GB2628139A - Tripeptide and composition thereof - Google Patents

Abstract

A tripeptide capable of inducing dermal extracellular matrix protein upregulation and/or capable of inducing ECM repair, wherein the tripeptide is a fragment of an ECM protein. Preferably the tripeptide has the amino acid sequence U-XXX-Z, where X denotes any amino acid, U is selected from octanoyl, decanoyl, lauroyl, myristoyl, palmitoyl, stearoyl, biotinoyl, elaidoyl, oleoyle and lipoyle and Z is selected from a OH, OR1, NHR1 NR1R2, and R1 and R2 are selected from alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide or aryloxy group. Preferably the tripeptide has an amino acid sequence selected from; GPE, GPS, GPP, LSV, LSP, KGP, KGD, PKG, LRG, SPD, RGD, SVD, YIL AND GFP. Also disclosed is a cosmetic composition comprising the tripeptide present at 0.1 to 10,000ppm weight of the composition, a method for stimulating the production of ECM proteins in humans by administering to the skin an effective amount of the tripeptide or composition comprising the tripeptide and a use of the tripeptide or composition as a non-therapeutic treatment to improve the condition of the skin or lines or wrinkles or imperfections or skin firmness and elasticity.

Description

TRIPEPTIDE AND COMPOSITION THEREOF

Technical Field

The present invention relates to tripeptides, compositions comprising said tripeptides, and methods of stimulating the production of dermal extracellular proteins.

Background to the invention

The largest component of normal skin is the dermal extracellular matrix (ECM) which is a gel-like matrix produced by the cells that it surrounds. The ECM comprises two major elements, structural proteins and proteoglycans. Changes to skin come about naturally over time (ageing) as a result of changes in the composition and crosslinked state of the elements of the ECM which cause changes at the structural and behavioural level. Structural changes affect the integrity of the skin. Ageing skin exhibits both an increased degradation of skin dermal extracellular matrix (ECM) proteins (such as collagen, laminin, elastin, fibronectin) and reduced production of the same proteins.

Cellular behavioural changes influence the rate of cell differentiation and proliferation, and therefore the rate of skin repair and renewal. The ECM is also believed to be responsible for producing cell signals which facilitate epithelial cell proliferation and migration, further influencing the skin's ability to repair. Changes in the ECM also affect cell-adhesion, signalling, and cell-behaviour mediation.

Particularly imporat ECM proteins include collagen, fibrillin, fibroncctin and decorin. Collagen is responsible for providing" elements of the structural integrity of the skin. Collagen in the dermal matrix is composed primarily of type I (80-85%) and type ITT (8-I l?/) collagens, both of which are fibrillar" or rod-shaped, collagens. The tensile strength of skin is predominately produced through the fibrillar cross-linked arrangement of the molecules of collagen 1. There are also other functionally important although less abundant collagen types in skin, including collagen IV located at the basement membrane of the dermal epidermal junction. This forms sheet-like structures and is more pliable than the fibrillar collagens. Damage to the collagen network of the skin, by for example, free-radical damage, induces the generation of collagen fragments in the ECM, followed by skin regeneration and repair.

Fibrillin is a component of elastic fibres in the ECM and also contributes to the structural integrity of die skin. The most abundant fibrillin in elastic fibres of skin is the FBNI encoded protein, fibrillin-I.

Fibroneetin is a glycoprotein of the ECM and is primarily responsible for mediating a wide variety of cellular interactions within the ECM, playing an important role in cell adhesion, migration, growth and differentiation.

Deeorin (DCN) is a roteoglycan, belonging to the leticinc-rich protcoglyean (SLAP) family. The peptide is believed to be important as a component of connective tissue and binds to type I collagen, regulating collagen ECM assembly.

Ageing changes in the skin can occur intrinsically as a consequence of time and extrinsically as a consequence of external mechanisms, including UV-related damage and pollution. Extrinsic mechanisms can result in the increased availability of reactive oxygen species (UV-ROS). These reactive species are known to cause ECM fragmentation and the upregulation of Matrix Metallopeptidases (MMPs) and other ECM protcascs. ECM fragmentation may bring about damage to and/or remodelling of the structural ECM proteins and reduce the integrity of the skin.

The fragmentation of ECM proteins can also result in the release of small bioactive peptides or matrikines which act as cell signalling molecules promoting skin repair by uprcgulating protein production, cell proliferation and differentiation. Both intrinsic and extrinsic ageing can lead to protein fragmentation and the subsequent release of bioactive peptide marnikines.

A number of natural proteins and synthetic peptide matrikines have been used in cosmetic compositions and products for a number of years to stimulate protein upregulation, skin repair and regeneration. The most commonly used peptide composition comprises Pal-KKTKS and the combination of palmitoyl oligopeptide (Pal-GHK), which acts as a messenger peptide for collagen renewal and consists of a sequence derived from collagen 1, and palmitoyl tetrapeptide-7 (PalGQPR), which reduces the production of interleukin-6 (IL-6), therefore acting as an anti-inflammatory and inhibiting ECM degradation, with sequence derived from immunoglobulin G. The said peptide combinations are available from Sedenna under the trade names Matrixyff and Matrixv I'm 3000.

Whilst a number of natural proteins and synthetic peptides have been in use for a number of years. there remains a need to identify new and improved biologically active peptides to support the skin's natural behaviours.

Summary of the invention

According to the present invention, there is provided a tripeptide, capable of inducing dermal extracellular matrix (ECM) protein uprcgulation and/or capable of inducing ECM repair, wherein the tripeptide is a fragment of an ECM protein.

Detailed description of the invention

The present invention is directed toward tripeptides that act as signalling matrikincs to upregulatc the production of proteins of the dermal ECM (including at least one of the proteins fibrillin-1, fibronectin, decorin and collagen I) and/or induce ECM repair, wherein the tripeptide is a fragment of an ECM protein.

Tripeptides One embodiment of the present invention is directed toward a tripeptide, capable of inducing dermal extracellular matrix protein upregulation and/or capable of inducing ECM repair. The tripeptide may be a matrikine. Thus, the tripeptide of the invention may be used in a skincare composition. The tripeptides of the invention arc particularly advantageous because they are more likely to penetrate the skin barrier than larger/longer peptides (e.g., peptides with a molecular weight of more than about 500Da). Preferably therefore the tripeptide has a molecular mass of less than about 500Da.

The tripeptide may have an amino acid sequence selected from the group consisting of GPE. GPS, GPP, LSV, LSP, KGP, KGD, PKG, LRG, SPD, RGD, SVD, Y1L, and GFP.

Some tripeptides have limited solubility in the skin due to their hydrophilic nature. The tripeptides may therefore be modified to make them more lipophilic, and this more soluble in skin. For example, the tripeptide may be modified by cov-alently attaching a lipophilic group, such as a fatty acid (e.g., palmitic acid), to a terminus. Thus, the tripeptide may have the generic formula UXXX-Z wherein X denotes an amino acid selected from the group consisting of Valinc (V), Aspartic acid (D), Proline (P), Glycine (G), alanine (A), arginine (R), asparagine (N), cysteine (C), glutamic acid (E), glutamine (Q), glutamic acid (Z), histidine (H), isoleucine (I), leucine (L), lysine (K), methionine (M), phenylalanine (F), serine (S), threonine (T), tryptophan (W), tyrosine (Y) and mixtures thereof At the N-terminal end, U is selected from the group consisting of H, -CO-1Z' , -5O2-R' or a biotinyl group. At the C-terminal end, Z is selected from the group consisting of OH, 0 121,NHP: or NR' R2. R' and R2 are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorvlated and/or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms 0, S and/or N. Where, at the N-terminal, U is H then the amino acid is not modified. When, at the C-terminal, Z is OH then the amino acid is not modified. The tripeptide is thus not in derivatised form. When other than U is H and Z is OH, then the tripeptide is derivatised. Derivation of the tripeptide is intended to increase the bioavailability of the peptide by improving the ability of the tripeptide to pass through the skin. An increase in bioavailability can also be achieved through vectoring, for example by encapsulation of the peptide. in a preferred embodiment, at least one terminal of the tripeptide is modified. in one embodiment, when U is H then Z cannot be OH. In a preferred embodiment of the present invention the tripeptide is modified at the N-terminal and/or the C-tenninal end. In one embodiment, the tripeptide is modified at the N-terminal. In one embodiment, the tripeptide is modified at the C-terminal. In one embodiment, the tripeptide is modified at both the N-terminal and the C-terminal.

In a preferred embodiment of the present invention, 12..' and/or R2 is an alkyl chain of from 1 to 24 carbon atoms, preferably a lipophilic alkyl chain of 3 to 24 carbon atoms.

in a further preferred embodiment of the present invention U is an acyl group -CO-Wand Z is selected from the group consisting of OH, mcthoxy, ethoxy and NH2, preferably OH. In a further embodiment, U is preferably independently selected from the group consisting of octanoyl (C8), decanoyl (CIO), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18), biotinoyl, elaidoyl, oleoyle and lipoyle. hi a preferred embodiment of the present u is selected from lauroyl (C I 2), myristoyl (C14) and palmitoyl (C16).

In a further preferred embodiment Z is OH and U is independently selected from the group consisting of palmitoyl (C16), myristoyl (C14) and lauroyl (C12). Most preferably U is palmitoyl (C16) and Z is OH.

The tripeptides may comprise amino acids in the D-or L-configuration. The tripeptides may comprise an acid C-terminus, such as -CO2H.

The amino acids making up the tripeptides according to the invention may be optically pure, be made up of L or D isomers or a mixture of both. L-isomers are those present in the natural state and may be preferred.

The present invention also envisages further derivatives of the tripeptide, including for example modification and/or addition of a chemically functional group to one or more of the amino acids but without a change in the carbon skeletal. The present invention also envisages further analogues of the tripeptide, including modification and/or addition of a chemically functional group to one or more of the amino acids with a change in the carbon skeletal and complexes of the tripeptide with other species such as a metal ion (e.g. copper, zinc, manganese, magnesium, and others).

Tripeptides may be found in the form of salts, including hydrochloric salt, or acetate.

Tripeptides according to the invention may naturally be generated within the skin (i) through the action of enzymes that play a role in skin remodelling and/or (ii) by external mechanisms, such as photoaging. Both processes cause skin ECM proteins to degrade into peptide fragments, including tripeptides according to the invention, tetrapeptides, pentapeptides or hexapeptides. As mentioned above, these fragments are biologically active and thus exert their effects by binding to and activating receptors found on cells within the skin. These effects include for example promoting skin repair by upregulating protein production, cell proliferation and differentiation.

It will be appreciated that the shorter a particular peptide fragment is, the more widely distributed that it will be in the skin proteome (i.e., the entire set of proteins found within the skin). Thus, it is more likely that it will be possible to cleave and thus release the peptide from different types of ECM protein. Similarly, receptors for biologically active peptides (e.g., matrikines) are more likely to be widely distributed within the skin. Advantageously, therefore, shorter peptides, such as tripeptides according to the invention, are more likely to have pleiotropic effects within the skin.

In other words, tripeptides are likely to have many more targets as intact 3 amino acid peptides and are likely found in more source ECM proteins than longer chain peptides. This allows biologically active tripeptides to stimulate the natural production of many more structural proteins, enabling the tripeptides to have more diverse effects on dermal repair, impacting on many different stmetural proteins and impacting not only matrix quantity but also matrix quality. Longer or larger biologically active peptides (e.g., peptides with a molecular weight greater than 500 Da) are less likely to be found within intact ECM proteins, and although the peptides may be biologically active their effects on the skin will be more specific than peptides of the present invention.

Excipient composition The tripeptides of the present invention are provided by the supplier to the cosmetic composition formulator as a concentrated excipient composition. The excipient composition is therefore a cosmetic composition ingredient. The excipient composition comprises tripeptides at from 250 to 2500 ppm. In an alternative embodiment, the excipient composition comprises tripeptides at a level of from 0.1 to 50,000ppm. in a further alternative embodiment, the excipient composition comprises from 1 to 5,000ppm. In a further alternative embodiment, the excipient composition comprises tripeptide at a level of from 10 to 500ppm.

The excipient composition, in addition to tripeptides, may optionally comprise ingredients selected from the group consisting of water, surfactants, diols, triols, glycerine, thickener and mixtures thereof. All suitable surfactants, diols (also known as glycols), triols, glycerine and thickener ingredients may be incorporated into the present excipient composition. Preferred surfactants for the excipient composition are selected from the group consisting of alkyl polyglucosides (preferably decyl glucoside, coco glucoside, lauryl glucoside), sodium lauroyl lactylate, polysorbate 20, polysorbate 60, sorbitan laurate, PEG/PPG-18/18 dimethicone, Cetyl PEG/PPG-10/1 dimethicone, Polyglycery1-4 isostearate, Hexyl laurate, steareth-21, steareth-2 and mixtures thereof Preferred diols are selected from the group consisting of pentylene glycol, caprylyl glycol, butylene glycol, di-propylene glycol, ethylhexylglycerine, propanedia hexonedio1 glycerol, butylene glycol, propylene glycol, isoprene glycol, dipropylene glycol, pentylene glycol, hexylene glycol, polypropylene glycol, butylene glycol, polyethylene glycol, sorbitol, glucitol, mannitol, hydroxypropyl sorbitol, crythritol, threitol, pcntacrythritol and xylitol.

Preferred triols are selected from the group consisting of hexanetriol, glycerine, ethoxylated glycerin, propoxylated glycerin and mixtures thereof.

Preferred thickeners are selected from the group consisting of xanthan gum, ammonium acryloyldimethyltaurate/vinyl pyrrolidone copolymer, dimethicone crosspolymer, carbomer, hydroxyethyl cellulose, polyacrylamide" polyacrylate erosspolymer-6, and mixtures thereof.

Cosmetic Composition The present invention also encompasses cosmetic compositions comprising tripeptides of the present invention. The tripeptides are preferably incorporated into the cosmetic composition in amounts of from 0.10ppm to 10,000ppm, preferably from 0.50ppm to 5,000ppm, more preferably from 1ppm to 1000ppm, and most preferably from 1ppm to 500ppm. These are again based on a % wily basis. Thus 100,000ppm is 10% by weight of the emulsion.

A cosmetic composition is a product designed for use by a consumer and is preferably a skincare cosmetic composition, more preferably a facial skincare cosmetic composition.

The cosmetic composition of the present invention may be aqueous or non-aqueous and comprise of a single-phase system or multiple phase system. The composition may include but is not limited to liquids, gels, balms, oils or solids. Single or multiple phase compositions are envisaged. Multiple phase systems include but are not limited to microcmulsions, emulsions, and products with discrete separate phases. Emulsions include water-in-oil, oil-in-water emulsions and multiple emulsions (water in oil in water or oil in water in oil for example). Products with discrete separate phases include bi or triphasic systems where the individual water or oil phases can be visibly seen.

Where the composition is aqueous, it preferably comprises from 10% to 99.9% by weight water. in a preferred embodiment, aqueous compositions comprise from 20% to 80 % by weight water. In a preferred embodiment, aqueous compositions comprise from 40% to 70% by weight water.

Where the composition is non-aqueous it preferably comprises 0% to up to 10% water, more particularly from 0.1 to 8%. most preferably from 0.5 to 5% water.

Where the composition is an emulsion, it comprises an oil and a water phase. The oil phase of an emulsion can be provided by any suitable oily component. Suitable oils for the oil phase may comprise for example: (a) hydrocarbon oils, such as paraffin or mineral oils; (b) waxes, such as beeswax or paraffin wax; (c) natural oils, such as sunflower oil, apricot kernel oil, rhea butter or jojoba oil; (d) silicone oils, such as dimethicone, silicone elastomer, cyclomethicone or cetyl dimethicone; (e) fatty acid esters and ethers, such as isopropyl palmitate or isopropyl myristate and polypropylene glycol-15 stearyl ether; (f) fatty alcohols, such as cetyl alcohol or stearyl alcohol; or (g) mixtures thereof, for example, the blend of waxes available commercially under the trade name Cutina® (BASF).

The emulsion may comprise 0.1% to 55% by weight of the emulsion of oil phase. in one embodiment, the emulsion may comprise 3% to 25% by weight of the emulsion of oil phase, more preferably from 5% to 20% by weight of the emulsion of oil phase. In an alternative embodiment, the emulsion may comprise 10% to 50% by weight of the emulsion of oil phase, more preferably from 25-50% by weight of the emulsion of oil phase.

Preferably the oil phase of the emulsion comprises oil at a level between 50% and 100% by weight of the oil phase. More preferably the oil phase comprises oil at a level of from 60% to 100%, more preferably from 70% to 100%, and even more preferably from 80% to 100% by weight of the oil phase. Alternatively, the oil phase of the emulsion may comprise a combination of oil, wax or butter. Waxes and butters are hydrocarbons that consist of long aliphatic alkyl chains and may include aromatic groups. They are generally lipophilic and typically solid or malleable at room temperature. Melting points vary depending on the alkyl chain. chain length and associations.

Silicone waxes are the preferred type of suitable waxes based on alkylmethylsiloxane. Oils are typically lipophilic and liquid at room temperature with lower molecular weights than waxes. Where present wax or butter may be present at up to 40% of the oil phase of the emulsion. More preferably the oil phase may contain wax or butter at levels of up to 20% of the oil phase of the emulsion. In an alternative embodiment the oil phase may contain wax or butter at levels of up to 10% of the oil phase of the emulsion.

Preferably the oil phase of the water-in-oil emulsion comprises a silicone oil. Where present, the silicone-containing oil phase preferably comprises an organo polysiloxane oil. The organopolysiloxane oil for use in the composition may be volatile, non-volatile, or a mixture of volatile and non-volatile silicones. The term "nonvolatile" as used in this context refers to those silicones that are liquid or gel under ambient conditions and have a flash point (under one atmosphere of pressure) of greater than 100°C. The term "volatile" as used in this context refers to all other silicone oils. Suitable organopolysiloxanes can be selected from a wide variety of silicones spanning a broad range of volatilities and viscosities. Examples of suitable organopolysiloxane oils include polyalkylsiloxanes, cyclic polyalkylsiloxanes, and polyalkylarylsiloxanes.

Preferred for use herein are organopolysiloxanes selected from the group consisting of polyalkylsiloxanes which include low, medium and high molecular weight dimethicone and dimethiconols alkyl substituted dimethicones such as cetyl dimethicone and caprylyl methicone, cyclic organopolysiloxanes having from 3 to 6 silicon atoms are included, for example, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane etc. These are termed cyclomethicones. Also included are silicone resins of the type MQ and T-Propyl also known as trimethylsiloxysilicates and polypropylsilsesquioxane, polyalkylan4 siloxanes, and mixtures thereof. More preferred for use herein are polyalkylsiloxanes and cyclomethicones. Preferred among the polyalkylsiloxanes are dimethicones.

Alternatively, the silicone oil may be a silicone elastomer. Suitable for use herein are silicone elastomers which can be emulsifying or non-emulsifying crosslinked siloxanc elastomers or mixtures thereof. No specific restriction exists as to the type of curable organopolysiloxane composition that can serve as starting material for the crosslinked organopolysiloxane elastomer. Examples in this respect are addition reaction-curing organopolysiloxane compositions which cure under platinum metal catalysis by the addition reaction between SiH-containing diorganopolysiloxane and organopolysiloxane having silicon-bonded vinyl groups; condensation-curing organopolysiloxane compositions which cure in the presence of an organotin compound by a dehydrogenation reaction between hydroxyl-terminated diorganopolysiloxanc and SiH-containing diorganopolysiloxane and condensation-curing organopolysiloxane compositions which cure in the presence of an organotin compound or a titanate ester. Preferred silicone elastomers include dimethicone crosspolymer and Polysilicone-11.

Preferably the oil phase comprises silicone, and most preferably, a silicone elastomer. Preferably, the emulsion composition includes from 20% to 35%, by weight of the emulsion composition, of the silicone elastomer raw material.

When the composition is a water-in-oil emulsion it preferably comprises an emulsifier. In a preferred embodiment, the composition comprises from 0.1% to 10% emulsifier, more preferably from 0.25% to 7.5%, still more preferably from 0.5% to 5%, emulsifier by weight of the composition. The emulsifier helps disperse and suspend the aqueous water phase within the oil phase.

Emulsifiers The composition of the present invention may comprise an emulsifier. Suitable emulsifiers include all those suitable for the purpose and known by those skilled in the art for use in skin care products. Preferably these emulsifiers have an HLB value of or less than 14, more preferably from 2 to 14, and still more preferably from 4 to 14.

Silicone emulsifiers are preferred. A wide variety of silicone emulsifiers are useful herein. These silicone emulsifiers are typically organically modified organopolysiloxancs, also known to those skilled in the art as silicone surfactants. Useful silicone emulsifiers include 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 chains comprising moieties derived from both ethylene oxide and propylene oxide. Other examples include alkyl-modified dimethicone copolyols, i.e., compounds which comprise C2-C30 pendant side chains. Still other useful dimethicone copolyols include materials having various cationic, anionic, amphoteric and zwitterionic pendant moieties.

Nonlimiting examples of dimethicone copolyols and other silicone surfactants useful as emulsifiers herein include polydimethylsiloxane polyether copolymers with pendant polyethylene oxide side chains, polydimethylsiloxane polyether copolymers with pendant polypropylene oxide side chains, polydimethylsiloxane polyether copolymers with pendant mixed polyethylene oxide and polypropylene oxide side chains, polydimethylsiloxane polyether copolymers with pendant mixed poly (ethylene) (propylene) oxide side chains, polydimethylsiloxane polyether copolymers with pendant organobetaine side chains, polydimethylsiloxane polyether copolymers with pendant carboxylate side chains, polydimethylsiloxane polyether copolymers with pendant quaternary ammonium side chains; and also further modifications of the preceding copolymers comprising pendant C2-C;n straight, branched, or cyclic alkyl moieties. A particularly preferred emulsifier is PEG/PPG-I 8/1 8 dimethicone.

Suitable, cetyl dimethicone copolyol is commercially available as a mixture with polyglyceryl-4 isostearate (and) hexyl laurate or as a mixture with hexyl laurate and polyglyceryl-3 oleate. Other nonlimiting examples of dimethicone copolyols also include lauryl dimethicone copolyol, dimethicone copolyol acetate, diemethicone copolyol adipatc, dimethicone copolyolaminc, 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.

Among the non-silicone-comprising emulsifiers useful herein are various non-ionic and anionic emulsifying agents such as sugar esters and polyesters, alkoxylated sugar esters and polyesters, CI-1,30 fatty acid esters of CI-C.30 fatty alcohols, alkoxylated derivatives of CI-C30 fatty acid esters of Ci-C30 fatty alcools, alkoxylated ethers of C,-C30 fatty alcohols, polyglyceryl esters of CI-C30 fatty acids, C,-C30 esters of polyols, Ci-C30 ethers of polyols, alkyl phosphates, polyoxyalkylene fatty ether phosphates, fatty acid amides, acyl lactylates, soaps, and mixtures thereof. Nonlimiting preferred examples of these non-silicon-comprising 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-I 00 stearate, polyoxyethylene 20 sorbitan trioleate (Polysorbate 85), sorbitan monolaurate, polyoxyethylene 4 lauryl ether sodium stearate, polyglyceryl-4 isostearate, hexyl laurate, stearcth- 20, cetearcth-20, PPG-2 methyl glucose ether distearate, ceteth-10, diethanolamine cetyl phosphate, glyceryl stearate, PEG-100 stearate, and mixtures thereof Matrix metalloproteinase inhibitors (MMPi) The compositions of the present invention may optionally comprise matrix metalloproteinase inhibitors. The term "matrix metalloproteinase inhibitor" relates to all molecule and/or plant or bacterial extracts having an inhibitory activity on at least one of the matrix metalloproteinases expressed by or synthesised in the skin. The family of the matrix metalloproteinases is formed of several well-defined groups on the basis of their resemblance regarding structure and substrate specificity (Woessner J. F. 1991, Faseb Journal, vol. 5,-, 2145). Among these groups, there are collagenases able to degrade fibrillar collagens (MMP-1 or interstitial collagenase, MMP-8 or neutrophil collagenase. MMP-13 or collagenase 3. MMP-18 or collagenase 4), gelatinases degrading type TV collagen or other denatured collagen form (MMP-2 or A gelatinase (72 kDa), MMP-9 or B gelatinase (92 kDa)), stromelysins (MMP-3 or stromelysin 1, MMP-10 or stromelysin 2, MMP-11 or stromelysin 3) whose broad spectrum of activity targets proteins of the dermal extracellular matrix such as glycoproteins (fibronectin, laminin), proteoglycans etc., matrilysin (MMP-7). metalloelastase (MMP-12) or metalloproteinases (MMP-14, MMP-15, MMP-16 and MMP-17). Metalloproteinases (MMPs) are proteases that use a metal, (mostly zinc) coordinated to 3 cystcine residues and to a methioninc in their active site, that degrade macromolecular components of the dermal extracellular matrix and of basal layers at neutral pH (collagen, elastin, etc...). This group of enzymes is inactivated by metal chelators. The principal activity regulators of MMPs are the tissue inhibitors of metalloproteinases or T1MPs such T1MP1, T1MP-2, T1MP-3 and T1MP-4 (Wocssner J. F., Faseb Journal, 1991). Furthermore, MMP expression is also regulated by growth factors_ cytokines, oncogene products (ras. jun). or also matrix constituents.

The term "matrix metalloproteinase inhibitors" according to the present invention means all molecules able to reduce the MMP's activity regarding the gene expression (transcription and translation) or regarding the activation of the zymogen form of the MMP, or else regarding the local control of active forms. Furthermore, the metalloprotcinase inhibitors according to the present invention can also be MMP-1 inhibitors of natural or synthetic origin. The terms "natural origin" or "synthetic origin" mean both a metalloproteinase inhibitor at a pure state or in solution at different concentrations, but natural origin termed inhibitors are obtained by different extraction methods from a natural element (for example lycopene from a tomato) whereas the inhibitors of synthetic origin arc all obtained via chemical synthesis Preferred MMPi are selected from the group consisting of retinoid, N-acetyl cystcine, glutathione, 2-furildioxime, vitamin C, flavones, isoflavones, hydrolysed rice protein, alfalfa extract, white lupin, zizyphus jujube extract, dihydroxy methyl chromone, kudzu extract, vitis vinifera extract, Oenothera bicnnis extract Anogcissus lciocarpus extract and mixtures thereof Where present, MMPi are present at a level of from 0.01% to 10%, more preferably 0.1% to 5% and most preferably from 0.5% to 2.5% by weight of the cosmetic composition.

Skin Conditioning Agent The compositions of the present invention may optionally comprise a skin conditioning agent.

Said skin conditioning agents may preferably be selected from the group consisting of humectants, emollients, moisturisers, or mixtures thereof Where present, they are preferably present at a level of from 0.01% to 20%, more preferably from 0.1% to 10%, most preferably from 0.5% to 7.5% by weight of the cosmetic composition.

Preferred skin conditioning agents are selected from the group consisting of guanidine, urea, glycolic acid and glycolate salts, salicylic acid, lactic acid and lactate salts, aloe vera, shea butter, polyhydroxy alcohols, such as sorbitol, mannitol, xylitol, crythritol, glycerol, hexanetriol, butanitriol, (di) propylene glycol, butylene glycol, hexylene glycol, polyethylene glycol, sugars (e.g., fructose, glucose, xylose, honey, mannose, xylose), gluconodeltalactone, and starches and their derivatives, pyrrolidone, carboxylic acid, hyaluronic acid and salts thereof, lactamide monoethanolamine, acetamidc monoethanolamine, panthenol, allantoin and mixtures thereof More preferably said skin conditioning agent is selected from the group consisting of glycerine, arabinogalactan, butylene glycol, hyaluronic acid, shea butter, propylene glycol, ethylhexyl glycerine, hyaluronate and mixtures thereof Antioxidant Agent The compositions of the present invention may optionally comprise an antioxidant agent. Suitable antioxidant agents may include: (a) ascorbic acid and its derivatives, salts, esters, glucosides and glucosamines, particularly ethyl ascorbic acid, sodium ascorbyl phosphate, magnesium ascorbyl phosphate and ascorbyl palmitate, (b) vitamin E (tocopherol) and its esters, particularly tocopheiy1 acetate, as well as Dimethyl methoxy chromanol which is a synthetic analogue of gamma tocophcrol, available from Lipotcc S.A. polygon Industrial Camri Pal, under the tradenamc Lipochroman-6, (c) herbal extracts, particularly gingko biloba, such as that available under the trade name "Gingko Biloba Leaf Powder" from Univar PLC, morus alba, such as that available under the trade name "Mulberry Concentrate" from Solabia, origanum vulgare, such as that available under the trade name "Pronalen Origanum HSC" from S Black Ltd, panax ginseng, such as that available under the trade name "Panax ginseng 1.1 extract 4294"from S Black Ltd or "Phytexcell Panax ginseng" available from Croda Chemicals Ltd, birch extract such as those available from Cosmetochem (U.K.) Ltd under the trade names "Super Herbasol Extract Birch" and "HP Herbasol Betula" and those available from Blagden Chemicals under the tradenames "Phytelenc of Birch" and "Aqueous Spray Dried Birch", camellia sincnsis, such as that available under the trade name "Herbal Extract Green Tea 75% Solids" from Nichimen Europe, rosmarinus offieinalis, such as that available under the trade name "Pronalen Rosemary" from S. Black, Acerola cherry powder, such as that available as Acerola PE from Gee Lawson, Emblica extract sold under the tradename Emblica® by Merck Speciality chemicals, and Grape Seed oil, such as that available from Chesham Chemicals Limited, Camellia japonica flower extract (such as that available under the trade name "RedSnow®" from Clariant), Myrna commons leaf extract (such as that sold under the trade name of DEXOSINE BIG® from Silab), Quercus petraea fruit extract (such as that sold under the trade name of Phytessence French OakTM from Croda), Argania spinosa leaf extract (such as that sold under the trade name of ArganyIrm from BASF), Pinus pinaster bark extract (such as that sold under the trade name of Pycnogenor), synthesised chemical antioxidants that include fondle acid (also known as hydroxycinnamic acid), and Resveratrol (such as that sold under the trade name of REGUR-FADE from DSM).

The amounts of antioxidant agents used in the cosmetic composition are expressed as dry weights, as understood by a man skilled in the art. The total amount of antioxidant agents optionally present in the composition may range from 0.005% to 10% by weight, preferably 0.5% to 5%, most preferably 0.2% to 1.5% by weight of the composition.

Particularly preferred synergistic combinations of antioxidant agents suitable for inclusion in the cosmetic composition of the present invention are selected from the group consisting of: i) panax ginseng morus alba and magnesium ascorbyl phosphate, ii) panax ginseng, morus alba and sodium ascorbyl phosphate; iii) panax ginseng, moms alba and rosmarinus officinalis; iv) ginkgo biloba, phyllanthus cmblica and Dimethylincthoxy chromanok v) morus alba, camellia sinensis and dimethvlmethoxy chromanol; vi) moms alba, camellia sinensis and tocopheryl acetate; vii) panax ginseng, moms alba and origanum vulgare, viii) camellia sinensis, tocophervl acetate and dimethylmethoxychromanol, viv) morus alba, tocopheryl acetate and dimethylmethoxychromanol, vv) Argania spinosa, Firms pinaster and resvcratrol, vvi) Myrna communis, Ginkgo biloba and fendic acid, vvii) Myrius communis, Quercus petraea and Pinus pinaster, viii) Camellia sinensis, Quercus petraea and femlic acid.

In these preferred combinations (a) the panax ginseng is preferably present in an amount of 0.005% to 0.1%, more preferably 0.01% to 0.05% by weight of the composition; (b) the morus alba is preferably present in an amount of 0.0005% to 0.01%, more preferably 0.001% to 0.005% by weight of the composition; (c) the sodium magnesium ascorbyl phosphate or ethyl ascorbic acid is preferably present in an amount of 0.05% to 2.5%, preferably 0.1% to 2%, most preferably 0.15% to 1.5% by weight of the composition; (d) the rosmarinus officinalis or origanum vulgare or phyllanthus emblica is preferably present in an amount of 0.01% to 0.5%, more preferably 0.05% to 0.2% by weight of the composition; (e) the dimethylmethoxy chromanol is preferably present in an amount of 0.0005% to 0.1%, more preferably from 0.005% to 0.05% by weight of the composition; (0 the camellia sinensis is preferably present in an amount of 0.005% to 0.2%, more preferably from 0.01% to 0.1%; (g) the Tocopherol acetate is preferably present in an amount of 0.01 to 0.5%, more preferably from 0.05% to 0.25%; and (h) the Camellia japonica extract is preferably present in an amount of 0.001% to 5%, more preferably from 0.01% to 3%.

Vitamins The compositions of the present invention may comprise one or more vitamins. The compositions may comprise ascorbates, for example vitamin C, vitamin C derivatives, ascorbic acid, ascorbyl glucoside, ascorbyl palmitate, magnesium ascorbyl phosphate, sodium ascorbyl phosphate and ethyl ascorbic acid. The composition may comprise vitamin B, vitamin B derivatives, vitamin B1 to vitamin B12 and their derivatives. hi a further embodiment the composition comprising the Vitamin B3 derivative niacinamide.

In an alternative embodiment of the present the cosmetic composition comprises vitamin K, vitamin K derivatives, vitamin H, vitamin D, vitamin D derivatives and mixtures thereof in an alternative embodiment of the present the cosmetic composition comprises vitamin E, vitamin E derivatives such as tocophcrol and tocophcryl acetate, and provitamins thereof, such as panthenol and mixtures thereof in a further embodiment the present cosmetic composition comprises retinoid compounds, including retinoic acid, retinaldehyde, retinol and derivatives thereof in one embodiment the cosmetic composition comprises rctinyl palmitate, retinyl acetate, retinyl retinoatc, retinyl proprionate, retinyl ascorbatc, rctinyl linolcatc, rctinyl retinoatc, rctinyl sunflowersccdatc and mixtures thereof 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 (c. g. plant) sources. In one embodiment, when vitamin compounds are present in the compositions of the instant invention, the emulsion compositions comprise from about 0.0001% to 50%, more preferably from 0.001% to 10%, still more preferably from 0.01% to 8%, and still more preferably from 0.1% to 5%, by weight of the composition, of the vitamin compound.

Salicylic Acid Compound The compositions of the present invention may comprise a salicylic acid compound, its esters, its salts, or combinations thereof in one embodiment of the compositions of the present invention, the salicylic acid compound preferably comprises from 0.0001% to 25%, more preferably from 0.001% to 15%, even more preferably from 0.01% to 10%, still more preferably from 0.1% to 5%, and even more preferably from 0.01% to 2%, more preferably 0.1% to 2% by weight of the composition, of salicylic acid.

Sunscreen The compositions of the present invention may optionally comprise a sunscreen component. The sunscreen may comprise organic or inorganic sun filters or a combination of the two. Suitable inorganic sun filters include those selected from the group consisting of microfine titanium dioxide, microfilm zinc oxide, boron nitride and mixtures thereof Suitable organic sunscreens include those selected fro m the group consisting of: a) p-aminobenzoic acids, their esters and derivatives (for example, 2ethylhexyl p-dimethylaminobenzoate), b) methoxycinnamate esters (for example, 2-ethylhexyl pmethoxycinnamate, 2-ethoxyethyl p-methoxycinnamate or a, p-di-(p-methoxycinnamoy1)-a'-(2ethylhexanoy1)-glycerin, c) benzophenones (for example oxybenzone), d) dibenzoylmethanes such as 4-(tort-butyl)-4'-methoxydibenzoylmethanc, c) 2-phenylbcnzimidazolc-5 sulfonic acid and its salts, f) alkyl-ss, ss-diphenylacrylates for example alkyl a-cyano-ss, ss-diphenylacrylates such as octocrylenc, g) triazines such as 2,4,6-trianilino-(p-carbo-2-ethyl-hexyl-1-oxi)-1, 3,5 triazine, h) camphor derivatives such as methylbenzylidene camphor and i) mixtures thereof. Other preferred sunscreen ingredients include those selected from the group consisting of homosalate. Ethylhexyl salicylate, Dicthylhexylbutamido triazonc, Bis-ethylhexyloxyphenol mcthoxyphcnyl triazinc, Diethylamino hydroxybcnzoyl hcxyl benzoate, Butyl methoxydibenzoylmethanc, Methylene bis-bcnzotriazoyl tctramcthylbutylphenol, Polysiliconc15 and mixtures thereof. A sunscreen agent is optionally present in an amount from 0.1 to 10% by weight of the composition.

Other Optional Ingredients The compositions of the present invention may also optionally comprise one or more of the following optional ingredients. Preservatives may be added to the emulsion such as 2-bromo2-nitropropane-L3-diol (bronopol, which is available commercially under the trade name Myacidc RTM), benzyl alcohol, diazolidinyl urea, imidazolidinyl urea, methyl paraben, phenoxy ethanol, ethyl paraben, propyl paraben, sodium methyl paraben, sodium dehydroacetate, polyhexamethylenebiguanide hydrochloride, isothiazolone and sodium propyl paraben, suitably in an amount of from 0.01% to 10% by weight of the emulsion.

Thickeners, viscosity modifying agents and/or gelling agents may be added to the emulsion composition, such as acrylic acid polymers c. g. available commercially under the trade name Carbopol or Ultrez (Lubrizol) or modified celluloses e.g., hydroxyethylcellulose available commercially under the trade name Natrosol (Hercules) or hydroxypropylmethyl cellulose, amine oxides, block polymers of ethylene oxide and propylene oxide (for example, those available from BASF Wyandotte under the trade name "Pluronic"1(), PVM, MA, or a decadicne crosspolymcr (available under the trade name Stabilez 60), ethoxylated fatty alcohols, salt (magnesium chloride, sodium chloride), Aristoflex AVC (Clariant), phthalic acid amide, xanthan gum, sodium polyacrylate, polyvinyl alcohols, fatty alcohols and alkyl galactomannans available under the trade name N-Hance from Hercules, suitably in an amount of from 0.5% to 10% by weight of the composition.

Sequestering agents may be added to the emulsion composition, such as ethylenediamine tetraacetic acid and salts thereof, suitably in an amount of from 0.005% to 0.5% by weight of the composition.

The composition may also include waxes such as cocoa butter suitably in an amount of from 1% to 99% by weight of the composition.

The composition may also comprise suitable, cosmetically acceptable diluents, carriers and/or propellants such as dimcthyl ether.

The composition may also include pearlising agents such as stcaric monoethanolamide and/or mica, suitably in an amount of from 0.01% to 10% by weight of the composition.

Perfumes may be added suitably in an amount of from 0.01% to 2% by weight of the composition, as may water soluble dyes such as tartrazine, suitably in an amount of from a trace amount (such as 1 x 10-5 %) to 0.1 % by weight of the composition.

The composition may also include pH adjusting agents such as sodium hydroxide, aminomethyl propanol, triethanolamine, suitably in an amount of from 0.01 % to 10% by weight of the composition. The composition may be buffered by means well known in the art, for example by use of buffer systems comprising succinic acid, citric acid, lactic acid, and acceptable salts thereof, phosphoric acid, mono-or disodium phosphate and sodium carbonate. Suitably, the composition may have a pH between 3 and 10, preferably between 4 and 8.

Methods of use The present invention also relates to a method for stimulating the production of dermal extracellular proteins in a subject. Preferably the subject is a human. The dermal extracellular proteins may include collagen, fibrillin, fibronectin and dccorin. The method may comprise administering to said subject the tripeptide composition (e.g., in a cosmetically or therapeutically effective amount) according to the present invention or a cosmetic composition comprising the same.

The invention may comprise a method of inducing dermal ECM protein upregulation and/or inducing ECM repair using a tripeptide or a composition as described herein. Thus, in one embodiment, the invention provides the use of a tripeptide or a composition as described herein as a non-therapeutic cosmetic treatment to improve the condition of the skin and/or reduce lines and/or reduce wrinkles and/or reduce imperfections (e.g., pigmentation) and/or improve skin firmness and elasticity.

In one embodiment, the invention relates to a cosmetic method for improving the condition and/or appearance of the skin and/or lines and/or wrinkles and/or reduce imperfections (e.g., pigmentation) and/or improve skin firmness and elasticity, comprising topically administering a peptide combination or a cosmetic composition of the invention.

All of the embodiments and features described herein (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined with any of the above aspects or embodiments in ally combination, unless stated otherwise with reference to specific combinations, for example, combinations where at least some of such features and/or steps are mutually exclusive.

Figures For a better understanding of the invention, and to show embodiments of the invention may be put into effect, reference will now be made, by way of example, to the accompanying drawings, in which:-Figure 1 shows the in-silico discovery pipeline. The entire human proteome was filtered to identify 205 human skin ECM proteins. An initial protein cohort (key structural ECM and/or higher predicted susceptibility to proteases and UVR/ROS) was further filtered based on reported age-related remodelling to a target cohort of 27 proteins. This cohort was subjected to in silico digestion and peptide prediction generating 620 tri-peptides putative candidates with each ECM protein differing in their richness as a tri-peptide source (See figure 2).

Figure 2 shows bioinformatic prediction and selection of candidate peptides. (A) Defining protein targets for in silico protease cleavage. An initial cohort of 69 proteins (protease and UVR/ROS-susceptible and key structural ECM components) was filtered to identify 27 abundant and/or skin ageing-susceptible target proteins classified into seven categories. (B) In silica prediction of protease cleavage sites and liberated small peptides. Each of the 27 proteins was screened using a bespoke Python algorithm interacting with the PROSPER protease cleavage server to identify' cleavage sites with a probability cleavage scores of >=0.7. In this hypothetical example a single tripeptide (dotted box) would be liberated. (C) Source proteins differed in their richness as sources of tripeptides with HSPG2 for example harbouring 85 potential tri-peptides, versus MFAP2 which harbours only 2 tri-peptides. Collectively this screening process identified 620 unique putative tri-peptide matrikines.

Figure 3 is a table that shows example ELISA data for selected tripeptides peptides. Human fibroblast cell cultures would be exposed to candidate tri-pcptides, control tri-peptides (not predicted to be found naturally in skin) and positive control. Two independent experiments (Exp I and Exp2) would be performed and production of procollagen-I, fibronectin, decorin, and collagen-IV would be detected by ELTSA. Data would be reported as percentage changes against solvent control with significant differences indicated by * (p<0.05) and * (p<0.0 I).

Examples

In this study, the inventors will test the hypothesis that small bioactive peptides (matrikines) can be predicted by the in-silico digestion of dermal proteins via action of ECM proteases. In contrast to enzymes such as trypsin, where cleavage sites can be predicted with a great deal of certainty, identifying putative cleavage sites of endogenous tissue ECM proteases (such as members of matrix metalloprotcinases [MIVIPs] and cathepsins) requires the use of machine learning algorithms which can predict cleavage sites in protein sequences.

Experimental protocol and results Candidate tripeptides would be progressed to initial efficacy screening after evaluation of their solubility, toxicology and stability. These efficacy tests would be carried out through ELISA, and immunofluorescence against ECM markers of repair (e.g.. fibrillin-1). Primary Human Dermal Fibroblasts (HDFs) would be were cultured with medium 10% FBS, 100 U/mL penicillin, 100 tig/mL streptomycin, ittg/mL fungizone and 1mM L-glutamine under 5% CO2 and 90% humidity atmosphere at 37°C. Medium would be renewed every 48h to 72h to allow outgrowth and then HDFs treated with various concentrations of the tri-peptides peptides dissolved in solvent (e.g. DMSO), solvent alone or a positive control (e.g.. TGF-(31). Cell culture media would then be collected and ELISA assays performed as per the manufacturer's instructions to detect ECM proteins. All treatments would be run in triplicate and One-way 394 analysis of variance (ANOVA) carried out to determine statistically significant differences between the means of two or more independent groups in the ELISA assays. An example of the results that could be generated are shown in Figure 3.

Examples of cosmetic compositions The tripeptides of the present invention may be incorporated into cosmetic compositions, representative examples of which are described below.

Cosmetic composition 1 -Representative water-in-oil emulsion cosmetic composition Material % w /w Dimethicone 73.83 Water 37.11 Glycerin 5.00 Dimethicone crosspolymer & Dimethcone 32.31 Butylene glycol 2.60 PEG/PPG-18/18 dimethicone & Polyglyceryl -4 isostearate & Hexyl laurate 3,00 Cctyl PEG/PPG-10/1 dimcth conc 2,00 Magnesium sulphate 0.60 Phenoxyethanol & Methylparabcn & Ethylparaben 0.55 Peptide excipient composition comprising propanediol & Pentylene glycol & Decyl glucoside & Water excipient composition 3.00 Method of manufacture In the main vessel add Dimethicone, Dimethicone crosspolymer, PEG/PPG-18/18 dimethicone & polyglyceryl-4 isostearate & hexyl laurate and Cetyl PEG/PPG-10/1 dimethicone to make the oil phase.

2. Separately weigh out water, magnesium sulphate, glycerine, phenoxyethanol & methylparaben & ethylparaben and peptide & propanediol & pentylene glycol & decyl glucoside & water stir until solids are dissolved to make the water phase.

3. Add the water phase to the oil phase slowly with constant stirring at high speed (creating a vortex). Continue stirring for 5 minutes.

4. Homogenise the product for 5 minutes at 3500 rpm using a S Iverson mixer or equivalent.

Composition 2 Representative oil-in-wale emulsion cosmetic co nposi/ion Material % w /w Dimethicone 5.50 Water 79.95 Glycerin 5.00 Dimethicone crosspolymer & Dimethicone 1.00 Phenoxyethanol & Methylparaben & Ethvlparaben 0.80 Glyceryl stearate & PEG-100 stearate 2.00 Cetearyl alcohol 2.00 Sodium polyaerylate 0.60 Xanthan gum 0.10 Tetrasodium EDTA 0.05 Peptide excipient composition comprising propanediol & Pentylene glycol & Decyl glucoside & Water excipient composition 3.00 Method of manufac u e To water add glycerine and dissolve tetrasodium EDTA.

2. Using homogenisation sprinkle in xanthan gum and continue to homogenise for 5 minutes or until hydrated.

3. Heat water phase to 70-75°C 4. in a separate vessel weigh out oil phase and heat to 70-75°C. (Dimethicone, cetearyl alcohol, glycerol stearate & PEG-100 stearate) When at temperature stir in the sodium polyacrylate.

5. With both phases at 70-75°C add the oil phase to the water phase and homogenise for 2 minutes.

6. Add dimethicone crosspolymer & dimethicone and homogenise for 2 minutes.

7. Cool to room temperature.

8. Stir in phenoxyethanol & methylparaben & ethylparaben and peptide & propanediol & pentylene glycol & decyl glucoside & water.

9. Make to weight with water and stir smooth.

Composition 3 -Representative Gel-based cosmetic composition Material % w/w Glycerin 5.00 Propanediol 2.00 Acrylates/C10-30 alkyl acrylate crosspolymer 1.00 Alcohol denat. 0.50 Phenoxycthanol & Mcthylparabcn & Ethylparaben 0.40 Potassium hydroxide 0.29 Tetrasodiurn EDTA 0.05 Peptide excipient composition comprising propanediol & Pentylene glycol & Decyl glucoside & Water cxcipient composition 3.00 Water 87.76 Method of manufacture To water add glycerine and propanediol and dissolve tetrasodium EDTA.

2. Using homogenisation sprinkle in acrylates/C10-30 alkyl acrylate crosspolymer and continue to homogenise for 5 minutes or until hydrated.

3. Stir in potassium hydroxide to form gel.

4. Stir in alcohol dcnat., phcnoxyethanol & mothylparaben & cthylparabcn and peptide & propanediol & pentylene glycol & decyl glucoside & water. Make to weight with water and stir smooth.

Claims (9)

1. 23 Claims 1. A tripeptide capable of inducing dermal extracellular matrix protein upregulation and/or capable of inducing ECM repair. wherein the tripeptide is a fragment of an ECM protein.
2. 2. A tripeptide according to claim 1, wherein the tripeptide has the amino acid sequence U-XXX-Z, wherein X denotes an amino acid selected from the group consisting of Valine (V), Aspartic acid (D), Proline (P), Glycine (G), alanine (A), arginine (R), asparagine (19). cysteine (C), glutamic acid (E), glutamine (Q), glutamic acid (Z). histidine (H), isoleucine (1), leucine (L), lysine (K), methionine (M), phenylalanine (F), serine (S), threonine (T), tryptophan (W), tyrosine (Y) and mixtures thereof, at the N-terminal end, U is selected from the group consisting of H, - -SO2-R' or a biotinyl group, at the C-tenninal end, Z is selected from the group consisting of OH, 0 NHR1 or NR'R2, wherein if U is H then Z cannot be OH, and R' and R2 are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, saccharide and aryloxy group, which may be linear, branched, cyclical, polycyclic, unsaturated, hydroxylates, carbonylated, phosphorylated and/or sulphurous, said groups comprising from 1 to 24 carbon atoms and being capable of including one or more heteroatoms 0, S and/or N.
3. 3. A tripeptide according to claim 1 or claim 2 wherein U of the tripeptide is independently selected from the group consisting of octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stcaroyl (C18), biotinoyl, elaidoyl, olcoyle and lipoylc.
4. 4. A tripeptide according to claim 2 or claim 3 wherein U of the tripeptide is independently selected from the group consisting of lauroyl (C12), myristoyl (C14) and palmitoyl (C16).
5. 5. A tripeptide according to claim 1, wherein the tripeptide has an amino acid sequence selected from the group consisting of GPE, GPS, GPP, LSV, LSP, KGP, KGD. PKG. LRG, SPD. RGD, SVD, YIL. and GFP.
6. 6. A cosmetic composition comprising a tripeptide according to any one of the preceding claims.
7. 7. A cosmetic composition according to claim 6 wherein the tripeptide is present at from 0.1 to 10,000ppm by weight of the composition.
8. 8. A method for stimulating the production of extra cellular matrix proteins in humans, the method comprising administering to the skin of said human a cosmetically effective amount of a tripeptide or a cosmetic composition according to any one of the preceding claims.
9. 9. The use of a tripeptide according to any one of claims 1 to 5 or a composition according to any one of claims 6 to 7 as a non-therapeutic cosmetic treatment to improve the condition of the skin and/or lines and/or wrinkles and/or imperfections and/or skin firmness and elasticity.