U.S. patent application number 12/834465 was filed with the patent office on 2010-11-04 for compositions containing chalcones and use thereof.
Invention is credited to Michael Anthonavage, Sekhar Boddupalli, Kelly Huang, Khalid Mahmood, Claude Saliou.
Application Number | 20100279987 12/834465 |
Document ID | / |
Family ID | 39029960 |
Filed Date | 2010-11-04 |
United States Patent
Application |
20100279987 |
Kind Code |
A1 |
Saliou; Claude ; et
al. |
November 4, 2010 |
COMPOSITIONS CONTAINING CHALCONES AND USE THEREOF
Abstract
The present invention features composition comprising a chalcone
and the use thereof for treating acne and reducing the appearance
of oil or pores on the skin, hair and scalp.
Inventors: |
Saliou; Claude;
(Bernardsville, NJ) ; Boddupalli; Sekhar; (Palo
Alto, CA) ; Mahmood; Khalid; (Palo Alto, CA) ;
Anthonavage; Michael; (Lebanon, NJ) ; Huang;
Kelly; (Hillsborough, NJ) |
Correspondence
Address: |
PHILIP S. JOHNSON;JOHNSON & JOHNSON
ONE JOHNSON & JOHNSON PLAZA
NEW BRUNSWICK
NJ
08933-7003
US
|
Family ID: |
39029960 |
Appl. No.: |
12/834465 |
Filed: |
July 12, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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11462390 |
Aug 4, 2006 |
7781410 |
|
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12834465 |
|
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Current U.S.
Class: |
514/161 ;
514/456 |
Current CPC
Class: |
A61Q 19/008 20130101;
A61K 31/353 20130101; A61P 17/10 20180101; A61P 17/08 20180101;
A61K 8/498 20130101; A61K 31/353 20130101; A61K 31/121 20130101;
A61K 2300/00 20130101; Y10S 514/859 20130101; A61P 17/00 20180101;
A61K 2300/00 20130101; A61K 2300/00 20130101; A61K 31/05 20130101;
A61K 2300/00 20130101; A61K 2300/00 20130101; A61K 8/35 20130101;
A61K 31/327 20130101; A61K 31/121 20130101; A61K 31/05 20130101;
A61K 31/60 20130101; A61K 31/60 20130101; A61K 31/327 20130101 |
Class at
Publication: |
514/161 ;
514/456 |
International
Class: |
A61K 31/192 20060101
A61K031/192; A61K 31/353 20060101 A61K031/353; A61P 17/10 20060101
A61P017/10 |
Claims
1. A composition comprising: (a) a green tea extract comprising at
least one catechin, and (b) at least one chalcone selected from the
group consisting of chalcones of the formulae: ##STR00034## and
enantiomers, diastereomers, and cosmetically-acceptable salts
thereof.
2. The composition of claim 1 wherein said at least one chalcone
comprises 2'-hydroxy-2,3,5'-trimethoxychalcone,
2,2'-dyhydroxychalcone, or an enantiomer, diastereomer, or
cosmetically acceptable salt thereof.
3. The composition of claim 1 further comprising salicylic acid or
benzoyl peroxide.
4. The composition of claim 1 wherein said green tea extract is
present in an amount of 0.1 to 10% by weight of the
composition.
5. The composition of claim 1 wherein said catechin is selected
from the group consisting of catechin, catechin gallate,
epicatechin, gallocatechin, gallocatechin gallate,
epigallocatechin, epicatechin gallate, and epigallocatechin
gallate.
6. The composition of claim 1 wherein said at least one chalcone
comprises 2,2'-dyhydroxychalcone, or an enantiomer, diastereomer,
or cosmetically acceptable salt thereof and said green tea extract
was extracted using a solvent comprising water.
7. A method of treating acne or reducing the appearance of oil or
pores on the skin, said method comprising administering to skin in
need of such treatment a composition of claim 1.
8. A method of treating acne or reducing the appearance of oil or
pores on the skin, said method comprising administering to skin in
need of such treatment a composition of claim 2.
9. A method of treating acne or reducing the appearance of oil or
pores on the skin, said method comprising administering to skin in
need of such treatment a composition of claim 6.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This is a divisional of co-pending application Ser. No.
11/462,390, filed Aug. 4, 2006, which is hereby incorporated in its
entirety.
BACKGROUND OF THE INVENTION
[0002] Acne disorders are often classified as noninflammatory or
inflammatory types. Noninflammatory acne is characterized by closed
comedones (whiteheads) and open comedones (blackheads), consisting
of compact masses of keratin, sebum, and bacteria, which dilate the
follicular duct. A comedone forms when a pilo-sebaceous duct is
obstructed and/or when there is increased production of sebum by a
sebaceous gland. Formation of the comedone can be followed by
inflammation, resulting from bacterial proliferation and/or
overproduction of sebum. Typically, the bacteria are anaerobic
bacteria such as Propionibacteria (P. acnes). Inflammatory acne is
characterized by papules (pimples), pustules, and nodulocystic
lesions, which may lead to scarring. Several factors are believed
to play important roles in the pathogenesis of acne including:
sebum production, hormonal stimulation, plugged pores, and skin
pathogens. Sebum levels are increased in subjects with acne by
approximately 70% compared to sebum levels of control subjects.
[0003] The present invention relates to the unexpected discovery
that certain chalcones are topically effective for treating acne
and reducing the appearance of oil or pores on the skin.
SUMMARY OF THE INVENTION
[0004] In one aspect, the present invention features a method of
treating acne or reducing the appearance of oil or pores on the
skin by administering to skin in need of such treatment a
composition including a chalcone of Formula I
wherein,
##STR00001##
[0005] R is hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.10
alkenyl, acyl or glycosyl, and
[0006] m is 0 to 5; and
[0007] n is 0 to 5;
[0008] or a cosmetically-acceptable salt thereof; provided that the
sum of m and n is greater than or equal to 4.
[0009] In one aspect, the present invention features a method of
treating acne or reducing the appearance of oil or pores on the
skin by administering to skin in need of such treatment a
composition comprising
(a) a chalcones of Formula I wherein,
##STR00002##
[0010] R is hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.10
alkenyl, acyl or glycosyl, and
[0011] m is 0 to 5;
[0012] n is 0 to 5;
or a cosmetically-acceptable salt thereof; and (b) a catechin.
[0013] In another aspect, the present invention features a product
including (a) such a composition and (b) instructions directing the
user to administer said composition to skin in order to treat acne
or reduce the appearance of oil or pores on the skin.
[0014] In another aspect, the present invention features a method
of promoting such a composition by directing the user to administer
said composition to skin in order to treat acne or reduce the
appearance of oil or pores on the skin.
[0015] 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 THE INVENTION
[0016] 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.
[0017] 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 belongs. 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)).
DEFINITIONS
[0018] What is meant by "treating acne" is reducing or preventing
acne or rosacea.
[0019] What is meant by a "product" is a product in finished
packaged form. In one embodiment, the package is a container such
as a plastic, metal or glass tube or jar containing the
composition. The product may further contain additional packaging
such as a plastic or cardboard box for storing such container. In
one embodiment, the product contains instructions directing the
user to apply the composition to (i) treat acne or (ii) reduce the
appearance of oil or pores on the skin.
[0020] What is meant by "promoting" is promoting, advertising, or
marketing. Examples of promoting include, but are not limited to,
written, visual, or verbal statements made on the product or in
stores, magazines, newspaper, radio, television, internet, and the
like.
[0021] For promoting the treatment of acne, examples of such
statements include, but are not limited to, "treats acne,"
"prevents acne," "reduces acne lesions, comedones, or pimples,"
"reduces the appearance of acne lesions, comedones, or pimples,"
"reduces the appearance of acne breakouts and blemishes,"
"preventing, controlling or regulating the appearance of acne
breakouts and blemishes", and "reduces breakouts and
blemishes."
[0022] For promoting the reduction in the appearance of oil on the
skin, examples of such statements include, but are not limited to,
"reduces the appearance of sebum," "preventing, controlling or
regulating the production of sebum," "reduces sebum," "reduces the
appearance of oily/shiny skin," "reduces the appearance of greasy
skin," and "reduces shine on the skin, hair, or scalp." In one
embodiment, the composition is applied to skin not in need of
treatment for acne (i.e., skin not suffering from acne or the
scalp/hair).
[0023] For promoting the reduction in the appearance of pores on
the skin, examples of such statements include, but are not limited
to, "reduces the size of pores," "minimizes the appearance of
pores," "refines the appearance of pores," "reduces the visibility
or pores," and "closes pore opening." In one embodiment, the
composition is applied to skin not in need of treatment for acne
(i.e., skin not suffering from acne).
[0024] As used herein, "administering to skin in need of such
treatment" means contacting (e.g., by use of the hands or an
applicator such, but not limited to, a wipe, tube, roller, spray,
or patch) the area of skin in need such treatment or an area of
skin proximate to the area of skin in need of such treatment.
[0025] As used herein, "composition" means a composition suitable
for administration to the skin.
[0026] As used herein, "cosmetically-acceptable" means that the
ingredients which the term describes are suitable for use in
contact with the skin without undue toxicity, incompatibility,
instability, irritation, allergic response, and the like.
[0027] As used herein, "safe and effective amount" means an amount
of the compound, carrier, or of the composition sufficient to
induce an enhancement in tissue elasticity, but low enough to avoid
serious side effects. The safe and effective amount of the
compounds or composition will vary with the area being treated, the
age, health and skin type of the end user, the duration and nature
of the treatment, the specific compound or composition employed,
the particular cosmetically-acceptable carrier utilized, and like
factors.
Compounds
[0028] The compositions of the present invention contain at least
one compound of the formula I a chalcone of Formula I
##STR00003##
wherein,
[0029] R is hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.10
alkenyl, acyl or glycosyl, and
[0030] m is 0 to 5; and
[0031] n is 0 to 5;
[0032] or a cosmetically-acceptable salt thereof.
[0033] In one embodiment, the sum of m and n is greater than or
equal to 4 (such as equal to 4, 5 or 6)
[0034] Examples of compounds of formula I include, but are not
limited to, those compounds set forth below in Table 1 of Example
1.
[0035] The compounds of the present invention may also be present
in the form of cosmetically acceptable salts. For use in medicine,
the salts of the compounds of this invention refer to non-toxic
"cosmetically acceptable salts," cosmetically acceptable
acidic/anionic or basic/cationic salts. Cosmetically acceptable
acidic/anionic salts include, and are not limited to acetate,
benzenesulfonate, benzoate, bicarbonate, bitartrate, bromide,
calcium edetate, camsylate, carbonate, chloride, citrate,
dihydrochloride, edetate, edisylate, estolate, esylate, fumarate,
glyceptate, gluconate, glutamate, glycollylarsanilate,
hexylresorcinate, hydrabamine, hydrobromide, hydrochloride,
hydroxynaphthoate, iodide, isethionate, lactate, lactobionate,
malate, maleate, mandelate, mesylate, methylbromide, methylnitrate,
methylsulfate, mucate, napsylate, nitrate, pamoate, pantothenate,
phosphate/diphospate, polygalacturonate, salicylate, stearate,
subacetate, succinate, sulfate, tannate, tartrate, teoclate,
tosylate and triethiodide. Cosmetically acceptable basic/cationic
salts include, and are not limited to aluminum, benzathine,
calcium, chloroprocaine, choline, diethanolamine, ethylenediamine,
lithium, magnesium, meglumine, potassium, procaine, sodium and
zinc. Other salts may, however, be useful in the preparation of
compounds according to this invention or of their cosmetically
acceptable salts. Organic or inorganic acids also include, and are
not limited to, hydriodic, perchloric, sulfuric, phosphoric,
propionic, glycolic, methanesulfonic, hydroxyethanesulfonic,
oxalic, 2-naphthalenesulfonic, p-toluenesulfonic,
cyclohexanesulfamic, saccharinic or trifluoroacetic acid.
[0036] In one embodiment, the compositions of present invention
contain from about 0.01% to about 10% by weight of such compound,
such as from about 0.1% to about 5% by weight of such compound,
such as from about 0.5% to about 3% by weight of such compound. In
one embodiment, the composition contains at least 1% by weight of
such compound, such as at least about 2% by weight of such
compound. The compounds of the invention may be synthesized by
those having ordinary skill in the art and/or purchased from
commercial sources such as Indofine Chemicals Inc. (Somerville,
N.J.).
Compositions
[0037] The compositions useful in the present invention involve
formulations suitable for administering to the target tissues, such
as mammalian skin such as human skin. In one embodiment, the
composition contains a safe and effective amount of (i) a chalcone
of formula I and (ii) a cosmetically-acceptable carrier. In one
embodiment, the cosmetically-acceptable carrier is from about 50%
to about 99.99%, by weight, of the composition (e.g., from about
80% to about 99%, by weight, of the composition).
[0038] The compositions may be made into a wide variety of product
types that include but are not limited to solutions, suspensions,
lotions, creams, gels, toners, sticks, sprays, ointments, cleansing
liquid washes and solid bars, shampoos and hair conditioners,
pastes, foams, powders, mousses, shaving creams, wipes, strips,
patches, electrically-powered patches, wound dressing and adhesive
bandages, hydrogels, film-forming products, facial and skin masks,
make-up such as foundations, eye liners, and eye shadows, and the
like. These product types may contain several types of
cosmetically-acceptable carriers including, but not limited to
solutions, suspensions, emulsions such as microemulsions and
nanoemulsions, gels, solids and liposomes. The following are
non-limitative examples of such carriers. Other carriers can be
formulated by those of ordinary skill in the art.
[0039] The compositions useful in the present invention can be
formulated as solutions. Solutions typically include an aqueous or
organic solvent (e.g., from about 50% to about 99.99% or from about
90% to about 99% of a cosmetically acceptable aqueous or organic
solvent). Examples of suitable organic solvents include: propylene
glycol, polyethylene glycol (200-600), polypropylene glycol
(425-2025), glycerol, 1,2,4-butanetriol, sorbitol esters,
1,2,6-hexanetriol, ethanol, and mixtures thereof.
[0040] A lotion can be made from such a solution. Lotions typically
contain from about 1% to about 20% (e.g., from about 5% to about
10%) of an emollient(s) and from about 50% to about 90% (e.g., from
about 60% to about 80%) of water. As used herein, "emollients"
refer to materials used for the prevention or relief of dryness, as
well as for the protection of the skin or hair. Examples of
emollients include, but are not limited to, those set forth in the
International Cosmetic Ingredient Dictionary and Handbook, eds.
Wenninger and McEwen, pp. 1656-61, 1626, and 1654-55 (The Cosmetic,
Toiletry, and Fragrance Assoc., Washington, D.C., 7.sup.th Edition,
1997) (hereinafter "ICI Handbook").
[0041] Another type of product that may be formulated from a
solution is a cream. A cream typically contains from about 5% to
about 50% (e.g., from about 10% to about 20%) of an emollient(s)
and from about 45% to about 85% (e.g., from about 50% to about 75%)
of water.
[0042] Yet another type of product that may be formulated from a
solution is an ointment. An ointment may contain a simple base of
animal, vegetable, or synthetic oils or semi-solid hydrocarbons. An
ointment may contain from about 2% to about 10% of an emollient(s)
plus from about 0.1% to about 2% of a thickening agent(s). Examples
of thickening agents include, but are not limited to, those set
forth in the ICI Handbook pp. 1693-1697.
[0043] The compositions useful in the present invention can also be
formulated as emulsions. If the carrier is an emulsion, from about
1% to about 10% (e.g., from about 2% to about 5%) of the carrier
contains an emulsifier(s). Emulsifiers may be nonionic, anionic or
cationic. Examples of emulsifiers include, but are not limited to,
those set forth in the ICI Handbook, pp. 1673-1686.
[0044] Lotions and creams can be formulated as emulsions. Typically
such lotions contain from 0.5% to about 5% of an emulsifier(s),
while such creams would typically contain from about 1% to about
20% (e.g., from about 5% to about 10%) of an emollient(s); from
about 20% to about 80% (e.g., from 30% to about 70%) of water; and
from about 1% to about 10% (e.g., from about 2% to about 5%) of an
emulsifier(s).
[0045] Single emulsion skin care preparations, such as lotions and
creams, of the oil-in-water type and water-in-oil type are
well-known in the art and are useful in the subject invention.
Multiphase emulsion compositions, such as the water-in-oil-in-water
type or the oil-in-water-in-oil type, are also useful in the
subject invention. In general, such single or multiphase emulsions
contain water, emollients, and emulsifiers as essential
ingredients.
[0046] The compositions of this invention can also be formulated as
a gel (e.g., an aqueous, alcohol, alcohol/water, or oil gel using a
suitable gelling agent(s)). Suitable gelling agents for aqueous
and/or alcoholic gels include, but are not limited to, natural
gums, acrylic acid and acrylate polymers and copolymers, and
cellulose derivatives (e.g., hydroxymethyl cellulose and
hydroxypropyl cellulose). Suitable gelling agents for oils (such as
mineral oil) include, but are not limited to, hydrogenated
butylene/ethylene/styrene copolymer and hydrogenated
ethylene/propylene/styrene copolymer. Such gels typically contains
between about 0.1% and 5%, by weight, of such gelling agents.
[0047] The compositions of the present invention can also be
formulated into a solid formulation (e.g., a wax-based stick, soap
bar composition, powder, and wipe containing powder).
[0048] The compositions useful in the subject invention may
contain, in addition to the aforementioned components, a wide
variety of additional oil-soluble materials and/or water-soluble
materials conventionally used in compositions for use on skin at
their art-established levels.
Additional Cosmetically Active Agents
[0049] In one embodiment, the composition further contains another
cosmetically active agent in addition to the above compounds. What
is meant by a "cosmetically active agent" is a compound (e.g., a
synthetic compound or a compound isolated 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
limiting to, lightening agents, darkening agents such as
self-tanning agents, anti-acne agents, shine control agents,
anti-microbial agents such as anti-yeast agents, anti-fungal, and
anti-bacterial agents, anti-inflammatory agents, anti-parasite
agents, external analgesics, sunscreens, photoprotectors,
antioxidants, keratolytic agents, detergents/surfactants,
moisturizers, nutrients, vitamins, energy enhancers,
anti-perspiration agents, astringents, deodorants, hair removers,
hair growth enhancing agents, hair growth delaying agents, firming
agents, anti-callous agents, agents for skin conditioning,
anti-cellulite agents, fluorides, and odor-control agents such as
odor masking or pH-changing agents.
[0050] In one embodiment, the cosmetically active agent is selected
from, but not limited to, the group consisting of hydroxy acids,
benzoyl peroxide, D-panthenol, octyl methoxycinnimate, titanium
dioxide, octyl salicylate, homosalate, avobenzone, carotenoids,
free radical scavengers, spin traps, retinoids and retinoid
precursors such as retinol and retinyl palmitate, ceramides,
polyunsaturated fatty acids, essential fatty acids, enzymes, enzyme
inhibitors, minerals, hormones such as estrogens, steroids such as
hydrocortisone, 2-dimethylaminoethanol, copper salts such as copper
chloride, peptides containing copper such as Cu:Gly-His-Lys,
coenzyme Q10, amino acids such a proline, vitamins, lactobionic
acid, acetyl-coenzyme A, niacin, riboflavin, thiamin, ribose,
electron transporters such as NADH and FADH2, and other botanical
extracts such as aloe vera, Feverfew, and Soy, and derivatives and
mixtures thereof. The cosmetically active agent will typically be
present in the composition of the invention in an amount of from
about 0.001% to about 20% by weight of the composition, e.g., about
0.005% to about 10% such as about 0.01% to about 5%.
[0051] Examples of vitamins include, but are not limited to,
vitamin A, vitamin Bs such as vitamin B3, vitamin B5, and vitamin
B12, vitamin C, vitamin K, vitamin E such as alpha, gamma or
delta-tocopherol, and derivatives (such as salts and esters) and
mixtures thereof.
[0052] Examples of hydroxy acids include, but are not limited, to
glycolic acid, lactic acid, malic acid, salicylic acid, citric
acid, and tartaric acid.
[0053] Examples of antioxidants 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 not limited to,
extracts containing flavonoids, isoflavonoids, and their
derivatives such as genistein and diadzein (e.g., such as Soy and
Clover extracts, extracts containing resveratrol and the like.
Examples of such natural extracts include grape seed, green tea,
pine bark, and propolis.
[0054] Examples of enzymes include, but are not limited to,
proteases such as fungal proteases, bacterial proteases or
mammalian proteases. Examples of such proteases include, but are
not limited to, pepsin, cathepsin, human urinary acid protease,
fungal proteases derived from Neurospora oryzae, Mucor pusillus,
Mucor miehei, Rhizopus chinensis, or Endothia parasitica, and
bacterial proteases rhizopuspepsin, penicillopepsin, and
endothiapepsin. Further, the proteases may be derived from
processes involving genetic engineering processes and
techniques.
[0055] Examples of fungal extracts include, but are not limited to,
extracts from Neurospora oryzae, Mucor pusillus, Mucor miehei,
Rhizopus chinensis, or Endothia parasitica Mucor Miehei. Examples
of compositions containing such proteases and fungal extracts are
disclosed in U.S. Pat. No. 5,976,556.
Anti-Acne Agents
[0056] In one embodiment, the present invention relates to topical
compositions including an anti-acne agent. What is meant by an
anti-acne agent is an compound that has been approved by the U.S.
Food and Drug Administration for the topical treatment of acne.
Examples of anti-acne agents include, but are not limited to,
salicylic acid, benzoyl peroxide, sulphur, retinoic acid, candida
bombicola/glucose/methyl rapeseedate ferment, peat water,
resorcinol, silt, peat, permethin, azelaic acid, clindamycin,
adapalene, erythromycin, sodium sulfacetamide, and combinations
thereof. In one embodiment, the amount of anti-acne agent in the
composition is from about 0.01% to about 10%, for example from
about 0.1% to about 5%, or from about 0.5% to about 2% by weight,
based on the total weight of the composition.
Catechins
[0057] In one embodiment, the compositions of the present invention
further contain a catechin. The term "catechin" refers to a
polyphenolic substance that belongs to the flavan-3-ol class of
flavonoids. The catechins may be synthetically made or naturally
made (e.g., such as part of a plant extract). Exemplary catechins
include but are not limited to, catechin (C), catechin gallate
(CG), epicatechin (EC), gallocatechin (GC), gallocatechin gallate
(GCG), epigallocatechin (EGC), epicatechin gallate (ECG), and
epigallocatechin gallate (EGCG). Exemplary plants which have a
content of catechins include but are not limited to Catechu, Green
Tea (Camellia sinensis, Camellia oleifera), Vitis vinifera, grape
(Vitis vinifera), agrimony (Agrimonia eupatoria), cotton (Gossypium
sp), black currant (Ribes nigrum), cowberry (Vaccinium vitis-idaea
var. minus), Alpinia galanga and Alpinia katsumada. Catechins can
be synthetically made or are available commercially, for example
from Indofine (Somerville, N.J.) or from Aldrich (Milwaukee,
Wis.).
Plant Extract
[0058] In one embodiment, the compositions of present invention
further contain another plant extract. What is meant by a "plant
extract" is a blend of compounds isolated from a plant. Such
compounds may be isolated from one or more part of the plant (e.g.,
the whole plant, flower, seed, root, rhizome, stem, fruit and/or
leaf of the plant) by physically removing a piece of such plant,
such as grinding a flower of the plant. Such compounds may also be
isolated from the plant by using extraction procedures well known
in the art (e.g., the use of organic solvents such as lower
C.sub.1-C.sub.8 alcohols, C.sub.1-C.sub.8 alkyl polyols,
C.sub.1-C.sub.8 alkyl ketones, C.sub.1-C.sub.8 alkyl ethers, acetic
acid C.sub.1-C.sub.8 alkyl esters, and chloroform, and/or inorganic
solvents such as water, inorganic acids such as hydrochloric acid,
and inorganic bases such as sodium hydroxide).
[0059] In one embodiment, the plant extract (e.g., an alpinia
extract, a green tea extract, a feverfew extract, an agrimony
extract, a cotton extract, a grape extract, a black currant
extract, a cowberry extract or a soybean extract) is present in the
composition in an amount from about 0.001% to about 20% by weight,
in particular in an amount from about 0.1% to about 10% by weight
of the composition. Unless stated otherwise, the weight of the
extract refers to the dry weight of the extract.
Feverfew Extract
[0060] In one embodiment, the compositions of present invention
further contain a feverfew extract. What is meant by a "feverfew
extract" is a blend of compounds isolated from a feverfew plant.
Examples of such compounds, include, but are not limited to,
apigenin-7-glucoside, apigenin-7-glucuronide,
1-.beta.-hydroxyarbusculin,
6-hydroxykaempferol-3,7-4'-trimethylether (Tanetin),
6-hydroxykaempferol-3,7-dimethyl ether, 8-.beta.-reynosin,
10-epicanin, ascorbic acid, beta-carotene, calcium, chromium,
chrysanthemolide, chrysanthemomin, chrysarten-A, chrsyarten-c,
chrysoeriol-7-glucuronide, cobalt, cosmosiin, epoxyartemorin,
luteolin-7-glucoside, luteolin-7-glucuronide, mangnoliolide,
parthenolide, quercetagentin-3,7,3'-trimethylether,
quercetagetin-3'7-dimethylether, reynosin, tanaparthin,
tanaparthin-1.alpha.,4.alpha.-epoxide,
tanaparthin-1.beta.,4.beta.-epoxide, .beta.-costunolide,
3-.beta.-hydroxy-parthenolide, and 3,7,3'-trimethoxyquercetagetin.
The .alpha.-unsaturated .gamma.-lactones present in the feverfew
plant, such as parthenolide, are known to cause the allergic
reactions. Therefore, in one embodiment, the feverfew extract is
substantially free of the allergy causing .alpha.-unsaturated
.gamma.-lactones. The preparation of feverfew extract that is
substantially free of parthenolide is disclosed in Example 1 in
U.S. Patent Application No. 20040105905.
Soybean Extract
[0061] In one embodiment, the compositions of present invention
further contain a soybean extract. What is meant by a "soybean
extract" is a blend of compounds isolated from soybean. The soybean
extract may contain only a portion of the soybean (e.g., an extract
of the soybean such as a lipid reduced soybean powder or filtered
soymilk) or may contain the entire soybean (e.g., a ground powder
of the soybean). The soybean extract may be in the form of a fluid
(e.g., soymilk) or a solid (e.g., a soybean powder or soymilk
powder).
[0062] The soybean extract may be soybean powder. Soybean powder
may be made by grinding dry soybeans. The soybean powder may be
lyophilized. Soymilk and soymilk powder are also useful soybean
extracts. Soymilk is a combination of solids derived from soybeans
and water, the mixture of which has some or all of the insoluble
constituents filtered off. Soymilk powder is evaporated soymilk,
which in one embodiment, is in a lyophilized or spray-dried form.
Procedures for manufacturing soymilk include, but are not limited
to, the following three procedures. First, soymilk may be made by
placing soybeans into water to allow them to absorb the water. The
swelled beans are then ground and additional water is then added.
The mixture may then be filtered to remove any insoluble residue.
Second, soymilk may also be prepared from soybean powder. Soybean
powder is thoroughly mixed with water (e.g., for at least one
hour), which may then be followed by a filtration process to remove
insoluble residues. Third, soymilk can also be reconstituted from
soymilk powder by adding water. The soymilk may comprise from about
1% to about 50%, by weight (e.g., from about 5% to about 20%, by
weight) of solids from the soybean.
[0063] The known active ingredients of soybeans include, but not
limiting to, isoflavones, phytoestrogens, genistein, daidzein,
glycitein, saponins, and phytosterols. The soybean extracts useful
in this invention may be produced from all soybean species,
regardless of their geographic origin, sun exposure, harvest time
and the like. However, specific strains, geographic origins or
growth conditions might be preferred. For example, but not limiting
to, soybean strains particularly rich in its Soybean Trypsin
Inhibitor (STI) content or in isoflavone content, or growth
conditions that result in STI or isoflavone enrichment in the bean,
might be preferred.
[0064] In one embodiment, the soybean extract is a non-denatured
soybean extract. "Denaturation" is defined in the Bantam Medical
Dictionary (1990 edition) as "the change in the physical and the
physiological properties of a protein, that are brought about by
heat, X-rays or chemicals. These changes include loss of activity
(in the case of enzymes) and loss (or alteration) of antigenicity
(in the case of antigens)". What is meant by "non-denatured plant
extract" is a product extracted or derived from a plant in which
the processing for the derivation of such plant extract (e.g., the
temperature, extraction media) did not eliminate its protease
inhibitory activity. One such protease is trypsin. In one
embodiment, the non-denatured state of the soybean extract of this
invention is measured by the presence of an intact soybean trypsin
inhibitor (STI) protein, or by its trypsin inhibitory activity.
[0065] It should be noted that the soybean extracts useful in the
compositions of this invention may have a distinctive odor. If
necessary, the odor of the extracts may be reduced by using soybean
products derived from specific strains of soybeans known to produce
reduced-odor, including, but not limited to,
lipoxygenase-2-deficient beans and those having modified sugar
profile, and the like. A process to reduce oxygen levels in the
formulation may also reduce the odor. Various masking agents or
fragrances may also be used to mask the odor. One way to make
soymilk is to soak the soybeans in deionized or purified water for
several hours, and grind them after they were fully hydrated, with
the addition of small quantities of water. The grinding process
allows the soybean milk to be extracted. After collection, the
soybean milk may be filtered to remove any residual parts of the
bean husk.
[0066] The soymilk used in the formulations described below can be
fresh soymilk as described above, or may be made from soybean
powder and water. The soybean powder is milled from soybeans and
may also be lyophilized, spray dried, or freeze-dried and the
resulting soymilk may or may not be filtered. Such prepared soymilk
may have from about 1 to about 90% by weight dry soybean powder.
Another example is the use of soymilk powder, made from
lyophilized, spray dried or freeze-dried soymilk, with the addition
of water and finished with or without filtration or homogenization.
Other methods of soybean extraction could also be used to create
the active ingredients in the formulations described below.
[0067] For example, the active ingredients could be extracted from
ground soybeans using ethanol/water mixtures, followed by the
removal of the ethanol from the extract, in such ways that the
serine protease inhibitory activity of the soybean will be
retained, and preferably that the protein STI will remain
intact.
[0068] In one embodiment, the soybean extracts utilized in the
present invention have a microbial content of less than about 1,000
cfu per gram (such as less than about 100 cfu per gram) of the
soybean extract.
[0069] The soybean extract may be exposed to gamma irradiation. The
soybean extract may be exposed to from about 2 to about 30 kGy of
gamma irradiation, such as from about 5 and about 10 kGy of gamma
irradiation. Such treatment reduces the microbial content of the
soybean extract, while maintaining its biological activity (e.g.,
serine protease inhibitory activity). The treatment of soybean
extracts with gamma irradiation maintains the cosmetic elegance of
the composition, such as maintained natural colors and does not
induce significant malodors.
[0070] Other anti-microbial processes that also maintain the
protease inhibitory activity of the soybean extract that can be
practiced alone or in combination with gamma irradiation, include,
but are not limited to, exposure to x-rays, high energy electron or
proton beams, ultraviolet radiation, hydrostatic pressure, and
addition of chemical agents possessing antimicrobial activity, and
combinations thereof.
Other Materials
[0071] Various other materials may also be present in the
compositions useful in the subject invention. These include
humectants, proteins and polypeptides, preservatives and an
alkaline agent. Examples of such agents are disclosed in the ICI
Handbook, pp. 1650-1667. The compositions of the present invention
may also contain chelating agents (e.g., EDTA) and preservatives
(e.g., parabens). Examples of suitable preservatives and chelating
agents are listed in pp. 1626 and 1654-55 of the ICI Handbook. In
addition, the compositions useful herein can contain conventional
cosmetic adjuvants, such as colorants such as dyes and pigments,
opacifiers (e.g., titanium dioxide), and fragrances.
Mineral Water
[0072] The compositions of the present invention may be prepared
using a mineral water, for example mineral water that has been
naturally mineralized such as Evian.RTM. Mineral Water (Evian,
France). In one embodiment, the mineral water has a mineralization
of at least about 200 mg/L (e.g., from about 300 mg/L to about 1000
mg/L). In one embodiment, the mineral water contains at least about
10 mg/L of calcium and/or at least about 5 mg/L of magnesium.
Use
[0073] The composition according to the invention can be used to
treat a variety of skin conditions, including but not, limited to
acne. In one embodiment, the composition is used to treat other
sebum disorders such as hyperlipidemia, hyperandrogenia, seborrhea,
seborrheic dermatitis, seborrhea capitis, eczematoid seborrhea,
seborrhea faciei, seborrhea oleosa, seborrhea sicca, seborrhea
squamosa neonatorum, sebacious hyperplasia, Rosacea, follicular
rash, demodex folliculorum, oily skin, Keratinous cyst,
Pseudofolliculitis barbae and hypertrichosis.
[0074] The compositions of the present invention can also be used
to reduce the appearance of pores and oil on the skin (e.g., the
face, scalp, or hair).
[0075] The composition of the present invention can also be used to
reduce acne lesions, comedones, or pimples, reduce the appearance
of acne lesions, comedones, or pimples, reduces the appearance of
acne breakouts and blemishes, prevent, control or regulate the
appearance of acne breakouts and blemishes, and reduce breakouts
and blemishes.
[0076] The composition of the present invention can also be used to
promote the reduction in the appearance of oil on the skin, such as
reducing the appearance of sebum, preventing, controlling or
regulating the production of sebum, reducing sebum, reducing the
appearance of oily/shiny skin, reducing the appearance of greasy
skin, and reducing shine on the skin, hair, or scalp.
[0077] The composition and formulations containing such
compositions of the present invention may be prepared using
methodology that is well known by an artisan of ordinary skill.
Example 1
In Vitro Sebocyte Lipogenesis Assay
[0078] Samples of facial skin obtained from subjects undergoing
facelift surgeries were used. Upon arrival, the top 0.4 mm skin
section, obtained by a dermatome was removed and the second 0.4 mm
dermal section (previously shown to be rich in sebaceous glands)
was used to isolate sebaceous cells. The tissue was digested with
Dispase in Dulbecco's Modified Eagle Medium (DMEM) containing
penicillin and streptomycin and 10% calf serum for 20 min at
37.degree. C., and then with 0.3% trypsin/0.1%
ethylenediaminetetraacetic acid (EDTA) in phosphate buffered saline
(PBS) for 10 min at 37.degree. C. Single cell suspensions were
obtained by scraping the tissue vigorously with a scalpel blade.
The released cells were seeded on a feeder layer of mitomycin C
inactivated 3T3 fibroblasts and cultured in growth medium for 3
days at 37.degree. C. The growth medium contained DMEM and F12
media (3:1), L-glutamine, sodium pyruvate, penicillin,
streptomycin, 8% fetal bovine serum, 2% heat-inactivated human
serum, epidermal growth factor, insulin, hydrocortisone, and either
with or without cholera toxin (ChT). The cultures treated with ChT
were shifted to a low-serum medium for 3 days and followed by a
serum-free medium for another 7 days for the induction of lipid
formation and storage, while the cultures without ChT treatment
were maintained in growth medium (non-induced condition) for 10
days. The low-serum medium consisted of DMEM and F12 media (3:1)
supplemented with L-glutamine, sodium pyruvate, penicillin,
streptomycin, 2% heat-inactivated bovine serum and 2%
heat-inactivated human serum, 1.times.
insulin-transferrin-selenium, 1.times. trace elements. The
serum-free medium contained DMEM and F12 media (3:1) supplemented
with L-glutamine, sodium pyruvate, penicillin, streptomycin,
1.times. insulin-transferrin-selenium, 1.times. trace elements,
3,3',5-triiodo-L-thyronine sodium. For neutral lipid analysis by
Nile Red staining, cells were grown in 96-well plates and for lipid
analysis by thin layer chromatography, cells were grown in 6-well
plates and harvested at the end of the culturing by scraping.
Testing Stimulators or Inhibitors of Sebocyte Differentiation and
Lipid Production
[0079] Hormones, mixture of hormones i.e. bovine pituitary extract
or compounds to be tested were added to the culture at the
beginning of serum free media addition. Two criteria were used to
evaluate the effect of these materials on sebaceous cultures: 1)
visual observations and 2) evaluation of sebaceous lipid
accumulation and synthesis. The evaluation of lipid accumulation
completed using the Nile red method. This method relies on
visualization of neutral lipids by Nile red and quantitation by
reading of fluorescence at 535 nm excitation, 580 nm emission using
a plate reader. The lipid synthesis was evaluated by radioactive
labeling using 14C acetate and quantified by Bio Rad Phosphoimager
(Molecular Imager, FX) using 4.1 Software.
[0080] Morphological evaluation of lipid accumulation was easily
recognized since the cells enlarged displayed lipid granules that
in bright field light microscopy appeared as yellowish circles in
the cells. Quantitation of accumulation/inhibition of neutral
lipids in sebocytes was accomplished by Nile red binding assay.
Briefly, following exposure of sebocytes to test compounds, the
cells were allowed to interact with 1 .mu.M Nile red in Hanks
buffered saline solution containing DMSO and Pluronic F127. After 4
hours of incubation, washing and incubation overnight, the
fluorescence was read at 535 nm excitation and 580 nm emission
using a fluorescence plate reader and compared to an induction
agent (i.e. cholera toxin). To determine whether the compounds had
an inhibitory effect on cell growth, cell counts were
performed.
[0081] Following the procedure described above, compounds of the
present invention were tested for visual and Nile red evaluation of
lipid accumulation, the results of which are depicted in Table
1.
TABLE-US-00001 TABLE 1 % Reduction in Lipid Synthesis in Sebocytes
Structure [3uM] ##STR00004## 12.4 ##STR00005## Not Active
##STR00006## 12.8 ##STR00007## Not Active ##STR00008## 20.5
##STR00009## Not Active ##STR00010## 25.6 ##STR00011## Not Active
##STR00012## 26.9 ##STR00013## Not Active ##STR00014## 28.4
##STR00015## Not Active ##STR00016## 28.7 ##STR00017## Not Active
##STR00018## 47.3 ##STR00019## Not Active ##STR00020## Not Active
##STR00021## Not Active ##STR00022## Not Active ##STR00023## Not
Active ##STR00024## Not Active ##STR00025## Not Active ##STR00026##
Not Active ##STR00027## Not Active ##STR00028## Not Active
##STR00029## Not Active ##STR00030## Not Active ##STR00031## Not
Active ##STR00032## Not Active ##STR00033## Not Active
[0082] In the same assay, synergism between the chalcones of the
present invention and Green Tea extract was also found (See Table
2).
TABLE-US-00002 TABLE 2 2,2'-dihydroxy- Green Tea Extract chalcone %
Cholera Toxin Concentration Concentration Reduction 0.0 .mu.g/mL
3.0 .mu.M 50.8 0.0 .mu.g/mL 1.0 .mu.M 38.2 0.0 .mu.g/mL 0.3 .mu.M
14.3 1.25 .mu.g/mL 0 .mu.M 13.3 2.5 .mu.g/mL 0 .mu.M 24.2 1.25
.mu.g/mL 3.0 .mu.M 71.1 2.5 .mu.g/mL 3.0 .mu.M 84.1 1.25 .mu.g/mL
1.0 .mu.M 63.3 2.5 .mu.g/mL 1.0 .mu.M 77.1 1.25 .mu.g/mL 0.3 .mu.M
46.5 2.5 .mu.g/mL 0.3 .mu.M 65.9
* * * * *