WO2009052518A2 - Procédés et compositions destinés à réduire l'hirsutisme se manifestant par une pilosité du visage chez les femmes - Google Patents

Procédés et compositions destinés à réduire l'hirsutisme se manifestant par une pilosité du visage chez les femmes Download PDF

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WO2009052518A2
WO2009052518A2 PCT/US2008/080546 US2008080546W WO2009052518A2 WO 2009052518 A2 WO2009052518 A2 WO 2009052518A2 US 2008080546 W US2008080546 W US 2008080546W WO 2009052518 A2 WO2009052518 A2 WO 2009052518A2
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acid
composition
hair
hirsutism
agent
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PCT/US2008/080546
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WO2009052518A3 (fr
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Randall Wilkinson
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Aspen Benefits Group, Llc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth
    • A61Q7/02—Preparations for inhibiting or slowing hair growth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/27—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/347—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/362—Polycarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/63—Steroids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/645—Proteins of vegetable origin; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A61K8/673—Vitamin B group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782—Enzyme inhibitors; Enzyme antagonists

Definitions

  • Hirsutism is the presence of terminal hair in females in locations that normally are vellus hair, primarily the face. The causes underlying the appearance of unwanted facial hair in women, or hirsutism, appear to be primarily hormonal. From childhood onward, other than terminal scalp hair, the entire body is covered by vellus hair (with the exception of a few areas such as the lips, palms, soles of the feet and genital areas). At puberty, some vellus hair is transformed into terminal hair by the action of androgens. This transformation takes place in both sexes in areas where the follicles are sensitive to androgen action, such as the pubic, axillary (arm pits), lower leg and forearm areas. In males, the transformation occurs with wider distribution, usually including portions of the abdomen, chest and face.
  • DHT dihydrotestosterone
  • a hormone strongly associated with the conversion from vellus to terminal hair is dihydrotestosterone (DHT), the 5-alpha reduced form of testosterone.
  • DHT does not circulate in the bloodstream in appreciable quantities. Instead, it is created by the conversion of testosterone in the tissue by the action of the 5-alpha-reductase enzyme.
  • 5-alpha-reductase enzyme There are two forms of 5-alpha-reductase. Type 1 is primarily present in the skin, whereas Type 2 is associated primarily with male genital tissue such as the testes and prostate, but is also present in genital skin in both sexes.
  • Type 1 5-alpha-reductase is not evenly distributed through the skin of the body.
  • PSU pilosebaceous unit
  • Testosterone levels increase in both sexes with the onset of puberty, albeit in considerably higher concentrations in the male.
  • DHT which has an 8-fold higher affinity for androgen receptors than testosterone, binds with androgen receptors in the hair follicle and drives the production of the terminal hair. It is estimated that DHT is 30 times more potent than testosterone in driving processes mediated by androgen receptors.
  • females have a lower level of testosterone substrate available for conversion into DHT and different patterns of androgen receptor sensitivity when compared to males, the expression of terminal hair is more limited.
  • Hirsutism is not the only skin-related disorder mediated by DHT via the 5-alpha- reductase mechanism.
  • DHT is considered a primary causative factor in acne vulgaris.
  • Type 1 5-alpha-reductase is particularly concentrated in the sebaceous glands of the PSU, and more specifically in sebaceous glands of acne-prone areas like the face, neck, upper chest and back.
  • DHT is also considered a primary cause of male pattern baldness, also known as androgenic alopecia.
  • estradiol a primary female hormone, which has a direct inhibitory effect on the conversion of testosterone to DHT, through its stimulation of the action of the aromatase enzyme. As menopause approaches, the glandular secretion of estradiol decreases along with other female hormones.
  • Plucking and tweezing are forms of epilation, defined as the removal of the entire hair shaft, including that beneath the surface of the skin. It involves the removal of the hair shaft from the follicle in whole. This is typically accomplished by tools which grasp the hair shaft at some point above the skin and mechanically pull until the shaft is released from the papilla. Tweezers are a common instrument used. A variation on tweezing is threading, in which a trained operator rotates a filament of thread alongside the affected area of skin and catches the hair shaft in the thread, thus removing it. Other mechanical devices have been developed which automatically grasp the shaft and extract it before moving on to other hairs.
  • Waxing can be considered a variant of plucking and another form of epilation.
  • a specially prepared wax is heated beyond its melting point, then applied to areas of skin with unwanted hair. The wax cools and adheres to the shafts of hair it surrounds. The wax is then peeled away from the skin and pulls the hair shafts out with it.
  • a similar process of epilation is sugaring.
  • Shaving is a form of depilation, defined as the removal of the hair shaft above the surface of the skin. It is the process of severing the shaft of the growing hair at the level of the skin's surface by use of a blade. Any hair extending beyond the skin's surface is removed, but the hair continues to grow and reappears quickly.
  • the very act of shaving may stimulate hair growth [PMID: 6140129], a significant frustration that largely offsets the convenience of shaving when compared with other treatment forms.
  • a woman choosing shaving as her preferred method of control of unwanted facial hair must frequently shave to keep the hair controlled. Trimming can be considered as effectively the same, although the trimmer usually does not sever the shaft as close to the surface as shaving and is not presumed to stimulate hair growth.
  • Electrolysis involves the insertion of a fine wire into the hair follicle by a trained professional. A current of electricity is discharged through the wire, ideally resulting in the destruction of the papilla and matrix, thus preventing recurrence of hair in the follicle. Disadvantages include the tedious, slow and painful process as well as the significant cost and scheduling challenges. Further, for many women, the process is ineffective.
  • Lasers have been developed which deliver focused thermal energy to the hair shaft and from the hair shaft to the papilla and matrix, destroying them.
  • the procedure results in the inability of the follicle to regrow hair.
  • many women find the procedure to be ineffective in that their hair does regrow. Because it is a medical procedure, it must be performed under the care of a physician and trained staff. Women with dark skin are ineligible for treatment because the skin itself will absorb the laser's thermal energy and be damaged. Also ineligible are women whose terminal hair is blonde, gray or white as these colors will not absorb adequate thermal energy to destroy the papilla and matrix. Other disadvantages include the high cost of the procedure as well as the multiple treatments required to accomplish the desired result.
  • compositions, systems, etc. reduce unwanted hirsutism, for example excess terminal facial hair, in women, including ethnically-based excess facial hair in women.
  • the compositions, etc. can also reduce other unwanted hair in women, such as leg hair, pubic hair and/or arm pit hair.
  • the current compositions, etc. can have the benefit, if desired, of being odorless and painless, and their use can consume little time at relatively low cost.
  • the methods can comprise topically administering the compositions to affected areas, resulting in a lessening of the presence of terminal hairs.
  • suitable agents suitable for use in the compositions, methods, etc. include azelaic acid, vitamin B6, zinc, camella sinensis extract, nordihydroguaiaretic acid, oleanolic acid and retinol, which are skin Type 1 5 -alpha reductase inhibitors.
  • the compositions comprise dermatological, anti-hirsutism compositions capable of reducing unwanted terminal facial hair, the composition comprising a first agent comprising an adequate amount of least one dermatologically acceptable skin Type 1 5 -alpha reductase inhibitor and a second agent comprising an adequate amount of least one dermatologically acceptable that agent that inhibits unwanted terminal facial hair without inhibiting skin Type 1 5 -alpha reductase, wherein the first and second agents are provided in an amount sufficient to reduce unwanted terminal facial hair in women, compared to untreated excess facial hair, by at least about 20% in at least about 80% of women administering the composition to the unwanted terminal facial hair.
  • the first agent can comprise at least one of azelaic acid, vitamin B6, zinc, camella sinensis extract, nordihydroguaiaretic acid, oleanolic acid and retinol.
  • the second agent can comprise at least one of dihydromyricetin (wax myrtle extract), Fibraurea Recia extract, and hydrolyzed soy protein.
  • the anti-hirsutism composition can be configured to be administered topically to the face or other affected area of the user.
  • FIG. 1 is a representative depiction of a pilosebaceous unit (PSU).
  • Figure 2 is a representative depiction of the pathways of steroidogenesis.
  • compositions, systems, etc. reduce unwanted hirsutism, in particular excess facial hair, in women, including ethnically-based excess facial hair in women.
  • the mechanism of action does not form part of the methods, compositions, systems, etc., herein, it may be that such compositions, etc., act by effective inhibition of the conversion of testosterone to dihydrotestosterone (DHT), and generally of androgens, to their 5 -alpha-reduced state.
  • DHT dihydrotestosterone
  • the current compositions, etc. can have the benefit, if desired, of being odorless and painless, and their use can consume little time at relatively low cost.
  • compositions can be administered by topical application to affected areas of a combination of agents, resulting in substantial reduction in the stimulation of the androgen receptors of the hair follicle and resulting in a lessening of the presence of terminal hairs.
  • suitable agents suitable for use in the compositions, methods, etc., and thus capable of inhibition, possibly even synergistic inhibition, of unwanted female hirsutism include azelaic acid, vitamin B6, zinc, camella sinensis extract, nordihydroguaiaretic acid, oleanolic acid and retinol, which are skin Type 1 5 -alpha reductase inhibitors.
  • Further efficacy can be achieved by the combination of one or more of these inhibitors of unwanted female hirsutism with one or more agents which inhibit hirsutism by approaches other than the inhibition of 5-alpha-reductase.
  • suitable agents of this type include dihydromyricetin (wax myrtle extract), Fibraurea Recia extract, and hydro lyzed soy protein.
  • compositions, methods, etc., herein further comprise anti-aging agents such as retinol, retinoic acid, green tea extract, gamma-linolenic acid, alpha-linolenic acid, linoleic acid, oleanolic acid, ganoderma lucidum, myricetin, quercitin, dermal peptides, alpha hydroxy acids and beta hydroxy acids.
  • anti-aging agents such as retinol, retinoic acid, green tea extract, gamma-linolenic acid, alpha-linolenic acid, linoleic acid, oleanolic acid, ganoderma lucidum, myricetin, quercitin, dermal peptides, alpha hydroxy acids and beta hydroxy acids.
  • Such agents have one or more of the following bioactivities: a.) Decreasing local type 1 5-alpha-reductase activity in the follicle; b.) Decreasing local type 2 5-alpha-reductase activity in the follicle; c.) Offsetting loss of the local effects of estradiol, such as in menopause, in suppressing DHT expression; d.) Decreasing the proportion of follicles in the anagen phase of hair production and increasing the proportion in the telogen (non-growing) phase; e.) Decreasing the melanin content expressed in the facial hair; f.) Decreasing the thickness of the expressed facial hair.
  • Topical application is one route of delivery of the compositions herein, although other routes may be used. Topical can be useful for at least two reasons.
  • topical delivery is an efficient route of delivery to the hair follicle.
  • Appropriately-formulated, topically-applied agents can easily penetrate into the follicle between the hair shaft and follicular wall. This, then, is a direct route of delivering an agent to the region of the dermal papilla at the base of the follicle, the location of the key biochemical events affecting hair production.
  • topical application may enhance safety. While the agents used in the present method are safe, their application directly to the skin of the affected area limits any unwanted effects elsewhere in the body. Nevertheless, other routes such as oral or subcutaneous or otherwise as desired may be advantageous for persons desiring to reduce overall hair growth or for other desired purposes.
  • Azelaic acid is a saturated dicarboxylic acid derived from grains such as rye, wheat and barley. At a concentration of 20%, it has been shown effective in the treatment of acne. However, in much lower concentrations, it is an effective inhibitor of 5-alpha- reductase in vitro. Its efficacy may be enhanced by zinc and by vitamin B6.
  • Use of azelaic acid has been recommended for treatment of androgenic alopecia (male-pattern baldness), a DHT-dependent skin condition which paradoxically yields loss of hair in contrast to hirsutism's excess of hair and that leads away from the current methods, compositions, etc.
  • the present application incorporates by reference PCT Published Application WO 2007 053422 Al related to treatment of acne, for all its teachings and disclosures.
  • Zinc and other cations have been identified as strong (cadmium, copper, zinc) and moderate (nickel, iron) inhibitors of type 1 5-alpha-reductase.
  • Zinc can be important in normal skin function by means of its function as a catalyst in a variety of metalloproteinases. Zinc deficiency is correlated with, among other symptoms, hair loss, confirming its importance in the normal function of the hair follicle, which paradoxically contrasts from and leads away from the current methods, compositions, etc.
  • the zinc is provided in a form such as zinc sulfate and/or an organic complexed zinc which may be produced as a product or byproduct of fermentation.
  • Oleanolic acid is a compound extracted from olive leaves and has long been used in herbal medicine as an anti-diabetic and anti-hypertensive agent. [PMID: 17825251] Further, it has been identified as an effective inhibitor of 5-alpha-reductase. [00043] Nordihydroguaiaretic acid, derived from the chaparral (creosote) plant is a potent antioxidant compound which also has significant inhibitory effects on 5-alpha-reductase, particularly type 1. [PMID: 11931815]
  • Extracts of saw palmetto are rich in phytosterols and fatty acids.
  • the long chain free fatty acids present in extracts contribute to its efficacy in inhibition of both type 1 and type 2 5-alpha-reductase.
  • Green tea (Camella sinensis) extracts include EGCG (epigallocatechin-3-gallate) and epicatechin-3-gallate. Both have been identified as effective inhibitors of type 1 5- alpha-reductase. [PMID: 7575552].
  • catechols in general, particularly those that show selectivity for the type 1 isozyme of 5 alpha-reductase.
  • EGCG gallate esters can be replaced with long chain fatty acids.
  • Salicylic acid has substantial activity in the hair follicle, affecting particularly the epidermal lining of the follicle. It normalizes the lining when hyperkeratosis occurs, by means of exfoliating the stratum corneum. Hyperkeratosis in the hair follicle is suspected to be another outcome of elevated DHT within the follicle.
  • An additional agent that can be provided in the methods herein is dihydromyricetin.
  • Dihydromyricetin is an extract of wax myrtle and is known to influence the amount of time spent by the hair follicle in the anagen and telogen phases of hair growth. Specifically, when applied to skin in concentrations of 2%, it decreases the proportion of hair follicles in the anagen (growth) phase of the cycle and increases the proportion in the telogen (resting) phase. Because the anagen phase is that in which hairs actively grow and lengthen and the telogen phase is one where they are quiescent and do not grow, the effect is to slow the overall growth of a population of hair. In addition, it causes a decrease in the thickness of the hair shaft.
  • Palmitoleic acid Palmitoleic acid
  • Torilin (Torilis japonica extract) Chlorophorin (Artocarpus incisus extract)
  • 15 -lipoxygenase metabolites of PUFA's such as eicosapentaenoic acid 15S-hydroxyeicosaenoic acid 15S-hydroxyeicosatrienoic acid
  • Extracts of marine soft coral such as
  • the present compositions, etc. can be configured to additionally attack other points in the development of hirsutism. The following are some of those other points. Suitable components to attack such points may also be suitable to inhibit 5 alpha reductase. [00050] Tyrosine Kinase
  • This enzyme is involved in the process of hair growth. Inhibiting it results in slowed hair growth, smaller hair diameters, longer time spent by the follicle in the telogen (quiet) phase and less in the anagen (growing) phase.
  • Dihydromyricetin is an inhibitor of tyrosine kinase and is an ingredient in Reductase-5.
  • Ornithine Decarboxylase Similar to tyrosine kinase, this enzyme is also involved in the process of hair growth. It is inhibited by eflornithine, for example Vaniqa a commercially available treatment for hirsutism.
  • Aromatase This enzyme can impact the amount of testosterone available for conversion into DHT, thus potentially lessening the amount of DHT driving the virilization of the hair follicle.
  • Cholesterol is the beginning point of steroid production in the body. From it, a wide range of closely related steroids are produced. These include testosterone, estrogens, progesterone, DHEA, etc. These various steroid molecules differ from each other as specific small changes are made in molecular construction. Those changes are driven by specific enzymes. 5 alpha-reductase is one such enzyme. Aromatase is another. A review of the pathways of steroidogenesis found in Figure 2 will show that testosterone is converted to estradiol by the aromatase enzyme.
  • the present compositions can include aromatase enhancers or stimulators and/or estradiol increasers.
  • aromatase enhancers or stimulators and/or estradiol increasers examples include: alcohol, estradiol, phytogenic plant estrogens, aminoglutethimide, dibutyryl adenosine 3',5'-monophosphate, calcitriol (vitamin D3) and potentially others, black cohosh, wild yam, soy isoflavones, flax lignans, sapogenins, diosgenin.
  • the compositions and methods herein can also be used with and/or incorporated with other modalities for hirsutism treatment including those above. For example:
  • Ornithine Decarboxylase inhibitors e.g., eflornithine
  • Oral medications (fmisteride, cyproterone, hormones, etc.)
  • the compositions herein are used as follows. If desired, the face is cleansed with a simple facial cleanser as a well-cleansed face is more able to effectively absorb the active agent.
  • the composition in the form of a lotion is applied to the face.
  • the compositions can be applied once, twice, thrice or more or less times daily as desired.
  • the current composition comprises (in descending order of amount of component): Water (Aqua), Cetcaryl Alcohol &. Cetearcth-20. C 12-Cl 5 Alkyl Benzoate, Glycerelh-26, Glyceryl Stearate, PC 1 XJ- I OO Stearate, Dimethicone, Methyl Gliiceth-20. Butylene Glycol, Octyldodccy!
  • compositions include derivatives, salts, etc., of the stated molecules.
  • compositions, methods, etc. can be included in the compositions, methods, etc., herein.
  • US patent 6,492,326, incorporated herein by reference for its discussion of certain active agents discusses a variety of such components that may be suitable. The following is substantially a reproduction of some of the components mentioned in such patent. Some of the discussion may include certain components already mentioned in the embodiments discussed elsewhere herein.
  • Additional Skin Care Active agents should be suitable for application to keratinous tissue, that is, when incorporated into the composition they are suitable for use in contact with human keratinous tissue without undue toxicity, incompatibility, instability, allergic response, and the like within the scope of sound medical judgment.
  • CTFA Cosmetic Ingredient Handbook, Second Edition (1992) discusss a wide variety of nonlimiting cosmetic and pharmaceutical ingredients commonly used in the skin care industry, which are suitable for use in the compositions. Examples of these ingredient classes include: abrasives, absorbents, aesthetic components such as fragrances, pigments, colorings/colorants, essential oils, skin sensates, astringents, etc.
  • anti-acne agents e.g., clove oil, menthol, camphor, eucalyptus oil, eugenol, menthyl lactate, witch hazel distillate
  • anti-acne agents e.g., clove oil, menthol, camphor, eucalyptus oil, eugenol, menthyl lactate, witch hazel distillate
  • antimicrobial agents e.g., iodopropyl butylcarbamate
  • antioxidants e.g., iodopropyl butylcarbamate
  • binders biological additives, buffering agents, bulking agents, chelating agents, chemical additives, colorants, cosmetic astringents, cosmetic biocides, denaturants, drug astringents, external analgesics, film formers or materials, e.g., polymers, for aiding the film- forming properties and substantivity of the composition (e.g., copolymer
  • the topical compositions may contain a safe and effective amount of farnesol.
  • Farnesol is a naturally occurring substance which may act as a precursor and/or intermediate in the biosynthesis of squalene and sterols, especially cholesterol. Farnesol is also involved in protein modification and regulation (e.g., farnesylation of proteins), and there is a cell nuclear receptor which is responsive to farnesol.
  • protein modification and regulation e.g., farnesylation of proteins
  • farnesol is [2E,6E]-3,7,l l-trimethyl-2,6,10-dodecatrien-l-ol and as used herein "farnesol” includes isomers and tautomers of such.
  • Farnesol is commercially available, e.g., under the names farnesol (a mixture of isomers from Dragoco, 10 Gordon Drive, Totowa, N.J.) and trans-trans-farnesol (Sigma Chemical Company, P.O. Box 14508, St. Louis, Mo.).
  • farnesol a mixture of isomers from Dragoco, 10 Gordon Drive, Totowa, N.J.
  • trans-trans-farnesol Sigma Chemical Company, P.O. Box 14508, St. Louis, Mo.
  • the farnesol generally contains from about 0.001% to about 50%, by weight of the composition, more generally from about 0.01% to about 20%, even more generally from about 0.1% to about 15%, even more generally from about 0.1% to about 10%, still more generally from about 0.5% to about 5%, and still more generally from about 1% to about 5% of farnesol.
  • Phytantriol [00068] The topical compositions may contain a safe and effective amount of phytantriol.
  • Phytantriol is the common name for the chemical known as 3,7,11,15, tetramethylhexadecane-1,2,3, -triol.
  • Phytantriol is commercially available from BASF (1609 Biddle Avenue, Whyandotte, Mich.).
  • phytantriol is useful as a spider vessel/red blotchiness repair agent, a dark circle/puffy eye repair agent, sallowness repair agent, a sagging repair agent, an anti-itch agent, a skin thickening agent, a pore reduction agent, oil/shine reduction agent, a post-inflammatory hyperpigmentation repair agent, wound treating agent, an anti-cellulite agent, and regulating skin texture, including wrinkles and fine lines.
  • the phytantriol generally is included in an amount from about 0.001% to about 50% by weight of the composition, more generally from about 0.01% to about 20%, even more generally from about 0.1% to about 15%, even more generally from about 0.2% to about 10%, still more generally from about 0.5% to about 10%, and still more generally from about 1% to about 5%.
  • a safe and effective amount of a desquamation active may be added to the compositions, more generally from about 0.1% to about 10%, even more generally from about 0.2% to about 5%, also generally from about 0.5% to about 4%, by weight of the composition.
  • Desquamation active agents enhance the skin appearance benefits. For example, the desquamation active agents tend to improve the texture of the skin (e.g., smoothness).
  • One desquamation system that is suitable for use herein contains sulfhydryl compounds and zwitterionic surfactants and is discussed in U.S. Pat. No. 5,681,852, to Bissett, incorporated herein by reference.
  • compositions may further contain a safe and effective amount of one or more anti-wrinkle active agents or anti-atrophy active agents.
  • anti-wrinkle/anti- atrophy active agents suitable for use in the compositions include sulfur-containing D and L amino acids and their derivatives and salts, particularly the N-acetyl derivatives, a certain example of which is N-acetyl-L-cysteine; thiols, e.g.
  • compositions may contain a safe and effective amount of a vitamin B 3 compound.
  • Vitamin B 3 compounds are particularly useful for regulating skin condition as discussed in co-pending U.S. application Ser. No. 08/834,010, filed Apr. 11, 1997 (corresponding to international publication WO 97/39733 Al, published Oct. 30, 1997).
  • the compositions generally contain from about 0.01% to about 50%, more generally from about 0.1% to about 10%, even more generally from about 0.5% to about 10%, and still more generally from about 1% to about 5%, still more generally from about 2% to about 5%, by weight of the composition, of the vitamin B 3 compound.
  • vitamin B3 compound means a compound having the formula:
  • R is -CONH 2 (i.e., niacinamide), --COOH (i.e., nicotinic acid) or -CH 2 OH (i.e., nicotinyl alcohol); derivatives thereof; and salts of any of the foregoing.
  • exemplary derivatives of the foregoing vitamin B3 compounds include nicotinic acid esters, including non-vasodilating esters of nicotinic acid (e.g., tocopheryl nicotinate), nicotinyl amino acids, nicotinyl alcohol esters of carboxylic acids, nicotinic acid N-oxide and niacinamide N-oxide.
  • vitamin B3 compounds are well known and are commercially available from a number of sources, e.g., the Sigma Chemical Company (St. Louis, Mo.); ICN Biomedicals, Inc. (Irvin, Calif.) and Aldrich Chemical Company (Milwaukee, Wis.).
  • the vitamin compounds may be included as the substantially pure material, or as an extract obtained by suitable physical and/or chemical isolation from natural (e.g., plant) sources.
  • compositions may also contain a retinoid.
  • retinoid includes all natural and/or synthetic analogs of Vitamin A or retinol-like compounds which possess the biological activity of Vitamin A in the skin as well as the geometric isomers and stereoisomers of these compounds.
  • the retinoid is generally retinol, retinol esters (e.g., C 2 - C 2 2 alkyl esters of retinol, including retinyl palmitate, retinyl acetate, retinyl propionate), retinal, and/or retinoic acid (including all-trans retinoic acid and/or 13-cis-retinoic acid), more generally retinoids other than retinoic acid.
  • retinoids include all-trans retinoic acid and/or 13-cis-retinoic acid
  • These compounds are well known and are commercially available from a number of sources, e.g., Sigma Chemical Company (St. Louis, Mo.), and Boerhinger Mannheim (Indianapolis, Ind.).
  • Other retinoids which are useful herein are discussed in U.S. Pat.
  • Suitable retinoids are tocopheryl-retinoate [tocopherol ester of retinoic acid (trans- or cis-), adapalene ⁇ 6-[3-(l-adamantyl)-4-methoxyphenyl]-2-naphthoic acid ⁇ , and tazarotene (ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)-ethynyl]nicotinate).
  • Certain retinoids are retinol, retinyl palmitate, retinyl acetate, retinyl propionate, retinal and combinations thereof.
  • the retinoid may be included as the substantially pure material, or as an extract obtained by suitable physical and/or chemical isolation from natural (e.g., plant) sources.
  • the retinoid is generally substantially pure, more generally essentially pure.
  • the compositions may contain a safe and effective amount of the retinoid, such that the resultant composition is safe and effective for regulating keratinous tissue condition, generally for regulating visible and/or tactile discontinuities in skin, more generally for regulating signs of skin aging, even more generally for regulating visible and/or tactile discontinuities in skin texture associated with skin aging.
  • the compositions generally contain from or about 0.005% to or about 2%, more generally 0.01% to or about 2%, retinoid.
  • Retinol is generally used in an amount of from or about 0.01% to or about 0.15%; retinol esters are generally used in an amount of from or about 0.01% to or about 2% (e.g., about 1%); retinoic acids are generally used in an amount of from or about 0.01% to or about 0.25%; tocopheryl-retinoate, adapalene, and tazarotene are generally used in an amount of from or about 0.01% to or about 2%.
  • compositions contain both a retinoid and a Vitamin B3 compound
  • the retinoid is generally used in the above amounts
  • the vitamin B3 compound is generally used in an amount of from or about 0.1% to or about 10%, more generally from or about 2% to or about 5%.
  • (c) Hydroxy Acids may contain a safe and effective amount of a Hydroxy Acid. Certain hydroxy acids for use in the compositions include salicylic acid and salicylic acid derivatives.
  • salicylic acid When present in the compositions, salicylic acid is generally used in an amount of from about 0.01% to about 50%, more generally from about 0.1% to about 20%, even more generally from about 0.1% to about 10%, still more generally from about 0.5% to about 5%, and still more generally from about 0.5% to about 2%.
  • peptides include but not limited to, di-, tri-, and tetrapeptides and derivatives thereof, may be included in the compositions in amounts that are safe and effective.
  • peptides refers to both the naturally occurring peptides and synthesized peptides. Also useful herein are naturally occurring and commercially available compositions that contain peptides.
  • Suitable dipeptides for use herein include Carnosine (beta-ala-his).
  • Suitable tripeptides for use herein include, gly-his-lys, arg-lys-arg, his-gly-gly.
  • Certain tripeptides and derivatives thereof include palmitoyl-gly-his-lys, which may be purchased as Biopeptide CL ® (100 ppm of palmitoyl-gly-his-lys commercially available from Sederma, France); Peptide CK (arg-lys-arg); Peptide CK+(ac-arg-lys-arg-NH2); and a copper derivative of his-gly-gly sold commercially as lamin, from Sigma (St. Louis, Mo.).
  • Suitable tetrapeptides for use herein include Peptide E, arg-ser-arg-lys (SEQ ID NO: 1).
  • the additional peptide is selected from palmitoyl-gly-his-lys, beta-ala- his, their derivatives, and combinations thereof. More generally, the additional peptide is selected from palmitoyl-gly-his-lys, their derivatives, and combinations thereof.
  • the additional peptides are generally included in amounts of from about 1x10 6 % to about 10%, more generally from about IxIO "6 % to about 0.1%, even more generally from about IxIO 5 % to about 0.01%, by weight of the composition.
  • the compositions generally contain from about 0.1% to about 5%, by weight of the composition, of such peptides. In other embodiments wherein the peptide-containing composition Biopeptide CL ® is included, the resulting composition generally contains from about 0.1% to about 10%, by weight of the composition, of the Biopeptide CL ® .
  • compositions may include a safe and effective amount of an anti- oxidant/radical scavenger.
  • the anti-oxidant/radical scavenger is especially useful for providing protection against UV radiation which can cause increased scaling or texture changes in the stratum corneum and against other environmental agents which can cause skin damage.
  • a safe and effective amount of an anti-oxidant/radical scavenger may be added to the compositions, generally from about 0.1% to about 10%, more generally from about 1% to about 5%, of the composition.
  • Anti-oxidants/radical scavengers such as ascorbic acid (vitamin C) and its salts, ascorbyl esters of fatty acids, ascorbic acid derivatives (e.g., magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl sorbate), tocopherol (vitamin E), tocopherol sorbate, tocopherol acetate, other esters of tocopherol, butylated hydroxy benzoic acids and their salts, ⁇ -hydroxy-l ⁇ J ⁇ -tetramethylchroman-l-carboxylic acid (commercially available under the tradename Trolox ® ), gallic acid and its alkyl esters, especially propyl gallate, uric acid and its salts and alkyl esters, ⁇ -
  • Certain anti-oxidants/radical scavengers are selected from tocopherol sorbate and other esters of tocopherol, more generally tocopherol sorbate.
  • tocopherol sorbate for example, the use of tocopherol sorbate in topical compositions is discussed in U.S. Pat. No. 4,847,071, issued on JuI. 11, 1989 to Donald L. Bissett, Rodney D. Bush and Ranjit Chatterjee.
  • Chelators [00099]
  • the compositions may also contain a safe and effective amount of a chelator or chelating agent.
  • chelator or “chelating agent” means an active agent capable of removing a metal ion from a system by forming a complex so that the metal ion cannot readily participate in or catalyze chemical reactions.
  • the inclusion of a chelating agent is especially useful for providing protection against UV radiation which can contribute to excessive scaling or skin texture changes and against other environmental agents which can cause skin damage.
  • a safe and effective amount of a chelating agent may be added to the compositions, generally from about 0.1% to about 10%, more generally from about 1% to about 5%, of the composition.
  • Exemplary chelators that are useful herein are disclosed in U.S. Pat. No. 5,487,884, issued Jan. 30, 1996 to Bissett et al; International Publication No. 91/16035, Bush et al., published Oct. 31, 1995; and International Publication No. 91/16034, Bush et al., published Oct. 31, 1995.
  • Certain chelators useful in compositions are furildioxime, furilmonoxime, and derivatives thereof.
  • Flavonoids [000102] The compositions may optionally contain a flavonoid compound.
  • Flavonoids are broadly disclosed in U.S. Pat. Nos. 5,686,082 and 5,686,367, both of which are herein incorporated by reference. Flavonoids suitable for use are flavanones selected from unsubstituted flavanones, mono-substituted flavanones, and mixtures thereof; chalcones selected from unsubstituted chalcones, mono-substituted chalcones, di-substituted chalcones, tri-substituted chalcones, and mixtures thereof; flavones selected from unsubstituted flavones, mono-substituted flavones, di-substituted flavones, and mixtures thereof; one or more isoflavones; coumarins selected from unsubstituted coumarins, mono- substituted coumarins, di-substituted coumarins, and mixtures thereof; chromones selected from unsubstitute
  • substituted means flavonoids wherein one or more hydrogen atom of the flavonoid has been independently replaced with hydroxyl, C1-C8 alkyl, C1-C4 alkoxyl, O- glycoside, and the like or a mixture of these substituents.
  • suitable flavonoids include, but are not limited to, unsubstituted flavanone, mono-hydroxy flavanones (e.g., 2'-hydroxy flavanone, 6-hydroxy flavanone, 7- hydroxy flavanone, etc.), mono-alkoxy flavanones (e.g., 5-methoxy flavanone, 6-methoxy flavanone, 7-methoxy flavanone, 4'-methoxy flavanone, etc.), unsubstituted chalcone (especially unsubstituted trans-chalcone), mono-hydroxy chalcones (e.g., 2'-hydroxy chalcone, 4'-hydroxy chalcone, etc.), di-hydroxy chalcones (e.g., 2',4-dihydroxy chalcone, 2',4'-dihydroxy chalcone, 2,2'-dihydroxy chalcone, 2',3-dihydroxy chalcone, 2',5'-dihydroxy chal
  • Flavonoid compounds useful herein are commercially available from a number of sources, e.g., Indofme Chemical Company, Inc. (Somerville, N. J.), Steraloids, Inc. (Wilton, N. H.), and Aldrich Chemical Company, Inc. (Milwaukee, Wis.).
  • a safe and effective amount of an anti-inflammatory agent may be added to the compositions, generally from about 0.1% to about 10%, more generally from about 0.5% to about 5%, of the composition.
  • the anti-inflammatory agent enhances the skin appearance benefits, e.g., such agents contribute to a more uniform and acceptable skin tone or color.
  • Steroidal anti-inflammatory agents including but not limited to, corticosteroids such as hydrocortisone, hydroxyltriamcinolone, alpha-methyl dexamethasone, dexamethasone-phosphate, beclomethasone dipropionates, clobetasol valerate, desonide, desoxymethasone, desoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, fludrocortisone, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortine butylesters, fluocortolone, fluprednidene (fluprednylidene)
  • corticosteroids such as hydrocortisone, hydroxyltriamcinolone, alpha-methyl dexamethasone, dexa
  • a second class of anti-inflammatory agents which is useful in the compositions includes the nonsteroidal anti-inflammatory agents.
  • the variety of compounds encompassed by this group are well-known.
  • Anti-inflammatory and Anti-Rheumatic Drugs K. D. Rainsford, Vol. I-III, CRC Press, Boca Raton, (1985)
  • Anti-inflammatory Agents Chemistry and Pharmacology, 1, R. A. Scherrer, et al., Academic Press, New York (1974).
  • non-steroidal anti-inflammatory agents useful in the composition include, but are not limited to: 1) the oxicams, such as piroxicam, isoxicam, tenoxicam, sudoxicam, and CP-14,304; 2) the salicylates, such as aspirin, disalcid, benorylate, trilisate, safapryn, solprin, diflunisal, and fendosal; 3) the acetic acid derivatives, such as diclofenac, fenclofenac, indomethacin, sulindac, tolmetin, isoxepac, furofenac, tiopinac, zidometacin, acematacin, fentiazac, zomepirac, clindanac, oxepinac, felbinac, and ketorolac; 4) the fenamates, such as mefenamic, meclofenamic, flufenamic;
  • non-steroidal anti-inflammatory agents may also be employed, as well as the dermatologically acceptable salts and esters of these agents.
  • etofenamate a flufenamic acid derivative
  • Particular nonsteroidal anti-inflammatory agents include ibuprofen, naproxen, flufenamic acid, etofenamate, aspirin, mefenamic acid, meclofenamic acid, piroxicam and felbinac, more particularly ibuprofen, naproxen, ketoprofen, etofenamate, aspirin and flufenamic acid.
  • So-called "natural" anti-inflammatory agents can also be useful in methods.
  • Such agents may suitably be obtained as an extract by suitable physical and/or chemical isolation from natural sources (e.g., plants, fungi, by-products of microorganisms) or can be synthetically prepared.
  • natural sources e.g., plants, fungi, by-products of microorganisms
  • bisabolol e.g., alpha bisabolol
  • aloe vera e.g., plant sterols (e.g., phytosterol)
  • Additional anti-inflammatory agents useful herein include compounds of the Licorice (the plant genus/species Glycyrrhiza glabra) family, including glycyrrhetic acid, glycyrrhizic acid, and derivatives thereof (e.g., salts and esters).
  • Suitable salts of the foregoing compounds include metal and ammonium salts.
  • Suitable esters include C 2 -C 2 4 saturated or unsaturated esters of the acids, generally C 10 -C 2 4, more generally C 16 -C 2 4.
  • compositions may also contain a safe and effective amount of an anti-cellulite agent.
  • Suitable agents may include, but are not limited to, xanthine compounds (e.g., caffeine, theophylline, theobromine, and aminophylline).
  • Topical Anesthetics e.g., topical Anesthetics
  • compositions may also contain a safe and effective amount of a topical anesthetic.
  • topical anesthetic drugs include benzocaine, lidocaine, bupivacaine, chlorprocaine, dibucaine, etidocaine, mepivacaine, tetracaine, dyclonine, hexylcaine, procaine, cocaine, ketamine, pramoxine, phenol, and pharmaceutically acceptable salts thereof.
  • compositions may contain a tanning active.
  • the compositions may contain from about 0.1% to about 20%, more generally from about 2% to about 7%, and still more generally from about 3% to about 6%, by weight of the composition, of dihydroxyacetone as an artificial tanning active.
  • Dihydroxyacetone which is also known as DHA or l,3-dihydroxy-2-propanone, is a white to off-white, crystalline powder.
  • This material can be represented by the chemical formula C 3 H 6 O 3 and the following chemical structure.
  • the compound can exist as a mixture of monomers and dimers, with the dimers predominating in the solid crystalline state. Upon heating or melting, the dimers break down to yield the monomers. This conversion of the dimeric form to the monomeric form also occurs in aqueous solution. Dihydroxyacetone is also known to be more stable at acidic pH values. See The Merck Index, Tenth Edition, entry 3167, p. 463 (1983), and "Dihydroxyacetone for Cosmetics", E. Merck Technical Bulletin, 03-304 110, 319 897, 180 588.
  • the compositions may contain a skin lightening agent.
  • the compositions When used, the compositions generally contain from about 0.1% to about 10%, more generally from about 0.2% to about 5%, also generally from about 0.5% to about 2%, by weight of the composition, of a skin lightening agent.
  • Suitable skin lightening agents include those known, including kojic acid, arbutin, ascorbic acid and derivatives thereof (e.g., magnesium ascorbyl phosphate or sodium ascorbyl phosphate), and extracts (e.g., mulberry extract, placental extract).
  • Skin lightening agents suitable for use herein also include those discussed in the PCT publication No.
  • the compositions may comprise a skin soothing or skin healing active.
  • Skin soothing or skin healing active agents suitable for use herein include panthenoic acid derivatives (including panthenol, dexpanthenol, ethyl panthenol), aloe vera, allantoin, bisabolol, and dipotassium glycyrrhizinate.
  • a safe and effective amount of a skin soothing or skin healing active may be added to the present composition, generally, from about 0.1% to about 30%, more generally from about 0.5% to about 20%, still more generally from about 0.5% to about 10 %, by weight of the composition formed.
  • a) bisabolol may also contain a safe and effective amount of bisabolol.
  • Bisabolol is a naturally occurring unsaturated monocyclic terpene alcohol having the following structure
  • Bisabolol can be synthetic (d,l-alpha-isomer or (+/-)-alpha-isomer) or natural ((-)-alpha-isomer) in origin and can be used as essentially pure compounds or mixtures of compounds (e.g., extracts from natural sources such as chamomile).
  • the alpha form of bisabolol (a-bisabolol) is used in a variety of cosmetic products as a skin conditioning or soothing agent.
  • bisabolol includes chamomile extract or oil and any isomers and tautomers of such.
  • Suitable bisabolol compounds are commercially available as a natural material from Dragoco (Totowa, N.J.) under the product name alpha-bisabolol natural and as a synthetic material from Fluka (Milwaukee, Wis.) under the product name alpha-bisabolol.
  • the composition generally contains from about 0.001% to about 50%, by weight of the composition, more generally from about 0.01% to about 20%, even more generally from about 0.01% to about 15%, and still more generally from about 0.1% to about 10%, of bisabolol, even more generally from about 0.1% to about 5%.
  • compositions may contain an antimicrobial or antifungal active.
  • active agents are capable of destroying microbes, preventing the development of microbes or preventing the pathogenic action of microbes.
  • a safe and effective amount of an antimicrobial or antifungal active may be added to the present compositions, generally, from about 0.001% to about 10%, more generally from about 0.01% to about 5%, and still more generally from about 0.05% to about 2%.
  • antimicrobial and antifungal active agents include ⁇ -lactam drugs, quinolone drugs, ciprofloxacin, norfloxacin, tetracycline, erythromycin, amikacin, 2,4,4'- trichloro-2'-hydroxy diphenyl ether, 3,4,4'-trichlorobanilide, phenoxyethanol, phenoxy propanol, phenoxyisopropanol, doxycycline, capreomycin, chlorhexidine, chlortetracycline, oxytetracycline, clindamycin, ethambutol, hexamidine isethionate, metronidazole, pentamidine, gentamicin, kanamycin, lineomycin, methacycline, methenamine, minocycline, neomycin, netilmicin, paromomycin, streptomycin, tobramycin, miconazole, tetracycline hydrochlor
  • active agents useful herein include those selected from salicylic acid, benzoyl peroxide, 3 -hydroxy benzoic acid, gly colic acid, lactic acid, 4- hydroxy benzoic acid, acetyl salicylic acid, 2-hydroxybutanoic acid, 2-hydroxypentanoic acid, 2-hydroxyhexanoic acid, cis-retinoic acid, trans-retinoic acid, retinol, phytic acid, N- acetyl-L-cysteine, lipoic acid, azelaic acid, arachidonic acid, benzoylperoxide, tetracycline, ibuprofen, naproxen, hydrocortisone, acetominophen, resorcinol, phenoxyethanol, phenoxypropanol, phenoxyisopropanol, 2,4,4'-trichloro-2'-hydroxy diphenyl ether, 3,4,4'- trichlorocarban
  • compositions may optionally contain a sunscreen active.
  • sunscreen active includes both sunscreen agents and physical sunblocks. Suitable sunscreen active agents may be organic or inorganic.
  • Inorganic sunscreens useful herein include the following metallic oxides; titanium dioxide having an average primary particle size of from about 15 nm to about 100 nm, zinc oxide having an average primary particle size of from about 15 nm to about 150 nm, zirconium oxide having an average primary particle size of from about 15 nm to about 150 nm, iron oxide having an average primary particle size of from about 15 nm to about 500nm, and mixtures thereof.
  • the inorganic sunscreens are present in the amount of from about 0.1% to about 20%, generally from about 0.5% to about 10%, more generally from about 1% to about 5%, by weight of the composition.
  • a wide variety of conventional organic sunscreen active agents are suitable for use herein.
  • sunscreen active agents include, for example: p-aminobenzoic acid, its salts and its derivatives (ethyl, isobutyl, glyceryl esters; p-dimethylaminobenzoic acid); anthranilates (i.e., o-amino- benzoates; methyl, menthyl, phenyl, benzyl, phenylethyl, linalyl, terpinyl, and cyclohexenyl esters); salicylates (amyl, phenyl, octyl, benzyl, menthyl, glyceryl, and di- pro-pyleneglycol esters); cinnamic acid derivatives (menthyl and benzyl esters, a-phenyl cinnamonitrile;
  • These embodiments include 2-ethylhexyl-p-methoxycinnamate (commercially available as PARSOL MCX), 4,4'-t-butyl methoxydibenzoyl-methane (commercially available as PARSOL 1789), 2-hydroxy-4-methoxybenzophenone, octyldimethyl-p- aminobenzoic acid, digalloyltrioleate, 2,2-dihydroxy-4-methoxybenzophenone, ethyl-4- (bis(hydroxy-propyl))aminobenzoate, 2-ethylhexyl-2-cyano-3,3-diphenylacrylate, 2- ethylhexyl-salicylate, glyceryl-p-aminobenzoate, 3,3,5-tri-methylcyclohexylsalicylate, methylanthranilate, p-dimethyl-aminobenzoic acid or aminobenzoate, 2-ethylhe
  • Certain organic sunscreen active agents useful in the compositions useful are 2- ethylhexyl-p-methoxycinnamate, butylmethoxydibenzoyl-methane, 2-hydroxy-4- methoxybenzo-phenone, 2-phenylbenzimidazole-5-sulfonic acid, octyldimethyl-p- aminobenzoicacid, octocrylene and mixtures thereof.
  • sunscreen active agents such as those disclosed in U.S. Pat. No. 4,937,370 issued to Sabatelli on Jun. 26, 1990, and U.S. Pat. No. 4,999,186 issued to Sabatelli & Spirnak on Mar. 12, 1991.
  • the sunscreening agents disclosed therein have, in a single molecule, two distinct chromophore moieties which exhibit different ultra-violet radiation absorption spectra. One of the chromophore moieties absorbs predominantly in the UVB radiation range and the other absorbs strongly in the UVA radiation range.
  • sunscreening agents are 4-N,N-(2-ethylhexyl)methyl- aminobenzoic acid ester of 2,4-dihydroxybenzophenone; N,N-di-(2-ethylhexyl)-4- aminobenzoic acid ester with 4-hydroxydibenzoylmethane; 4-N,N-(2-ethylhexyl)methyl- aminobenzoic acid ester with 4-hydroxydibenzoylmethane; 4-N, N-(2-ethylhexyl)methyl- aminobenzoic acid ester of 2-hydroxy-4-(2-hydroxyethoxy)benzophenone; 4-N,N-(2- ethylhexyl)-methylaminobenzoic acid ester of 4-(2-hydroxyethoxy)dibenzoylmethane; N,N-di-(2-ethylhexyl)-4-aminobenzoic acid ester of 2-hydroxy-4-(2- hydroxy
  • Certain sunscreen active agents include 4,4'-t-butylmethoxydibenzoylmethane, 2- ethylhexyl-p-methoxycinnamate, phenyl benzimidazole sulfonic acid, and octocrylene.
  • a safe and effective amount of the organic sunscreen active is used, typically from about 1% to about 20%, more typically from about 2% to about 10% by weight of the composition. Exact amounts will vary depending upon the sunscreen or sunscreens chosen and the desired Sun Protection Factor (SPF).
  • SPF Sun Protection Factor
  • Particulate Material may contain a particulate material, generally a metallic oxide. These particulates can be coated or uncoated, charged or uncharged.
  • Particulate materials useful herein include; bismuth oxychloride, iron oxide, mica, mica treated with barium sulfate and TiO2, silica, nylon, polyethylene, talc, styrene, polyproylene, ethylene/acrylic acid copolymer, sericite, aluminum oxide, silicone resin, barium sulfate, calcium carbonate, cellulose acetate, titanium dioxide, polymethyl methacrylate, and mixtures thereof.
  • Inorganic particulate materials e.g., TiO2, ZnO, or ZrO2 are commercially available from a number of sources.
  • a suitable particulate material contains the material available from U.S. Cosmetics (TRONOX TiO2 series, SAT-T CR837, a rutile TiO2).
  • particulate materials are present in the composition in levels of from about 0.01% to about 2%, more generally from about 0.05% to about 1.5%, still more generally from about 0.1% to about 1%, by weight of the composition.
  • compositions may contain a conditioning agent selected from humectants, moisturizers, or skin conditioners.
  • a conditioning agent selected from humectants, moisturizers, or skin conditioners.
  • humectants selected from humectants, moisturizers, or skin conditioners.
  • these materials can be employed and each can be present at a level of from about 0.01% to about 20%, more generally from about 0.1% to about 10%, and still more generally from about 0.5% to about 7% by weight of the composition.
  • These materials include, but are not limited to, guanidine; urea; glycolic acid and glycolate salts (e.g.
  • aloe vera in any of its variety of forms (e.g., aloe vera gel); polyhydroxy alcohols such as sorbitol, mannitol, xylitol, erythritol, glycerol, hexanetriol, butanetriol, propylene glycol, butylene glycol, hexylene glycol and the like; polyethylene glycols; sugars (e.g., melibiose) and starches; sugar and starch derivatives (e.g., alkoxylated glucose, fructose, glucosamine); hyaluronic acid; lactamide monoethanolamine; acetamide monoethanolamine; panthenol; allantoin; and mixtures thereof. Also useful herein are the propoxylated gly
  • Ci -C3O monoesters and polyesters of sugars and related materials are also useful. These esters are derived from a sugar or polyol moiety and one or more carboxylic acid moieties. Such ester materials are further discussed in, U.S. Pat. No. 2,831,854, U.S. Pat. No. 4,005,196, to Jandacek, issued Jan. 25, 1977; U.S. Pat. No. 4,005,195, to Jandacek, issued Jan. 25, 1977, U.S. Pat. No. 5,306,516, to Letton et al, issued Apr. 26, 1994; U.S. Pat. No. 5,306,515, to Letton et al, issued Apr. 26, 1994; U.S. Pat. No.
  • the conditioning agent is selected from urea, guanidine, sucrose polyester, panthenol, dexpanthenol, allantoin, and combinations thereof.
  • Structuring Agents are selected from urea, guanidine, sucrose polyester, panthenol, dexpanthenol, allantoin, and combinations thereof.
  • compositions hereof, and especially the emulsions hereof may contain a structuring agent.
  • Structuring agents can be used in the oil-in-water emulsions. Without being limited by theory, it may be that the structuring agent assists in providing rheological characteristics to the composition which contribute to the stability of the composition. For example, the structuring agent tends to assist in the formation of the liquid crystalline gel network structures.
  • the structuring agent may also function as an emulsifier or surfactant. Certain compositions contain from about 0.1% to about 20%, more generally from about 0.1% to about 10%, still more generally from about 0.5% to about 9%, of one or more structuring agents.
  • Certain structuring agents are those having an HLB of from about 1 to about 8 and having a melting point of at least about 45 C.
  • Suitable structuring agents are those selected from saturated Ci 4 to C3O fatty alcohols, saturated C 16 to C3O fatty alcohols containing from about 1 to about 5 moles of ethylene oxide, saturated C 16 to C3O diols, saturated C 16 to C3O monoglycerol ethers, saturated C 16 to C3O hydroxy fatty acids, C14 to C3O hydroxylated and nonhydroxylated saturated fatty acids, Ci 4 to C3O saturated ethoxylated fatty acids, amines and alcohols containing from about 1 to about 5 moles of ethylene oxide diols, Ci 4 to C 3 O saturated glyceryl mono esters with a monoglyceride content of at least 40%, Ci 4 to C3O saturated polyglycerol esters having from about 1 to about 3 alkyl group and from about 2 to about 3 saturated glycerol units, Ci 4
  • Certain structuring agents are selected from stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, stearic acid, palmitic acid, the polyethylene glycol ether of stearyl alcohol having an average of about 1 to about 5 ethylene oxide units, the polyethylene glycol ether of cetyl alcohol having an average of about 1 to about 5 ethylene oxide units, and mixtures thereof.
  • Certain structuring agents are selected from stearyl alcohol, cetyl alcohol, behenyl alcohol, the polyethylene glycol ether of stearyl alcohol having an average of about 2 ethylene oxide units (steareth-2), the polyethylene glycol ether of cetyl alcohol having an average of about 2 ethylene oxide units, and mixtures thereof.
  • compositions can contain one or more thickening agents, generally from about 0.1% to about 5%, more generally from about 0.1% to about 4%, and still more generally from about 0.25% to about 3%, by weight of the composition.
  • Nonlimiting classes of thickening agents include those selected from the following: [000160] a) Carboxylic Acid Polymers [000161] These polymers are crosslinked compounds containing one or more monomers derived from acrylic acid, substituted acrylic acids, and salts and esters of these acrylic acids and the substituted acrylic acids, wherein the crosslinking agent contains two or more carbon-carbon double bonds and is derived from a polyhydric alcohol. Polymers useful are more fully discussed in U.S. Pat. No. 5,087,445, to Haffey et al, issued Feb. 11, 1992; U.S. Pat. No. 4,509,949, to Huang et al, issued Apr. 5, 1985; U.S. Pat. No. 2,798,053, to Brown, issued JuI. 2, 1957; and in CTFA International Cosmetic Ingredient Dictionary, Fourth Edition, 1991, pp. 12 and 80.
  • carboxylic acid polymers useful herein include the carbomers, which are homopolymers of acrylic acid crosslinked with allyl ethers of sucrose or pentaerytritol.
  • the carbomers are available as the Carbopol ® 900 series from B.F. Goodrich (e.g., Carbopol ® 954).
  • other suitable carboxylic acid polymeric agents include copolymers of Cio-30 alkyl acrylates with one or more monomers of acrylic acid, methacrylic acid, or one of their short chain (i.e., Ci-4 alcohol) esters, wherein the crosslinking agent is an allyl ether of sucrose or pentaerytritol.
  • copolymers are known as acrylates/Cio -C3O alkyl acrylate crosspolymers and are commercially available as Carbopol ® 1342, Carbopol ® 1382, Pemulen TR-I, and Pemulen TR-2, from B.F. Goodrich.
  • carboxylic acid polymer thickeners useful herein are those selected from carbomers, acrylates/Cio -C3O alkyl acrylate crosspolymers, and mixtures thereof.
  • compositions can optionally contain crosslinked polyacrylate polymers useful as thickeners or gelling agents including both cationic and nonionic polymers.
  • crosslinked nonionic polyacrylate polymers and crosslinked cationic polyacrylate polymers are those discussed in U.S. Pat. No. 5,100,660, to Hawe et al, issued Mar. 31, 1992; U.S. Pat. No. 4,849,484, to Heard, issued JuI. 18, 1989; U.S. Pat. No. 4,835,206, to Farrar et al, issued May 30, 1989; U.S. Pat. No. 4,628,078 to Glover et al issued Dec. 9, 1986; U.S. Pat. No. 4,599,379 to Flesher et al issued JuI. 8, 1986; and EP 228,868, to Farrar et al, published JuI. 15, 1987.
  • compositions can optionally contain polyacrylamide polymers, especially nonionic polyacrylamide polymers including substituted branched or unbranched polymers.
  • polyacrylamide polymers especially nonionic polyacrylamide polymers including substituted branched or unbranched polymers.
  • Certain among these polyacrylamide polymers is the nonionic polymer given the CTFA designation polyacrylamide and isoparaff ⁇ n and laureth-7, available under the Tradename Sepigel 305 from Seppic Corporation (Fairf ⁇ eld, N. J.).
  • polyacrylamide polymers useful herein include multi-block copolymers of acrylamides and substituted acrylamides with acrylic acids and substituted acrylic acids.
  • Commercially available examples of these multi-block copolymers include Hypan SR150H, SS500V, SS500W, SSSAlOOH, from Lipo Chemicals, Inc., (Patterson, N.J.).
  • Polysaccharides refer to gelling agents which contain a backbone of repeating sugar (i.e., carbohydrate) units.
  • Nonlimiting examples of polysaccharide gelling agents include those selected from cellulose, carboxymethyl hydroxyethylcellulose, cellulose acetate propionate carboxylate, hydroxyethylcellulose, hydroxyethyl ethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, methyl hydroxyethylcellulose, microcrystalline cellulose, sodium cellulose sulfate, and mixtures thereof.
  • alkyl substituted celluloses are also useful herein.
  • the hydroxy groups of the cellulose polymer is hydroxyalkylated (generally hydroxyethylated or hydroxypropylated) to form a hydroxyalkylated cellulose which is then further modified with a C 10 -C3O straight chain or branched chain alkyl group through an ether linkage.
  • these polymers are ethers of Cio -C3O straight or branched chain alcohols with hydroxyalkylcelluloses.
  • alkyl groups useful herein include those selected from stearyl, isostearyl, lauryl, myristyl, cetyl, isocetyl, cocoyl (i.e.
  • alkyl groups derived from the alcohols of coconut oil palmityl, oleyl, linoleyl, linolenyl, ricinoleyl, behenyl, and mixtures thereof.
  • alkyl hydroxyalkyl cellulose ethers Certain among the alkyl hydroxyalkyl cellulose ethers is the material given the CTFA designation cetyl hydroxyethylcellulose, which is the ether of cetyl alcohol and hydroxyethylcellulose. This material is sold under the tradename Natrosol ® CS Plus from Aqualon Corporation (Wilmington, Del.).
  • scleroglucans which are a linear chain of (1- 3) linked glucose units with a (1-6) linked glucose every three units, a commercially available example of which is Clearogel.TM. CSI l from Michel Mercier Products Inc. (Mountainside, N.J.).
  • e) Gums Other thickening and gelling agents useful herein include materials which are primarily derived from natural sources.
  • Nonlimiting examples of these gelling agent gums include acacia, agar, algin, alginic acid, ammonium alginate, amylopectin, calcium alginate, calcium carrageenan, carnitine, carrageenan, dextrin, gelatin, gellan gum, guar gum, guar hydroxypropyltrimonium chloride, hectorite, hyaluroinic acid, hydrated silica, hydroxypropyl chitosan, hydroxypropyl guar, karaya gum, kelp, locust bean gum, natto gum, potassium alginate, potassium carrageenan, propylene glycol alginate, sclerotium gum, sodium carboyxmethyl dextran, sodium carrageenan, tragacanth gum, xanthan gum, and mixtures thereof.
  • compositions include a thickening agent selected from carboxylic acid polymers, crosslinked polyacrylate polymers, polyacrylamide polymers, and mixtures thereof, more generally selected from carboxylic acid polymers, polyacrylamide polymers, and mixtures thereof.
  • the topical compositions also contain a dermatologically acceptable carrier.
  • a dermatologically acceptable carrier means that the carrier is suitable for topical application to the keratinous tissue, has good aesthetic properties, is compatible with the active agents and any other components, and will not cause any untoward safety or toxicity concerns.
  • a safe and effective amount of carrier is from about 50% to about 99.99%, generally from about 80% to about 99.9%, more generally from about 90% to about 98%, and even more generally from about 90% to about 95% of the composition.
  • the carrier can be in a wide variety of forms.
  • emulsion carriers including, but not limited to, oil-in-water, water-in-oil, water-in-oil-in-water, and oil-in- water-in-silicone emulsions, are useful herein; certain of such compositions are known as liposomal compositions wherein active ingredients are contained in, and delivered via, liposomes.
  • Certain carriers contain an emulsion such as oil-in-water emulsions, water-in-oil emulsions, and water-in-silicone emulsions.
  • a given component will distribute primarily into either the water or oil/silicone phase, depending on the water solubility/dispersibility of the component in the composition.
  • Oil-in-water emulsions are Certain.
  • Emulsions generally contain a solution as discussed above and a lipid or oil.
  • Lipids and oils may be derived from animals, plants, or petroleum and may be natural or synthetic (i.e., man-made). Certain emulsions also contain a humectant, such as glycerin. Emulsions will generally further contain from about 0.01% to about 10%, more generally from about 0.1% to about 5%, of an emulsifier, based on the weight of the carrier.
  • Emulsifiers may be nonionic, anionic or cationic. Suitable emulsifiers are disclosed in, for example, U.S. Pat. No. 3,755,560, issued Aug. 28, 1973, Dickert et al.; U.S. Pat. No.
  • the emulsion may also contain an anti-foaming agent to minimize foaming upon application to the keratinous tissue.
  • Anti-foaming agents include high molecular weight silicones and other materials well known for such use.
  • Suitable emulsions may have a wide range of viscosities, depending on the desired product form.
  • Exemplary low viscosity emulsions have a viscosity of about 50 centistokes or less, more generally about 10 centistokes or less, still more generally about 5 centistokes or less.
  • Water-in-silicone emulsions contain a continuous silicone phase and a dispersed aqueous phase.
  • Certain water-in- silicone emulsions contain from about 1% to about 60%, generally from about 5% to about 40%, more generally from about 10% to about 20%, by weight of a continuous silicone phase.
  • the continuous silicone phase exists as an external phase that contains or surrounds the discontinuous aqueous phase discussed hereinafter.
  • the continuous silicone phase contains a polyorganosiloxane oil.
  • a Certain water- in-silicone emulsion system is formulated to provide an oxidatively stable vehicle for the retinoid.
  • the continuous silicone phase of these Certain emulsions contain between about 50% and about 99.9% by weight of organopolysiloxane oil and less than about 50% by weight of a non-silicone oil.
  • the continuous silicone phase contains at least about 50%, generally from about 60% to about 99.9%, more generally from about 70% to about 99.9%, and even more generally from about 80% to about 99.9%, polyorganosiloxane oil by weight of the continuous silicone phase, and up to about 50% non-silicone oils, generally less about 40%, more generally less than about 30%, even more generally less than about 10%, and even more generally less than about 2%, by weight of the continuous silicone phase.
  • These emulsion systems provide more oxidative stability to the retinoid over extended periods of time than comparable water-in-oil emulsions containing lower concentrations of the polyorganosiloxane oil.
  • the organopolysiloxane oil for use in the composition may be volatile, nonvolatile, or a mixture of volatile and non- volatile silicones.
  • nonvolatile refers to those silicones that are liquid under ambient conditions and have a flash point (under one atmospheric of pressure) of or greater than about 100 C.
  • volatile refers to all other silicone oils.
  • Suitable organopolysiloxanes can be selected from a wide variety of silicones spanning a broad range of volatilities and viscosities.
  • organopolysiloxane oils examples include polyalkylsiloxanes, cyclic polyalkylsiloxanes, and polyalkylarylsiloxanes.
  • Polyalkylsiloxanes useful in the composition herein include polyalkylsiloxanes with viscosities of from about 0.5 to about 1,000,000 centistokes at 25 C.
  • Such polyalkylsiloxanes can be represented by the general chemical formula R 3 SiO[R 2 SiO] x SiR 3 wherein R is an alkyl group having from one to about 30 carbon atoms (generally R is methyl or ethyl, more generally methyl; also mixed alkyl groups can be used in the same molecule), and x is an integer from 0 to about 10,000, chosen to achieve the desired molecular weight which can range to over about 10,000,000.
  • Commercially available polyalkylsiloxanes include the polydimethylsiloxanes, which are also known as dimethicones, examples of which include the Vicasil ® series sold by General Electric Company and the Dow Corning ® 200 series sold by Dow Corning Corporation.
  • suitable polydimethylsiloxanes include Dow Corning ® 200 fluid having a viscosity of 0.65 centistokes and a boiling point of 100 C, Dow Corning ® 225 fluid having a viscosity of 10 centistokes and a boiling point greater than 200 C, and Dow Corning ® 200 fluids having viscosities of 50, 350, and 12,500 centistokes, respectively, and boiling points greater than 200 C.
  • Suitable dimethicones include those represented by the chemical formula (CH 3 ) 3 SiO[(CH 3 ) 2 SiO] x [CH 3 RSiO] y Si(CH 3 ) 3 wherein R is straight or branched chain alkyl having from two to about 30 carbon atoms and x and y are each integers of 1 or greater selected to achieve the desired molecular weight which can range to over about 10,000,000.
  • alkyl-substituted dimethicones include cetyl dimethicone and lauryl dimethicone.
  • Cyclic polyalkylsiloxanes suitable for use in the composition include those represented by the chemical formula [SiR 2 --O] n wherein R is an alkyl group (generally R is methyl or ethyl, more generally methyl) and n is an integer from about 3 to about 8, more generally n is an integer from about 3 to about 7, and still more generally n is an integer from about 4 to about 6.
  • R is an alkyl group
  • n is an integer from about 3 to about 8
  • n is an integer from about 3 to about 7
  • n is an integer from about 4 to about 6.
  • R is methyl
  • these materials are typically referred to as cyclomethicones.
  • Commercially available cyclomethicones include Dow Corning ® 244 fluid having a viscosity of 2.5 centistokes, and a boiling point of 172 C, which primarily contains the cyclomethicone tetramer (i.e.
  • n 4 and 5
  • trimethylsiloxysilicate which is a polymeric material corresponding to the general chemical formula [(CH 2 ) 3 SiO i/2 ] x [SiO 2 ] y , wherein x is an integer from about 1 to about 500 and y is an integer from about 1 to about 500.
  • a commercially available trimethylsiloxysilicate is sold as a mixture with dimethicone as Dow Corning ® 593 fluid.
  • Dimethiconols are also suitable for use in the composition. These compounds can be represented by the chemical formulas R 3 SiO[R 2 SiO] x SiR 2 OH and HOR 2 SiO[R 2 SiO] x SiR 2 OH wherein R is an alkyl group (generally R is methyl or ethyl, more generally methyl) and x is an integer from O to about 500, chosen to achieve the desired molecular weight.
  • Commercially available dimethiconols are typically sold as mixtures with dimethicone or cyclomethicone (e.g. Dow Corning ® 1401, 1402, and 1403 fluids).
  • Po lyalkylaryl siloxanes are also suitable for use in the composition. Polymethylphenyl siloxanes having viscosities from about 15 to about 65 centistokes at 25 C. are especially useful.
  • organopolysiloxanes selected from polyalkylsiloxanes, alkyl substituted dimethicones, cyclomethicones, trimethylsiloxy silicates, dimethiconols, polyalkylaryl siloxanes, and mixtures thereof, particularly polyalkylsiloxanes and cyclomethicones, particular among the polyalkylsiloxanes are dimethicones.
  • the continuous silicone phase may contain one or more non- silicone oils. Concentrations of non- silicone oils in the continuous silicone phase are generally minimized or avoided altogether so as to further enhance oxidative stability of the selected retinoid in the compositions. Suitable non- silicone oils have a melting point of about 25 C. or less under about one atmosphere of pressure. Examples of non-silicone oils suitable for use in the continuous silicone phase are those well known in the chemical arts in topical personal care products in the form of water-in-oil emulsions, e.g., mineral oil, vegetable oils, synthetic oils, semisynthetic oils, etc. [000195] (2) Dispersed Aqueous Phase
  • the topical compositions contain from about 30% to about 90%, more generally from about 50% to about 85%, and still more generally from about 70% to about 80% of a dispersed aqueous phase.
  • the term "dispersed phase” is a well- known term which means that the phase exists as small particles or droplets that are suspended in and surrounded by a continuous phase.
  • the dispersed phase is also known as the internal or discontinuous phase.
  • the dispersed aqueous phase is a dispersion of small aqueous particles or droplets suspended in and surrounded by the continuous silicone phase discussed hereinbefore.
  • the aqueous phase can be water, or a combination of water and one or more water soluble or dispersible ingredients.
  • Nonlimiting examples of such ingredients include thickeners, acids, bases, salts, chelants, gums, water-soluble or dispersible alcohols and polyols, buffers, preservatives, sunscreening agents, colorings, and the like.
  • the topical compositions will typically contain from about 25% to about 90%, generally from about 40% to about 80%, more generally from about 60% to about 80%, water in the dispersed aqueous phase by weight of the composition.
  • Emulsif ⁇ er for Dispersing the Aqueous Phase [000200]
  • the water-in-silicone emulsions generally contain an emulsif ⁇ er.
  • the composition contains from about 0.1% to about 10% emulsif ⁇ er, more generally from about 0.5% to about 7.5%, still more generally from about 1% to about 5%, emulsif ⁇ er by weight of the composition.
  • the emulsif ⁇ er helps disperse and suspend the aqueous phase within the continuous silicone phase.
  • emulsifying agents can be employed herein to form the certain water-in-silicone emulsion.
  • Known or conventional emulsifying agents can be used in the composition, provided that the selected emulsifying agent is chemically and physically compatible with components of the composition, and provides the desired dispersion characteristics.
  • Suitable emulsif ⁇ ers include silicone emulsif ⁇ ers, non-silicon-containing emulsif ⁇ ers, and mixtures thereof, known for use in topical personal care products. Generally these emulsif ⁇ ers have an HLB value of or less than about 14, more generally from about 2 to about 14, and still more generally from about 4 to about 14. Emulsif ⁇ ers having an HLB value outside of these ranges can be used in combination with other emulsif ⁇ ers to achieve an effective weighted average HLB for the combination that falls within these ranges. [000202] Silicone emulsif ⁇ ers can be used. A wide variety of silicone emulsif ⁇ ers are useful herein.
  • silicone emulsif ⁇ ers are typically organically modified organopolysiloxanes, also known as silicone surfactants.
  • Useful silicone emulsif ⁇ ers include dimethicone copolyols. These materials are poly dimethyl siloxanes which have been modified to include polyether side chains such as polyethylene oxide chains, polypropylene oxide chains, mixtures of these chains, and polyether chains containing moieties derived from both ethylene oxide and propylene oxide.
  • Other examples include alkyl-modif ⁇ ed dimethicone copolyols, i.e., compounds which contain C2-C30 pendant side chains.
  • Still other useful dimethicone copolyols include materials having various cationic, anionic, amphoteric, and zwitterionic pendant moieties.
  • dimethicone copolyol emulsif ⁇ ers useful herein can be discussed by the following general structure:
  • R is C1-C30 straight, branched, or cyclic alkyl and R 2 is selected from the group consisting of
  • n is an integer from 3 to about 10; R 3 and R 4 are selected from the group consisting of H and C1-C6 straight or branched chain alkyl such that R 3 and R 4 are not simultaneously the same; and m, o, x, and y are selected such that the molecule has an overall molecular weight from about 200 to about 10,000,000, with m, o, x, and y being independently selected from integers of zero or greater such that m and o are not both simultaneously zero, and z being independently selected from integers of 1 or greater. It is recognized that positional isomers of these copolyols can be achieved.
  • the chemical representations depicted above for the R 2 moieties containing the R 3 and R 4 groups are not meant to be limiting but are shown as such for convenience.
  • silicone surfactants as depicted in the structures in the previous paragraph wherein R 2 is: — (CH j ) consult — O — R ⁇ ,
  • R 5 is a cationic, anionic, amphoteric, or zwitterionic moiety.
  • dimethicone copolyols and other silicone surfactants useful as emulsif ⁇ ers herein include polydimethylsiloxane polyether copolymers with pendant polyethylene oxide sidechains, polydimethylsiloxane polyether copolymers with pendant polypropylene oxide sidechains, polydimethylsiloxane polyether copolymers with pendant mixed polyethylene oxide and polypropylene oxide sidechains, polydimethylsiloxane polyether copolymers with pendant mixed poly(ethylene)(propylene)oxide sidechains, polydimethylsiloxane polyether copolymers with pendant organobetaine sidechains, polydimethylsiloxane polyether copolymers with pendant carboxylate sidechains, polydimethylsiloxane polyether copolymers with pendant quaternary ammoni
  • dimethicone copolyols useful herein sold by Dow Corning Corporation are Dow Corning ® 190, 193, Q2-5220, 2501 Wax, 2-5324 fluid, and 3225C (this later material being sold as a mixture with cyclomethicone). Cetyl dimethicone copolyol is commercially available as a mixture with polyglyceryl-4 isostearate (and) hexyl laurate and is sold under the tradename ABIL ® WE-09 (available from Goldschmidt).
  • Cetyl dimethicone copolyol is also commercially available as a mixture with hexyl laurate (and) polyglyceryl-3 oleate (and) cetyl dimethicone and is sold under the tradename ABIL ® WS- 08 (also available from Goldschmidt).
  • dimethicone copolyols also include lauryl dimethicone copolyol, dimethicone copolyol acetate, diemethicone copolyol adipate, dimethicone copolyolamine, dimethicone copolyol behenate, dimethicone copolyol butyl ether, dimethicone copolyol hydroxy stearate, dimethicone copolyol isostearate, dimethicone copolyol laurate, dimethicone copolyol methyl ether, dimethicone copolyol phosphate, and dimethicone copolyol stearate. See International Cosmetic Ingredient Dictionary, Fifth Edition, 1993.
  • Dimethicone copolyol emulsif ⁇ ers useful herein are discussed, for example, in U.S. Pat. No. 4,960,764, to Figueroa, Jr. et al, issued Oct. 2, 1990; European Patent No. EP 330,369, to SanoGueira, published Aug. 30, 1989; G. H. Dahms, et al., "New Formulation Possibilities Offered by Silicone Copolyols," Cosmetics & Toiletries, vol. 110, pp. 91-100, March 1995; M. E. Carlotti et al., "Optimization of W/O-S Emulsions And Study Of The Quantitative Relationships Between Ester Structure And Emulsion Properties," J.
  • non-silicone-containing emulsif ⁇ ers useful herein are various non- ionic and anionic emulsifying agents such as sugar esters and polyesters, alkoxylated sugar esters and polyesters, C1-C30 fatty acid esters of C1-C30 fatty alcohols, alkoxylated derivatives of C1-C30 fatty acid esters of C1-C30 fatty alcohols, alkoxylated ethers of Cl- C30 fatty alcohols, polyglyceryl esters of C1-C30 fatty acids, C1-C30 esters of polyols, Cl- C30 ethers of polyols, alkyl phosphates, polyoxyalkylene fatty ether phosphates, fatty acid amides, acyl lactylates, soaps, and mixtures thereof.
  • non-silicone-containing emulsif ⁇ ers useful herein are various non- ionic and anionic emulsifying agents such as sugar esters and polyesters
  • Nonlimiting examples of these non-silicon-containing emulsifiers include: polyethylene glycol 20 sorbitan monolaurate (Polysorbate 20), polyethylene glycol 5 soya sterol, Steareth-20, Ceteareth-20, PPG-2 methyl glucose ether distearate, Ceteth-10, Polysorbate 80, cetyl phosphate, potassium cetyl phosphate, diethanolamine cetyl phosphate, Polysorbate 60, glyceryl stearate, PEG-100 stearate, polyoxyethylene 20 sorbitan trioleate (Polysorbate 85), sorbitan monolaurate, polyoxyethylene 4 lauryl ether sodium stearate, polyglyceryl-4 isostearate, hexyl laurate, steareth-20, ceteareth-20, PPG-2 methyl glucose ether distearate, ceteth-10, diethanolamine cetyl phosphate, glyceryl stearate, PEG
  • oil-in-water emulsions having a continuous aqueous phase and a hydrophobic, water-insoluble phase ("oil phase") dispersed therein.
  • oil phase hydrophobic, water-insoluble phase
  • suitable oil-in-water emulsion carriers are discussed in U.S. Pat. No. 5,073,371, to Turner, D. J. et al., issued Dec. 17, 1991, and U.S. Pat. No. 5,073,372, to Turner, D. J. et al., issued Dec. 17, 1991.
  • An Certain oil-in-water emulsion, containing a structuring agent, hydrophilic surfactant and water, is discussed in detail hereinafter.
  • a certain oil-in-water emulsion contains a structuring agent to assist in the formation of a liquid crystalline gel network structure.
  • the structuring agent may assist in providing rheological characteristics to the composition which contribute to the stability of the composition.
  • the structuring agent may also function as an emulsifier or surfactant.
  • Certain compositions contain from about 0.5% to about 20%, more generally from about 1% to about 10%, even more generally from about 1% to about 5%, by weight of the composition, of a structuring agent.
  • Certain structuring agents include stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, stearic acid, palmitic acid, the polyethylene glycol ether of stearyl alcohol having an average of about 1 to about 21 ethylene oxide units, the polyethylene glycol ether of cetyl alcohol having an average of about I to about 5 ethylene oxide units, and mixtures thereof.
  • Certain structuring agents are selected from stearyl alcohol, cetyl alcohol, behenyl alcohol, the polyethylene glycol ether of stearyl alcohol having an average of about 2 ethylene oxide units (steareth-2), the polyethylene glycol ether of stearyl alcohol having an average of about 21 ethylene oxide units (steareth-21), the polyethylene glycol ether of cetyl alcohol having an average of about 2 ethylene oxide units, and mixtures thereof.
  • Certain structuring agents are selected from stearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, steareth-2, steareth-21, and mixtures thereof.
  • hydrophilic Surfactant Certain oil-in- water emulsions contain from about 0.05% to about 10%, generally from about 1% to about 6%, and more generally from about 1% to about 3% of at least one hydrophilic surfactant which can disperse the hydrophobic materials in the water phase (percentages by weight of the topical carrier). The surfactant, at a minimum, must be hydrophilic enough to disperse in water.
  • Certain hydrophilic surfactants are selected from nonionic surfactants. Among the nonionic surfactants that are useful herein are those that can be broadly defined as condensation products of long chain alcohols, e.g.
  • C8-30 alcohols with sugar or starch polymers, i.e., glycosides.
  • sugar or starch polymers i.e., glycosides.
  • These compounds can be represented by the formula (S) n --O--R wherein S is a sugar moiety such as glucose, fructose, mannose, and galactose; n is an integer of from about 1 to about 1000, and R is a C8-30 alkyl group.
  • Examples of long chain alcohols from which the alkyl group can be derived include decyl alcohol, cetyl alcohol, stearyl alcohol, lauryl alcohol, myristyl alcohol, oleyl alcohol, and the like.
  • surfactants include those wherein S is a glucose moiety, R is a C8-20 alkyl group, and n is an integer of from about 1 to about 9.
  • Commercially available examples of these surfactants include decyl polyglucoside (available as APG 325 CS from Henkel) and lauryl polyglucoside (available as APG 600 CS and 625 CS from Henkel).
  • Other useful nonionic surfactants include the condensation products of alkylene oxides with fatty acids (i.e. alkylene oxide esters of fatty acids). These materials have the general formula RCO(X) n OH wherein R is a C 10-30 alkyl group, X is -OCH 2 CH 2 - (i.e.
  • nonionic surfactants are the condensation products of alkylene oxides with 2 moles of fatty acids (i.e. alkylene oxide diesters of fatty acids). These materials have the general formula RCO(X) n OOCR wherein R is a C 10-30 alkyl group, X is --OCH 2 CH 2 — (i.e. derived from ethylene glycol or oxide) or --OCH 2 CHCH 3 — (i.e. derived from propylene glycol or oxide), and n is an integer from about 6 to about 100.
  • nonionic surfactants are the condensation products of alkylene oxides with fatty alcohols (i.e. alkylene oxide ethers of fatty alcohols). These materials have the general formula R(X) n OR' wherein R is a C 10-30 alkyl group, X is — OCH 2 CH 2 — (i.e. derived from ethylene glycol or oxide) or --OCH 2 CHCH 3 - (i.e. derived from propylene glycol or oxide), and n is an integer from about 6 to about 100 and R is H or a C 10-30 alkyl group. Still other nonionic surfactants are the condensation products of alkylene oxides with both fatty acids and fatty alcohols [i.e.
  • polyalkylene oxide portion is esterif ⁇ ed on one end with a fatty acid and etherif ⁇ ed (i.e. connected via an ether linkage) on the other end with a fatty alcohol].
  • These materials have the general formula RCO(X) n OR wherein R and R' are C 10-30 alkyl groups, X is -OCH 2 CH 2 (i.e. derived from ethylene glycol or oxide) or -OCH 2 CHCH 3 — (derived from propylene glycol or oxide), and n is an integer from about 6 to about 100.
  • Nonlimiting examples of these alkylene oxide derived nonionic surfactants include ceteth-6, ceteth-10, ceteth-12, ceteareth-6, ceteareth-10, ceteareth-12, steareth-6, steareth-10, steareth-12, steareth-21, PEG-6 stearate, PEG-IO stearate, PEG-100 stearate, PEG- 12 stearate, PEG-20 glyceryl stearate, PEG-80 glyceryl tallowate, PEG-IO glyceryl stearate, PEG-30 glyceryl cocoate, PEG-80 glyceryl cocoate, PEG-200 glyceryl tallowate, PEG-8 dilaurate, PEG-IO distearate, and mixtures thereof.
  • Still other useful nonionic surfactants include polyhydroxy fatty acid amide surfactants corresponding to the structural formula:
  • R 1 is H, Ci -C 4 alkyl, 2-hydroxyethyl, 2-hydroxy- propyl, generally Ci - C 4 alkyl, more generally methyl or ethyl, most generally methyl
  • R 2 is Cs -C 3 I alkyl or alkenyl, generally C 7 -C 19 alkyl or alkenyl, more generally C 9 -Ci 7 alkyl or alkenyl, most generally Cn -C 15 alkyl or alkenyl
  • Z is a polhydroxyhydrocarbyl moiety having a linear hydrocarbyl chain with a least 3 hydroxyls directly connected to the chain, or an alkoxylated derivative (generally ethoxylated or propoxylated) thereof.
  • Z generally is a sugar moiety selected from the group consisting of glucose, fructose, maltose, lactose, galactose, mannose, xylose, and mixtures thereof.
  • An Certain surfactant corresponding to the above structure is coconut alkyl N-methyl glucoside amide (i.e., wherein the R 2 CO— moiety is derived from coconut oil fatty acids).
  • Processes for making compositions containing polyhydroxy fatty acid amides are disclosed, for example, in G. B. Patent Specification 809,060, published Feb. 18, 1959, by Thomas Hedley & Co., Ltd.; U.S. Pat. No. 2,965,576, to E. R. Wilson, issued Dec. 20, 1960; U.S. Pat. No.
  • nonionic surfactants are those selected from the group consisting of steareth-21, ceteareth-20, ceteareth-12, sucrose cocoate, steareth-100, PEG- 100 stearate, and mixtures thereof.
  • nonionic surfactants suitable for use herein include sugar esters and polyesters, alkoxylated sugar esters and polyesters, Ci -C30 fatty acid esters of Ci -C30 fatty alcohols, alkoxylated derivatives of C1-C30 fatty acid esters of C1-C30 fatty alcohols, alkoxylated ethers of C1-C30 fatty alcohols, polyglyceryl esters of Ci -C30 fatty acids, Cl- C30 esters of polyols, C1-C30 ethers of polyols, alkyl phosphates, polyoxyalkylene fatty ether phosphates, fatty acid amides, acyl lactylates, and mixtures thereof.
  • Nonlimiting examples of these emulsif ⁇ ers include: polyethylene glycol 20 sorbitan monolaurate (Polysorbate 20), polyethylene glycol 5 soya sterol, Steareth-20, Ceteareth-20, PPG-2 methyl glucose ether distearate, Ceteth-10, Polysorbate 80, cetyl phosphate, potassium cetyl phosphate, diethanolamine cetyl phosphate, Polysorbate 60, glyceryl stearate, polyoxyethylene 20 sorbitan trioleate (Polysorbate 85), sorbitan monolaurate, polyoxyethylene 4 lauryl ether sodium stearate, polyglyceryl-4 isostearate, hexyl laurate, PPG-2 methyl glucose ether distearate, PEG-100 stearate, and mixtures thereof.
  • Polysorbate 20 polyethylene glycol 5 soya sterol
  • Steareth-20 Ceteareth-20
  • PPG-2 methyl glucose ether distearate Ceteth
  • Non-ionic surfactants useful herein are fatty acid ester blends based on a mixture of sorbitan or sorbitol fatty acid ester and sucrose fatty acid ester, the fatty acid in each instance being generally Cs -C 2 4, more generally C 10 -C 2 O.
  • a certain fatty acid ester emulsifier is a blend of sorbitan or sorbitol C 16 -C 2 O fatty acid ester with sucrose Cio -Ci6 fatty acid ester, especially sorbitan stearate and sucrose cocoate. This is commercially available from ICI under the trade name Arlatone 2121.
  • Suitable surfactants useful herein include a wide variety of cationic, anionic, zwitterionic, and amphoteric surfactants such as are known and discussed more fully below. See, e.g., McCutcheon's, Detergents and Emulsif ⁇ ers, North American Edition (1986), published by Allured Publishing Corporation; U.S. Pat. No. 5,011,681 to Ciotti et al, issued Apr. 30, 1991; U.S. Pat. No. 4,421,769 to Dixon et al, issued Dec. 20, 1983; and U.S. Pat. No. 3,755,560 to Dickert et al., issued Aug. 28, 1973; these four references are incorporated herein by reference in their entirety.
  • the hydrophilic surfactants useful herein can contain a single surfactant, or any combination of suitable surfactants. The exact surfactant (or surfactants) chosen will depend upon the pH of the composition and the other components present.
  • cationic surfactants especially dialkyl quaternary ammonium compounds, examples of which are discussed in U.S. Pat. No. 5,151,209; U.S. Pat. No. 5,151,210; U.S. Pat. No. 5,120,532; U.S. Pat. No. 4,387,090; U.S. Pat. No. 3,155,591; U.S. Pat. No. 3,929,678; U.S. Pat. No. 3,959,461; McCutcheon's Deterrents & Emulsif ⁇ ers, (North American edition 1979) M. C.
  • cationic surfactants useful herein include cationic ammonium salts such as those having the formula:
  • Ri is an alkyl group having from about 12 to about 30 carbon atoms, or an aromatic, aryl or alkaryl group having from about 12 to about 30 carbon atoms
  • R 2 , R3, and R 4 are independently selected from hydrogen, an alkyl group having from about 1 to about 22 carbon atoms, or aromatic, aryl or alkaryl groups having from about 12 to about 22 carbon atoms
  • X is any compatible anion, generally selected from chloride, bromide, iodide, acetate, phosphate, nitrate, sulfate, methyl sulfate, ethyl sulfate, tosylate, lactate, citrate, glycolate, and mixtures thereof.
  • Ri is an alkyl group having from about 12 to about 22 carbon atoms
  • R 2 is selected from H or an alkyl group having from about 1 to about 22 carbon atoms
  • R 3 and R 4 are independently selected from H or an alkyl group having from about 1 to about 3 carbon atoms
  • X is as discussed previously.
  • Ri is an alkyl group having from about 12 to about 22 carbon atoms
  • R 2 , R 3 , and R 4 are selected from H or an alkyl group having from about 1 to about 3 carbon atoms
  • X is as discussed previously.
  • other useful cationic emulsif ⁇ ers include amino-amides, wherein in the above structure Ri is alternatively R5 CONH ⁇ (CH 2 ) n , wherein R5 is an alkyl group having from about 12 to about 22 carbon atoms, and n is an integer from about 2 to about 6, more generally from about 2 to about 4, and still more generally from about 2 to about 3.
  • Nonlimiting examples of these cationic emulsifiers include stearamidopropyl PG- dimonium chloride phosphate, behenamidopropyl PG dimonium chloride, stearamidopropyl ethyldimonium ethosulfate, stearamidopropyl dimethyl (myristyl acetate) ammonium chloride, stearamidopropyl dimethyl cetearyl ammonium tosylate, stearamidopropyl dimethyl ammonium chloride, stearamidopropyl dimethyl ammonium lactate, and mixtures thereof. Certain is behenamidopropyl PG dimonium chloride.
  • Nonlimiting examples of quaternary ammonium salt cationic surfactants include those selected from cetyl ammonium chloride, cetyl ammonium bromide, lauryl ammonium chloride, lauryl ammonium bromide, stearyl ammonium chloride, stearyl ammonium bromide, cetyl dimethyl ammonium chloride, cetyl dimethyl ammonium bromide, lauryl dimethyl ammonium chloride, lauryl dimethyl ammonium bromide, stearyl dimethyl ammonium chloride, stearyl dimethyl ammonium bromide, cetyl trimethyl ammonium chloride, cetyl trimethyl ammonium bromide, lauryl trimethyl ammonium chloride, lauryl trimethyl ammonium bromide, stearyl trimethyl ammonium bromide, lauryl trimethyl ammonium bromide, stearyl trimethyl ammonium bromide, lauryl dimethyl ammonium chloride, stearyl trimethyl am
  • Additional quaternary ammonium salts include those wherein the C 12 to C 3 O alkyl carbon chain is derived from a tallow fatty acid or from a coconut fatty acid.
  • tallow refers to an alkyl group derived from tallow fatty acids (usually hydrogenated tallow fatty acids), which generally have mixtures of alkyl chains in the C 16 to C 18 range.
  • coconut refers to an alkyl group derived from a coconut fatty acid, which generally have mixtures of alkyl chains in the C 12 to C 14 range.
  • Examples of quaternary ammonium salts derived from these tallow and coconut sources include ditallow dimethyl ammonium chloride, ditallow dimethyl ammonium methyl sulfate, di(hydrogenated tallow) dimethyl ammonium chloride, di(hydrogenated tallow) dimethyl ammonium acetate, ditallow dipropyl ammonium phosphate, ditallow dimethyl ammonium nitrate, di(coconutalkyl)dimethyl ammonium chloride, di(coconutalkyl)dimethyl ammonium bromide, tallow ammonium chloride, coconut ammonium chloride, stearamidopropyl PG- dimonium chloride phosphate, stearamidopropyl ethyldimonium ethosulfate, stearamidopropyl dimethyl (myristyl acetate) ammonium chloride, stearamidopropyl dimethyl cetearyl ammonium tosylate
  • Certain cationic surfactants are those selected from behenamidopropyl PG dimonium chloride, dilauryl dimethyl ammonium chloride, distearyl dimethyl ammonium chloride, dimyristyl dimethyl ammonium chloride, dipalmityl dimethyl ammonium chloride, distearyl dimethyl ammonium chloride, stearamidopropyl PG-dimonium chloride phosphate, stearamidopropyl ethyldiammonium ethosulfate, stearamidopropyl dimethyl (myristyl acetate) ammonium chloride, stearamidopropyl dimethyl cetearyl ammonium tosylate, stearamidopropyl dimethyl ammonium chloride, stearamido
  • Certain cationic surfactants are those selected from behenamidopropyl PG dimonium chloride, dilauryl dimethyl ammonium chloride, distearyl dimethyl ammonium chloride, dimyristyl dimethyl ammonium chloride, dipalmityl dimethyl ammonium chloride, and mixtures thereof.
  • a certain combination of cationic surfactant and structuring agent is behenamidopropyl PG dimonium chloride and/or behenyl alcohol, wherein the ratio is generally optimized to maintain or to enhance physical and chemical stability, especially when such a combination contains ionic and/or highly polar solvents.
  • This combination is especially useful for delivery of sunscreening agents such as zinc oxide and octyl methoxy cinnamate .
  • anionic surfactants are also useful herein. See, e.g., U.S. Pat. No. 3,929,678, to Laughlin et al., issued Dec. 30, 1975, which is incorporated herein by reference in its entirety.
  • anionic surfactants include the alkoyl isethionates, and the alkyl and alkyl ether sulfates.
  • the alkoyl isethionates typically have the formula RCO-OCH 2 CH 2 SO 3 M wherein R is alkyl or alkenyl of from about 10 to about 30 carbon atoms, and M is a water-soluble cation such as ammonium, sodium, potassium and triethanolamine.
  • Nonlimiting examples of these isethionates include those alkoyl isethionates selected from ammonium cocoyl isethionate, sodium cocoyl isethionate, sodium lauroyl isethionate, sodium stearoyl isethionate, and mixtures thereof.
  • the alkyl and alkyl ether sulfates typically have the respective formulae ROSO 3 M and RO(C 2 H 4 O) x SO3 M, wherein R is alkyl or alkenyl of from about 10 to about 30 carbon atoms, x is from about 1 to about 10, and M is a water-soluble cation such as ammonium, sodium, potassium and triethanolamine.
  • anionic surfactants are the water-soluble salts of the organic, sulfuric acid reaction products of the general formula: [000238] wherein Ri is chosen from the group including a straight or branched chain, saturated aliphatic hydrocarbon radical having from about 8 to about 24, generally about 10 to about 16, carbon atoms; and M is a cation.
  • Still other anionic synthetic surfactants include the class designated as succinamates, olefin sulfonates having about 12 to about 24 carbon atoms, and ⁇ -alkyloxy alkane sulfonates. Examples of these materials are sodium lauryl sulfate and ammonium lauryl sulfate.
  • soaps i.e. alkali metal salts, e.g., sodium or potassium salts
  • fatty acids typically having from about 8 to about 24 carbon atoms, generally from about 10 to about 20 carbon atoms.
  • the fatty acids used in making the soaps can be obtained from natural sources such as, for instance, plant or animal-derived glycerides (e.g., palm oil, coconut oil, soybean oil, castor oil, tallow, lard, etc.)
  • the fatty acids can also be synthetically prepared. Soaps are discussed in more detail in U.S. Pat. No. 4,557,853.
  • Amphoteric and zwitterionic surfactants are also useful herein.
  • amphoteric and zwitterionic surfactants which can be used in the compositions are those which are broadly discussed as derivatives of aliphatic secondary and tertiary amines in which the aliphatic radical can be straight or branched chain and wherein one of the aliphatic substituents contains from about 8 to about 22 carbon atoms (generally Cs -C is) and one contains an anionic water solubilizing group, e.g., carboxy, sulfonate, sulfate, phosphate, or phosphonate.
  • alkyl imino acetates examples are alkyl imino acetates, and iminodialkanoates and aminoalkanoates of the formulas RN[CH 2 ) m CO 2 M] 2 and RNH(CH 2 ) m CO 2 M wherein m is from 1 to 4, R is a Cs -C 2 2 alkyl or alkenyl, and M is H, alkali metal, alkaline earth metal ammonium, or alkanolammonium. Also included are imidazolinium and ammonium derivatives.
  • amphoteric surfactants include sodium 3- dodecyl-aminopropionate, sodium 3-dodecylaminopropane sulfonate, N-alkyltaurines such as the one prepared by reacting dodecylamine with sodium isethionate according to the teaching of U.S. Pat. No. 2,658,072 which is incorporated herein by reference in its entirety; N-higher alkyl aspartic acids such as those produced according to the teaching of U.S. Pat. No. 2,438,091 which is incorporated herein by reference in its entirety; and the products sold under the trade name "Miranol" and discussed in U.S. Pat. No.
  • amphoterics include phosphates, such as coamidopropyl PG-dimonium chloride phosphate (commercially available as Monaquat PTC, from Mona Corp.).
  • amphoteric or zwitterionic surfactants useful herein include betaines.
  • betaines include the higher alkyl betaines, such as coco dimethyl carboxymethyl betaine, lauryl dimethyl carboxymethyl betaine, lauryl dimethyl alphacarboxyethyl betaine, cetyl dimethyl carboxymethyl betaine, cetyl dimethyl betaine (available as Lonzaine 16SP from Lonza Corp.), lauryl bis-(2-hydroxyethyl) carboxymethyl betaine, stearyl bis-(2-hydroxypropyl) carboxymethyl betaine, oleyl dimethyl gamma- carboxypropyl betaine, lauryl bis-(2-hydroxypropyl)alpha-carboxyethyl betaine, coco dimethyl sulfopropyl betaine, stearyl dimethyl sulfopropyl betaine, lauryl dimethyl sulfoethyl betaine, lauryl bis-(2-hydroxyethyl betaine,
  • amphoteric and zwitterionic surfactants include the sultaines and hydroxysultaines such as cocamidopropyl hydroxysultaine (available as Mirataine CBS from Rhone-Poulenc), and the alkanoyl sarcosinates corresponding to the formula RCON(CH 3 )CH 2 CH 2 CO 2 M wherein R is alkyl or alkenyl of about 10 to about 20 carbon atoms, and M is a water-soluble cation such as ammonium, sodium, potassium and trialkanolamine (e.g., triethanolamine), a certain example of which is sodium lauroyl sarcosinate.
  • R alkyl or alkenyl of about 10 to about 20 carbon atoms
  • M is a water-soluble cation
  • ammonium, sodium, potassium and trialkanolamine e.g., triethanolamine
  • Certain oil-in-water emulsion contains from about 25% to about 98%, generally from about 65% to about 9
  • the hydrophobic phase is dispersed in the continuous aqueous phase.
  • the hydrophobic phase may contain water insoluble or partially soluble materials such as are known, including but not limited to the silicones discussed herein in reference to silicone - in- water emulsions, and other oils and lipids such as discussed above in reference to emulsions.
  • the topical compositions may contain a dermatologically acceptable emollient.
  • emollient refers to a material useful for the prevention or relief of dryness, as well as for the protection of the skin.
  • suitable emollients are known and may be used herein. Sagarin, Cosmetics Science and Technology, 2nd Edition, Vol. 1, pp. 32-43 (1972), incorporated herein by reference, contains numerous examples of materials suitable as an emollient.
  • a certain emollient is glycerin. Glycerin is generally used in an amount of from or about 0.001 to or about 30%, more generally from or about 0.01 to or about 20%, still more generally from or about 0.1 to or about 10%, e.g., 5%.
  • Lotions and creams generally contain a solution carrier system and one or more emollients. Lotions and creams typically contain from about 1% to about 50%, generally from about 1% to about 20%, of emollient; from about 50% to about 90%, generally from about 60% to about 80%, water; and the pentapeptide and/or pentapeptide derivative and the additional skin care active (or active agents) in the above discussed amounts. Creams are generally thicker than lotions due to higher levels of emollients or higher levels of thickeners.
  • Ointments may contain a simple carrier base of animal or vegetable oils or semisolid hydrocarbons (oleaginous); absorption ointment bases which absorb water to form emulsions; or water soluble carriers, e.g., a water soluble solution carrier. Ointments may further contain a thickening agent, such as discussed in Sagarin, Cosmetics, Science and Technology, 2nd Edition, Vol. 1, pp. 72-73 (1972), incorporated herein by reference, and/or an emollient.
  • a thickening agent such as discussed in Sagarin, Cosmetics, Science and Technology, 2nd Edition, Vol. 1, pp. 72-73 (1972), incorporated herein by reference, and/or an emollient.
  • an ointment may contain from about 2% to about 10% of an emollient; from about 0.1% to about 2% of a thickening agent; and the pentapeptide and/or pentapeptide derivative and the additional skin care active (or active agents) in the above discussed amounts.
  • Compositions useful for cleansing are formulated with a suitable carrier, e.g., as discussed above, and generally contain, in addition to the pentapeptide and/or pentapeptide derivative and the additional skin care active (or active agents) in the above discussed amounts, from about 1% to about 90%, more generally from about 5% to about 10%, of a dermato logically acceptable surfactant.
  • the surfactant is suitably selected from anionic, nonionic, zwitterionic, amphoteric and ampho lytic surfactants, as well as mixtures of these surfactants.
  • Such surfactants are well known in the detergency art.
  • Nonlimiting examples of possible surfactants include isoceteth-20, sodium methyl cocoyl taurate, sodium methyl oleoyl taurate, and sodium lauryl sulfate. See U.S. Pat. No. 4,800,197, to Kowcz et al, issued Jan. 24, 1989, which is incorporated herein by reference in its entirety, for exemplary surfactants useful herein.
  • the cleansing compositions can optionally contain, at their art-established levels, other materials which are conventionally used in cleansing compositions.
  • the physical form of the cleansing compositions is not critical.
  • the compositions can be, for example, formulated as toilet bars, liquids, shampoos, bath gels, hair conditioners, hair tonics, pastes, or mousses.
  • Rinse-off cleansing compositions, such as shampoos require a delivery system adequate to deposit sufficient levels of active agents on the skin and scalp.
  • a certain delivery system involves the use of insoluble complexes. For a more complete disclosure of such delivery systems, see U.S. Pat. No. 4,835,148, Barford et al., issued May 30, 1989.
  • the term "foundation” refers to a liquid, semi-liquid, semi-solid, or solid skin cosmetic which includes, but is not limited to lotions, creams, gels, pastes, cakes, and the like. Typically the foundation is used over a large area of the skin, such as over the face, to provide a particular look. Foundations are typically used to provide an adherent base for color cosmetics such as rouge, blusher, powder and the like, and tend to hide skin imperfections and impart a smooth, even appearance to the skin. Foundations include a dermatologically acceptable carrier and may include conventional ingredients such as oils, colorants, pigments, emollients, fragrances, waxes, stabilizers, and the like.
  • compositions useful for the methods are generally prepared by conventional methods such as are known of making topical compositions. Such methods typically involve mixing of the ingredients in one or more steps to a relatively uniform state, with or without heating, cooling, application of vacuum, and the like. [000254] Methods for Regulating Skin Condition
  • compositions are useful for regulating certain mammalian skin conditions.
  • Such regulation of keratinous tissue conditions can include prophylactic and therapeutic regulation.
  • regulating methods are directed to thickening keratinous tissue (i.e., building the epidermis and/or dermis layers of the skin and where applicable the keratinous layers of the nail and hair shaft) and preventing and/or retarding atrophy of mammalian skin, preventing and/or retarding the appearance of spider vessels and/or red blotchiness on mammalian skin, preventing and/or retarding the appearance of dark circles under the eye of a mammal, preventing and/or retarding sallowness of mammalian skin, preventing and/or retarding sagging of mammalian skin, softening and/or smoothing lips, hair and nails of a mammal, preventing and/or relieving itch of mammalian skin, regulating skin texture (e.g.
  • Regulating keratinous tissue condition involves topically applying to the keratinous tissue a safe and effective amount of a composition.
  • the amount of the composition which is applied, the frequency of application and the period of use will vary widely depending upon the level of pentapeptides and/or pentapeptide derivatives and the additional skin care active or active agents, in a given composition and the level of regulation desired, e.g., in light of the level of keratinous tissue damage present or expected to occur.
  • the composition is chronically applied to the skin.
  • chromenic topical application continued topical application of the composition over an extended period during the subject's lifetime, generally for a period of at least about one week, more generally for a period of at least about one month, even more generally for at least about three months, even more generally for at least about six months, and more generally still for at least about one year. While benefits are obtainable after various maximum periods of use (e.g., five, ten or twenty years), chronic application may continue throughout the subject's lifetime. Typically applications would be on the order of about once per day over such extended periods, however application rates can vary from about once per week up to about three times per day or more.
  • a wide range of quantities of the compositions can be employed to provide a skin appearance and/or feel benefit.
  • Quantities of the present compositions which are typically applied per application are, in mg composition/cm 2 skin, from about 0.1 mg/cm 2 to about 10 mg/cm 2 .
  • a particularly useful application amount is about 1 mg/cm 2 to about 2 mg/cm 2 .
  • Applying the anti-hirsutism components, etc. is generally practiced by applying a composition in the form of a skin lotion, cream, gel, foam, ointment, paste, emulsion, spray, conditioner, tonic, cosmetic, lipstick, foundation, nail polish, after-shave, or the like which is generally intended to be left on the skin or other keratin structure for some esthetic, prophylactic, therapeutic or other benefit (i.e., a "leave-on" composition).
  • composition After applying the composition to the skin, it is generally left on the skin for a period of at least about 15 minutes, more generally at least about 30 minutes, even more generally at least about 1 hour, still more generally for at least several hours, e.g., up to about 12 hours.
  • Any part of the external portion of the face, hair, and/or nails can be treated, e.g., face, lips, under-eye area, eyelids, scalp, neck, torso, arms, hands, legs, feet, fingernails, toenails, scalp hair, eyelashes, eyebrows, etc.
  • the composition can be applied with the fingers or with an implement or device (e.g., pad, cotton ball, applicator pen, spray applicator, and the like).
  • Another approach to ensure a continuous exposure of the skin to at least a minimum level of the anti-hirsutism components and, if present, the additional skin care active (or active agents) is to apply the compound by use of a patch applied, e.g., to the face.
  • the patch can be occlusive, semi-occlusive or non-occlusive and can be adhesive or non-adhesive.
  • the anti-hirsutism components and the additional skin care active (or active agents) composition can be contained within the patch or be applied to the skin prior to application of the patch.
  • the patch can also include additional active agents such as chemical initiators for exothermic reactions such as those discussed in U.S. Pat. Nos.
  • the patch is generally left on the skin for a period of at least about 5 minutes, more generally at least about 15 minutes, more generally still at least about 30 minutes, even more generally at least about 1 hour, still more generally at night as a form of night therapy.
  • composition according to the disclosure herein was made as follows, including the following ingredients (w/w) as well as various fillers, carriers, etc.:
  • compositions for application of the composition above, the user's face was cleansed with a simple facial cleanser prior to applying the composition.
  • the composition in the form of a lotion was applied to the face twice daily.
  • the chart below demonstrates the results from a survey of patients that used both the compositions, etc., herein as well as other available treatments for hirsutism. The number within the parentheses shows the number of respondents comparing a given treatment to the current compositions.
  • the compositions herein were topically applied by patients for 13 weeks. Only 3.3% in saw no improvement in symptoms at the end of 13 weeks, while 96.7% saw at least some improvement and 83.4% had at least 20% improvement based upon subjective self-assessment. Further, each week of the study, the average severity score dropped compared to the previous week and appeared to be continuing at the end of the study.
  • Example 2 [000265] Further comparison with the "Standard" Treatments. [000266] A composition similar to the composition in Example 1 was made, except that the EGCG was removed and the phospholipids content was increased as the composition was administered via a liposomal modality. The composition included (w/w): Xxx
  • Telocapil 1.50 Myrica Cerifera Extract Water & Phospholipids & Tocotrienols&Superoxide Dismutase &

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Abstract

L'invention concerne des procédés, des compositions, des systèmes, etc. visant à réduire l'hirsutisme non désiré, par exemple les poils terminaux du visage en excès, chez les femmes. Les compositions etc. peuvent également réduire d'autres types de pilosité non désirés chez les femmes, comme les poils des jambes, les poils pubiens et/ou les poils sous les aisselles. Les compositions etc. de l'invention peuvent, si souhaité, avoir pour avantage d'être inodores et indolores, et leur utilisation peut prendre relativement peu de temps à un coût relativement faible. Les procédés peuvent comprendre l'administration topique des compositions sur les zones affectées, qui permet la réduction de la présence des poils terminaux. Des exemples d'agents appropriés à une utilisation dans les compositions, procédés, etc., et donc capables d'une inhibition, éventuellement d'une inhibition synergique, de l'hirsutisme féminin non désiré, comprennent l'acide azélaïque, la vitamine B6, le zinc, un extrait de Camella sinensis, l'acide nordihydroguaïarétique, l'acide oléanolique et le rétinol, qui sont des inhibiteurs de 5-alpha réductase Type 1 cutanée.
PCT/US2008/080546 2007-10-19 2008-10-20 Procédés et compositions destinés à réduire l'hirsutisme se manifestant par une pilosité du visage chez les femmes WO2009052518A2 (fr)

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DE102009055916A1 (de) * 2009-11-27 2011-06-01 Beiersdorf Ag Verwendung von Dihydromyricetin gegen Altershaut
CN103497091A (zh) * 2013-09-24 2014-01-08 江南大学 一种具酪氨酸酶抑制活性的化合物及其制备方法
CN104042450A (zh) * 2014-07-08 2014-09-17 谢振文 柠檬特色皮肤贴膜及其制备方法
EP2872133A4 (fr) * 2012-07-13 2016-01-20 Phyto Tech Corp Compositions et méthodes destinées à traiter la chute des cheveux et à retarder le vieillissement de la peau
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WO2018134713A1 (fr) * 2017-01-21 2018-07-26 R&R Salons Pvt. Ltd. Composition ralentissant la pousse des poils
IT201700027628A1 (it) * 2017-03-13 2018-09-13 Neilos S R L Composizione per uso nella riduzione della crescita dei peli
CN111020027A (zh) * 2019-12-30 2020-04-17 山东农业大学 一种评估植物酚类物质抗镉损伤能力的环状rna标志物的应用
CN114028279A (zh) * 2021-10-26 2022-02-11 上海应用技术大学 一种灵芝自乳化油脂发酵液、发酵方法和应用

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JP2010065008A (ja) * 2008-09-12 2010-03-25 Maruzen Pharmaceut Co Ltd 抗男性ホルモン剤、及び毛乳頭細胞増殖促進剤、並びに頭皮頭髪用外用剤
DE102009055916A1 (de) * 2009-11-27 2011-06-01 Beiersdorf Ag Verwendung von Dihydromyricetin gegen Altershaut
US9283170B2 (en) 2010-05-18 2016-03-15 Conopco, Inc. Personal care composition
US9789047B2 (en) 2012-07-13 2017-10-17 Phyto Tech Corp. Treating hair loss and delaying aging of skin
US10426718B2 (en) 2012-07-13 2019-10-01 Phyto Tech Corp. Compositions and methods for treating hair loss and delaying aging of skin
US9949912B2 (en) 2012-07-13 2018-04-24 Phyto Tech Corp. Compositions and methods for treating hair loss and delaying aging of skin
EP2872133A4 (fr) * 2012-07-13 2016-01-20 Phyto Tech Corp Compositions et méthodes destinées à traiter la chute des cheveux et à retarder le vieillissement de la peau
AU2013289963B2 (en) * 2012-07-13 2017-08-24 Phyto Tech Corp. Treating hair loss and delaying aging of skin
CN103497091B (zh) * 2013-09-24 2015-06-24 江南大学 一种具酪氨酸酶抑制活性的化合物及其制备方法
CN103497091A (zh) * 2013-09-24 2014-01-08 江南大学 一种具酪氨酸酶抑制活性的化合物及其制备方法
CN104042450A (zh) * 2014-07-08 2014-09-17 谢振文 柠檬特色皮肤贴膜及其制备方法
WO2018134713A1 (fr) * 2017-01-21 2018-07-26 R&R Salons Pvt. Ltd. Composition ralentissant la pousse des poils
IT201700027628A1 (it) * 2017-03-13 2018-09-13 Neilos S R L Composizione per uso nella riduzione della crescita dei peli
WO2018167657A1 (fr) * 2017-03-13 2018-09-20 Neilos S.r.l. Composition destinée à être utilisée dans la réduction de la pousse des poils
CN111020027A (zh) * 2019-12-30 2020-04-17 山东农业大学 一种评估植物酚类物质抗镉损伤能力的环状rna标志物的应用
CN114028279A (zh) * 2021-10-26 2022-02-11 上海应用技术大学 一种灵芝自乳化油脂发酵液、发酵方法和应用
CN114028279B (zh) * 2021-10-26 2023-10-27 杭州慧农生物科技有限公司 一种灵芝自乳化油脂发酵液、发酵方法和应用

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