U.S. patent application number 14/138338 was filed with the patent office on 2015-06-25 for topical gel compositions including polycaprolactone polymer and methods for enhancing the topical application of a benefit agent.
This patent application is currently assigned to McNeil-PPC, Inc.. The applicant listed for this patent is McNeil-PPC, Inc.. Invention is credited to Anna Gosiewska, Dennis Jamiolkowski, Ying Sun, Jeffrey M. Wu.
Application Number | 20150174254 14/138338 |
Document ID | / |
Family ID | 52347424 |
Filed Date | 2015-06-25 |
United States Patent
Application |
20150174254 |
Kind Code |
A1 |
Sun; Ying ; et al. |
June 25, 2015 |
TOPICAL GEL COMPOSITIONS INCLUDING POLYCAPROLACTONE POLYMER AND
METHODS FOR ENHANCING THE TOPICAL APPLICATION OF A BENEFIT
AGENT
Abstract
A composition comprising: a benefit agent; at least one polymer
including a polycaprolactone polymer; at least one lower alcohol;
and at least one co-solvent; and a method for enhancing topical
delivery of a benefit agent is disclosed.
Inventors: |
Sun; Ying; (Belle Mead,
NJ) ; Gosiewska; Anna; (Skillman, NJ) ;
Jamiolkowski; Dennis; (Long Valley, NJ) ; Wu; Jeffrey
M.; (Princeton, NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
McNeil-PPC, Inc. |
Skillman |
NJ |
US |
|
|
Assignee: |
McNeil-PPC, Inc.
Skillman
NJ
|
Family ID: |
52347424 |
Appl. No.: |
14/138338 |
Filed: |
December 23, 2013 |
Current U.S.
Class: |
514/275 ;
514/785 |
Current CPC
Class: |
A61K 31/192 20130101;
A61P 17/10 20180101; A61K 8/345 20130101; A61K 8/4953 20130101;
A61K 47/10 20130101; A61P 31/04 20180101; A61K 9/0014 20130101;
A61Q 7/00 20130101; A61P 17/00 20180101; A61K 8/042 20130101; A61P
25/04 20180101; A61P 31/12 20180101; A61Q 19/00 20130101; A61K
47/34 20130101; A61Q 19/08 20130101; A61K 2800/591 20130101; A61K
31/506 20130101; A61K 8/34 20130101; A61K 8/85 20130101; A61P 29/00
20180101; A61P 43/00 20180101; A61P 17/14 20180101; A61Q 19/02
20130101 |
International
Class: |
A61K 47/34 20060101
A61K047/34; A61K 31/506 20060101 A61K031/506; A61K 47/10 20060101
A61K047/10 |
Claims
1. A topical composition comprising: a benefit agent; at least one
polymer including a polycaprolactone polymer; at least one lower
alcohol; and at least one co-solvent.
2. The topical composition according to claim 1, wherein wherein
the benefit agent is selected from the group consisting of hair
growth agents, anti-acne and/or anti-rosacea agents, anti-aging
agents, depigmentation agent, anti-microbial agents, anti-viral
agents, anti-inflammatory agents and analgesics, the
polycaprolactone polymer is selected from the group consisting of
hydroxypolycaprolactone; polycaprolactone diol; polycaprolactone
triol; .alpha., .omega.-dihydroxy oligo(.epsilon.-caprolactone);
.alpha.-carboxy, .omega.-hydroxy poly(.epsilon.-caprolactone)
.alpha., .omega.-dicarboxy poly(.epsilon.-caprolactone) and
mixtures thereof; the at least one lower alcohol is selected from
the group consisting of ethyl alcohol, n-propyl alcohol, isopropyl
alcohol, n-butyl alcohol, isobutyl alcohol, amyl alcohol, benzyl
alcohol, octyldocanol, hexyldecanol, butyloctanol, and mixtures
thereof; and the at least one co-solvent is selected from the group
consisting of glycerol, polyglycerols, glycols, polyglycols, and
mixtures thereof.
3. The topical composition according to claim 2, wherein the
polycaprolactone polymer is polycaprolactone diol polymer.
4. The topical composition according to claim 2, wherein the
polyglycerols are selected from the group consisting of diglycerol,
triglycerol, tetraglycerol, polyglycerol-n, where n>4, and
mixtures thereof.
5. The topical composition according to claim 2, wherein the
glycols are selected from the group consisting of propylene glycol,
ethylene glycol, butylene glycol, 1,2-butanediol, 1,3-butanediol,
1,4-butanediol, 2,3-butanediol, pentylene glycol, hexylene glycol,
propanediol, dipropylene glycol, ethoxydiglycol, methylpropanediol,
isopentyldiol, and mixtures thereof.
6. The topical composition according to claim 2 wherein the
polyglycols are selected from the group consisting of polyethylene
glycol, polypropylene glycol and mixtures thereof.
7. The topical composition according to claim 2, wherein the
benefit agent is minoxidil.
8. The topical composition according to claim 2, wherein the
benefit agent is in an amount from about 0.001% to about 20% by
weight of the composition; the polycaprolactone polymer is
polycaprolactone diol polymer in an amount from about 0.05% to
about 20% by weight of the composition; the lower alcohol is in an
amount from about 2% to about 90% by weight of the composition; and
the co-solvent is in an amount from about 1% to about 50% by weight
of the composition.
9. The topical composition according to claim 8, wherein the
benefit agent is in an amount from about 0.01% to about 10% by
weight of the composition; the polycaprolactone diol polymer is in
an amount from about 1% to about 10% by weight of the composition;
the lower alcohol is in an amount from about 5% to about 40% by
weight of the composition; and the co-solvent is in an amount from
about 5% to about 40% by weight of the composition.
10. The topical composition according to claim 9, wherein the
benefit agent is in an amount from about 1% to about 5% by weight
of the composition; the polycaprolactone diol polymer is in an
amount from about 1% to about 5% by weight of the composition; the
lower alcohol is in an amount from about 10% to about 30% by weight
of the composition; and the co-solvent is an amount from about 10%
to about 20% by weight of the composition.
11. The topical composition according to claim 10, wherein the
benefit agent is minoxidil.
12. A method for enhancing the topical application of a benefit
agent which comprises topically administering to a human or animal
a composition comprising a composition according to claim 1.
13. The method according to claim 12, wherein the polycaprolactone
polymer is polycaprolactone diol polymer.
14. The method according to claim 12, wherein the benefit agent is
selected from the group consisting of hair growth agents, anti-acne
and/or anti-rosacea agents, anti-aging agents, depigmentation
agent, anti-microbial agents, anti-viral agents, anti-inflammatory
agents and analgesics, the polycaprolactone polymer is selected
from the group consisting of hydroxypolycaprolactone;
polycaprolactone diol; polycaprolactone triol; .alpha.,
.omega.-dihydroxy oligo(.epsilon.-caprolactone); .alpha.-carboxy,
.omega.-hydroxy poly(.epsilon.-caprolactone) .alpha.,
.omega.-dicarboxy poly(.epsilon.-caprolactone) and mixtures
thereof; the at least one lower alcohol is selected from the group
consisting of ethyl alcohol, n-propyl alcohol, isopropyl alcohol,
n-butyl alcohol, isobutyl alcohol, amyl alcohol, benzyl alcohol,
octyldocanol, hexyldecanol, butyloctanol, and mixtures thereof; and
the at least one co-solvent is selected from the group consisting
of glycerol, polyglycerols, glycols, polyglycols, and mixtures
thereof.
15. The method according to claim 14, wherein the polyglycerols are
selected from the group consisting of diglycerol, triglycerol,
tetraglycerol, polycerol-n, where n>4, and mixtures thereof.
16. The method according to claim 14, wherein the glycols are
selected from the group consisting of propylene glycol, ethylene
glycol, butylene glycol, 1,2-butanediol, 1,3-butanediol,
1,4-butanediol, 2,3-butanediol, pentylene glycol, hexylene glycol,
propanediol, dipropylene glycol, ethoxydiglycol, methylpropanediol,
isopentyldiol, and mixtures thereof.
17. The method according to claim 14, wherein the polyglycols are
selected from the group consisting of polyethylene glycol,
polypropylene glycol and mixtures thereof.
18. The method according to claim 12, wherein the composition
comprises a benefit agent in an amount from about 0.001% to about
20% by weight of the composition; polycaprolactone diol polymer in
an amount from about 0.05% to about 20% by weight of the
composition; a lower alcohol in an amount from about 2% to about
90% by weight of the composition; and a co-solvent in an amount
from about 1% to about 50% by weight of the composition.
19. The method according to claim 18, wherein the composition
comprises a benefit agent in an amount from about 0.01% to about
10% by weight of the composition; polycaprolactone diol polymer in
an amount from about 1% to about 10% by weight of the composition;
a lower alcohol in an amount from about 5% to about 40% by weight
of the composition; and a co-solvent in an amount from about 5% to
about 40% by weight of the composition.
20. The method according to claim 19, wherein the composition
comprises a benefit agent in an amount from about 1% to about 5% by
weight of the composition; polycaprolactone diol polymer in an
amount from about 1% to about 5% by weight of the composition; a
lower alcohol in an amount from about 10% to about 30% by weight of
the composition; and a co-solvent in an amount from about 10% to
about 20% by weight of the composition.
21. The method according to claim 20, wherein the benefit agent is
minoxidil.
22. The method according to claim 13, wherein the benefit agent is
minoxidil.
23. A topical composition comprising minoxidil in an amount from
about 1% to about 5% by weight of the composition; polycaprolactone
diol in an amount from about 1% to about 5% by weight of the
composition; ethyl alcohol in an amount from about 15% to about 25%
by weight of the composition; and a co-solvent in an amount from
about 10% to about 20% by weight of the composition.
Description
[0001] The present invention relates to compositions and methods
for enhancing the topical application of a benefit agent. The
compositions may be gels including a benefit agent, at least one
polymer including a polycaprolactone polymer, at least one lower
alcohol, and at least one co-solvent. The compositions are useful
in topically applied personal care applications.
BACKGROUND OF THE INVENTION
[0002] Liquid compositions for delivering benefit agents are well
known. Typical formulations include solutions, emulsions,
suspensions and gels. The viscosity may vary based on intended area
for application, intended use (leave on or rinse off), or consumer
preference. Liquids are typically easy to dispense and spread out.
There is a continuing need for improved liquid compositions.
[0003] There is also a need for compositions that improve skin
penetration of benefit agents. U.S. Pat. No. 6,419,913 teaches
micellar compositions that enhance skin penetration. Although
effective, these compositions can be difficult to manufacture and
the cost of the products are relatively high.
[0004] Polycaprolactone (PCL) is a polymer used for
implantable/injectable drug delivery systems for medical implants
(M. A. Woodruff & D. W. Hutmacher, The return of a forgotten
polymer--Polycaprolactone in the 21st century, Progress in Polymer
Science, Vol. 35 (10), 2010, pages 1217-1256), or as a carrier to
encapsulate or immoblize a drug for sustained release purpose (H.
I. Chang, et. al, Delivery of the antibiotic gentamicin sulphate
from precipitation cast matrices of polycaprolactone, J. Controlled
Release, Vol. 110, 2:10, 2006, pages 414-421).
[0005] However, PCL has not been shown as a skin permeation
enhancing component in a topical composition to enhance a topical
applied drug to penetrate into the intact skin.
[0006] Applicants have now discovered novel compositions and a
method of enhancing the topical application of benefit agents. The
compositions include gels including a benefit agent, at least one
polymer including a polycaprolactone polymer, at least one lower
alcohol, at least one co-solvent and water. The compositions can be
used in cosmetic, skin care, wound care, dermatologic, and other
personal care products, as well as in other applications and
industries.
SUMMARY OF THE INVENTION
[0007] The invention provides a topical composition comprising at
least one polycaprolactone polymer, at least one lower alcohol, and
at least one co-solvent. The invention also provides a personal
care composition comprising the above composition and a method for
enhancing the topical application of a benefit agent.
DETAILED DESCRIPTION OF THE INVENTION
[0008] As used herein, unless otherwise specified, all percentages
are by weight based on the total weight of composition referred
to.
[0009] The disclosures of all patents and published applications
referred to herein are incorporated by reference in their
entirety.
[0010] As used herein, "benefit agent" is a compound (e.g., a
synthetic compound or a compound isolated from a natural source)
that has a cosmetic or therapeutic effect on tissue (e.g., a
material capable of exerting a biological effect on the human body)
such as therapeutic drugs or cosmetic agents. Examples of benefit
agents include small molecules, peptides, proteins, nucleic acid
materials, and nutrients such as minerals and extracts. The amount
of the benefit agent used will depend on the benefit agent and/or
the intended use of the end product. Benefit agents may be liquid,
solid, or semi-solid.
[0011] As used herein, "pharmaceutically acceptable," "cosmetically
acceptable," or "dermatologically acceptable" means suitable for
use in contact with tissues (e.g., the skin, hair, mucosa,
epithelium or the like) without undue toxicity, incompatibility,
instability, irritation, or allergic response.
[0012] As used herein, "safe and effective amount" means an amount
sufficient to provide a desired benefit at a desired level, but low
enough to avoid serious undesirable side effects. The safe and
effective amount of the ingredient or composition will vary with
the area being treated, the age of the end user, the duration and
nature of the treatment, the specific ingredient or composition
employed, the particular carrier utilized, and like factors.
[0013] As used herein, the term "treating" or "treatment" means the
alleviation or elimination of symptoms, cure, prevention, or
inhibition of a disease or medical condition, or improvement of
tissue growth/healing or cosmetic conditions such as reducing
appearance of skin wrinkles/fine lines, under-eye bags, cellulites,
skin marks/hyperpigmentation or uneven tone.
[0014] To provide a more concise description, some of the
quantitative expressions given herein are not qualified with the
term "about". It is understood that whether the term "about" is
used explicitly or not, every quantity given herein is meant to
refer to the actual given value, and it is also meant to refer to
the approximation to such given value that would reasonably be
inferred based on the ordinary skill in the art, including
approximations due to the experimental and/or measurement
conditions for such given value.
[0015] To provide a more concise description, some of the
quantitative expressions herein are recited as a range from about
amount X to about amount Y. It is understood that wherein a range
is recited, the range is not limited to the recited upper and lower
bounds, but rather includes the full range from about amount X
through about amount Y, or any amount or range therein.
[0016] The polymers used to make the compositions of the present
invention include a polycaprolactone polymer. The polycaprolactone
polymer can be selected from the group consisting of
hydroxypolycaprolactone; polycaprolactone diol (.alpha.,
.omega.-dihydroxy poly(.epsilon.-caprolactone)); polycaprolactone
triol; .alpha., .omega.-dihydroxy oligo(.epsilon.-caprolactone);
.alpha.-carboxy, .omega.-hydroxy poly(.epsilon.-caprolactone)
.alpha., .omega.-dicarboxy poly(.epsilon.-caprolactone) and
mixtures thereof.
[0017] Polycaprolactone [poly(.epsilon.-caprolactone)] can be made
by a ring opening polymerization of the lactone monomer
.epsilon.-caprolactone using an alcohol, such as dodecanol, as an
initiator and a catalyst, such as stannous octoate. The resulting
polymer contains an alkyl functionality at one end and an alcohol
functionality at the other. If however the initiator is chosen to
be a diol, both ends of the formed polymer will be hydroxy
terminated. Polycaprolactone made by ring-opening polymerization
using either a monol or a diol as initiator will be linear in
molecular structure.
[0018] The relative molar amount of the initiator present during
the polymerization controls the molecular weight of the formed
polymer. The higher the relative amount of initiator, the lower the
molecular weight of the formed polymer.
[0019] It is possible to produce polycaprolactone without hydroxyl
groups at the chain ends. This could be accomplished by capping the
chain ends, using for instance succinic anhydride to result in a
carboxy end group instead of a hydroxyl end group, as part of the
synthesis of the resin.
[0020] .alpha., .omega.-dicarboxy poly(.epsilon.-caprolactone) can
be made by using a diol such as diethylene glycol as the
polymerization initiator followed by reaction with a cyclic
anhydride such as diglycolic anhydride or succinic anhydride; an
alternate route to this polymer is using a hydroxy acid such as
glycolic acid as the polymerization initiator followed by reaction
with a cyclic anhydride such as diglycolic anhydride or succinic
anhydride.
[0021] Additionally the polycaprolactone polymer can be a
hydroxylated polycaprolactone polymer. The polymer may have between
1 and 3 hydroxyl substitutions. The polymer can be a
hydroxypolycaprolactone, polycaprolactone diol; polycaprolactone
triol and mixtures thereof. The polycaprolactone triol can be made
by using a triol initiator, such as glycerol, or trimethylolpropane
(TMP); polycaprolactone triol does not possess a linear structure
but is a branched polymer.
[0022] Compositions of the present invention preferably include a
polycaprolactone diol polymer. The polycaprolactone diol polymer
molecular weight may range from about 500 Dalton to about 50,000
Dalton, for example from about 1,000 Dalton to about 5,000 Dalton,
or from about 1,200 Dalton to about 2,500 Dalton, or from about
1,250 Dalton to about 2,000 Dalton. The amount of the polymer is
sufficient to form a gel and may range from about 0.05% to about
20%, or from 0.1% to about 20%, or from about 0.5% to about 10%, or
from about 1% to about 10%, or from about 1% to about 5% by weight
based on the total weight of the composition. The methods for
measuring the molecular weight are those known in the art.
[0023] The topical compositions of the present invention also
include at least one lower alcohol. Suitable alcohols include ethyl
alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol,
isobutyl alcohol, amyl alcohol, benzyl alcohol, octyldocanol,
hexyldecanol, butyloctanol, and mixtures thereof. The amount of
alcohol may range from about 2% to about 90% or from about 5% to
about 80%, or from about 5% to about 40%, or from about 10% to
about 30%, or from about 15% to about 25% by weight based on the
total weight of the composition.
[0024] Compositions according to the present invention also include
a co-solvent. Suitable co-solvents include one or more polyols.
Such polyols include, but are not limited to glycerol (glycerin),
polyglycerols, glycols, polyglycols, and mixtures thereof.
[0025] Examples of polyglycerols include, but are not limited to
diglycerol (diglycerin), triglycerol (polyglcerin-3 or
polyglycerol-3), tetraglycerol (polyglycerin-4 or polyglycerol-4),
other polyglycerols (polycerol-n, where n>4), and mixtures
thereof.
[0026] Examples of glycols include, but are not limited to
propylene glycol, ethylene glycol, butylene glycol and its isomers
(e.g., 1,2-butanediol, 1,3-butanediol, 1,4-butanediol and
2,3-butanediol), pentylene glycol, hexylene glycol and its isomers,
propanediol, dipropylene glycol, ethoxydiglycol, methylpropanediol,
isopentyldiol, and mixtures thereof.
[0027] Examples of polyglycols include, but are not limited to,
polyethylene glycol of various molecular weights, namely, molecular
weights ranging from 300 g/mol to 10,000,000 g/mol, (e.g., PEG-200,
PEG-400, PEG-1000, PEG-2000 PEG-4000, PEG-6000), polypropylene
glycol (PPG) of various molecular weights, and mixtures
thereof.
[0028] The amount of co-solvent may range from about 1% to about
50%, or from about 5% to about 50%, or from about 10% to about 40%
or from about 10% to about 20% by weight based on the total weight
of the composition.
[0029] The compositions of the present invention may also include
water. The amount of water may range from about 20% to about 80%,
or from about 30% to about 60%, or from about 40% to about 50% by
weight based on the total weight of the composition.
[0030] In one embodiment, the composition may further comprise at
least one hydrophilic polymer, e.g., natural or synthetic
hydrophilic polymers. Such hydrophilic polymer may be soluble or
partially soluble in the gel. Suitable hydrophilic polymers
include, but are not limited to, homo- and copolymers of vinyl
pyrrolidone (e.g., PVP, or PVP/PVA copolymer), homo- or copolymers
of vinyl alcohol (e.g., polyvinyl alcohol or PVA), polyacrylamide,
homo- or copolymers of acrylic and/or methacrylic acids, and salts
and esters thereof (e.g., CARBOPO/CARBOMER 934, 940, 941, 980,
1342, and 1382, and ULTREZ 10 and 21), cellulosic polymers (e.g.,
hydroxymethylcellulose, hydroxyethyl cellulose, carboxy methyl
cellulose, carboxy ethyl cellulose), polyurethanes, starch and its
derivatives, and synthetic and natural gums (e.g., gum arabic or
xanthan gum). Preferred hydrophilic polymers are acrylate polymers
and copolymers, particularly polyacrylate neutralized by anhydrous
neutralizers.
[0031] If used, the amount of the hydrophilic polymer is usually up
to about 10%, or equal to or less than about 5%, or equal to or
less than about 3%, or equal to or less than about 2%, by weight of
the composition.
[0032] In general, the topical composition may contain any
additional ingredients (e.g., benefit agents or formulation
excipients) soluble or dispersible in the gel or its components.
Pharmaceutically or cosmetically acceptable benefit agents or
excipients, such as extracts of plants or minerals, natural or
synthetic compounds of small molecular weight or polymers, acids or
bases (particularly week acids or bases) for acidity adjustment,
buffers, chelators, antioxidants, thickeners or gelling agents can
be used.
[0033] The topical composition has great versatility in
application, and can be used in many consumer and medical products
for human and animal use such topical compositions (such as creams,
lotions, gels, shampoos, cleansers, powders patches, bandages, and
masks for application to the skin or mucosal membranes), garments
(such as undergarments, underwear, bras, shirts, pants, pantyhose,
socks, head caps, facial masks, gloves, and mittens), linens (such
as towels, pillow covers or cases and bed sheets), sanitizing
products for household and clinical settings, microcides for
plants, and devices (such as toothbrushes, dental flosses,
periodontal implants or inserts, orthodontic braces, joint
wraps/supports, buccal patches, ocular inserts or implants such as
contact lenses, nasal implants or inserts, and contact lens
cleaning products, wound dressings, diapers, sanitary napkins,
wipes, tampons, rectal and vaginal suppositories, and in coatings
or embedded surfaces on medical devices and other surfaces where
antimicrobial or other beneficial effects are desired).
[0034] The topical composition may be any form suitable for
application to the skin or an animal or human. The forms may
include gels, solutions, lotions, ointments, mousses, foams,
sprays, aerosols, shampoos, creams, pastes or other topical
composition forms known in the art.
[0035] When applied to the skin the topical composition is
formulated to be readily absorbed into the skin with minimal amount
of rubbing. The composition provides an easy to apply topical
composition that can be used to delivery numerous benefit agents to
the skin.
[0036] The topical composition can be incorporated onto fibers,
nonwovens, hydrocolloids, adhesives, films, polymers, and other
substrates. In one embodiment, the composition is in contact with a
tissue interface. Methods of applying the composition on substrates
include spray coating, co-extrusion, and adhesive spraying.
[0037] The topical composition may contain a wide range of benefit
agents used for various applications as described in the sections
below.
[0038] The composition may be administered topically, locally (via
buccal, nasal, rectal or vaginal route) to a subject (e.g., a
human) in need of treatment for a condition or disease, or to
otherwise provide a therapeutic effect. Such therapeutic effects
include, but are not limited to: antimicrobial effects (e.g.,
antibacterial, antifungal, antiviral, and anti-parasitic effects);
anti-inflammation effects including effects in the superficial or
deep tissues (e.g., reduce or elimination of soft tissue edema or
redness); elimination or reduction of pain, itch or other sensory
discomfort; regeneration or healing enhancement of hard tissues
(e.g., enhancing growth rate of the nail or regrowth of hair loss
due to alopecia) or increase soft tissue volume (e.g., increasing
collagen or elastin in the skin or lips); increasing adipocyte
metabolism or improving body appearance (e.g., effects on body
contour or shape, and cellulite reduction); and increasing
circulation of blood or lymphocytes.
[0039] In one embodiment, the composition further contains a safe
and effective amount of a benefit agent, for example, from about
0.001% to about 20%, or from about 0.01% to about 10%, or from
about 1% to about 5% by weight of the composition of the benefit
agent.
[0040] In one embodiment, the invention provides a topical
composition containing the composition that is suitable for
administering to mammalian skin, such as human skin. In one
embodiment, such topical composition contains a safe and effective
amount of (i) the composition, and (ii) a cosmetically- or
pharmaceutically-acceptable carrier.
[0041] The topical compositions may be made into a wide variety of
products that include but are not limited to leave-on products
(such as lotions, creams, gels, sticks, sprays, and ointments),
skin cleansing products (such as liquid washes, solid bars, and
wipes), hair products (such as shampoos, conditioners, sprays, and
mousses), shaving creams, film-forming products (such as masks),
make-up (such as foundations, eye liners, and eye shadows),
deodorant and anti-perspirant compositions, and the like. These
product types may contain any of several cosmetically- or
pharmaceutically-acceptable carrier forms including, but not
limited to solutions, suspensions, emulsions such as microemulsions
and nanoemulsions, gels, and solids carrier forms. Other product
forms can be formulated by those of ordinary skill in the art.
[0042] In one embodiment, the topical composition is used for the
treatment of skin conditions. Examples of such skin conditions
include, but are not limited to acne (e.g., blackheads and
whiteheads), rosacea, nodule-cystic, and other microbial infections
of the skin; visible signs of skin aging (e.g., wrinkles, sagging,
sallowness, and age-spots); loose or lax skin, folliculitis and
pseudo-folliculitis barbae; excess sebum (e.g., for sebum reduction
or oily/shining skin appearance inhibition or control);
pigmentation (e.g., for reduction of hyperpigmentation such as
freckles, melasma, actinic and senile lentigines, age-spots,
post-inflammatory hypermelanosis, Becker's naevus, and facial
melanosis or enhancing the pigmentation of light skin); excess hair
growth (e.g., skin on the leg), or insufficient hair growth (e.g.,
on the scalp); dermatitis (e.g., atopic, contact, or seborrheic
dermatitis), dark circles under the eye, stretch marks, cellulite,
excessive sweating (e.g., hyperhidrosis), and/or psoriasis.
(a) Topical Anti-Acne/Anti-Rosacea Compositions
[0043] In one embodiment, the topical composition also contains an
anti-acne and/or anti-rosacea active agent. Examples of anti-acne
and anti-rosacea agents include, but are not limited to: retinoids
such as tretinoin, isotretinoin, motretinide, adapalene,
tazarotene, azelaic acid, and retinol; salicylic acid; resorcinol;
sulfacetamide; urea; antibiotics such as tetracycline, clindamycin,
metronidazole, and erythromycin; anti-inflammatory agents such as
corticosteroids (e.g., hydrocortisone), ibuprofen, naproxen, and
hetprofen; and imidazoles such as ketoconazole and elubiol; and
salts and prodrugs thereof. Other examples of anti-acne active
agents include essential oils, alpha-bisabolol, dipotassium
glycyrrhizinate, camphor, .beta.-glucan, allantoin, feverfew,
flavonoids such as soy isoflavones, saw palmetto, chelating agents
such as EDTA, lipase inhibitors such as silver and copper ions,
hydrolyzed vegetable proteins, inorganic ions of chloride, iodide,
fluoride, and their nonionic derivatives chlorine, iodine,
fluorine, and synthetic phospholipids and natural phospholipids
such as ARLASILK.TM. phospholipids CDM, SV, EFA, PLN, and GLA
(commercially available from Uniqema, ICI Group of Companies,
Wilton, UK).
(b) Topical Anti-Aging Compositions
[0044] In one embodiment, the topical composition also contains an
anti-aging agent. Examples of suitable anti-aging agents include,
but are not limited to; retinoids; dimethylaminoethanol (DMAE),
copper containing peptides, vitamins such as vitamin E, vitamin A
(retinol and its derivatives, e.g., retinyl palmitate), vitamin C
(ascorbic acid and its derivative, e.g., Ascorbic Acid
2-Glucoside/AA2G), and vitamin B (e.g., niacinamide, niacin) and
vitamin salts or derivatives such as ascorbic acid di-glucoside and
vitamin E acetate or palmitate; alpha hydroxy acids and their
precursors such as glycolic acid, citric acid, lactic acid, malic
acid, mandelic acid, ascorbic acid, alpha-hydroxybutyric acid,
alpha-hydroxyisobutyric acid, alpha-hydroxyisocaproic acid,
atrrolactic acid, alpha-hydroxyisovaleric acid, ethyl pyruvate,
galacturonic acid, glucoheptonic acid, glucoheptono 1,4-lactone,
gluconic acid, gluconolactone, glucuronic acid, glucuronolactone,
isopropyl pyruvate, methyl pyruvate, mucic acid, pyruvic acid,
saccharic acid, saccharic acid 1,4-lactone, tartaric acid, and
tartronic acid; beta hydroxy acids such as beta-hydroxybutyric
acid, beta-phenyl-lactic acid, and beta-phenylpyruvic acid;
tetrahydroxypropyl ethylene-diamine,
N,N,N',N'-Tetrakis(2-hydroxypropyl)ethylenediamine (THPED); and
botanical extracts such as green tea, soy, milk thistle, algae,
aloe, angelica, bitter orange, coffee, goldthread, grapefruit,
hoellen, honeysuckle, Job's tears, lithospermum, mulberry, peony,
puerarua, nice, and safflower; and salts and prodrugs thereof.
(c) Topical Depigmentation Compositions
[0045] In one embodiment, the topical composition contains a
depigmentation agent. Examples of suitable depigmentation agents
include, but are not limited to: soy extract; soy isoflavones;
retinoids such as retinol; kojic acid; kojic dipalmitate;
hydroquinone; arbutin; transexamic acid; vitamins such as
niacinamide, niacin and vitamin C (ascorbic acid and AA2G; azelaic
acid; linolenic acid and linoleic acid; placertia; licorice; and
extracts such as chamomile, grape seeds and green tea; and salts
and prodrugs thereof.
(d) Topical Antipsoriatic Compositions
[0046] In one embodiment, the topical composition contains an
antipsoriatic active agent. Examples of antipsoriatic active agents
(e.g., for seborrheic dermatitis treatment) include, but are not
limited to, corticosteroids (e.g., betamethasone dipropionate,
betamethasone valerate, clobetasol propionate, diflorasone
diacetate, halobetasol propionate, triamcinonide, dexamethasone,
fluocinonide, fluocinolone acetonide, halcinonide, triamcinolone
acetate, hydrocortisone, hydrocortisone verlerate, hydrocortisone
butyrate, aclometasone dipropionte, flurandrenolide, mometasone
furoate, methylprednisolone acetate), methotrexate, cyclosporine,
calcipotriene, anthraline, shale oil and derivatives thereof,
elubiol, ketoconazole, coal tar, salicylic acid, zinc pyrithione,
selenium sulfide, hydrocortisone, sulfur, menthol, and pramoxine
hydrochloride, and salts and prodrugs thereof
(e) Other Topical Ingredients
[0047] In one embodiment, the topical composition contains a plant
extract as a benefit agent. Examples of plant extracts include, but
are not limited to, feverfew, soy, glycine soja, oatmeal, what,
aloe vera, cranberry, witch-hazel, alnus, arnica, artemisia
capillaris, asiasarum root, birch, calendula, chamomile, cnidium,
comfrey, fennel, galla rhois, hawthorn, houttuynia, hypericum,
jujube, kiwi, licorice, magnolia, olive, peppermint, philodendron,
salvia, sasa albo-marginata, natural isoflavonoids, soy
isoflavones, and natural essential oils.
[0048] In one embodiment, the topical composition contains one or
more buffering agents such as citrate buffer, phosphate buffer,
lactate buffer, gluconate buffer, or gelling agent, thickener, or
polymer.
[0049] In one embodiment, the composition or product contains a
fragrance effective for reducing stress, calming, and/or affecting
sleep such as lavender and chamomile.
[0050] The composition can be incorporated into compositions for
the treatment of periodontal disease with actives such as, but not
limited to minocycline.
[0051] In one embodiment, the composition is incorporated into
wound dressings or bandages to provide healing enhancement or scar
prevention. Wounds or lesions that may be treated include, but are
not limited to acute wounds as well as chronic wounds including
diabetic ulcer, venus ulcer, and pressure sores.
[0052] In one embodiment, the wound dressing or bandage contains a
benefit agent commonly used as for topical wound and scar
treatment, such as antibiotics, anti-microbials, wound healing
enhancing agents, antifungal drugs, anti-psoriatic drugs, and
anti-inflammatory agents.
[0053] Examples of antifungal drugs include but are not limited to
miconazole, econazole, ketoconazole, sertaconazole, itraconazole,
fluconazole, voriconazole, clioquinol, bifoconazole, terconazole,
butoconazole, tioconazole, oxiconazole, sulconazole, saperconazole,
clotrimazole, undecylenic acid, haloprogin, butenafine, tolnaftate,
nystatin, ciclopirox olamine, terbinafine, amorolfine, naftifine,
elubiol, griseofulvin, and their pharmaceutically acceptable salts
and prodrugs. In one embodiment, the antifungal drug is an azole,
an allylamine, or a mixture thereof.
[0054] Examples of antibiotics (or antiseptics) include but are not
limited to mupirocin, neomycin sulfate bacitracin, polymyxin B,
1-ofloxacin, tetracyclines (chlortetracycline hydrochloride,
oxytetracycline-10 hydrochloride and tetrachcycline hydrochloride),
clindamycin phosphate, gentamicin sulfate, metronidazole,
hexylresorcinol, methylbenzethonium chloride, phenol, quaternary
ammonium compounds, tea tree oil, and their pharmaceutically
acceptable salts and prodrugs.
[0055] Examples of antimicrobials include but are not limited to
salts of chlorhexidine, such as lodopropynyl butylcarbamate,
diazolidinyl urea, chlorhexidene digluconate, chlorhexidene
acetate, chlorhexidene isethionate, and chlorhexidene
hydrochloride. Other cationic antimicrobials may also be used, such
as benzalkonium chloride, benzethonium chloride, triclocarbon,
polyhexamethylene biguanide, cetylpyridium chloride, methyl and
benzethonium chloride. Other antimicrobials include, but are not
limited to: halogenated phenolic compounds, such as
2,4,4',-trichloro-2-hydroxy diphenyl ether (Triclosan);
parachlorometa xylenol (PCMX); and short chain alcohols, such as
ethanol, propanol, and the like. In one embodiment, the alcohol is
at a low concentration (e.g., less than about 10% by weight of the
carrier, such as less than 5% by weight of the carrier) so that it
does not cause undue drying of the barrier membrane.
[0056] Examples of anti-viral agents for viral infections such as
herpes and hepatitis, include, but are not limited to, imiquimod
and its derivatives, podofilox, podophyllin, interferon alpha,
acyclovir, famcyclovir, valcyclovir, reticulos and cidofovir, and
salts and prodrugs thereof.
[0057] Examples of anti-inflammatory agents include, but are not
limited to, suitable steroidal anti-inflammatory agents such as
corticosteroids such as hydrocortisone, hydroxyltriamcinolone
alphamethyl dexamethasone, dexamethasone-phosphate, beclomethasone
dipropionate, clobetasol valerate, desonide, desoxymethasone,
desoxycorticosterone acetate, dexamethasone, dichlorisone,
diflorasone diacetate, diflucortolone valerate, fluadrenolone,
fluclarolone acetonide, fludrocortisone, flumethasone pivalate,
fluosinolone acetonide, fluocinonide, flucortine butylester,
fluocortolone, fluprednidene (fluprednylidene)acetate,
flurandrenolone, halcinonide, hydrocortisone acetate,
hydrocortisone butyrate, methylprednisolone, triamcinolone
acetonide, cortisone, cortodoxone, flucetonide, fludrocortisone,
difluorosone diacetate, fluradrenalone acetonide, medrysone,
amciafel, amcinafide, betamethasone, chlorprednisone,
chlorprednisone acetate, clocortelone, clescinolone, dichlorisone,
difluprednate, flucloronide, flunisolide, fluoromethalone,
fluperolone, fluprednisolone, hydrocortisone valerate,
hydrocortisone cyclopentylproprionate, hydrocortamate,
meprednisone, paramethasone, prednisolone, prednisone,
beclomethasone dipropionate, betamethasone dipropionate,
triamcinolone, and salts are prodrugs thereof. In one embodiment,
the steroidal anti-inflammatory for use in the present invention is
hydrocortisone. A second class of anti-inflammatory agents which is
useful in the compositions of the present invention includes the
nonsteroidal anti-inflammatory agents.
[0058] Examples of wound healing enhancing agents include
recombinant human platelet-derived growth factor (PDGF) and other
growth factors, ketanserin, iloprost, prostaglandin E1 and
hyaluronic acid, scar reducing agents such as mannose-6-phosphate,
analgesic agents, anesthetics, hair growth enhancing agents such as
minoxadil, hair growth retarding agents such as eflornithine
hydrochloride, antihypertensives, drugs to treat coronary artery
diseases, anticancer agents, endocrine and metabolic medication,
neurologic medications, medication for cessation of chemical
additions, motion sickness, protein and peptide drugs.
[0059] In one embodiment, the composition is used, with or without
other antifungal active agents, to treat or prevent fungal
infections (e.g., dermatophytes such as trichophyton
mentagrophytes), including, but not limited to, onychomycosis,
sporotrichosis, tinea unguium, tinea pedis (athlete's foot), tinea
cruris (jock itch), tinea corporis (ringworm), tinea capitis, tinea
versicolor, and candida yeast infection-related diseases (e.g.,
candida albicans) such as diaper rash, oral thrushm, cutaneous and
vaginal candidiasis, genital rashes, Malassezia furfur
infection-related diseases such as Pityriasis versicolor,
Pityriasis folliculitis, seborrhoeic dermatitis, and dandruff.
[0060] In another embodiment, the composition is used, with or
without other antibacterial active agents, to treat and prevent
bacterial infections, including, but not limited to, acne,
cellulitis, erysipelas, impetigo, folliculitis, and furuncles and
carbuncles, as well as acute wounds and chronic wounds (venous
ulcers, diabetic ulcers and pressure ulcers).
[0061] In another embodiment, the composition is used, with or
without other antiviral active agents, to treat and prevent viral
infections of the skin and mucosa, including, but not limited to,
molluscum contagiosum, warts, herpes simplex virus infections such
as cold sores, kanker sores and genital herpes.
[0062] In another embodiment, the composition is used, with or
without other antiparasitic active agents, to treat and prevent
parasitic infections, including, but not limited to, hookworm
infection, lice, scabies, sea bathers' eruption and swimmer's
itch.
[0063] In one embodiment, the composition is administered to treat
ear infections (such as those caused by streptococcus pneumoniae),
rhinitis and/or sinusitis (such as caused by Haemophilus
influenzae, Moraxella catarrhalis, Staphylococcus aureus and
Streptococcus pneumoniae), and strep throat (such as caused by
Streptococcus pyogenes).
[0064] The composition can also be used to stimulate nail growth,
enhance nail strength, and reduce nail infection or discoloration.
The composition can be incorporated into compositions for the
treatment of onychomychosis with actives such as, but not limited
to miconazole, econazole, ketoconazole, sertaconazole,
itraconazole, fluconazole, voricoriazole, clioquinol, bifoconazole,
terconazole, butoconazole, tioconazole, oxiconazole, sulconazole,
saperconazole, clotrimazole, undecylenic acid, haloprogin,
butenafine, tolnaftate, nystatin, ciclopirox olamine, terbinafine,
amorolfine, naftifine, elubiol, griseofulvin, and their
pharmaceutically acceptable salts and prodrugs. The composition can
be incorporated into compositions for improving the look and feel
of nails with ingredients such as, but not limited to: biotin,
calcium panthotenate, tocopheryl acetate, panthenol, phytantriol,
cholecalciferol, calcium chloride, Aloe Barbadensis (Leaf Juice),
silk protein, soy protein, hydrogen peroxide, carbamide peroxide,
green tea extract, acetylcysteine and cysteine.
[0065] The composition can be combined with certain active agents
for the growth of hair, or improving or thickening of hair of the
scalp, eye brow or eye lash, may be used to treat hair conditions
topically. Compositions containing drug(s) and/or active agents to
stimulate hair growth and/or prevent hair loss and/or regrow hair,
including, but not limited to, minoxidil, finasteride, or lumigan
may be employed.
[0066] The composition has a unique advantage over conventional
hair treatment compositions due to its excellent flowability. For
example, the gel can easily reach the scalp through thinned hair in
the case of alopecia treatment.
[0067] The composition may contain certain analgesic active agents
and as such may be prepared for topical treatment of pain, such as
pain at or from the back, shoulder, joints, muscle sore/pain,
menstrual cramps, or pain from cold sore or canker sore. Benefit
agents to relieve pain include, but are not limited to,
NonSteroidal Anti-Inflammatory Drugs (NSAIDs) such as ibuprofen,
naproxen, salicylic acid, ketoprofen, and diclofenac and their
pharmaceutically acceptable salts thereof. Other topical analgesic
active agents for treating pain and itch include, but are not
limited to, methyl salicylate, menthol, trolamine salicylate,
capsaicin, lidocaine, benzocaine, pramoxine hydrochloride, and
hydrocortisone.
EXAMPLES
[0068] Examples are set forth below to further illustrate the
nature of the invention and the manner of carrying it out. However,
the invention should not be considered as being limited to the
details thereof.
Example 1
[0069] Polycaprolactone diol was purchased from Polysciences, Inc.
(Warrington, Pa.). One sample was 1,250 Daltons; the other sample
was molecular weight 2,000 Daltons.
[0070] A gel was made with the ingredients in Table 1 and following
the procedure below:
TABLE-US-00001 TABLE 1 Chemical Name Formula A Formula B Formula C
Ethyl Alcohol 20.00 20.00 20.00 Pentylene Glycol 4.00 4.00 4.00
Glycerin 12.00 12.00 12.00 Lactic Acid 3.20 3.20 3.20 Minoxidil
5.00 5.00 5.00 Butylated 0.10 0.10 0.10 Hydroxytoluene Water 52.20
49.2 49.2 Steareth-10 1.50 1.5 1.5 Steareth-2 2.00 2.00 2.00
Polycaprolactone diol 0.0 3.0 0.0 (Mwt = 1250) Polycaprolactone
diol 0.0 0.0 3.0 (Mwt = 2000) Total 100.00 100.00 100.00
[0071] Step 1--20 parts of ethyl alcohol, 4 parts of pentylene
glycol, 12 parts of glycerin, 3.2 parts of lactic acid, 0.10 parts
of butylated hydroxytoluene, and 5 parts of minoxidil were added to
a glass container and mixed until the solution is clear at room
temperature.
[0072] Step 2--In a separate glass container, 49.2 parts of water,
3 parts of polycaprolactone diol (if present), 1.5 parts of
steareth-10, and 2 parts of steareth-2 were added. The mixture was
heated to about 75.degree. C. to melt the contents and a mixer was
used to mix it for 5-10 minutes until completely uniform.
[0073] After the water phase in step 2 cooled back to room
temperature the mix from step #1 was added and, using a high speed
homogenizer, the mixture was homogenized for about 5 minutes.
Example 2
In Vitro Skin Permeation of 5% Minoxidil Compositions Through Human
Cadaver Skin
[0074] A skin penetration study evaluated the penetration of
minoxidil into different skin layers for the inventive samples
(Formulas B and C) prepared as disclosed in Example 1 vs. a test
sample without the PCL polymer (Formula A). A well-known Franz
diffusion cell method (as taught in US20020006418 A1, which is
hereby incorporated by reference) was used. Franz cells had a
diameter of 0.5 cm.sup.2 and a volume of liquid receptor of 5 ml. A
magnetic stirrer bar was added in the donor compartment. The liquid
receptor was filled with Phosphate-buffered saline (PBS) solution.
Air bubbles in the donor compartment were removed. The system was
thermostated at 37.degree. C. above a magnetic stirrer to ensure
the homogeneity of the liquid receptor during the experiment. A
cadaver skin sample from a commercial tissue bank (Ohio Valley
Tissue and Skin Center, Cincinnati, Ohio, dermatomed to
approximately 0.4 mm) was cut to fit the glass diffusion cell and
mounted skin on the Franz cell. A test sample of 20 microliters was
applied on the skin surface. Samples were collected from the
receptor compartment at scheduled time points of 0, 1, 3 and 6
hours. At the end of the study the skin surface was washed with a
cotton swab soaked with PBS (total four times). The cotton swabs
were collected for drug analysis later. After washing, D-squame
tape (CuDerm Corp., Dallas, Tex.) was used to separate the stratum
corneum from epidermis by pressing the tape onto the skin surface
and remove it. The same process of tape-stripping was repeated four
more times (total 5 times). All the tapes were collected for each
skin samples for drug extraction later. Epidermis layer was
separated from dermis tissue by pressing the epidermis side of the
skin onto a 60.degree. C. hot plate for 1 minute, then peeling off
the epidermis layer from the dermis tissue with a pair of forceps.
Extraction was performed using methanol as extraction solvent from
the collected tapes (drug on and in the stratum corneum), epidermis
(drug penetrated into the epidermis tissue) and dermis (drug
penetrated into the dermis tissue). Samples collected from the
receptor compartment and from the extraction processes, as well as
from the washing process were analyzed for minoxidil levels with a
Waters High-performance liquid chromatography (HPLC) system with
the procedure listed below. The results are shown in Tables 2 and
3. The final average minoxidil levels in different skin layers are
reported in micrograms (.mu.g) for 3 different replicates. A
minoxidil mass balance study was also conducted and the % of
recovery of minoxidil was equal or better than 94% for both the
control (Formula A) and the inventive formulations (Formulas B and
C).
TABLE-US-00002 TABLE 2 Time Formula A Formula B Ratio Formula (hr)
(microgram) (microgram) B/Formula A Cumulative 0 0 0 0 Minoxidil in
3 14.7 22.3 1.52 Receptor 6 37.3 48.8 1.31 Dermis 6 10.2 10.4 1.02
Epidermis 6 12.7 21.6 1.70 Tapes 6 5.2 12.4 -- Wash 6 770 749 -- %
Recovered 6 95% 96%
TABLE-US-00003 TABLE 3 Ratio between Time Formula A Formula C
Formula C vs. (hr) (microgram) (microgram) Formula A Cumulative 0 0
0 0 Minoxidil in 3 14.7 22.6 1.54 Receptor 6 37.3 50.3 1.35 Dermis
6 10.2 15.0 1.47 Epidermis 6 12.7 21.3 1.68 Tapes 6 5.2 13.5 --
Wash 6 770 764 -- % Recovered 6 95% 94% --
[0075] Because the target tissue for topical minoxidil delivery is
the hair follicles (hair "roots") residing deep in the dermis, only
minoxidil that penetrated into and across the dermis layer could
reach the hair follicles, and therefore, are of practical
significance. The cumulative minoxidil in the receptor is the
measurement of the total minoxidil that penetrated across all the
layers of the skin including the dermis. It is surprising that the
gel compositions of the present invention have enhanced minoxidil
delivery deep into and across the human skin in comparison to the
control formulation with the same drug concentration, as
demonstrated by the results in Tables 2 and 3. This is an
unexpected finding since all three formulas have the same solvents
at the same amounts.
HPLC Procedure for Minoxidil Quantification
[0076] A HPLC System (Waters Alliance.RTM. HPLC system) was used to
measure minoxidil with UV absorption response at 286 nm. A Luna 5
.mu.M C18(2) 250.times.4.6-mm HPLC column (Phenomenex) was used to
separate the minoxidil analyte from other impurities in the extract
samples for surface rinse, stripped tape, epidermis, dermis, and
receptor solution. The mobile phase was an isocratic 80% (70:29:1
water/methanol/acetic acid--pH 3.3): 20% methanol.
Example 3
[0077] Polycaprolactone diol was purchased from Polysciences, Inc.
(Warrington, Pa.). One sample was 1,250 Daltons; the other sample
was molecular weight 2,000 Daltons.
[0078] Gels were made with the ingredients in Table 4 and following
the procedure below:
TABLE-US-00004 TABLE 4 Chemical Name Formula D Formula E Ethyl
Alcohol, USP 20.00 20.00 (95%) Pentylene Glycol 4.00 4.00 Glycerin
12.00 12.00 Sodium Hydroxide 1.00 1.00 Ibuprofen 5.00 5.00
Butylated 0.10 0.10 Hydroxytoluene Water 51.40 51.40 Steareth-10
1.50 1.50 Steareth-2 2.00 2.00 Polycaprolactone diol 1.0 0.0 (Mwt =
1250) Polycaprolactone diol 0.0 1.0 (Mwt = 2000) Sodium Hydroxide
(20% Adjust the Adjust the in water) aqueous aqueous phase to phase
to pH 6 pH 6 Water Add To 100 Add To 100 Hydroxypropylcellulose
1.00 1.00 (KLUCEL, HF Pharm) Total 101.00 101.00
[0079] Step 1--20 parts of ethyl alcohol, 4 parts of pentylene
glycol, 12 parts of glycerin, 0.10 parts of butylated
hydroxytoluene, 5 parts of ibuprofen, and 30 parts of purified
water were added to a glass container. The pH was adjusted to pH 6
using 20% NaOH aqueous solution at room temperature. The amount of
NaOH and water added was recorded.
[0080] Step 2--1 part of polycaprolactone diol, 1.5 parts of
steareth-10, and 2 parts of steareth-2 were added in a separate
glass container. The remaining parts of purified water were added
until the total amount of the composition was equal to 100 parts.
The mixture was heated to about 75.degree. C. to melt the contents,
and use a mixer was used to mix it for 5-10 minutes until
completely uniform.
[0081] After the water phase in step 2 cooled back to room
temperature the mix from step 1 was added and a high speed
homogenizer was used to homogenize the mixture for about 5 minutes.
1 part of hydroxypropylcellulose was added and mixed until a
uniform translucent gel was formed. The pH was measured to confirm
the final pH of the composition.
[0082] While the invention has been described above with reference
to specific embodiments thereof, it is apparent that many changes,
modifications, and variations can be made without departing from
the inventive concept disclosed herein. Accordingly, it is intended
to embrace all such changes, modifications, and variations that
fall within the spirit and broad scope of the appended claims.
* * * * *