AU2012203806A1 - Personal care compositions - Google Patents

Abstract

Personal care compositions comprising a dipeptide and methods of using such compositions to treat the condition of keratinous tissue. The C terminal amino acid of said dipeptide is threonine. The personal care composition can be applied topically, ingested orally, injected, or 5 used as part of a combined treatment regimen.

Description

AUSTRALIA Patents Act COMPLETE SPECIFICATION (ORIGINAL) Class Int. Class Application Number: Lodged: Complete Specification Lodged: Accepted: Published: Priority Related Art: Name of Applicant: The Procter & Gamble Company Actual Inventor(s): Rosemarie Osborne Address for Service and Correspondence: PHILLIPS ORMONDE FITZPATRICK Patent and Trade Mark Attorneys 367 Collins Street Melbourne 3000 AUSTRALIA Invention Title: PERSONAL CARE COMPOSITIONS Our Ref: 945351 POF Code: 103357/44135 The following statement is a full description of this invention, including the best method of performing it known to applicant(s): -001q la PERSONAL CARE COMPOSITIONS The present application is a divisional from Australian Patent Application No. 2006239234, which claims priority from US Provisional Application No. 60/675,264, filed 27 April 2005, the entire disclosure of which is incorporated herein by reference. 5 TECHNICAL FIELD The present invention relates to personal care compositions comprising a dipeptide and optionally one or more other ingredients. Such compositions are useful for regulating the condition of mammalian keratinous tissue (e.g., skin, hair, and/or nails), especially regulating the cosmetic appearance of mammalian keratinous tissue. 10 BACKGROUND Many personal care products currently available to consumers are directed primarily to improving the health and/or physical appearance of the skin, hair, or nails. Among these skin, hair, or nail care products, many are directed to delaying, minimizing or even eliminating skin, hair, or nail changes typically associated with the aging or the environmental damage to 15 human skin, hair, or nails. Numerous compounds have been described in the art as being useful for regulating skin, hair, or nail condition. Skin, hair, and nails are subject to insults by many extrinsic and intrinsic factors. Extrinsic factors include ultraviolet radiation (e.g., from sun exposure), environmental pollution, wind, heat, low humidity, harsh surfactants, abrasives, and the like. Intrinsic factors 20 include chronological aging and other biochemical changes from within the skin, hair, or nails. Whether extrinsic or intrinsic, these factors result in visible signs of skin, hair, and nail aging and environmental damage (e.g., such as sunlight damage, smoke damage, and damage from pollutants such as nitrogen oxides, sulfur oxides, ozone, and metals such as lead). To many people, the loss of the attractiveness of skin, hair, or nails is a reminder of the disappearance of 25 youth. As a result, the maintenance of a youthful appearance has become a booming business in youth-conscious societies. Numerous products and treatments are available in various forms to help maintain the appearance of younger hair, skin, and nails. Extrinsic or intrinsic factors may result in the thinning and general degradation of the skin, hair, or nails. For example, as the skin, hair, and nails naturally age, there is a reduction 30 in the cells and blood vessels that supply the skin, hair, or nails. There is also a flattening of the dermal-epidermal junction which results in weaker mechanical resistance of this junction. See, for example, Oikarinen, "The Aging of Skin: Chronoaging Versus Photoaging," Photodermatol. Photoimmunol. Photomed., vol. 7, pp. 3-4, 1990.

2 A large number of skin, hair, and nail care actives are used to improve the health and/or cosmetic appearance of the skin, hair, or nails. For instance, various peptides are included in skin, hair, and nail care compositions to provide skin, hair, or nail care benefits. However, not all peptides can provide the benefits desired. For instance, C terminal serine residues can yield dipeptides which may not be dermopharmaceutically and/or cosmetically active or which may not be useful in preferred applications. For instance, depeptides including, for example, lysine and serine (Lys-Ser) can have inadequate properties for many dermopharmaceutical and cosmetic applications. Thus, it would be desirable to provide personal care compositions comprising a dipeptide that can provide superior properties when compared to the corresponding Lys-Ser dipeptide. A reference herein to a patent document or other matter which is given as prior art is not to be taken as an admission that that document or matter was known or that the information it contains was part of the common general knowledge as at the priority date of any of the claims. Throughout the description and claims of the specification, the word "comprise" and variations of the word, such as "comprising" and "comprises", is not intended to exclude other additives, components, integers or steps. SUMMARY The present invention provides personal care compositions comprising a dipeptide that can provide superior properties when compared to the corresponding Lys-Ser dipeptide. The dipeptide of the present invention is a dipeptide wherein the C terminal amino acid is threonine ("Thr"). More preferably, the N terminal amino acid of such dipeptide is a basic amino acid, and still more preferably one which is positively charged at a pH of 6.0. These include the naturally occurring amino acids lysine (Lys), arginine (Arg) and histidine (His). Most preferred is the use of lysine. Thus, a particularly preferred dipeptide in accordance with the present invention has the sequence Lys-Thr and N-acyl derivatives and esters, and nitrogen containing C terminal derivatives thereof. The personal care compositions comprise one or more of such dipeptides and/or derivatives of such dipeptides, preferably in a safe and effective amount. 2369126.1 2a In one aspect, the present invention provides a personal care composition comprising: (a) a dipeptide based molecule, wherein the C terminal amino acid of said dipeptide based molecule is threonine and wherein the N-terminus is substituted by a palmitoyl group; and (b) a dermatologially or orally acceptable carrier or injectible liquid. The present invention also relates to methods of using such compositions to regulate the condition of mammalian keratinous tissue (e.g., skin, hair, or nails). Said methods generally comprise the step of topically applying a composition of the present invention to the keratinous tissue (e.g., skin, hair, or nails) of a mammal in need of such treatment. In another aspect, the method comprises the step of orally ingesting the dipeptide, preferably a safe and effective amount of the dipeptide, to regulate the condition of mammalian keratinous tissue (e.g., skin, hair, or nails). In one embodiment, the method 2369126.1 WO 2006/116731 PCT/US2006/016418 3 comprises a dual treatment regimen comprising both oral ingestion of a composition and topical application of a composition, wherein at least one of the compositions comprises a dipeptide according to the present invention. In another aspect, the method comprises the step of injecting the dipeptide, 5 preferably injecting the dipeptide into and/or under the skin. In a particular embodiment, the method comprises a treatment regimen comprising a combination of injection and/or oral administration and/or topical application. These and other features, aspects, and advantages of the present invention will become evident to those skilled in the art from a reading of the present disclosure. 10 DETAILED DESCRIPTION While the specification concludes with the claims particularly pointing out and distinctly claiming the invention, it is believed that the present invention will be better understood from the following description. As used herein, the singular term "dipeptide" is broad enough to include one or 15 more dipeptides, dipeptide derivatives, or combinations thereof. Thus, the terms "dipeptide", "dipeptides", and "derivatives of dipeptides" are used interchangeably throughout. "Dipeptide" refers to both naturally occurring dipeptides and synthesized dipeptides, including naturally occurring and commercially available compositions that contain at least one dipeptide. 20 As used herein, the singular term "peptide" is broad enough to include one or more peptides, peptide derivatives, or combinations thereof. Thus, the terms "peptide", "peptides", and "derivatives of peptides" are used interchangeably throughout. "Peptide" refers to both naturally occurring peptides and synthesized peptides, including naturally occurring and commercially available compositions that contain at least one peptide. 25 All percentages and ratios used herein are by weight of the total composition and all measurements made are at 25 0 C, unless otherwise designated. The term "keratinous tissue," as used herein, refers to keratin-containing layers disposed as the outermost protective covering of mammals (e.g., humans, dogs, cats, etc.) which includes, but is not limited to, skin, mucosa, lips, hair, toenails, fingernails, 30 cuticles, hooves, etc.

WO 2006/116731 PCT/US2006/016418 4 The terms "topical application", "topically", and "topical", as used herein, mean to apply (e.g., spread, spray) the compositions of the present invention onto the surface of the keratinous tissue. The terms "oral", "orally", and "oral administration", as used herein, refer to 5 orally ingesting a composition of the present invention. The term "dermatologically acceptable," as used herein, means that the compositions or components thereof so described are suitable for use in contact with mammalian keratinous tissue without undue toxicity, incompatibility, instability, allergic response, and the like. 10 The term "orally acceptable", as used herein, means that the compositions or components thereof so described are suitable for oral ingestion by a mammal without undue toxicity, incompatibility, instability, allergic response, and the like. As used herein, "effective amount" means an amount of a compound or composition sufficient to significantly induce a positive keratinous tissue benefit, 15 including independently or in combination with other benefits disclosed herein. This means that the content and/or concentration of dipeptide in the formulation is sufficient that when the formulation is applied with normal frequency and in a normal amount, the formulation can result in the treatment of one or more undesired keratinous tissue conditions (e.g., skin wrinkles). For instance, the amount can be an amount sufficient to 20 inhibit or enhance some biochemical function occurring within the keratinous tissue. This amount of dipeptide may vary depending upon the type of product, the type of keratinous tissue condition to be addressed, and the like. The term "safe and effective amount" as used herein means an amount of a compound or composition sufficient to significantly induce a positive benefit, preferably a 25 positive keratinous tissue appearance or feel benefit, including independently or in combinations with the benefits disclosed herein, but low enough to avoid serious side effects, i.e., to provide a reasonable benefit to risk ratio, within the scope of sound judgment of the skilled artisan. The personal care compositions of the present invention can be useful for treating 30 keratinous tissue (e.g., hair, skin, or nails) condition. As use herein, "treating" or "treatment" or "treat" includes regulating and/or immediately improving keratinous tissue WO 2006/116731 PCT/US2006/016418 5 cosmetic appearance and/or feel. As used herein, "regulating" or "regulation" means maintaining or improving the health and/or cosmetic appearance, and includes both prophylactically regulating and/or therapeutically regulating. Regulation of keratinous tissue condition, namely mammalian and in particular human skin, hair, or nail condition, 5 is often required due to conditions which may be induced or caused by factors internal and/or external to the body. Examples include environmental damage, radiation exposure (including ultraviolet radiation), chronological aging, menopausal status (e.g., post menopausal changes in skin, hair, or nails), stress, diseases, disorders, etc. For instance, "regulating skin, hair, or nail condition" includes prophylactically regulating and/or 10 therapeutically regulating skin, hair, or nail condition, and may involve one or more of the following benefits: thickening of skin, hair, or nails (e.g, building the epidermis and/or dermis and/or sub-dermal [e.g., subcutaneous fat or muscle] layers of the skin, and where applicable the keratinous layers of the nail and hair shaft) to reduce skin, hair, or nail atrophy, increasing the convolution of the dermal-epidermal border (also known as the 15 rete ridges), preventing loss of skin or hair elasticity (loss, damage and/or inactivation of functional skin elastin) such as elastosis, sagging, loss of skin or hair recoil from deformation; melanin or non-melanin change in coloration to the skin, hair, or nails such as under eye circles, blotching (e.g., uneven red coloration due to, e.g., rosacea) (hereinafter referred to as "red blotchiness"), sallowness (pale color), discoloration caused 20 by telangiectasia or spider vessels, and graying hair. As used herein, prophylactically regulating keratinous tissue condition includes delaying, minimizing and/or preventing visible and/or tactile discontinuities in keratinous tissue (e.g., texture irregularities in the skin, hair, or nails which may be detected visually or by feel), including signs of skin, hair, or nail aging. This is also encompassed within 25 the term "treating." As used herein, therapeutically regulating keratinous tissue condition includes ameliorating, e.g., diminishing, minimizing and/or effacing, discontinuities in keratinous tissue (e.g., skin, hair, or nails). This is also encompassed within the term "treating." As used herein, "personal care composition" means a composition in a form 30 intended for topical application to keratinous tissue, and/or oral ingestion, and/or WO 2006/116731 PCT/US2006/016418 6 injection, for the purpose of treating keratinous tissue (e.g., skin, hair, nails), and not intended for subsequent manufacture or modification. The compositions of the present invention can also be useful for immediately improving keratinous tissue (e.g., skin, hair, or nail) cosmetic appearance and/or feel. For 5 example, topical compositions of the present invention can be useful for regulating the cosmetic appearance of skin, hair, or nail condition by providing an immediate visual improvement in skin, hair, or nail appearance following application of the composition to the skin, hair, or nails. Generally speaking, topical compositions of the present invention which further contain particulate materials (e.g., pigments) can be most useful for 10 providing immediate visual improvement. The term "sagging" as used herein means the laxity, slackness, or the like condition of skin that occurs as a result of loss of, damage to, alterations to, and/or abnormalities in dermal elastin, muscle and/or subcutaneous fat. The terms "smoothing" and "softening" as used herein mean altering the surface 15 of the keratinous tissue such that its tactile feel is improved. "Signs of keratinous tissue aging" include, but are not limited to, all outward visibly and tactilely perceptible manifestations as well as any other macro or micro effects due to keratinous tissue aging. Such signs may be induced or caused by intrinsic factors or extrinsic factors, e.g., chronological aging and/or environmental damage. These signs 20 may result from processes which include, but are not limited to, the development of textural discontinuities such as wrinkles and coarse deep wrinkles, fine lines, skin lines, crevices, bumps, large pores (e.g., associated with adnexal structures such as sweat gland ducts, sebaceous glands, or hair follicles), or unevenness or roughness, loss of skin elasticity (loss and/or inactivation of functional skin elastin), sagging (including puffiness 25 in the eye area and jowls), loss of skin firmness, loss of skin tightness, loss of skin recoil from deformation, discoloration (including undereye circles), blotching, sallowness, hyperpigmented skin regions such as age spots and freckles, keratoses, abnormal differentiation, hyperkeratinization, elastosis, collagen breakdown, and other histological changes in the stratum corneum, dermis, epidermis, the skin vascular system (e.g., 30 telangiectasia or spider vessels), and underlying tissues (e.g., fat and/or muscle), especially those proximate to the skin.

WO 2006/116731 PCT/US2006/016418 7 The compositions of the present invention are described in detail hereinafter. I. PERSONAL CARE COMPOSITIONS In one aspect, the personal care compositions of the present invention comprise: (1) a dipeptide; 5 (2) a dermatologically or orally acceptable carrier or injectible liquid; and (3) optionally, optional components. The personal care compositions of the present invention can be in any suitable form. All forms of topical and oral personal care compositions comprising these dipeptides are contemplated and can include, for instance, creams, gels, lotions, 10 emulsions, serums, colloids, solutions, suspensions, ointments, milks, sprays, capsules, tablets, liquids, sticks, solids, pastes, powders, compacts, pencils, spray-on formulations, brush-on formulations, cloths, wipes, and the like. Non-limiting examples of topical personal care compositions can include, without limitation, lipstick, mascara, rouge, foundation, blush, eyeliner, lipliner, lip gloss, facial or 15 body powder, sunscreens and blocks, nail polish, mousse, sprays, styling gels, nail conditioner, bath and shower gels, shampoos, conditioners, cream rinses, hair dyes and coloring products, leave-on conditioners, sunscreens and sunblocks, lip balms, skin conditioners, cold creams, moisturizers, hair sprays, soaps, body scrubs, exfoliants, astringents, depilatories and permanent waving solutions, antidandruff formulations, 20 antisweat and antiperspirant compositions, shaving, preshaving and after shaving products, moisturizers, deodorants, cold creams, cleansers, skin gels, and* rinses. Furthermore, the composition can be applied topically through the use of a patch or other delivery device. Delivery devices can include, but are not limited to, those that can be heated or cooled, as well as those that utilize iontophoresis or ultrasound. 25 Non-limiting examples of oral personal care compositions can include, without limitation, tablets, pills, capsules, drinks, beverages, powders, vitamins, supplements, health bars, candies, chews, and drops. In another aspect, the present invention provides a personal care regimen comprising the use of at least one topical composition in combination with at least one 30 oral composition. At least one of the compositions in this regimen comprises a dipeptide according to the present invention. Preferably, the regimen includes at least one topical WO 2006/116731 PCT/US2006/016418 8 composition comprising such dipeptide and at least one oral composition comprising such dipeptide. In another aspect, the method comprises the step of injecting the dipeptide, preferably injecting the dipeptide into and/or under the skin. In a particular embodiment, 5 the method comprises a treatment regimen comprising a combination of injection and/or oral administration and/or topical application of the dipeptide of the present invention. II. DIPEPTIDE The compositions of the present invention comprise a dipeptide active. As used herein, the term "dipeptide" is broad enough to include one or more dipeptides, one or 10 more derivatives of dipeptides, and combinations thereof. Preferably, the compositions comprise an effective amount, preferably a safe and effective amount, of such dipeptide. A suitable peptide active for use herein is the dipeptide lys-thr and derivatives thereof. A preferred dipeptide derivative-containing composition is palmitoyl-lys-thr from Sederma, France. The use of threonine (Thr) as the C terminal residue in a dipeptide is 15 particularly desirable, and can provide superior attributes in comparison to similar dipeptides terminating with a serine. For instance, the dipeptide Lys-Thr and N-acyl derivatives and esters, and nitrogen containing C terminal derivatives thereof can provide superior properties when compared to the corresponding Lys-Ser dipeptide. Thus, the dipeptide of the present invention is a dipeptide where the C terminal 20 amino acid is threonine ("Thr"). More preferably, the N terminal amino acid of such dipeptides is a basic amino acid, one which is positively charged at a pH of 6.0. These include the naturally occurring amino acids lysine (Lys), arginine (Arg) and histidine (His). Most preferred is the use of lysine. Thus, a particularly preferred dipeptide in accordance with the present invention has the sequence Lys-Thr and N-acyl derivatives 25 and esters, and nitrogen containing C terminal derivatives thereof. Dipeptides and derivatives in accordance with the present invention include, without limitation, His-Thr, Arg-Thr, Lys-Thr, Alk-His-Thr, Alk-Arg-Thr, Alk-Lys-Thr, His-Thr-OAlk, Arg-Thr-OAlk, Lys-Thr-OAlk, His-Thr-NRIR 2 , Arg-Thr-NRIR2, Lys-Thr NRiR 2 , Alk-His-Thr-OAlk, Alk-Lys-Thr-NRIR2, Alk-Lys-Thr-OAlk. When used on the 30 left side of the sequence, "Alk" refers to an N-acyl derivative as defined herein. When WO 2006/116731 PCT/US2006/016418 9 used on the right side of the sequence, "OAlk" refers to an ester group attached to the C terminal carbonyl of Thr (e.g., COOAlk). "NRIR 2 " is as defined herein. In accordance with another aspect of the present invention, dipeptides of the present invention have the following structure: A 0 H N B E 0 5 OH wherein A= NH3*(CH 2

)

4 -,

NH

2 *=C(NH 2 )NH-(CH 2

)

3 - or

H

2 ... C H- N NH +\/ C H B = -NH 2 , -NH 3 *, -NH-D, D = an acyl group of 2-22 carbon atoms in length, or biotinyl and 10 E = -0-Alk, -NRIR 2 , -H, -0, or -OH, wherein Alk is an alkyl group of 1-24 carbons in length, and R, and R 2 are independently H or an alkyl group of 1-12 carbons in length. In a particularly preferred embodiment, B= -NH-D. Note that the molecules of A (Lys, Arg and His respectively) are shown in their respective charged states at pH 6.0. It is understood that they may be present in an 15 uncharged state as well and the representation of A above is meant to include both. The dipeptides in accordance with the present invention, when provided in personal care compositions, are preferably provided in an amount which is safe and effective to treat at least one sign of an undesired keratinous tissue (e.g., skin, hair, or nail) condition. The phrase "to treat at least one undesired keratinous tissue (e.g., skin, 20 hair, or nail) condition" as used herein means that the dipeptide provides an objectively WO 2006/116731 PCT/US2006/016418 10 measurable increase in its effect on some aspect of the keratinous tissue (e.g., skin, hair, or nail) condition when used topically and/or orally in an effective amount. This can be, for example, a greater reduction in wrinkles, increased potency, the ability to stimulate or inhibit at least one biochemical process within the skin, hair, or nails to a greater degree, 5 and the like. Generally, this is determined based on comparison to a control. The dipeptide is preferably included in an amount of from about lxlO-6% to about 10%, more preferably from about 1x10-6% to about 0.1%, and even more preferably from about 1x10-5% to about 0.01%, by weight of the personal care composition. Reference to a "dipeptide" in accordance with the present invention means a 10 dipeptide whose C terminal amino acid is Thr. These include, unless the context specifies otherwise, N-acyl derivatives thereof, as well as C terminal derivatives such as esters, acid halides, and nitrogen containing compounds as discussed herein. The N-acyl derivatives are groups attached to the N terminal amino acid in place of a hydrogen and can include alkyl chains of carbon lengths of between 2 and 22 15 carbons. These can be linear or branched, substituted or unsubstituted, saturated or unsaturated, hydroxylated or not, containing sulfur or not. N-Acyl may also represent a biotinyl group. Similarly, the threonine may be in the form of a C terminal derivative including, for example, an acid, an ester with an alkyl chain having a carbon length of between 1 and 24 carbons ("Oalk"), preferably I to 3 carbons or 14 to 18 carbons. These 20 can be linear or branched, substituted or unsubstituted, saturated or unsaturated, hydroxylated or not, containing sulfur or not. The C terminal derivative may also be NR1R2, in which R1 and R2 are independent of each other H or an alkyl chain of carbon length of between 1 and 12 carbons. These can be linear or branched, substituted or unsubstituted, saturated or unsaturated, hydroxylated or not, containing sulfur or not. 25 Preferably, the acyl derivative attached to the N terminal amino acid is a palmitoyl group and most preferably, the C terminal amino acid is in the form of an acid. All terms such as "skin aging", "signs of skin aging", and the like are used in the sense in which they are generally and widely used in the art of developing, testing and marketing personal care products. "Wrinkles" means furrows in the otherwise smooth 30 surface of the facial skin, visible to the naked eye, generally in the average depth of 50 to more than 200 pm and essentially appearing with progressive age.

WO 2006/116731 PCT/US2006/016418 11 The term "amino acid" as employed herein includes and encompasses all of the naturally occurring and synthetic amino acids, either in the D- or L-configuration if optically active. The term "dipeptide" means a molecule comprising two amino acids as defined herein. 5 In order to enhance the bioavailability and cutaneous and/or epithelial barrier crossing of those peptides, their lipophilicity or lipophilic character can be increased either by acylation of the N-terminal NH 2 group of the peptide, by esterification of the carboxyl group with an alcohol, linear or branched, saturated or unsaturated, hydroxylated or not, or both. 10 In preferred methods of implementation of the invention, N-acyl groups used are lauroyl (C 1 2 ) or myristoyl (C 1 4 ) or palmitoyl (C 1 6 ) or stearoyl (C 1 8 ) or oleoyl (C 18 :i) or arachidic (C 20 ) or linoleoyl (C 18

:

2 ). Biotinyl groups (biotin or derivatives) are also preferred. In a particularly preferred embodiment, the N terminal group is either H or Palmitoyl. 15 III. OPTIONAL COMPONENTS / INGREDIENTS The compositions of the present invention can comprise one or more suitable desired optional components. For example, the composition can optionally include other active or inactive ingredients. Compositions comprising a peptide in combination with an optional keratinous tissue active, such as niacinamide, can be capable of providing 20 additive and/or synergistic keratinous tissue (e.g., skin, hair, or nail) benefits. For instance, such materials can be selected from the group consisting of sugar amines (e.g., N-acetylglucosamine), vitamin B3 compounds, sodium dehydroacetate, dehydroacetic acid and its salts, phytosterols, soy derivatives (e.g., equol and other isoflavones), niacinamide, phytantriol, farnesol, bisabolol, salicylic acid compounds, 25 hexamidines, dialkanoyl hydroxyproline compounds, flavonoids, N-acyl amino acid compounds, retinoids (e.g., retinyl propionate), water-soluble vitamins, ascorbates (e.g., vitamin C, ascorbic acid, ascorbyl glucoside, ascorbyl palmitate, magnesium ascorbyl phosphate, sodium ascorbyl phosphate), particulate materials, sunscreen actives, anti cellulite agents, butylated hydroxytoluene, butylated hydroxyanisole, their derivatives, and 30 combinations thereof. Other examples of optional ingredients can include cationic polymers, conditioning agents (hydrocarbon oils, fatty esters, silicones), anti dandruff WO 2006/116731 PCT/US2006/016418 12 agents, antiseborrheic agents, antipsoriasis agents, suspending agents, viscosity modifiers, dyes, nonvolatile solvents or diluents (water soluble and insoluble), pearlescent aids, foam boosters, surfactants, nonionic cosurfactants, pediculocides, pH adjusting agents, perfumes, preservatives, chelants, chelating agents, proteins, UV absorbers, pigments, 5 other amino acids, and other vitamins. For instance, the compositions of the present invention may comprise one or more vitamins and/or amino acids such as: water soluble vitamins such as vitamin BI, B2, B6, B12, C, pantothenic acid, pantothenyl ethyl ether, panthenol, biotin, and their derivatives, water soluble amino acids such as asparagine, alanine, indole, glutamic acid and their 10 salts, water insoluble vitamins such as vitamin A, D, E, and their derivatives, water insoluble amino acids such as tyrosine, tryptamine, and their salts. The compositions of the present invention may also contain one or more pigment materials such as inorganic, nitroso, monoazo, disazo, carotenoid, triphenyl methane, triaryl methane, xanthene, quinoline, oxazine, azine, anthraquinone, indigoid, 15 thionindigoid, quinacridone, phthalocianine, botanical, natural colors, including: water soluble components such as those having C. I. Names. The compositions of the present invention may also contain antimicrobial agents which are useful as cosmetic biocides and antidandruff agents including: water soluble components such as piroctone olamine, water insoluble components such as 3,4,4'- trichlorocarbanilide (trichlosan), triclocarban 20 and zinc pyrithione. Furthermore, the composition can comprise other peptides, such as those disclosed in U.S. Patent No. 6,492,326, issued December 10, 2002, to Robinson et al. (e.g., pentapeptides such as lys-thr-thr-lys-ser, and derivatives thereof). Suitable pentapeptide derivatives include palmitoyl-lys-thr-thr-lys-ser, available from Sederma, France. 25 Another optional dipeptide that can be used in the composition herein is carnosine. As used herein, the term "peptide" is broad enough to include one or more peptide, one or more peptide derivatives, and combinations thereof. In one embodiment, the optional ingredients do not comprise a peptide. In a particular embodiment, the optional ingredients comprise a peptide wherein said peptide 30 is not a pentapeptide (e.g., palmitoyl-lys-thr-thr-lys-ser). In another embodiment, the optional ingredients do not comprise the pentapeptide palmitoyl-lys-thr-thr-lys-ser. In yet WO 2006/116731 PCT/US2006/016418 13 another embodiment, the optional ingredients comprise a peptide, such as a pentapeptide (e.g., palmitoyl-lys-thr-thr-lys-ser) but said peptide is not present in an effective amount (e.g., it is included for a purpose other than the desired benefits disclosed herein) or such peptide is not present in a safe and effective amount. 5 Any other suitable optional component can also be included in the personal care composition of the present invention, such as those ingredients that are conventionally used in given product types. The CTFA Cosmetic Ingredient Handbook, Tenth Edition (published by the Cosmetic, Toiletry, and Fragrance Association, Inc., Washington, D.C.) (2004) (hereinafter "CTFA"), describes a wide variety of nonlimiting materials that can be 10 added to the composition herein. Examples of these ingredient classes include, but are not limited to: abrasives, absorbents, aesthetic components such as fragrances, pigments, colorings/colorants, essential oils, skin sensates, astringents, etc. (e.g., clove oil, menthol, camphor, eucalyptus oil, eugenol, menthyl lactate, witch hazel distillate), anti-acne agents, anti-caking agents, antifoaming agents, antimicrobial agents (e.g., iodopropyl 15 butylcarbamate), antibacterial agents, antifungal agents, 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 eicosene and vinyl 20 pyrrolidone), opacifying agents, pH adjusters, plant derivatives, plant extracts, plant tissue extracts, plant seed extracts, plant oils, botanicals, botanical extracts, preservatives, propellants, reducing agents, , sebum control agents, sequestrants, skin bleaching and lightening agents, (e.g. hydroquinone, kojic acid, ascorbic acid, magnesiuim ascorbyl phosphate, ascorbyl glucoside, pyridoxine), enzymes, coenzymes, skin-conditioning 25 agents (e.g. humectants and occlusive agents) , skin soothing and/or healing agents and derivatives (e.g. panthenol, and derivatives such as ethyl panthenol, aloe vera, pantothenic acid and its derivatives, allantoin, bisabolol, and dipotassium glycyrrhizinate) , skin treating agents (e.g. vitamin D compounds, mono-,di-, and tri-terpenoids, beta-ionol, cedrol), thickeners, and vitamins and derivatives thereof. 30 WO 2006/116731 PCT/US2006/016418 14 IV. CARRIER The compositions of the present invention can comprise an orally or a dermatologically acceptable carrier, or injectible liquid, depending upon the desired product form. 5 a. Dermatologically Acceptable Carrier The topical compositions of the present invention can also comprise a dermatologically acceptable carrier for the composition. In one embodiment, the carrier is present at a level of from about 50% to about 99.99%, preferably from about 60% to about 99.9%, more preferably from about 70% to about 98%, and even more preferably 10 from about 80% to about 95%, by weight of the composition. The carrier can be in a wide variety of forms. Non-limiting examples include simple solutions (water or oil based), emulsions, and solid forms (gels, sticks). For example, emulsion carriers can include, but are not limited to, oil-in-water, water-in-oil, water-in-silicone, water-in-oil-in-water, and oil-in-water-in-silicone emulsions. 15 Depending upon the desired product form, preferred carriers can comprise an emulsion such as oil-in-water emulsions (e.g., silicone in water) and water-in-oil emulsions, (e.g., water-in-silicone emulsions). As will be understood by the skilled artisan, a given component will distribute primarily into either the water or oil phase, depending on the water solubility/dispensability of the component in the composition. In 20 one embodiment, oil-in-water emulsions are especially preferred. Emulsions according to the present invention can contain an aqueous phase 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). Preferred emulsions can also contain a humectant, such as glycerin. Emulsions can further comprise from about 0.1% to about 25 10%, more preferably from about 0.2% to about 5%, of an emulsifier, based on the weight of the composition. Emulsifiers may be nonionic, anionic or cationic. Suitable emulsifiers are disclosed in, for example, U.S. Patent 3,755,560, U.S. Patent 4,421,769, and McCutcheon's Detergents and Emulsifiers, North American Edition, pages 317-324 (1986). Suitable emulsions may have a wide range of viscosities, depending on the 30 desired product form. The compositions of the present invention can be in the form of pourable liquids WO 2006/116731 PCT/US2006/016418 15 (under ambient conditions). The compositions can therefore comprise an aqueous carrier, which is typically present at a level of from about 20% to about 95%, preferably from about 60% to about 85%. The aqueous carrier may comprise water, or a miscible mixture of water and organic solvent, but preferably comprises water with minimal or no 5 significant concentrations of organic solvent, except as otherwise incidentally incorporated into the composition as minor ingredients of other essential or optional components. b. Orally Acceptable Carrier The compositions of the present invention can also comprise an orally acceptable 10 carrier if they are to be ingested. Any suitable orally ingestible carrier or carrier form, as known in the art or otherwise, can be used. Non-limiting examples of oral personal care compositions can include, but are not limited to, tablets, pills, capsules, drinks, beverages, powders, vitamins, supplements, health bars, candies, chews, and drops. c. Injectible Liquid 15 The compositions of the present invention can also comprise a liquid that is acceptable for injection in and/or under the skin if the composition is to be injected. Any suitable acceptable liquid as known in the art or otherwise can be used. V. COMPOSITION PREPARATION The compositions useful for the methods of the present invention are generally 20 prepared by conventional methods such as are known in the art of making topical and oral compositions and compositions for injection. Such methods typically can 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. VI. METHODS FOR TREATING KERATINOUS TISSUE CONDITION 25 The compositions of the present invention can be useful for treating a number of mammalian keratinous tissue conditions. Such treatment of keratinous tissue conditions can include prophylactic and therapeutic regulation, including regulating the cosmetic appearance of the mammalian keratinous tissue. More specifically, such treatment methods can be directed to, but are not limited to, preventing, retarding, and/or treating 30 uneven skin tone, reducing the size of pores in mammalian skin, regulating oily/shiny appearance of mammalian skin, thickening keratinous tissue (i.e., building the epidermis WO 2006/116731 PCT/US2006/016418 16 and/or dermis and/or subcutaneous layers of the skin and where applicable the keratinous layers of the nail and hair shaft), preventing, retarding, and/or treating uneven skin tone by acting as a lightening or pigmentation reduction cosmetic agent, preventing, retarding, and/or treating atrophy of mammalian skin, softening and/or smoothing lips, hair and 5 nails of a mammal, preventing, retarding, and/or treating itch of mammalian skin, preventing, retarding, and/or treating the appearance of dark under-eye circles and/or puffy eyes, preventing, retarding, and/or treating sallowness of mammalian skin, preventing, retarding, and/or treating sagging (i.e., glycation) of mammalian skin, preventing and/or retarding tanning of mammalian skin, desquamating, exfoliating, and/or 10 increasing turnover in mammalian skin, preventing, retarding, and/or treating hyperpigmentation such as post-inflammatory hyperpigmentation, preventing, retarding, and/or treating the appearance of spider vessels and/or red blotchiness on mammalian skin, preventing, retarding, and/or treating fine lines and wrinkles of mammalian skin, preventing, retarding, and/or treating skin dryness (i.e., roughness, scaling, flaking) and 15 preventing, retarding, and/or treating the appearance of cellulite in mammalian skin. In a preferred embodiment, the composition is used to treat the signs of aging; in one aspect, the composition is used to regulate the signs of aging; in another aspect, the composition is used to reduce or decrease the signs of aging; in yet another aspect the composition is used to prevent the signs of aging in keratinous tissue (e.g., skin, hair, or nails). 20 For instance, the present invention can be useful for therapeutically regulating visible and/or tactile discontinuities in mammalian keratinous tissue, including discontinuities in skin texture and color. For example, the apparent diameter of pores can be decreased, the apparent height of tissue immediately proximate to pore openings can approach that of the interadnexal skin, the skin tone/color can become more uniform, 25 and/or the length, depth, and/or other dimension of lines and/or wrinkles can be decreased. Furthermore, compositions of the present invention can also be useful for cleansing (e.g, hair, body, facial), improving keratinous tissue feel (wet & dry) such as for hair (e.g., improving appearance/look, detangling, shine, gloss, decrease coefficient of 30 friction, increase smoothness, color retention, decrease split ends, prevent hair breakage, prevent environmental damage such as sunlight damage, smoke damage, and damage WO 2006/116731 PCT/US2006/016418 17 from pollutants such as nitrogen oxides, sulfur oxides, ozone, and metals such as lead), odor control, oil control, conditioning, hair volume control, hair growth, and hair growth inhibition. Regulating keratinous tissue conditions can involve topically applying to the 5 keratinous tissue a safe and effective amount of a composition of the present invention. The amount of the composition that is applied, the frequency of application, and the period of use will vary widely depending upon the level of components of a given composition and the level of regulation desired, e.g., in view of the level of keratinous tissue damage present or expected to occur. 10 Furthermore, regulating keratinous tissue conditions can involve orally ingesting a safe and effective amount of a composition of the present invention. The amount of the composition that is ingested, the frequency of ingestion, and the period of use will vary widely depending upon the level of components of a given composition and the level of regulation desired, e.g., in view of the level of keratinous tissue damage present or 15 expected to occur. In one embodiment, the composition is chronically applied to the skin, e.g. topically. By "chronic 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 20 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 preferred that chronic applications continue throughout the subject's lifetime. Typically applications would be on the order of about once per day over such extended periods, 25 however, application rates can vary, and can include 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 invention can be employed to provide a keratinous tissue appearance and/or feel benefit when applied topically. For example, quantities of the present compositions, which are typically 30 applied per application are, in mg composition/cm 2 keratinous tissue, from about 0.1 WO 2006/116731 PCT/US2006/016418 18 mg/cm 2 to about 20 mg/cm 2 . A particularly useful application amount is about 0.5 mg/cm 2 to about 10 mg/cm 2 . Treating keratinous tissue condition can be practiced, for example, by applying a composition in the form of a skin lotion, clear lotion, milky lotion, cream, gel, foam, 5 ointment, paste, 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 keratinous tissue for some aesthetic, prophylactic, therapeutic or other benefit (i.e., a "leave-on" composition). After applying the composition to the keratinous tissue (e.g., skin), it is preferably left on for a period of at least about 15 minutes, more preferably at least about 10 30 minutes, even more preferably at least about 1 hour, even more preferably 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 application of the present compositions may be done using the palms of the hands and/or 15 fingers or a device or implement (e.g., a cotton ball, swab, pad, applicator pen, spray applicator, etc.) Another approach to ensure a continuous exposure of the keratinous tissue to at least a minimum level of the composition is to apply the compound by use of a patch applied, e.g., to the face. Such an approach is particularly useful for problem skin areas 20 needing more intensive treatment (e.g., facial crows feet area, frown lines, under eye area, upper lip, and the like). The patch can be occlusive, semi-occlusive or non-occlusive, and can be adhesive or non-adhesive. The 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 actives such as chemical initiators for exothermic reactions such as those 25 described in PCT application WO 9701313, and in U.S. Patents numbered 5,821,250, 5,981,547, and 5,972,957 to Wu, et al. The patch can also contain a source of electrical energy (e.g., a battery) to, for example, increase delivery of the composition and active agents (e.g., iontophoresis). The patch is preferably left on the keratinous tissue for a period of at least about 5 minutes, more preferably at least about 15 minutes, more 30 preferably still at least about 30 minutes, even more preferably at least about 1 hour, even more preferably at night as a form of night therapy.

WO 2006/116731 PCT/US2006/016418 19 In another embodiment, a personal care regimen is used to regulate the condition of keratinous tissue. By "regimen" is meant the use of an oral composition in conjunction with a topical composition. In a particular embodiment, the oral composition and the topical composition are packaged together as a kit. In another embodiment, the oral 5 composition and the topical composition are not packaged together as a kit, but potential users of the regimen are informed (e.g. through advertisements, product labeling) that the oral and the topical compositions may be used in conjunction with one another to regulate the condition of kerationous tissue. At least one of the compositions, either oral or topical, comprises a dipeptide of the present invention. Preferably, both the oral and the 10 topical compositions comprise a dipeptide of the present invention. EXAMPLES The following are non-limiting examples of compositions of the present invention. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present invention, as many variations thereof are possible without 15 departing from the spirit and scope of the invention, which would be recognized by one of ordinary skill in the art. In the examples, all concentrations are listed as weight percent, unless otherwise specified and may exclude minor materials such as diluents, filler, and so forth. The listed formulations, therefore, comprise the listed components and any minor materials 20 associated with such components. As is apparent to one of ordinary skill in the art, the selection of these minors will vary depending on the physical and chemical characteristics of the particular ingredients selected to make the present invention as described herein. Examples 1-5: Moisturizing oil-in-water lotions/creams 1 2 3 4 5 Water Phase: Water Qs qs Qs qs qs Glycerin 3 5 7 10 15 Disodium EDTA 0.1 0.1 0.05 0.1 0.1 Methylparaben 0.1 0.1 0.1 0.1 0.1 Niacinamide 2 0.5 -- 3 5 Triethanolamine ---- 0.25 --- --- D-panthenol 0.5 0.1 |--- 0.5 1.5 WO 2006/116731 PCT/US2006/016418 20 Sodium Dehydroacetate 0.5 0.1 0.5 0.1 0.5 Benzyl alcohol 0.25 0.25 0.25 0.25 0.25 GLW75CAP-MP (75% aq. -- 0.5 0.5 -- TiO2 dispersion)' Hexamidine diisethionate --- 0.1 -- __ _ -_ Palmitoyl-dipeptide 2 0.00055 0.00055 0.0001 0.00055 0.00055 N-acetyl glucosamine 2 1 2 2 1 Soy Isoflavone 0.5 --- --- Oil Phase: Salicylic Acid ----- --- 1.5 - Isohexadecane 3 3 3 4 3 PPG15 Stearyl Ether _ _------ 4 -- Isopropyl Isostearate 1 0.5 1.3 1.5 1.3 Sucrose polyester 0.7 --- 0.7 1 0.7 Dipalmitoylhydroxyproline .- ---- - 1-0 Undecylenoyl 0.5 - --- Phenylalanine I_ _ Phytosterol ---- --- 0.5 -- 1.0 Cetyl alcohol 0.4 0.3 0.4 0.5 0.4 Stearyl alcohol 0.5 0.35 0.5 0.6 0.5 Behenyl alcohol 0.4 0.3 0.4 0.5 0.4 PEG-100 stearate 0.1 0.1 0.1 0.2__ 0 Cetearyl glucoside 0.1 0.1 0.1 0.25 0.1 Thickener: Polyacrylamide/C13-14 1.5 --- 2 2.5 2 isoparaffin/laureth-7 Sodium acrylate/sodium - 3 --- - acryloyldimethyl taurate copolymer/isohexadecane/p olysorbate 80 Additional Inredients: Dimethicone/dimethiconol -- 1 2 0.5 2 Polymethylsilsequioxane -- --- 0.25 --- 1 Nylon-12 -_ 0.5 ----

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Prestige Silk Violet 3 ___ _ .-- 1 WO 2006/116731 PCT/US2006/016418 21 Timiron Splendid Red 4 1.0 1-- 2 1Available from Kobo products 2 Palmitoyl-lysine-threonine available from Sederma 3 Titanium dioxide coated mica violet interference pigment available from Eckart 4 Silica and titanium dioxide coated mica red interference pigment available from Rona 5 In a suitable vessel, combine the water phase ingredients and heat to 75*C. In a separate suitable vessel, combine the oil phase ingredients and heat to 75*C. Next, add the oil phase to the water phase and mill the resulting emulsion (e.g., with a Tekmar T 25). Then, add the thickener to the emulsion and cool the emulsion to 45*C while stirring. At 45*C, add the remaining ingredients. Cool the product and stir to 30*C and 10 pour into suitable containers. Examples 6-11: Moisturizing silicone-in-water serums/lotions: 6 7 8 9 10 11 Water Phase: Water Qs Os qs Qs qs Qs Glycerin 3 5 7 10 15 10 Disodium EDTA 0.1 0.1 0.05 0.1 0.1 0.1 Niacinamide 2 0.5 --- 3 5 3 Sodium 0.5 0.1 -- 0.1 0.5 0.1 Dehydroacetate D-panthenol 0.5 0.1 0.5 1.5 0.5 GLW75CAP-MP ---- 0.4 ---- ---- 0.4 (75% aq. TiO2 dispersion)' Ascorbyl Glucoside --- ---- ---- --- ---- 1 Palmitoyl 0.0005 0.0005 0.0005 0.0005 0.00055 0.00055 dipeptide 2 5 5 5 5 Soy Isoflavone ..-- 1 --- --- ---

--

N-acetyl 2 ---- 2 --- 5 glucosamine Silicone/Oil Phase: Cyclomethicone D5 10 5 5 10 7.5 10 Dow Corning 9040 ---- 10 5 5 7.5 5 Silicone elastomer? WO 2006/116731 PCT/US2006/016418 22 KSG-15AP silicone 5 -- 5 5 7.5 5 Elastomer_ Dimethione/ -- 2 2 1 2 1 dimethiconol Dimethicone 50 csk 1 -- -- -- - Salicylic Acid -- ---- 1.5 -- -- - Phytosterol -- -- 1.0 ---- 0.1 PPG-15 Stearyl ---- -- 4 4 ---- - Ether Dehydroacetic acid ---- 0.5 1 --- ---- -- Undecylenoyl -- - 0.5 -- - Phenylalanine BHT 0.5 -- - Vitamin E Acetate 0.5 0.1 1 0.1 -- 0.1 Thickener: Polyacrylamide/C1 2.5 2.5 --- -- 3 3-14 isoparaffin/laureth 7 Sodiumacrylate/ -- -- --- 3sodium acryloyl dimethyl taurate copolymer/isohexa decane/polysorbate 80 Acrylates/C1O-30 -- -- 0.6 - 0.5 alkyl acrylates crosspolymer Undecylenoyl Phenylalanine Premix Undecylenoyl -- -- -- -- 1 Phenylalanine I I Water -- --- --- -- 24--- Triethanolamine -- -- -- --- 0.5 Dipalmitoyl Hydro-Proline Premixi Water -- - --- 4.4 Triethanolamine ---- --. -- ---.. 0.1 WO 2006/116731 PCT/US2006/016418 23 Dipalmitoylhyroxy --- -- -- 0 proline | |1. Additional Ingredients: __ Triethanolamine --- - --- 0.6 -- Polymethylsilse- 0.5 0.5 1.0 1 1 0.5 quioxane . Polyethylene --- 0.5 0.5 1.0 Flamenco Summit -- --- 1.0 -- Green G30D 5 Silca ---- -- 1 0.5 -- Prestige Silk Red 6 -- 6 . ---- --- 1.0 1.0 1.0 ' GLW75CAP-MP, 75% aqueous titanium dioxide dispersion from Kobo 2 Palmitoyl-lysine-threonine available from Sederma 3 A silicone elastomer dispersion from Dow Coming Corp 4 A silicone elastomer dispersion from Shin Etsu, 5 5 Titanium dioxide and tin oxide coated mica green interference pigment from Engelhard 6 Titanium dioxide coated mica red interference pigment from Eckart In a suitable vessel, combine the water phase ingredients and mix until uniform. In a separate suitable container, combine the silicone/oil phase ingredients and mix until uniform. Separately, prepare the dipalmitoyl hydroxyproline premix and/or undecylenoyl 10 phenylalanine premix by combining the premix ingredients in a suitable container, heat to about 70*C while stirring, and cool to room temperature while stirring. Add half the thickener and then the silicone/oil phase to the water phase and mill the resulting emulsion (e.g., with a Tekmar T-25). Add the remainder of the thickener, the dipalmitoyl hydroxyproline premix and/or undecylenoyl phenylalanine premix, and then the 15 remaining ingredients to the emulsion while stirring. Once the composition is uniform, pour the product into suitable containers. Examples 12-1 7 : Moisturizing water-in-silicone creams/lotions: Component 12 13 14 15 16 17 Phase A Water qs qs Qs qs qs qs Allantoin 0.2 0.2 0.2 0.2 0.2 0.2 disodium EDTA 0.1 0.1 0.1 0.1 0.1 0.1 WO 2006/116731 PCT/US2006/016418 24 ethyl paraben 0.2 0.2 0.2 0.2 0.2 0.2 propyl paaben 0.1 0.1 0.1 0.1 0.1 0.1 Caffeine -- 1 ---- -- -- 1 BHT --..- 0.1 -...-- 0.015 -- Dexpanthenol 1 0.5 1 1 1 1 Glycerin 7.5 10 15 7.5 5 15 hexamidine isethionate --- -- 0.1 0.5 -- ___ Niacinamide 2 --- -- 2 3.5 5 Palmitoyl-dipeptidel 0.0005 0.0005 0.0005 0.0005 0.0005 0.0005 5 5 5 5 5 5 Phenylbenzimidazole ---- -- --- ---- 1 sulfonic acid Sodium Dehydroacetate 0.5 --- --- 0.1 0.5 0.5 benzyl alcohol 0.25 0.25 0.25 0.25 0.25 0.25 Triethanolamine -- -- --- -- 0.6 green tea extract 1 1 1 1 1 1 Soy Isoflavone -- 0.5 -- -- -- -- . N-acetyl glucosamine 5 --- 2 5 2 - Sodium metabisulfite 0.1 0.1 0.1 0.1 0.1 0.1 Phase B Cyclopentasiloxane 15 15 18 15 15 18 Titanium dioxide 0.5 0.5 0.75 | 0.5 0.5 0.75 Phase C C12- C15 alkyl benzoate ---- ---- --- 1.5 1.5 - Vitamin E acetate 0.5 -- 1 0.5 0.5 1 retinyl propionate 0.3 ---- 0.2 0.2 - Undecylenoyl -- -- 0.5 --- --. Phenylalanine Dipalmitoyl hydroxyproline --- 1 -- -- -- Salicylic Acid -- 1.5 1.5 -- _-- - PPG-15 Stearyl Ether 4 4 4 ---- - Dehydroacetic Acid --- 0.5 0.1 Phytosterol 1 0.5 -- -- - - Phase D KSG-21 silicone elastomer 2 4 4 5 4 4 5 WO 2006/116731 PCT/US2006/016418 25 Dow Corning 9040 silicone 15 15 12 15 15 12 elastomer 3 Abil EM-97 Dimethicone 0.5 ---- -- 0.5 0.5 - Copolyol 4 Polymethylsilsesquioxane 2.5 2.5 2 2.5 2.5 2 Undecylenoyl Phenylalanine Premix __ Undecylenoyl - -- -- 1 Phenylalanine Water --- -- - --- 24 Triethanolamine --- --- -- ---- 0.5 ___ Phase E Water 8.8 -- --- ---- 8.85 Triethanolamine 0.2 -- -- - - 0.25 Dipalmitoylhyroxyproline 0.5 -- -1 - 1 ' Palmitoyl-lysine-threonine available from Sederma 2 KSG-21 is an emulsifying silicone elastomer available from Shin Etsu 3 A silicone elastomer dispersion from Dow Coming Corp 4 Abil EM-97 available from Goldschmidt Chemical Corporation 5 In a suitable vessel, blend the Phase A components together with a suitable mixer (e.g., Tekmar model RW20DZM) and mix until all of the components are dissolved. Then, blend the Phase B components together in a suitable vessel and mill using a suitable mill (e.g., Tekmar RW-20) for about 5 minutes. Add the Phase C components to the Phase B mixture with mixing. Then, add the Phase D components to the mixture of 10 Phases B and C and then mix the resulting combination of Phase B, C and D components using a suitable mixer (e.g., Tekmar RW-20) for about 1 hour. If applicable, prepare the undecylenoyl phenylalanine premix and/or Phase E by combining all ingredients, heating the ingredients to 70*C while stirring, and cooling back to room temperature while stirring. Add the undecylenoyl phenylalanine premix and/or Phase E to Phase A while 15 mixing. Next, slowly add Phase A to the mixture of Phases B, C and D with mixing. Mix the resulting mixture continually until the product is uniform. Mill the resulting product for about 5 minutes using an appropriate mill (e.g., Tekmar T-25). Examples 18-22: Oil in Water Mousse 18 19 20 21 22 WO 2006/116731 PCTIUS2006/016418 26 Water Phase: Water Qs qs Qs qs qs Glycerin 3 5 7 10 15 Disodium EDTA 0.1 0.1 0.05 0.1 0.1 Methylparaben 0.1 0.1 0.1 0.1 0.1 Niacinamide 2 0.5 -- 3 5 Triethanolamine -- 0.25 --

---

D-panthenol 0.5 0.1 -- 0.5 1.5 Sodium Dehydroacetate 0.5 0.1 0.5 0.1 0.5 Benzyl alcohol 0.25 0.25 0.25 0.25 0.25 GLW75CAP-MP (75% -- 0.5 0.5 -- aq. TiO2 dispersion)' Undecylenoyl 1 -- 0.5

--

Phenylalanine ..- - .- -- - Hexamidine diisethionate -- 0.1 -- -- - Palmitoyl-dipeptide 2 0.00055 0.00055 0.0001 0.00055 0.00055 N-acetyl glucosamine 2 1 2 2 1 Soy Isoflavone 0.5 --- -- ---

--

Oil Phase: Salicylic Acid 1.5 -- _ - Isohexadecane 3 3 3 4 3 PPG15 Stearyl Ether --- --- 4 -- - Isopropyl Isostearate 1 0.5 1.3 1.5 1.3 Sucrose polyester 0.7 --- 0.7 1 0.7 Undecylenoyl --- 0.5

--

Phenylalanine Dipalmitoylhyroxyproline -- ---- --- 1.0 Phytosterol --- -- 0.5 --- 1.0 Cetyl alcohol 0.4 0.3 0.4 0.5 0.4 Stearyl alcohol 0.5 0.35 0.5 0.6 0.5 Behenyl alcohol 0.4 0.3 0.4 0.5 0.4 PEG-100 stearate 0.1 0.1 0.1 0.2 0.1 Cetearyl glucoside 0.1 0.1 0.1 0.25 0.1 Thickener: Polyacrylamide/C13-14 1.5 --- 2 2.5 2 WO 2006/116731 PCT/US2006/016418 27 isoparaffin/laureth-7 Sodium acrylate/sodium

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3 acryloyldimethyl taurate copolymer/isohexadecane /polysorbate 80 Additional Ingredients: Dimethicone/dimethicon ---- 1 2 0.5 2 ol Polymethylsilsequioxane ---- --- 0.25 ---- 1 Nylon-12 ._--- _0.5 ----- Prestige Silk Violet 3 ----- ___ .. _ ---. Timiron Splendid Red 4 --- 1.0 -- 2 Propellant Phase 152 A HFC Propellant 3 4 2 3 2 A-70 Propellant 3 2 4 3 4 'Available from Kobo products 2 Palmitoyl-lysine-threonine available from Sederma 3 Titanium dioxide coated mica violet interference pigment available from Eckart 4 Silica and titanium dioxide coated mica red interference pigment available from Rona 5 In a suitable vessel, combine the water phase ingredients and heat to 75*C. In a separate suitable vessel, combine the oil phase ingredients and heat to 75*C. Next, add the oil phase to the water phase and mill the resulting emulsion (e.g., with a Tekmar T 25). Add the thickener to the emulsion and cool the emulsion to 45*C while stirring. At 45*C, add the remaining ingredients. Cool the product with stirring to 30*C and pour into 10 suitable containers. Add propellant and product to a suitable aerosol container, and seal the container. Examples 23-28: Silicone in Water Mousse 23 24 25 26 27 28 Water Phase: Water Qs Qs qs Qs qs qs Glycerin 3 5 7 10 15 10 Disodium EDTA 0.1 0.1 0.05 0.1 0.1 0.1 Niacinamide 2 0.5 ---- 3 5 3 Sodium 0.5 0.1 -- 0.1 0.5 0.1 WO 2006/116731 PCT/US2006/016418 28 Dehydroacetate D-panthenol 0.5 0.1 ---- 0.5 1.5 0.5 GLW75CAP-MP --- 0.4 --- ---- --- 0.4 (75% aq. TiO2 dispersion)' Ascorbyl Glucoside ---- -- -- --- _-- I Palmitoyl dipeptide 2 0.0005 0.0005 0.0005 0.0005 0.00055 0.00055 5 5 5 5 Soylsoflavone ---- 1 --- -- -~~ N-acetyl glucosamine 2 ---- 2 _5_---- ___ Silicone/Oil Phase: Cyclomethicone D5 10 5 5 10 7.5 10 Dow Coming 9040 -- 10 5 5 7.5 5 Silicone elastomer 3 KSG-15AP silicone 5 5 5 7.5 5 Elastomer 4 Dimethione/ --- 2 2 1 2 1 Dimethiconol Dimethicone 50 csk 1 --- -- - Salicylic Acid 1.5 -- -- - Phytosterol ---- - -- 1.0 --- 0.1 PPG-15 Stearyl Ether ---- - 4 4 _---- --- Dehydroacetic acid 0.5 - Undecylenoyl 0.5 Phenylalanine BHT ----- 0.5 --- -- -- - Vitamin E Acetate -- _ 0.5 0.1 0.1 -- 0.1 Thickener: Polyacrylamide/C13- 2.5 2.5 --- --- 3 14 isoparaffin/laureth 7 Sodiumacrylate/ --- 3 --- - 3 --- Sodium acryloyl dimethyl taurate copolymer/isohexadec ane/polysorbate 80 WO 2006/116731 PCT/US2006/016418 29 Acrylates/CIO-30 0.6 0.5 alkyl acrylates crosspolymer Undecylenoyl Phenylalanine/Dipalmitoyl Hydroxyproline Premix__ Undecylenoyl 1 -- Phenylalanine --- I I Water -- -- 24 9 Triethanolamine -- 0.5 0.2 Dipalmitoylhyroxypro -- - 1.0 line Additional Ingredients: Triethanolamine ---- --.

--

Polymethyl 0.5 0.5 1.0 1 1 0.5 Silsequioxane _ Polyethylene --- 0.5 0.5 1.0 -- Flamenco Summit -- -- 1.0 --

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Green G30D 5 _ Silica -- 1 0.5 - Prestige Silk Red 6 - 1.0 1.0 1.0 Propellant Phase 152A HFCPropellant 3 2 4 1 5 3 A-70 Propellant 3 4 2 5 1 3 1 GLW75CAP-MP, 75% aqueous titanium dioxide dispersion from Kobo 2 Palmitoyl-lysine-threonine available from Sederma 3 A silicone elastomer dispersion from Dow Coming Corp 4 A silicone elastomer dispersion from Shin Etsu, 5 5 Titanium dioxide and tin oxide coated mica green interference pigment from Engelhard 6 Titanium dioxide coated mica red interference pigment from Eckart In a suitable vessel, combine the water phase ingredients and mix until uniform. In a separate suitable container, combine the silicone/oil phase ingredients and mix until uniform. Separately, prepare the undecylenoyl phenylalanine and/or dipalmitoyl 10 hydroxyproline premix by combining the premix ingredients in a suitable container, heat to about 70*C while stirring, and cool to room temperature while stirring. Add half the thickener and then the silicone/oil phase to the water phase and mill the resulting WO 2006/116731 PCT/US2006/016418 30 emulsion (e.g., with a Tekmar T-25). Add the remainder of the thickener, the undecylenoyl phenylalanine and/or dipalmitoyl hydroxyproline premix, and then the remaining ingredients to the emulsion while stirring. Once the composition is uniform, pour the product into suitable containers. Add the product and propellant into an aerosol 5 container. Seal the aerosol container. Examples 29-34: Water Based Stick Formulations 29 30 31 32 33 Water Phase: Water Qs q qs qs qs Qs Palmitoyl 0.00055 0.00055 0.00055 0.00055 0.00055 0.00055 dipeptide' Propylene Glycol 15 25 20 15 25 20 Dipropylene Glycol 50 40 45 50 40 45 Sodium Stearate 6 6 6 6 6 6 Triethanolamine 0.2 0.25 ---- 0.7 0.6 -- N-Acetyl-D- ---- 2.0 0.5 ---- --- 2.0 Glucosamine Undecyenoyl ---- 0.5 --- I

--

Phenylalanine Niacinamide 2 3.5 2 3.5 Sodium 0.5 0.5 0.1 0.1 0.5 1.0 Dehydroacetate Dipalmitoyl 1 ---- --- 1 0.5 -- Hydroxyproline 'Palmitoyl-lysine-threonine available from Sederma All ingredients are combined into an appropriate size container, heated to 85*C, cooled and poured into stick containers at approximately 65*C. 10 Examples 35-40: Anhydrous Stick Formulations 35 36 37 38 39 40 Oil Phase: Isopropyl 5 4 3 5 4 3 Isostearate Palmitoyl 0.00055 0.00055 0.00055 0.00055 0.00055 WO 2006/116731 PCT/US2006/016418 31 dipeptidel Octylmethoxycinna 5 2 2 5 2 2 mate Cyclomethicone Qs qs qs q s s I q Phenyl 5 5 5 5 5 5 trimethicone Stearyl Alcohol 15 17 15 15 17 15 _ Behenyl Alcohol 1 1 1 1 1 1 Undecylenoyl -- 0.5 -- 1.0 0.5 0.5 Phenyl alanine Dehydroacetic acid 0.1 0.5 0.1 0.5 0.1 1.0 Dipalmitoyl 1 -- 1.0 ---- 0.5 - Hydroxyproline Phytosterol 1 0.5 -- -- 0.5 1 Salicylic Acid - -- 1 - 0.5 1.5 ---- 1.0 Palmitoyl-lysine-threonine available from Sederma All ingredients added to an appropriate size container, heated to 75*C then cooled with stirring until mixture reaches approximately 45*C. The mixture is poured into stick containers. 5 While particular embodiments of the present invention have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention. 10

Claims (3)

1. A personal care composition comprising: (a) a dipeptide based molecule, wherein the C terminal amino acid of said dipeptide based molecule is threonine and wherein the N-terminus is substituted by a palmitoyl group; and (b) a dermatologially or orally acceptable carrier or injectible liquid.

2. The composition of claim 1 wherein said composition comprises a dermatologically acceptable carrier, and wherein said composition comprises said dipeptide in an amount effective to regulate the cosmetic appearance of mammalian keratinous tissue wherein said amount is from 0.000001% to 10%, by weight based on the weight of said composition.

3. The composition of claim I or claim 2, substantially as hereinbefore described with reference to the Examples and excluding any comparative Examples.