Classifications

• • 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
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
  • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
  • A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/04—Antipruritics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/16—Emollients or protectives, e.g. against radiation
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin

Definitions

• the present invention relates to methods of regulating the condition of mammalian keratinous tissue using select xanthine compounds wherein the methods include, a) regulating visible and/or tactile discontinuities in the texture of mammalian skm, b) preventing and/or retarding the appearance of spider vessels and/or red blotchmess on mammalian skm, c) preventing and/or retarding the appearance of dark circles under the eye of a mammal as well as puffy eyes, d) preventing and/or retarding sallowness of mammalian skin, e) preventing and/or retarding sagging of mammalian skm, f) desquamating mammalian skin, g) softening and/or smoothing lips, hair and nails of a mammal, and h) preventing and/or relieving itch of mammalian skin. These methods are accomplished via the topical application of compositions containing select xanthine compounds to the keratinous tissue of
• Mammalian keratinous tissue is subjected to a variety of insults by both extrinsic and intrinsic factors.
• extrinsic factors mclude ultraviolet radiation, environmental pollution, wind, heat, infrared radiation, low humidity, harsh surfactants, abrasives, etc
• Intrinsic factors include chronological aging and other biochemical changes from within the skm Whether extrinsic or intrinsic, these factors result visible signs of skin damage Typical skm damage includes uneven texture, spider vessels or red blotchmess, under eye circles, puffy eyes, sallowness. sagging, dead sk . rough skm.
• compositions that contain certain xanthine compounds may be used to provide prophylactic as well as therapeutic treatments for these keratinous tissue conditions. For instance, Applicants have found that such compositions may be useful for treating uneven skm texture, spider vessels or red blotchmess. under eye circles, puffy eyes, sallowness, skm sagging, dead sk , rough keratinous tissue including, but not limited to, skm, hair, and/or nails, and skm irritation which results in an itch.
• the present mvention relates to methods for regulating the condition of mammalian keratinous tissue where the methods comprise the step of topically applying to the keratinous tissue of a mammal m need of such treatment a safe and effective amount of a composition
• a safe and effective amount of a composition comprising' a) a safe and effective amount of a repair agent consisting essentially of a xanthine compound selected from the group consistmg of theophyllme, theobromme, and combinations thereof; and b) a dermatologically acceptable carrier for the repair agent.
• compositions or modified versions thereof are suitable for regulating visible and/or tactile discontinuities m the texture of mammalian sk , preventing and/or retarding the appearance of spider vessels and/or red blotchmess on mammalian skm, preventing and/or retarding the appearance of dark circles under the eye of a mammal as well as their puffy eyes, desquamating mammalian skm, preventing and/or retarding sallowness of mammalian skm, preventing and/or retarding sagging of mammalian skm, softening and/or smoothing lips, hair and nails of a mammal, and preventing and/or relieving itch of mammalian skm.
• compositions of the present invention can comprise, consist essentially of. or consist of, the essential as well as optional ingredients and components described herein As used herein, "consisting essentially of means that the composition or component may include additional ingredients, but only if the additional ingredients do not materially alter the basic and novel characteristics of the claimed compositions or methods All publications cited herein are hereby incorporated by reference in their entirety
• keratinous tissue refers to keratin-contammg layers disposed as the outermost protective covering of mammals which includes, but is not limited to, skm, hair, and nails (e.g., toenails, fingernails, hooves, cuticles, etc.)
• topical application means to apply or spread the compositions of the present invention onto the surface of mammalian keratinous tissue.
• the term "dermatologically acceptable,” as used herein, means that the compositions or components thereof so described are suitable for use in contact with human keratinous tissue without undue toxicity, incompatibility, instability, allergic response, and the like.
• safe and effective amount means an amount of a compound or composition sufficient to significantly induce a positive benefit, preferably a positive keratinous tissue appearance or feel benefit, including independently the benefits disclosed herein, but low enough to avoid serious side effects, i.e., to provide a reasonable benefit to risk ratio, withm the scope of sound judgment of the skilled artisan.
• the terms “desquamation, exfoliation, and/or increasing turnover” as used herein mean the removal of the upper layers of the stratum corneum (comprising the horny and granular layers). Without intending to be limited by theory, it is believed that these benefits may be accomplished via chemical and physical means that remove these layers from the top down. Additionally, it is possible to elicit exfoliation via a biological means that drives the turnover of the epidermal layers from the basal layers upwards. It is believed that this involves the process of keratinocyte proliferation as well as induction of differentiation. The latter leads to an elevation in keratinization levels as well, which ultimately lead to a reorganization of the upper epidermal layers that comprise the stratum corneum and stratum granular layers.
• sagging refers to the laxity, slackness, or the like condition of skm that occurs as a result of loss of, damage to, alterations to, and /or abnormalities in dermal elastin.
• smoothing and “softening” as used herein means altering the surface of the keratinous tissue such that its tactile feel is improved.
• compositions of the present invention are useful for topical application and for regulating keratinous tissue condition. Regulation of keratinous tissue condition is often required due to conditions that may be induced or caused by internal and/or external factors.
• regulating skin condition includes prophylactically regulating and or therapeutically regulating skin condition, including preventing loss of skm elasticity (loss and/or inactivation of functional skm elast ) such as elastosis. sagging, loss of skin recoil from deformation; non-melanin skm discoloration such as under eye circles, blotching (e.g..).
• prophylactically regulating skm condition includes delaying, minimizing and/or preventing visible and or tactile discontinuities m skm
• therapeutically regulating skin condition includes ameliorating, e.g., diminishing, minimizing and/or effacing, discontinuities in skm.
• Regulating skin condition involves improving skm appearance and/or feel, especially facial skin (1. e., regulating visible and/or tactile discontinuities m the texture of mammalian skm).
• regulating skm condition is intended to include regulation of such signs irrespective of the mechanism of origin.
• compositions of the present invention including the essential and optional components thereof, are described in detail hereinafter.
• compositions of the present invention comprise a safe and effective amount of various repair agents that consist essentially of a xanthine compound selected from the group consisting of theophylhne, theobromme, and combinations thereof.
• Theophyllme also referred to as 7-D ⁇ hydro-l,3-d ⁇ methyl-lH-purme-2,6-d ⁇ one or 1,3- dimethylxanthme
• theobromme also referred to as 3,7-D ⁇ hydro-3,7-d ⁇ methyl-lH-pu ⁇ ne-2,6- dione
• the xanthine compound preferably comprises from about 0.01% to about 50%, by weight of the composition, more preferably from about 0.1% to about 20%, even more preferably from about 1% to about 10%, even still more preferably from about 2% to about 8%, and most preferably from about 4% to about 6%.
• these xanthine compounds increase the turnover rate of the epidermis, which m turn leads to an ultimate improvement in the texture appearance of skm, especially facial skin.
• xanthine compounds that involve an increase in cellular cyclic adenosine monophosphate (cAMP) levels which leads to induction of secondary signaling pathways such as increases in intracellular calcium and inositol phosphate formation. Ultimately, this leads to alterations m gene expression patterns that impact the homeostasis of cells.
• cAMP cyclic adenosine monophosphate
• compositions of the present invention also comprise a dermatologically acceptable carrier for the xanthine compound.
• dermatologically acceptable carrier means that the carrier is suitable for topical application to mammalian keratinous tissue, has good aesthetic properties, is compatible with the actives of the present invention 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%, preferably from about 80% to about 99.9%, more preferably from about 90% to about 98%, and most preferably 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-m-water, water-m-oil, water-m-oil-in-water, and oil-in-water-in-sihcone emulsions
• Preferred carriers comprise an emulsion such as oil-in-water emulsions or water-in-oil emulsions (e.g., sihcone-in-water or water-m-sihcone)
• a given component will distribute primarily mto either the water or oil phase, depending on the water solubihty/dispersibility of the component in the composition.
• the xanthine compounds distribute primarily into the water phase. Oil-m-water emulsions are especially preferred.
• Emulsions according to the present invention generally contain a solution as described above and a hpid or oil.
• Lipids and oils may be derived from animals, plants, or petroleum and may be natural or synthetic (i.e., man-made).
• Preferred emulsions also contain a humectant, such as glycerin.
• Emulsions will preferably further contain from about 1% to about 10%, more preferably from about 2% to about 5%, of an emulsifier, based on the weight of the carrier.
• Emulsifiers may be nonionic, anionic or cationic. Suitable emulsifiers are disclosed m, for example, U.S. Patent No.
• the emulsion may also contain an anti-foammg agent to minimize foaming upon application to the skin.
• Anti-foammg agents include high molecular weight sihcones and other materials well known in the art for such use.
• Water-in-sihcone emulsions contain a continuous sihcone phase and a dispersed aqueous phase.
• Continuous sihcone phase Preferred water-m-sihcone emulsions of the present invention comprise from about 1% to about 60%, preferably from about 5% to about 40%, more preferably from about 10% to about 20%, by weight of a continuous sihcone phase
• the continuous sihcone phase exists as an external phase that contains or surrounds the discontinuous aqueous phase described hereinafter.
• the continuous sihcone phase contains a polyorganosiloxane oil.
• a preferred water-in- si cone emulsion system is formulated to provide an oxidatively stable vehicle for the optional retmoid.
• the continuous sihcone phase of these preferred emulsions comprises between about 50% and about 99.9% by weight of organopolysiloxane oil and less than about 50% by weight of a non-sihcone oil.
• the continuous sihcone phase comprises at least about 50%, preferably from about 60% to about 99.9%, more preferably from about 70% to about 99.9%, and even more preferably from about 80% to about 99.9%, polyorganosiloxane oil by weight of the continuous sihcone phase, and up to about 50% non- sihcone oils, preferably less about 40%, more preferably less than about 30%, even more preferably less than about 10%, and most preferably less than about 2%, by weight of the continuous sihcone phase.
• These preferred emulsion systems provide more oxidative stability to the retmoid over extended periods of time than comparable water-m-oil emulsions containing lower concentrations of the polyorganosiloxane oil.
• the organopolysiloxane oil for use in the composition may be volatile, non-volatile, or a mixture of volatile and non-volatile sihcones.
• nonvolatile as used m this context refers to those sihcones that are liquid under ambient conditions and have a flash point (under one atmospheric of pressure) of or greater than about 100°C.
• volatile as used in this context refers to all other sihcone oils.
• Suitable organopolysiloxanes can be selected from a wide variety of sihcones spanning a broad range of volatilities and viscosities. Examples of suitable organopolysiloxane oils include polyalkylsiloxanes, cychc 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 R3S ⁇ O[R2S ⁇ O] x S ⁇ R3 wherein R is an alkyl group having from one to about 30 carbon atoms (preferably R is methyl or ethyl, more preferably 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
• Corning® 200 fluid having a viscosity of 0.65 centistokes and a boiling point of 100°C.
• Suitable dimethicones include those represented by the chemical formula (CH3)3S ⁇ O[(CH3)2S ⁇ O] x [CH RS ⁇ O] y S ⁇ (CH3)3 wherem 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 [S ⁇ R2-0] n wherem R is an alkyl group (preferably R is methyl or ethyl, more preferably methyl) and n is an integer from about 3 to about 8, more preferably n is an integer from about 3 to about 7, and most preferably n is an integer from about 4 to about 6.
• cyclomethicones When 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
• n 4 and 5
• mate ⁇ als such as trimethylsiloxysilicate, which is a polymeric material corresponding to the general chemical formula [(CH2)3S ⁇ O ⁇ 2] x [S ⁇ 2Jy, 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 R3S ⁇ O[R 2 S ⁇ O] ⁇ S ⁇ R 2 OH and HOR 2 S ⁇ O[R S ⁇ O] x S ⁇ R2 ⁇ H wherein R is an alkyl group (preferably R is methyl or ethyl, more preferably methyl) and ⁇ is an integer from 0 to about 500, chosen to achieve the desired molecular weight.
• dimethiconols are typically sold as mixtures with dimethicone or cyclomethicone (e.g Dow Corning® 1401, 1402, and 1403 fluids).
• Polyalkylaryl 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 the group consisting of polyalkylsiloxanes, alky l substituted dimethicones, cyclomethicones, trimethylsiloxysihcates, dimethiconols, polyalkylaryl siloxanes, and mixtures thereof. More preferred for use herem are polyalkylsiloxanes and cyclomethicones. Preferred among the polyalkylsiloxanes are dimethicones.
• the continuous sihcone phase may contain one or more non-sihcone oils. Concentrations of non-sihcone oils in the continuous sihcone phase are preferably minimized or avoided altogether so as to further enhance oxidative stability of the selected retmoid in the compositions. Suitable non-sihcone oils have a melting point of about 25°C or less under about one atmosphere of pressure. Examples of non-sihcone oils suitable for use in the continuous sihcone phase are those well known in the chemical arts in topical personal care products m the form of water-m-oil emulsions, e.g., mineral oil, vegetable oils, synthetic oils, semisynthetic oils, etc..
• compositions of the present invention comprise from about 30% to about 90%, more preferably from about 50% to about 85%, and most preferably from about 70% to about 80% of a dispersed aqueous phase.
• dispersed phase is a term well-known to one skilled in the art 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 m and surrounded by the continuous sihcone phase described hereinbefore.
• the aqueous phase can be water, or a combination of water and one or more water soluble or dispersible ingredients.
• optional ingredients include thickeners, acids, bases, salts, chelants, gums, water-soluble or dispersible alcohols and polyols, buffers, preservatives, sunscreenmg agents, colorings, and the like.
• compositions of the present invention will typically comprise from about 25% to about 90%, preferably from about 40% to about 80%, more preferably from about 60% to about 80%, water in the dispersed aqueous phase by weight of the composition.
• the water-in-sihcone emulsions of the present invention preferably comprise an emulsifier.
• the composition contains from about 0.1% to about 10% emulsifier, more preferably from about 0.5% to about 7.5%, most preferably from about 1% to about 5%, emulsifier by weight of the composition.
• the emulsifier helps disperse and suspend the aqueous phase within the continuous sihcone phase.
• emulsifying agents can be employed herein to form the preferred water- m-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 essential components of the composition, and provides the desired dispersion characteristics.
• Suitable emulsifiers include sihcone emulsifiers, non-silicon-containmg emulsifiers, and mixtures thereof, known by those skilled in the art for use in topical personal care products.
• these emulsifiers Preferably these emulsifiers have an HLB value of or less than about 14, more preferably from about 2 to about 14, and most preferably from about 4 to about 14.
• Emulsifiers having an HLB value outside of these ranges can be used m combination with other emulsifiers to achieve an effective weighted average HLB for the combination that falls with these ranges.
• Sihcone emulsifiers are preferred.
• a wide variety of sihcone emulsifiers are useful herein. These sihcone emulsifiers are typically organically modified organopolysiloxanes, also known to those skilled in the art as sihcone surfactants.
• Useful sihcone emulsifiers mclude dimethicone copolyols These materials are polydimethyl 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 de ⁇ ved from both ethylene oxide and propylene oxide.
• dimethicone copolyols examples include alkyl-modified dimethicone copolyols, i.e., compounds which contain C2-C30 pendant side chains.
• Still other useful dimethicone copolyols include materials having various catiomc, a onic, amphote ⁇ c, and zwitteriomc pendant moieties.
• dimethicone copolyol emulsifiers useful herem can be described by the following general structure:
• R is C1-C30 straight, branched, or cyclic alkyl and R ⁇ 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
• sihcone surfactants as depicted in the structures in the previous paragraph wherem R ⁇ is: ⁇ (CH 2 ) n -O-R5, wherein R is a catiomc, anionic, amphote ⁇ c, or zwitte ⁇ onic moiety.
• Nonhmitmg examples of dimethicone copolyols and other sihcone surfactants useful as emulsifiers herein include polydimethylsiloxane polyether copolymers with pendant polyethylene oxide sidechams, polydimethylsiloxane polyether copolymers with pendant polypropylene oxide sidechams, polydimethylsiloxane polyether copolymers with pendant mixed polyethylene oxide and polypropylene oxide sidechams, polydimethylsiloxane polyether copolymers with pendant mixed poly(ethylene)(propylene)ox ⁇ de sidechams, polydimethylsiloxane polyether copolymers with pendant organobetame sidechams, polydimethylsiloxane polyether copolymers with pendant carboxylate sidechams, polydimethylsiloxane polyether copolymers with pendant quaternary ammonium sidechams; and also further modifications of the preceding copolymers containing pendant C2-C30 straight,
• 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 copolyolamme, 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 emulsifiers useful herein are described, for example, in U.S. Patent No. 4,960,764, to Figueroa, Jr et al., issued October 2, 1990; European Patent No. EP 330,369, to SanoGueira, published August 30, 1989; G.H. Dahms, et al., "New Formulation Possibilities Offered by Sihcone Copolyols," Cosmetics & Toiletries, vol. 1 10, pp. 91-100, March 1995; M.E. Carlotti et al., "Optimization of W/O-S Emulsions And Study Of The Quantitatn e Relationships Between Ester Structure And Emulsion Properties," J.
• non-sihcone-contammg emulsifiers useful herein are various non-iomc and aniomc 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 C 1-C30 fatty acid esters of C1 -C30 fatty alcohols, alkoxylated ethers of C1 -C30 fatty alcohols, polyglyceryl esters of C 1 -C30 fatty acids, C1 -C30 esters of polyols.
• non-ihcone-contammg emulsifiers useful herein are various non-iomc and aniomc emulsifying agents such as sugar esters and polyesters, alkoxylated sugar esters and polyesters, C1 -C30 fatty acid esters of C1 -C30 fatty alcohols, alk
• suitable emulsifiers are described, for example, in McCutcheon's, Detergents and Emulsifiers, North American Edition (1986), published by Allured Publishing Corporation; U.S. Patent No. 5,011 ,681 to Ciotti et al., issued April 30, 1991 ; U.S. Patent No. 4,421 ,769 to Dixon et al., issued December 20, 1983; and U.S. Patent No. 3,755,560 to Dickert et al., issued August 28, 1973.
• Nonhmitmg examples of these non-sihcon-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 include oil-m-water emulsions, having a continuous aqueous phase and a hydrophobic, water-insoluble phase ("oil phase") dispersed therein.
• suitable carriers comprising oil-m-water emulsions are described 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.
• a preferred oil-m-water emulsion comprises a structuring agent to assist in the formation of a liquid crystalline gel network structure. Without being limited by theory, it is believed that the structuring agent assists 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.
• Preferred compositions of this invention comprise from about 0.5% to about 20%, more preferably from about 1% to about 10%, most preferably from about 1% to about 5%, by weight of the composition, of a structuring agent.
• the preferred structuring agents of the present invention are selected from the group consisting of steanc acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, stea ⁇ c 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 1 to about 5 ethylene oxide units, and mixtures thereof More preferred structuring agents of the present invention are selected from the group consisting of 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.
• Even more preferred structuring agents are selected from the group consisting of steanc acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, steareth-2, steareth-21 , and mixtures thereof.
• Hydrophihc surfactant is selected from the group consisting of steanc acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenyl alcohol, steareth-2, steareth-21 , and mixtures thereof.
• the preferred oil-in-water emulsions comprise from about 0.05% to about 10%, preferably from about 1% to about 6%, and more preferably from about 1% to about 3% of at least one hydrophihc 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 hydrophihc enough to disperse m water.
• Suitable surfactants include any of a wide variety of known cationic, anionic, zwitte ⁇ onic, and amphote ⁇ c surfactants. See, McCutcheon's, Detergents and Emulsifiers. North American Edition (1986), published by Allured Publishing Corporation; U.S. Patent No. 5,011,681 ; U.S. Patent No. 4,421,769; and U.S. Patent No. 3,755,560. The exact surfactant 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 described in U.S. Patent No. 5,151 ,209; U.S. Patent No. 5,151,210; U.S. Patent No. 5,120,532; U.S Patent No. 4,387,090; U.S. Patent No. 3,155,591; U.S. Patent No. 3,929,678; U.S. Patent No. 3,959,461 ; McCutcheon's. Detergents & Emulsifiers. (North).
• 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;
• R2, R3, and R4 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: and
• X is any compatible anion, preferably selected from the group consisting of chloride, bromide, iodide, acetate, phosphate, nitrate, sulfate, methyl sulfate, ethyl sulfate, tosylate, lactate, citrate, glycolate, and mixtures thereof.
• alkyl groups of R ] , R2. R3, and R4 can also contain ester and or ether linkages, or hydroxy or ammo group substituents (e.g., the alkyl groups can contain polyethylene glycol and polypropylene glycol moieties).
• Ri is an alkyl group having from about 12 to about 22 carbon atoms
• R2 is selected from H or an alkyl group having from about 1 to about 22 carbon atoms
• R3 and R4 are independently selected from H or an alkyl group having from about 1 to about 3 carbon atoms
• X is as described previously.
• R j is an alkyl group having from about 12 to about 22 carbon atoms
• R3, and R4 are selected from H or an alkyl group having from about 1 to about 3 carbon atoms; and X is as described previously.
• cationic emulsifiers include ammo-amides, wherem in the above structure Ri is alternatively R5CONH-(CH2) n , wherem 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 preferably from about 2 to about 4, and most preferably from about 2 to about 3.
• Nonhmitmg examples of these cationic emulsifiers include stearamidopropyl PG-dimomum chloride phosphate, behenamidopropyl PG dimonium chloride, stearamidopropyl ethyldimonium ethosulfate, stearamidopropyl dimethyl (my ⁇ styl acetate) ammonium chloride, stearamidopropyl dimethyl cetearyl ammonium tosylate, stearamidopropyl dimethyl ammonium chloride, stearamidopropyl dimethyl ammonium lactate, and mixtures thereof.
• behenamidopropyl PG dimonium chloride is especially preferred.
• Nonhmitmg examples of quaternary ammonium salt cationic surfactants include those selected from the group consisting of 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 t ⁇ methyl ammonium bromide, lauryl trimethyl ammonium chloride, lauryl trimethyl ammonium bromide, stearyl trimethyl ammonium chloride, stearyl trimethyl ammonium bromide, lauryl dimethyl ammonium chloride, stearyl dimethyl cetyl di
• Additional quaternary ammonium salts mclude those wherein the C ⁇ 2 to C30 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 to
• Ci g range refers to an alkyl group derived from a coconut fatty acid, which generally have mixtures of alkyl chains in the C12 to C14 range.
• Examples of quaternary ammonium salts derived from these tallow and coconut sources include ditallow dimethyl ammonium chloride, ditallow dimethyl ammonium methyl sulfate, d ⁇ (hydrogenated tallow) dimethyl ammonium chloride.
• More preferred cationic surfactants are those selected from the group consisting of behenamidopropyl PG dimonium chloride, dilauryl dimethyl ammonium chloride, distearyl dimethyl ammonium chloride, dimy ⁇ styl dimethyl ammonium chloride, dipalmityl dimethyl ammonium chloride, distearyl dimethyl ammonium chloride, stearamidopropyl PG-dimonium chloride phosphate, stearamidopropyl ethyldiammonium ethosulfate, stearamidopropyl dimethyl (my ⁇ styl acetate) ammonium chlo ⁇ de, stearamidopropyl dimethyl cetearyl ammonium tosylate, stearamidopropyl dimethyl ammonium chloride, stearamidopropyl dimethyl ammonium lactate, and mixtures thereof.
• Most preferred cationic surfactants are those selected from the group consisting of behenamidopropyl PG dimonium chloride, dilauryl dimethyl ammonium chloride, distearyl dimethyl ammonium chloride, dimy ⁇ styl dimethyl ammonium chloride, dipalmityl dimethyl ammonium chloride, and mixtures thereof.
• a preferred combination of cationic surfactant and structuring agent is behenamidopropyl
• PG dimonium chloride and/or behenyl alcohol wherem the ratio is preferably optimized to maintained 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 sunscreemng agents such as zmc oxide and octyl methoxycmnamate.
• anionic surfactants are also useful herein. See, e.g., U.S. Patent No.
• Nonhmitmg examples of anionic surfactants include the alkoyl lsethionates, and the alkyl and alkyl ether sulfates
• the alkoyl lsethionates typically have the formula RCO-OCH 2 CH ? S0 3 M wherem 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 triethanolamme.
• Nonhmitmg examples of these lsethionates include those alkoyl lsethionates selected from the group consisting of ammonium cocoyl lsethionate, sodium cocoyl lsethionate, sodium lauroyl lsethionate, sodium stearoyl lsethionate, and mixtures thereof.
• alkyl and alkyl ether sulfates typically have the respective formulae ROSO ⁇ M and
• RO(C-,H .0) SO.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 triethanolamme.
• R- --SO 3 --M Another suitable class of anionic surfactants are the water-soluble salts of the organic, sulfu ⁇ c acid reaction products of the general formula: R- --SO 3 --M wherem R 1 is chosen from the group consisting of a straight or branched chain, saturated aliphatic hydrocarbon radical having from about 8 to about 24, preferably about 10 to about 16, carbon atoms; and M is a cation.
• anionic synthetic surfactants include the class designated as succmamates, 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, preferably 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 glyce ⁇ des (e.g., palm oil, coconut oil, soybean oil. castor oil, tallow, lard, etc.)
• the fatty acids can also be synthetically prepared. Soaps are described in more detail m U.S. Patent No. 4,557,853. cited above.
• Amphote ⁇ c and zwitte ⁇ omc surfactants are also useful herein
• Examples of amphote ⁇ c and zwitte ⁇ onic surfactants which can be used m the compositions of the present invention are those which are broadly described as derivatives of aliphatic secondary and tertiary amines in which the aliphatic radical can be straight or branched chain and ⁇ herein one of the aliphatic substituents contains from about 8 to about 22 carbon atoms (preferably Cg - Ci g) and one contains an anionic water solubihzmg group, e.g., carboxy, sulfonate, sulfate, phosphate, or phosphonate.
• alkyl lmmo acetates examples are alkyl lmmo acetates, and lmmodialkanoates and ammoalkanoates of the formulas RN[CH 2 ) m C0 2 M] 2 and RNH(CH 2 ) m C0 2 M wherem m is from 1 to 4, R is a
• Suitable amphote ⁇ c surfactants include sodium 3-dodecyl-am ⁇ noprop ⁇ onate, sodium 3-dodecylam ⁇ nopropane sulfonate, N-alkyltau ⁇ nes such as the one prepared by reacting dodecylamine with sodium lsethionate according to the teaching of U.S. Patent No. 2,658,072; N-higher alkyl aspartic acids such as those produced according to the teaching of U.S. Patent No.
• amphote ⁇ cs include phosphates, such as coamidopropyl PG-dimonium chlo ⁇ de phosphate (commercially available as Monaquat PTC,
• betaines include the higher alkyl betaines, such as coco dimethyl carboxymethyl betame, lauryl dimethyl carboxymethyl betame, lauryl dimethyl alphacarboxyethyl betame, cetyl dimethyl carboxymethyl betame, cetyl dimethyl betame (available as Lonzaine 16SP from Lonza Corp.), lauryl b ⁇ s-(2-hydroxyethyl) carboxymethyl betame, stearyl b ⁇ s-(2-hydroxypropyl) carboxymethyl betame, oleyl dimethyl gamma-carboxypropyl betame, lauryl b ⁇ s-(2-hydroxypropyl)alpha-carboxyethyl betame, coco dimethyl sulfopropyl betame, stearyl dimethyl sulfopropyl betame, lauryl dimethyl sulfoethyl betame,
• Velvetex OLB-50 from Henkel and cocamidopropyl betame (available as Velvetex BK-35 and BA-35 from Henkel).
• amphote ⁇ c and zwitte ⁇ onic surfactants include the sultames and hydroxysultaines such as cocamidopropyl hydroxysultaine (available as Miratame CBS from
• Rhone-Poulenc and the alkanoyl sarcosmates corresponding to the formula RCON(CH )CH 2 CH 2 C0 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 t ⁇ alkanolamme (e.g , triethanolamme), a preferred example of which is sodium lauroyl sarcosmate.
• the preferred oil-m-water emulsion comprises from about 25% to about 98%, preferably from about 65% to about 95%, more preferably from about 70% to about 90% water by weight of the topical carrier.
• 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 in the art, including but not limited to the sihcones described herein m reference to sihcone-m-water emulsions, and other oils and hpids such as described above in reference to emulsions.
• compositions of the subject invention may comprise 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. Saga ⁇ n, Cosmetics. Science and Technology. 2nd Edition, Vol. 1, pp. 32-43 (1972), contains numerous examples of materials suitable as an emollient.
• a preferred emollient is glycerin.
• Glycerin is preferably used in an amount of from or about 0.001 to or about 20%, more preferably from or about 0.01 to or about 10%, most preferably from or about 0.1 to or about 5%, e.g., 3%.
• Lotions and creams according to the present invention generally comprise a solution carrier system and one or more emollients. Lotions typically comprise from about 1% to about 20%, preferably from about 5% to about 10%, of emollient; from about 50% to about 90%, preferably from about 60% to about 80%, water; and the xanthine compound m the above described amounts.
• a cream typically comprises from about 5% to about 50%, preferably from about 10% to about 20%, of emollient; from about 45% to about 85%, preferably from about 50% to about 75%, water; and the xanthine compound m the above described amounts.
• Ointments of the present invention may comprise a simple carrier base of animal or vegetable oils or semi-solid hydrocarbons (oleaginous); absorption ointment bases which absorb water to form emulsions; or water soluble carriers, e.g., a water soluble solution earner.
• Ointments may further comprise a thickening agent, such as described in Sagarin, Cosmetics. Science and Technology. 2nd Edition, Vol. 1, pp. 72-73 (1972), and/or an emollient.
• an ointment may comprise from about 2% to about 10% of an emollient; from about 0.1% to about 2% of a thickening agent; and the xanthine compound in the above described amount.
• compositions of this invention useful for cleansing are formulated with a suitable carrier, e.g., as described above, and preferably contain, in addition to the xanthme compound in the above described amounts, from about 1% to about 90%. more preferably from about 5% to about 10%, of a dermatologically acceptable surfactant
• the surfactant is suitably selected from anionic, nonionic, zwitte ⁇ onic, amphote ⁇ c and ampholytic surfactants, as well as mixtures of these surfactants.
• surfactants are well known to those skilled in the detergency art.
• Nonhmitmg examples of possible surfactants include ⁇ soceteth-20, sodium methyl cocoyl taurate, sodium methyl oleoyl taurate, and sodium lauryl sulfate. See U.S. Patent No. 4,800,197, to Kowcz et al., issued January 24, 1989, which is incorporated herem by reference m its entirety, for exemplary surfactants useful herein. Examples of a broad variety of additional surfactants useful herein are described in McCutcheon's Detergents and Emulsifiers. North American Edition (1986), published by Allured Publishing Corporation.
• 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. Toilet bars are most preferred since this is the form of cleansing agent most commonly used to wash the skm.
• Rmse-off cleansing compositions such as shampoos, require a delivery system adequate to deposit sufficient levels of actives on the skm and scalp.
• a preferred delivery system involves the use of insoluble complexes. For a more complete disclosure of such delivery systems, see U.S. Patent 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.
• the foundation is used over a large area of the skm, 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 skm imperfections and impart a smooth, even appearance to the skm.
• Foundations of the present invention include a dermatologically acceptable carrier for the xanthine compound and may include conventional ingredients such as oils, colorants, pigments, emollients, fragrances, waxes, stabilizers, and the like.
• exemplary carriers and such other ingredients which are suitable for use herein are described, for example, in copendmg patent application Serial No. 08/430,961, filed on April 28, 1995 in the names of Marcia L. Canter, Brain D. Barford, and Brian D. Hof ⁇ chter, and U.K. Patent Application GB 2274585-A, published on Jan. 23, 1993.
• compositions of the present invention preferably exhibit a pH of from about 4 to about 10. More preferably, the pH is from about 4.5 to 9.5, even more preferably from about 5 to 9, and most preferably from about 7 to 9. In even more preferred embodiments, the pH is from about 4 to about 6 or from about 8 to 10, more preferably from about 5 to about 6 or from about 8 to about 9. Without being limited by theory, it is believed that such a defined pH aids in penetration of the xanthine compound of the present compositions mto the skm, hair, or nails of a mammal. This penetration occurs due to charge distribution on the xanthme molecule, thereby making it more amenable to penetration.
• compositions of the present invention may contain a variety of other ingredients such as are conventionally used in a given product type provided that they do not unacceptably alter the benefits of the invention.
• the optional components should be suitable for application to skm, that is, when incorporated into the composition they are suitable for use m contact with human skin without undue toxicity, incompatibility, instability, allergic response, and the like within the scope of sound medical judgment.
• CTFA Cosmetic Ingredient Handbook, Second Edition (1992) desc ⁇ bes a wide variety of nonhmitmg cosmetic and pharmaceutical ingredients commonly used in the sk care industry, which are suitable for use m the compositions of the present invention. Examples of these ingredient classes include: abrasives, absorbents, aesthetic components such as fragrances, pigments, colormgs/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., lodopropyl butylcarbamate
• antioxidants e.g., lodopropyl butylcarbamate
• antioxidants 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 of
• humectants including miscellaneous and occlusive
• skin soothing and/or healing agents e.g. panthenol and derivatives (e.g., ethyl panthenol), aloe vera, pantothenic acid and its de ⁇ vatives allantom, bisabolol, and dipotassium glycyrrhizmate.
• skm treating agents thickeners, and vitamins and derivatives thereof.
• the actives useful herein can be categorized by the benefit they provide or by their postulated mode of action. However, it is to be understood that the actives useful herein can m some instances provide more than one benefit or operate via more than one mode of action. Therefore, classifications herein are made for the sake of convenience and are not intended to limit the active to that particular application or applications listed.
• Desquamation Actives A safe and effective amount of a desquamation active may be added to the compositions of the present invention, more preferably from about 0.1% to about 10%, even more preferably from about 0.2% to about 5%. also preferably from about 0.5% to about 4%, by weight of the composition. Desquamation actives enhance the skm appearance benefits of the present invention. For example, the desquamation actives tend to improve the texture of the skin (e.g., smoothness).
• One desquamation system that is suitable for use herein comprises sulfhydryl compounds and zwitte ⁇ onic surfactants and is described m copendmg application Serial No. 08/480,632, filed on June 7, 1995 in the name of Donald L. Bissett.
• compositions of the present mvention may comprise a safe and effective amount of one or more anti-acne actives.
• useful anti-acne actives include resorcmol, sulfur, salicylic acid, erythromycin, zinc, etc. Further examples of suitable anti-acne actives are described in further detail in U. S. Patent No. 5,607,980, issued to McAtee et al, on March 4, 1997.
• compositions of the present invention may further comprise a safe and effective amount of one or more anti-wrmkle actives or anti-atrophy actives.
• anti-w ⁇ nkle/anti- atrophy actives suitable for use in the compositions of the present invention include sulfur- containing D and L ammo acids and their derivatives and salts, particularly the N-acetyl derivatives, a preferred example of which is N-acetyl-L-cysteme, thiols. e.g.
• Vitamin B 2 Compounds
• compositions of the present invention may comprise a safe and effective amount of a vitamin B3 compound.
• Vitamin B compounds are particularly useful for regulating skin condition as described in co-pendmg U. S. Application Serial No 08/834,010, filed April 1 1, 1997 (corresponding to international publication WO 97/39733 Al , published October 30, 1997).
• the compositions of the instant invention preferably comprise from about 0.01% to about 50%, more preferably from about 0.1% to about 10%, even more preferably from about 0.5% to about 10%, and still more preferably from about 1% to about 5%, most preferably from about 2% to about 5%, by weight of the composition, of the vitamin B3 compound.
• vitamin B3 compound means a compound having the formula:
• R is - CONH2 (i.e., macinamide), - COOH (i.e., nicotimc acid) or - CH2OH (i.e., mcotinyl alcohol); derivatives thereof; and salts of any of the foregoing.
• exemplary derivatives of the foregoing vitamin B3 compounds include nicotimc acid esters, including non-vasodilatmg esters of nicotimc acid (e.g., tocpheryl nicotmate), mcotmyl ammo acids, mcotmyl alcohol esters of carboxyhc acids, nicotimc acid N-oxide and macinamide N-oxide.
• vitamin B3 compounds are well known m the art and are commercially available from a number of sources, e.g., the Sigma Chemical Company (St. Louis, MO); ICN Biomedicals, Inc. (Irvin, CA) and Ald ⁇ ch Chemical Company (Milwaukee, WI).
• the vitamin B-, compound is macinamide
• 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.
• the compositions of the present invention may also comprise a retmoid unless otherwise specified.
• retmoid includes all natural and/or synthetic analogs of Vitamin A or retmol-hke compounds which possess the biological activity of Vitamin A in the skin as well as the geometric isomers and stereoisomers of these compounds.
• the retmoid is preferably retmol, retinol esters (e.g., C2 - C 2 2 alkyl esters of retmol, including retinyl palmitate, retinyl acetate, retinyl propionate). retinal, and/or retmoic acid (including all-trans retmoic acid and/or 13-c ⁇ s-retmo ⁇ c acid), more preferably retmoids other than retmoic acid. These compounds are well known m the art and are commercially available from a number of sources, e.g., Sigma Chemical Company (St.
• retmoids are tocopheryl-retmoate [tocopherol ester of retmoic acid (trans- or cis-), adapalene ⁇ 6-[3-(l-adamantyl)-4-methoxyphenyl]-2-naphtho ⁇ c acid ⁇ , and tazarotene (ethyl 6-[2-(4,4-d ⁇ methylth ⁇ ochroman-6-yl)-ethynyl]n ⁇ cotmate).
• Preferred retmoids are retinol, retinyl palmitate, retinyl acetate, retinyl prop ⁇ onate, retinal and combinations thereof.
• the retmoid 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 retmoid is preferably substantially pure, more preferably essentially pure.
• compositions of this invention may contain a safe and effective amount of the retmoid, such that the resultant composition is safe and effective for regulating keratinous tissue condition, preferably for regulating visible and/or tactile discontinuities in skin texture.
• the compositions preferably contain from or about 0.005% to or about 2%, more preferably 0.01% to or about 2%, retmoid.
• Retinol is most preferably used in an amount of from or about 0.01% to or about 0.15%; retmol esters are most preferably used m an amount of from or about 0.01% to or about 2% (e.g., about 1%); retmoic acids are most preferably used in an amount of from or about 0.01% to or about 0.25%; tocopheryl-retmoate, adapalene, and tazarotene are most preferably used in an amount of from or about 0.01% to or about 2% Where the compositions of the present invention contain both a retmoid and a Vitamin
• the retmoid is preferably used in the above amounts, and the vitamin B3 compound is preferably used in an amount of from or about 0.1% to or about 10%, more preferably from or about 2% to or about 5%.
• Anti-Oxidants/Radical Scavengers are preferably used in the above amounts, and the vitamin B3 compound is preferably used in an amount of from or about 0.1% to or about 10%, more preferably from or about 2% to or about 5%.
• compositions of the present invention 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 skm damage.
• a safe and effective amount of an anti-oxidant/radical scavenger may be added to the compositions of the subject invention, preferably from about 0.1% to about 10%, more preferably 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), tocopherol
• vitamin E tocopherol sorbate, tocopherol acetate, other esters of tocopherol, butylated hydroxy benzoic acids and their salts, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxyhc acid
• Trolo ⁇ R gallic acid and its alkyl esters, especially propyl gallate, uric acid and its salts and alkyl esters, sorbic acid and its salts, amines (e.g., N,N- diethylhydroxylamme, ammo-guanidme), sulfhydryl compounds (e.g., glutathione), dihydroxy fuma ⁇ c acid and its salts, lycme pidolate, argmine pilolate, nordihydroguaiaretic acid, bioflavonoids, lysme, methionme, prohne, superoxide dismutase, silymarm, tea extracts, grape skm/seed extracts, melanin, and rosemary extracts may be used.
• amines e.g., N,N- diethylhydroxylamme, ammo-guanidme
• sulfhydryl compounds e.g., glutathione
• Preferred anti-oxidants/radical scavengers are selected from tocopherol sorbate and other esters of tocopherol, more preferably tocopherol sorbate.
• tocopherol sorbate in topical compositions and applicable to the present invention is described in U.S. Patent No. 4,847,071, issued on July 1 1, 1989 to Donald L. Bissett, Rodney D. Bush and Ranjit Chatterjee.
• Chelators The compositions of the present invention may also comprise a safe and effective amount of a chelator or chelating agent.
• chelator or “chelatmg 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 m 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 skm texture changes and against other environmental agents which can cause skm damage.
• a safe and effective amount of a chelatmg agent may be added to the compositions of the subject mvention, preferably from about 0.1% to about 10%. more preferably from about 1% to about 5%, of the composition.
• Exemplary chelators that are useful herein are disclosed in U.S. Patent No. 5,487,884, issued 1/30/96 to Bissett et al.; International Publication No.
• compositions of the present invention may optionally comprise a flavonoid compound Flavonoids are broadly disclosed in U S. Patents Nos 5,686.082 and 5,686,367.
• Flavonoids suitable for use in the present invention are flavanones selected from the group consisting of unsubstituted flavanones, mono-substituted flavanones, and mixtures thereof; chalcones selected from the group consisting of unsubstituted chalcones, mono-substituted chalcones, di-substituted chalcones, t ⁇ -substituted chalcones, and mixtures thereof; flavones selected from the group consisting of unsubstituted flavones, mono-substituted flavones, di- substituted flavones, and mixtures thereof, one or more lsoflavones, couma ⁇ ns selected from the group consisting of unsubstituted coumarms, mono-substituted coumarms, di-substituted coumarms, and mixtures thereof; chromones selected from the group consisting of unsubstituted
• substituted means flavonoids wherem 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-hydro ⁇ y flavanone, 7-hydroxy flavanone, etc ), mono-alkoxy flavanones (e.g , 5-mefhoxy 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.
• mono-hydroxy flavanones e.g., 2'-hydroxy flavanone, 6-hydro ⁇ y flavanone, 7-hydroxy flavanone, etc
• mono-alkoxy flavanones e.g , 5-mefhoxy flavanone. 6-methoxy flavanone, 7- methoxy flavanone, 4'-methoxy flavan
• di-hydroxy chalcones e.g., 2',4-d ⁇ hydroxy chalcone, 2 ',4 '-dihydroxy chalcone, 2,2'-d ⁇ hydroxy chalcone, 2',3-d ⁇ hydroxy chalcone, 2 ',5 '-dihydroxy chalcone, etc
• t ⁇ -hydroxy chalcones e.g., 2',3',4'-t ⁇ hydroxy chalcone, 4,2',4'-t ⁇ hydroxy chalcone, 2,2',4'-t ⁇ hydroxy chalcone, etc.
• unsubstituted flavone 7,2'-d ⁇ hydroxy flavone, 3',4'-d ⁇ hydroxy naphthoflavone, 4'-hydroxy flavone, 5,6-benzoflavone, and 7,8-benzoflavone, unsubstituted isoflavone, daidzein (7,4'- dihydroxy
• Preferred for use herein are couma ⁇ ns, unsubstituted flavanone, methoxy flavanones, unsubstituted chalcone, 2',4-d ⁇ hydro ⁇ y chalcone, and mixtures thereof Most preferred are unsubstituted flavanone, unsubstituted chalcone (especially the trans isomer), and mixtures thereof.
• Flavonoid compounds useful herein are commercially available from a number of sources, e.g., Indofine Chemical Company, Ine (Somerville, New Jersey), Steraloids, Inc. (Wilton, New Hampshire), and Ald ⁇ ch Chemical Company, Inc. (Milwaukee, Wisconsin)
• the herein described flavonoid compounds are preferably present in the instant invention at concentrations of from about 0.01% to about 20%, more preferably from about 0.1% to about 10% , and most preferably from about 0.5% to about 5%.
• a safe and effective amount of an anti-inflammatory agent may be added to the compositions of the present mvention, preferably from about 0.1% to about 10%, more preferably from about 0.5% to about 5%, of the composition
• the anti-mflammatory agent enhances the skin appearance benefits of the present invention, e g., such agents contribute to a more uniform and acceptable skm tone or color
• the exact amount of anti-mflammatory agent to be used in the compositions will depend on the particular anti-mflammatory agent utilized since such agents vary widely m potency.
• Steroidal anti-inflammatory agents including but not limited to, corticosteroids such as hydrocortisone, hydroxylt ⁇ amcmolone, alpha-methyl dexamethasone, dexamethasone- phosphate, beclomethasone dipropionates, clobetasol valerate, desonide, desoxymethasone, desoxycorticosterone acetate, dexamethasone, dichlo ⁇ sone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetomde, fludrocortisone, flumethasone pivalate, fluosinolone acetomde, fluocmonide, flucortme butylesters, fluocortolone, flupredmdene (fluprednyhdene) acetate, flurandrenolone, halcmomde, hydrocortisone acetate, hydrocortisone
• 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 to those skilled in the art
• Anti-mflammatory and Anti-Rheumatic Drugs K. D. Ramsford, Vol. I-III, CRC Press, Boca Raton, (1985), and Anti-inflammatory Agents.
• compositions include, but are not limited to:
• the oxicams such as piroxicam, isoxicam, tenoxicam, sudoxicam, and CP-14,304;
• the sahcylates such as aspirin, disalcid, benorylate, t ⁇ hsate, safapryn, solp ⁇ n, diflumsal, and fendosal
• the acetic acid derivatives such as diclofenac, fenclofenac, lndomethacin, sulmdac, tolmetm, isoxepac, furofenac, tiopmac, zidometacm, acematacin, fentiazac, zomepirac, chndanac, oxepinac, felbmac, and ketorolac
• the fenamates such as mefenamic, meclofenamic, flufenamic, niflumic, and tolfenamic acids
• the propionic acid derivatives such as ibuprofen, naproxen, benoxaprofen,
• 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
• ibuprofen, naproxen, flufenamic acid, etofenamate, aspirin, mefenamic acid, meclofenamic acid, piroxicam and felbmac are preferred, ibuprofen, naproxen, ketoprofen.
• etofenamate, aspirin and flufenamic acid are most preferred
• agents are useful m methods of the present invention
• 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)
• natural sources e.g., plants, fungi, by-products of microorganisms
• Manjistha extracted from plants in the genus Rubia, particularly Rubia Cordifoha
• Guggal extended from plants m the genus Commiphora. particularly Commiphora Mukul.
• kola extract, chamomile, and sea whip extract may be used.
• Additional anti-inflammatory agents useful herem m clude compounds of the Licorice
• Suitable salts of the foregoing compounds include metal and ammonium salts
• Suitable esters include C2 - C24 saturated or unsaturated esters of the acids, preferably C I Q - C24, more preferably Cjg - C24.
• oil soluble licorice extract examples include oil soluble licorice extract, the glycyrrhizic and glycyrrhetic acids themselves, monoammonium glycyrrhizinate, monopotassium glycyrrhizinate, dipotassium glycyrrhizinate, 1 -beta-glycyrrhetic acid, stearyl glycyrrhetmate, and 3-stearyloxy-glycyrrhet ⁇ n ⁇ c acid, and disodium 3-succmyloxy-beta-glycyrrhetmate. Stearyl glycyrrhetmate is preferred.
• compositions of the present invention may also comprise a safe and effective amount of a topical anesthetic
• topical anesthetic drugs include benzocame, hdocaine, bupivacame, chlorprocame, dibucame, etidocame, mepivacame, tetraca e, dyclonme, hexyl- came, procaine, cocaine, ketamine, pramoxine, phenol, and pharmaceutically acceptable salts thereof.
• compositions of the present invention may comprise a tanning active.
• the compositions comprise from about 0.1% to about 20%, more preferably from about 2% to about 7%, and most preferably 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 1.3-d ⁇ hydroxy-2-propanone, is a white to off-white, crystalline powder
• This material can be represented by the chemical formula C3H6O3 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 dime ⁇ c form to the monome ⁇ c form also occurs m aqueous solution. Dihydroxyacetone is also known to be more stable at acidic pH values. See The Merck
• compositions of the present invention may comprise a skm lightening agent
• the compositions preferably comprise from about 0 1% to about 10%, more preferably from about 0.2% to about 5%, also preferably from about 0.5% to about 2%, by weight of the composition, of a skm lightening agent.
• Suitable sk lightening agents include those known the art, including kojic acid, arbutm, ascorbic acid and derivatives thereof, e.g., magnesium ascorbyl phosphate or sodium ascorbyl phosphate.
• Skm lightening agents suitable for use herein also include those described in copendmg patent application Serial No. 08/479,935, filed on June 7, 1995 in the name of Hillebrand, corresponding to PCT Application No.
• compositions of the present invention may comprise an antimicrobial or antifungal active.
• Such actives 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, preferably, from about 0.001% to about 10%, more preferably from about 0.01% to about 5%, and most preferably from about 0.05% to about 2%.
• antimicrobial and antifungal actives examples include ⁇ -lactam drugs, qumolone drugs, ciprofloxacm, norfloxacm, tetracyclme, erythromycin, amikacm, 2,4,4'-t ⁇ chloro-2'- hydroxy diphenyl ether, 3,4,4'-t ⁇ chloroban ⁇ hde, phenoxyethanol, phenoxy propanol, phenoxyisopropanol, doxycyclme, capreomycm, chlorhexidme, chlortetracychne, oxytetracyclme.
• clmdamycm ethambutol, hexamidme lsethionate, metronidazole, pentamidme, gentamicm, kanamycm, hneomycm. methacychne, methenamine, mmocychne, neomycm, netilmicm, paromomycm, streptomycin, tobramycm, miconazole, tetrac ⁇ cl ⁇ ne hydrochlo ⁇ de, erythromycm, zinc erythromycin, erythromycin estolate.
• actives useful herein include those selected from the group consisting of salicylic acid, benzoyl peroxide, 3-hydroxy benzoic acid, glyco c acid, lactic acid, 4-hydroxy benzoic acid, acetyl salicylic acid, 2-hydroxybutano ⁇ c acid, 2-hydroxypentano ⁇ c acid, 2-hydroxyhexano ⁇ c acid, cis-retmoic acid, trans-retinoic acid, retinol, phytic acid, N-acetyl-L- cysteine, hpoic acid, azelaic acid, arachidomc acid, benzoylperoxide, tetracycline, ibuprofen, naproxen, hydrocortisone, acetominophen, resorcmol, phenoxyethanol.
• compositions of the subject invention may optionally contain a sunscreen active.
• sunscreen active includes both sunscreen agents and physical sunblocks. Suitable sunscreen actives may be organic or inorganic.
• sunscreen actives are suitable for use herein. Sagarin, et al., at Chapter VIII, pages 189 et seq., of Cosmetics Science and Technology (1972). discloses numerous suitable actives. Specific suitable sunscreen actives 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); sahcylates (amyl, phenyl, octyl, benzyl, menthyl, glyceryl, and di-pro-pyleneglycol esters); cmnamic acid derivatives (menthyl and benz
• MCX 4,4'-t-butyl methoxydibenzoyl-methane (commercially available as PARSOL 1789), 2- hydroxy-4-methoxybenzophenone, octyldimethyl-p-aminobenzoic acid, digalloylt ⁇ oleate, 2,2- d ⁇ hydroxy-4-methoxybenzophenone, ethyl-4-(b ⁇ s(hydroxy-propyl))am ⁇ nobenzoate, 2-ethylhexyl- 2-cyano-3,3-d ⁇ phenylacrylate, 2-ethylhexyl-sal ⁇ cylate, glyceryl-p-aminobenzoate, 3,3,5-t ⁇ - methylcyclohexylsahcylate, methylanthranilate, p-dimethyl-ammobenzoic acid or aminobenzoate, 2-ethylhexyl-p-dimethyl-amino-benzoate,
• More prefened organic sunscreen actives useful in the compositions useful in the subject invention are 2-ethylhexyl-p-methoxycmnamate, butylmethoxydibenzoyl-methane, 2-hydroxy-4- methoxybenzo-phenone, 2-phenylbenz ⁇ m ⁇ dazole-5-sulfon ⁇ c acid, octyldimethyl-p-ammobenzoic acid, octocrylene and mixtures thereof
• sunscreen actives such as those disclosed in U S Patent No 4,937,370 issued to Sabatelh on June 26, 1990, and U S Patent No 4,999,186 issued to Sabatelh & Spirnak on March 12, 1991
• the sunscreenmg 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
• Prefened members of this class of sunscreenmg agents are 4-N,N-(2-ethylhexyl)methyl- aminobenzoic acid ester of 2.4-d ⁇ hydroxybenzophenone; N.N-d ⁇ -(2-ethylhexyl)-4-am ⁇ nobenzo ⁇ c acid ester with 4-hydroxyd ⁇ benzoylmethane, 4-N,N-(2-ethylhexyl)methyl-ammobenzo ⁇ c
• sunscreen actives include 4,4'-butylmethoxyd ⁇ benzoylmethane, 2- ethylhexyl-p-methoxycinnamate, phenyl benzimidazole sulfomc acid, and octocrylene
• a safe and effective amount of the 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 chosen and the desired Sun Protection Factor (SPF). Conditioning Agents
• compositions of the present invention may comprise a conditioning agent selected from the group consisting of humectants, moisturizers, or skin conditioners.
• a conditioning agent selected from the group consisting of humectants, moisturizers, or skin conditioners.
• a variety of these materials can be employed and each can be present at a level of from about 0.01% to about 20%>, more preferably from about 0.1% to about 10%, and most preferabh from about 0.5% to about 7% by weight of the composition.
• These materials mclude, but are not limited to, guanidine; glycohc acid and glycolate salts (e.g.
• ammonium and quaternary alkyl ammonium salicylic acid; lactic acid and lactate salts (e.g., ammonium and quaternary alkyl ammonium); aloe vera in any of its variety of forms (e.g., aloe vera gel); polyhydroxy alcohols such as sorbitol, glycerol, hexanet ⁇ ol, butanet ⁇ ol, propylene glycol, butylene glycol, hexylene glycol and the like; polyethylene glycols; sugars (e.g., mehbiose) and starches; sugar and starch derivatives (e.g., alkoxylated glucose and fucose); hyaluromc acid; lactamide monoethanolamine; acetamide monoethanolamme; and mixtures thereof. Also useful herein are the propoxylated glycerols described in U. S. Patent No. 4,976,953, to On et al, issued December 1 1, 1990.
• esters are derived from a sugar or polyol moiety and one or more carboxyhc acid moieties Such ester materials are further described in, U. S. Patent No. 2.831,854, U. S. Patent No. 4,005,196, to Jandacek, issued January 25, 1977, U. S. Patent No. 4,005,195, to Jandacek. issued January 25, 1977, U. S. Patent No. 5,306,516, to Letton et al, issued April 26, 1994; U. S. Patent No. 5,306,515, to Letton et al, issued April 26, 1994; U. S. Patent No. 5,305,514.
• compositions of the present invention can comprise one or more thickening agents, preferably from about 0.1% to about 5%, more preferably from about 0 ⁇ % to about 3%, and most preferably from about 0.25% to about 2%, by weight of the composition.
• Nonhmitmg classes of thickening agents mclude those selected from the group consisting of a) Carboxyhc Acid Polymers
• polymers are crosslmked 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, wherem the crosslmkmg agent contains two or more carbon-carbon double bonds and is derived from a polyhydric alcohol
• Polymers useful in the present invention are more fully described in U. S. Patent No. 5,087,445, to Haffey et al, issued February 1 1, 1992; U. S. Patent No. 4,509,949, to Huang et al, issued April 5, 1985, U. S Patent No.
• carboxyhc acid polymers useful herein include the carbomers, which are homopolymers of acrylic acid crosslmked with allyl ethers of sucrose or pentaeryt ⁇ tol The carbomers are available as the Carbopol® 900 series from B.F Goodrich
• carboxyhc acid polymeric agents include copolymers of C j Q -30 alkyl acrylates with one or more monomers of acrylic acid, mefhacryhc acid, or one of their short chain (I e., C1.4 alcohol) esters, wherein the crosslmkmg agent is an allyl ether of sucrose or pentaeryt ⁇ tol. These copolymers are known as acrylates/C ⁇ 0 . 30 alkyl acrylate crosspolymers and are commercially available as Carbopol® 1342, Carbopol® 1382, Pemulen TR-1 , and Pemulen TR-2, from B.F. Goodrich.
• examples of carboxyhc acid polymer thickeners useful herein are those selected from the group consistmg of carbomers, acrylates/Ci o -C-, 0 alkyl acrylate crosspolymers, and mixtures thereof b) Crosslmked Polvacrylate Polymers
• compositions of the present invention can optionally comprise crosslmked polyacrylate polymers useful as thickeners or gelling agents including both cationic and noniomc polymers, with the catio cs being generally prefened.
• useful crosslmked nomonic polyacrylate polymers and crosslmked cationic polyacrylate polymers are those described m U. S. Patent No. 5,100,660, to Hawe et al. issued March 31 , 1992; U. S. Patent No. 4,849,484, to Heard, issued July 18, 1989; U. S Patent No 4,835,206, to Fanar et al, issued May 30, 1989, U.S. Patent No. 4,628,078 to Glo ⁇ er et al issued December 9, 1986; U.S. Patent No. 4,599,379 to Flesher et al issued July 8, 1986; and EP 228,868, to Fanar et al, published July 15, 1987.
• compositions of the present invention can optionally comprise polyacrylamide polymers, especially nomonic polyacrylamide polymers including substituted branched or unbranched polymers. Most prefened among these polyacrylamide polymers is the nomonic polymer given the CTFA designation polyacrylamide and lsoparaffm and laureth-7, available under the Tradename Sepigel 305 from Seppic Corporation (Fairfield, NJ)
• polyacrylamide polymers useful herem 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, SSSA100H, from Lipo Chemicals, Inc., (Patterson, NJ) d) Polvsaccha ⁇ des
• Polysaccha ⁇ des refer to gelling agents which contain a backbone of repeating sugar (i.e., carbohydrate) units
• Nonhmitmg examples of polysaccharide gelling agents include those selected from the group consisting of 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 (preferably hydroxyethylated or hydroxypropylated) to form a hydroxyalkylated cellulose which is then further modified with a C l0 -C 30 straight chain or branched chain alkyl group through an ether linkage.
• these polymers are ethers of C ⁇ 0 -C 30 straight or branched chain alcohols with hydroxyalkylcelluloses.
• alkyl groups useful herein include those selected from the group consisting of stearyl, isostearyl, lauryl, myristyl, cetyl, isocetyl, cocoyl (i.e.
• Prefened among the alkyl hydroxyalkyl cellulose ethers is the matenal 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, DE)
• polysaccha ⁇ des include scleroglucans comprising 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 ClearogelTM CSl 1 from Michel Mercier Products Ine (Mountainside, NJ) e) Gums
• Nonhmitmg examples of these gelling agent gums include materials selected from the group consisting of acacia, agar, algm, alginic acid, ammonium alginate, amylopectm, calcium alginate, calcium canageenan, carnitme, canageenan, dextrin, gelatin, gellan gum, guar gum, guar hydroxypropylt ⁇ monium chloride, hecto ⁇ te, hyaluroi c acid, hydrated silica, hydroxypropyl chitosan, hydroxypropyl guar.
• karaya gum kelp, locust bean gum, natto gum, potassium algmate, potassium canageenan, propylene glycol alginate, sclerotium gum, sodium carboyxmethyl dextran, sodium canageenan, tragacanth gum, xanthan gum, and mixtures thereof
• compositions of the present invention include a thickening agent selected from the group consisting of carboxyhc acid polymers, crosslmked polyacrylate polymers, polyacrylamide polymers, and mixtures thereof, more preferably selected from the group consisting of carboxyhc acid polymers, polyacrylamide polymers, and mixtures thereof
• a thickening agent selected from the group consisting of carboxyhc acid polymers, crosslmked polyacrylate polymers, polyacrylamide polymers, and mixtures thereof
• the compositions are preferably free of retmoids, especially when such compositions are intended for regulating visible and/or tactile discontinuities in mammalian skin texture
• the compositions are preferably free of procaine when such compositions are utilized for prevention and relief of itch
• free of means that the compound or component may not be detected in the compositions Composition Preparation
• compositions of the present invention are generally prepared by conventional methods such as are known in the art 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 Methods for Regulating Keratinous Tissue Condition
• compositions of the present mvention are useful for regulating mammalian keratinous tissue condition, namely skm condition
• Such regulation includes prophylactic and therapeutic regulation More specifically, such regulating methods are directed to preventing and or retarding the appearance of spider vessels and/or red blotchmess on mammalian skin, preventing and/or retarding the appearance of puffy eyes and/or dark circles under the eye of a mammal, desquamating mammalian skm, preventing and/or retarding sallowness of mammalian skin, preventing and/or retarding sagging of mammalian skm, softening and/or smoothing lips, hair and nails of a mammal, and preventing and/or relieving itch of mammalian skm.
• Regulating keratinous tissue condition involves topically applying to the keratinous tissue of a mammal m need of treatment a safe and effective amount of a composition of the present invention.
• 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 the xanthine compound and/or other components of a given composition and the level of regulation desired, e.g., in light of the level of skm damage present or expected to occur
• the composition is chromcalh applied to the skm.
• chronic topical application is meant continued topical application of the composition over an extended period during the subject's lifetime, preferably for a period of at least about one week, more preferably for a period of at least about one month, even more preferably for at least about three months, even more preferably for at least about six months, and more preferably still for at least about one year. While benefits are obtainable after various maximum periods of use (e.g., five, ten or twenty years), it is prefened that chronic application 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 of the present mvention can be employed to provide a keratinous tissue appearance and/or feel benefit Quantities of the present compositions which are typically applied per application are, in mg skm, from about 0.1 mg/cm ⁇ to about 10 mg/cm-A A particularly useful application amount is about 1 mg/cm 2 to about 2 mg/cm ⁇ .
• Regulating skin condition is preferably practiced by applying a composition in the form of a skm lotion, cream, gel, foam, emulsion, spray, conditioner, tonic, cosmetic, lipstick, foundation, nail polish, after-shave, or the like which is 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)
• a composition in the form of a skm lotion, cream, gel, foam, emulsion, spray, conditioner, tonic, cosmetic, lipstick, foundation, nail polish, after-shave, or the like which is 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)
• the composition is preferably left on the skin for a period of at least about 15 minutes, more preferabl) at least about 30 minutes, even more preferably at least about 1 hour, most preferably for
• 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, fingernails, toenails, scalp hair, eyelashes, eyebrows, etc
• the patch can be occlusive, semi- occlusive or non-occlusive
• the xanthine compound-containing composition can be contained withm the patch or be applied to the skm prior to application of the patch
• the patch can also include additional actives such as chemical initiators for exothermic reactions such as those described in PCT application WO 9701313 to Burkett et al
• the patch is preferably left on the skm for a period of at least about 5 minutes, more preferably at least about 15 minutes, more preferably still at least about 30 minutes, even more preferably at least about 1 hour, most preferably at night as a form of night therapy
• compositions of the present invention may be presented to a user or potential user (hereinafter "users") of the composition in association with information which informs such users that use of the composition will provide one or more benefits, mcludmg, but not limited to, preventing and/or retarding the appearance of spider vessels and/or red blotchmess on mammalian skin, preventing and/or retarding the appearance of puffy eyes and/or dark circles under the eye of a mammal, desquamating mammalian skm, 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, and preventing and/or relieving itch of mammalian skm, and the like
• Such information may also include instructions for use to obtain such benefits, e.g , including the method steps described above
• in association with information it is meant that the information is either directly printed on the container for the
• Example 1 A skin cream is prepared by conventional methods from the following components
• Blend the A phase components with a suitable mixer e.g., Tekmar model RW20DZM
• a suitable mixer e.g., Tekmar model RW20DZM
• At temperature add theophyllme.
• add phase C to phase B and mill for 5 minutes e.g., using a Tekmar T50 Mill
• phase D and mix for 5 minutes. Allow to cool to 50°C and then add phase A.
• composition to the facial skm of a subject in need of treatment at the rate of 2 mg composition/cm ⁇ skin once or twice daily for a period of at least 3-6 months.
• Example 2 An emulsion is prepared by conventional methods from the following components
• Form Phase A (water phase) in a suitable vessel charged with the water as follows: gradually add the remaining components with stimng and heat to 55°C.
• Form Phase B (oil phase) m a separate suitable vessel by adding and stimng together the components of Phase B. Begin heating and stimng to 50°C.
• composition to the facial skm of a subject in need of treatment at the rate of 2 mg skm once or twice daily for a period of at least 3-6 months.
• Example 3 A skin cream is prepared by conventional methods from the following components.
• Blend the A phase components with a suitable mixer e.g., Tekmar model RW20DZM
• a suitable mixer e.g., Tekmar model RW20DZM
• composition to the facial skm of a subject in need of treatment at the rate of 2 mg skin once or twice daily for a period of at least 3-6 months.

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