Tetrapeptides and compositions containing tetrapeptides

Abstract

According to the present invention, there is provided a tetrapeptide capable of inducing increased expression of skin extracellular matrix proteins, selected from the group consisting of tetrapeptides having the amino acid sequence U-LSXX-Z, wherein, according to the internationally accepted one-letter code for amino acids, L is used to represent the amino acid leucine, S is used to represent serine, X represents an amino acid selected from the group consisting of valine (V), aspartic acid (D), proline (P), glycine (G), and combinations thereof, and the N-terminal U is selected from the group consisting of H, -CO-R 1 , -SO2-R 1 or a biotinyl group, and Z at the C-terminus is selected from the group consisting of OH, OR 1 , NHR 1 , or NR 1 R 2 When U is H, Z cannot be OH; and R 1 and R 2 are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, sugar, and aryloxy groups, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated, and / or sulfur-containing, and which groups contain from 1 to 24 carbon atoms and may contain one or more heteroatoms O, S, and / or N.

Description

[Technical Field]

[0001] This invention relates to a novel tetrapeptide and a composition containing the tetrapeptide for use in cosmetic applications. [Background technology]

[0002] The largest component of normal skin is the extracellular matrix (ECM), a gel-like matrix produced by the cells surrounding it. The ECM contains two main components: structural proteins and proteoglycans. Skin changes occur naturally over time (aging) as a result of changes in the composition and cross-linking of ECM components, which cause changes at the structural and behavioral levels. Structural changes affect the integrity of the skin. Aging skin shows both increased degradation of extracellular matrix (ECM) proteins (e.g., collagen, laminin, elastin, fibronectin) and decreased production of these proteins.

[0003] Changes in cell behavior affect the rate of cell differentiation and proliferation, and consequently, the rate of skin repair and regeneration. The epidermal cell mass (ECM) is also thought to be responsible for generating cellular signals that promote epithelial cell proliferation and migration, further influencing the skin's repair capacity. Changes in the ECM also affect cell adhesion, signal transduction, and the mediation of cell behavior.

[0004] Particularly important ECM proteins include collagen, fibrillin, fibronectin, and decorin. Collagen plays a role in providing elements of the structural integrity of the skin. Collagen in the skin matrix is ​​mainly composed of type I (80%-85%) and type III (8%-11%) collagen, both of which are fibrous or rod-shaped collagen. The tensile strength of the skin is mainly provided by the fibrous structure in which collagen I molecules are cross-linked. There are other functionally important types of collagen that are less abundant in the skin, such as collagen IV, which is present in the basement membrane at the dermal epidermal junction. Collagen IV forms a sheet-like structure and is more flexible than fibrous collagen. For example, damage to the skin's collagen network due to free radical injury induces the generation of collagen fragments in the ECM, which in turn induces skin regeneration and repair.

[0005] Fibrillin is a component of elastic fibers in the extracellular matrix (ECM) and contributes to the structural integrity of the skin. The most abundant fibrillin in the elastic fibers of the skin is fibrillin-1, a protein encoded by FBN1.

[0006] Fibronectin is an ECM glycoprotein that primarily mediates a wide variety of intercellular interactions within the extracellular matrix (ECM), playing a crucial role in cell adhesion, migration, proliferation, and differentiation.

[0007] Decorin (DCN) is a proteoglycan belonging to the leucine-rich proteoglycan (SLRP) family. This peptide is considered to be an important component of connective tissue, binding to type I collagen and thereby regulating the construction of the collagen extracellular matrix (ECM).

[0008] Age-related skin changes can occur intrinsically as a result of time, and extrinsically as a result of extrinsic mechanisms, including UV-related injury and contamination. Extrinsic mechanisms can lead to increased utilization of reactive oxygen species (UV-ROS). These reactive oxygen species are known to cause ECM fragmentation and increased expression of matrix metallopeptidases (MMPs) and other ECM proteases. ECM fragmentation can lead to damage and / or remodeling of ECM structural proteins and can reduce skin integrity.

[0009] ECM protein fragmentation can lead to the release of low-molecular-weight bioactive peptides or matricine, which act as cell signaling molecules that promote skin repair by upregulating proteinogenesis, cell proliferation, and differentiation. Both intrinsic and extrinsic aging can lead to protein fragmentation and the subsequent release of the bioactive peptide matricine.

[0010] Numerous natural and synthetic peptide matricanes have been used for many years in cosmetic compositions and products to stimulate increased peptide expression, skin repair, and regeneration. The most commonly used peptides are Pal-KKTKS and a combination of palmitoyl oligopeptide (Pal-GHK), which acts as a messenger peptide for collagen regeneration and consists of a sequence derived from collagen I, and palmitoyl tetrapeptide-7 (Pal-GQPR), which has a sequence derived from immunoglobulin G and reduces the production of interleukin-6 (IL-6), thereby acting as an anti-inflammatory agent and inhibiting ECM degradation. The above peptide combinations are available from Sederma under the trade names Matrixyl and Matrixyl 3000. [Overview of the Initiative] [Problems that the invention aims to solve]

[0011] Many natural and synthetic peptides have been used for many years, but there remains a need for the identification of new and improved physiologically active peptides to assist the natural behavior of the skin. [Means for Solving the Problems]

[0012] According to the present invention, there is provided a tetrapeptide capable of inducing increased expression of skin extracellular matrix proteins, selected from the group consisting of tetrapeptides having the amino acid sequence U-LSXX-Z, wherein according to the internationally accepted one-letter amino acid code, L is used to represent the amino acid leucine, and S is used to represent serine. X represents an amino acid selected from the group consisting of valine (V), aspartic acid (D), proline (P), glycine (G), and combinations thereof. N-terminal U is selected from the group consisting of H, -CO-R 1 , -SO2-R 1 , or a biotinyl group. C-terminal Z is selected from the group consisting of OH, OR 1 , NHR 1 , or NR 1 R 2 . R 1 and R 2 are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, sugar, and aryloxy groups, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated, and / or sulfur-containing, said groups containing from 1 to 24 carbon atoms and possibly containing one or more heteroatoms O, S, and / or N.

[0013] In one aspect, the present invention relates to a tetrapeptide capable of inducing increased expression of skin extracellular matrix protein, selected from the group consisting of tetrapeptides having the amino acid sequence U-LSXX-Z, wherein according to the internationally recognized one-letter code for amino acids, L is used to represent the amino acid leucine, S is used to represent serine, X represents an amino acid selected from the group consisting of valine (V), aspartic acid (D), proline (P), glycine (G), and combinations thereof, and N-terminal U is H, -CO-R 1 , -SO2-R 1 , or a biotinyl group selected from the group consisting thereof, and C-terminal Z is OH, OR 1 , NHR 1 , or NR 1 R 2 selected from the group consisting thereof, with the proviso that when U is H, Z must not be OH, and R 1 and R 2 are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, sugar, and aryloxy groups, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated, and / or sulfur-containing, said groups having 1 to 24 carbon atoms and possibly containing one or more heteroatoms O, S, and / or N. A tetrapeptide is provided.

[0014] In an alternative aspect, the present invention relates to a tetrapeptide capable of inducing increased expression of skin extracellular matrix protein, selected from the group consisting of tetrapeptides having an amino acid sequence selected from the group consisting of U-(SEQ ID NO: 2)-Z, U-(SEQ ID NO: 3)-Z, U-(SEQ ID NO: 4)-Z, U-(SEQ ID NO: 5)-Z, U-(SEQ ID NO: 6)-Z, U-(SEQ ID NO: 7)-Z, U-(SEQ ID NO: 10)-Z, U-(SEQ ID NO: 11)-Z, and U-(SEQ ID NO: 12)-Z, wherein N-terminal U is H, -CO-R 1 , -SO2-R 1, or a biotinyl group, and the C-terminal Z is selected from the group consisting of OH, OR 1 , NHR 1 , or NR 1 R 2 There is provided a tetrapeptide selected from the group consisting of. R 1 and R 2 are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, sugar, and aryloxy groups, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated, and / or sulfur-containing, said groups containing 1 to 24 carbon atoms and optionally containing one or more heteroatoms O, S, and / or N. [Brief Description of the Drawings]

[0015] [Figure 1] This is a bubble plot showing the overall effect of each tested peptide on these four protein families. [Modes for Carrying Out the Invention]

[0016] The present invention relates to a tetrapeptide that acts as a signaling matrikine for increasing the expression of production of proteins of the skin extracellular matrix (ECM), including at least fibrillin, fibronectin, decorin, and collagen I.

[0017] Tetrapeptide One embodiment of the present invention relates to a tetrapeptide of general formula: U-LSXX-Z (wherein L is used to represent the amino acid leucine and S is used to represent serine, according to internationally recognized one-letter amino acid codes), which can induce increased expression of extracellular matrix proteins in skin cells. X represents an amino acid selected from the group consisting of valine (V), aspartic acid (D), proline (P), glycine (G), and combinations thereof. The N-terminal U is H, -CO-R 1 , -SO2-R 1 Selected from the group consisting of a biotinyl group. The Z at the C-terminus is OH, OR 1 NHR 1 , or NR 1 R 2 Selected from the group consisting of R. 1 and R 2 The group is independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, sugar, and aryloxy groups, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated, and / or sulfur-containing, and the group may contain 1 to 24 carbon atoms and may contain one or more heteroatoms O, S, and / or N.

[0018] The tetrapeptide of the present invention is preferably selected from the group consisting of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12.

[0019] In another embodiment of the present invention, the tetrapeptide is preferably selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 9, and SEQ ID NO: 8.

[0020] In another embodiment of the present invention, the tetrapeptide is preferably selected from the group consisting of SEQ ID NO: 1.

[0021] In another embodiment of the present invention, the tetrapeptide is preferably selected from the group consisting of SEQ ID NO: 9.

[0022] In another embodiment of the present invention, the tetrapeptide is preferably selected from the group consisting of SEQ ID NO: 8.

[0023] In a preferred embodiment of the tetrapeptide combination of the present invention, tetrapeptide a) is selected from the group consisting of U-LSVD-Z, U-LSVP-Z, U-LSVG-Z, U-LSDV-Z, U-LSDP-Z, U-LSDG-Z, U-LSPV-Z, U-LSPD-Z, U-LSPG-Z, U-LSGV-Z, U-LSGD-Z, and U-LSGP-Z. In another embodiment, tetrapeptide is selected from the group consisting of U-LSVD-Z, U-LSPG-Z, and U-LSPD-Z. In another embodiment, tetrapeptide is Pal-LSVD-OH. In another embodiment, tetrapeptide is Pal-LSPG-OH. In another embodiment, tetrapeptide is Pal-LSPD-OH.

[0024] If the N-terminal Y is H, the amino acid is unmodified. If the C-terminal Z is OH, the amino acid is unmodified. Therefore, the tetrapeptide is not in a derivatized form. If U is not H and Z is not OH, the tetrapeptide is derivatized. Derivatization of tetrapeptides aims to increase the bioavailability of the peptide by improving its ability to pass through the skin. Increased bioavailability may be achieved by vectorization, such as encapsulation of the peptide. In a preferred embodiment, at least one end of the tetrapeptide is modified. In one embodiment, if U is H, Z must not be OH.

[0025] In a preferred embodiment of the present invention, the tetrapeptide is modified at its N-terminus and / or C-terminus. In one embodiment, the tetrapeptide is modified at its N-terminus. In one embodiment, the tetrapeptide is modified at its C-terminus. In one embodiment, the tetrapeptide is modified at both its N-terminus and C-terminus.

[0026] In a preferred embodiment of the present invention, R 1 and / or R 2 This is an alkyl chain of 1 to 24 carbon atoms, preferably a lipophilic alkyl chain of 3 to 24 carbon atoms.

[0027] In a further preferred embodiment of the present invention, U is -CO-R 1 The acyl group is Z, which is selected from the group consisting of OH, methoxy, ethoxy, and NH2, and is preferably OH. In further embodiments, U is preferably independently selected from the group consisting of octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18), biotinoyl, elidoyl, oleoyl, and lipoyl. In preferred embodiments of the present invention, u is selected from lauroyl (C12), myristoyl (C14), and palmitoyl (C16).

[0028] 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.

[0029] The tetrapeptide may contain D- or L-configured amino acids. The tetrapeptide may also contain an acid C-terminus such as -CO2H.

[0030] The amino acids constituting the tetrapeptide according to the present invention may be optically pure, or may consist of L or D isomers or mixtures thereof. The L isomer is naturally occurring and may be preferred. The present invention includes, for example, the modification of one or more amino acids and / or the addition of chemical functional groups to one or more amino acids, but also envisions further derivatives of tetrapeptides that do not involve changes in the carbon skeleton. The present invention also envisions further analogues of tetrapeptides with altered carbon skeletons, including the modification of one or more amino acids and / or the addition of chemical functional groups to one or more amino acids, and complexes of tetrapeptides with other chemical species, such as metal ions (e.g., copper, zinc, manganese, magnesium, etc.).

[0031] Tetrapeptides in salt form, including hydrochloride or acetate salts, may also be found.

[0032] Additive composition The tetrapeptide of the present invention is provided by the supplier to the compounder of the cosmetic composition as a concentrated additive composition. Therefore, the additive composition is an ingredient of the cosmetic composition. The additive composition contains the tetrapeptide at a concentration of 250 ppm to 1650 ppm. In an alternative embodiment, the additive composition contains the tetrapeptide at a concentration of 0.1 ppm to 50000 ppm. In a further alternative embodiment, the additive composition contains the tetrapeptide at a concentration of 1 ppm to 5000 ppm. In a further alternative embodiment, the additive composition contains the tetrapeptide at a concentration of 10 ppm to 500 ppm.

[0033] The additive composition may optionally contain, in addition to the tetrapeptide, components selected from the group consisting of water, surfactants, diols, triols, glycerin, thickeners, and mixtures thereof. All suitable surfactants, diols (also known as glycols), triols, glycerin, and thickener components may be incorporated into the additive composition of the present invention. Preferred surfactants for the additive composition are selected from the group consisting of alkyl polyglucosides (preferably decyl glucoside, coconut oil alkyl glucoside, lauryl glucoside), sodium lauroyl lactylate, polysorbate 20, polysorbate 60, sorbitan laurate, PEG / PPG-18 / 18 dimethicone, cetyl PEG / PPG-10 / 1 dimethicone, polyglyceryl-4 isostearate, hexyl laurate, steareth-21, steareth-2, and mixtures thereof.

[0034] Preferred diols are selected from the group consisting of pentylene glycol, caprylyl glycol, butylene glycol, dipropylene glycol, ethylhexylglycerin, propanediol, hexendiol, glycerol, butylene glycol, propylene glycol, isoprene glycol, dipropylene glycol, pentylene glycol, hexylene glycol, polypropylene glycol, butylene glycol, polyethylene glycol, sorbitol, glucitol, mannitol, hydroxypropyl sorbitol, erythritol, treitol, pentaerythritol, and xylitol.

[0035] Preferred triols are selected from the group consisting of hexanetriol, glycerin, ethoxylated glycerin, propoxylated glycerin, and mixtures thereof.

[0036] Preferred thickeners are selected from the group consisting of xanthan gum, ammonium acryloyldimethyltaurate / vinylpyrrolidone copolymer, dimethicone crosspolymer, carbomer, hydroxyethylcellulose, polyacrylamide, polyacrylate crosspolymer-6, and mixtures thereof.

[0037] Cosmetic composition The present invention also includes cosmetic compositions containing the tetrapeptide of the present invention. The tetrapeptide is incorporated into the cosmetic composition in an amount preferably 0.10 ppm to 10,000 ppm, preferably 0.50 ppm to 5,000 ppm, more preferably 1 ppm to 1,000 ppm, and most preferably 1 ppm to 500 ppm. These are also based on a % w / w basis. Therefore, 100,000 ppm is 10% of the weight of the emulsion.

[0038] A cosmetic composition is a product designed for use by consumers, and is preferably a facial skincare cosmetic composition.

[0039] The cosmetic composition of the present invention may be aqueous or non-aqueous, and may consist of a single-phase or multi-phase system. The composition may include, but is not limited to, liquids, gels, balms, oils, or solids. Single-phase or multi-phase compositions are envisioned. Multi-phase systems may include, but are not limited to, microemulsions, emulsions, and products having separate, isolated phases. Emulsions may include water-in-oil, oil-in-water, and multiple emulsions (e.g., water-in-oil-in-water or oil-in-water). Products having separate, isolated phases may include two-phase or three-phase systems in which individual aqueous or oil phases are clearly visible.

[0040] If the composition is aqueous, it preferably contains 10% to 99.9% by weight of water. In a preferred embodiment, the aqueous composition contains 20% to 80% by weight of water. In a preferred embodiment, the aqueous composition contains 40% to 70% by weight of water. If the composition is non-aqueous, it preferably contains 0% to a maximum of 10% of water, more specifically 0.1% to 8%, and most preferably 0.5% to 5% of water.

[0041] If the composition is an emulsion, the composition comprises an oil phase and an aqueous phase. The oil phase of the emulsion may be provided by any suitable oil component. Suitable oils for the oil phase include, for example, a) hydrocarbon oils, e.g., paraffin or mineral oil; b) waxes, e.g., beeswax or paraffin wax; c) natural oils, e.g., sunflower oil, apricot kernel oil, shea butter, or jojoba oil; d) silicone oils, e.g., dimethicone, silicone elastomer, cyclomethicone, or cetyl dimethicone; e) fatty acid esters and ethers, e.g., isopropyl palmitate or isopropyl myristate and polypropylene glycol-15 stearyl ether; f) aliphatic alcohols, e.g., cetyl alcohol or stearyl alcohol; or g) mixtures thereof, e.g., wax formulations commercially available under the trade name Cutina (BASF).

[0042] The emulsion may contain 0.1% to 55% of the oil phase relative to the weight of the emulsion. In one embodiment, the emulsion may contain 3% to 25% of the oil phase, more preferably 5% to 20% of the oil phase relative to the weight of the emulsion. In an alternative embodiment, the emulsion may contain 10% to 50% of the oil phase, more preferably 25% to 50% of the oil phase relative to the weight of the emulsion.

[0043] Preferably, the oil phase of the emulsion contains oil at a concentration of 50% to 100% of the weight of the oil phase. More preferably, the oil phase contains oil at a concentration of 60% to 100%, more preferably 70% to 100%, and even more preferably 80% to 100% of the weight of the oil phase. Alternatively, the oil phase of the emulsion may contain a combination of oil, wax, or butter. Waxes and butters are hydrocarbons consisting of long-chain aliphatic alkyl chains, which may contain aromatic groups. They are generally lipophilic and are usually solid or flexible at room temperature. The melting point varies depending on the alkyl chain, chain length, and association. Silicone waxes are preferred types of waxes that are alkylmethylsiloxane-based. Oils are usually lipophilic, liquid at room temperature, and have a lower molecular weight than waxes. If present, wax or butter may be present in up to 40% of the oil phase of the emulsion. More preferably, the oil phase may contain wax or butter at a concentration of up to 20% of the oil phase of the emulsion. In an alternative embodiment, the oil phase may contain wax or butter at a concentration of up to 10% of the oil phase of the emulsion.

[0044] Preferably, the oil phase of the water-in-oil emulsion contains a silicone oil. If present, the silicone-containing oil phase preferably contains an organopolysiloxane oil. The organopolysiloxane oil used in the composition may be a volatile silicone, a non-volatile silicone, or a mixture of volatile and non-volatile silicones. As used in this context, the term "non-volatile" refers to a silicone that is a liquid or gel under ambient conditions and has a flash point greater than 100°C (at 1 atmosphere). As used in this context, the term "volatile" refers to all other silicone oils. Suitable organopolysiloxanes can be selected from a wide variety of silicones with a broad range of volatility and viscosity. Examples of suitable organopolysiloxane oils include polyalkylsiloxanes, cyclic polyalkylsiloxanes, and polyalkylarylsiloxanes.

[0045] Organopolysiloxanes selected from the group consisting of polyalkylsiloxanes such as dimethicone and dimethiconol with low, intermediate, and high molecular weights, alkyl-substituted dimethicones, such as cetyldimethicone and caprylylmethicone, and cyclic organopolysiloxanes having 3 to 6 silicon atoms, such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, etc. (these are referred to as cyclomethicone) are preferred for use herein. Also mentioned are MQ-type and T-propyl-type silicone resins, also known as trimethylsiloxysilicate and polypropylsilsesquioxane, polyalkylarylsiloxanes, and mixtures thereof. Polyalkylsiloxanes and cyclomethicone are more preferred for use herein. Among polyalkylsiloxanes, dimethicone is preferred.

[0046] Alternatively, the silicone oil may be a silicone elastomer. Silicone elastomers that may be emulsifying or non-emulsifying crosslinked siloxane elastomers, or mixtures thereof, are suitable for use herein. There are no particular restrictions on the types of curable organopolysiloxane compositions that can serve as starting materials for crosslinked organopolysiloxane elastomers. Examples in this regard include addition-curable organopolysiloxane compositions cured under platinum metal catalyst action by an addition reaction between an SiH-containing diorganopolysiloxane and an organopolysiloxane having silicon-bonded vinyl groups; condensation-curable organopolysiloxane compositions cured in the presence of an organotin compound by a dehydrogenation reaction between a hydroxyl-terminated diorganopolysiloxane and an SiH-containing diorganopolysiloxane; and condensation-curable organopolysiloxane compositions cured in the presence of an organotin compound or titanate ester. Preferred silicone elastomers include dimethicone crosspolymer and polysilicone-11.

[0047] Preferably, the oil phase contains silicone, most preferably a silicone elastomer. Preferably, the emulsion composition contains 20% to 35% of the silicone elastomer raw material relative to the weight of the emulsion composition.

[0048] If the composition is a water-in-oil emulsion, the composition preferably contains an emulsifier. In a preferred embodiment, the composition contains 0.1% to 10% of the emulsifier, more preferably 0.25% to 7.5%, and even more preferably 0.5% to 5%, relative to the weight of the composition. The emulsifier helps to disperse and suspend the aqueous water phase in the oil phase.

[0049] emulsifier The composition of the present invention may contain an emulsifier. Suitable emulsifiers include all those known to those skilled in the art that are suitable for use in skincare products. Preferably, these emulsifiers have an HLB value of 14 or less, more preferably 2 to 14, and even more preferably 4 to 14.

[0050] Silicone emulsifiers are preferred. A wide variety of silicone emulsifiers are useful herein. These silicone emulsifiers are typically organically modified organopolysiloxanes, also known to those skilled in the art as silicone surfactants. Useful silicone emulsifiers include dimethicone copolyols. These materials are polydimethylsiloxanes modified to include polyether side chains such as polyethylene oxide chains, polypropylene oxide chains, mixtures of these chains, and chains containing portions derived from both ethylene oxide and propylene oxide. Other examples include alkyl-modified dimethicone copolyols, i.e., compounds containing C2-C30 pendant side chains. Further useful dimethicone copolyols include materials having various cationic, anionic, amphoteric, and zwitterionic pendant portions.

[0051] Non-limiting examples of dimethicone copolyols and other silicone surfactants useful as emulsifiers in this specification include polydimethylsiloxane polyether copolymers having polyethylene oxide pendant side chains, polydimethylsiloxane polyether copolymers having polypropylene oxide pendant side chains, polydimethylsiloxane polyether copolymers having mixed polyethylene oxide and polypropylene oxide pendant side chains, polydimethylsiloxane polyether copolymers having mixed poly(ethylene)(propylene) oxide pendant side chains, polydimethylsiloxane polyether copolymers having organobetaine pendant side chains, polydimethylsiloxane polyether copolymers having carboxylate pendant side chains, polydimethylsiloxane polyether copolymers having quaternary ammonium pendant side chains; and further modifications of the above copolymers, including linear, branched, or cyclic C2-C30 alkyl pendant moieties. A particularly preferred emulsifier is PEG / PPG-18 / 18 dimethicone.

[0052] Suitable cetyl dimethicone copolyols are commercially available as mixtures with polyglyceryl-4 isostearate and hexyl laurate, or as mixtures with hexyl laurate and polyglyceryl-3 oleate. Other non-limiting examples of dimethicone copolyols include lauryl dimethicone copolyol, dimethicone copolyol acetate, dimethicone copolyol adipate, dimethicone copolyol amine, dimethicone copolyol behenate, dimethicone copolyol butyl ether, dimethicone copolyol hydroxystearate, dimethicone copolyol isostearate, dimethicone copolyol laurate, dimethicone copolyol methyl ether, dimethicone copolyol phosphate, and dimethicone copolyol stearate.

[0053] Useful silicone-free emulsifiers in this specification include various nonionic and anionic emulsifiers such as sugar esters and polyesters, alkoxylated sugar esters and polyesters, C1-C30 fatty acid esters of C1-C30 aliphatic alcohols, alkoxylated derivatives of C1-C30 fatty acid esters of C1-C30 aliphatic alcohols, alkoxylated ethers of C1-C30 aliphatic alcohols, polyglyceryl esters of C1-C30 fatty acids, C1-C30 esters of polyols, C1-C30 ethers of polyols, alkyl phosphates, polyoxyalkylene fatty acid ether phosphates, fatty acid amides, acyl lactylates, soaps, and mixtures thereof. Non-limiting preferred examples of these silicone-free emulsifiers include polyethylene glycol 20 sorbitan monolaurate (polysorbate 20), polyethylene glycol 5 soy sterols, 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, and PEG-100 steareth-20. Examples include stearate, polyoxyethylene 20-sorbitan trioleate (polysorbate 85), sorbitan monolaurate, polyoxyethylene 4-lauryl ether sodium stearate, polyglyceryl-4 isostearate, hexyl laurate, steareth-20, ceteareth-20, PPG-2 methyl glucose ether distearate, ceteth-10, diethanolamine cetyl phosphate, glyceryl stearate, PEG-100 stearate, and mixtures thereof.

[0054] Further peptides The compositions of the present invention may contain further peptides. Preferably, the additional peptides are selected from the group consisting of dipeptides, tripeptides, additional tetrapeptides, pentapeptides, and mixtures thereof. A tripeptide means a compound containing a sequence of three amino acids. A tetrapeptide means a compound containing a sequence of four amino acids, and when further tetrapeptides are used, the tetrapeptides are referred to as "additional tetrapeptides." A pentapeptide means a compound containing a sequence of five amino acids.

[0055] Dipeptides: The compositions of the present invention include acetyl dipeptide-1 cetyl ester, aminohexanoic acid acetyl dipeptide-3, azera oil bis dipeptide-10, coumaroyl dipeptide-3, dicetyl dipeptide-9, dipeptide diaminobutyroyl benzylamide diacetate, dipeptide-1, dipeptide-10, dipeptide-11, dipeptide-12, dipeptide-15, dipeptide-16, dipeptide-17, dipeptide-18, dipeptide-19, dipeptide-2, dipeptide-20, dipeptide-3, dipeptide-4, dipeptide-5, dipeptide-6, dipeptide-7, dipeptide-8, dipeptide-8HCl, dipeptide The dipeptides may also include dipeptides selected from the group consisting of thio-9, hexanoyl dipeptide-3 norleucine acetate, methyl undecylenoyl dipeptide-16, nicotinoyl dipeptide-22, nicotinoyl dipeptide-23, nicotinoyl dipeptide-24, nicotinoyl dipeptide-26, oleoyl dipeptide-15, palmitoyl dipeptide-10, palmitoyl dipeptide-13, palmitoyl dipeptide-17, palmitoyl dipeptide-5 diaminobutyroyl hydroxythreonine, palmitoyl dipeptide-5 diaminohydroxybutyrate, palmitoyl dipeptide-7, and mixtures thereof.

[0056] The dipeptide is incorporated into the cosmetic composition of the present invention at a concentration of preferably 0.1 ppm to 50,000 ppm, more preferably 1 ppm to 5,000 ppm, and most preferably 10 ppm to 500 ppm.

[0057] Tripeptide: The emulsion of the present invention preferably contains a tripeptide. The tripeptide may be naturally occurring or of synthetic origin. Suitable tripeptides include tripeptides-1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, their derivatives, and mixtures thereof.

[0058] Particularly preferred tripeptides include one or more His-based tripeptides. However, another preferred tripeptide may be Arg-Lys-Arg. Particularly preferred tripeptides are based on the structure of GluU-His-Lys and its analogues and derivatives. These are collectively known herein as GHK-tripeptides. In fact, preferred tripeptides according to this embodiment of the present invention have precisely this amino acid sequence. Useful preferred tripeptide analogues herein include those in which one or more of the three amino acids are rearranged or rearranged within the sequence (e.g., GluU-Lys-His), and / or in which two or fewer amino acids are substituted (e.g., His-Ala-Orn). However, most preferably, the amino acid substituted with Gly includes an aliphatic side chain and is, for example, but not limited to, β-Ala, Ala, Val, Leu, Pro, sarcosine (Sar), and Ile. Ala, Leu, and Ile are most preferred. The most preferred amino acids to be substituted for Lys or His are those having a nitrogen-containing side chain that is mainly charged at pH 6, such as, but not limited to, Pro, Lys, Arg, His, desmosine, and isodesmosine. Most preferably, Lys is replaced with Orn, Arg, or citrulline.

[0059] Derivatives are also considered to be included in the term GHK-tripeptide according to the present invention (and therefore also in the more general term tripeptide). Examples of derivatives of GHK-tripeptide according to the present invention include the substituted and rearranged tripeptide derivatives described herein. These derivatives include, in particular, acyl derivatives which are tripeptides substituted with a hydroxyl group, an amino group, an acylamino group, a sulfate group, or a sulfide group, or which are unsubstituted with one or more linear or branched, long or short, saturated or unsaturated linear or branched groups, which may be derived from acetic acid, capric acid, lauric acid, myristic acid, octanoic acid, palmitic acid, stearic acid, behenic acid, linoleic acid, linolenic acid, lipoic acid, oleic acid, isostearic acid, elaidic acid, 2-ethylhexanoic acid, coconut oil fatty acid, tallow fatty acid, hydrogenated tallow fatty acid, palm kernel oil fatty acid, lanolin fatty acid, etc. Preferred examples of acyl groups include acetyl, palmitoyl, elidoyl, myristyl, biotinyl, and octanoyl groups. These may be substituted or unsubstituted. If substituted, they are preferably substituted with hydroxyl or sulfur-containing groups, such as, but not limited to, SO3H, SH, or SS.

[0060] His-based tripeptides contain at least one histidine amino acid. The other two amino acids in the sequence may be the same or different. Thus, but are not limited to, His-Xaa-Xaa, His-Xaa-Xbb, His-Xbb-Xaa, Xbb-His-Xbb, Xbb-His-Xaa, Xaa-His-Xbb, Xaa-Xaa-His, Xaa-Xbb-His, Xbb-Xaa-His, and Xbb-Xbb-His, where Xaa and Xbb are two different amino acids, either of which may be His. Preferably, at least one of the other amino acids is Gly, β-Ala, Ala, Val, Leu, Pro, sarcosine (Sar), or Ile. Preferably, at least one of the other amino acids is Pro, Lys, Arg, His, desmosine, and isodesmosine. Most preferably, Lys is replaced with Orn, Arg, or citrulline.

[0061] Derivatives are also considered to be included in the term His-based tripeptide according to the present invention (and therefore also in the more general term tripeptide). These derivatives include, in particular, acyl derivatives, which are tripeptides substituted with one or more linear or branched, long or short, saturated or unsaturated, substituted or unsubstituted acyl groups having 1 to 29 carbon atoms. The acyl groups that can be used are the same as those described for GHK-tripeptides.

[0062] A particularly preferred embodiment of the tripeptide according to the present invention comprises N-acyl-GluU-His-Lys, and most preferably comprises N-palmitoyl-GluU-His-Lys. Preferred commercially available compositions comprising tripeptides and tripeptide derivatives include SEDERMA's Biopeptide-CL, SEDERMA's Maxilip®, and SEDERMA's Biobustyl®.

[0063] If tripeptides are present, they are incorporated into the cosmetic composition in amounts preferably 0.10 ppm to 10,000 ppm, preferably 0.50 ppm to 5,000 ppm, more preferably 1 ppm to 1,000 ppm, and most preferably 1 ppm to 500 ppm. These amounts are based on a % w / w basis. Therefore, 100,000 ppm is 10% of the emulsion by weight.

[0064] Additional tetrapeptides: The cosmetic composition may also contain additional tetrapeptides. These may be one or more ligin-based tetrapeptides, one or more ALAMCAT-tetrapeptides, or mixtures thereof. These tetrapeptides may be naturally occurring or of synthetic origin. Suitable tetrapeptides for use in the compositions of the present invention include those selected from the group consisting of known tetrapeptides-1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 34, 35, their derivatives, and mixtures thereof.

[0065] The ligin-based tetrapeptides according to the present invention are based on the structure of GlU-Gln-Pro-Arg (ligin) and include its analogues and derivatives. Ligin is an additional tetrapeptide. Useful tetrapeptides of the present invention include ligin analogues in which one or more of the four amino acids are rearranged or repositioned within the sequence, and / or two or fewer amino acids are substituted (e.g., Ala-Gln-Thr-Arg). More preferably, at least one of the amino acids in the sequence is Pro or Arg, and most preferably, the tetrapeptide contains both Pro and Arg, although their order and position may differ. Amino acid substitutions may arise from any amino acids as defined herein. Particularly preferred ligin-based tetrapeptides include Xaa-Xbb-Arg-Xcc, Xaa-Xbb-Xcc-Pro, and Xaa-Xbb-Pro-Arg, where Xaa, Xbb-Pro-Xcc, Xaa-Xbb-Xcc-Arg, Xaa, Xbb, and Xcc may be the same or different, or selected from the following: Xaa is Gly or a substitute amino acid, Xbb is Gln or a substitute amino acid, and Xcc may be Pro or Arg or a substitute amino acid. The most preferred amino acids to be substituted for Gly include aliphatic side chains and include, for example, but are not limited to, β-Ala, Ala, Val, Leu, Pro, sarcosine (Sar), and Ile. The most preferred amino acids to substitute for Gln are those having a side chain containing an amine group that is mainly uncharged at a neutral pH (pH 6-7), such as, but not limited to, Asn, Lys, Orn, 5-hydroxyproline, citrulline, and canavanine. If Arg is substituted, it is preferably replaced with an amino acid having a side chain containing a nitrogen that is mainly charged at pH 6, such as, but not limited to, Pro, Lys, His, desmosine, and isodesmosine.

[0066] Derivatives are also considered to be included in the term ligin-based tetrapeptide (and therefore in the more general term tetrapeptide). Examples of derivatives include substituted and rearranged derivatives of ligin-based tetrapeptides described herein. These derivatives include, in particular, acyl derivatives, which are tetrapeptides substituted with or unsubstituted linear or branched, long or short, saturated or unsaturated groups having 1 to 29 carbon atoms, and either substituted with a hydroxyl group, amino group, aminoacyl group, sulfate group, or sulfide group. N-acyl derivatives include acyl groups that may be derived from acetic acid, capric acid, lauric acid, myristic acid, octanoic acid, palmitic acid, stearic acid, behenic acid, linoleic acid, linolenic acid, lipoic acid, oleic acid, isostearic acid, elaidic acid, 2-ethylhexanoic acid, coconut oil fatty acid, tallow fatty acid, hydrogenated tallow fatty acid, palm kernel oil fatty acid, lanolin fatty acid, etc. Preferred examples of acyl groups include acetyl, palmitoyl, elidoyl, myristyl, biotinyl, and octanoyl groups. These may be substituted or unsubstituted. If substituted, they are preferably substituted with hydroxyl or sulfur-containing groups, such as, but not limited to, SO3H, SH, or SS.

[0067] Derivatives are thought to include peptide-divalent ion complexes as well. Cu 2+ -Peptide derivatives are preferred because they can provide enhanced biological effects compared to peptides alone.

[0068] ALAMCAT tetrapeptides are tetrapeptides comprising at least one amino acid with a side chain containing an aliphatic group. These amino acids include, but are not limited to, Gly, β-Ala, Ala, Val, Leu, sarcosine (Sar), and Ile. These tetrapeptides also comprise at least one amino acid with a side chain containing at least one NH2 group. These amino acids comprise a side chain having an amine group that is predominantly uncharged at neutral pH (pH 6-7), and include, but are not limited to, Gln, Asn, Lys, Orn, 5-hydroxyproline, citrulline, and canavanine. ALAMCAT tetrapeptides comprise at least one amino acid with at least one side chain containing at least one cationic amine (the main chemical species is NH3). + NH2 + This also includes basic amino acids that are charged, i.e., positively charged at pH 6.0. These amino acids include, but are not limited to, Pro, Arg, Lys, His, desmosine, and isodesmosine. The remaining amino acids may be any of the above, but preferably contain an aliphatic group, a pendant amino group, or a pendant cationic group. Derivatives are also considered to be included in the term ALAMCAT tetrapeptide according to the present invention (and therefore also in the more general term tetrapeptide). These derivatives include, in particular, acyl derivatives, which are tetrapeptides substituted with one or more linear or branched, substituted or unsubstituted, long or short, saturated or unsaturated acyl groups having 1 to 29 carbon atoms. The acyl groups that can be used are the same as those described for ligin-based tetrapeptides.

[0069] A preferred embodiment comprises peptide E, arg-ser-arg-lys, N-acyl-GlU-Gln-Pro-Arg peptide, most preferably N-palmitoyl-GlU-Gln-Pro-Arg.

[0070] Preferred commercial sources of tetrapeptides include RIGIN, EYELISS, Haloxyl, and MATRIXYL 3000, commercially available from SEDERMA (France), which contain 50 ppm to 500 ppm of palmitoyl-GlU-Gln-Pro-Arg, as well as other components, such as peptides, chalcones, and additives. Tego Pep 417 is sold by Evonik. These may be used to prepare the compositions of the present invention by adding at least one tripeptide described herein to them.

[0071] If used, additional tetrapeptides are incorporated into the cosmetic composition in an amount of 0.1 ppm (0.00001% w / w (also referred to herein as "weight percent," "weight %," or simply "relative to weight")) to 10,000 ppm (1.0% w / w), preferably 0.5 ppm to 1,000 ppm (0.1% w / w), and most preferably 1 ppm to 500 ppm (0.05% w / w), relative to the weight of the composition.

[0072] A combination of tripeptides and additional tetrapeptides may be particularly preferred. If present, the preferred ratio of additional tetrapeptides to tripeptides, or in practice, the ratio of molecules having four amino acids to molecules having three amino acids, may be in the range of 100:1 to 1:100, more preferably 50:1 to 1:50, even more preferably 30:1 to 1:30, and even more preferably 10:1 to 1:10. Most preferably, the ratio of additional tetrapeptides to tripeptides is in the range of 3:1 to 1:3. These ratios are on a weight basis (%w / w, e.g., mg of pure peptide per kilogram in the final formulation). In particularly preferred embodiments, when considered in parts per million and based on the total weight of the composition, the amount of tripeptide used is greater than the amount of additional tetrapeptides used. In a particularly preferred embodiment, the cosmetic composition of the present invention comprises an additional tetrapeptide of the sequence GlU-Gln-Pro-Arg, its analogues and derivatives, combined with one or more tripeptides of the sequence GlU-His-Lys, its analogues and derivatives.

[0073] Pentapeptide The compositions of the present invention may optionally contain pentapeptides, derivatives of pentapeptides, and mixtures thereof. As used herein, "pentapeptide" refers to both naturally occurring pentapeptides and synthetic pentapeptides. Naturally occurring and commercially available compositions containing pentapeptides are also useful herein. Preferred pentapeptides are selected from the group consisting of pentapeptides-1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 24, 25, 26, 28, 29, 30, 31, 33, 34, 35, 36, 38, 39, their derivatives, and mixtures thereof.

[0074] Suitable pentapeptides for use in this specification are the lys-thr-thr-lys-ser, Arg-asp-lys-tyr-val pentapeptides (pentapeptide-1) and their derivatives. A preferred commercially available composition containing a pentapeptide derivative is Matrixyl, commercially available from Sederma (France), containing 100 ppm palmitoyl-lys-thr-thr-lys-ser.

[0075] When used, pentapeptides are incorporated into cosmetic compositions in amounts of 0.1 ppm (0.00001% w / w (also referred to herein as "weight percent," "weight %," or simply "relative to weight")) to 10,000 ppm (1.0% w / w), preferably 0.5 ppm to 1,000 ppm (0.1% w / w), and most preferably 1 ppm to 500 ppm (0.05% w / w), relative to the weight of the composition.

[0076] Matrix metalloproteinase inhibitors (MMPi) The term "matrix metalloproteinase inhibitor" refers to all molecules and / or plant or bacterial extracts that have inhibitory activity against at least one of the matrix metalloproteinases expressed or synthesized by or in the skin. The family of matrix metalloproteinases is formed from several clearly defined groups based on their similarities in structure and substrate specificity (Woessner JF, 1991, Faseb Journal, vol. 5, 2145). Among these groups are collagenases that can degrade fibrous collagen (MMP-1 or interstitial collagenase, MMP-8 or neutrophil collagenase, MMP-13 or collagenase 3, MMP-18 or collagenase 4), gelatinases that degrade type IV collagen or other denatured collagen forms (MMP-2 or gelatinase A (72kDa), MMP-9 or gelatinase B (92kDa)), stromelysin (MMP-3 or stromelysin) There are several types of enzymes (MMPs): tromelysin 1, MMP-10, or stromelysin 2, MMP-11, or stromelysin 3 (their broad activity range targets proteins in the extracellular matrix of the skin, such as glycoproteins (fibronectin, laminin) and proteoglycans), matrilysin (MMP-7), metalloelastase (MMP-12), or metalloproteinases (MMP-14, MMP-15, MMP-16, and MMP-17). Metalloproteinases (MMPs) are proteases that use metals (mainly zinc) coordinated to three cysteine ​​residues and methionine in their active site to degrade high molecular weight components (collagen, elastin, etc.) in the extracellular matrix and basal layer of the skin at a neutral pH. These enzymes are inactivated by metal chelating agents. The main regulators of MMP activity are tissue metalloproteinase inhibitors or TIMPs, such as TIMP-I, TIMP-2, TIMP-3, and TIMP-4 (Woessner JF, Faseb Journal, 1991). Furthermore, MMP expression is also regulated by growth factors, cytokines, oncogene products (ras, jun), or even matrix components.

[0077] According to the present invention, the term "matrix metalloproteinase inhibitor" means all molecules that can reduce the activity of MMPs with respect to gene expression (transcription and translation), activation of the enzyme precursor form of MMPs, or further local control of the active form. Furthermore, the metalloproteinase inhibitors according to the present invention may be naturally occurring or synthetically occurring MMP-1 inhibitors. The terms "naturally occurring" and "synthetically occurring" mean both metalloproteinase inhibitors in their pure state and metalloproteinase inhibitors in solution at various concentrations, but inhibitors referred to as naturally occurring are obtained from natural elements by various extraction methods (e.g., lycopene from tomatoes), while inhibitors of synthetic origin are anything obtained by chemical synthesis.

[0078] Preferred MMPi are selected from the group consisting of retinoids, N-acetylcysteine, glutathione, 2-furyldioxime, vitamin C, flavonoids, isoflavones, hydrolyzed rice protein, alfalfa extract, white lupin, jujube extract, dihydroxymethylchromone, kudzu extract, European grape extract, evening primrose extract, Anogeisus leiocarpus extract, and mixtures thereof.

[0079] If present, MMPi is present in a concentration of 0.01% to 10%, more preferably 0.1% to 5%, and most preferably 0.5% to 2.5% relative to the weight of the cosmetic composition.

[0080] Skin conditioning agent The composition of the present invention may optionally contain a skin conditioning agent. The skin conditioning agent may preferably be selected from the group consisting of humectants, emollients, moisturizers, or mixtures thereof. If present, they are preferably present in a concentration of 0.01% to 20%, more preferably 0.1% to 10%, and most preferably 0.5% to 7% based on the weight of the cosmetic composition.

[0081] 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, erythritol, glycerol, hexanetriol, butanetriol, (di)propylene glycol, butylene glycol, hexylene glycol, polyethylene glycol, sugars (such as fructose, glucose, xylose, honey, mannose, xylose), glucono delta-lactone, as well as starch and its derivatives, pyrrolidone, carboxylic acids, hyaluronic acid and its salts, lactamide monoethanolamine, acetamide monoethanolamine, panthenol, allantoin, and mixtures thereof.

[0082] More preferably, the skin conditioning agent is selected from the group consisting of glycerin, arabinogalactan, butylene glycol, hyaluronic acid, shea butter, propylene glycol, ethylhexylglycerin, hyaluronic acid salts, and mixtures thereof.

[0083] Antioxidants The composition of the present invention may optionally contain an antioxidant. Suitable antioxidants include: a) ascorbic acid, its salts, esters, glucosides and glucosamines, especially sodium ascorbyl phosphate, magnesium ascorbyl phosphate and ascorbyl palmitate; b) vitamin E (tocopherol) and its esters, especially tocopheryl acetate, and dimethylmethoxychromanol, a synthetic analog of γ-tocopherol sold by Lipotec SA (Polygon Industrial Camri Ral) under the trade name Lipochroman-6; c) herbal extracts, especially ginkgo biloba, e.g., available from Univar PLC under the trade name "Gingko Biloba Leaf Powder"; morus alba, e.g., available from Solavia under the trade name "Mulberry Concentrate"; oregano (origanum vulgare), e.g., available from S Black Ltd under the trade name "Pronalen Origanum HSC"; ginseng, e.g., S Black Available from Ltd under the trade name "Panax ginseng 1.1 extract 4294" or from Croda Chemicals Ltd as "Phytexcell Panax ginseng", birch extract, for example, available from Cosmetochem (UK) under the trade names "Super Herbasol Extract Birch" and "HP Herbasol Betula", and available from Blagden Chemicals under the trade names "Phytelene of Birch" and "Aqueous Spray Dried Birch", tea plant (camellia sinensis), for example, available from Nichimen Europe under the trade name "Herbal Extract Green Tea 75% Solids", rosemary (rosmarinus officinalis), for example, S.This includes ingredients available from Black under the trade name "Pronalen Rosemary," acerola cherry powder (for example, available from Gee Lawson as Acerola PE), Emblica extract sold by Merck Speciality Chemicals under the trade name Emblica®, and grape seed oil (for example, available from Chesham Chemicals Limited).

[0084] The amount of antioxidant used in a cosmetic composition is expressed as dry weight, as will be understood by those skilled in the art. The total amount of antioxidant optionally present in the composition may range from 0.005% to 10% by weight, preferably 0.5% to 5% of the composition's weight, and most preferably 0.2% to 1.5%.

[0085] Particularly preferred combinations of antioxidants exhibiting synergistic effects, 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, Morus alba, and rosemary; iv) Ginkgo biloba, phyllanthus emblica, and dimethylmethoxychromanol; v) Morus alba, Camellia sinensis, and dimethylmethoxychromanol; vi) Morus alba, Camellia sinensis, and tocopheryl acetate; vii) Panax ginseng, Morus alba, and oregano; viiii) Camellia sinensis, tocopheryl acetate, and dimethylmethoxychromanol; viv) Morus alba, tocopheryl acetate, and dimethylmethoxychromanol.

[0086] In these preferred combinations, (a) Panax ginseng is preferably present in an amount of 0.005% to 0.1%, more preferably 0.01% to 0.05% of the weight of the composition; (b) Morus alba is preferably present in an amount of 0.0005% to 0.01%, more preferably 0.001% to 0.005% of the weight of the composition; and (c) Sodium ascorbyl phosphate, magnesium ascorbyl phosphate, or ethyl ascorbic acid is preferably present in an amount of 0.05% to 2.5%, more preferably 0.1% to 2%, most preferably 0.15% to 1.5% of the weight of the composition. (d) Rosemary, oregano, or eucalyptus is preferably present in an amount of 0.01% to 0.5%, more preferably 0.05% to 0.2% of the weight of the composition; e) Dimethylmethoxychromanol is preferably present in an amount of 0.0005% to 0.1%, more preferably 0.005% to 0.05% of the weight of the composition; f) Tea plant is preferably present in an amount of 0.005% to 0.2%, more preferably 0.01% to 0.1%; g) Tocopherol acetate is preferably present in an amount of 0.01% to 0.5%, more preferably 0.05% to 0.25%.

[0087] vitamin The composition of the present invention may contain one or more vitamins. The composition may contain ascorbate, 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 also contain vitamin B, vitamin B derivatives, vitamins B1 to B12, and their derivatives. In a further embodiment, the composition contains niacinamide, which is a vitamin B3 derivative.

[0088] In an alternative embodiment of the present invention, 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 invention, the cosmetic composition comprises vitamin E, vitamin E derivatives, such as tocopherol and tocopheryl acetate, and their provitamins, such as panthenol, and mixtures thereof.

[0089] In further embodiments, the cosmetic composition of the present invention comprises retinoid compounds including retinoic acid, retinal hydrate, retinol, and derivatives thereof. In one embodiment, the cosmetic composition comprises retinyl palmitate, retinyl acetate, retinyl retinoic acid, retinyl propionate, retinyl ascorbate, retinyl linoleate, retinyl retinoic acid, sunflower seed oil fatty acid retinyl, and mixtures thereof.

[0090] The vitamin compounds may be included as substantially pure material or as extracts obtained by suitable physical and / or chemical isolation from natural sources (e.g., plants). In one embodiment, when the vitamin compounds are present in the composition of the present invention, the emulsion composition contains the vitamin compounds in an amount of about 0.0001% to 50%, more preferably 0.001% to 10%, even more preferably 0.01% to 8%, and even more preferably 0.1% to 5%, relative to the weight of the composition.

[0091] Salicylate compounds The compositions of the present invention may include salicylic acid compounds, esters thereof, salts thereof, or combinations thereof. In one embodiment of the compositions of the present invention, the salicylic acid compound preferably contains salicylic acid in an amount of 0.0001% to 25%, more preferably 0.001% to 15%, even more preferably 0.01% to 10%, still more preferably 0.1% to 5%, even more preferably 0.01% to 2%, and even more preferably 0.1% to 2%, based on the weight of the composition.

[0092] sunscreen The composition of the present invention may optionally contain a sunscreen component. The sunscreen may include an organic or inorganic sun filter, or a combination of both. Suitable inorganic sun filters include those selected from the group consisting of fine-particle titanium dioxide, fine-particle zinc oxide, boron nitride, and mixtures thereof.

[0093] Suitable organic sunscreens include those selected from the group consisting of: a) p-aminobenzoic acid, its esters and derivatives (e.g., 2-ethylhexyl p-dimethylaminobenzoate), b) methoxycinnamate esters (e.g., 2-ethylhexyl p-methoxycinnamate, 2-ethoxyethyl p-methoxycinnamate, or a,p-di-(p-methoxycinnamoyl)-a'-(2-ethylhexanoyl)-glycerin), c) benzophenone (e.g., oxybenzone), d) dibenzoylmethane, e.g. i) 4-(tert-butyl)-4'-methoxydibenzoylmethane, e) 2-phenylbenzimidazole-5-sulfonic acid and its salts, f) alkyl-ss,ss-diphenyl acrylate, e.g., alkyl-a-cyano-ss,ss-diphenyl acrylate, e.g., octocrylene, g) triazine, e.g., 2,4,6-trianilino-(p-carbo-2-ethyl-hexyl-1-oxy)-1,3,5-triazine, h) camphor derivatives, e.g., methylbenzylidene camphor, and i) mixtures thereof. Other preferred sunscreen ingredients include those selected from the group consisting of homosalate, ethylhexyl salicylate, diethylhexyl butamide triazone, bis-ethylhexyloxyphenol methoxyphenyl triazine, diethylamino hydroxybenzoyl hexyl benzoate, butyl methoxydibenzoylmethane, methylene bis-benzotriazoyl tetramethylbutylphenol, polysilicone-15, and mixtures thereof. The sunscreen is optionally present in an amount of 0.1% to 10% of the weight of the composition.

[0094] Other arbitrary components The composition of the present invention may optionally contain one or more of the following components: preservatives, such as 2-bromo-2-nitropropane-1,3-diol (bronopol, commercially available under the trade name Myacide®), benzyl alcohol, diazolidinyl urea, imidazolidinyl urea, methylparaben, phenoxyethanol, ethylparaben, propylparaben, sodium methylparaben, sodium dehydroacetate, polyhexamethylene biguanide hydrochloride, isothiazolone, and sodium propylparaben may preferably be added to the emulsion in an amount of 0.01% to 10% of the weight of the emulsion.

[0095] Thickeners, viscosity modifiers, and / or gelling agents, such as acrylic polymers, for example, those commercially available under the trade names Carbopol or Ultrez (Lubrizol), or modified celluloses, for example, hydroxyethylcellulose or hydroxypropylmethylcellulose commercially available under the trade name Natrosol (Hercules), amine oxides, ethylene oxide and propylene oxide block polymers (for example, those available from BASF (Wyandotte) under the trade name "Pluronic" (trademark)), PVM, MA, or decadien crosspolymers (available under the trade name Stabilez 60), ethoxylated aliphatic alcohols, salts (magnesium chloride, sodium chloride), Aristoflex AVC (Clariant), phthalamides, xanthan gum, sodium polyacrylate, polyvinyl alcohol, aliphatic alcohols, and alkylgalactomannan available from Hercules under the trade name N-Hance may preferably be added to the emulsion composition in an amount of 0.5% to 10% of the weight of the composition.

[0096] A metal ion chelating agent, such as ethylenediaminetetraacetic acid and its salts, may preferably be added to the emulsion composition in an amount of 0.005% to 0.5% of the weight of the composition.

[0097] The composition may also preferably contain waxes such as cocoa butter in an amount of 1% to 99% of the composition's weight.

[0098] The composition may also include a suitable cosmetically acceptable diluent, carrier, and / or spray agent, such as dimethyl ether.

[0099] The composition may also preferably contain a pearlescent agent, such as monoethanolamide stearate and / or mica, in an amount of 0.01% to 10% of the weight of the composition.

[0100] The fragrance may preferably be added in an amount of 0.01% to 2% relative to the weight of the composition, and the water-soluble dye such as tartrazine may preferably be added in a trace amount (e.g., 1 × 10) relative to the weight of the composition. -5 It may be added in an amount of 0.1% to 0.1%.

[0101] The composition may also contain pH adjusters, such as sodium hydroxide, aminomethylpropanol, and triethanolamine, preferably in an amount of 0.01% to 10% of the weight of the composition. The composition may be buffered by means known in the art, for example, by using a buffer system containing succinic acid, citric acid, lactic acid, and acceptable salts thereof, phosphoric acid, monosodium phosphate or disodium phosphate, and sodium carbonate. Preferably, the composition may have a pH of 3 to 10, more preferably 4 to 8.

[0102] How to use The present invention also relates to a method for stimulating the production of extracellular skin proteins, including collagen, fibrillin, fibronectin, and decorin, in humans using a tetrapeptide combination of the present invention that exhibits a synergistic effect. The method comprises administering the tetrapeptide composition according to the present invention and a cosmetic composition containing the same (for example, in a cosmetically effective amount or a therapeutically effective amount) to the human subject.

[0103] In one embodiment, the present invention provides the use of tetrapeptides or compositions described herein as a non-therapeutic cosmetic treatment for improving the condition of the skin and / or lines and / or wrinkles and / or imperfections.

[0104] In one embodiment, the present invention relates to a cosmetic method for improving the condition and / or appearance and / or lines and / or wrinkles of the skin, comprising topically administering a peptide combination or cosmetic composition of the present invention. [Examples]

[0105] The present invention is further illustrated by the following embodiments.

[0106] Examples of tetrapeptide synthesis General formula: pal-X 1 X 2 X 3 X 4 The tetrapeptide of the present invention having -OH is prepared by peptide synthesis. In the first step, X is synthesized in the presence of a coupling agent. 4 The N-terminus of is bonded to the resin via the terminal acidic functional group. Then, in the presence of a coupling agent, the N-terminal amine is bonded to the next amino acid X in the sequence. 3 The peptide is reacted with the other compound. The same process is repeated until the desired sequence is obtained, and a suitable C-terminal functional group is added. Suitable coupling agents include DCC (dicyclohexylcarbodiimide) / NHS (N-hydroxysuccinimide) or HBTU (2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate) / HOBT (1-hydroxybenzotriazole). The obtained peptide is then cleaved from the resin in an acidic medium, precipitated, washed and dried to obtain the peptide in solid form.

[0107] Examples of effectiveness The activity of the tetrapeptide of the present invention was evaluated using three different methods: A) ELISA assay, B) immunofluorescence assay, and C) liquid chromatography-tandem mass spectrometry (LC-MS / MS).

[0108] ELISA is a commonly used immunoassay to measure the presence and abundance of specific proteins (antibodies, antigens, proteins, and glycoproteins) in biological samples. In this case, ELISA is used to quantify the expression of collagen-1, decorin, and fibronectin, which are extracellular proteins of the skin. The amount of collagen-1 is assessed by the amount of PIP ("carboxy-terminal propeptide of procollagen-1"), a peptide fragment produced by the enzymatic degradation of procollagen present outside fibroblasts, in the supernatant of the culture medium.

[0109] Immunofluorescence is based on the use of antibodies that label specific proteins with fluorescent dyes such as fluorescein isothiocyanate (FITC). In the following experiment, indirect immunofluorescence is used, in which a primary antibody first recognizes and binds to a specific protein, in this case fibrillin-1, and then a secondary antibody conjugated with FITC, directed toward the primary antibody, is used for detection.

[0110] For all experiments, a control stock solution was prepared by dissolving the powdered peptide in DMSO (dimethyl sulfoxide solvent). The peptide powder was dissolved in DMSO at the recommended parts per million concentration, then further diluted with cell culture medium and mixed to obtain the desired peptide ratio.

[0111] The tetrapeptide of the present invention has been demonstrated to have a remarkably high effect on increasing the expression of ECM proteins. The test methods and data are shown below.

[0112] A) ELISA assay Normal human dermal fibroblasts (HDFs) were cultured for 72 hours in contact with a composition containing neither the tetrapeptide nor the peptide of the present invention (negative control). The culture supernatant was then removed, and the amount of extracellular skin protein was determined using an ELISA assay for the protein of interest. For ELISA quantification, Hoechst staining was used to calculate cell viability, allowing for weighting of skin protein levels against the number of viable cells.

[0113] The amount of collagen I is evaluated by the amount of PIP ("procollagen type I carboxy-terminal propeptide"), which is a peptide fragment produced by the enzymatic degradation of procollagen present outside fibroblasts in the supernatant of the culture medium.

[0114] result The following table (Table 1) shows the effect of LSXX tetrapeptides (columns 1-3) on ECM protein expression by fibroblasts, as measured by ELISA, compared to tetrapeptides that do not satisfy the LSXX structure (column 4). The peptide concentrations in each experiment are listed in the table below. Results are expressed as a percentage increase compared to the negative control.

[0115] [Table 1]

[0116] B) Immunofluorescence Fibrillin-1 expression was determined using immunofluorescence. Primary human dermal fibroblasts (HDF) were purchased from Promo Cell. These cells were derived from a 29-year-old female donor. The cells were grown in wells of a black-walled / clear-bottomed 96-well plate (Peirce, Thermo Fisher). The cells were cultured in HDF medium (PromoCell) supplemented with 1 ng / ml basic fibroblast growth factor (recombinant human) and 5 μg / ml insulin. The cells were cultured for 5 days in the presence of tetrapeptide, with the medium and peptide changed every 48 hours, followed by evaluation by immunofluorescence. At the time of treatment, the cells were in the 3rd or 4th passage. After 5 days, the medium was discarded and the cells were fixed with methanol. Fibrillin-1 fibrillation was examined using a fibrillin-1 monoclonal primary antibody designed to detect the fibrillin-1 protein (11C1.3; mouse monoclonal antibody (Thermo Fisher), 1:100 dilution, overnight). Next, fibrillin-1 fibrillation was examined using goat anti-mouse secondary IgG (Thermo Fisher) containing a fluorescent tag designed to reveal the binding pattern of the primary antibody (1 part antibody: 1000 parts buffer for 1 hour).

[0117] Antibody binding to fibrillin-1 fibers was visualized using a Nikon Eclipse 100 microscope with fluorescence settings and an excitation lens for fluorescein isothiocyanate (FITC). Images were acquired using a 6-second UV exposure. Using ImageJ software and a threshold of 235, the abundance and extent of fibrillin-1 fibers in each image were quantified, and fiber density was measured.

[0118] The results are expressed as the percentage increase in fibrillin abundance compared to the untreated control.

[0119] result Table 2 shows the fibrillin-1 expression in HDF cells treated with tetrapeptides that satisfy the LSXX structure (Pal-LSPG-OH, Pal-LSPD-OH, and Pal-LSVD-OH) and tetrapeptides that do not satisfy the LSXX structure (Pal-GYIL-OH). The peptide concentrations used resulted in the highest fibrillin-1 production yield.

[0120] [Table 2]

[0121] The above results demonstrate that the tetrapeptides of the present invention have a significant effect on enhancing ECM protein production compared to tetrapeptides that do not fall within the scope of the present invention.

[0122] C) Liquid chromatography-tandem mass spectrometry (LC-MS / MS) analysis After incubation with peptides, liquid chromatography-tandem mass spectrometry (LC-MS / MS) was used to quantify the difference in relative abundance between proteins identified in the secretome / matrisome compared to an untreated control. HDF from a 25-year-old donor, seeded at 50,000 cells per well, was cultured with either of the peptides dissolved in cell culture medium to achieve a final concentration of 8 ppm, or in a medium without any peptide as a negative control. Treated and control cells were tested in triplicates. Cells were cultured for 5 days in serum-supplemented medium as usual, followed by a further 2 days in serum-free medium (7 days of culture in total). Cell medium containing the secretome (protein secreted by cells) and the ECM containing the matrisome (a collection of ECM-related proteins), which had been decellularized by incubation with EDTA (ethylenediaminetetraacetic acid), were collected. The combined secretome and matrisome fractions were then analyzed by LC-MS / MS using the following protocol.

[0123] The proteins were denatured (in urea), reduced (in dithiothreitol), mechanically dissociated (using sonication), and then digested overnight with trypsin (SMART Digest® Trypsin Kit; Thermo Fisher). After digestion, impurities were removed from the samples by removing organic molecules and surfactants using two-phase extraction, and the samples were desalted using OLIGO® R3 Reversed Phase Resin (Thermo Fisher).

[0124] Samples (200 ng) were analyzed using an UltiMate® 3000 Rapid Separation Liquid Chromatograph connected to a Q Exactive® Hybrid Quadrupole-Orbitrap® mass spectrometer, with a 90-minute analysis time per sample. Spectral data were retrieved from the Uniprot human proteome database using Mascot v2.5.1. Subsequent protein identification and data-based quantification were performed using Progenesis QI. Normalized protein abundances were compared between treatments and controls for each peptide. Statistical analysis was performed within Progenesis QI using ANOVA between samples.

[0125] Mass spectrometry data for each peptide are shown in Table 3 and Figure 1 below. Changes in protein synthesis abundance due to each peptide, including changes in specific proteins and the protein families to which they belong, are described below (Table 3). Proteins identified by mass spectrometry (indicating p<0.01) were classified into functional protein families (proteins with similar functions) to obtain an overview of the effects of each peptide sequence on broader protein expression and, therefore, on metabolism within cell culture systems. These protein families were: antioxidants, cell stress proteins, ECM cleavage enzymes, and ECM adhesion proteins. All of these are functional protein families that potentially play important roles in skin repair and remodeling.

[0126] The bubble plot (Figure 1) shows the overall effect of each peptide tested on these four protein families. The bubble size was calculated by summing the percentage changes of all key proteins within the family that showed at least a significant enhancement tendency (p<0.1 or p<0.05), and then assigning the bubble size based on the percentile in which that percentage change would be located, taking into account the enhancements observed across all four protein families and all four peptide sequences tested. In the bubble plot, a larger bubble size indicates a stronger enhancement of the protein within that protein family.

[0127] result The results of the above mass spectrometry experiments, in which various tetrapeptides were applied to HDF to induce an extracellular protein expression response, are shown in Table 3 below. The protein family to which the protein belongs is also indicated. For comparison, the results of mass spectrometry using peptide sequences according to the present invention (columns 1 and 2) and peptide sequences not according to the present invention (columns 3 and 4) are also shown in the table.

[0128] [Table 3]

[0129] 1) Results of mass spectrometry after treatment with pal-LSVD-OH Treatment of human skin fibroblasts with the pal-LSVD-OH peptide resulted in an overall enhancement of protein synthesis compared to the control. Proteins that were either significantly enhanced or showed a trend of enhancement compared to the untreated control are shown in Table 3. Proteins identified as significantly enhanced (p<0.05) include the antioxidant PRDX4, the cellular stress protein HSPA8, the ECM cleavage enzyme CTSL, and the ECM adhesion protein CD44. Proteins that showed a trend of enhancement (0.05<p<0.1) include the antioxidant SOD1 and the cellular stress protein HSP90B1. These results can be compared to similar experiments in which HDF cells were treated with QTAV and EKGD, tetrapeptides not according to the present invention, and showed no or limited protein expression.

[0130] 2) Mass spectrometry results upon treatment with pal-LSPG-OH Treatment of HDF with the pal-LSPG-OH peptide resulted in an overall enhancement of protein synthesis compared to the control. Proteins that were either significantly enhanced or showed a trend of enhancement compared to the untreated control are shown in Table 3. Proteins identified as significantly enhanced (p<0.05) include the antioxidant PRDX4, the cellular stress proteins HSP90B1 and HSPA8, the ECM cleavage enzyme CTSL, and the ECM adhesion protein CD44. The antioxidant SOD1 showed a trend of enhancement by the tetrapeptide (0.05<p<0.1). These results can be compared to similar experiments in which HDF cells were treated with QTAV and EKGD, tetrapeptides not according to the present invention, and showed no or limited protein expression.

[0131] Figure 1 shows bubble plots illustrating the enhancement of functional protein families by peptides with various sequences. Larger bubble sizes indicate stronger enhancement. The tested peptides with the pal-LSXX-OH sequence strongly enhanced the antioxidant protein family, the cellular stress response protein family, the ECM adhesion protein family, and the ECM cleavage enzyme protein family. These enhancements were significantly stronger than those observed with peptides of different sequences.

[0132] Additive composition This specification includes examples of the preparation of the additive composition of the present invention.

[0133] To produce a tetrapeptide additive composition, the tetrapeptide prepared according to this specification is combined with an oily matrix containing a fatty acid ester, and the mixture is stirred and heated until the tetrapeptide is completely solubilized and the additive composition becomes clear. In a preferred example, 1200 ppm of tetrapeptide is used in the additive composition.

[0134] Examples of cosmetic compositions The tetrapeptide of the present invention can be incorporated into cosmetic compositions. Representative examples are described below.

[0135] Cosmetic Composition 1 - Representative Water-in-Oil Emulsion Cosmetic Composition

[0136] [Table 4]

[0137] Manufacturing method 1. Add dimethicone, dimethicone crosspolymer, PEG / PPG-18 / 18 dimethicone, polyglyceryl-4 isostearate, hexyl laurate, and cetyl PEG / PPG-10 / 1 dimethicone to the main container to prepare the oil phase. 2. Separately, water, magnesium sulfate, glycerin, phenoxyethanol, methylparaben, ethylparaben, peptides, propanediol, pentylene glycol, decyl glucoside, and water are weighed out and stirred until the solids are dissolved to prepare an aqueous phase. 3. Slowly add the aqueous phase to the oil phase under constant high-speed stirring (generating a vortex). Continue stirring for 5 minutes. 4. Use a Silverson mixer or equivalent to homogenize the product at 3500 rpm for 5 minutes.

[0138] Composition 2 - Typical Oil-in-Water Emulsion Cosmetic Composition

[0139] [Table 5]

[0140] Manufacturing method 1. Add glycerin to water and dissolve tetrasodium EDTA. 2. Using a homogenizer, sprinkle in the xanthan gum and continue homogenizing for 5 minutes or until hydrated. 3. Heat the aqueous phase to 70°C to 75°C. 4. Divide the oil phase into separate containers and heat to 70°C-75°C (dimethicone, cetearyl alcohol, glyceryl stearate, and PEG-100 stearate). Once it reaches that temperature, add sodium polyacrylate and stir. 5. Heat both phases to 70°C-75°C, add the oil phase to the aqueous phase, and homogenize for 2 minutes. 6. Add dimethicone crosspolymer and dimethicone, and homogenize for 2 minutes. 7. Cool to room temperature. 8. Add phenoxyethanol, methylparaben, ethylparaben, peptides, propanediol, pentylene glycol, decyl glucoside, and water, and stir. 9. Add water to reach the desired weight and stir until smooth.

[0141] Composition 3 - Typical gel-based cosmetic composition

[0142] [Table 6]

[0143] Manufacturing method 1. Add glycerin and propanediol to water and dissolve tetrasodium EDTA. 2. Mix with the acrylate / alkyl acrylate (C10-C30) crosspolymer using a homogenizer and continue homogenizing for 5 minutes or until hydrated. 3. Add potassium hydroxide and stir to form a gel. 4. Add denatured alcohol, phenoxyethanol, methylparaben, ethylparaben, peptides, propanediol, pentylene glycol, decyl glucoside, and water, and stir. 5. Add water to reach the desired weight and stir until smooth.

Claims

1. A cosmetic composition comprising a tetrapeptide capable of inducing increased expression of skin extracellular matrix proteins, selected from the group consisting of a tetrapeptide having the amino acid sequence U-LSVD-Z, a tetrapeptide having the amino acid sequence U-LSPG-Z, and a tetrapeptide having the amino acid sequence U-LSPD-Z, wherein according to the internationally accepted one-letter code for amino acids, L is used to represent the amino acid leucine, S is used to represent serine, V is used to represent valine, D is used to represent aspartic acid, P is used to represent proline, G is used to represent glycine, and U at the N-terminus is H, -CO-R １ , -SO ２ -R １ , or a biotinyl group, Z at the C-terminus is selected from the group consisting of OH, OR １ , NHR １ , or NR １ R ２ , and when U is H, Z must not be OH, R １ and R ２ are independently selected from the group consisting of alkyl, aryl, aralkyl, alkylaryl, alkoxy, sugar, and aryloxy groups, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated, and / or sulfur-containing, said groups containing 1 to 24 carbon atoms and optionally containing one or more heteroatoms O, S, and / or N. A cosmetic composition.

2. The cosmetic composition according to claim 1, wherein the tetrapeptide is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 9, and SEQ ID NO:

8.

3. The cosmetic composition according to claim 1 or 2, wherein the tetrapeptide is U-LSVD-Z.

4. The cosmetic composition according to claim 1 or 2, wherein the tetrapeptide is U-LSPG-Z.

5. The cosmetic composition according to claim 1 or 2, wherein the tetrapeptide is U-LSPD-Z.

6. The cosmetic composition according to any one of claims 1 to 5, wherein U of the tetrapeptide is independently selected from the group consisting of octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18), biotinoyl, elidoyl, oleoyl, and lipoyl.

7. The cosmetic composition according to any one of claims 1 to 6, wherein U of the tetrapeptide is independently selected from the group consisting of lauroyl (C12), myristoyl (C14), and palmitoyl (C16).

8. The cosmetic composition according to any one of claims 1 to 7, wherein the tetrapeptide is present in an amount of 0.1 ppm to 10,000 ppm relative to the weight of the composition.

9. The cosmetic composition according to any one of claims 1 to 8, further comprising additional further peptides selected from the group consisting of dipeptides, tripeptides, additional tetrapeptides, pentapeptides, and mixtures thereof.

10. Use of a tetrapeptide selected from the group consisting of a tetrapeptide having the amino acid sequence U-LSVD-Z, a tetrapeptide having the amino acid sequence U-LSPG-Z, and a tetrapeptide having the amino acid sequence U-LSPD-Z, for producing a cosmetic composition according to any one of claims 1 to 9 used for a cosmetic treatment to improve the condition of the skin and / or lines and / or wrinkles and / or defects.

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