved by
20%-28%. Notable, while 12% ammonium lactate is a prescription drug
with known side effects, the lanolin foam compositions can be
generally considered as safe and can be used daily without safety
concerns.
TABLE-US-00003 TABLE 1 Moisturizing Test: Two Lanolin Based Foams
vs. No Treatment, using Corneometer CM825 Corneometer CM825 Values
Time (min) No Treatment LAN1 LAN2 0 41 40 38 60 41 48 47 120 40 47
49 180 40 47 49 240 42 49 49
TABLE-US-00004 TABLE 2 Moisturizing Test: The Absolute
(Incremental) Skin Hydrating Effect of Two Lanolin, Using
Corneometer CM825 Corneometer CM825 Values Time (min) LAN1 LAN2 60
7.75 (+19.4%) 9.46 (+24.9%) 120 6.71 (+16.7%) 11.04 (+29.1%) 180
6.75 (+16.9%) 11.25 (+29.6%) 240 8.96 (+22.4%) 11.21 (+29.5%)
* * * * *