U.S. patent application number 16/983975 was filed with the patent office on 2021-02-25 for honey-based gel composition.
This patent application is currently assigned to Derma Sciences, Inc.. The applicant listed for this patent is Derma Sciences, Inc.. Invention is credited to Fatma Bilge THOMPSON.
Application Number | 20210052668 16/983975 |
Document ID | / |
Family ID | 1000005197397 |
Filed Date | 2021-02-25 |
United States Patent
Application |
20210052668 |
Kind Code |
A1 |
THOMPSON; Fatma Bilge |
February 25, 2021 |
HONEY-BASED GEL COMPOSITION
Abstract
A honey based composition is described. The composition includes
a mixture of honey, a short chain fatty alcohol and a fatty ester
or wax. The composition has applications for use in wound dressings
and in one embodiment may be a gel. The composition has a higher
than expected storage stability, remaining stable for many weeks
when held at elevated temperatures and retains all of the other
desirable characteristics including anti-microbial activity.
Inventors: |
THOMPSON; Fatma Bilge; (Pyes
Pa, NZ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Derma Sciences, Inc. |
Princeton |
NJ |
US |
|
|
Assignee: |
Derma Sciences, Inc.
Princeton
NJ
|
Family ID: |
1000005197397 |
Appl. No.: |
16/983975 |
Filed: |
August 3, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14942721 |
Nov 16, 2015 |
10765707 |
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16983975 |
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13637261 |
Oct 24, 2012 |
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PCT/NZ2011/000046 |
Apr 7, 2011 |
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14942721 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 31/23 20130101;
A61K 9/0014 20130101; A61K 31/7028 20130101; A61L 26/0057 20130101;
A61K 35/644 20130101; A61K 9/06 20130101 |
International
Class: |
A61K 35/644 20060101
A61K035/644; A61L 26/00 20060101 A61L026/00; A61K 9/00 20060101
A61K009/00; A61K 9/06 20060101 A61K009/06; A61K 31/23 20060101
A61K031/23; A61K 31/7028 20060101 A61K031/7028 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 7, 2010 |
NZ |
NZ584463 |
Claims
1. A composition for treating a patient wherein the composition
comprises: a. 70-90 wt % honey; b. 2-10 wt % caprylyl/capryl
glucoside; and c. 2-15 wt % myristyl myristate; wherein the
composition has been subjected to a sterilization effective dosage
of radiation and is storage stable for a time period of at least 24
hours at 40.degree. C.
2. The composition as claimed in claim 1, wherein the composition
is stable for at least 8 days when stored at 40.degree. C.
3. The composition as claimed in claim 1, wherein the composition
is stable for at least 21 days when stored at 40.degree. C.
4. The composition as claimed in claim 1, wherein the composition
is stable for at least 15 weeks when stored at 40.degree. C.
5. The composition as claimed in claim 1, wherein the composition
is a gel.
6. The composition as claimed in claim 1, wherein the composition
has a viscosity of 50.times.10.sup.3 to 600.times.10.sup.3 cPs at
25.degree. C.
7. The composition as claimed in claim 1, wherein the myristyl
myristate has a melting point of about 37.degree. C. or
greater.
8. The composition as claimed in claim 1, wherein the honey has
both peroxide and non-peroxide activity.
9. The composition as claimed in claim 1, wherein the pH is between
3.0 and 6.0 for the duration of storage.
10. The composition as claimed in claim 1, wherein the pH is
between 4.0 and 5.0 for the duration of storage.
11. The composition as claimed in claim 1, wherein the
sterilization effective dosage of radiation is greater than 10
kGy.
12. The composition as claimed in claim 1, wherein the
sterilization effective dosage of radiation is greater than 20
kGy.
13. The composition as claimed in claim 1, wherein the
sterilization effective dosage of radiation is 25 kGy.
14. The composition as claimed in claim 1, wherein the composition
has an antibacterial activity >10% phenol equivalent or >10
unique manuka factor activity over the shelf life.
15. The composition as claimed in claim 1, wherein the honey is
manuka honey.
16. The composition as claimed in claim 15, wherein the composition
is stable for at least 8 days when stored at 40.degree. C.
17. The composition as claimed in claim 15, wherein the composition
is stable for at least 21 days when stored at 40.degree. C.
18. The composition as claimed in claim 15, wherein the composition
is stable for at least 15 weeks when stored at 40.degree. C.
19. The composition as claimed in claim 15, wherein the composition
has a viscosity of 50.times.10.sup.3 to 600.times.10.sup.3 cPs at
25.degree. C.
20. The composition as claimed in claim 15, wherein the pH is
between 4.0 and 5.0 for the duration of storage.
21. A composition for treating a patient consisting essentially of:
a. 70-90 wt % honey; b. 2-10 wt % caprylyl/capryl glucoside; and c.
2-15 wt % myristyl myristate; wherein the composition has been
subjected to a sterilization effective dosage of radiation and is
storage stable for a time period of at least 24 hours at 40.degree.
C.
Description
RELATED APPLICATIONS
[0001] This application claims priority from NZ584463 dated 7 Apr.
2010, the contents of which are incorporated herein by
reference.
TECHNICAL FIELD
[0002] The present application relates to a gel composition. More
specifically, the application relates to a storage stable and
natural based composition containing honey that has a gel structure
and, on application to a wound, forms a skin over the wound.
BACKGROUND ART
[0003] Honey used in wound dressings has been extensively discussed
and taught in the art.
[0004] One of the difficulties of honey for use in wound dressing
applications is that honey is a naturally sticky substance that if
applied to a wound can be difficult to apply and runny. Solutions
have as been proposed in the art to overcome this drawback of honey
and yet still maintain the honey efficacy in wound treatment.
[0005] One example is the use of alginate gums mixed with the honey
to form gels. Another alternative is that described in U.S.
Published Application No. 2010/0233283. This composition is useful
in that the honey composition is a gel paste or ointment that can
be easily packaged in a tube or other pliable container. The gel
can easily be squeezed out of the tube and applied to a wound. The
gel described in U.S. Published Application No. 2010/0233283 forms
a skin over the wound, keeps its shape when applied to a wound
(i.e. does not melt or run), and is easier to apply than pure
honey. Further, the composition still retains sufficient honey to
provide the desired honey antibacterial and wound healing effects.
A drawback of the composition as described in U.S. Published
Application No. 2010/0233283 is that the composition when stored in
the container over time can separate, particularly at temperatures
over 30.degree. C. This is undesirable as separation reduces
efficacy and aesthetic characteristics of the gel.
[0006] Natural based products may also be desirable in many
applications, sometimes for improved efficacy and often to aid in
marketing the products as being natural based and therefore able to
be used in a variety nutraceutical applications. A further drawback
of the composition described in U.S. Published Application No.
2010/0233283 is that it uses a non-natural ingredient being an
ethoxylated oil or PEG60.
[0007] It should be appreciated from the above that it would be
useful to have a honey based wound dressing gel that was both shelf
stable and utilised natural based ingredients. It is an object of
the present application to address the foregoing problems or at
least to provide the public with a useful choice.
[0008] All references, including any patents or patent applications
cited in this specification are hereby incorporated by reference.
No admission is made that any reference constitutes prior art. The
discussion of the references states what their authors assert, and
the applicants reserve the right to challenge the accuracy and
pertinence of the cited documents. It will be clearly understood
that, although a number of prior art publications are referred to
herein, this reference does not constitute an admission that any of
these documents form part of the common general knowledge in the
art, in New Zealand or in any other country.
[0009] It is acknowledged that the tem `comprise` may, under
varying jurisdictions, be attributed with either an exclusive or an
inclusive meaning. For the purpose of this specification, and
unless otherwise noted, the term `comprise` shall have an inclusive
meaning--i.e. that it will be taken to mean an inclusion of not
only the listed components it directly references, but also other
non-specified components or elements. This rationale will also be
used when the term `comprised` or `comprising` is used in relation
to one or more steps in a method or process.
[0010] Further aspects and advantages of the gel composition
described herein will become apparent from the ensuing description
that is given by way of example only.
SUMMARY
[0011] The application broadly relates to a composition containing
honey for use in wound dressings. The composition has a gel
consistency that, on application to a wound forms skin over the
wound. The composition is shelf stable and uses naturally produced
products.
[0012] In some embodiments, there is provided a composition for
treating a patient wherein the composition comprises: [0013] a. at
least 50% wt honey or a honey derivative; [0014] b. 2-15% wt of a
naturally derived short chain fatty alcohol with non-ionic
surfactant properties; [0015] c. 1 to 50% wt of a naturally derived
fatty ester, a wax and wax-like compounds or mixtures thereof
having a set point of 45.degree. C. or less, wherein the
composition has been subjected to a sterlisation effective dosage
of radiation and is storage stable for a time period of at least 24
hours at 40.degree. C.
[0016] In some embodiments, there is provided a gel composition
consisting of: [0017] a. 70-90% wt honey [0018] b. 2-15% wt
myristyl myristate [0019] c. 2-10% wt caprylyl capryl
glucoside.
[0020] The compositions have been found to have a far higher level
of stability than existing art compositions. In some embodiments
the applicant has noted a stability of over 5 weeks at 40.degree.
C. or at least 9 weeks when stored at 30.degree. C., well beyond
that of similar products that became unstable and separated after
only 12 hours. A further advantage is that the compositions are
naturally derived and do not use synthetically derived
ingredients.
[0021] The compositions have applications as a wound gel stored in
a tube and applied to the wound by dispensing the gel from the tube
and then applying the gel to the wound surface. The composition
acts to block egress of debris from outside the wound into the
wound and, due to the antimicrobial and healing effects of honey,
acts to prevent infection and assist wound healing. Since the honey
levels in the composition can be kept high, the efficacy due the
honey is retained. Conversely, the other ingredients used avoid
other difficulties associated with using honey such as being
difficult to apply due to it's stickiness and the fact that body
temperature causes the honey to run or flow from the wound.
[0022] A further advantage of the above composition is that it may
be irradiated using standard conditions with no loss in stability
of other characteristics including efficacy. The art teaches about
the difficulties of irradiation and how irradiation can reduce the
efficacy, stability and physical properties of honey based
compositions. Irradiation is however essential and an accepted form
of sterilising honey based compositions used in wound healing. In
the applicant's experience, irradiation of the honey based
composition described herein does not alter the characteristics of
the composition including stability.
DETAILED DESCRIPTION
[0023] As noted above, the application broadly relates to a
composition containing honey for use in wound dressings. The
composition has a gel consistency that, on application to a wound
forms skin over the wound. The composition is shelf stable and uses
naturally produced products.
[0024] For the purposes of this specification, the term
`surfactant` refers to a compound that is a wetting agent that
reduces the surface tension of a liquid. Surfactants reduce the
interfacial tension between oil and water by adsorbing at the
liquid-liquid interface.
[0025] The term `gel` refers to a fluidity that lies between a
liquid and solid and may incorporate a degree of
viscoelasticity.
[0026] The term `stable` refers to the composition remaining in
suspension and not undergoing physical, chemical, microbial growth
change, or any loss in antibacterial action when stored for a
period of time.
[0027] The terms `UMF` and `non-peroxide activity` refer to the
activity of honey not directly attributable to the antimicrobial
effects of honey conferred from the normal honey pH and osmolarity,
for example that observed and measured in a naturally derived
clover honey.
[0028] The term `honey or honey derivative` refers to naturally
derived honey or mixtures of honey but may also include honey
analogues or derivatives such as sugar syrup solutions.
[0029] The term `honey analogue` refers to a sugar syrup solution
approximating that of honey e.g. including glucose, fructose, water
and either hydrogen peroxide and/or one or more hydrogen peroxide
precursors.
[0030] The term `glucoside` in this specification may be used
interchangeably with the term `glycoside`.
[0031] The term `sterilisation effective dosage of radiation`
refers to a dose of radiation being at least 1 kGy or Ideally 10
kGy or higher.
[0032] The term `natural based` refers to compounds obtained from
nature or one or more synthesised versions of compounds found in
nature. Ideally, the compound or compounds used meet the Natural
Products Association (NPA) guidelines i.e. they are derived from
renewable sources in nature` they do not use petroleum compounds,
they meet generally recognised as safe or GRAS standard as set by
the USA FDA and they are manufactured based on NPA approved
processes.
[0033] In some embodiments, a composition is provided for treating
a patient wherein the composition comprises: [0034] a. at least 50%
wt honey or a honey derivative; [0035] b. 2-15% wt of a naturally
derived short chain fatty alcohol with non-ionic surfactant
properties; [0036] c. 1 to 50% wt of a naturally derived fatty
ester, a wax and wax-like compounds or mixtures thereof having a
set point of 45.degree. C. or less [0037] wherein the composition
has been subjected to a sterilisation effective dosage of radiation
and is storage stable for a time period of at least 24 hours at
40.degree. C.
[0038] The composition has an unexpected and improved stability
over the art. In some embodiments, the composition is stable for at
least 8 days when stored at 40.degree. C. In some embodiments, the
composition is stable for at least 21 days when stored at
40.degree. C. In some embodiments, the composition is stable for at
least 9 weeks when stored at 30.degree. C. In in some embodiments,
the composition is stable for at least 15 weeks at 30.degree. C.
The anticipated stability when stored at typical ambient conditions
is likely to be at least 3 years based on accelerated trials
completed by the applicant. This degree of stability goes well
beyond that observed by the applicants for equivalent compositions
containing honey, particularly those that have a gel viscosity. For
example, in the applicant's experience, the closest similar
composition becomes unstable and phase separates after only 12
hours when stored at 40.degree. C.
[0039] The composition is a gel. Gels are a useful consistency for
application to wounds as the gel can easily by packaged, dispersed
form the packaging and applied to almost any shaped wound. In some
embodiments, the composition may have a viscosity of approximately
50.times.10.sup.3 to 600.times.10.sup.3 cPs at 25.degree. C. In
some embodiments, the viscosity may be 100.times.10.sup.3 to
500.times.10.sup.3 cPs at 25.degree. C. In some embodiments, the
viscosity may be 300.times.10.sup.3 to 400.times.10.sup.3 cPs at
25.degree. C. In some embodiments, the viscosity may be
100.times.10.sup.3 to 300.times.10.sup.3 cPs at 25.degree. C. The
variation in viscosity may be due to specific applications where a
more runny composition is preferred while other applications may
require a more viscous composition. By way of example, the
composition may easily be made with a lower and higher viscosity as
well without departing from the scope of the invention. For
example, another gel product, Solosite.TM. has a viscosity of
45-90.times.10.sup.3 cPs at 25.degree. C.
[0040] As noted above, the composition includes at least one
topical carrier or vehicle. A wide variety of carriers or vehicles
may be used. In some embodiments the at least one carrier or
vehicle may have a melting point of about 37.degree. C. or greater.
Preferred carriers or vehicles understood by the applicant to be
useful may include those selected from the group consisting of: a
fatty ester, synthetic wax, beeswax, vegetal wax, mineral wax, a
spermaceti wax constituent, carnauba wax and jojoba liquid wax. In
a specific embodiment, the topical carrier or vehicle is myristyl
myristate.
[0041] Myristyl myristate is a natural vegetable derived ester
compound with emulsifier and opacifier characteristics. Myristyl
myristate is often used in skin lotions to improve the feel of the
compositions as it has the effect of thickening compositions.
Myristyl myristate is an ester of myristic acid, which occurs
naturally in animal or vegetable fats and oils.
[0042] In some embodiments, the at least one topical carrier or
vehicle comprises from about 10% to about 30% wt of the
composition. More specifically, the at least one topical carrier or
vehicle comprises about 15% wt of the composition.
[0043] The Interaction of honey and the other compounds of the
composition is understood to be very important to achieve the
desired characteristics. Honey naturally includes water (up to 18%
wt). Therefore, in order to combine and stabilise a myristyl
myristate and honey emulsion, a surfactant/emulsifier is required.
Olive oil used in the art is an oil and is not soluble in water.
Due to these properties, olive oil will only mix with melted
myristyl myristate, but not the honey. In the absence of a
surfactant, once the mixture is cool, myristyl myristate will go
back to its solid phase, but will not be fully dispersed within the
honey. Instead, the myristyl myristate and olive oil exist as a
separate phase. As will be appreciated from the above, use of a
surfactant and the type of surfactant is of importance.
[0044] The applicant has unexpectedly found that naturally derived
short chain fatty alcohols with non-ionic surfactant properties
provide the necessary surfactant properties to successfully combine
the honey and wax and confer the properties desired. These
compounds also tend to be milder on the skin and have a low
toxicity. Unexpectedly, the short chain fatty alcohols confer a
greatly increased level of stability over the art, well beyond that
expected or currently observed. In some embodiments, the carbon
chain length of the tail of the fatty alcohol may be from about 6
carbon atoms to about 10 carbon atoms long. In some embodiments,
the carbon chain length tail may be 7 to 9 carbon atoms long. In
some embodiments, the carbon chain length tall may be 8 carbon
atoms long.
[0045] By way of example, non-limiting examples of short chain
fatty alcohols that may be used may be selected from the group
consisting of: caprylyl capryl glucoside, coco glucoside, lauryl
glucoside, cetearyl olivate, sorbitan olivate, polyglyceryl-6
caprylate, polyglyceryl-6 laurate, polyglyceryl-10 laurate,
polyglyceryl-5 oleate, polyglyceryl-5 dioleate, polyglyceryl-10
diisostearate, polyglyceryl-3 stearate, polyglyceryl-3 palmitate,
polyglyceryl-3 polyricinoleate, glyceryl oleate, sodium stearoyl
lactylate, glyceryl stearate citrate, and combinations thereof.
[0046] In a specific embodiment, the applicant has found that the
naturally derived short chain fatty alcohol may be caprylyl capryl
glucoside and derivatives thereof. This particular glucoside has
been found by the applicants to confer the ideal properties to the
composition including achieving the desired viscosity, the
conversion from a gel to a skin on the wound when applied, the
reduced stickiness of the composition, still allowing sufficient
honey to be present in the composition to achieve the desired
antibacterial function. Also a further advantage is that the
glucoside is natural based being plant derived and has non-ionic
surfactant properties. The fact that caprylyl capryl glucoside was
successful was unexpected as this type of glucoside is normally
used in various foaming and cleaning compositions rather than wound
care compositions owing to its surfactant and foaming
characteristics. In honey compositions, the surfactant properties
appear to assist but foaming does not occur as in art compositions
such as shampoos. In addition, use of glucoside and caprylyl capryl
glucoside in particular conferred an improved stability, well
beyond that found from other art compositions and beyond what might
have been expected in the art based on published information about
glucoside, particularly in combination with honey of which there is
no known art to the applicant's knowledge.
[0047] In some embodiments the composition contains from about 2%
to about 10% wt naturally derived short chain fatty alcohol. More
specifically, the composition contains from about 2% to about 7% wt
naturally derived short chain fatty alcohol. In some embodiments,
the composition contains about 4-6% wt naturally derived short
chain fatty alcohol. In some embodiments, the composition may
contain about 5% wt naturally derived short chain fatty
alcohol.
[0048] In some embodiments, the honey used may have both peroxide
and non-peroxide activity. Non-peroxide activity is often used
interchangeably with the measurement of `unique manuka factor` or
UMF activity. Honey has inherent physical characteristics such as
low pH and osmolarity that deter microbial growth however honeys
with non-peroxide activity are often desired or preferred in
medical applications due to the enhanced anti-microbial effects
observed from such honeys including those honeys derived from the
species Leptospermum and specifically either Leplospermum scoparium
or manuka honey and/or Leptospermum polygalifolium or jellybush
honey.
[0049] In some embodiments, the composition may constitute
approximately 70-90% wt honey. As should be appreciated, this is
ample honey and ensures activity well beyond that of more dilute
formulations with less than 50% wt such as those taught in the
art.
[0050] Also as noted in the definition above, although the term
`honey` has been used, a honey derivative or honey analogue may
equally be used without departing from the scope of the
invention.
[0051] The sterilisation effective dose as noted above may be
greater than 10 kGy. In some embodiments the dose may be greater
than 20 kGy. In some embodiments, the dose may be greater than 30
kGy. In some embodiments, the dose may be 32.5 kGy to 60 kGy. The
applicant has found that irradiation of the composition does not
appreciably alter the stability and physical characteristics of the
composition unlike some art compositions that become unstable and
separate post irradiation treatment. Irradiation is important in
many applications such as medical applications to ensure that there
are no residual microbes that may cause infection of a wound.
[0052] The pH of the composition also remains stable during
storage. In some embodiments the pH of the composition post
manufacture and during storage may be between 3.0 and 6.0. The pH
may be 3.0 to 5.0. The pH may be 4.0 to 5.0. The pH remains within
the specified range for the duration of storage.
[0053] In some embodiments there is provided a gel composition
consisting of: [0054] a. 70-90% wt honey [0055] b. 2-15% wt
myristyl myristate [0056] c. 2-10% wt caprylyl capryl
glucoside.
[0057] In some embodiments, the composition is irradiated with a
sterlisation effective dose of radiation.
[0058] In some embodiments, the composition is a gel with similar
viscosity to that described above.
[0059] Further, the above embodiments have the same stability
characteristics as that described above including stability for at
least 8 days when stored at 40.degree. C.
[0060] Aspects of the broadly described gel composition described
above may also apply to more specific embodiments without departing
from the scope of the invention.
[0061] As should be appreciated from the above description, the
intended use of the gel composition described herein is as a wound
gel that is ideally applied to wounds as a gel. The myristyl
myristate or other wax helps to provide the gel consistency but
without a surfactant, the myristyl myristate will not disperse into
the emulsion. Instead, if it mixes at all, it will exist in the
mixture as hard globules within a matrix of liquid honey. This will
fail the required outcome as, in the wound, once the honey melts
due to the amount of exudate, the waxes will stick to the wound bed
and will be hard to wash away. The use of a non-Ionic surfactant
being a short chain fatty acid and, in some embodiments being
caprylyl capryl glucoside, meets the desired criteria well
including conferring longevity during storage.
WORKING EXAMPLES
[0062] The gel composition of the present application Is now
described with reference to examples illustrating embodiments of
the composition.
Example 1
[0063] A composition containing honey (manuka honey with a UMF
level of 12+) (80% wt), myristyl myristate (15% wt) and caprylyl
capryl glyceride (5% wt) was manufactured and added to a tube
container. The tube container was then irradiated at 25 kGy
following standard irradiation protocols used for medical wound
dressings that contain honey.
[0064] Baseline control tests were completed and the composition
appeared smooth and free of grittiness having a cream like
consistency, a soft fine grain and little or no glucose
crystals.
[0065] The pH of the composition was 3.5-4.5 and an antibacterial
activity >10% phenol equivalent or >10 UMF activity over the
shelf life.
Example 2
[0066] A composition containing honey (Jellybush honey with a UMF
level of 12+) (80% wt), myristyl myristate (15% wt) and caprylyl
capryl glucoside (5% wt) was manufactured and added to a tube
container. The tube container was then irradiated at 25 kGy
following standard irradiation protocols used for medical wound
dressings that contain honey.
[0067] Baseline control tests were completed and the composition
appeared smooth and free of grittiness having a cream like
consistency, a soft fine grain and little or no glucose
crystals.
[0068] The pH of the composition was 3.5-4.5 and an antibacterial
activity >10% phenol equivalent or >10 UMF activity over the
shelf life.
Example 3
[0069] Further formulation examples are illustrated in Table 1
below showing how the composition may be made using different
compounds.
TABLE-US-00001 TABLE 1 Example Compositions (Excludes Carriers)
Composition Honey Short Chain Fatty Acid Fatty Ester, wax or wax
like compound Number MH JB AN CCG CG LG CO FE SW BW VW MW SW CW JW
1 80 5 15 2 80 5 15 15 3 80 5 15 4 50 5 45 5 90 5 5 6 88 2 10 7 85
10 5 8 60 15 10 5 10 9 75 5 5 5 5 5
Legend:
MH: Manuka Honey
JB: Jellybush Honey
AN: Honey Analogue
[0070] CCG: caprylyl capryl glucoside, CG: coco glucoside, LG:
lauryl glucoside, FE: fatty ester, SW: synthetic wax, BW: beeswax,
VW: vegetal wax, MW: mineral wax, SW: a spermaceti wax constituent,
CW: carnauba wax JW: Jojoba liquid wax
Example 4
[0071] In this example, the composition of Example 1 was stored at
freezer temperatures (-18.degree. C.) and at high temperature
(40.degree. C.) for 21 days and measurements of colour, odour,
appearance, texture and phase separation tested at time zero and
after 3 weeks. These temperatures were chosen to simulate either
extreme of shipping temperature.
[0072] The results found are summarised in Table 2 below.
TABLE-US-00002 TABLE 2 Sample Test Results Post Storage Storage
Storage Time Appearance/ Phase Conditions (Weeks) Colour Odour
Texture Separation Freezer 3 Light tan to Honey Smooth No brown
odour cream like separation opaque consistency colour 40.degree. C.
3 Light tan to Honey Smooth No brown odour cream like separation
opaque consistency colour
Example 5
[0073] In this example, the composition of Example 1 was stored at
an elevated temperature 40.degree. C. for one week and then at
30.degree. C. for a further 5 to 8 weeks and measurements of
colour, odour, appearance, texture, phase separation, pH were
tested at time zero, after 6 weeks and after 9 weeks. These
temperatures were chosen to simulate a shipping temperature.
[0074] The results found are summarised in Table 3 below.
TABLE-US-00003 TABLE 3 Accelerated Stability at 40/30.degree. C.
Test Results Storage Time Appearance/ Phase (Weeks) Colour Odour
Texture Separation pH 0 Light tan to brown Honey Smooth cream No
4.4 opaque emulsion odour like consistency separation 6 Light tan
to brown Honey Smooth cream No 4.4 opaque emulsion odour like
consistency separation 9 Light tan to brown Honey Smooth cream No
4.3 opaque emulsion odour like consistency separation
[0075] There was no total weight change (0.00%) after 9 weeks
storage (total weight change calculated as percent weight change of
container, initial compared to 9 week test weight).
Example 6
[0076] The composition described in Example 1 was tested by wound
dressing clinicians and a clinical nurse with experience in the
area of wound dressings and in particular honey based wound
dressing gels.
[0077] Observations were collated.
[0078] All observations made were that the composition of Example
1: [0079] 1. Was easy to apply to a wound. [0080] 2. Was easy to
clean from the wound and surrounding area post application. [0081]
3. Had a uniform consistency when administered to the patient post
manufacture and storage. [0082] 4. No pain or adverse effects were
noted except in two cases where a slight stinging was noted by the
patient on application that quickly dissipated. This observation is
commensurate or better than that observed with art formulations.
[0083] 5. The wound to which the composition was applied healed as
per prior art formulations.
[0084] The above findings showed that the new formulation not only
has increased stability but still meets all other functional
criteria.
Example 7
[0085] In this Example, a trial is presented where the stability at
40.degree. C. of a composition of Example 1 is compared to a
composition modelled on that described in the art, specifically
U.S. Pat. No. 6,482,442 (two formulations) and U.S. Published
Application No. 2010/0233283. The specific amounts and compounds
used in each composition are shown in Table 4 below.
TABLE-US-00004 TABLE 4 Compositions Used in 40.degree. C. Stability
Trial Example 1 US '442 US '442 Composition Composition 1
Composition 2 US '931 [wt %] [wt %] [wt %] [wt %] Honey 80 80 80 80
Myristyl 15 5 18 15 Myristate Olive Oil -- 15 2 -- PEG60 -- -- -- 5
Caprylyl 5 -- -- -- capryl glusoside
[0086] As should be apparent from Table 4, the key difference
between the different compositions was the surfactant/emulsifier
used. All compositions used the same type and amount of honey while
the amount of myristyl myristate was varied to either extreme
taught as being acceptable in the US '442 specification.
[0087] The Example 1 composition was mixed, irradiated and then
stored at 40.degree. C. When the trial ended at Day 8, the Example
1 composition had identical characteristics to that at the start of
the trial, remaining stable for the 8-day duration.
[0088] The composition based on US '283 was mixed together and
irradiated in the same manner as the composition of Example 1.
Initial characteristics of the US '283 composition were the same as
that of the Example 1 composition at the beginning of the trial.
However, within a 12 hour time period, the US '283 composition
separated and hence was unstable at elevated storage
temperatures.
[0089] Both of the compositions based on US '442 were highly
unstable. Neither sample could be mixed together even before
irradiation took place. In the case of the US '442 Composition 1
mixture, despite vigorous mixing the oil formed a separate layer on
the top of the honey and myristyl myristate. In the case of the US
'442 Composition 2 mixture, again despite vigorous mixing, the
myristyl myristate formed a separate layer on the top of the honey
and oil.
[0090] The above results confirm the need for a
surfactant/emulsifier in order to have the honey and wax such as
myristyl myristate combine. The results also demonstrate how use of
caprylyl capryl glucoside confers considerably greater stability
than that observed using other surfactants/emulsifiers such as
PEG60.
Example 8
[0091] The microbial growth stability of the composition was tested
to confirm that, post storage, microbial growth did not occur. As
may be appreciated, particularly for medical applications,
microbial growth is of significant concern and must be avoided.
[0092] A total of five separate samples were taken based on the
composition described in Example 1. The samples were stored at
40.degree. C. for 8 days. Following storage, the samples were
stored aseptically and transported to a laboratory where they were
analysed for microbial growth by reference to tests for: [0093] (a)
Growth on tryptone soya broth at 22.5+/-2.5.degree. C. for 14 days;
and, [0094] (b) Growth on thioglycollate medium at
32.5+/-2.5.degree. C. for 14 days.
[0095] None of the five samples tested had any microbial growth
detected via either test illustrating that the composition of the
present invention is stable with respect to microbial growth.
Example 9
[0096] A further test was completed to determine the stability of
the composition for an extended time period.
[0097] A composition containing honey (manuka honey with a UMF
level of 12+) (80% wt), myristyl myristate (15% wt) and caprylyl
capryl glucoside (5% wt) was manufactured and added to a tube
container. The tube container was then irradiated at 35 kGy
following standard irradiation protocols used for medical wound
dressings that contain honey.
[0098] The trial comprised of two tests, one being a comparison
between samples stored at -18 C against the same sample stored at
40 C. A second trial studied the stability of the composition in an
accelerated study with honey stored at 30 C.
[0099] Table 5 below shows the results of the first study while
Table 6 below shows the results of the second study.
TABLE-US-00005 TABLE 5 High versus Low Temperature Comparison Study
Storage time & Appearance & Phase conditions Colour Odour
texture Separation 1 wk -18.degree. C. Caramel Sweet Smooth cream
No & 3 wks 40.degree. C. brown honey like consistency,
separation few glucose crystals 2 wk -18.degree. C. Opaque tan
Honey Smooth cream No & 3 wks 40.degree. C. colour like
consistency separation 3 wks -18.degree. C. Light tan to Honey
Smooth cream No & 3 wks 40.degree. C. Brown like consistency
separation
TABLE-US-00006 TABLE 6 Accelerated stability at 30 C. Storage
Activity time Appearance/ Phase Packaging (non- (weeks) Colour
Odour Texture Separation integrity pH peroxide) 0 Light tan to
Honey Smooth No Intact. Text 4.4 Error with brown cream like
separation legible testing consistency 3 Light brown/ Sharp Smooth
No Intact. Text 4.5 11.89 yellow Honey cream like separation
legible consistency 6 Light tan to Honey Smooth No Intact. Text 4.4
14.25 brown opaque cream like separation legible consistency 9
Light brown/ Sharp Smooth No Intact. Text 4.3 16.24 yellow opaque
honey cream like separation legible consistency 12 Light brown/
Sharp Smooth No Intact. Text 4 15.52 yellow opaque honey cream like
separation legible consistency 15 Light brown/ Sharp Smooth No
Intact. Text 4 18.39 yellow opaque honey cream like separation
legible consistency
[0100] The above results show that the composition is stable for at
least 15 weeks when stored at 30 C and illustrates minimal
difference between freezer storage versus 400 storage. The results
when applied to more normal ambient conditions support a shelf life
of at least 3 years.
Example 10
[0101] A test to confirm the efficacy of the composition was
completed. Ordinary honey with or without non-peroxide activity is
known to have an antibacterial effect. The aim of the trial was to
ensure that the composition of the invention did not compromise the
antibacterial efficacy of key importance in proposed wound dressing
applications.
[0102] Samples produced as per Example 1 were stored at 40.degree.
C. for 48 hours, 7 days, 14 days and 28 days and at each stage
tested for microbial count. The initial inoculum and a time zero
count were also measured. The results found are illustrated in
Table 7 below.
TABLE-US-00007 TABLE 7 Antibacterial Effects for the Composition
[CPU = colony forming units; <=less than] Initial Recovery
Counts (CFU/gram) Challenge Inoculum Time 48 7 14 28 Organism
(CFU/gram) "0" hrs days days days S. aureus 2.9 .times. 10.sup.6
1.8 .times. 10.sup.5 <10 <10 -- <10 P. aeruginosa 3.4
.times. 10.sup.6 1.4 .times. 10.sup.5 <10 <10 <10 C.
albicans 5.6 .times. 10.sup.6 4.7 .times. 10.sup.4 -- -- <10
<10 A. niger 3.6 .times. 10.sup.6 4.3 .times. 10.sup.5 -- --
<10 <10
[0103] As shown above, the composition in accordance with
embodiments described herein had an immediate and catastrophic
effect on microbial growth with microbes tested being killed to
less than detectable levels within 48 hours. This effect is the
same as that observed using honey hence it can be concluded that
the composition described herein retains the antibacterial effects
of honey.
Example 11
[0104] In this example the viscosity of the composition described
in Example 1 was tested. Three samples of the composition were
tested and averaged to establish a viscosity figure. The method
used a Brookfleld Viscometer with Helipath Spindle F at 1.5 rpm and
25.degree. C.
[0105] The test identified that the viscosity was approximately
300-400.times.10.sup.3 cPs@25.degree. C.
Example 12
[0106] Further viscosity measurements were taken of varying
formulations based on the same method as that described in Example
11 above.
[0107] Results found are illustrated below in Table 8.
TABLE-US-00008 TABLE 8 Viscosity Measurements Sample Number
Viscosity [cPs @.degree.25] 1 254000 2 210000 3 454000 4 180000 5
423000 6 168000 7 158000 8 158000 9 189200
[0108] The variation shown above lustrates how the composition
viscosity may be varied for differing applications.
[0109] Aspects of the gel composition described herein have been
described by way of example only and it should be appreciated that
modifications and additions may be made thereto without departing
from the scope of the claims herein.
* * * * *