U.S. patent application number 11/249496 was filed with the patent office on 2006-03-09 for pharmaceutical compositions and methods for managing skin conditions.
Invention is credited to Howard Murad.
Application Number | 20060051429 11/249496 |
Document ID | / |
Family ID | 26789222 |
Filed Date | 2006-03-09 |
United States Patent
Application |
20060051429 |
Kind Code |
A1 |
Murad; Howard |
March 9, 2006 |
Pharmaceutical compositions and methods for managing skin
conditions
Abstract
This application relates to a stable pharmaceutical composition
and methods for the cleaning of skin to facilitate the prevention,
treatment, and management of skin conditions, such as seborrheic
dermatitis, psoriasis, folliculitis, rosacea, perioral dermatitis,
acne, impetigo and other inflammatory skin conditions, and the
like, including a sufficient amount of an acidic component of a
hydroxyacid or tannic acid, or a pharmaceutically acceptable salt
thereof, to exfoliate a portion of the skin, a sufficient amount of
stabilized hydrogen peroxide to facilitate cleansing of the skin
without substantial irritation thereof, and an antimicrobial agent
including at least one of an antibacterial agent, antimicrobial
agent, antiviral agent, anthelmintic, or a combination thereof, in
an amount sufficient to inhibit or reduce microorganisms on the
skin.
Inventors: |
Murad; Howard; (Marina del
Rey, CA) |
Correspondence
Address: |
KENYON & KENYON
1500 K STREET NW
SUITE 700
WASHINGTON
DC
20005
US
|
Family ID: |
26789222 |
Appl. No.: |
11/249496 |
Filed: |
October 14, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10093443 |
Mar 11, 2002 |
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11249496 |
Oct 14, 2005 |
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09878231 |
Jun 12, 2001 |
6383523 |
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10093443 |
Mar 11, 2002 |
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09549202 |
Apr 13, 2000 |
6296880 |
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09878231 |
Jun 12, 2001 |
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09330127 |
Jun 11, 1999 |
6071541 |
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09549202 |
Apr 13, 2000 |
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60094775 |
Jul 31, 1998 |
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Current U.S.
Class: |
424/616 ;
514/557 |
Current CPC
Class: |
A61K 2800/75 20130101;
Y02A 50/473 20180101; A61Q 19/00 20130101; C11D 3/2086 20130101;
Y02A 50/30 20180101; A61K 8/602 20130101; C11D 3/48 20130101; A61K
31/19 20130101; A61K 8/365 20130101; A61K 8/9794 20170801; A61K
33/40 20130101; A61K 8/9789 20170801; A61P 17/00 20180101; A61K
45/06 20130101; A61K 8/22 20130101; A61K 33/40 20130101; A61K
2300/00 20130101; A61K 31/19 20130101; A61K 2300/00 20130101 |
Class at
Publication: |
424/616 ;
514/557 |
International
Class: |
A61K 33/40 20060101
A61K033/40; A61K 31/19 20060101 A61K031/19 |
Claims
1. A skin cleansing pharmaceutical composition comprising: an
acidic component comprising a hydroxy acid or tannic acid, or a
pharmaceutically acceptable salt thereof, present in an amount
greater than about 4 weight percent sufficient to exfoliate at
least a portion of the skin; hydrogen peroxide in an amount
sufficient to cleanse the skin without substantial irritation
thereof; and an anthelmintic in an amount sufficient to at least
inhibit microorganisms on the skin.
2. The pharmaceutical composition of claim 1, wherein the
composition further comprises a pharmaceutically acceptable carrier
or excipient.
3. The pharmaceutical composition of claim 1, wherein the acidic
component comprises glycolic acid, lactic acid, citric acid,
salicylic acid, or tannic acid.
4. The pharmaceutical composition of claim 1, further comprising an
amount of amphoteric surfactant and an amount of citric acid
sufficient to inhibit hydrogen peroxide decomposition for at least
three months.
5. The pharmaceutical composition of claim 4, wherein the amount of
amphoteric surfactant and citric acid is sufficient to inhibit
hydrogen peroxide decomposition at 40.degree. C. for at least three
months.
6. The pharmaceutical composition of claim 1, wherein the acidic
component is present in an amount from about 4 to 12 weight
percent, the hydrogen peroxide is present in an amount from about
0.01 to 6 weight percent, and the anthelmintic is present in an
amount from about 0.01 to 1.5 weight percent, of the
composition.
7. The pharmaceutical composition of claim 1, further comprising at
least one of a surfactant, a stabilizer, a preservative, a
moisturizer, anti-inflammatory agent, anti-oxidant, or a coloring
agent, which together may be present in an amount from about 10.1
to 99.1 weight percent of the composition.
8. A gel, paste, cream, lotion, emulsion, or ointment comprising
the pharmaceutical composition of claim 1.
9. A method of managing a skin condition comprising administering
to a patient a therapeutically effective amount of the
pharmaceutical composition of claim 1.
10. The method of claim 9, wherein the skin condition is selected
from the group consisting of seborrheic dermatitis, psoriasis,
folliculitis, rosacea, perioral dermatitis, acne, and impetigo.
11. The method of claim 10, wherein the skin condition is
rosacea.
12. The method of claim 9, wherein the skin condition is a
tricomona infection.
13. The method of claim 9, wherein the pharmaceutical composition
is administered topically.
14. A method of managing a skin condition comprising administering
to a patient a therapeutically effective amount of the
pharmaceutical composition of claim 8.
15. A method of managing a skin condition comprising administering
to a patient a therapeutically effective amount of the
pharmaceutical composition of claim 7.
16. A method of managing a skin condition comprising administering
to a patient a therapeutically effective amount of the
pharmaceutical composition of claim 3.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of application Ser. No.
09/549,202, filed Apr. 13, 2000, now allowed, which is a
continuation-in-part of application Ser. No. 09/330,127, filed Jun.
11, 1999, currently U.S. Pat. No. 6,071,541, which is a
continuation-in-part of provisional Application No. 60/094,775,
filed Jul. 31, 1998.
TECHNICAL FIELD
[0002] This application relates to pharmaceutical compositions and
methods to cleanse skin and facilitate the prevention, treatment,
and management of skin conditions.
BACKGROUND OF THE INVENTION
[0003] Human skin is a composite material of the epidermis and the
dermis. The topmost part of the epidermis is the stratum corneum.
This layer is the stiffest layer of the skin, as well as the one
most affected by the surrounding environment. Below the stratum
corneum is the internal portion of the epidermis. Below the
epidermis, the topmost layer of the dermis is the papillary dermis,
which is made of relatively loose connective tissues that define
the micro-relief of the skin. The reticular dermis, disposed
beneath the papillary dermis, is tight, connective tissue that is
spatially organized. The reticular dermis is also associated with
coarse wrinkles. At the bottom of the dermis lies the subcutaneous
layer.
[0004] The principal functions of the skin include protection,
excretion, secretion, absorption, thermoregulation,
pigmentogenesis, accumulation, sensory perception, and regulation
of immunological processes. These functions are detrimentally
affected by, for example, dryness, yeast, and structural changes in
the skin, such as due to aging and excessive sun exposure.
[0005] Various pharmaceuticals have been used for the treatment or
prevention of skin conditions, including skin cleansing
compositions. Some of these compositions are discussed below.
[0006] Canadian Patent No. 1,174,976 discloses a germ-killing skin
medication including two gels to be applied and mixed in situ, the
first gel having sodium chlorite in an aqueous form and the second
gel having lactic acid in an aqueous gel.
[0007] Great Britain Application No. 2,076,286 A discloses a
dermatological composition of an oil medium dispersed in an aqueous
medium that contains hydrogen peroxide, a buffer to maintain the
composition below a pH of 7, and a starch gelled in situ. The
buffer may include lactic, citric, tartaric, maleic, or
hydroxysuccinic acids with an acid salt.
[0008] Great Britain Application No. 2,189,394 A discloses a
concentrate that can be mixed with hydrogen peroxide to become an
effective disinfectant for water, foodstuff, animal feeds,
equipment, packages, and the like. The concentrate includes an
inorganic acid with a pH less than 1.6, a silver compound or
colloidal silver, an organic acid stabilizer such as tartaric,
lactic, salicylic, or citric acid, and optionally gelatin.
[0009] European Patent Application No. 0,191,214 A2 discloses a
cosmetic liquid cleanser for treating blemished, scarred, or
inflamed skin having boric acid or borax, ammonium hydroxide, a
peroxide, and optionally salicylic acid.
[0010] European Patent No. 0,250,539 B1 discloses a stabilized
aqueous hydrogen peroxide composition having 0.1 to 4 weight
percent hydrogen peroxide and 0.5 to 5 weight percent
.beta.-crystals of one or more lipids selected from monoglycerides
of fatty acids, ascorbic acid, phosphate or lactic acid esters of
fatty acids and monoglycerol ethers, said fatty acids and ether
chains being saturated and having 12 to 18 carbons.
[0011] European Patent No. 0,425,507 B1 discloses compositions for
treating abnormal or damaged conditions of the epithelium including
skin, which include 0.01 to 12 weight percent of an activated
protein containing at least 0.5 weight percent cysteine, 0.1 to 15
weight percent of a reducing agent to reduce cystine to cysteine,
and 81.0 to 99.889 weight percent water, acids, bases, buffering
agents, emulsifying agents, thickeners, solvents, preservatives,
coloring agents, and perfuming agents. The reducing agent may be a
salt of a thioglycolic acid. In a preferred embodiment, the
composition also includes an oxidizing agent, such as hydrogen
peroxide.
[0012] U.S. Pat. No. 3,297,456 discloses cleaning and polishing
compositions, particularly for floor waxing, having lactic acid,
methanol, hydrogen peroxide, and aqua ammonia in a particular
ratio.
[0013] U.S. Pat. Nos. 4,015,058 and 4,015,059 disclose stable
peroxy-containing concentrates useful for the production of
microbicidal agents consisting essentially of an aqueous mixture of
0.5 to 20 weight percent peracetic or perpropionic acid or their
precursors, 25 to 40 weight percent hydrogen peroxide, and
optionally up to 5 weight percent anionic surface-active compounds
of the sulfonate and sulfate type. Also disclosed are compositions
that further include 0.25 to 10 weight percent organic phosphonic
acid capable of sequestering bivalent metal cations and their
water-soluble acid salts.
[0014] U.S. Pat. No. 4,203,765 discloses an aqueous acidic
etch-bleach solution of hydrogen peroxide, iron ions, and inorganic
anions that form a silver salt, such that in the dissolved state
the solution contains citric acid and a polymer of alkylene oxide
units for stabilization of the hydrogen peroxide.
[0015] U.S. Pat. No. 4,438,102 discloses compositions containing
gelatin, hydrogen peroxide, ammonium hydroxide, thioglycolic acid,
and a lower alkanol to promote the growth of dermal and epidermal
tissue.
[0016] U.S. Pat. No. 4,534,945 discloses an aqueous 25 to 35 weight
percent solution of hydrogen peroxide stabilized against
decomposition with up to 1.4 mg/L tin, which is maintained in
solution by particular amounts of phosphate in the form of
phosphonic acid and hydroxycarboxylic acid.
[0017] U.S. Pat. No. 4,557,935 discloses a germicidal composition
of hydrophilic lipid crystals of 1-monolaurin, and preferably
1-monomyristin, and hydrogen peroxide, whereby the former stabilize
the latter. Optionally, the compositions further contain salicylic
acid.
[0018] U.S. Pat. No. 4,900,721 discloses liquid, aqueous
disinfectants based on alcohol and hydrogen peroxide that contain
one or more C.sub.2-8 alcohols, hydrogen peroxide or a hydrogen
peroxide forming compound, one or more carboxylic acids, one or
more microbicidally active nitrogen-containing organic compounds,
one or more microbicidally active phenolic compounds for
disinfection of the skin and mucous membrane.
[0019] U.S. Pat. No. 5,139,788 discloses an antimicrobial surface
sanitizing composition having a diluent and antimicrobial agent of
an antimicrobially effective amount of alpha-hydroxyacid
substituted mono- or di-carboxylic acid and an antimicrobially
effective amount of hydrogen peroxide, such that the composition
leaves a non-contaminating residue after contact with surfaces to
be disinfected.
[0020] U.S. Pat. No. 5,693,318 discloses phosphate esters for the
improvement of water solubility of salicylic acid and peroxide
compounds in an aqueous cleanser.
[0021] Despite these references, a stable composition of hydrogen
peroxide, a hydroxy acid, and an antimicrobial agent has not been
prepared and used for cleansing skin and managing skin conditions.
Thus, there is still a need for improved pharmaceutical
compositions and methods capable of cleansing the skin to
facilitate the prevention, treatment, and management of skin
conditions, such as folliculitis, seborrheic dermatitis, psoriasis,
rosacea, perioral dermatitis, acne, impetigo and other inflammatory
skin conditions, and the like. The present invention advantageously
provides pharmaceutical compositions and methods for cleansing skin
to facilitate the prevention, treatment, and management of one or
more skin conditions.
SUMMARY OF THE INVENTION
[0022] The present invention relates to a skin cleansing
pharmaceutical composition, preferably for administration to a
patient, including an acidic component having a hydroxy acid or
tannic acid, or a pharmaceutically acceptable salt thereof, in an
amount sufficient to exfoliate at least a portion of the skin,
hydrogen peroxide in an amount sufficient to cleanse the skin
without substantial irritation thereof, and an antimicrobial agent
including at least one of an antibacterial agent, an antifungal
agent, an antiviral agent, an anthelmintic, or a combination
thereof, in an amount sufficient to at least inhibit microorganisms
on the skin. In a preferred embodiment, the composition further
includes a pharmaceutically acceptable carrier or excipient.
[0023] In one embodiment, the acidic component includes an
alpha-hydroxy acid, beta-hydroxy acid, or tannic acid. In a
preferred embodiment, the acidic component includes glycolic acid,
lactic acid, citric acid, salicylic acid, or tannic acid.
[0024] Advantageously, the acidic component is present in an amount
from about 0.1 to 8 weight percent, the hydrogen peroxide is
present in an amount from about 0.01 to 6 weight percent, and the
antimicrobial agent is present in an amount from about 0.01 to 1.5
weight percent of the composition. In a preferred embodiment, the
composition further includes at least one of a surfactant, a
stabilizer, a preservative, a moisturizer, anti-inflammatory agent,
anti-oxidant, and a coloring agent, which together may be present
in an amount from about 10.1 to 99.1 weight percent of the
composition.
[0025] The acidic component can include an amount of citric acid
sufficient to inhibit hydrogen peroxide decomposition over at least
three months. In a more preferred embodiment, the amount of citric
acid is sufficient to inhibit hydrogen peroxide decomposition at
40.degree. C. over at least three months. The invention also
relates to a gel, paste, cream, lotion, emulsion, or ointment that
includes these pharmaceutical compositions.
[0026] In one preferred embodiment, the antimicrobial agent
includes an antifungal agent. In a more preferred embodiment, the
antifungal agent is selected from the group of farnesol,
clotrimazole, ketoconazole, econazole, fluconazole, calcium or zinc
undecylenate, undecylenic acid, butenafine hydrochloride,
ciclopirox olaimine, miconazole nitrate, nystatin, sulconazole,
terbinafine hydrochloride, and mixtures thereof.
[0027] In another preferred embodiment, the antimicrobial agent
includes an antibacterial agent. In a more preferred embodiment,
the antibacterial agent is selected from the group of triclosan,
neomycin, clindamycin, polymyxin, bacitracin, benzoyl peroxide, a
tetracycline such as doxycycline or minocycline, a sulfa drug such
as sulfacetamide, a penicillin, a cephalosporin such as cephalexin,
a quinolone such as lomefloxacin, olfloxacin, or trovafloxacin, and
mixtures thereof.
[0028] In yet another preferred embodiment, the antimicrobial agent
includes an antiviral agent. In a more preferred embodiment, the
antiviral agent is selected from the group of acyclovir, tamvir,
penciclovir, and mixtures thereof.
[0029] The invention further relates to a method of managing a skin
condition by administering to a patient a therapeutically effective
amount of: (1) an acidic component including a hydroxy acid or
tannic acid, or a pharmaceutically acceptable salt thereof, (2)
hydrogen peroxide, and (3) an antimicrobial agent including at
least one of an antibacterial agent, an antifungal agent, antiviral
agent, an anthelmintic, or a combination thereof, to at least
inhibit the growth of microorganisms on the skin that contributes
to, or causes, the skin condition.
[0030] The types of skin conditions that can be treated include
seborrheic dermatitis, psoriasis, folliculitis, rosacea, perioral
dermatitis, acne, or impetigo or other inflammatory skin
conditions. The administration of the components may be topical,
such as by at least one of a gel, paste, cream, lotion, emulsion,
or ointment. About 1 mg to 10,000 mg of the acidic component,
hydrogen peroxide, and antimicrobial agent are administered
together for satisfactory results in most cases. In a preferred
embodiment, the acidic component, hydrogen peroxide, and
antimicrobial agent are administered concurrently. In another
embodiment, the acidic component, hydrogen peroxide, and
antimicrobial agent are administered concurrently with at least one
additional pharmaceutical composition for the prevention or
treatment of a skin condition. In this embodiment, the method
further includes administering at least one of a surfactant,
stabilizer, preservative, moisturizer, anti-inflammatory agent,
anti-oxidant, or coloring agent. Alternatively, the acidic
component can include an alpha-hydroxy acid, beta-hydroxy acid, or
tannic acid and the antimicrobial agent can include an
antibacterial agent. In a more preferred embodiment, the acidic
component includes glycolic, lactic, tannic, citric, or salicylic
acid, and the antimicrobial agent includes triclosan.
[0031] The invention also relates to a skin cleansing
pharmaceutical composition including an acidic component containing
a hydroxy acid or tannic acid, or a pharmaceutically acceptable
salt thereof, present in an amount greater than about 1 weight
percent to exfoliate at least a portion of the skin, hydrogen
peroxide in an amount sufficient to cleanse the skin without
substantial irritation thereof, and an antimicrobial agent that
essentially includes at least one of an antibacterial agent,
antifungal agent, antiviral agent, an anthelmintic, or a
combination thereof, in an amount sufficient to at least inhibit
microorganisms on the skin.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0032] A formulation for the prevention, treatment, and management
of skin conditions, such as seborrheic dermatitis, psoriasis,
folliculitis, rosacea, perioral dermatitis, acne, impetigo and
other inflammatory skin conditions, and the like, has now been
discovered. Moreover, the management of these skin conditions may
advantageously be accomplished by the administration of the
pharmaceutical composition of the present invention.
[0033] The term "skin conditions," as used herein, means conditions
present anywhere on the skin including seborrheic dermatitis,
psoriasis, folliculitis, rosacea, perioral dermatitis, acne,
impetigo and other inflammatory skin conditions, and the like.
[0034] The terms "managing" or "management," as used herein,
includes one or more of the prevention, treatment, or modification
of a skin condition.
[0035] The term "inhibit hydrogen peroxide decomposition," as used
herein, means to at least stop the rate of decomposition from
increasing, preferably to inhibit the decomposition entirely, and
more preferably to substantially inhibit the decomposition
altogether. "Substantially inhibit," as used herein, means that
less than about 10 weight percent, preferably less than about 3
weight percent, and more preferably less than about 1 weight
percent, of the hydrogen peroxide decomposes over a three month
period of time.
[0036] Methods for administering the compositions herein are also
encompassed by the invention. Such methods are used for the
prevention, treatment, or management of one or more of: eczema,
psoriasis, folliculitis, scaling, seborrhea or seborrheic
dermatitis, rosacea, perioral dermatitis, acne, impetigo and other
inflammatory skin conditions, all while substantially avoiding
irritation to the skin. The compositions may be prepared in high
concentrations for administration as a cleanser to be removed
shortly thereafter, as well as in lower concentrations that are
safer for products that can remain in contact with the skin for
longer times.
[0037] The pharmaceutical compositions of the invention include the
combination of a number of different components that interact to
provide the desired management of the skin. The compositions
include an acidic component including one or more mono- or
poly-hydroxy acids or tannic acid, a mixture thereof, or a
pharmaceutically acceptable salt or ester thereof. One of ordinary
skill in the art will be readily able to select and prepare
suitable mono- or poly-hydroxy acids for use in the composition of
the invention, for example, alkyl hydroxycarboxylic acids, aralkyl
and aryl hydroxycarboxylic acids, polyhydroxy-carboxylic acids, and
hydroxy-polycarboxylic acids. One of ordinary skill in the art
would typically select one or more of the following mono- or
poly-hydroxy acids: 2-hydroxyacetic acid (glycolic acid);
2-hydroxypropanoic acid (lactic acid); 2-methyl 2-hydroxypropanoic
acid; 2-hydroxybutanoic acid; phenyl 2-hydroxyacetic acid; phenyl
2-methyl 2-hydroxyacetic acid; 3-phenyl 2-hydroxyacetic acid;
2,3-dihydroxypropanoic acid; 2,3,4-trihydroxybutanoic acid;
2,3,4,5,6-pentahydroxyhexanoic acid; 2-hydroxydodecanoic acid;
2,3,4,5-tetrahydroxypentanoic acid;
2,3,4,5,6,7-hexahydroxyheptanoic acid; diphenyl 2-hydroxyacetic
acid; 4-hydroxymandelic acid; 4-chloromandelic acid;
3-hydroxybutanoic acid; 4-hydroxybutanoic acid; 2-hydroxyhexanoic
acid; 5-hydroxydodecanoic acid; 12-hydroxydodecanoic acid;
10-hydroxydecanoic acid; 16-hydroxyhexadecanoic acid;
2-hydroxy-3-methylbutanoic acid; 2-hydroxy-4-methylpentanoic acid;
3-hydroxy-4-methoxymandelic acid; 4-hydroxy-3-methoxymandelic acid;
2-hydroxy-2-methylbutanoic acid; 3-(2-hydroxyphenyl) lactic acid;
3-(4-hydroxyphenyl) lactic acid; hexahydromandelic acid;
3-hydroxy-3-methylpentanoic acid; 4-hydroxydecanoic acid;
5-hydroxydecanoic acid; aleuritic acid; 2-hydroxypropanedioic acid;
2-hydroxybutanedioic acid; erythraric acid; threaric acid;
arabiraric acid; ribaric acid; xylaric acid; lyxaric acid; glucaric
acid; galactaric acid; mannaric acid; gularic acid; allaric acid;
altraric acid; idaric acid; talaric acid;
2-hydroxy-2-methylbutanedioic acid; citric acid, isocitric acid,
agaricic acid, quinic acid, glucoronic acid, glucoronolactone,
galactoronic acid, galactoronolactone, uronic acids, uronolactones,
ascorbic acid, dihydroascorbic acid, dihydroxytartaric acid, tropic
acid, ribonolactone, gluconolactone, galactonolactone,
gulonolactone, mannonolactone, citramalic acid; pyruvic acid,
hydroxypyruvic acid, hydroxypyruvic acid phosphate and esters
thereof; methylpyruvate, ethyl pyruvate, propyl pyruvate, isopropyl
pyruvate; phenyl pyruvic acid and esters thereof; methyl phenyl
pyruvate, ethyl phenyl pyruvate, propyl phenyl pyruvate; formyl
formic acid and esters thereof; methyl formyl formate, ethyl formyl
formate, propyl formyl formate; benzoyl formic acid and esters
thereof; methyl benzoyl formate, ethyl benzoyl formate and propyl
benzoyl formate; 4-hydroxybenzoyl formic acid and esters thereof;
4-hydroxyphenyl pyruvic acid and esters thereof; and
2-hydroxyphenyl pyruvic acid and esters thereof. The hydroxy acids
are preferably selected from one or more alpha-hydroxy acids or
beta-hydroxy acids, more preferably from glycolic, lactic, citric,
tannic, or salicylic acid, and most preferably from citric and
salicylic acids. It should be understood that one or more
derivatives of the above acidic component, such as esters or
lactones thereof, are also suitably used. One of ordinary skill in
the art will also understand that various hydroxy acids described
in U.S. Pat. Nos. 5,547,988 and 5,422,370 are also suitable for use
in the compositions and methods of the invention. The acidic
component is present in the composition and methods in an amount
sufficient to exfoliate, i.e., remove dead or dying skin cells,
from at least a portion of the skin. The acidic component is
typically present in an amount from about 0.1 to 12 weight percent,
preferably about 1 to 111 weight percent, more preferably from
about 4 to 10 weight percent of the composition. For example, the
acidic component may be from about 0.1 to 3 weight percent citric
acid in combination with up to about 2 weight percent salicylic
acid.
[0038] Compositions and methods for managing eczema, psoriasis,
folliculitis, scaling, seborrhea or seborrheic dermatitis, rosacea,
perioral dermatitis, acne, impetigo and other inflammatory skin
conditions, and the like, also include hydrogen peroxide and an
antimicrobial agent. The hydrogen peroxide is present in an amount
sufficient to cleanse at least a portion of the skin. "Cleanse" as
used herein includes the removal of dirt, debris, air pollutants,
desquamating cells, and cutaneous secretions of the skin. The
hydrogen peroxide is typically present in an amount from about 0.01
to 6 weight percent, preferably 0.05 to 4 weight percent, and more
preferably 0.1 to 1 weight percent of the composition.
[0039] Any pharmaceutically acceptable antimicrobial agent
available to those of ordinary skill in the art may be used, but
preferably at least one of an antibacterial agent, antifungal
agent, antiviral agent, or anthelmintic will be used according to
the invention. A single broad spectrum antimicrobial agent, i.e.,
one that is believed to have at least two of antibacterial,
antifungal, and antiviral efficacy, include: echinacea, golden
seal, benzalkonium chloride, benzethonium chloride, iodine, grape
seed extract, pomegranate extract, green tea extract or
polyphenols, and the like, or combinations thereof, may be
included. Another suitable antimicrobial agent includes the class
of anthelmintics, such as metronidazole, to facilitate treatment
of, e.g., tricomona infection. Preferred antiviral agents include,
but are not limited to, acyclovir, tamvir, penciclovir, and the
like, and mixtures thereof. Preferred antibacterial agents include,
but are not limited to, triclosan, neomycin, polymyxin, bacitracin,
clindamycin, benzoyl peroxide, a tetracycline, a sulfa drug, a
penicillin, a quinolone, a cephalosporin, and mixtures thereof.
Preferred antifungal agents include, but are not limited to,
farnesol, econazole, fluconazole, clotrimazole, ketoconazole,
calcium or zinc undecylenate, undecylenic acid, butenafine
hydrochloride, ciclopirox olaimine, miconazole nitrate, nystatin,
sulconazole, terbinafine hydrochloride, and the like, and mixtures
thereof. Exemplary tetracyclines include doxycycline and
minocycline. An exemplary sulfa drug includes sulfacetamde. An
exemplary cephalosporin includes cephalexin (commercially available
as KEFLEX). Exemplary quinolones include the floxacins, such as
loemfloxacin, ofloxacin, and trovafloxacin. It should be readily
understood that any salts, isomers, pro-drugs, metabolites, or
other derivatives of these antimicrobial agents may also be
included as the antimicrobial agent in accordance with the
invention. The antimicrobial agent is typically present in an
amount from about 0.01 to 1.5 weight percent, preferably from about
0.1 to 1.2 weight percent, and more preferably from about 0.3 to 1
weight percent of the composition. The antimicrobial agent inhibits
the formation, and may further reduce, the presence of microbes
that cause redness, inflammation, and irritation of the skin.
Together, the acidic component, hydrogen peroxide, and
antimicrobial agent facilitate exfoliation of dead skin, cleanse
the skin, remove substances foreign to the skin, inhibit or reduce
the presence of microorganisms, and generally facilitate management
of skin conditions, such as seborrheic dermatitis, psoriasis,
folliculitis, rosacea, perioral dermatitis, acne, impetigo and
other inflammatory skin conditions, and the like.
[0040] In a preferred embodiment, the compositions further include
one or more of Arnica Montana (a healing herb); any vitamin A
source including retinyl palmitate or other retinyl esters,
retinoic acid, or Retinol; and Vitamin K. These components
facilitate the skin cleansing and management of skin conditions
accomplished by the acidic component, hydrogen peroxide, and
antimicrobial agent. The Arnica Montana facilitates skin healing
and acts as an antiseptic and local anti-inflammatory, and, when
used, is typically present in an amount from about 0.1 to 2 weight
percent, preferably about 0.2 to 1 weight percent. The Retinol
facilitates normal skin production, particularly epidermal
normalization, and, when used, is typically present in an amount
from about 0.01 to 6 weight percent, preferably about 0.1 to 5
weight percent. The Vitamin K inhibits or suppresses inflammation
and bruising (i.e., acts as an anti-inflammatory and anti-bruising
agent) and, when used, is typically present in an amount from about
0.01 to 1 weight percent, preferably from about 0.1 to 0.5 weight
percent.
[0041] In a preferred embodiment, the compositions all contain one
or more surfactants, stabilizers, preservatives, moisturizers,
coloring agents, anti-inflammatory agents, anti-oxidants, water,
acids, bases, buffering agents, emulsifying agents, thickeners,
solvents, perfuming agents, and the like, and mixtures thereof. The
water used is preferably deionized water. It should be understood
that water includes the remainder of a given composition after
other ingredients are determined. Although any pharmaceutically
acceptable surfactant, stabilizer, preservative, moisturizer,
coloring agent, acids, bases, buffering agents, emulsifying agents,
thickeners, solvents, or perfuming agents may be used, certain
compounds or mixtures are preferred as discussed below.
[0042] Preferred surfactants, including both the foaming and
non-foaming type, include sodium laureth sulfate, sodium laureth-13
carboxylate, disodium laureth sulfosuccinate, disodium
cocoamphodiacetate, and the like, and mixtures thereof. More
preferably, at least one amphoteric surfactant is included in the
composition, such as disodium cocoamphodiacetate. The amphoteric
surfactant, in combination with citric acid, inhibits hydrogen
peroxide decomposition. The surfactant component may be present in
an amount from about 10 to 90 weight percent, preferably about 20
to 80, and more preferably about 30 to 70 weight percent of the
composition.
[0043] A preferred stabilizer includes glycol stearate or PEG-150
distearate. The stabilizer, when used, is typically present in an
amount from about 0.1 to 5 weight percent of the composition.
[0044] Preferred preservatives include tetrasodium ethylene-diamine
tetraacetic acid (EDTA), methylparaben, benzophenone-4,
methylchloroisothiazolinone, methylisothiazolinone, and the like,
and mixtures thereof. Preservatives, when used, are typically
present in an amount from about 0.01 to 6 weight percent,
preferably about 0.05 to 4 weight percent, and more preferably from
about 0.1 to 2 weight percent.
[0045] Preferred moisturizers include wheat protein (e.g.,
laurdimonium hydroxypropyl hydrolyzed wheat protein), hair keratin
amino acids, sodium peroxylinecarbolic acid, panthenol, tocopherol
(Vitamin E), dimethicone, and the like, and mixtures thereof.
Sodium chloride may also be present, particularly when hair keratin
amino acids are included as a moisturizer. Moisturizers, when used,
are typically present in an amount from about 0.01 to 2 weight
percent, preferably about 0.05 to 1.5 weight percent, more
preferably from about 0.1 to 1 weight percent of the
composition.
[0046] Preferred coloring agents include FD&C Green No. 3, Ext.
D&C Violet No. 2, FD&C Yellow No. 5, FD&C Red No. 40,
and the like, and mixtures thereof. The coloring agents, when used,
are typically present in an amount from about 0.001 to 0.1 weight
percent, and preferably from about 0.005 to 0.05 weight percent of
the composition.
[0047] Preferred anti-inflammatory agents include any
pharmaceutically acceptable compounds suitable for administration
orally or topically, preferably at least one of aloe vera gel, aloe
vera, licorice extract, pilewort, Canadian willow root, zinc, or
allantoin, more preferably allantoin. The anti-inflammatory agents,
when present, are used in an amount sufficient to inhibit or reduce
inflammation, preferably in an amount from about 0.1 to 2 weight
percent, preferably from about 0.3 to 1.5 weight percent, and more
preferably from about 0.3 to 1 weight percent of the composition.
It should be understood, with reference to managing skin
conditions, that the anti-inflammatory agents facilitate inhibition
or suppression of inflammation anywhere on the skin.
[0048] Anti-oxidants of both the enzymatic and non-enzymatic type
may be included in the compositions and methods of the invention.
For example, superoxide dismutase (SOD), catalase, and glutathione
peroxidase are natural enzymatic anti-oxidants used by the body
that may be supplemented with the compositions herein. Suitable
non-enzymatic anti-oxidants include such as Vitamin E (e.g.,
tocopherol), Vitamin C (ascorbic acid), carotenoids, Echinacoside
and caffeoyl derivatives, oligomeric proanthocyanidins or
proanthanols (e.g., grape seed extract), silymarin (e.g., milk
thistle extract, Silybum marianum), ginkgo biloba, green tea
polyphenols, and the like, and mixtures thereof. Carotenoids are
powerful anti-oxidants, and they include beta-carotene,
canthaxanthin, zeaxanthin, lycopen, lutein, crocetin, capsanthin,
and the like. Indeed, any pharmaceutically acceptable compounds
suitable for administration orally or topically may be used as an
anti-oxidant in the compositions. Preferably, the anti-oxidant
component includes Vitamin E, Vitamin C, or a carotenoid. The
anti-oxidant component, when used, is present in an amount
sufficient to inhibit or reduce the effects of free-radicals at the
scalp. The anti-oxidant component may be present in an amount from
about 0.001 to 1 weight percent, preferably from about 0.01 to 0.5
weight percent of the composition.
[0049] The ranges of the components of the pharmaceutical
composition may vary, but the active ingredients should be
understood to add to 100 weight percent of the active
pharmaceutical composition.
[0050] The term "therapeutically effective amount" means that
amount of the pharmaceutical composition that provides a
therapeutic benefit in the treatment, prevention, or management of
one or more skin conditions.
[0051] The magnitude of a prophylactic or therapeutic dose of the
composition in the acute or chronic management of skin conditions
will vary with the severity of the condition to be treated and the
route of administration. The dose, and perhaps the dose frequency,
will also vary according to the age, body weight, and response of
the individual patient. In general, a preferred topical daily dose
range, in single or divided doses, for the conditions described
herein should be from about 1 mg to 20,000 mg, more preferably
about 2,000 mg to 16,000 mg, and most preferably about 6,000 mg to
10,000 mg of the active components (i.e., excluding excipients and
carriers).
[0052] Those of ordinary skill in the art will also understand that
topical effectiveness of pharmaceuticals requires percutaneous
absorption and bioavailability to the target site. Thus, the
compositions and methods of the invention require penetration
through the stratum corneum into the epidermal layers, as well as
sufficient distribution to the sites targeted for pharmacologic
action.
[0053] It is further recommended that children, patients aged over
65 years, and those with impaired renal or hepatic function
initially receive low doses, and that they then be titrated based
on individual response(s) or blood level(s). It may be necessary to
use dosages outside these ranges in some cases, as will be apparent
to those of ordinary skill in the art. Further, it is noted that
the clinician or treating physician will know how and when to
interrupt, adjust, or terminate therapy in conjunction with
individual patient response.
[0054] The term "unit dose" is meant to describe a single dose,
although a unit dose may be divided, if desired. About 1 to 2 unit
doses of the present invention are typically administered per day,
preferably about 1 dose per day.
[0055] Any suitable route of administration may be employed for
providing the patient with an effective dosage of the composition
according to the methods of the present invention, including oral,
intraoral, rectal, parenteral, topical, epicutaneous, transdermal,
subcutaneous, intramuscular, intranasal, sublingual, buccal,
intradural, intraocular, intrarespiratory, or nasal inhalation and
like forms of administration. Topical administration is generally
preferred for the compositions and methods of the invention.
Suitable dosage forms include dispersions, suspensions, solutions,
aerosols, sponges, cotton applicators, and the like, with topical
dosage forms such as shampoos being preferred.
[0056] The pharmaceutical compositions used in the methods of the
present invention include the active ingredients described above,
and may also contain pharmaceutically acceptable carriers,
excipients and the like, and optionally, other therapeutic
ingredients.
[0057] The term "pharmaceutically acceptable salt" refers to a salt
prepared from pharmaceutically acceptable non-toxic acids or bases
including inorganic or organic acids. Examples of such inorganic
acids are hydrochloric, hydrobromic, hydroiodic, sulfuric, and
phosphoric. Appropriate organic acids may be selected, for example,
from aliphatic, aromatic, carboxylic and sulfonic classes of
organic acids, examples of which are formic, acetic, propionic,
succinic, glycolic, glucoronic, maleic, furoic, glutamic, benzoic,
anthranilic, salicylic, phenylacetic, mandelic, embonic (pamoic),
methanesulfonic, ethanesulfonic, pantothenic, benzenesulfonic,
stearic, sulfanilic, algenic, and galacturonic. Examples of such
inorganic bases, for potential salt formation with the sulfate or
phosphate compounds of the invention, include metallic salts made
from aluminum, calcium, lithium, magnesium, potassium, sodium, and
zinc. Appropriate organic bases may be selected, for example, from
N,N-dibenzylethylenediamine, chloroprocaine, choline,
diethanolamine, ethylenediamine, meglumaine (N-methylglucamine),
and procaine.
[0058] The compositions for use in the methods of the present
invention may include components such as suspensions, solutions and
elixirs; aerosols; or other suitable carriers such as starches,
sugars, microcrystalline cellulose, diluents, granulating agents,
lubricants, binders, disintegrating agents, and the like, with the
topical preparations being preferred.
[0059] Because of its ease of administration, a cream, lotion, or
ointment represents the most advantageous topical dosage unit form,
in which case liquid pharmaceutical carriers may be employed in the
composition. These creams, lotions, or ointments, may be prepared
as rinse-off or leave-on products, as well as two stage treatment
products for use with other skin cleansing or managing
compositions. In a preferred embodiment, the compositions are
administered as a rinse-off product in a higher concentration form,
such as a gel, and then a leave-on product in a lower concentration
to avoid irritation of the skin. Each of these forms is well
understood by those of ordinary skill in the art, such that dosages
may be easily prepared to incorporate the pharmaceutical
composition of the invention.
[0060] Pharmaceutical compositions for use in the methods of the
present invention suitable for topical administration may be
presented as discrete units including aerosol sprays, each
containing a predetermined amount of the active ingredient, as a
powder, stick, or granules, as creams (e.g., a conditioner),
pastes, gels, lotions (e.g., a sunscreen), syrups, or ointments, on
sponges or cotton applicators, or as a solution or a suspension in
an aqueous liquid, a non-aqueous liquid, an oil-in-water emulsion,
or a water-in-oil liquid emulsion. Such compositions may be
prepared by any of the methods of pharmacy, but all methods include
the step of bringing into association the carrier(s) with the
active ingredient, which constitutes one or more necessary
ingredients. In general, the compositions are prepared by uniformly
and intimately admixing the active ingredient with liquid carriers
or finely divided solid carriers or both, and then, if necessary,
shaping the product into the desired presentation.
[0061] Other suitable dosage forms include tablets, troches,
capsules, patches, gel caps, magmas, lozenges, plasters, discs,
suppositories, nasal or oral sprays, and the like. When an oral
dosage unit form is used instead of the preferred topical dosage
form, tablets, capsules, and gel caps are preferred, in which case
solid pharmaceutical carriers may be employed. If desired, tablets
may be coated by standard aqueous or nonaqueous techniques.
[0062] In addition to the common dosage forms set out above, the
compound for use in the methods of the present invention may also
be administered by controlled release means and/or delivery devices
such as those described in U.S. Pat. Nos. 3,845,770; 3,916,899;
3,536,809; 3,598,123; and 4,008,719, the disclosures of which are
expressly incorporated herein by reference thereto.
[0063] For example, a tablet may be prepared by compression or
molding, optionally, with one or more accessory ingredients.
Compressed tablets may be prepared by compressing in a suitable
machine the active ingredient in a free-flowing form such as powder
or granules, optionally mixed with a binder, lubricant, inert
diluent, surface active or dispersing agent. Molded tablets may be
made by molding, in a suitable machine, a mixture of the powdered
compound moistened with an inert liquid diluent.
[0064] Desirably, each unit dose, e.g., gel, cream, or ointment,
contains from about 1 mg to 2,000 mg of the active ingredient,
preferably about 200 mg to 1,600 mg, and more preferably about 600
mg to 1,000 mg of the composition.
EXAMPLES
[0065] The invention is further defined by reference to the
following examples describing in detail the preparation of the
compound and the compositions used in the methods of the present
invention, as well as their utility. The examples are
representative, and they should not be construed to limit the scope
of the invention.
Example 1
Skin Cleanser Formulation
[0066] A pharmaceutical composition according to the invention may
be prepared for cleansing skin as set forth below: TABLE-US-00001
Ingredient Trade Name/Supplier % by Weight Part A Deionized Water
N/A 49.2 Trisodium Ethylene-Diamine- HAMP-ENE Na.sub.3T/Akzo Nobel
0.2 Tetraacetic Acid (EDTA) Sodium Laureth-13 SURFINE WLL/Finetex
10 Carboxylate Disodium Laureth MACKANATE EL/McIntyre 17
Sulfosuccinate Group Disodium Cocoamphodiacetate MONATERIC
CDX-38/Mona 11 PEG-150 Pentaerythrityl CROTHIX/Croda 1.5
Tetrastearate PEG-150 Distearate KESSCO PEG 6000 DS/Stepan .7
Methylparaben N/A 0.2 Part B Salicylic Acid Salicylic Acid, powder,
1.6 USP/Spectrum Citric Acid N/A 1.5 Triclosan IRGASAN DP300/Ciba
0.3 Part C PPG-26-Buteth-26, PEG-40 SOLUBILISANT LR1/Les 2
Hydrogenated Castor Oil Colorant Wackherr SA Fragrance (Parfum)
Fragrance - BELL #J7393/Bell 0.3 Flavors and Fragrances Menthol
Menthol Crystals, USP 0.1 Part D Butylene Glycol, Deionized
ACTIPHYTE OF BLACK 0.1 water, Black Cohosh SNAKEROOT BG50/Active
(Cimicifuga Racemosa) Extract Organics Butylene Glycol, Deionized
ACTIPHYTE OF JAPANESE 0.1 water, Camellia Oleifera GREEN TEA
BG50/Active Extract Organics Sodium Peroxylinecarbolic
AJIDEW-50/Ajinomoto 0.2 Acid (PCA) Cocamidopropyl PG-Dimonium
PHOSPHOLIPID PTC/Mona 1 Chloride Phosphate Part E Hydrogen Peroxide
Hydrogen Peroxide, 35% 3 solution, technical 100% HAMP-ENE
Na.sub.3T is commercially available from Akzo Nobel Inc. of Dobbs
Ferry, NY; SURFINE WLL is commercially available from Finetex, Inc.
of Elmwood Park, NJ; MACKANATE EL is commercially available from
McIntyre Group of University Park, IL; MONATERIC CDX-38 and
PHOSPHOLIPID PTC are commercially available from Mona Industries
Inc. of Patterson, NJ; CROTHIX is commercially available from Croda
Inc. of Parsippany, NJ; KESSCO PEG 600 DS is commercially available
from Stepan Co. of Northfield, IL; IRGASAN DP300 is commercially
available from Ciba Specialty Chemicals Corp. of Albemarle, NC;
SOLUBILISANT LR1 is commercially available from Les Colorant
Wackherr SA of St. Ouen L'Aumone, France; BELL #J7393 is
commercially available from Bell Flavors and Fragrances of
Northbrook, IL; ACTIPHYTE OF BLACK SNAKEROOT BG50 and ACTIPHYTE OF
JAPANESE GREEN TEA BG50 are commercially available from Active
Organics of Dallas, TX; and AJIDEW-50 is commercially available
from Ajinomoto USA Inc. of Teaneck, NJ.
[0067] Deionized water was metered into the processing tank and
mixing subsequently begun. The water was heated to 75.degree. C.
and the remainder of Part A was added and mixed until uniform. The
mixture was cooled to 60.degree. C. and the Part B ingredients were
added and mixed until uniform. The mixture was then cooled to
50.degree. C. In a separate vessel, Part C was premixed until
uniform and then added to the mixture of Parts A and B. Parts A, B,
and C were mixed until uniform and cooled to 40.degree. C. The Part
D ingredients were added and mixed until uniform, then cooled to
30.degree. C. Part E was added and mixed until uniform, resulting
in a colorless, clear, slightly viscous fluid having a pH at
25.degree. C. of between 4 to 4.5 and a viscosity between 3,000 to
4,000 cps (RVT: #4 @ 10 rpm @ 25.degree. C.).
Example 2
Advanced Acne Prone Skin Formulation
[0068] A pharmaceutical composition according to the invention may
be prepared for treating skin prone to acne as set forth below:
TABLE-US-00002 Ingredient Trade Name/Supplier % by Weight Part A
Deionized Water N/A 46.7 Hydroxyethylcellulose CELLOSIZE 1
QP52,000H/Amerchol Part B Tetrasodium Ethylene-Diamine- HAMP-ENE
220/Akzo Nobel 0.1 Tetraacetic Acid (EDTA) Butylene Glycol
1,3-butylene glycol/Ashland 5 Aloe Barbadensis Gel Aloe Vera Freeze
Dried 0.1 Powder 200:1/Aloe Methyl Gluceth-10 GLUCAM E-10/Amerchol
3 Witch Hazel (Hamamelis Witch Hazel Distillate, 14% 3 Virginiana)
Distillate Zinc Acetate Zinc Acetate, crystals, 0.5 USP/FCC Orange
(Citrus Aurantium NATURAL ORANGE 0.3 Dulcis) ExtractMethylparaben
EXTRACT #71689/ Flavurence Dipotassium Glycyrrhizate N/A 0.3
Lecithin, Tocopherol and OXYSOMES/Barnett 0.3 Magnesium Ascorbyl
Phosphate Palmitoyl GLYCOSPHERE PCO/Kobo 0.2 Hydroxypropyltrimonium
Amylopectin/Glycerin Crosspolymer, Lecithin, Grape (Vitis Vinifera)
Seed Extract Palmitoyl GLYCOSPHERE GT/Kobo 0.5
Hydroxypropyltrimonium Amylopectin/Glycerin Crosspolymer, Lecithin,
Camellia Sinensis Extract Epilobium Angustifolium Canadian
Willowherb Whole 0.5 Extract Extract (5% in water)/Fytokem Butylene
Glycol and Water and ACTIPHYTE OF ARNICA 0.5 Arnica Montana Extract
BG50/Active Organics Part C Alcohol (denatured) SD Alcohol 40-B,
Anhydrous/ 20 Salicylic Acid Salicylic Acid, powder, 1
USP/FCC/Spectrum Triclosan IRGASAN DP300/Ciba 0.4 Part D
PPG-5-Ceteth-20 PROCETYL AWS/Croda 1 PEG-40 Hydrogenated Castor
CREMOPHOR RH-40/BASF 0.6 Oil Retinol and Polysorbate 20 RETINOL
50C/BASF 0.1 Phytonadione N/A 0.1 Linoleic Acid EMERSOL 315/Henkel
0.3 Part E Glycolic Acid GLYPURE = 70% Glycolic 9 Acid/DuPont Part
F Deionized water N/A 2 Sodium Hydroxide Sodium Hydroxide, pellets,
2 USP/NF Part G Hydrogen Peroxide Hydrogen Peroxide, 35% 1.5
solution, technical 100% CELLOSIZE QP52,000H and GLUCAM E-10 are
commercially available from Amerchol Corp. of Edison, NJ; HAMP-ENE
220 is commercially available from Akzo Nobel Inc. of Dobbs Ferry,
NY; Aloe Vera Freeze Dried Powder 200:1 is commercially available
from Aloe Corp. of TX; OXYSOMES is commercially available from
Barnet Products Corporation of Englewood Cliffs, NJ; Canadian
Willowherb Whole Extract (5% in water) is commercially available
from Fytokem, Inc. of Saskatoon, SK CANADA; GLYCOSPHERE PCO and
GLYCOSPHERE GT are commercially available from Kobo Products Inc.
of South Plainfield, NJ; ACTIPHYTE OF ARNICA BG50 is commercially
available from Active Organics of Dallas, TX; PROCETYL AWS is
commercially available from Croda Inc. of Parsippany, NJ; CREMOPHOR
RH-40 and RETINOL 50C are commercially available from BASF
Corporation of Budd Lake, NJ; GLYPURE = 70% Glycolic Acid is
commercially available from DuPont of Wilmington, DE; EMERSOL 315
is commercially available from Henkel Corp. of Hoboken, NJ.
[0069] Deionized water was metered into the processing tank and
mixing subsequently begun. CELLOSIZE QP52,000H was sprinkled in,
heated to 70.degree. C., and mixed until clear and uniform. The
mixture was cooled to 40.degree. C. Part B ingredients were added
in the order above, with sufficient mixing after each ingredient
was added. The mixture was cooled to 25.degree. C. and premixed
Part C ingredients were added and mixed until uniform. In a
separate tank, Part D was heated to 40.degree. C. until the solids
were dissolved and then added to the batch of Parts A, B, and C.
The mixture was mixed until uniform, then Part E was added and
mixed until uniform. Premixed Part F was slowly added in increments
as needed to obtain the desired pH of 3.3 to 3.8 at 25.degree. C.,
then Part G was added and mixed until completely uniform. This
resulted in a straw-colored, clear to slightly hazy, slightly
viscous liquid having a pH @ 25.degree. C. of 3.3 to 3.8 and a
viscosity between 400 to 800 cps (RVT: #2 @ 10 rpm @ 25.degree.
C.).
Example 3
Skin Perfecting Lotion
[0070] A pharmaceutical composition according to the invention may
be prepared for treating skin as set forth below: TABLE-US-00003
Ingredient Trade Name/Supplier % by weight Part A Water (Aqua)
Deionized water 63.6 Carbomer CARBOPOL ULTREZ 10/ 0.3 B. F.
Goodrich Sclerotium Gum AMIGEL/Tri-K 0.6 Glycerin Glycerin
99.5%/Ashland 6.0 Butylene Glycol 1,3-butylene glycol/Ashland 6.0
Allantoin Allantoin/ISP 0.6 Panthenol DEXPANTHENOL/Roche 0.6
Tetrasodium EDTA HAMP-ENE 220/Akzo 0.2 Methylparaben
Methylparaben/Ueno 0.3 Sodium PCA AJIDEW-50/Ajinomoto 0.5 Part B
Dicapryl Maleate BERNEL ESTER DCM/Bernel 6.0 Squalene
PHYTOLANE/Barnet 0.8 Sorbitan Stearate ARLACEL 60/ICI 1.5 Stearic
Acid EMERSOL 132/Henkel 1.3 Dimethicone DOW CORNING 200, 350 0.8
cs./Dow Corning C12-C15 Alkyl Benzoate FINSOLV TN/Finetex 3.0
Cetearyl Alcohol and Ceteareth HEXOTOL D/Heterene 0.6 Propylparaben
Propylparaben/Ueno 0.2 Part C Water (Aqua) Deionized water 0.3
Triethanolamine Triethanolamine 99%/Ashland 0.3 Part D Orange
(Citrus Aurantium NATURAL ORANGE 0.3 Dulcis) Extract EXTRACT
#71689/Flavurence Diazolidinyl Urea GERMALL II/ISP 0.3 Glycolipids
and Hyaluronic Acid PHYTO/CER HA/Tri-K 0.3 Palmitoyl GLYCOSPHERES
PCO/Kobo 0.3 Hydroxypropyltrimonium Amylopectin/Glycerin
Crosspolymer and Lecithin and grape (Vitis Vinifera) Seed Extract
Palmitoyl GLYCOSPHERES GT/Kobo 0.3 Hydroxypropyltrimonium
Amylopectin/Glycerin Crosspolymer and Lecithin and Camellia
Sinensis Extract Propylene Glycol Propylene Glycol/Ashland 0.6
Algae Extract HAWAIIAN SEAPLANT 0.2 EXTRACT-J/Tri-K Lecithin and
Tocopherol and OXYSOMES/Barnet 0.6 Magnesium Ascorbyl Phosphate
Butylene Glycol and Honey ACTIPLEX 1072/Active 1.1 Extract (Mel)
and Meadowsweet Organics (Spiraea Ulmaria) Extract Talc and C9-C13
Fluoroalcohol PF-5 TALC JA-46R/Kobo 0.8 and Phosphoric Acid
Hydrolyzed Soy Flour RAFFERMINE/R.I.T.A. 0.3 Oat (Avena Sativa)
Protein REDUCTINE/R.I.T.A. 0.3 Phytonadione Phytonadione/Roche 0.01
Retinol and Polysorbate 20 RETINOL 50C/BASF 0.1 Epilobium
Angustifolium Extract Canadian Willowherb Whole 0.5 Extract (5% in
water)/Fytokem Arnica Montana Extract ACTIPHYTE OF ARNICA 0.5
BG50/Active Organics 100.0 CARPOL ULTREZ 10 is commercially
available from B.F. Goodrich Co. of Richfield, OH; AMIGEL,
PHYTO/CER and HAWAIIAN SEA PLANT EXTRACT are available from
Tri-K-Chemical of Fairview, MT; Allantoin and GERMALL II are
available from ISP Chemicals Inc. of Calvert City, KY; DEXPANTHENOL
and Phytonadione are available from Roche Holdings, Inc. of
Wilmington, DE; Methylparaben and Propylparaben are commercially
available from Ueno Fine Chemicals Inc. of New York, NY AJIDEW N-50
is commercially available from Ajinomoto USA Inc. of Teaneck, NJ;
BERNEL ESTER is commercially available from Bernel Chemical Co. of
Englewood, NJ; PHYTOLANE is commercially available from Barnet
Products Corporation of Englewood Cliffs, NJ; ARLACEL 60 is
commercially available from ICI Americas Inc. of Wilmington, DE;
EMERSOL 132 is commercially available from Henkel Corp. of Hoboken,
NJ; DOW CORNING 200, 350 cs. is commercially available from Dow
Corning Corp. of Auburn, MI; FINSOLV TN is commercially available
from Finetex Inc. of Elmwood Park, NJ; HETOXOL D is commercially
available from Heterene Chemical Co. of Paterson, NJ; NATURAL
ORANGE EXTRACT #71689 is commercially available from Flavurence
Corp. of Annandale, NJ; ACTIPLEX 1072 is commercially available
from Active Organics Inc. of Lewisville, TX; PF-5 TALC JA-46R is
commercially available from Kobo Products Inc. of South Plainfield,
NJ; RAFFERMINE and REDUCTINE are commercially available from RITA
Chemical Corp of East Northport, NY.
[0071] The Skin Perfecting Lotion was prepared by metering
deionized water into a processing tank and mixing at high speed.
CARBOPOL ULTREZ 10 was sprinkled in. When the CARBOPOL ULTREZ 10
was completely dispersed, AMIGEL was added and the mixture mixed
until smooth and uniform. The mixture was heated to 80.degree. C.,
the remaining Part A ingredients were added, and then mixed until
uniform. In a separate tank, the Part B ingredients were combined
and heated to 80.degree. C. until all the solids were completely
dissolved. Part B was added to Part A and the resulting batch was
mixed until uniform. Premixed Part C was added and the batch mixed
until homogeneous. The batch was cooled to 40.degree. C. and the
Part D ingredients were added and mixing continued until the
temperature of the mixture was 35.degree. C. The resulting Skin
Perfecting Lotion was a light beige, opaque, viscous lotion having
a pH at 25.degree. C. of 6.2 to 7.2 and a viscosity of 14,000 to
24,000 cps. (RVT: #5 @10 rpm @ 25.degree. C.).
Example 4
Acne Management Formula
[0072] A pharmaceutical composition according to the invention may
be prepared for managing acne as set forth below: TABLE-US-00004
Ingredients Trade Name/Supplier % by weight Part A Water (Aqua)
Deionized Water 56.8 Sclerotium Gum AMIGEL/Alban Muller 0.4
Disodium EDTA HAM-ENE NA.sub.2/Akzo 0.3 Allantoin Allantoin/ISP 0.2
Methylparaben Methylparaben/Ueno 0.3 Zinc Oxide 66 ZINC OXIDE 0.3
U.S.P./Whitaker, Clark & Daniels Part B Water (Aqua) Deionized
Water 10 Hydrolyzed Oat Flour and Oat RITAVENA 5/R.I.T.A. 2.8
Betaglucan Dicaprylyl maleate BERNEL ESTER DCM/Bernel 3 Glycerayl
Stearate and PEG- ARLACEL 165/ICI 3 100 Stearate Cetearyl Alcohol
and HEXOTOL D/Heterene 3 Ceteareth-20 Propylparaben
Propylparaben/Ueno 0.1 Part D Salicylic Acid Salicylic Acid,
powder, U.S.P.- 1.3 N.F./Spectrum Sulfur Sulfur, precipitated,
U.S.P.- 6.5 N.F./Spectrum Part E Water (Aqua) Deionized Water 3
Sodium Hydroxide Sodium Hydroxide, pellets, 0.1
U.S.P.-N.F./Spectrum Glycolic Acid GLYPURE 70% GLYCOLIC 6.5
ACID/DuPont Part F Orange (Citrus Aurantium ORANGE EXTRACT 1.1
Dulcis) Extract PRODUCT #61522/Sunkist Diazolidinyl Urea GERMALL
II/ISP 0.4 Dipotassium Glycyrrhizate Dipotassium 0.3
Glycyrrhizinate/Int'l Sourcing Lecithin and Tocopherol and
OXYZOMES/Barnett 0.3 Magnesium Ascorbyl Phosphate Palmitoyl
GLYCOSPHERES PCO/Kobo 0.3 Hydroxypropyltrimonium
Amylopectin/Glycerin Crosspolymer and Lecithin and Grape (Vitis
Vinifera) Seed Extract 100.0 AMIGEL is commercially available from
Alban Muller International of Vincennes, France; HAM-ENE NA.sub.2
is commercially available from Akzo Chemicals Inc. of Deer Park,
TX; 66 ZINC OXIDE U.S.P. is commercially available from Whitaker,
Clark & Daniels of South Plainfield, NJ; Salicylic Acid,
powder, U.S.P.-N.F., Sulfur, precipitated, U.S.P.-N.F. and Sodium
Hydroxide, pellets, U.S.P.-N.F. are commercially available from
Spectrum Mfg. Corp of New Brunswick, NJ; ORANGE EXTRACT PRODUCT
#61522 is commercially available from Sunkist Growers, Inc. of Van
Nuys, CA; Dipotassium Glycyrrhizinate is commercially available
from International Sourcing Inc. of Upper Saddle River, NJ.
[0073] The Acne Management Formula was prepared by metering
deionized water into a processing tank and mixing at high speed.
AMIGEL was sprinkled in. When the AMIGEL was completely dispersed,
the mixture was heated to 85.degree. C. and the remaining Part A
ingredients were added and the mixture mixed well after each
addition. In a separate tank, Part B was heated to 100.degree. C.,
mixed until smooth, cooled to 80.degree. C. and added to the batch.
The resulting batch was mixed well. In another tank, the Part C
ingredients were heated to 75.degree. C. When all the solids
dissolved, Part C was added to the batch, the batch was mixed until
smooth and uniform, and the batch cooled to 50.degree. C. Part D
ingredients were added to the batch, the batch was homogenized for
5 to 10 minutes until the batch was smooth and uniform, and the
batch was cooled to 40.degree. C. The deionized water of part E was
premixed with the sodium hydroxide pellets and the resulting
solution was mixed well until all solids were dissolved. While
mixing the solution, glycolic acid was slowly added in increments
and the solution was mixed until homogeneous. The solution was
added to the batch and the Part F ingredients were added to the
batch. The batch was mixed and cooled to 35.degree. C. The Acne
Management Formula was a light yellow, opaque smooth lotion having
a pH at 25.degree. C. of 3.8 to 4.8 and a viscosity of 10,000 to
2,000 cps. (RVT: #5 @10 rpm @ 25.degree. C.).
Example 5
Clarifying Skin Cleanser
[0074] A pharmaceutical composition according to the invention may
be prepared for managing acne as set forth below: TABLE-US-00005
Ingredients Trade Name/Supplier % by weight Part A Water (Aqua)
Deionized Water 48.5 Sodium Lauroyl Oat Amino PROTEOL O.A.T./Seppic
2 Acid Decyl Glucoside ORAMIX NS-10/Seppic 3 Cocamidopropyl Betaine
AMPHOSOL CA/Stephan 12.5 Disodium Laureth MACKANATE EL/McIntyre 24
Sulfosuccinate PEG-120 Methyl Glucose GLUCAMATE DOE- 3.5 Dioleate
120/Amerchol Methylparaben Methylparaben/Ueno 0.2 PEG-150
Pentaerythrityl CROTHIX/Croda 0.25 Tetrastearate Part B Salicylic
Acid Salicylic Acid, powder, 2 USP/Spectrum Tetrasodium EDTA
HAMP-ENE-100/Akzo 0.3 Triclosan IRGASAN D300/Ciba Specialty 0.2
Chemicals Part C PPG-26-Buteth-26 and PEG SOLUBILISANT LRI/ 2
40Hydrogenated castor Oil Whittaker, Clark & Daniels Fragrance
Fragrance-BELL #J7393/Bell 0.3 Menthol Menthol Crystals, USP/ 0.1
Spectrum Part D Butylene Glycol and water ACTIPHYTE OF BLACK 0.2
(aqua) and Black Cohosh SNAKEROOT BG50/Active (Cimicifuga Racemosa)
Extract Organics Butylene Glycol and water ACTIPHYTE OF JAPANESE
0.2 (aqua) and Camellia Oleifera GREEN TEA BG50/Active Extract
Organics Sodium PCA AJIDEW N-50/Ajinomoto 0.4 Imidazolidinyl Urea
GERMALL 115/ISP 035 100.0 PROTEAL O.A.T. is commercially available
from Seppic Inc. of Fairfield, NJ; AMPHOSOL CA is commercially
available from Stephan Co. Inc. of Fort Lauderdale, FL; GLUCAMATE
DOE-120 is commercially available from Amerchol Corp. of Edison,
NJ; HAMP-ENE-100 is commercially available from Akzo Nobel Inc. of
Dobbs Ferry, NY; SOLUBILISANT LRI is commercially available from
Whitaker, Clark & Daniels of South Plainfield, NJ; GERMALL 115
is commercially available from ISP Chemicals Inc. of Calvert City,
KY.
[0075] The Clarifying Skin Cleanser was prepared by metering
deionized water into a processing tank, mixing, and heating to
75.degree. C. The part A ingredients were added and mixed until all
the solids dissolved. The resulting mixture was cooled to
60.degree. C. In a separate vessel the Part B ingredients were
combined. The Part B ingredients were then added to Part A and the
resulting batch was mixed until uniform. The resulting mixture was
cooled to 50.degree. C. In a separate vessel the Part C ingredients
were mixed until uniform. The part C ingredients were added to the
batch and the resulting batch was mixed until uniform. The batch
was cooled to 40.degree. C. and the part D ingredients were added
and mixing continued until uniform followed by cooling to
30.degree. C. The Clarifying Skin Cleanser Formula was a pale
yellow, slightly viscous liquid having a pH at 25.degree. C. of 4.5
to 5.5 and a viscosity of 5,000 to 9,000 cps. (RVT: # @10 rpm @
25.degree. C.).
Example 6
Antimicrobial Effectiveness of the Invention--Advanced Acne Prone
Skin Formulation
[0076] Culture Preparation
[0077] Escherichia coli (ATCC # 8739), Staphylococcus pureus (ATCC
# 6533), Pseudomonas aeruginosa (ATCC # 9027) were each propagated
in Trypicase Soy Broth (TSB) at 35.degree. C. for 24 hrs. Candida
albicans (ATCC # 10231), and Aspergillus niger (ATOC # 16404) were
propagated in Yeast and Mold Broth (YM) at 24.degree. C. for 72 h.
One loop of each bacteria culture was streaked onto Trypticase Soy
Agar (TSA) and the yeast and mold onto Sabouraud Dextrose Agar
(SDA). The bacterial and yeast cultures were incubated for 24 h at
35.degree. C. and 48 h at 24.degree. C., respectively. The mold
culture was incubated for 5 days at 24.degree. C. Following
appropriate incubation, the surface growth of the organisms were
washed with sterile Saline TS. Additional saline was added to
reduce the microbial count. Each respective cell suspension was
further diluted with sterile saline TS to an appropriate
concentration.
[0078] Product Inoculation
[0079] Five 20-g portions of the Advanced Acne Prone Skin Formula
of Example 2 was aseptically placed into sterile bottles. Each
bottle was independently inoculated with 0.1 mL of the inoculum
suspension.
[0080] Target Inoculation Concentration
[0081] A final concentration of 10.sup.5 and 10.sup.6 cfu/g of
product was obtained. This spike suspension was assayed for each
respective organism to determine the initial microbial load in the
product. All enumeration analyses were performed by preparing
serial 10-fold dilutions in Butterfield's Phosphate Buffered
Diluent (BPBD), and then plated using the pour plate technique on
respective media.
[0082] Test Intervals
[0083] An enumeration of the target organisms were performed on
each inoculum. Immediately after inoculation (less than 1 minute),
each product was assayed to determine the density of viable target
organisms according to the pour plate technique. Each sample was
tested again after 2 and 4 minutes. A 1-g portion was removed and
mixed with 9.9 mL of BPBD. Serial dilutions were prepared as
appropriate. Test samples containing bacterial cultures were plated
with TSA and incubated for 48 h at 35.degree. C. Samples containing
yeast and mold were plated with SDA and incubated for 5 days at
24.degree. C.
[0084] Results
[0085] The following results were obtained for each of the five
organisms. [0086] Test Organism: Candida albicans (ATOC #
10231)
[0087] Theoretical Inoculum Level: 400,000 cfu/g TABLE-US-00006
Testing Schedule Recovery Levels (cfu/g) (Time: minutes) Advanced
Acne Prone Skin Formula 0 (less than 1) <10 2 <10 4
<10
[0088] Test Organism: Aspergillus niger (ATCC # 16404)
[0089] Theoretical Inoculum Level: 160,000 cfu/g TABLE-US-00007
Testing Schedule Recovery Levels (cfu/g) (Time: minutes) Advanced
Acne Prone Skin Formula 0 (less than 1) <10 2 <10 4
<10
[0090] Test Organism: Escherichia coli (ATCC # 8739)
[0091] Theoretical Inoculum Level: 1,000,000 cfu/g TABLE-US-00008
Testing Schedule Recovery Levels (cfu/g) (Time: minutes) Advanced
Acne Prone Skin Formula 0 (less than 1) <10 2 <10 4
<10
[0092] Test Organism: Staphylococcus aureus (ATCC # 6538)
[0093] Theoretical Inoculum Level: 700,000 TABLE-US-00009 Testing
Schedule Recovery Levels (cfu/g) (Time: minutes) Advanced Acne
Prone Skin Formula 0 (less than 1) <10 2 <10 4 <10
[0094] Test Organism: Pseudomonas aeruginosa (ATCC # 9027)
[0095] Theoretical Inoculum Level: 260,000 TABLE-US-00010 Testing
Schedule Recovery Levels (cfu/g) (Time: minutes) Advanced Acne
Prone Skin Formula 0 (less than 1) <10 2 <10 4 <10
[0096] Discussion and Conclusion
[0097] The Advanced Acne Prone Skin Formulation prepared according
to the present invention exhibited excellent antimicrobial
properties. In less than one minute there was greater than a 99.99%
reduction in levels of Candida albicans, Escherichia coli,
Staphylococcus aureus, Pseudomonas aeruginosa, and Aspergillus
niger.
Example 7
Antimicrobial Effectiveness of Another Formulation of the
Invention--Clarifying Skin Cleanser
[0098] Culture Preparation
[0099] Escherichia coli (ATCC # 8739), Staphylococcus pureus (ATCC
# 6533), and Pseudomonas aeruginosa (ATCC # 9027) were propagated
in Trypicase Soy Broth (TSB) at 35.degree. C. for 24 h. Candida
albicans (ATCC # 10231) and Aspergillus niger (ATOC # 16404) were
propagated in Yeast and Mold Broth (YM) at 24.degree. C. for 72 h.
One loop of each bacteria culture was streaked onto Trypticase Soy
Agar (TSA) and the yeast and mold onto Sabouraud Dextrose Agar
(SDA). The bacterial and yeast cultures were incubated for 24 h at
35.degree. C. and 48 h at 24.degree. C., respectively. The mold
culture was incubated for 5 days at 24.degree. C. Following
appropriate incubation, the surface growth of the organisms were
washed with sterile Saline TS. Additional saline was added to
reduce the microbial count. Each respective cell suspension was
further diluted with sterile saline TS to an appropriate
concentration.
[0100] Product Inoculation
[0101] Five 20-g portions of the Clarifying Skin Cleanser of
Example 1 was aseptically placed into sterile bottles. Each bottle
was independently inoculated with 0.1 mL of the inoculum
suspension.
[0102] Target Inoculation Concentration
[0103] A final concentration of 10.sup.5 and 10.sup.6 cfu/g of
product was obtained. This spike suspension was assayed for each
respective organism to determine the initial microbial load in the
product. All enumeration analyses were performed by preparing
serial 10-fold dilution's in Butterfield's Phosphate Buffered
Diluent (BPBD), and then plated using the pour plate technique on
respective media.
[0104] Test Intervals
[0105] An enumeration of the target organisms were performed on
each inoculum. Immediately after inoculation (less than 1 minute),
each product was assayed to determine the density of viable target
organisms according to the pour plate technique. Each sample was
tested again after 2 and 4 minutes. A 1-g portion was removed and
mixed with 9.9 mL of BPBD. Serial dilutions were prepared as
appropriate. Test samples containing bacterial cultures were plated
with TSA and incubated for 48 h at 35.degree. C. Samples containing
yeast and mold were plated with SDA and incubated for 5 days at
24.degree. C.
[0106] Results
[0107] The following results were obtained for each of the five
organisms. [0108] Test Organism: Candida albicans (ATOC #
10231)
[0109] Theoretical Inoculum Level: 400,000 cfu/g TABLE-US-00011
Testing Schedule Recovery Levels (cfu/g) (Time: minutes) Clarifying
Skin Cleanser 0 (less than 1) 25,000 2 20,000 4 14,000
[0110] Test Organism: Aspergillus niger (ATCC # 16404)
[0111] Theoretical Inoculum Level: 160,000 cfu/g TABLE-US-00012
Testing Schedule Recovery Levels (cfu/g) (Time: minutes) Clarifying
Skin Cleanser 0 (less than 1) 1,400 2 1,200 4 1,000
[0112] Test Organism: Escherichia coli (ATCC # 8739)
[0113] Theoretical Inoculum Level: 1,000,000 cfu/g TABLE-US-00013
Testing Schedule Recovery Levels (cfu/g) (Time: minutes) Clarifying
Skin Cleanser 0 (less than 1) <10 2 <10 4 <10
[0114] Test Organism: Staphylococcus aureus (ATCC # 6538)
[0115] Theoretical Inoculum Level: 700,000 TABLE-US-00014 Testing
Schedule Recovery Levels (cfu/g) (Time: minutes) Clarifying Skin
Cleanser 0 (less than 1) <10 2 <10 4 <10
[0116] Test Organism: Pseudomonas aeruginosa (ATCC #9027)
[0117] Theoretical Inoculum Level: 260,000 TABLE-US-00015 Testing
Schedule Recovery Levels (cfu/g) (Time: minutes) Clarifying Skin
Cleanser 0 (less than 1) <10 2 <10 4 <10
[0118] Discussion and Conclusion
[0119] The Clarifying Skin Cleanser exhibited excellent
antimicrobial properties. In less than one minute there was a
>99.99% reduction in levels of Escherichia coli, Staphylococcus
aureus, and Pseudomonas aeruginosa. In less than one minute, levels
of Aspergillus niger and Candida albicans were reduced by 99.1% and
94.0%, respectively.
Example 8
Irritation Test Using the Invention
[0120] Irritation potential following epidermal contact by
compositions prepared according to the invention was examined.
Fifty-three subjects ranging from 18 to 77 were evaluated. The
patients were administered 0.2 mL, or an amount sufficient to cover
the upper back between the scapulae, of a 10 percent dilution of
the formulation used in Example 2. The administration occurred by
applying the composition to a 1''.times.3/4'' absorbent pad portion
of an adhesive dressing, which was secured to the treatment site on
each patient. The test material remained in contact for a total of
48 hours, and the test sites were evaluated at that time and at 72
hours (24 hours later) for changes using a 6-point scale ranging
from no visible skin reaction up to severe erythema, possible
edema, vesiculation, bullae and/or ulceration. One test subject did
not complete the study. Observations indicated negative irritation
throughout the test interval, i.e. no visible skin reaction on a
single patient.
Example 9
Hydrogen Peroxide Stability Test
[0121] The formulations prepared according to Examples 1 of the
invention having hydrogen peroxide, citric acid, salicylic acid, an
antibacterial agent, and an amphoteric surfactant were heated to
between 40.degree. C. to 45.degree. C. for three months in an oven
test. The oxygen content of the formula which was assayed after the
stability test, showed no more than 3 weight percent loss of the
original hydrogen peroxide content. Such high stability provides an
improved composition having a long shelf-life without substantial
loss of efficacy.
Examples 10-12
Acne Treatment Regimen
[0122] An acne treatment regimen comprising Clarifying Cleanser,
Advanced Acne Prone Skin Formula, Skin Perfecting Lotion and Acne
Management Formula (Examples 1, 2, 3, and 4, respectively) was
administered to 15 subjects. Subjects were evaluated after 2 weeks
and 4 weeks use of the treatment regimen. Subjects were evaluated
for total facial lesions, skin hydration and overall appearance of
acne.
[0123] Testing of the Treatment Regimen
[0124] The acne treatment regimen comprising a ADVANCED ACNE PRONE
SKIN FORMULA, SKIN PERFECTING LOTION, ACNE MANAGEMENT FORMULA, and
CLARIFYING SKIN CLEANSER, prepared according to Examples 2, 3, 4,
and 5, respectively, was administered to 15 subjects who exhibited
a Grade 2-4 acne condition according to the grading scale provided
below:
[0125] 0: Facial skin need not be perfectly clear. A few scattered
comedones or papules may be present, but these should be visible
only on close examination.
[0126] 2: About one fourth of facial area is involved, with small
papules and large or small comedones. A few pustules or large
prominent papules may be present.
[0127] 4: About half of facial area is involved, with small papules
and large or small comedones. A few pustules or large prominent
papules are usually present. (If lesions are large, subject may
have Grade 4 severity, although less than half of facial area is
involved).
[0128] 6: About three-fourths of facial area is involved, with
papules and/or large open comedones. (Lesser facial area of
involvement is permissible if inflammatory lesions are large)
numerous pustules are usually present, some of which may be
large.
[0129] 8: Practically all of facial area is involved, with lesions.
Large prominent pustules are usually visible. Lesions are usually
highly inflammatory. Other types of acne (such as conglobata,
including sinus and cystic types).
[0130] On the first day of the study all subjects were acclimated
to ambient temperature and relative humidity for fifteen minutes.
After the equilibration period, a trained technician examined each
subject's face and recorded the number of inflammatory and
non-inflammatory lesions in each of six sections of the face. The
lesions of the six sections were totaled to obtain a global
assessment score for each subject. Clinical photographs were taken
in various poses for each subject and three Corneometer
measurements were taken.
[0131] Subjects were provided with the treatment regimen and were
given the following instructions for the treatment regimen:
[0132] CLARIFYING CLEANSER: Apply twice per day (once in the
morning and once in the evening). Pour a small amount into hand or
wash cloth. Apply to dampened face and neck. Massage gently into
full lather. Rinse thoroughly with warm water and pat dry. Follow
with ACNE PRONE SKIN FORMULA.
[0133] ACNE PRONE SKIN FORMULA: Apply after cleansing twice per
daily (once in the morning and once in the evening). Apply a small
amount to face and neck or areas affected with acne. Follow with
SKIN PERFECTING LOTION.
[0134] SKIN PERFECTING LOTION: Use twice per day after cleansing
and treating skin. Apply a small amount to face and neck.
[0135] ACNE MANAGEMENT FORMULA: Use twice a day after using
CLARIFYING CLEANSER, ACNE PRONE SKIN FORMULA, and SKIN PERFECTING
LOTION. Apply a small amount to affected area to spot treat.
[0136] Subjects were required to maintain a daily diary indicating
date, time of use and comments. Subjects were permitted to use
their customary make-up products during the study. However,
subjects were instructed not to introduce any new cosmetic or
facial treatment products during the study. Following the two week
test material use period subjects were evaluated for an interim
count of total facial lesions, Comeometer readings and clinical
photographs. After four weeks of test material use subjects
returned with their diaries for a final lesion count, Comeometer
readings and clinical photographs. Standard paired t-tests were
used to determine statistically significant differences between
baseline and two (2) and four (4) week total facial lesion counts
and Corneometer readings. Statistical significance exists for all
p-values less than or equal to 0.05 at the 95% confidence level.
Improvement scores for the appearance of acne in clinical
photographs were analyzed using Z-tests.
[0137] A total of fourteen subjects finished the study. One subject
was disqualified immediately for lack of compliance with the
Inclusion Criteria of the protocol. A review of the daily diaries
indicated that four (4) subjects reported redness, burning,
stinging and/or "irritation" during the study period. One (1) of
the subjects reported the onset of redness and burning on day five
(5) of the study immediately after product application and lasting
for fifteen (15) to twenty (20) minutes. The subject was instructed
to discontinue test material use on day ten (10) of the study. On
day fourteen (14) the subject was examined by a doctor and no
evidence of skin irritation was observed. The subject was
instructed to begin use of the treatment material at this time. The
subject reported no evidence of irritation until day twenty four
(24) of the study and completed study participation. No evidence of
irritation was observed at the final visit. The subjects reaction
was diagnosed as dermatitis. The remaining subjects reported
symptoms following one (1) to two (2) uses of the test material and
completed study participation without further complaints.
Example 10
Total Lesion Count Following Treatment Regimen
[0138] The acne present on the skin of each subject was evaluated
by visual examination using the grading scale described herein. The
number of lesions on the face were counted at each visit. The
number of open and closed comedones, as well as papules and
pustules, were recorded. A global assessment score, the total of
all lesions, was recorded for each visit. Reductions in the global
assessment score are indicative of a reduced incidence and/or
severity of acne lesions. The data for total lesion count is
provided below. TABLE-US-00016 Total Lesion Count Baseline 2 Weeks
4 Weeks Mean 44.4 33.4 27.6 Mean Percent Difference from Baseline
-26% -40% .sigma. 30% 22%
[0139] The regimen showed a statistically significant decrease of
twenty-six percent (26%) in the number of lesions observed after
using the treatment regimen for two (2) weeks and a statistically
significant decrease of forty (40%) after using the treatment
regimen for four (4) weeks compared to baseline (p=0.02 and p=1.07
E-05, respectively).
Example 11
Photographic Evaluation Following Treatment Regimen
[0140] Photographs of subjects were taken at designated visits
using the Canfield Clinical System of imaging equipment. This
particular system permits comparison of photographs to be made with
the confidence that the only factors which may have changed are
those resulting from treatment. This is achieved by precisely and
reproducibly positioning the head of the subject and carefully
controlling the lighting, film type and processing. Photographs
were visually assessed and evaluated by a trained technician before
and after use of the test material. The following scoring scale was
used for visual assessment of the skin: [0141] 1=no improvement
[0142] 2=slight improvement [0143] 3=mild improvement [0144]
4=moderate improvement [0145] 5=extreme improvement
[0146] Improvement scores for the appearance of acne in clinical
photographs were analyzed using Z-tests. For the two (2) and four
(4) week scores, the number of subjects exhibiting improvements
scoring a two (2), three (3), four (4) or five (5) was compared to
the number of subjects exhibiting no improvement, scored as a one
(1). The improvement assessment of the overall appearance of acne,
rated from clinical photographs, is provided below. TABLE-US-00017
Photographic Evaluation Score: 1 2 3 4 5 Week 2 Number of Subjects
5 5 2 2 0 Assigned each Score Percentage 35.7% 64.3% Z-Score -1.12
Week 4 Number of Subjects 4 4 5 1 0 Assigned each Score Percentage
28.6% 71.4% Z-Score -1.77
[0147] The number of subjects exhibiting improvement from baseline
in the overall appearance of acne at two (2) weeks was greater than
subjects with no improvement. The Z-score obtained at two (2) weeks
corresponds to improved skin appearance having a statistical
significance at a 74% confidence level. In the four (4) week
photograph the number of subjects exhibiting improvement from
baseline in the overall appearance of acne was greater than
subjects with no improvement. The Z-score obtained at four (4)
weeks corresponds to improved skin appearance having statistical
significance at a 92% confidence level.
Example 12
Moisturization Via Corneometer Following Treatment Regimen
[0148] Changes in skin hydration were measured with a CORNEOMETER
which is a commercially available instrument (CM-820, Courage and
Khazaka Germany) designed to measure changes in the capacitance of
the skin resulting from small changes in the degree of hydration.
The CORNEOMETER expresses the capacitance of the skin in arbitrary
unit of skin hydration (H). The instrument is capable of measuring
the moisture of the stratum corneum to a depth of 0.1 mm and is
used to measure the effects of cosmetic preparations on the
moisture content of the skin. Tests using the CORNEOMETER were
conducted by taking 3 measurements, one at the right and left cheek
and one at the center of the skin, for each subject. The three
measurements were then averaged for each subject. The data for skin
hydration (H) is provided below. TABLE-US-00018 Skin Hydration (H)
Baseline 2 Weeks 4 Weeks Mean 70.8 51.6 49.5 Mean Percent
Difference from Baseline -26% -29% .sigma. 14% 12%
[0149] The regimen showed a statistically significant decrease in
Skin Hydration, H, of twenty-six percent (26%) after using the
treatment regimen for two (2) weeks and a statistically significant
decrease of twenty-nine (29%) after using the treatment regimen
four (4) weeks compared to baseline (p=2.27 E-05 and p=5.38 E-06,
respectively). A loss in skin hydration is typically observed
following treatment with anti-acne products.
Example 13
Skin Cleanser of Invention with Antifingal and Antibacterial
Agents
[0150] A pharmaceutical composition according to the invention may
be prepared for cleansing skin as set forth below: TABLE-US-00019
Ingredient Trade Name/Supplier % by Weight Part A Deionized Water
N/A 50 Trisodium Ethylene-Diamine- HAMP-ENE Na.sub.3T/Akzo Nobel
0.2 Tetraacetic Acid (EDTA) Sodium Laureth-13 SURFINE WLL/Finetex
10 Carboxylate Disodium Laureth MACKANATE EL/McIntyre 17
Sulfosuccinate Group Disodium Cocoamphodiacetate MONATERIC
CDX-38/Mona 11 PEG-150 Pentaerythrityl CROTHIX/Croda 1.5
Tetrastearate PEG-150 Distearate KESSCO PEG 6000 DS/Stepan 0.7
Methylparaben N/A 0.2 Part B Clotrimazole N/A 0.8 Citric Acid N/A
1.5 Triclosan IRGASAN DP300/Ciba 0.3 Part C PPG-26-Buteth-26,
PEG-40 SOLUBILISANT LR1/Les 2 Hydrogenated Castor Oil Colorant
Wackherr SA Fragrance (Parfum) Fragrance - BELL #J7393/Bell 0.3
Flavors and Fragrances Menthol Menthol Crystals, USP 0.1 Part D
Butylene Glycol, Deionized ACTIPHYTE OF BLACK 0.1 water, Black
Cohosh SNAKEROOT BG50/Active (Cimicifuga Racemosa) Extract Organics
Butylene Glycol, Deionized ACTIPHYTE OF JAPANESE 0.1 water,
Camellia Oleifera GREEN TEA BG50/Active Extract Organics Sodium
Peroxylinecarbolic AJIDEW-50/Ajinomoto 0.2 Acid (PCA)
Cocamidopropyl PG-Dimonium PHOSPHOLIPID PTC/Mona 1 Chloride
Phosphate Part E Hydrogen Peroxide Hydrogen Peroxide, 35% 3
solution, technical 100%
[0151] Deionized water was metered into the processing tank and
mixing subsequently begun. The water was heated to 75.degree. C.
and the remainder of Part A was added and mixed until uniform. The
mixture was cooled to 60.degree. C. and the Part B ingredients were
added and mixed until uniform. The mixture was then cooled to
50.degree. C. In a separate vessel, Part C was premixed until
uniform and then added to the mixture of Parts A and B. Parts A, B,
and C were mixed until uniform and cooled to 40.degree. C. The Part
D ingredients were added and mixed until uniform, then cooled to
30.degree. C. Part E was added and mixed until uniform, resulting
in a colorless, clear, slightly viscous fluid having a pH at
25.degree. C. of between 4 to 6 and a viscosity between 3,000 to
4,000 cps (RVT: #4 @ 10 rpm @ 25.degree. C.).
Example 14
Skin Cleanser of Invention with Antifungal and Antibacterial
Agents
[0152] A pharmaceutical composition according to the invention may
be prepared for cleansing skin as set forth below: TABLE-US-00020
Ingredient Trade Name/Supplier % by Weight Part A Deionized Water
N/A 50 Trisodium Ethylene-Diamine- HAMP-ENE Na.sub.3T/Akzo Nobel
0.2 Tetraacetic Acid (EDTA) Sodium Laureth-13 SURFINE WLL/Finetex
10 Carboxylate Disodium Laureth MACKANATE EL/McIntyre 17
Sulfosuccinate Group Disodium Cocoamphodiacetate MONATERIC
CDX-38/Mona 11 PEG-150 Pentaerythrityl CROTHIX/Croda 1.5
Tetrastearate PEG-150 Distearate KESSCO PEG 6000 DS/Stepan .7
Methylparaben N/A 0.2 Part B Ciclopirox Olamine N/A 0.8 Citric Acid
N/A 1.5 Triclosan IRGASAN DP300/Ciba 0.3 Part C PPG-26-Buteth-26,
PEG-40 SOLUBILISANT LR1/Les 2 Hydrogenated Castor Oil Colorant
Wackherr SA Fragrance (Parfum) Fragrance - BELL #J7393/Bell 0.3
Flavors and Fragrances Menthol Menthol Crystals, USP 0.1 Part D
Butylene Glycol, Deionized ACTIPHYTE OF BLACK 0.1 water, Black
Cohosh SNAKEROOT BG50/Active (Cimicifuga Racemosa) Extract Organics
Butylene Glycol, Deionized ACTIPHYTE OF JAPANESE 0.1 water,
Camellia Oleifera GREEN TEA BG50/Active Extract Organics Sodium
Peroxylinecarbolic AJIDEW-50/Ajinomoto 0.2 Acid (PCA)
Cocamidopropyl PG-Dimonium PHOSPHOLIPID PTC/Mona 1 Chloride
Phosphate Part E Hydrogen Peroxide Hydrogen Peroxide, 35% 3
solution, technical 100%
[0153] Deionized water was metered into the processing tank and
mixing subsequently begun. The water was heated to 75.degree. C.
and the remainder of Part A was added and mixed until uniform. The
mixture was cooled to 60.degree. C. and the Part B ingredients were
added and mixed until uniform. The mixture was then cooled to
50.degree. C. In a separate vessel, Part C was premixed until
uniform and then added to the mixture of Parts A and B. Parts A, B,
and C were mixed until uniform and cooled to 40.degree. C. The Part
D ingredients were added and mixed until uniform, then cooled to
30.degree. C. Part E was added and mixed until uniform, resulting
in a colorless, clear, slightly viscous fluid having a pH at
25.degree. C. of between 4 to 6 and a viscosity between 3,000 to
4,000 cps (RVT: #4 @ 10 rpm @ 25.degree. C.).
[0154] Various modifications of the invention in addition to those
shown and described herein will be apparent to those skilled in the
art from the foregoing description. Such modifications are also
intended to fall within the scope of the appended claims. The
foregoing disclosure includes all the information deemed essential
to enable those skilled in the art to practice the claimed
invention.
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