U.S. patent application number 12/967113 was filed with the patent office on 2011-11-10 for compositions comprising extracts of southernwood and an amine compound.
Invention is credited to Michael Anthonavage, Meghan Russell, Samantha Tucker-Samaras.
Application Number | 20110274776 12/967113 |
Document ID | / |
Family ID | 44902104 |
Filed Date | 2011-11-10 |
United States Patent
Application |
20110274776 |
Kind Code |
A1 |
Anthonavage; Michael ; et
al. |
November 10, 2011 |
COMPOSITIONS COMPRISING EXTRACTS OF SOUTHERNWOOD AND AN AMINE
COMPOUND
Abstract
The present invention relates to compositions comprising a
Southernwood extract and an amine compound, and methods treating
skin with said compositions.
Inventors: |
Anthonavage; Michael;
(Lebanon, NJ) ; Russell; Meghan; (Lawrenceville,
NJ) ; Tucker-Samaras; Samantha; ( Long Valley,
NJ) |
Family ID: |
44902104 |
Appl. No.: |
12/967113 |
Filed: |
December 14, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12775938 |
May 7, 2010 |
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12967113 |
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Current U.S.
Class: |
424/740 |
Current CPC
Class: |
A61K 31/132 20130101;
A61K 8/41 20130101; A61P 17/00 20180101; A61K 31/133 20130101; A61P
17/06 20180101; A61P 17/16 20180101; A61K 36/282 20130101; A61K
8/9789 20170801; A61Q 19/007 20130101; A61K 31/132 20130101; A61K
2300/00 20130101; A61K 31/133 20130101; A61K 2300/00 20130101; A61K
36/282 20130101; A61K 2300/00 20130101 |
Class at
Publication: |
424/740 |
International
Class: |
A61K 36/282 20060101
A61K036/282; A61P 17/00 20060101 A61P017/00; A61P 17/16 20060101
A61P017/16 |
Claims
1. A composition comprising a Southernwood extract and an amine
compound of formula I or formula II shown below: ##STR00004##
wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5
independently are selected from the group consisting of hydrogen,
C.sub.1-C.sub.6 alkyl, and C.sub.1-C.sub.6 hydroxyalkyl; or a
cosmetically-acceptable salt thereof.
2. The composition of claim 1, wherein the amine compound is an
amine compound of formula I.
3. The composition of claim 1, wherein the amine compound is
THPED.
4. The composition of claim 1, wherein said composition comprises
from about 0.5% to about 10% of said Southernwood extract.
5. The composition of claim 1, wherein said composition comprises
from about 0.25% to about 2.5% of said amine compound.
6. The composition of claim 1, wherein said composition comprises
from about 0.25% to about 2% of said amine compound.
7. The composition of claim 3, wherein said composition comprises
from about 0.5% to about 10% of said Southernwood extract and from
about 0.25% to about 2% of THPED.
8. The composition of claim 3, wherein said composition comprises
from about 0.5% to about 5% of said Southernwood extract and about
0.25% to about 2% of THPED.
9. The composition of claim 3, wherein said Southernwood extract
and said THPED are present in a weight ratio of about 0.5 to about
5.
10. A method of treating visibly dry skin, which comprises
topically applying to said visibly dry skin a composition
comprising a Southernwood extract and an amine compound of formula
I or formula II, shown below: ##STR00005## wherein R.sub.1,
R.sub.2, R.sub.3, R.sub.4, and R.sub.5 independently are selected
from the group consisting of hydrogen, C.sub.1-C.sub.6 alkyl, and
C.sub.1-C.sub.6 hydroxyalkyl; or a cosmetically-acceptable salt
thereof.
11. The method of claim 10, wherein said visibly dry skin is
xerotic skin.
12. The method of claim 10, wherein said skin is characterized by
an eczematic disease state.
13. The method of claim 10, wherein said skin is characterized by a
psoriatic disease state.
14. The method of claim 10, wherein said composition comprises from
about 0.5% to about 10% of said Southernwood extract.
15. The method of claim 10, wherein said amine compound is THPED.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation-in-part of U.S. Ser. No.
12/775,938 filed May 7, 2010. The complete disclosure of the
aforementioned application is hereby incorporated herein by
reference for all purposes.
FIELD OF THE INVENTION
[0002] The present invention relates to compositions comprising
extracts of Southernwood and an amine compound, as well as methods
of using these compositions. The compositions are useful, for
example for treating visibly dry skin.
BACKGROUND OF THE INVENTION
[0003] The top layer of human skin, the stratum corneum (SC)
consists of protein enriched corneocytes embedded in a lipid
matrix. The major function of the structure, as the body's
protective barrier to the environment that prevents the loss of
water and nutrients from within, is predominantly determined by the
levels, composition and structure of the SC lipids. The SC lipids
also influence the mechanical and desquamatory (skin cell shedding)
activities of the SC. Abnormalities in the SC lipids can occur in
connection with various conditions such as aged or photo damaged
skin, or in connection with xerosis (a condition of abnormal
dryness) such as during winter months.
[0004] Replenishing SC lipids by topical application of hydrophobic
compounds is an approach that has been used with limited success. A
longer lasting approach is to exploit the robust epidermal lipid
biosynthetic pathways of the viable epidermis using natural
extracts or compounds that upregulate the body's natural production
of these lipids, and particularly a class of critically important
SC lipids known as ceramides. Nicotinamide, for example, has been
reported to increase the synthesis of ceramides, major constituents
of lipids present as lamellar sheets in intercellular spaces of the
SC. Br. J. Dermatol. (2000 September) 143(3):524-31. In addition,
certain isomers of lactic acid are also reported to stimulate
ceramide biosynthesis. Arch. Dermatol. Res. (1996) 288:
383-390.
[0005] It is well recognized that ceramides are functionally and
structurally distinct from lipids that are present in deeper layers
(i.e., the hypodermis) of the skin. For example, while ceramides
are a class of polar lipids that play a role in cell membrane
structures to enhance skin barrier function, the deeper hypodermal
lipids are non-polar lipids whose function relates to energy
storage, thermal insulation, and protection of internal organs from
mechanical injury.
[0006] It has been reported that Southernwood extract is suitable
for "fat restructuring" and stimulating adipogenesis, presumably by
affecting the non-polar lipids of hypodermis. See US 2009/0285868
A1. Surprisingly, the inventors have now found that Southernwood
extract, acting on an entirely different biological pathway, is
suitable to enhance the biosynthesis of ceramides. Accordingly, the
inventors have found that Southernwood extracts are remarkably
suitable for treating completely different need states, and
completely different skin, than what is known in the art.
Specifically, the inventors have found that Southernwood extract is
surprisingly suitable for the topical treatment of visibly dry,
e.g., xerotic skin.
[0007] Furthermore, the inventors have now found that Southernwood
extracts, when combined with particular amine compounds, provide
surprisingly improved ability to enhance ceramide synthesis as well
as maintain hydration (water levels) in the upper layers of the
stratum corneum.
SUMMARY OF THE INVENTION
[0008] The present invention relates to a composition comprising a
Southernwood extract and an amine compound of formula I or formula
II shown below:
##STR00001##
wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5
independently are selected from the group consisting of hydrogen,
C1-C6 alkyl, and C1-C6 hydroxyalkyl; or a cosmetically-acceptable
salt thereof.
[0009] The compositions may be used to treating visibly dry skin.
Accordingly, in another aspect the invention relates to a method
for treating visibly dry skin. The method includes topically
applying to said skin, a composition comprising a Southernwood
extract and an amine compound described above.
[0010] Other features and advantages of the present invention will
be apparent from the detailed description of the invention and from
the claims.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0011] Unless defined otherwise, all technical and scientific terms
used herein have the same meaning as commonly understood by one of
ordinary skill in the art to which the invention pertains. Also,
all publications, patent applications, patents, and other
references mentioned herein are incorporated by reference. Unless
otherwise indicated, a percentage refers to a percentage by weight
(i.e., % (W/W). Unless stated otherwise, all ranges are inclusive
of the endpoints, e.g., "from 4 to 9" includes the endpoints 4 and
9.
[0012] As used herein, "visibly dry skin" refers to dry or
dehydrated skin that shows visible signs of flaking In certain
embodiments of the invention, visibly dry skin is characterized
clinically according to Rawlings et al., J. Soc. Cosmet. Chem. 45:
203-220 July/August 1994, in one or more of the following manners:
skin having small flakes of dry skin and whitening of
dermatoglyphic triangles (mild xerosis); skin having small, dry
flakes giving a light powdery appearance--corners of dermatoglyphic
triangles have started to uplift (moderate xerosis); or skin in
which the entire length of a number of dermatoglyphic triangles
have uplifted to generate large, dry skin flakes--roughness is very
evident (well-defined xerosis). In certain other embodiments of the
invention, the visibly dry skin has deficient levels of ceramides
in the stratum corneum.
[0013] In certain embodiments, the visibly dry skin may be, but is
not necessarily, classified as skin having compromised barrier
properties, or skin characterized by certain disease states such as
eczematic skin, psoriatic skin, or skin characterized by atopic
dermatitis. As used herein, "eczema" refers to a chronic skin
disorder that involves inflammation of the epidermis and often
presents as scaly and itchy rashes. As used herein, "atopic
dermatitis" refers to a type of chronically relapsing,
non-contagious and pruritic form of eczema. As used herein,
"psoriasis" refers to a chronic, non-infectious disease that
presents as red, scaly patches or plaques of excessive inflammation
or excessive skin production, often present on extensor surfaces
such as knees and elbows.
[0014] The visibly dry skin may be present on the face or body,
including the hands, feet, scalp, elbows, knees, ankles, nape of
the neck, among other areas of the body.
[0015] As used herein, "treating" refers to mitigating, reducing,
preventing, improving, or eliminating the presence or appearance of
a condition or disease.
[0016] As used herein, "cosmetic" refers to a beautifying substance
or preparation which preserves, restores, bestows, simulates, or
enhances the appearance of bodily beauty or appears to enhance
beauty or youthfulness, specifically as it relates to the
appearance of tissue or skin.
[0017] As used herein, "cosmetically acceptable" means suitable for
use in contact with (human) tissues (e.g., the skin) without undue
toxicity, incompatibility, instability, irritation, allergic
response, and the like, commensurate with a reasonable benefit/risk
ratio.
[0018] It is believed that one skilled in the art can, based upon
the description herein, utilize the present invention to its
fullest extent. The following specific embodiments are to be
construed as merely illustrative, and not limitative of the
remainder of the disclosure in any way whatsoever.
Southernwood Extract
[0019] As used herein the term "Southernwood" refers to plants of
the genus/species Artemesia arbrotaum. As used herein the term
"extract of Southernwood" or "Southernwood extract" refers to
extract obtained from one or more parts of the Southernwood plant
(e.g., flower, seed, root, rhizome, stem, fruit and/or leaf), which
may be optionally isolated. The Southernwood extract may for
example be prepared by finely dividing the harvested plant or parts
thereof, such as by crushing, grinding, or milling to a finely
divided solid or powder. The plant or portions thereof are
preferably contacted with a solvent, e.g., steam, water (that may
or not be heated), or other solvents, to extract portions
thereof.
[0020] In certain embodiments of the invention, the Southernwood
extract comprises a mixture of oligosaccharides. In certain
embodiments, the Southernwood extract comprises oligosaccharides
having a degree of polymerization of 1 to 4, and polyphenols. In
another embodiment, the Southernwood extract comprises
oligosaccharides having a degree of polymerization of 1 to 4,
proteins, and polyphenols. For example, the Southernwood extract
may have an actives content (i.e., the portion that excludes all
solvents employed in the extraction process) comprising about 1%
polyphenols, about 16% proteins, and about 83% saccharides having a
degree of polymerization of 1 to 4. The saccharides may comprise
monosaccharides, trisaccharides, and tetrasaccharides. In one
embodiment, the saccharides may include monosaccharides (e.g.,
about 54%), trisaccharides (about 12%), and tetrasaccharides (e.g.,
about 34%).
[0021] The amount of Southernwood extract in the composition may be
from about 0.5% to about 10% by weight of the composition,
preferably from about 0.5% to about 5%, more preferably from about
0.75% to about 5%, even more preferably from about 1% to about 4%,
and most preferably from about 2% to about 3%.
[0022] One particularly suitable Southernwood extract is
commercially available as PULPACTYL from Silab of France, which is
an aqueous-glycolic extract of Southernwood and includes water and
butylene glycol.
[0023] A suitable extraction process may comprise contacting one or
more parts of the Southernwood plant with a solvent system
comprising water and/or butylene glycol.
[0024] For example, the plant may be powdered and mixed in a
water/butylene glycol mixture, phase separated, filtered and
sterilized. See, e.g., FR2890312 A1.
Amine Compound
[0025] Compositions of the present invention include an amine
compound of formula I or formula II:
##STR00002##
wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5
independently are selected from the group consisting of hydrogen,
C1-C6 alkyl, and C1-C6 hydroxyalkyl; or a cosmetically-acceptable
salt thereof.
[0026] Examples of preferred amine compounds of formula I include,
but are not limited to,
N,N,N',N'-Tetrakis(2-hydroxypropyl)ethylenediamine (THPED),
N,N,N',N'-Tetrakis (2-hydroxyethyl)ethylene diamine (THEED), and
N,N,N',N'-tetramethylethylene diamine (TEMED), the structures of
which are set forth below, enantiomers thereof, diastereoisomers
thereof, and cosmetically-acceptable salts thereof
##STR00003##
[0027] In a preferred embodiment, the amine compound is THPED.
THPED is commercially available as NEUTROL TE from BASF.
[0028] The amount of the amine compound in the composition may be
from about 0.1% to about 10% by weight of the composition,
preferably from about 0.2% to about 5%, more preferably from about
0.25% to about 2.5%, and most preferably from about 0.5% to about
2%, by weight of the composition.
[0029] In certain embodiments of the invention, the weight ratio of
Southernwood extract to amine compound in the composition is from
about 0.3 to about 10, preferably from about 0.5 to about 5, more
preferably from about 1 to about 4, and most preferably from about
2 to about 3.
Topical Compositions
[0030] The Southernwood extract may be combined with one or more
cosmetically acceptable carriers to form a composition (e.g.,
formulation) suitable for use on visibly dry skin.
[0031] Suitable carriers of this invention include, but are not
limited to, water, as well as diols or polyols, such as those
having humectancy properties, including 1,2-propanediol, glycerin,
propylene glycol, butylene glycol, polyethylene glycol (PEG), and
combinations thereof. While in certain embodiments lower alcohols
such as ethanol and isopropanol may be included, in other
embodiments, in order to reduce likelihood of sky drying, these
alcohols are excluded from the composition (e.g., present in less
than 0.5%).
[0032] In order to facilitate treatment of visibly dry skin, in
certain embodiments of the invention the cosmetically acceptable
carrier includes both a humectant as well as an emollient. By
emollient it is meant cosmetic ingredients that are generally
insoluble in water and suitable for "leave on" applications for the
skin.
[0033] The emollient may include a hydrophobic moiety that meets
one or more of the following three criteria: (a) has a carbon chain
of at least six carbons in which none of the six carbons is a
carbonyl carbon or has a hydrophilic moiety (defined below) bonded
directly to it; (b) has two or more alkyl siloxy groups; or (c) has
two or more oxypropylene groups in sequence. The hydrophobic moiety
may include linear, cyclic, aromatic, saturated or unsaturated
groups. One skilled in the art will recognize that emollients do
not include amphiphilic molecules such as emulsifiers, surfactants
and other surface active compounds. Amphilphilic molecules that
will be understood to be excluded from emollients include those
compounds that include both (a) a hydrophobic moiety defined above,
and (b) a hydrophilic moiety, such as anionic, cationic,
zwitterionic, or nonionic group, that is polar, including sulfate,
sulfonate, carboxylate, phosphate, phosphonates, ammonium,
including mono-, di-, and trialkylammonium species, pyridinium,
imidazolinium, amidinium, poly(ethyleneiminium),
ammonioalkylsulfonate, ammonioalkylcarboxylate, amphoacetate,
hydroxyl, and poly(ethyleneoxy)sulfonyl. Emulsifiers, surfactants
and other surface active compounds are commonly used for
emulsification and wetting rather than for film-formation,
spreading and the like.
[0034] Examples of emollients include mineral oils/waxes, including
petrolatum; vegetable oils (glyceryl esters of fatty acids,
triglycerides), waxes, other fatty esters. Specific non-limiting
examples include, without limitation, isopropyl palmitate,
isopropyl myristate, dimethicone, shea butter, petrolatum, C12-C15
alkyl benzoates, caprylic/capric triglycerides, various vegetable
waxes, and mineral oil.
[0035] Various compounds may be included in the
cosmetically-acceptable carrier to alter osmolarity and/or pH to
acceptable levels. These include, but are not limited to sodium
chloride, sodium phosphate monobasic, sodium phosphate dibasic,
sodium hydroxide, and citric acid.
[0036] In order to facilitate the formulation of a suitable
cosmetically-acceptable carrier, one may include any of various
functional ingredients in the composition. For example, one may
include any of a number of sequesterants, emulsifiers, thickeners,
polymers, preservatives, colorants, fragrances, antioxidants, and
other ingredients commonly used in personal care and cosmetic
products. Suitable emulsifiers include, for example, non-ionic
emulsifiers such as fatty alcohols including polyethoxylated fatty
alcohols, esters of glycerol; anionic emulsifiers such as alkyl
phosphates; cationic emulsifiers such as alkyl quaternary ammonium
compounds. Suitable thickeners include hydrophobically modified
acrylic polymers, cellulose polymers and clays.
[0037] While in certain embodiments (in which the product is in the
form of a cleanser) cleansing surfactants such as betaines,
sulfates, sulfonates, polyglycosides, among other wetting agents
typically utilized for wetting and foam generation may be included,
in other embodiments, in order to reduce likelihood of skin drying
and to make the product suitable for a "leave-on" application,
cleansing surfactants are excluded from the composition.
[0038] The pH chosen is not critical, but may be in a range, for
example that is from about 4 to about 8, such as from about 5 to
about 7.
[0039] The cosmetically acceptable carrier in the topical
composition may constitute from about 40% to about 99.99%, by
weight, of the composition, more preferably from about 80% to about
95%, by weight, of the composition. In a particularly preferred
embodiment, the composition includes at least about 25% by weight
water, more preferably at least about 50% by weight water. In other
embodiments, the carrier (and the composition) is anhydrous. Such
anhydrous compositions may be suitable for, for example, lip
treatment products or color cosmetic (e.g., foundation).
[0040] In one embodiment, the compositions according to this
invention may further contain one or more additional cosmetically
active agent(s) as well as the above-mentioned components. What is
meant by a "cosmetically active agent" is a compound, which may be
a synthetic compound or a compound extracted, isolated, purified or
concentrated from a natural source, or a natural extract containing
a mixture of compounds, that has a cosmetic or therapeutic effect
on the tissue, including, but not limited to: anti-microbial agents
such as anti-yeast, anti-fungal, and anti-bacterial agents,
anti-inflammatory agents, anti-aging agents, depigmentaion agents,
anti-parasite agents, antioxidants, ant-acne agents, keratolytic
agents, nutrients, vitamins, minerals, energy enhancers,
sunscreens, sebum modulators, anti-cellulite agents and the
like.
[0041] Examples of vitamins that may be constituents of the
compositions of this invention include, but are not limited to,
vitamin A, vitamin Bs such as vitamin B3, vitamin B5, vitamin B7
and vitamin B12, vitamin C, vitamin K, vitamin E such as alpha,
gamma or delta-tocopherol, and their derivatives (such as salts and
esters) and mixtures thereof.
[0042] Examples of antioxidants which may be utilized in the
compositions and methods of this invention include, but are not
limited to, water-soluble antioxidants such as sulfhydryl compounds
and their derivatives (e.g., sodium metabisulfite and
N-acetyl-cysteine), lipoic acid and dihydrolipoic acid,
resveratrol, lactoferrin, and ascorbic acid and ascorbic acid
derivatives (e.g., ascorbyl palmitate and ascorbyl polypeptide).
Oil-soluble antioxidants suitable for use in the compositions of
this invention include, but are not limited to, butylated
hydroxytoluene, retinoids (e.g., retinol and retinyl palmitate),
different types of tocopherols (e.g., alpha-, gamma-, and
delta-tocopherols and their esters such as acetate) and their
mixtures, tocotrienols, and ubiquinone. Natural extracts containing
antioxidants suitable for use in the compositions of this invention
include, but are not limited to, extracts containing flavinoid,
isoflavinoid, and their derivatives such as genistein and diadzein
(e.g., such as soy and clover extracts, extracts containing
resveratrol and the like. The one or more additional cosmetically
active agent(s) may be present in any suitable concentration, such
as, for example from about 0.01% to about 10% by weight.
[0043] Examples of anti-aging agents that which may be utilized in
the compositions and methods of this invention include, but are not
limited to, retinoids (e.g., retinol and retinyl palmitate).
[0044] Other examples of anti-aging actives include copper
containing peptides; vitamins such as vitamin E, vitamin C, vitamin
B, and derivatives thereof such as vitamin E acetate, vitamin C
palmitate, and the like; antioxidants including beta carotene,
alpha hydroxy acids such as glycolic acid, citric acid, lactic
acid, malic acid, mandelic acid, ascorbic acid,
alpha-hydroxybutyric acid, pyruvic acid; beta hydroxy acids such as
beta-hydroxybutyric acid, beta-phenyl-lactic acid,
beta-phenylpyruvic acid; polyphenolics; botanical extracts such as
green tea, soy products, milk thistle, algae, aloe, angelica,
bitter orange, coffee, goldthread, grapefruit, hoellen,
honeysuckle, Job's tears, lithospermum, mulberry, peony, puerarua,
nice, safflower, and mixtures thereof.
[0045] Examples of suitable depigmentation agents include, but are
not limited to soy products, retinoids such as retinol; Kojic acid
and its derivatives such as, for example, kojic dipalmitate;
hydroquinone and it derivatives such as arbutin; transexamic acid;
vitamins such as niacin, vitamin C and its derivatives; azelaic
acid; placertia; licorice; extracts such as chamomile and green
tea, and mixtures thereof, with retinoids, Kojic acid, soy
products, and hydroquinone being particularly suitable
examples.
[0046] Examples of sebum inhibitors include, for example, licorice
root extracts, zinc salts such as zinc gluconate, dehydroacetic
acid, and glycine derivatives. Examples of anti-cellulite agents
include, for example, vasodilators such as green tea, and
caffeine.
[0047] The Southernwood extract, amine compound and cosmetically
acceptable topical carrier and optional additional cosmetically
active agents may be combined in any proportion to form a
composition suitable for topical use.
[0048] The composition may be formulated into any of various
product types including, but not limited to solutions, suspensions,
emulsions such as microemulsions and nanoemulsions, gels, solids
and liposomes. The compositions may be made into a wide variety of
cosmetic articles that include but are not limited to lotions,
creams, gels, sticks, sprays, ointments, cleansing liquid washes
and solid bars, pastes, foams, powders, mousses, wipes, strips,
patches, wound dressings and adhesive bandages, hydrogels,
film-forming products, as well as facial and skin masks. Other
forms can be formulated by those of ordinary skill in the art.
[0049] The compositions may be topically applied to mammalian skin,
preferably human skin. The skin may, in certain embodiments, be
visibly dry or xerotic mammalian skin in order to reduce xerosis
present on the face or body, including the hands, feet, scalp,
elbows, knees, ankles, nape of the neck, among other areas portions
of the skin.
[0050] In one embodiment, the compositions of the invention are
used to treat mildly xerotic skin. In another embodiment, the
compositions are used to treat moderately xerotic skin. In another
embodiment, the compositions are used to treat skin having
well-defined xerosis.
[0051] In certain other embodiments, topical compositions
comprising Southernwood extract are topically applied to skin
having compromised barrier properties, or skin characterized by
certain disease states such as eczematic skin, psoriatic skin, or
skin characterized by atopic dermatitis.
[0052] The compositions may be applied to the skin in need of such
treatment according to a suitable treatment regimen, e.g., every
month, every week, every other day, every day, twice a day, or the
like.
[0053] According to the invention, the composition treats visibly
dry skin by, inter alia, increasing the level of ceramides in such
skin.
[0054] In certain embodiments of the invention, the compositions
are applied to visibly dry skin in a manner sufficient to increase
the expression of glucosyl ceramide synthase in such skin when
tested according to the Gene Expression Test as described in
Example 3 in this specification. In one embodiment, the composition
is applied in a manner sufficient to increase the expression of
glucosyl ceramide synthase after 5 days of treatment by at least
10%, preferably at least 15%, more preferably at least 20%, and
most preferably at least 30%, as compared to the skin prior to such
treatment.
[0055] In another embodiment, compositions of the invention are
applied to skin having other need states, such as, for example, for
treating signs of skin aging. As used herein, "signs of skin aging"
includes the presence of lines and wrinkles, loss of elasticity,
uneven skin, and blotchiness. In a particularly preferred
embodiment, the sign of aging is the presence of lines and wrinkles
and/or loss of elasticity.
[0056] In another embodiment, compositions of the invention are
applied to skin in order to treat external aggressions in skin.
Examples of external aggressions include, but are not limited to,
damage to the skin from the use or cleansers (e.g., topical
cleansers containing surfactants), make-up, shaving as well as
environmental damage such as from UV light (e.g., sundamage from
sunlight or damage from non-natural sources such as UV lamps and
solar simulators), ozone, exhaust, pollution, chlorine and chlorine
containing compounds, and cigarette smoke. Effects of external
aggressions on the skin include, but are not limited to, oxidative
and/or nitrosative damage to and modifications on lipids,
carbohydrates, peptides, proteins, nucleic acids, and vitamins.
Effects of external aggressions on the skin also include, but are
not limited to, loss of cell viability, loss or alteration of cell
functions, and changes in gene and/or protein expression.
[0057] In another embodiment, compositions of the invention are
applied to skin in order to treat skin in need of reducing skin
inflammation. As used herein, "skin in need of reducing skin
inflammation" means a skin exhibiting redness or erythema, edema.
In certain other embodiments, "skin in need of reducing skin
inflammation" refers to skin that is particularly reactive or
sensitive to external elements. External elements include, but are
not limited to, sun rays (UV, visible, IR), microorganisms,
atmospheric pollutants such as ozone, exhaust pollutants, chlorine
and chlorine generating compounds, cigarette smoke, cold
temperature, heat. Inflammatory disorders and related conditions
which may be treated or prevented by use of the compositions of
this invention include, but are not limited to the following:
arthritis, bronchitis, contact dermatitis, atophic dermatitis,
psoriasis, seborrheic dermatitis, eczema, allergic dermatitis,
polymorphous light eruptions, inflammatory dermatoses,
folliculitis, alopecia, poison ivy, insect bites, acne
inflammation, irritation induced by extrinsic factors including,
but not limited to, chemicals, trauma, pollutants (such as
cigarette smoke) and sun exposure, secondary conditions resulting
from inflammation including but not limited to xerosis,
hyperkeratosis, pruritus, postinflammatory hyperpigmentation,
scarring and the like. Preferably, the inflammatory disorders and
related conditions which may be treated or prevented using the
methods of the invention are arthritis, inflammatory dermatoses,
contact dermatitis, allergic dermatitis, atopic dermatitis,
polymorphous light eruptions, irritation, including erythema
induced by extrinsic factors, acne inflammation, psoriasis,
seborrheic dermatitis, eczema, poison ivy, insect bites,
folliculitus, alopecia, and secondary conditions and the like.
[0058] It is believed that one skilled in the art can, based upon
the description herein, utilize the present invention to its
fullest extent. The following specific embodiments are to be
construed as merely illustrative, and not limitative of the
remainder of the disclosure in any way whatsoever. The following
non-limiting examples further illustrate the invention.
Example I
Inventive Composition with Extract of Southernwood and THPED Shows
Synergistic Moisturization
[0059] Composition 1 according to the invention was made using the
ingredients shown in Table 1.
TABLE-US-00001 TABLE 1 CONCENTRATION INGREDIENT CHEMICAL NAME (wt.
percent) WATER PHASE Deionized Water Water 83.00 Ultrez 10 Carbomer
0.60 Versene NA Disodium EDTA 0.20 Emery 917 Glycerin 3.00 OIL
PHASE Brij 72 Steareth-2 0.50 Brij 721 Steareth-21 1.00 Finsolv TN
C12-15 Alkyl Benzoate 2.00 Miglyol 812 Caprylic/capric triglyceride
2.50 POST ADDITIONS Dow Corning Dimethicone 2.00 Q7-9120 Fluid 20
cst Phenonip XB Phenoxyethanol (and) 1.00 Methylparaben (and)
Ethylparaben (and) Propylparaben Neutrol TE THPED 1.00 Sodium
Hydroxide Sodium Hydroxide q.s. Pulpactyl aqueous-glycolic extract
of 3.00 Southernwood Citric acid Citric acid 0.2
[0060] Composition 1 was prepared by adding water (Item#1) to a
beaker, and the vessel was heated to 55-60 C. Versene and Ultrez 10
were added and the temperature was held at 55-60 C while it was
mixed for 15 minutes or until homogeneous. In a separate vessel,
the oil phase ingredients were mixed and held at 55-65 C. The oil
phase was slowly added to the water phase. After the phases were
completely mixed, the mixture was allowed to cool. When the
temperature was below 50 C, dimethicone was added. Phenonip was
added when the temperature was below 40 C. The mixture was allowed
to mix for 10 minutes. Sodium hydroxide and/or citric acid was
added to a target pH of 5.4. The mixture was allowed to mix for 10
minutes. PULPACTYL (Southernwood extract) and THPED were added, and
the mixture was again allowed to mix for 10 minutes.
[0061] Comparative Composition A was prepared identically
Composition 1, but without PULPACTYL. Additional water was included
to compensate for the lack of PULPACTYL. Comparative Composition B
was similarly prepared, except without THPED. Comparative
Composition C (placebo) was also prepared the same way, except
without PULPACTYL or THPED.
[0062] Composition 1 and Comparative Compositions A, B and C were
tested for their ability to maintain skin hydration in the upper
layers of the stratum corneum as follows.
[0063] A skin conductance meter, a SKICON200EX with MT-8C probe
(available from I.B.S. Co. Ltd of Japan) that measures high
frequency conductance in the upper layers of the stratum corneum
level, was used as an indicator for degree of hydration.
[0064] Thirty human female subjects between the ages of 25 and 45
were evaluated for skin hydration on their legs, vertically from
the ankle bone, using the SKICON device. Baseline measurements were
performed prior to application of product.
[0065] A hand-held probe was placed on each of the two skin surface
locations to take measurements. The probe sampled conductance at
each surface location and measurements were taken in
triplicate.
[0066] The subjects washed their legs with JOHNSON'S HEAD TO TOE
BABY WASH daily for one week prior to the beginning of the study,
as well as during the entire term of the study. Each subject
applied either: Composition 1 to one leg and Comparative
Composition A to the other leg, or Comparative Composition B to one
leg and Comparative Composition C to the other leg. The test
materials were applied two times per day for 4 weeks. After 3 weeks
and after 4 weeks of treatment, SKICON measurements were again
taken.
[0067] The difference between the high frequency conductance during
one week of no product use following 4 weeks of product use (i.e.,
one week of regression) and the high frequency conductance at
baseline was calculated for each subject. The percentage of
subjects that showed a 10% or greater increase in high frequency
conductance (cf. surface hydration) after one week of regression
are shown in Table 2 below.
TABLE-US-00002 TABLE 2 Test Composition % of Subjects Composition 1
(THPED + Extract of Southernwood) 81.25* Composition A (THPED)
65.63 Composition B (extract of Southernwood) 55.17 Composition C
(neither extract of Southernwood, 58.62 nor THPED) *p < 0.05
compared to Comparative Example, Comp. 2
[0068] The statistical analytical method employed was a t-test with
a critical p value of 0.10. Composition 1 was also significantly
better (t-test p=0.09) over Composition C.
[0069] The above results suggest the combination of both extract of
Southernwood and THPED together provided surprisingly,
significantly better skin surface hydration than the other test
compositions after 4 weeks of treatment and 1 week of no product
use. Applicants have previously shown that Southernwood extract
improves skin barrier function and generates ceramides. However,
the combination of Southernwood extract and an amine compound
provides an additional, unexpected hydration benefit.
Example II
Inventive Composition with Extract of Southernwood and THPED Shows
Enhanced Ability to Produce Ceramides, In-Vivo
[0070] Composition 2 and Comparative Compositions D, E and F were
prepared in a similar manner to the compositions of Example 1,
except they included 0% rather than 3% glycerin, 5% rather than 2%
dimethicone, 0.75% rather than 0.5% of steareth-2, and 1.5% rather
than 1.0% of steareth-21.
[0071] Composition 2 was prepared according to the invention and
contained 1% THPED and 2% PULPACTYL. Comparative Composition D
contained 2% PULPACTYL, but no THPED. Comparative Composition E
contained 5% PULPACTYL, but no THPED. Comparative Composition F
(placebo) contained neither PULPACTYL nor THPED. As with Example I
above, additional water was included to compensate for the lack of
PULPACTYL or THPED as required.
[0072] Human female subjects between the ages of 25 and 45 were
evaluated for ceramide production. The subjects washed their legs
with JOHNSON'S HEAD TO TOE cleanser daily for one week prior to the
beginning of the study, as well as during the entire term of the
study. Each subject applied one test product per leg. The two test
materials were applied two times per day for 3 weeks. Composition 2
and Comparative Compositions D and E were used by five subjects.
Comparative Composition F was used by eight subjects. The test
compositions were applied on the subject's legs, vertically from
the ankle bone.
[0073] After 1 week and after 3 weeks of treatment, the treated
skin of the subjects was subjected to a conventional tape stripping
procedure to analyze for ceramide content. Tape strips were
extracted for 1 hour at room temperature with 8 mL of a
methanol:ethyl acetate mixture (80:20). After extraction, the tape
strips was discarded and the solvent was evaporated to dryness
under argon at room temperature. Thereafter, samples were stored at
-20.degree. C. until further analysis.
[0074] Each sample residue remaining after the tape strip
condensation step was dissolved in 200 uL of a chloroform:methanol
mixture (2:1). Twenty microliters and 40 uL of sample solution was
applied on a high performance thin layer chromatography (HPTLC)
plate (available from Whatman Partisil, GE Healthcare, Piscataway,
N.J.) using an automatic sampler (CAMAG Automatic TLC Sampler 4,
available from CAMAG Scientific Inc. of Wilmington, N.C.) and
separated using the following sequential development system: (1)
dichloromethane:ethyl acetate:acetone (80:16:4), (2)
chloroform:methanol:acetone (76:16:8), (3) hexane:chloroform:acetic
acid:acetone:methanol (6:80:0.1:10:4). The plates were stained with
3% copper acetate in 8% phosphoric acid and charred at 160.degree.
C.
[0075] Samples were applied in parallel for positional corrections
and compared to a similarly prepared blank extract (tape strip
without exposure to skin lipids). Quantification was performed
against known quantities of Ceramide III standard (Cosmoferm) by
densitometry. The calibration curve contained six concentrations of
ceramide III: 1 ug, 2 ug, 4 ug, 8 ug, 12 ug, and 16 ug.
[0076] Each HPTLC plate was scanned (Hewlett-Packard Scanjet 8250
from Hewlett-Packard of Houston, Tex.) and quantified using image
acquisition software (Image Pro 6.3 from MEDIA CYBERNETICS of
Silver Spring, Md. The optical density of each ceramide band was
measured and quantified against the standard calibration curve.
Where both sample levels, 20 uL and 40 uL, were inside the
linearity parameters of the calibration curve, an average of the
two values was reported. All results outside the standard linearity
parameters were disqualified. As one skilled in the art would
appreciate, the resulting optical density will correlate with the
amount of ceramide produced.
[0077] The results of the relative quantification of ceramide are
shown in Table 3.
TABLE-US-00003 TABLE 3 Optical Density (Absorbance EXAMPLE Units or
A.U.s) Composition 2 (1% THPED + 2% Extract of 113.9 Southernwood)
Composition D (2% extract of Southernwood) 83.5 Composition E (5%
extract of Southernwood) 113.3 Composition F (neither extract of
Southernwood nor 64.3 THPED)
[0078] While the application of a composition with 2% extract of
Southernwood provided some improvement in ceramide production (83.5
A.U.s vs. 64.3 A.U.s or about 30%) over placebo, when 2% extract of
Southernwood was used with 1% THPED, the amount of ceramides
produced increased much more dramatically (77% over placebo). The
amount of ceramides produced using the combination of Southernwood
extract and THPED was comparable to or better than the level
produced using a composition containing 2.5 times the amount of
Southernwood extract (without THPED).
Example III
Inventive Composition
[0079] The following composition according to the invention was
made.
TABLE-US-00004 TABLE 4 CONCEN- TRATION INGREDIENT CHEMICAL NAME
(wt. percent) Brij 721 Steareth-21 1.50 Purified Water Water 67.75
Cosvat Chlorphenesin 0.25 Natrosol Plus 330 CS Cetyl
Hydroxyethylcellulose; 0.05 Modified Sodium Phosphate; Disodium
Hydroxyethylcellulose Phosphate; Silica; Hydrated Silica Glycerin
99% USP Glycerin 8.00 Varisoft TA 100 Distearyldimonium Chloride
5.00 Propal NF Isoproply Palmitate 2.00 Lanette 16 Cetyl Alcohol
1.25 Dow Corning Q7-9120 Dimethicone 2.50 Silicone Fluid 20 CST
Benzyl Alcohol Pure NF Benzyl Alcohol 0.60 Beantree Oil
Methylheptyl Isostearate 2.00 Ceraphyl ICA Isocetyl Alcohol 2.00
Pulpactyl OP Butylene Glycol; 2.00 Artemisia Abrotanum
Flwer/Leaf/Stem Extract NAB Mushroom PF Algae Extract; Ganoderma
0.30 Lucidum (Mushroom) Stem Extract; Lentinus Edodes Extract;
Phenoxyethanol Structure XL Hydroxypropyl Starch 2.00 Phosphate;
Water Isofol 28 Alcohol Dodecylhexadecanol 1.25 Neutrol TE
Tetrahydroxypropyl 1.00 Ethylenediamine Waterfall Mod 307431
Fragrance 0.30 Citric Acid Anhydrous Citric Acid 0.25
[0080] This composition was prepared by adding water to a process
vessel, and heating the vessel 80-85 C. Natrusol Plus CS330 and
glycerin were premixed and added to the batch. Elestab Ultra Pure
CPN was added and the mixture was held for phasing. In a separate
container, Varisoft TA 100, cetyl alcohol, beantree, ceraphyl ICA,
isopropyl palmitate, dimethicone, Brij 721, and Isofol 28 were
added together. They were mixed and heated to 80-85 C. When both
phases were at 80-85 C, the oil phase was added to the water phase,
and the resulting combination was mixed for 10 minutes at 80-85 C.
The mixture was then removed from the heat and cooled to 40 C. In a
separate container Neutrol TE and 1% water were mixed until
dissolved. In another container, citric acid and water were mixed
until dissolved, and then added to the Neutrol TE premix and mixed
again until dissolved. At 45 C or below, the resulting Neutrol TE
premix was added to the batch. At 40 C or below, NAB mushroom,
Pulpactyl, and benzyl alcohol were added. The resulting mixture was
mixed and cooled to 30-35 C. Water was added to QS minus the amount
of Structure XL. The combination was mixed for at least 5 minutes,
Structure XL was added and the resulting product was mixed until
uniform.
[0081] It is understood that while the invention has been described
in conjunction with the detailed description thereof, that the
foregoing description is intended to illustrate and not limit the
scope the invention, which is defined by the scope of the appended
claims. Other aspects, advantages, and modifications are within the
claims.
* * * * *