US20050147631A1 - Cosmetic composition and method for retarding hair growth - Google Patents

Cosmetic composition and method for retarding hair growth Download PDF

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US20050147631A1
US20050147631A1 US11031172 US3117205A US2005147631A1 US 20050147631 A1 US20050147631 A1 US 20050147631A1 US 11031172 US11031172 US 11031172 US 3117205 A US3117205 A US 3117205A US 2005147631 A1 US2005147631 A1 US 2005147631A1
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extract
acid
group consisting
selected
alpha
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Mindy Goldstein
Chia Chen
Christina Fthenakis
Kenneth Marenus
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E-L Management Corp
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E-L Management Corp
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/30Cosmetics or similar toilet preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toilet preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35Ketones, e.g. benzophenone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic, hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/20Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365Lactones
    • A61K31/375Ascorbic acid, i.e. vitamin C; Salts thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/66Phosphorus compounds
    • A61K31/683Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin digitoxin or digoxin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/30Cosmetics or similar toilet preparations characterised by the composition containing organic compounds
    • A61K8/63Steroids; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/30Cosmetics or similar toilet preparations characterised by the composition containing organic compounds
    • A61K8/68Sphingolipids, e.g. ceramides, cerebrosides, gangliosides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/96Cosmetics or similar toilet preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toilet preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/96Cosmetics or similar toilet preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/98Cosmetics or similar toilet preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • A61K8/987Cosmetics or similar toilet preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of species other than mammals or birds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILET PREPARATIONS
    • A61Q7/00Preparations for affecting hair growth
    • A61Q7/02Preparations for inhibiting or slowing hair growth
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74Biological properties of particular ingredients
    • A61K2800/78Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782Enzyme inhibitors; Enzyme antagonists

Abstract

The present invention comprises cosmetic compositions and methods for retarding hair growth comprising a combination of an ornithine decarboxylase inhibitor, an anti-angiogenic active and an anti-inflammatory.

Description

  • This application claims priority of U.S. provisional application 60/535,125 filed Jan. 7, 2004.
  • FIELD OF THE INVENTION
  • The present invention relates to skin care cosmetic compositions and methods. In particular, the present invention relates to novel cosmetic compositions and methods for retarding hair growth.
  • BACKGROUND OF THE INVENTION
  • For years, companies have marketed products for either hair growth or hair growth retardation, with limited success. From mechanical procedures to compositions containing biologically active ingredients, numerous means are available for the consumer. Use of hair dyes to color hair, require frequent repetitions and are not often effective in hiding the appearance of hair on the skin.
  • Especially in suppressing hair growth, the prior art has taught the use of numerous actives including biological enzymes, plant extracts and enzyme inhibitors. For example, U.S. Pat. No. 6,375,948 teaches the use of an extract of a plant of the family Juniperus or a malt, an elastase inhibitor or neutral endopeptidase inhibitor and a proteolytic enzyme to suppress hair growth. In U.S. Pat. No. 6,407,056, the patent teaches a method of delaying mammalian hair growth comprising topically applying an effective amount of a composition comprising a serine protease and a pharmaceutically or cosmetically acceptable vehicle.
  • The references discussed above have limited and only short term usefulness. Other references turn to the factors that are believed to contribute to hair growth to develop formulas for regulating hair growth.
  • For example, angiogenesis is the fundamental process by which new blood vessels are formed. The process involves the migration of vascular endothelial cells into tissue, followed by the condensation of such endothelial cells into vessels. Angiogenesis involves a complex interplay of molecules that stimulate and molecules that inhibit the growth and migration of endothelial cells. In U.S. Pat. No. 6,391,850, it was found that an anti-angiogenic, SLED, stimulated the growth of hair. It was believed that SLED affected hair growth by mediating angiogenesis within the hair follicle.
  • Sphingo Glycolipids, such as phytosphingosine (known to be an anti-angiogenic), have been used in skin care compositions to aid in hair growth. For example, U.S. Pat. No. 5,565,207 (“patent '207”) teaches the use of a scalp moisturizer comprising a steroid glycoside and/or a triterpenoid glycoside, a sphingo glycolipid and a follicular hormone and/or an adrenocortical hormone. Patent '207 recognizes the use of the scalp moisturizer to stimulate hair growth.
  • It is important to note that the references discussed above teach the use of anti-angiogenics to aid in promoting hair growth.
  • Yet another factor believed to contribute to hair growth is Ornithine Decarboxylase (OCD), an enzyme that catalyzes the decarboxylation of ornithine to putrescine. The reaction is the first step in the biosynthesis of the polyamides known as spermidine and spermine. The polyamides are known to play an important role in cell growth and proliferation. U.S. Pat. No. 4,720,489 (“patent '489”) teaches the use of ornithine decarboxylase inhibitors to retard hair growth. Patent '489 specifically teaches against the use of certain ornithine decarboxylase inhibitors that can have secondary pharmacological effects.
  • In summary, the references discussed above teach that anti-angiogenic agents promote hair growth while certain ornithine decarboxylase inhibitors retard hair growth. Still other references teach compositions with only limited efficacy.
  • There still remains a need for a novel composition and method for inhibiting hair growth that has prolonged efficacy that can be accomplished preferably by manipulating the numerous factors that contribute to hair growth.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1. Chart depicting results of Self Assessment of product containing inventive composition of the present invention from the Clinical Study in Example 1.
  • FIG. 2. Chart depicting results of product evaluation after eight weeks of use from the Clinical Study in Example 1.
  • FIG. 3. Chart depicting results of image analysis of clinical study in Example 1 using inventive composition of the present invention.
  • FIG. 4. Chart depicting results of comparative study between inventive composition and conventional hair growth retardation product.
  • SUMMARY OF THE INVENTION
  • The present invention comprises a cosmetic composition comprising from 0.1 to 50% of an ornithine decarboxylase inhibitor, from 0.01 to 10% of an anti-angiogenic active, from 0.0001 to 20% of an anti-inflammatory and a cosmetically acceptable vehicle.
  • The present invention further comprises a method of retarding hair growth comprising applying a composition comprising from 0.1 to 50% of an ornithine decarboxylase inhibitor, from 0.01 to 10% of an anti-angiogenic active, from 0.0001 to 20% of an anti-inflammatory and a cosmetically acceptable vehicle.
  • DETAILED DESCRIPTION
  • Except in operating and comparative examples, or where otherwise explicitly indicated, all numbers in this description indicating amounts or ratios of material or conditions of reaction, physical properties of materials and/or use are to be understood as modified by the word “about.” All amounts are by weight of the final composition, unless otherwise specified.
  • It has been surprisingly discovered that the combination of an ornithine decarboxylase inhibitor with an anti-angiogenic active and an anti-inflammatory effectively suppresses hair growth.
  • In a preferred embodiment, the ornithine decarboxylase inhibitor is derived from a marine, synthetic, or naturally derived source as opposed to an animal derived source. Preferred inhibitors are pentacyclic triterpenes. Examples of pentacyclic triterpenes include ursolic acid, betulin, betulinic acid, oleanolic acid, betulin mono and di-succinate or glutarate. Particularly preferred is ursolic acid extracted from Rosmarinus officinalis, which is commercially available from Sabinsa Corporation in 121 Ethel Road West, Unit #6, Piscataway, N.J. 08854.
  • The amount will vary depending on the formulation and the performance desired. The ornithine decarboxylase inhibitor is used in an amount from 0.001% to 90% by weight of the composition is used. Preferably, an amount of from 0.001% to 60% is used and most preferably, an amount of from 0.01% to 3% is used.
  • The preferred composition further comprises an anti-angiogenic active. Although anti-angiogenic agents have been known to promote hair growth, it has been surprisingly found that an anti-angiogenic can aid in the inhibition of hair growth in the present inventive combination. Particularly preferred anti-angiogenics include sphingo lipids. Examples of sphingo lipids include phytosphingosine, dihydrosphingosine, sphingosine, dehydrophytosphingosine, monohexosylceramide, sphingoplamalogen, acetyl sphingosine and monohexaosylceramide fatty acid ester. Other anti-angiogenic agents include magnolia extract, MDI complex (shark cartilage) and tetrahydrocurcumin and extracts of green tea.
  • The amount will vary depending on the formulation and the performance desired. In general, the anti-angiogenic is used in an amount from 0.001% to 90% by weight of the composition is used. Preferably, an amount of from 0.01% to 60% and most preferably, an amount of from 0.1% to 2% is used.
  • Inflammation and related irritation can detrimentally interfere with the ability of actives to penetrate the skin and provide their intended benefit. Anti-inflammatories have been used in hair growth compositions to enhance the activity of hair growth promoting actives (See U.S. Pat. No. 6,451,777). However, in the present invention, it has been surprisingly discovered that an anti-inflammatory when combined with an ornithine decarboxylase inhibitor and an anti-angiogenic agent actually aids in inhibiting hair growth.
  • The anti-inflammatory used in the present invention can be selected from any known in the art. A particularly preferred anti-inflammatory is gorgonian extract. Gorgonian extract is a marine-derived, natural extract available from the Lipo Chemical Company, Patterson, N.J. as a liquid extract of Sea Whip, pseudopterogorgia elisabethae, supplied as a 4% Sea Whip extact in butylene glycol. The Caribbean Sea Whip pseudoptemgorgia elisabethae has been reported in Proc. Natl. Acad. Sci. USA, Vol. 83, pp. 6238-6240 (September 1986) as containing pseudopterosins which are diterpene-pentose glycosides. U.S. Pat. No. 4,849,410 and U.S. Pat. No. 4,745,104, incorporated by reference herein, provide further disclosure on the Caribbean gorgonians. Alternatively, anti-inflammatories such as boswellin, hoelen extract, ximenynic acid, hesperitin, tea polyphenols and licorice extract may be used.
  • The amount will vary depending on the formulation and the performance desired. Specifically, amounts of an anti-inflammatory such as gorgonian extract for purposes of this invention will range from 0.00001% to 20%, preferably from 0.0001% to 5%, and most preferably from 0.1% to 1% by weight.
  • It has been surprisingly found that hair growth can be significantly inhibited by addition of a 5 alpha reductase inhibitor to the inventive combination. It is known that 5 alpha reductase promotes the formation of 5 dihydrotestosterone (DHT), a product of testosterone. DHT is the hormone in skin that stimulates hirsutism, which is male pattern hair growth. It is believed that reducing DHT can result in reduction of hirsutism or male pattern hair loss. Therefore, inhibiting the formation of 5 alpha reductase is believed to prevent the formation of DHT and therefore prevent hirsutism and prevent male pattern hair loss. Surprisingly, however, it is believed that combining a 5 alpha reductase inhibitor with the presenting inventive composition helps retard hair growth in all areas of the body, including areas with typical male pattern hair loss, as shown in Example 3 below.
  • Suitable 5 alpha reductase inhibitors include inhibitors commonly known in the art and include but are not limited to saw palmetto, woodworm (Artemisinin), liposome encapsulated azuleic acid (Azelosome), clove extract (Chouji Liquid), Zinc salt of L-Pyrrolidone Carboxylic Acid (Zincidone®), mixture of water, hydrolyzed soy protein, 3-aminopropane, sulfonic acid and sodium chondroitin sulfate (Capigen), seaweed extract (Phlorogine), isolutrol, progesterone, (5, 20-R)-4-diazo-21-hydroxy-20-methyl pregnan-3-one, (4R)-5-10-seco-19-Norpregna4,5-diene-3,10,20 trione, 4-androstene-3-one-17-carboxylic acid, and its methyl ester, 17-beta-N,N-diethylcarbamoyl-9-methyl-4-aza-5-alpha-androstane-3-one, 11-alpha-OH-progesterone, 17-alpha-OH-progesterone, and 20-alpha-OH-progesterone.
  • The amount will vary depending on the formulation and the performance desired. Preferably, the 5 alpha reductase inhibitor is saw palmetto and is present in the amount from 0.0001% to 10%, more preferably from 0.001% to 5% and most preferable from 0.01% to 1%.
  • In yet another alternate preferred embodiment, the appearance of hair can be further reduced by the addition of a whitening agent in the inventive formulations. Suitable whitening agents include yeast extract (Yeast AE), ferulic acid, BV-OSC (vitamin C derivative from Barnet), Na+ hinokitiol, licorice extract (glabridin), etioline (extract of mitracarpus & bearberry in combination with glycerin and butylene glycol), phytoclar II (mulberry & scutellaria from Coletica), arbutin, resveratrol and kojic acid. Particularly preferred is glabridin obtained from Alchem Internationl Ltd., at 201, Empire Plaza, Mehrauli-Gurgaon Road, Sultanpur, New Delhi, India.
  • The amount will vary depending on the formulation and the performance desired. Preferably, the whitening agent is present in the amount from 0.0001% to 20%, more preferably from 0.001% to 15% and most preferable from 0.01% to 10%.
  • It is believed that a component with estrogen-like activity may surprisingly aid in compositions for the retardation of hair growth. Therefore, in an alternate preferred embodiment, the present invention further comprises an estrogen-like component. Particularly preferred supplements are plant extracts such as solgen-40 C (a soy extract), wild yarn and ginseng or phytoestrogens derived therefrom. Particularly preferred is solgen-40 C obtained from Solbar Hatzor Ltd. located in Kibbutz Hatzor, P.O. Box 2230, Ashdod, Israel, 77121.
  • The amount will vary depending on the formulation and the performance desired. Preferably, the plant extract is present in an amount of 0.0001% to 25%, more preferably from 0.001% to 15% and most preferably from 0.01% to 10%.
  • In yet another preferred embodiment, the present inventive composition may contain conventional hair removal ingredients (such as thioglycollate) in any amount desired as would be compatible with the present composition. A list of conventional hair removal ingredients can be found in the International Cosmetic Ingredient Dictionary, CTFA, Sixth Edition, 1995.
  • The composition further comprises a cosmetically acceptable vehicle that is suitable for topical application to skin, hair and/or nails. Cosmetically acceptable vehicles are well known in the art and are selected based on the end use of the application. For example, vehicles of the present invention include, but are not limited to, those suitable for application to the skin. Such vehicles are well known to those of ordinary skill in the art, and can include one or more compatible liquid or solid filler diluents or vehicles which are suitable for application to the skin. The exact amount of vehicle will depend upon the level of any other optional ingredients that one of ordinary skill in the art would classify as distinct from the vehicle (e.g., other active components). The compositions of the present invention preferably comprise from about 40% to about 99.99%, more preferably from about 70% to about 99.99%, and most preferably from about 80% to about 98%, by weight of the composition, of a vehicle.
  • The vehicle and the compositions herein can be formulated in a number of ways, including but not limited to emulsions. For example, suitable emulsions include oil-in-water, water-in-oil, water-in-oil-in-water, oil-in-water-in-oil, and oil-in-water-in-silicone emulsions. Preferred compositions comprise an oil-in-water emulsion.
  • The compositions of the present invention can be formulated into a wide variety of product types, including shampoos, creams, waxes, pastes, lotions, milks, mousses, gels, oils, tonics and sprays. Preferred compositions are formulated into lotions, creams, gels, shampoos and sprays. These product forms may be used for a number of applications, including but not limited to, hand and body lotions, cold creams, facial moisturizers, anti-acne preparations, topical analgesics, make-ups/cosmetics including foundations, eyeshadows, lipsticks and the like. Any additional components required to formulate such products vary with product type and can be routinely chosen by one skilled in the art.
  • If compositions of the present invention are formulated as an aerosol and applied to the skin as a spray-on product, a propellant is added to the composition. Examples of suitable propellants include chlorofluorinated lower molecular weight hydrocarbons. A more complete disclosure of propellants useful herein can be found in Sagarin, Cosmetics Science and Technology, 2nd Edition, Vol. 2, pp. 443-465 (1972).
  • Other Components
  • The formulation also can comprise other components that may be chosen depending on the carrier and/or the intended use of the formulation. Additional components include, but are not limited to, water soluble sunscreens (such as Eusolex 232); oil soluble sunscreens (such as octyl methoxycinnamate); and organic sunscreens (such as camphor derivatives, cinnamates, salicylates, benzophenones, triazines, PABA derivatives, diphenylacrylate derivatives, and dibenzoylmethane derivatives.); antioxidants (such as BHT); chelating agents (such as disodium EDTA); emulsion stabilizers (such as carbomer); preservatives (such as methyl paraben); fragrances (such as pinene); flavoring agents (such as sorbitol); humectants (such as glycerine); waterproofing agents (such as PVP/Eicosene copolymer); water soluble film-formers (such as hydroxypropyl methylcellulose); oil-soluble film formers (such as hydrogenated C-9 Resin); moisturizing agents, such as cholesterol; cationic polymers (such as Polyquatenium 10); anionic polymers (such as xanthan gum); vitamins (such as tocopherol); and the like.
  • The compositions can also encompass one or more active components, and as such can be either cosmetic or pharmaceutical compositions. Examples of useful actives include, but are not limited to, those that improve or eradicate age spots, keratoses and wrinkles, analgesics, anesthetics, anti-acne agents, antibacterials, antiyeast agents, antifungal agents, antiviral agents, antidandruff agents, antidermatitis agents, antipruritic agents, antiemetics, antihyperkeratolytic agents, anti-dry skin agents, antiperspirants, antipsoriatic agents, antiseborrheic agents, hair conditioners and hair treatment agents, antiaging agents, antiwrinkle agents, antiasthmatic agents and bronchodilators, sunscreen agents, antihistamine agents, depigmenting agents, wound-healing agents, vitamins, corticosteroids, tanning agents or hormones. More specific examples of useful active agents include retinoids such as retinol, and esters, acids, and aldehydes thereof; ascorbic acid, and esters and metal salts thereof, tocopherol and esters and amide derivatives thereof; shark cartilage; milk proteins; alpha- or beta-hydroxy acids; DHEA and derivatives thereof; topical cardiovascular agents; clotrimazole, ketoconazole, miconozole, griseofulvin, hydroxyzine, diphenhydramine, pramoxine, lidocaine, procaine, mepivacaine, monobenzone, erythromycin, tetracycline, clindamycin, meclocyline, hydroquinone, minocycline, naproxen, ibuprofen, theophylline, cromolyn, albuterol, hydrocortisone, hydrocortisone 21-acetate, hydrocortisone 17-valerate, hydrocortisone 17-butyrate, betamethasone valerate, betamethasone diproprionate, triaminolone acetonide, fluocinonide, clobetasol, proprionate, benzoyl peroxide, crotamiton, propranol, promethazine, and mixtures thereof.
  • Particularly preferred embodiments of the present formulations are moisturizing after-shaves. To that end, the present formulations are combined with agents that are moisturizers, emollients or humectants. Examples of useful combinations are oils, fats, waxes, esters, fatty acid alcohols, fatty acid ethoxylates, glycols, sugars, hyaluronic acid and hyaluronates, dimethicone, cyclomethicone, and the like. Further examples can be found in the International Cosmetic Ingredient Dictionary, CTFA, Sixth Edition, 1995.
  • Method of Retardation of Hair Growth
  • The present inventive compositions are particularly useful as hair growth retardation products. The present inventive compositions and methods of the present invention provide a unique combination that surprisingly retards hair growth. Hair growth can be retarded on the face including eyebrows, upper lips, and sideburns, on the body including legs, ears and back, and any other area of the body where undesired hair growth may occur. The present inventive compositions are particularly preferred to prevent hair growth after shaving.
  • The present inventive method comprises administering or topically applying to the skin a safe and effective amount of the combination of the present invention. The amounts of the components in the compositions will vary widely depending upon the level of hair growth already in existence in the subject (if such exists), the rate of further hair growth, and the level of regulation desired.
  • A preferred amount of cosmetically or pharmaceutically treating the skin is via chronic topical application of a safe and effective amount of the novel composition to regulate hair growth. The amount of the composition and the frequency of topical application to the skin can vary widely, depending upon the rate of hair growth for the individual. It is well within the purview of the skilled artisan, such as a dermatologist or other health care provider, to regulate pharmaceutical dosages according to patient needs. The method of the present invention is particularly useful after shaving.
  • It is suggested as an example that topical application range from about once per week to about 4 or 5 times daily, preferably from about 3 times a week to about 3 times daily, most preferably about once or twice per day. In a preferred embodiment, the present method is utilized as an aftershave and can be applied directly to the face after shaving. The compositions will comprise from about 0.001% to 5%, preferably from about 1% to 5%, and most preferably from about 1% to 4% of the active components.
  • The following examples further illustrate the invention, but the invention is not limited thereto.
  • EXAMPLE 1 Clinical Study
  • A composition comprising the preferred embodiment was applied on the face of male volunteers and evaluated for its ability to make beard hair less noticeable by retarding hair growth, lightening facial hair or reducing the appearance of 5 o'clock shadow.
  • Study Design:
  • 1. Subject Selection/Inclusion Criteria:
  • Fourteen men with normal to heavy and dark facial (beard) hair, who are in good general health and free of any dermatological disorders, were qualified for this study.
  • 2. Clinical Protocol:
  • At every visit the men arrive at the lab between 7-8 am without shaving. They bring their razor with a new blade and regular shave product and shave at the lab. Immediately after shaving, closeness of shave is documented by taking close-up photographs with the digital camera. The subjects return to the lab after 8 hours and 24 hours and are photographed again to document 5 o'clock shadow and 24 hour beard hair growth.
  • At the end of the first visit the subjects are given a product containing the inventive composition of the present invention (hereinafter “Product”), which they use 2 times a day for 4 weeks. For the duration of this study the subjects are asked to use the same shave product every time they shave. They are instructed not to use the product on the day of testing. The subjects are given a very brief questionnaire at every 8 and 24 hour time point to evaluate beard texture, color, and appearance. At the end of the study they are given more a comprehensive questionnaire to evaluate the product. At Weeks 1, 2, 4 and 8 the subjects return for testing and the above procedures are repeated every time.
    3. Composition:
    Ceteareth-12 Eumulgin B-1 3.2%
    PEG-10 Soya Sterol Generol 122   1%
    Sorbitan Sesquioleate Arlacel 83V 0.1%
    Glyceryl Stearate SE Glyceryl Monostearate 2.6%
    24 SE
    Coco-Caprylate/Caprate Cetiol LC   3%
    Stearic Acid Dermofat 4919 0.1%
    Stearyl Alcohol/ Promulgen G-CG 0.5%
    Ceteareth-20
    Hydrogenated Lecithin Lecinol S-10 0.1%
    Cholesterol NAB Cholesterol 0.2%
    Glycereth-26 Liponic EG1 0.2%
    Octyldodecanol Eutanol G NF 0.1%
    Phytoshingosine DS-Phytosphingosine 0.1%
    Purified Water Deionized Water 68.546%  
    Disodium EDTA Disodium EDTA/Trilon BD 0.1%
    Phenoxyethanol/
    Chlorphenesin/
    Glycerin/Methyl Paraben/
    Benzoic Acid Germazide MPB   1%
    Potassium Sorbate Sorbistat K 0.1%
    Methylparaben Methyl Paraben NF 0.35% 
    Pemulen TR-1   5%
    (2% Disp in MethylP)
    (Deionized water 4.8925%
    Pemulen TR-1
    Acrylates/C10-30
    Alkyl Acrylate
    Crosspolymer 0.1%
    Methyl Paraben Methyl
    Paraben NF 0.0075%)
    Purified Water (97.85%) Deionized Water   4%
    Polyquaternium-10 (2%) Polymer LR-400 (UCARE) 0.004% 
    Butylene Glycol (0.15%) 1,3 Butylene Glycol   5%
    Glycyrrhiza Glabra Glabridin 0.05% 
    (Licorice) Extract
    Ursolic Acid Ursolic Acid 90% 0.2%
    Cyclomethicone Dow Corning 245 Fluid   2%
    Hyaluronic Acid (1% SOL) 0.5%
    (Purified Water (98.10%) Deionized Water 0.4905%  
    Sodium Hyaluronate (1%) Sodium Hyaluronate HMW 0.005% 
    Phenoxyethanol (.70%) Emeressence 1160 0.0035%  
    (Rose Ether)
    Yeast Extract Yeast Extract AE   1%
    Soy Isoflavones/ Solgen 40 0.2%
    Butylene Glycol
    Sea Whip Extract Gorgonian Extract BG/NP 0.5%
    Phenoxyethanol Emeressence 1160 0.25% 
    (Rose Ether)

    Data Analysis:
  • Self-assessment and product evaluation questionnaires are compiled and the average results are shown on Tables 1-2 and FIGS. 1-2. Beard growth is evaluated from the digital photographs via image analysis. A template of the right and left side of the face of each subject is made and the amount of beard hair within this area is measured at each time point. The amount of hair covering the outlined area is directly related to hair length and therefore to hair growth.
  • Results:
  • The results of this study show that topical treatment with a product containing the above composition is effective in improving beard texture, color and appearance and reducing beard growth. Table 1 below and FIG. 1 summarize the results of the study.
    TABLE 1
    Self Assessment of Beard % Improvement of Texture, Color and Appearance
    8 hours after shaving 24 hours after shaving
    1 Wk 2 Wks 4 Wks 8 Wks 1 Wk 2 Wks 4 Wks 8 Wks
    TEXTURE 18.8 27.1 27.8 35.4 13.5 29.1 32.1 28.7
    COLOR 19.4 30.1 38.6 49.0 9.1 27.5 32.5 25.6
    APPEARANCE 23.8 27.4 32.1 43.6 15.0 30.2 31.3 25.6
  • As seen from Table 1 above and corresponding FIG. 1, self-assessment of beard texture, color and appearance at 8 and 24 hours after shaving clearly show an improvement with product use. After 1 week of treatment there was about a 20% improvement in texture, color and appearance of 5 o'clock shadow (8 hours after shaving) and it increased to about 35-50% after 8 weeks of treatment. At the 24 hour time point there was a 10-15% improvement after 1 week of treatment and increased to 25-30% between 2 and 8 weeks of treatment.
  • User's assessment of product's performance after 8 weeks of use are shown below. The users were asked to comment on the reduction of 5 o'clock shadow, beard growth, rate the product and likelihood to purchase it. Table 2 below and corresponding FIG. 2 summarize these results.
    TABLE 2
    Evaluation of Beard Growth Retardant Product after 8 Weeks of use
    Results based on a scale from 1 (Poor)-10 (Excellent)
    Comment Average Score S.D.
    Reduce appearance of 5 o'clock shadow 5.2 2.4
    Reduce beard growth 5.0 2.2
    Likelihood to buy a product like this 5.1 3.7
    Rate this product 4.9 3.3
  • As seen in Table 2 above and FIG. 2, on a scale of poor (1) to excellent (10) the participants rated the composition about a 5.
  • Beard growth is evaluated via image analysis from close up digital photographs. These results show that the composition was very effective in reducing beard growth. Table 3 below and corresponding FIG. 3 summarize these results.
    TABLE 3
    Evaluation of Beard Growth Retardant Product
    from Digital images via Image Analysis
    % Decrease in beard growth
    Time after shaving 1 Week 2 Weeks 4 Weeks 8 Weeks
    Immediately 48.0 52.9 41.5 51.8
    8 hours 48.1 73.1 77.6 83.0
    24 hours 38.8 68.3 52.4 40.6
  • As seen from Table 3 above and corresponding FIG. 3, after one week and up to 8 weeks of treatment there is a 40-50% beard reduction immediately after shaving, thereby indicating a closer shave. The best results are seen 8 hours after shaving at the 5 O'clock shadow, where after one week of treatment there is a 48% reduction in beard growth and it steadily improves to 83% after 8 weeks. Twenty four hours after shaving there is a 38-68% reduction in beard growth after 1-8 weeks of treatment with some variation in the data.
  • Based on the results of the study in the above Example 1, it is seen that topical treatment with the composition is effective in improving beard texture, color and appearance and reducing beard growth.
  • EXAMPLE 2 Comparative Study
  • The following example provides a clinical study comparing an embodiment of the present invention with a conventional hair growth retardation product, using a control to note the differences.
  • Formation of Study Panel:
  • Adult women are recruited from a local population. The following criteria for inclusion and exclusion are based on the information obtained from the candidates and from an examination of the area that is involved in the study.
  • Inclusion Criteria: To be considered as a potential subject, each candidate must:
      • shaved legs daily
      • express willingness to cooperate with the investigator;
      • convince the investigator that she was dependable and would comply with the study regimen;
      • demonstrate the ability to understand the purpose of the study and what was required of her to bring the study to a meaningful conclusion;
      • demonstrate the ability to understand the risks associated with participation; and
      • demonstrate the ability to read and understand all the items in the informed consent document.
        Exclusion Criteria: A prospective participant is excluded if the interview or examination disclosed any of the following:
      • a systemic illness that contra-indicates participation;
      • any dermatological disorders in the areas that are to be used in the study;
      • pregnant women or lactating mothers;
      • using systemic or topical retinoids, antihistamines or similar agents.
        Composition of Panel:
        19 women who satisfy all the requirements itemized in the list of inclusion and exclusion criteria.
        Test Products:
        Product A: Inventive Composition (hereinafter “Hair Growth Retardation Complex”)
      • Soy Extract (0.2% Solgen 40)
      • Phytospingosine 90.1%)
      • Gorgonian Extract (0.5%)
      • Yeast AE (1%)
      • Ursolic Acid (0.2%)
      • Glabridin (0.05%)
        Product B: Conventional Hair Growth Retardation Product
      • Sanguisorba Officinalis Root Extract
        Product C: Traditional Moisturizer (Control)
        Method of Application:
  • The women are instructed to apply the products to their legs three times a day, morning, afternoon, and evening, for 8 weeks. Group 1 applies product A to the right leg and product C to the left leg. Group 2 applies product B to the right leg and product C to the left leg. On the day of testing, the women do not apply the products for at least 12 hours before measurements were taken. Product use is monitored by a daily diary as well as assessment of remaining package content at the end of the study.
  • Clinical Test Procedure:
  • This is a double blinded study consisting of eight weeks of product use. The legs are the test site. The panelists refrain from using any treatment products on the test sites except for the test products provided. The panelists are instructed to shave their legs four days prior to each visit. Evaluations are carried out before product application (baseline), and at two, four, and eight weeks during the course of treatment. The panelists report to the Testing Center for testing.
  • Test Procedure:
  • 1. Reduction of Hair Growth
  • At the outset of the study a particular area on the legs of each panelist demonstrating four days of hair growth is marked. The images of that specific portion of the leg are obtained using a fiber optic microscope (Hi-Scope, Vacaville, Calif.) at a magnification of 40× (approximately 1 sq. cm.) Ten sites are chosen per leg per panelist. The same area is photographed at each time point following the initial visit. The stored images are digitized and analyzed using an image analysis program, Optimas 6.51. The average hair length is calculated using total area 4 days after shaving at each time point to determine the amount of hair growth.
  • 2. Results
    TABLE 4
    Comparative Study Results
    Time Point Average % Reduction p-value
    Hair Growth Retardation Product
    Baseline 0.97
    2 weeks 0.83 14% p > 0.05
    4 weeks 0.82 16% p > 0.05
    8 weeks 0.69 29% p < 0.05
    Conventional Hair Growth Retardation Product
    Baseline 1.09
    2 weeks 0.94 14% p > 0.05
    4 weeks 0.93 15% p > 0.05
    8 weeks 0.88 20% p < 0.05
    Control
    Baseline 1.12
    2 weeks 1.12  0% p > 0.05
    4 weeks 1.19  −6%   p > 0.05
    8 weeks 1.12  0% p > 0.05
  • As can be seen in Table 4 above and corresponding FIG. 4, the hair growth retardation product incorporating the inventive composition reduces hair growth by 29% after 8 weeks of use, as opposed to 20% reduction with the conventional hair growth retardation product and 0% using the control.
  • EXAMPLE 3 Comparative Study
  • The following example provides a clinical study comparing the inventive composition with the combination of ornithine decarboxylase inhibitor, anti-angiogenic active and an anti-inflammatory and the alteranate embodiment including the 5 alpha reductase inhibitor in retarding hair growth.
  • Formation of Study Panel:
  • Adult men who were interested in taking part in this study were recruited from a local population. The following criteria for inclusion and exclusion were based on the information obtained from the candidates and from an examination of the area that was involved in the study.
  • Inclusion Criteria: To be considered as a potential subject, each candidate must have:
      • a 5 o'clock shadow
        Exclusion Criteria: A prospective participant is excluded if the interview or examination disclosed any of the following:
      • a systemic illness that contra-indicates participation;
      • any dermatological disorders in the areas that were to be used in the study; or
      • uses systemic or topical retinoids, antihistamines or similar agents.
        Composition of Panel:
  • The panel is composed of 27 men who satisfy all the requirements itemized in the list of inclusion and exclusion criteria.
  • Test Products:
    • Group 1: Inventive composition with 0.1% 5 alpha reductase inhibitor, saw palmetto.
    • Group 2: Inventive composition without 5 alpha reductase inhibitor.
      Method of Application:
      Procedure for Shaving:
  • The panelists are instructed to report for all visits with a 24 hour beard growth. The men then shave with their own razor and shaving cream. Measurements are taken immediately after shaving, and after 8 and 24 hours.
  • The men are instructed to apply the product to their face two times a day, morning and evening, for 8 weeks. On the day of testing, the men do not apply the products for at least 12 hours before measurements were taken. Product use is monitored by a daily diary as well as assessment of remaining package content at the end of the study.
  • Clinical Test Procedure:
  • This is a double blinded controlled study consisting of eight weeks product use. The test site is the face. The men refrain from using any treatment products on the test sites except for the test products provided. The panelists are instructed to report to the testing center with at least a 24 hour beard growth. Evaluations are carried out before product application (baseline), and after four, and eight weeks during the course of treatment.
  • Test Procedure:
  • 1. Reduction of Hair Growth
  • At the outset of the study a particular area on the face of each panelist is marked. The images of that specific portion of the face are obtained using a Fuji S-2 Digital Camera with a Canfield epilume adaptation. The Canfield Epilume allows for close up contact photos to be taken at a fixed distance. The same area is photographed immediately, 8 hours, and 24 hours after shaving at each visit. The stored images are digitized and analyzed using an image analysis program, Optimas 6.51.
  • Shave Time—
  • At each time point the men use an electronic timer to measure the length of time needed to shave.
  • Self Evaluations—
  • A self evaluation is performed by each panelist on the appearance of their beard, 8 and 24 hours after shaving. The following 10 point analog scale is used:
    0 10
    Not Noticeable Extremely
    Noticeable
  • 2. Results of Hair Retardation
    TABLE 5
    Panelists Assessment
    Hair Retardation of Beard Appearance Shave
    8 hours 24 hours 5 hours 24 hours Time
    Group 1
    Inventive Composition with 5 alpha reductase inhibitor
    4 weeks 30% 29% 24% 21% 15%
    8 weeks 47% 39% 30% 27% 20%
    Group 2
    Inventive Composition without 5 alpha reductase inhibitor
    4 weeks 17% 27% 19% 15%  −6%  
    8 weeks 25% 38% 23% 19%  1%
  • As can be seen in Tables 4 and 5 above, after eight weeks of product use with the composition containing the 5 alpha reductase inhibitor, panelists experienced a 47% reduction in hair growth eight hours after shaving, as compared to a 17% reduction without the addition of the 5 alpha reductase inhibitor in the product. Reduction in the appearance of hair growth was 30% with the 5 alpha reductase inhibitor in the product and 23% without, eight hours after shaving.
  • It should be understood that the specific forms of the invention herein illustrated and described are intended to be representative only. Changes, including but not limited to those suggested in this specification, may be made in the illustrated embodiments without departing from the clear teachings of the disclosure. Accordingly, reference should be made to the following appended claims in determining the full scope of the invention.

Claims (30)

  1. 1. A cosmetic composition comprising:
    an ornithine decarboxylase inhibitor;
    an anti-angiogenic active;
    an anti-inflammatory; and
    a cosmetically acceptable vehicle.
  2. 2. The cosmetic composition of claim 1 wherein the ornithine decarboxylace inhibitor is a pentacyclic triterpene selected from the group consisting of ursolic acid, betulin, betulinic acid, oleanolic acid, betulin mono and di-succinate or glutarate and polyethylene glycol and wherein the ornithine decarboxylace inhibitor is present in an amount from 0.1% to 50%.
  3. 3. The cosmetic composition of claim 1 wherein the anti-angiogenic active is a sphingo lipid selected from the group consisting of phytosphingosine, dihydrosphingosine, sphingosine and dehydrosphingosine and wherein the anti-angiogenic active is present in an amount of from 0.01% to 10%.
  4. 4. The cosmetic composition of claim 1 wherein the anti-angiogenic active is selected from the group consisting of magnolia extract, shark cartilage and tetrahydrocurcumin.
  5. 5. The cosmetic composition of claim 1 wherein the anti-inflammatory is selected from the group consisting of gorgonian extract, hoelen extract, ximenynic acid, hesperitin, tea polyphenols and licorice extract and wherein the anti-inflammatory is present in an amount from 0.0001% to 20%.
  6. 6. The cosmetic composition of claim 1 further comprising a whitening agent selected from the group consisting of yeast extract, ferulic acid, vitamin C derivatives, Na+ hinokitiol, licorice extract, extracts of mitracarpus scaber/bearberry, extracts of mulberry/scutellaria, arbutin, resveratrol and kojic acid.
  7. 7. The cosmetic composition of claim 1 further comprising a plant extract selected from the list consisting of soy extract, wild yarn and ginseng.
  8. 8. The cosmetic composition of claim 1 further comprising a 5 alpha reductase inhibitor selected from the group consisting of saw palmetto, woodworm (Artemisinin), liposome encapsulated azuleic acid (Azelosome), clove extract (Chouji Liquid), Zinc salt of L-Pyrrolidone Carboxylic Acid (Zincidoneg), mixture of water, hydrolyzed soy protein, 3-aminopropane, sulfonic acid and sodium chondroitin sulfate (Capigen), seaweed extract (Phlorogine), isolutrol, progesterone, (5,20-R)-4-diazo-21-hydroxy-20-methyl pregnan-3-one, (4R)-5-10-seco-19-Norpregna4,5-diene-3,10,20 trione, 4-androstene-3-one-17-carboxylic acid, and its methyl ester, 17-beta-N,N-diethylcarbamoyl-9-methyl-4-aza-5-alpha-androstane-3-one, 11-alpha-OH-progesterone, 17-alpha-OH-progesterone, and 20-alpha-OH-progesterone.
  9. 9. A cosmetic composition comprising:
    from 0.1 to 50% of a penticylic triterpene;
    from 0.01 to 10% of a sphingo lipid;
    from 0.0001 to 20% of gorgonian extract; and
    a cosmetically acceptable vehicle.
  10. 10. The cosmetic composition of claim 9 wherein the pentacyclic triterpene is selected from the group consisting of ursolic acid, betulin, betulinic acid, oleanolic acid, betulin mono and di-succinate or glutarate and polyethylene glycol.
  11. 11. The cosmetic composition of claim 9 wherein the sphingo lipid is selected from the group consisting of phytosphingosine, dihydrosphingosine, sphingosine and dehydrosphingosine.
  12. 12. The cosmetic composition of claim 9 further comprising an anti-angiogenic active selected from the group consisting of magnolia extract, shark cartilage and tetrahydrocurcumin.
  13. 13. The cosmetic composition of claim 9 further comprising a whitening agent selected from the group consisting of yeast extract, ferulic acid, vitamin C derivatives, Na+ hinokitiol, licorice extract, extracts of mitracarpus scaber/bearberry, extracts of mulberry/scutellaria, arbutin, resveratrol and kojic acid.
  14. 14. The cosmetic composition of claim 9 further comprising a plant extract selected from the group consisting of soy extract, wild yarn, and ginseng.
  15. 15. The cosmetic composition of claim 9 further comprising a 5 alpha reductase inhibitor selected from the group consisting of saw palmetto, woodworm (Artemisinin), liposome encapsulated azuleic acid (Azelosome), clove extract (Chouji Liquid), Zinc salt of L-Pyrrolidone Carboxylic Acid (Zincidone®), mixture of water, hydrolyzed soy protein, 3-aminopropane, sulfonic acid and sodium chondroitin sulfate (Capigen), seaweed extract (Phlorogine), isolutrol, progesterone, (5,20-R)-4-diazo-21-hydroxy-20-methyl pregnan-3-one, (4R)-5-10-seco-19-Norpregna4,5-diene-3,10,20 trione, 4-androstene-3-one-17-carboxylic acid, and its methyl ester, 17-beta-N,N-diethylcarbamoyl-9-methyl-4-aza-5-alpha-androstane-3-one, 11-alpha-OH-progesterone, 17-alpha-OH-progesterone, and 20-alpha-OH-progesterone.
  16. 16. A method for retarding the growth hair comprising applying a composition comprising
    from 0.1 to 50% of an ornithine decarboxylase inhibitor;
    from 0.01 to 10% of an anti-angiogenic active;
    from 0.0001 to 20% of an anti-inflammatory; and
    a cosmetically acceptable vehicle.
  17. 17. The method of claim 16 wherein the ornithine decarboylace inhibitor is a pentacyclic triterpene selected from the group consisting of ursolic acid, betulin, betulinic acid, oleanolic acid, betulin mono and di-succinate or glutarate and polyethylene glycol.
  18. 18. The method of claim 16 wherein the anti-angiogenic active is a sphingo lipid selected from the group consisting of phytosphingosine, dihydrosphingosine, sphingosine and dehydrosphingosine.
  19. 19. The method of claim 16 wherein the anti-angiogenic active is selected from the group consisting of magnolia extract, shark cartilage and tetrahydrocurcumin.
  20. 20. The method of claim 16 wherein the anti-inflammatory is selected from the group consisting of gorgonian extract, hoelen extract, ximenynic acid, hesperitin, tea polyphenols and licorice extract.
  21. 21. The method of claim 16 wherein the composition further comprises a whitening agent selected from the group consisting of yeast extract, ferulic acid, vitamin C derivatives, Na+ hinokitol, licorice extract, extracts of mitracarpus scaber/bearberry, extract of mulberry/scutellaria, arbutin, resveratrol and kojic acid.
  22. 22. The method of claim 16 wherein the composition further comprises a plant extract selected from the group consisting of soy extract, wild yarn and ginseng.
  23. 23. The method of claim 16 wherein the composition further comprises a 5 alpha reductase inhibitor selected from the group consisting of saw palmetto, woodworm (Artemisinin), liposome encapsulated azuleic acid (Azelosome), clove extract (Chouji Liquid), Zinc salt of L-Pyrrolidone Carboxylic Acid (Zincidone®), mixture of water, hydrolyzed soy protein, 3-aminopropane, sulfonic acid and sodium chondroitin sulfate (Capigen), seaweed extract (Phlorogine), isolutrol, progesterone, (5,20-R)-4-diazo-21-hydroxy-20-methyl pregnan-3-one, (4R)-5-10-seco-19-Norpregna4,5-diene-3,10,20 trione, 4-androstene-3-one-17-carboxylic acid, and its methyl ester, 17-beta-N,N-diethylcarbamoyl-9-methyl-4-aza-5-alpha-androstane-3-one, 11-alpha-OH-progesterone, 17-alpha-OH-progesterone, and 20-alpha-OH-progesterone.
  24. 24. A method of retarding hair growth comprising applying a cosmetic composition comprising:
    from 0.1 to 50% of a penticylic triterpene;
    from 0.01 to 10% of a sphingo lipid;
    from 0.0001 to 20% of gorgonian extract; and
    a cosmetically acceptable vehicle.
  25. 25. The method of claim 24 wherein the pentacyclic triterpene is selected from the group consisting of ursolic acid, betulin, betulinic acid, oleanolic acid, betulin mono and di-succinate or glutarate and polyethylene glycol.
  26. 26. The method of claim 24 wherein the sphingo lipid is selected from the group consisting of phytosphingosine, dihydrosphingosine, sphingosine and dehydrosphingosine.
  27. 27. The method of claim 24 wherein the composition further comprises an anti-angiogenic active selected from the group consisting of magnolia extract, shark cartilage and tetrahydrocurcumin.
  28. 28. The method of claim 24 wherein the composition further comprises a whitening agent selected from the group consisting of yeast extract, ferulic acid, vitamin C derivatives, Na+ hinokitol, licorice extract, extracts of mitracarpus scaber/bearberry, extract of mulberry/scutellaria, arbutin, resveratrol and kojic acid.
  29. 29. The method of claim 24 wherein the composition further comprises a plant extract selected from the group consisting of soy extract, wild yarn, and ginseng.
  30. 30. The method of claim 24 wherein the composition further comprises a 5 alpha reductase inhibitor selected from the group consisting of saw palmetto, woodworm (Artemisinin), liposome encapsulated azuleic acid (Azelosome), clove extract (Chouji Liquid), Zinc salt of L-Pyrrolidone Carboxylic Acid (Zincidone®), mixture of water, hydrolyzed soy protein, 3-aminopropane, sulfonic acid and sodium chondroitin sulfate (Capigen), seaweed extract (Phlorogine), isolutrol, progesterone, (5,20-R)-4-diazo-21-hydroxy-20-methyl pregnan-3-one, (4R)-5-10-seco-19-Norpregna4,5-diene-3,10,20 trione, 4-androstene-3-one-17-carboxylic acid, and its methyl ester, 17-beta-N,N-diethylcarbamoyl-9-methyl-4-aza-5-alpha-androstane-3-one, 11-alpha-OH-progesterone, 17-alpha-OH-progesterone, and 20-alpha-OH-progesterone.
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