Compounds useful in the treatment and / or care of skin, hair, nails and / or mucous membranes

Abstract

The present invention provides compounds of formula (I), R1-W m -X n -AA1-AA2-AA3-AA4-Y o -Z p -R2, its stereoisomers and / or cosmetically acceptable salts, wherein AA1 is Leu, Ile or Val, AA2 is Pro, Ala or Gly, AA3 is Val, Ile or Leu, and AA4 is Thr, Val or no amino acid, the compounds are useful for treating and / or preventing symptoms of skin aging, in particular for treating and / or preventing skin wrinkles, improving or maintaining skin firmness, treating and / or preventing the appearance of sagging skin, and / or lifting the skin.

Description

[Technical Field]

[0001] The present invention relates to compounds useful for the treatment and / or care of skin, hair, nails and / or mucous membranes. In particular, the compounds are useful for the treatment and / or prevention of skin aging, in particular for the treatment and / or prevention of skin wrinkles, improving or maintaining skin firmness, treating and / or preventing the appearance of sagging skin, and / or lifting the skin. The invention also extends to compositions comprising the compounds and to methods of treatment using the compounds. [Background technology]

[0002] The effects of aging play a major role in the appearance of skin, with the most noticeable signs of facial aging including the appearance of facial wrinkles and sagging skin.

[0003] One of the most common methods for reducing facial sagging is a facelift. A facelift, also known as a rhytidectomy, is a cosmetic surgery performed to reduce sagging skin or wrinkles in the cheeks and jawline, as well as to address other changes in facial shape associated with aging. During a facelift, flaps of skin on each side of the face are pulled back, and the tissue underneath is surgically remodeled to restore a more youthful facial contour. Nevertheless, facelifts can be associated with different complications and risks. As with any other type of surgery, facelifts carry the risk of bleeding, infection, and adverse reactions to anesthesia. Some other risks include hematoma, scarring, nerve damage, hair loss, and skin thinning. Furthermore, facelift results are not permanent. With age, facial skin may begin to sag again. Generally, a facelift can be expected to last 10 years.

[0004] Not surprisingly, there has been growing interest in alternative, non-invasive methods to reduce facial sagging and combat the effects of skin aging. Microcurrent stimulation (MES) is a facial cosmetic procedure that has gained increasing interest in recent years. MES is distinguished by the use of very small electrical currents (i.e., millionths of an ampere, e.g., 300-500 μA) that are barely perceptible but mimic the body's own bioelectric currents. MES is used as a cosmetic, non-therapeutic cosmetic procedure to improve skin rejuvenation. This is known as an effective, non-invasive, and inexpensive technique for combating the appearance of skin aging [Goldbert, A. et al. "Skin Rejuvenation with Non-Invasive Pulsed Electric Fields", (2015), Nature Scientific Reports, Vol. 5(10187), pp. 1-18; Seniee, F. et al. "Consider the effect of microcurrents on the variation of facial wrinkle trend, Randomized Clinical Trial Study", (2012), Life Science Journal Vol. 9(3), pp. 1184-1189].

[0005] The top layer of human skin is the epidermis, a stratified epithelium composed primarily of different layers of keratinocytes. Beneath the epidermis is the dermis, which is composed of fibroblasts, blood and lymphatic vessels, nerve fibers, and the extracellular matrix (ECM). The extracellular matrix provides the necessary mechanical support for the skin. Collagen is the main structural component of the extracellular matrix. At the cellular level, MES is known to stimulate the production of type 1 collagen in fibroblasts and promote fibroblast-induced contraction of collagen, which improves skin appearance [Varani, J. et al., "Decreased Collagen Production in Chronologically Aged Skin: Roles of Age-Dependent Alteration in Fibroblast Function and Defective Mechanical Stimulation," (2006), American Journal of Pathology, Vol. 168(6), pp. 1861-1868].

[0006] Muscle-binding-like protein 1 (MBNL1) is an RNA-binding protein that is involved in differentiation and maintenance of splicing patterns required for healthy muscle function. Increased MBNL1 protein expression in fibroblasts has been shown to activate the process of transdifferentiation into myofibroblasts, a cell type capable of releasing large amounts of extracellular matrix proteins such as collagen, elastin, and fibronectin. Electrical stimulation has been shown to induce the emergence and function of myofibroblasts [Davis, J. et al., "MBNL1-mediated regulation of differentiation RNAs promotes myofibroblast transformation and the fibrotic response," (2015), Nature Communications, vol. 6 (10084), pp. 1-14; Jennings, J.A. et al., "Regulation of gene expression in response to continuous low-intensity direct current electrical fields," (2007), Doctoral Thesis, pp. 1-208]. Compounds effective in upregulating expression of MBNL1 in skin or muscle cells have been demonstrated to be useful in maintaining or improving skin firmness, preventing the appearance of sagging skin, and / or reducing facial asymmetry (WO 2020 / 161683(A1)). Although effective as a cosmetic treatment, the use of MES poses several drawbacks. For example, the intensity of the current may depend on the individual's skin thickness, which is subject to changes due to age or external factors, and therefore, there is high intra- and inter-individual variability. In addition, the health of the skin may affect the required intensity. For example, older or deteriorated skin is less conductive (i.e., less permeable to microcurrents) than healthy skin. In some cases, poor electrical contact between the electrodes and the surface being treated can cause discomfort and pain to the user and, in extreme cases, skin irritation. Some MES devices use electrodes and adhesive gels to improve conductivity, but this is expensive and inconvenient, especially on the face, because the electrodes have limited room to move once placed. Furthermore, some devices can be difficult to precisely follow the contours of the body surface being treated, which is problematic because stimulation must be able to address precise areas. For example, some devices require the use of a mirror to position the device's wand on the appropriate part of the face and squeeze or stretch the skin. Finally, some potential users have negative preconceptions about MES treatments, i.e., a prejudice against using electricity on the face as an everyday cosmetic treatment. There is a need to provide alternative methods for reducing or preventing signs of skin aging, for example, to reduce skin wrinkles, improve skin firmness, and reduce the appearance of sagging skin. There is a need to provide methods that overcome the problems associated with known methods such as facelifts or MES. There is a need to find new active compounds that can reduce or prevent signs of skin aging. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] International Publication No. 2020 / 161683 [Non-patent literature]

[0008] [Non-Patent Document 1] Goldbert, A. et al. "Skin Rejuvenation with Non-Invasive Pulsed Electric Fields", (2015), Nature Scientific Reports, Vol 5(10187), pp. 1-18 [Non-Patent Document 2] Seniee, F. et al. "Consider of Micro-Current’s effect to variation of Facial Wrinkle trend, Randomized Clinical Trial Study", (2012), Life Science Journal Vol 9(3), pp. 1184-1189 [Non-Patent Document 3] Varani, J. et al. "Decreased Collagen Production in Chronologically Aged Skin: Roles of Age-Dependent Alteration in Fibroblast Function and Defective Mechanical Stimulation", (2006), American Journal of Pathology, Vol.168(6), pp. 1861-1868 [Non-Patent Document 4] Davis, J. et al. "MBNL1-mediated regulation of differentiation RNAs promotes myofibroblast transformation and the fibrotic response", (2015), Nature communications, vol.6(10084), pp. 1-14, Jennings, J.A., et al. "Regulation of gene expression in response to continuous low intensity direct current electrical fields", (2007), Doctoral Thesis, pp-1-208 [Summary of the Invention] [Means for solving the problem]

[0009] In a first aspect, the present invention provides a compound represented by formula (I): R1-W m -X n -AA1-AA2-AA3-AA4-Y o -Z p -R2(I), Stereoisomers and / or cosmetically acceptable salts thereof are provided, wherein: AA1 is Leu, Ile, or Val, AA2 is Pro Ala or Gly, AA3 is Val, Ile, or Leu; AA4 is Thr, Val or no amino acid; W, X, Y, and Z are each independently any amino acid; m, n, p, and q are each independently 0 or 1; m+n+p+q is less than or equal to 2, R1 is selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, an alicyclyl, a heterocyclyl, a heteroarylalkyl, an aryl, an aralkyl, and R5-CO-, and R5 is selected from the group consisting of H, an acyclic aliphatic group, an alicyclyl, an aryl, an aralkyl, a heterocyclyl, and a heteroarylalkyl; R2 is selected from the group consisting of -NR3R4, -OR3, -SR3, where R3 and R4 are independently selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, and aralkyl; R1 and R2 are not amino acids.

[0010] It has been found that the compounds of the present invention can reduce the appearance of wrinkles on the skin, improve skin firmness, reduce the appearance of sagging skin, and are effective in lifting the skin.Skin lifting means tightening the skin.Skin lifting / tightening provides the skin with the appearance of moving from a lower position to an upper position, so as to counteract any downward gravitational movement of the skin that increases with aging.Furthermore, it has been found that the compounds of the present invention can act as an effective alternative to commercially available microcurrent facial adjustment devices for treating and / or preventing the symptoms of skin aging.In particular, it has been found that the compounds of the present invention can reduce the appearance of wrinkles on the skin, improve skin firmness, reduce the appearance of sagging skin, and are as effective in lifting the skin as commercially available microcurrent facial adjustment devices.

[0011] In another aspect, the present invention provides a cosmetic composition comprising a compound of formula (I), its stereoisomers and / or its cosmetically acceptable salts, together with at least one cosmetically acceptable excipient or adjuvant.

[0012] In another aspect, the present invention provides the use of a compound of formula (I), its stereoisomer and / or a cosmetically acceptable salt thereof, or the use of a composition comprising a compound of formula (I), its stereoisomer and / or a cosmetically acceptable salt thereof, for the treatment and / or care of skin, hair, nails and / or mucous membranes. The present invention provides the use of a compound of formula (I), its stereoisomer and / or a cosmetically acceptable salt thereof, or the use of a cosmetic composition comprising a compound of formula (I), its stereoisomer and / or a cosmetically acceptable salt thereof, for the cosmetic non-therapeutic treatment and / or care of skin, hair, nails and / or mucous membranes. The cosmetic non-therapeutic treatment and / or care may be the prevention or treatment of symptoms of skin aging, the treatment and / or prevention of skin wrinkles, the improvement or maintenance of skin firmness, the treatment and / or prevention of the appearance of sagging skin, and / or skin lifting.

[0013] In another aspect, the present invention provides a method for treating and / or caring for the skin, hair, nails, and / or mucous membranes of a subject, the method comprising administering to the subject an effective amount of a compound of formula (I), its stereoisomer, and / or a cosmetically or pharmaceutically acceptable salt thereof, or a composition comprising any of them. In particular, the present invention provides a method for cosmetic non-therapeutic treatment and / or care of the skin, hair, nails, and / or mucous membranes of a subject, the method comprising administering to the subject a cosmetically effective amount of a compound of formula (I), its stereoisomer, and / or a cosmetically acceptable salt thereof, or a cosmetic composition comprising any of them. Typically, the compound is administered topically. The cosmetic non-therapeutic treatment and / or care can be the prevention or treatment of symptoms of skin aging, the treatment and / or prevention of skin wrinkles, the improvement or maintenance of skin firmness, the treatment and / or prevention of the appearance of sagging skin, and / or skin lifting. DETAILED DESCRIPTION OF THE INVENTION

[0014] definition In the context of the present invention, "skin" is understood to mean the multiple layers that make up the skin, including both the uppermost epidermis or stratum corneum to the lowermost or subcutaneous tissue. These layers are composed of different types of cells, such as keratinocytes, fibroblasts, melanocytes, mast cells, neurons and / or adipocytes, among others. The term "skin" also includes the scalp. The term "skin" includes mammalian skin, including human skin. Similarly, the term "hair, nails and mucous membranes" includes mammalian, e.g., human, hair, nails and mucous membranes.

[0015] As used herein, the term "treatment," without the proviso "cosmetic, non-therapeutic," refers to therapeutic methods including methods directed to the administration of a compound according to the present invention to reduce or eliminate a disease or disorder, or to reduce or eliminate one or more symptoms associated with the disease or disorder. The term "treatment," without the proviso "cosmetic, non-therapeutic," also encompasses therapeutic methods directed to reducing or eliminating the physiological consequences of a disease or disorder.

[0016] The terms "treatment" and "care," when accompanied by the proviso "cosmetic non-therapeutic," mean that the treatment or care is aimed at improving or maintaining the aesthetic appearance of the skin, hair, nails, and / or mucous membranes. In particular, the treatment may have the purpose of improving the cosmetic properties of the skin, hair, nails, and / or mucous membranes, such as, but not limited to, hydration level, elasticity, firmness, lustre, color, or texture, which are properties that affect the aesthetic appearance of the skin, hair, nails, and / or mucous membranes. The term "care" in this context refers to the maintenance of the properties of the skin, hair, nails, and / or mucous membranes, which are susceptible to improvement or maintenance by cosmetic treatment and / or care of the skin, hair, nails, and / or mucous membranes, both in healthy subjects and in subjects exhibiting diseases and / or disorders of the skin, hair, nails, and / or mucous membranes.

[0017] The term "prevention" as used herein refers to the ability of the compounds of the present invention to prevent, delay, or hinder the appearance or development of a disease or disorder, or to prevent, delay, or hinder changes in the cosmetic properties of the skin, mucous membranes, and / or hair. The term "prevention" as used herein is interchangeable with the term "inhibition," i.e., refers to the ability of the compounds of the present invention to inhibit the appearance or development of a disease or disorder, or to inhibit changes in the cosmetic properties of the skin, hair, nails, and / or mucous membranes.

[0018] In the context of the present invention, the term "aging" refers to the changes that the skin undergoes as a result of the intrinsic aging process (i.e., chronoaging) or as a result of the extrinsic aging process of the skin induced by environmental factors (i.e., environmental factors such as exposure to the sun (photoaging) or cigarette smoke, extreme climatic conditions of cold or wind, chemical pollutants or pollutants). In the context of the present invention, ageing includes all external and / or tactile perceptible changes such as, for example but not limited to, the development of discontinuities on the skin such as wrinkles, fine lines, expression lines, stretch marks, deep wrinkles, unevenness or roughness, an increase in pore size, loss of moisture, loss of elasticity, loss of firmness, loss of smoothness, loss of ability to recover from deformations, loss of resilience, sagging skin such as sagging cheeks, the appearance of dark circles or a double chin, changes in skin color such as age spots, redness, dark circles or the appearance of hyperpigmented areas such as age spots or freckles, abnormal differentiation, hyperkeratinization, elastosis, hyperkeratosis, hair loss, orange peel skin, loss of collagen structure and other histological changes in the stratum corneum, dermis, epidermis, vasculature (e.g. the appearance of spider veins or telangiectasias) or in tissues close to the skin, among others. The term "photoaging" encompasses a series of processes resulting from prolonged exposure of skin to ultraviolet radiation that results in premature aging of the skin, which exhibits the same physical characteristics as aging, including, but not limited to, laxity, sagging, changes in color or pigmentation irregularities, and abnormal and / or excessive keratinization. The sum of various environmental factors, such as exposure to tobacco smoke, exposure to pollution, and climatic conditions, such as cold and / or wind, also contribute to skin aging.

[0019] The abbreviations used for amino acids herein follow the rules of the IUPAC-IUB Commission of Biochemical Nomenclature set forth in Eur. J. Biochem., (1984), 138, 9-37. Thus, for example, Gly represents NH-CH-COOH, Gly- represents NH-CH-CO-, -Gly represents -NH-CH-COOH, and -Gly- represents -NH-CH-CO-. Thus, a hyphen representing a peptide bond eliminates the OH in the 1-carboxyl group of an amino acid (represented here in conventional non-ionized form) when positioned to the right of the symbol, and eliminates the H in the 2-amino group of an amino acid when positioned to the left of the symbol; both modifications can be applied to the same symbol (see Table 1).

[0020] [Table 1]

[0021] As used herein, the term "acyclic aliphatic group" includes linear (i.e., straight-line and unbranched) or branched, saturated or unsaturated hydrocarbyl groups such as alkyl, alkenyl, and alkynyl. Acyclic aliphatic groups can be substituted (mono- or poly-) or unsubstituted.

[0022] As used herein, the term "alkyl" includes both saturated, straight-chain and branched-chain alkyl groups, and the groups can be substituted (mono- or poly) or unsubstituted. The alkyl group is attached to the remainder of the molecule by a single bond. The alkyl group has 1 to 24, preferably 1 to 16, more preferably 1 to 14, even more preferably 1 to 12, and even more preferably 1, 2, 3, 4, 5, or 6 carbon atoms. The term "alkyl" includes, for example, methyl, ethyl, isopropyl, isobutyl, tert-butyl, 2-methylbutyl, heptyl, 5-methylhexyl, 2-ethylhexyl, octyl, decyl, dodecyl, lauryl, hexadecyl, octadecyl, and amyl.

[0023] As used herein, the term "alkenyl" refers to a group containing one or more carbon-carbon double bonds, which may be straight or branched, substituted (mono- or poly-) or unsubstituted. Preferably, an alkenyl has one, two, or three carbon-carbon double bonds. When more than one carbon-carbon double bond is present, the double bonds may be conjugated or unconjugated. Preferably, an alkenyl group has 2 to 24, preferably 2 to 16, more preferably 2 to 14, even more preferably 2 to 12, and even more preferably 2, 3, 4, 5, or 6 carbon atoms. An alkenyl group is attached to the remainder of the molecule by a single bond. The term "alkenyl" includes, for example, vinyl (-CH2=CH2), allyl (-CH2-CH=CH2), prenyl, oleyl, linoleyl, and the like.

[0024] The term "alkynyl" refers to a group containing one or more carbon-carbon triple bonds, which may be straight or branched, substituted (mono- or poly-) or unsubstituted. Preferably, an alkynyl group has one, two, or three carbon-carbon triple bonds. The triple bonds may be conjugated or unconjugated. An alkynyl group has 2 to 24, preferably 2 to 16, more preferably 2 to 14, even more preferably 2 to 12, and even more preferably 2, 3, 4, 5, or 6 carbon atoms. An alkynyl group is attached to the remainder of the molecule by a single bond. The term "alkynyl" includes, for example, but is not limited to, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, pentynyl such as 1-pentynyl, and the like. Alkynyl groups can also contain one or more carbon-carbon double bonds and include, but are not limited to, for example, but-1-en-3-ynyl and pent-4-en-1-ynyl groups, and the like.

[0025] The term "alicyclyl" is used herein to encompass aliphatic cyclic (alicyclic) groups, such as, but not limited to, cycloalkyl, cycloalkenyl, or cycloalkynyl groups. The term "alicyclyl" refers to a monoradical containing one or more carbon atom rings; the rings can be saturated (e.g., cyclohexyl) or unsaturated (e.g., cyclohexenyl), provided they are not aromatic. More specifically, alicylic groups contain 3 or more, 3 to 24, 3 to 12, or 6 to 12 ring carbon atoms. Alicyclic groups can be monocyclic, bicyclic, or tricyclic; the rings can be fused or linked by linking groups, such as single bonds or methylene or other alkylene groups. Alicyclic groups can be substituted (mono- or polycyclic) or unsubstituted. In one embodiment, an alicyclyl group is a 6-12 membered ring system consisting of carbon atoms and optionally containing one or two double bonds.

[0026] The term "cycloalkyl" refers to a saturated monocyclic or polycyclic alkyl group, which may be substituted (mono- or poly) or unsubstituted. A cycloalkyl group has 3 to 24, preferably 3 to 16, more preferably 3 to 14, even more preferably 3 to 12, and even more preferably 3, 4, 5, or 6 carbon atoms. A cycloalkyl group is attached to the remainder of the molecule by a single bond. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, methylcyclohexyl, dimethylcyclohexyl, octahydroindene, decahydronaphthalene, dodecahydrophenalene, and similar groups.

[0027] The term "cycloalkenyl" refers to a non-aromatic monocyclic or polycyclic alkenyl group, which may be substituted (mono- or poly) or unsubstituted. Cycloalkenyl groups have 5 to 24, preferably 5 to 16, more preferably 5 to 14, even more preferably 5 to 12, and even more preferably 5 or 6 carbon atoms. Cycloalkenyl groups are attached to the rest of the molecule by a single bond. Preferably, cycloalkenyl groups contain one, two, or three carbon-carbon double bonds. When more than one carbon-carbon double bond is present, the double bonds may be conjugated or non-conjugated. Cycloalkenyl groups include, but are not limited to, cyclopent-1-en-1-yl groups and the like.

[0028] The term "cycloalkynyl" refers to a non-aromatic monocyclic or polycyclic alkynyl group, which may be substituted (mono- or poly) or unsubstituted. A cycloalkynyl group has 8 to 24, preferably 8 to 16, more preferably 8 to 14, even more preferably 8 to 12, and even more preferably 8 or 9 carbon atoms and is attached to the remainder of the molecule by a single bond. Preferably, a cycloalkynyl group contains one, two, or three conjugated or non-conjugated carbon-carbon triple bonds. Examples of cycloalkenyl groups include, but are not limited to, cyclooct-2-yn-1-yl and the like. Cycloalkynyl groups also contain one or more carbon-carbon double bonds, including, but not limited to, cyclooct-4-en-2-ynyl and the like.

[0029] As used herein, the term "heterocyclyl" or "heterocyclic" refers to a 3- to 10-membered hydrocarbon ring system in which one or more atoms in one or more rings are heteroatoms (i.e., not carbon atoms). Thus, "heterocyclyl" or "heterocyclic" refers to a cyclic group whose ring atoms are composed of carbon and one or more heteroatoms. The heteroatoms may be bonded to H or substituents to satisfy valency. Preferably, one, two, or three of the ring carbon atoms are heteroatoms. Each heteroatom may be independently selected from the group consisting of O, N, S, P, and B, or the group consisting of O, N, and S. Heterocyclyl groups can be substituted (mono- or poly) or unsubstituted. Heterocyclyl groups can be monocyclic, bicyclic, or tricyclic, and the rings may be fused or joined by a linking group such as, for example, a single bond or a methylene group or other alkylene group. The nitrogen, carbon, or sulfur atoms present in the heterocyclyl radical may be optionally oxidized, and the nitrogen atom may be optionally quaternized. The heterocyclyl radical may be unsaturated or partially or fully saturated. The heterocyclyl radical may be aliphatic or aromatic. In one embodiment, the heterocyclyl is aliphatic (also known as heteroalicyclyl) and is a 3- to 10-membered ring system in which one or more ring atoms consist of carbon atoms and 1 to 4, or 1, 2, or 3, heteroatoms. In one embodiment, the heterocyclyl group is a 6- to 10-membered ring system in which one or more ring atoms consist of carbon atoms and 1 to 4 heteroatoms, and the ring system optionally contains one or two double bonds. In one embodiment, the heterocyclyl is aromatic (also known as heteroaryl) and is a 6- to 10-membered ring system in which one or more ring atoms consist of carbon atoms and 1 to 4, or 1, 2, or 3 heteroatoms. The term heterocyclyl is primarily intended to refer to a 5- or 6-membered ring. Examples of saturated heteroalicyclyl groups are dioxane, piperidine, piperazine, pyrrolidine, morpholine, and thiomorpholine. Examples of aromatic heterocyclyl groups are pyridine, pyrrole, furan, thiophene, benzofuran, imidazoline, quinoline, quinoline, pyridazine, and naphthyridine.

[0030] The term "aryl group" refers to an aromatic group having 6 to 30, preferably 6 to 18, more preferably 6 to 10, and even more preferably 6 or 10 carbon atoms. Aryl groups contain one, two, three, or four aromatic rings which may be linked by carbon-carbon bonds or fused together, such as, but not limited to, phenyl, naphthyl, diphenyl, indenyl, phenanthryl, or anthranyl, among others. Aryl groups can be substituted (mono- or poly-) or unsubstituted.

[0031] The term "aralkyl group" refers to an alkyl group substituted with an aromatic group having 7 to 24 carbon atoms, such as, but not limited to, -(CH2) 1-6 -phenyl, -(CH2) 1-6 -(1-naphthyl), -(CH2) 1-6 -(2-naphthyl), -(CH2) 1-6 Includes -CH(phenyl)2, and the like.

[0032] The term "heteroarylalkyl" refers to an alkyl group substituted with a heteroaryl (also known as heteroaromatic) group, as defined above, where the alkyl group has 1 to 6 carbon atoms and the heteroaryl group has 2 to 24 carbon atoms and 1 to 3 heteroatoms. Heteroarylalkyl groups include, but are not limited to, -(CH2) 1-6 -Imidazolyl, -(CH2) 1-6 -Triazolyl, -(CH2) 1-6 -Thienyl, -(CH2) 1-6 -Frill, -(CH2) 1-6 -pyrrolidinyl, and the like.

[0033] As is understood in the art, some degree of substitution may exist in the groups described above. In particular, where explicitly indicated, any of the above-identified groups may be substituted. The above-referenced substituents (radicals) are groups (or radicals) that are substituted at one or more available positions with one or more substituents. Preferably, the substitution occurs at one, two, or three positions, more preferably at one or two positions, and even more preferably at one position. Suitable substituents include, for example, C1-C4 alkyl, hydroxyl, C1-C4 alkoxyl, amino, amino-C1-C4 alkyl, C1-C4 carbonyloxyl, C1-C4 oxycarbonyl, halogen such as fluoride, chlorine, bromine, or iodine, cyano, nitro, azido, C1-C4 alkylsulfonyl, thiol, C1-C4 alkylthio, aryloxy such as phenoxyl, -NR b (C=NR b )NR b R c In particular, the following compounds are included: b and R c are independently H, C1-C4 alkyl, C2-C4 alkenyl, alkynyl, C3-C 10 Cycloalkyl, C6-C 18 Aryl, C7-C 17 It is selected from the group formed by aralkyl, 3- to 10-membered heterocyclyl or a protecting group for an amino group.

[0034] As will be understood, and as noted above, when R is described herein as being alkyl, alkenyl, alkynyl, alicyclyl, cycloalkyl, cycloalkenyl, cycloalkenyl, heterocyclyl, heterocyclic, heteroarylalkyl, aryl, or aralkyl, etc., it is meant that R is such a group. For example, when R is described as being alkyl, it is meant that R is an alkyl group.

[0035] As used herein, the term "comprising" is inclusive or open-ended and does not exclude additional, unrecited elements or method steps, and is intended to encompass the phrases "consisting essentially of" and "consisting of" as alternative embodiments, where "consisting of" excludes any elements or steps not specified, and "consisting essentially of" permits the inclusion of additional, unrecited elements or steps that do not materially affect the essential or basic and novel characteristics of the composition or method under consideration.

[0036] Compounds of the Invention In a first aspect, the present invention provides a compound of formula (I): R1-W m -X n -AA1-AA2-AA3-AA4-Y o -Z p -R2(I), With respect to stereoisomers and / or cosmetically acceptable salts thereof, the formula: AA1 is Leu, Ile, or Val, AA2 is Pro Ala or Gly, AA3 is Val, Ile, or Leu; AA4 is Thr, Val or no amino acid; W, X, Y, and Z are each independently any amino acid; m, n, p, and q are each independently 0 or 1; m+n+p+q is less than or equal to 2, R1 is selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, an alicyclyl, a heterocyclyl, a heteroarylalkyl, an aryl, an aralkyl, and R5-CO-, and R5 is selected from the group consisting of H, an acyclic aliphatic group, an alicyclyl, an aryl, an aralkyl, a heterocyclyl, and a heteroarylalkyl; R2 is selected from the group consisting of -NR3R4, -OR3, -SR3, where R3 and R4 are independently selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, and aralkyl; R1 and R2 are not amino acids.

[0037] The compounds of formula (I) are peptides containing 3, 4, 5, or 6 amino acids linked in a chain, where R1 is attached to the amino terminus (N-terminus) of the peptide and R2 is attached to the carboxy terminus (C-terminus) of the peptide.

[0038] R1 is H, a polymer derived from polyethylene glycol having a molecular weight comprised between 200 and 35,000 daltons, and R5-CO- (wherein R5 is C1-C 24 Alkyl, C2-C 24 Alkenyl, C2-C 24 Alkynyl, C3-C 24 Cycloalkyl, C5-C 24 Cycloalkenyl, C8-C 24 Cycloalkynyl, C6-C 30 Aryl, C7-C 24 and heteroarylalkyl containing 2 to 24 carbon atoms and 1 to 3 heteroatoms, wherein the alkyl group has 1 to 6 carbon atoms.

[0039] R1 is H and R5—CO— (wherein R5 is C1 to C 18 Alkyl, C2-C 24 Alkenyl, C3-C 24 the group consisting of cycloalkyl, or C1-C 16 Alkyl, C2-C 18The R5-CO- group can be selected from the group consisting of acetyl (CH3-CO-, abbreviated herein as "Ac-"), myristoyl (abbreviated herein as "Myr-"), aryl (CH3-(CH2)), methyl (C3-C7 ... 12 —CO—), and palmitoyl (CH—(CH), abbreviated herein as “Palm-”) 14 -CO-) and other alkanoyl groups.

[0040] R1 can be selected from the group consisting of H and acetyl, tert-butanoyl, prenyl, hexanoyl, 2-methylhexanoyl, cyclohexanecarboxyl, octanoyl, decanoyl, lauroyl, myristoyl, palmitoyl, stearoyl, oleoyl, and linoleoyl.

[0041] R1 is H and R5—CO— (wherein R5 is C1 to C 16 Alkyl or C2-C 18 alkenyl).

[0042] R1 is H and R5—CO— (wherein R5 is C1 to C 15 and the aryl group may be selected from the group consisting of alkyl.

[0043] R1 can be selected from the group consisting of H, acetyl and palmitoyl. In particular, R1 is H.

[0044] R2 is -NR3R4, -OR3, -SR3 (wherein R3 and R4 are independently H, a polymer derived from polyethylene glycol, C1-C 24 Alkyl, C2-C 24 Alkenyl, C2-C 24 Alkynyl, C3-C 24 Cycloalkyl, C5-C 24 Cycloalkenyl, C8-C 24 Cycloalkynyl, C6-C 30 Aryl, C7-C 24aralkyl, 3-10 membered heterocyclyl ring, and heteroarylalkyl containing 2-24 carbon atoms and 1-3 heteroatoms, wherein the alkyl group has 1-6 carbon atoms. Optionally, R3 and R4 can be linked by a saturated or unsaturated carbon-carbon bond to form a ring with the nitrogen atom.

[0045] R2 can be -NR3R4 or -OR3. R3 and R4 can be independently selected from the group consisting of H, polymers derived from polyethylene glycol having a molecular weight of 200 to 35,000 daltons, methyl, ethyl, hexyl, dodecyl, and hexadecyl. Alternatively, R3 and R4 can be independently selected from the group consisting of H and C1-C 16 In one embodiment, R2 is not OR3, wherein R3 is a methyl group, i.e., R2 is not OCH3. In one embodiment, R3 is H and R4 is H and C1-C1 alkyl, including methyl, ethyl, hexyl, dodecyl, and hexadecyl. 16 alkyl.

[0046] R2 is -OH, -NH2, and -NHR4 (wherein R4 is C1 to C 16 alkyl, or C1-C3 alkyl, or C1-C2 alkyl).

[0047] R2 can be -OH or -NH2. In particular, R2 is OH.

[0048] R1 is H and R5—CO— (wherein R5 is C1 to C 18 Alkyl, C2-C 24 Alkenyl, C3-C 24 cycloalkyl), and R2 can be selected from the group consisting of -NR3R4 or -OR3 (wherein R3 and R4 are independently selected from H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16It may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0049] R1 can be selected from the group consisting of H and acetyl, tert-butanoyl, prenyl, hexanoyl, 2-methylhexanoyl, cyclohexanecarboxyl, octanoyl, decanoyl, lauroyl, myristoyl, palmitoyl, stearoyl, oleoyl, and linoleoyl; R2 can be -NR3R4 or -OR3, where R3 and R4 are independently selected from H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16 It may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0050] R1 is H and R5—CO— (wherein R5 is C1 to C 16 Alkyl or C2-C 18 alkenyl), and R2 can be selected from the group consisting of -NR3R4 or -OR3 (wherein R3 and R4 are independently selected from H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16 It may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0051] R1 can be selected from the group consisting of H, acetyl, myristoyl, or palmitoyl, and R2 can be -NR3R4 or -OR3 (wherein R3 and R4 are independently selected from H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16It may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0052] R1 is H and R5—CO— (wherein R5 is C1 to C 15 alkyl), and R2 may be selected from the group consisting of -NR3R4 or -OR3 (wherein R3 and R4 are independently H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16 It may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0053] R1 can be selected from the group consisting of H, acetyl, and palmitoyl, and R2 can be -NR3R4 or -OR3 (wherein R3 and R4 are independently H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16 It may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0054] R1 can be H and R2 can be -NR3R4 or -OR3 (wherein R3 and R4 are independently H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16 It may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0055] R1 can be H and R2 can be -NR3R4 (wherein R3 and R4 are independently H and C1-C 16In this embodiment, R3 can be H and R4 can be H, C1-C 16 R2 may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -NH2 and -NHR4 (wherein R4 is C1-C3 alkyl). R2 may be -NH2.

[0056] R1 can be H and R2 can be -OH or -NH2. R1 can be acetyl and R2 can be -OH or -NH2. R1 can be acetyl and R2 can be -NH2. R1 can be palmitoyl and R2 can be -OH.

[0057] The most preferred structure of the polymer derived from polyethylene glycol is the group (-CH2-CH2-O) r -H (wherein r is a number between 4 and 795), and

[0058] [ka] (wherein s is a number from 1 to 125).

[0059] The compound of formula (I) may have at least one of the following conditions: R1 is not H and R2 is not OH. That is, compounds of formula (I) are provided wherein R1 is not H and / or R2 is not OH.

[0060] In the compound of formula (I), AA1 is selected from the group consisting of Leu, Ile and Val, AA2 is selected from the group consisting of Pro, Ala and Gly, AA3 is selected from the group consisting of Val, Ile and Leu, and AA4 is selected from the group consisting of Thr, Val and no amino acid. When AA4 is no amino acid, it means that the amino acid AA4 is not present in the compound.

[0061] AA1 can be selected from the group consisting of Leu and Val, for example, in formula (I), AA1 is selected from the group consisting of Leu and Val, AA2 is selected from the group consisting of Pro, Ala and Gly, AA3 is selected from the group consisting of Val, Ile and Leu, and AA4 is selected from the group consisting of Thr, Val and no amino acid.

[0062] AA1 can be Val, for example, in formula (I), AA1 is Val, AA2 is selected from the group consisting of Pro, Ala and Gly, AA3 is selected from the group consisting of Val, Ile and Leu, and AA4 is selected from the group consisting of Thr, Val and no amino acid.

[0063] AA2 can be Pro, for example, in formula (I), AA1 is selected from the group consisting of Leu, Ile, and Val, AA2 is Pro, AA3 is selected from the group consisting of Val, Ile, and Leu, and AA4 is selected from the group consisting of Thr, Val, and no amino acid.

[0064] AA3 can be Val or Leu, for example, in formula (I), AA1 is selected from the group consisting of Leu, Ile, and Val, AA2 is selected from the group consisting of Pro, Ala, and Gly, AA3 is selected from the group consisting of Val and Leu, and AA4 is selected from the group consisting of Thr, Val, and no amino acid.

[0065] AA3 can be Val, for example, in formula (I), AA1 is selected from the group consisting of Leu, Ile and Val, AA2 is selected from the group consisting of Pro, Ala and Gly, AA3 is Val, and AA4 is selected from the group consisting of Thr, Val and no amino acid.

[0066] AA4 may be selected from the group consisting of Thr and Val, for example, in formula (I), AA1 is selected from the group consisting of Leu, Ile and Val, AA2 is selected from the group consisting of Pro, Ala and Gly, AA3 is selected from the group consisting of Val, Ile and Leu, and AA4 is selected from the group consisting of Thr and Val.

[0067] AA4 may be selected from the group consisting of Thr and no amino acid, for example, in formula (I), AA1 is selected from the group consisting of Leu, Ile and Val, AA2 is selected from the group consisting of Pro, Ala and Gly, AA3 is selected from the group consisting of Val, Ile and Leu, and AA4 is selected from the group consisting of Thr and no amino acid.

[0068] Compounds of formula (I) may have the proviso that if there is no amino acid at position AA4, then AA1 is Leu.

[0069] Compounds of formula (I) may have the proviso that if there is no amino acid at position AA4, then AA2 is Pro.

[0070] Compounds of formula (I) may have the proviso that if there is no amino acid at position AA4, then AA3 is Val.

[0071] The compound of formula (I) may have the proviso that it is not H-Lys-Leu-Pro-Val-Thr-OH or H-Leu-Pro-Val-Thr-Leu-Arg-OH.

[0072] The compound of formula (I) may have the proviso that it is not H-Leu-Pro-Ile-Thr-OH, H-Leu-Pro-Leu-Thr-OH, H-Leu-Pro-Val-Thr-Gly-OH, H-Lys-Leu-Pro-Val-Thr-OH or H-Leu-Pro-Val-Thr-Leu-Arg-OH.

[0073] In an exemplary embodiment of a compound of Formula (I), AA1 is Leu, AA2 is Pro, AA3 is Val, and AA4 is Thr; AA1 is Leu, AA2 is Ala, AA3 is Val, and AA4 is Thr; AA1 is Leu, AA2 is Pro, AA3 is Ile, and AA4 is Thr; AA1 is Val, AA2 is Pro, AA3 is Val, and AA4 is Thr; AA1 is Leu, AA2 is Gly, AA3 is Val, and AA4 is Thr; AA1 is Leu, AA2 is Pro, AA3 is Leu, and AA4 is Thr; AA1 is Leu, AA2 is Pro, and AA3 is Val; and AA1 is Ile, AA2 is Pro, AA3 is Ile, and AA4 is Thr.

[0074] In an exemplary embodiment of a compound of Formula (I), AA1 is Leu, AA2 is Pro, AA3 is Val, AA4 is Thr, R1 is H, and R2 is OH or NH2; AA1 is Leu, AA2 is Pro, AA3 is Val, AA4 is Thr, R1 is H or Ac, and R2 is NH2; and AA1 is Leu, AA2 is Pro, AA3 is Leu, AA4 is Thr, R1 is H, and R2 is OH.

[0075] The compounds of formula (I), their stereoisomers, and / or their cosmetically or pharmaceutically acceptable salts may be selected from the amino acid sequences listed in Table 2, which details the sequence identifiers of the amino acid sequences.

[0076] [Table 2]

[0077] Compounds of formula (I) include each of the amino acid sequences of Table 2 in which one of the amino acids AA1-AA4 is replaced by a replacement amino acid, selected from the alternative amino acids listed for the amino acid to be replaced in formula (I) above. The replacement amino acid is different from the amino acid being replaced. In the case of AA4, the replacement amino acid can be no amino acid. Thus, for example, the present invention provides compounds of formula (I) corresponding to SEQ ID NO: 1 in which one of the amino acids AA1-AA4 is replaced by an amino acid, where Leu (AA1) is replaced by Ile or Val, Pro (AA2) is replaced by Ala or Gly, Val (AA3) is replaced by Ile or Leu, and Thr (AA4) is replaced by Val or no amino acid.

[0078] In the amino acid sequences of Table 2, R1 and R2 are H and OH, respectively. Compounds of the invention include each of the sequences of Table 2 modified at the N-terminus and C-terminus by other R1 and R2 groups, respectively, as defined herein for Formula (I). For example, compounds of the invention include each sequence of Table 2, wherein when the N-terminal amino acid residue terminates in R1, as defined above for Formula (I), R1 is not H, and alternatively or additionally, when the C-terminal amino acid residue optionally terminates in R2, as defined above for Formula (I), R2 is not H.

[0079] Thus, in particular, the compound according to formula (I) may be any of the amino acid sequences SEQ ID NOs: 1-10, and stereoisomers thereof, and / or cosmetically acceptable salts thereof, optionally having its N-terminal amino acid modified by R1 as defined above for formula (I) (wherein R1 is not H), or alternatively, or in addition, having its C-terminal amino acid modified by R2 as defined above for formula (I) (wherein R2 is not OH). The amino acid sequence may be SEQ ID NO: 1.

[0080] The compounds of formula (I) can exist as stereoisomers or mixtures of stereoisomers; for example, the amino acids comprising them can have L-, D-, or racemic configurations independently of each other. Therefore, depending on the number of asymmetric carbons and whether an isomer or isomeric mixture is present, it is possible to obtain a racemic or diastereomeric mixture in addition to an isomeric mixture, or to obtain a pure diastereomer or enantiomer. A preferred structure of the compounds of the present invention is a pure isomer, i.e., an enantiomer or diastereomer. For example, if it is stated that AA2 can be Ala, it is understood that AA2 is selected from L-Ala, D-Ala, or a mixture of both, racemic or non-racemic, unless otherwise specified. The preparation procedures described herein allow one skilled in the art to obtain each stereoisomer of the compounds of the present invention by selecting the amino acid of the correct configuration.

[0081] In the context of the present invention, the term "amino acid" includes amino acids encoded by the genetic code and non-encoded amino acids, whether naturally occurring or not. Examples of non-encoded amino acids include, but are not limited to, citrulline, ornithine, sarcosine, desmosine, norvaline, 4-aminobutyric acid, 2-aminobutyric acid, 2-aminoisobutyric acid, 6-aminohexanoic acid, 1-naphthylalanine, 2-naphthylalanine, 2-aminobenzoic acid, 4-aminobenzoic acid, 4-chlorophenylalanine, 2,3-diaminopropionic acid, 2,4-diaminobutyric acid, cycloserine, carnitine, cystine, penicillamine, pyroglutamic acid, thienylalanine, hydroxyproline, allo-isoleucine, allo-threonine, isonipecotic acid, isoserine, phenylglycine, statin, β-alanine, norleucine, N-methylamino acids, α-amino acids and β-amino acids, and derivatives thereof, among others. A list of unnatural amino acids can be found in the article "Unusual amino acids in peptide synthesis" by DC Roberts and F. Vellaccio (The Peptides, Vol. 5 (1983), Chapter VI, Gross E. and Meienhofer J., Eds., Academic Press, New York, USA) or in commercial catalogs of companies specializing in this field.

[0082] When any of W, X, Y, and / or Z is present, i.e., when at least one of n, m, p, or q is not 0, it is understood that the nature of W, X, Y, and / or Z does not interfere with, but rather contributes to, or does not affect, the activity of the compounds of the present invention. W, X, Y, and Z can each independently be selected from the group consisting of Ala, Gly, Val, and He. W, X, Y, and Z can each independently be selected from the group consisting of Ala, Val, and He. W, X, Y, and Z can each independently be selected from the group consisting of Ala, Gly, and Val. W, X, Y, and Z can each independently be Ala or Gly. W, X, Y, and Z can each independently be Ala.

[0083] Each of m, n, p, and q may be 0, i.e., the compound of formula (I) is a peptide containing 3 or 4 amino acids linked in a chain (e.g., AA1-AA2-AA3-AA4 or AA1-AA2-AA3). Alternatively, the sum of m, n, p, and q may be 1, i.e., the compound of formula (I) is a peptide containing 4 or 5 amino acids linked in a chain. Alternatively, the sum of m, n, p, and q may be 2, i.e., the compound of formula (I) is a peptide containing 5 or 6 amino acids linked in a chain.

[0084] In particular, the compound of formula (I) may be selected from the group of compounds listed in Table 3, their stereoisomers, and / or cosmetically acceptable salts thereof.

[0085] [Table 3]

[0086] Compounds of formula (I) include each of the compounds in Table 3 in which one of the amino acids AA1-AA4 is replaced by a replacement amino acid, where the replacement amino acid is selected from the alternative amino acids listed for the amino acid being replaced in formula (I) above. The replacement amino acid is different from the amino acid being replaced. The replacement amino acid, in the case of AA4, can be no amino acid. Thus, for example, the invention provides compounds of formula (I) corresponding to PEP-1 in which one of the amino acids AA1-AA4 is replaced by an amino acid, where Leu (AA1) is replaced by Ile or Val, Pro (AA2) is replaced by Ala or Gly, Val (AA3) is replaced by Ile or Leu, and Thr (AA4) is replaced by Val or no amino acid.

[0087] The compound according to formula (I) may be selected from any of PEP-1 to PEP-13, their stereoisomers, and / or cosmetically or pharmaceutically acceptable salts thereof. The compound of formula (I) may be PEP-1.

[0088] Cosmetically or pharmaceutically acceptable salts of the compounds provided by the present invention are also found within the field of the present invention. The term "cosmetically or pharmaceutically acceptable salt" means a salt approved for its use in animals, e.g., mammals, more particularly humans, and includes base addition salts (salts that are inorganic, such as, but not limited to, lithium, sodium, potassium, calcium, magnesium, manganese, copper, zinc, or aluminum, among others, or salts that are organic, such as, but not limited to, ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, arginine, lysine, histidine, or piperazine, among others). The present invention also includes salts used to form cosmetically or pharmaceutically acceptable salts (including, but not limited to, organic salts such as, but not limited to, acetate, citrate, lactate, malonate, maleate, tartrate, fumarate, benzoate, aspartate, glutamate, succinate, oleate, trifluoroacetate, oxalate, pamoate, or gluconate, or inorganic salts such as, but not limited to, chloride, sulfate, borate, or carbonate). The nature of the salt is not critical, provided that it is cosmetically or pharmaceutically acceptable. Cosmetically or pharmaceutically acceptable salts of the compounds of the present invention can be obtained by conventional methods well known in the prior art [Berge SM et al., "Pharmaceutical Salts", (1977), J. Pharm. Sci., 66, 1-19].

[0089] The present invention also provides a combination comprising a compound of formula (I), its stereoisomers and / or cosmetically acceptable salts thereof, in any of the above embodiments, and a botulinum toxin, yr-Lys-NH2 (SEQ ID NO: 15), or H-Ala-Leu-Lys-Pro-Asn-Thr-NH2 (SEQ ID NO: 16), and / or Ac-Arg-Arg-Gln-Met-Glu-Glu-NH2 (SEQ ID NO: 17), or Ac-Arg-Arg-D-Gln-Met-Glu-Glu-NH2 (SEQ ID NO: 18), or Ac-Arg-Arg-Gln-D-Met-Glu-Glu-NH2 (SEQ ID NO: 19), or Ac-Arg-Arg-D-Gln-D-Met-Glu-Glu-NH2 (SEQ ID NO: 20) or combinations thereof.

[0090] Procedures for the preparation of compounds of the present invention The compounds of the present invention, their stereoisomers, mixtures thereof and / or cosmetically or pharmaceutically acceptable salts thereof can be synthesized by solid-phase peptide synthesis [Stewart J. Mand Young J. D., "Solid Phase Peptide Synthesis, 2nd edition", (1984), Pierce Chemical Company, Rockford, Illinois; Bodanzsky M. and Bodanzsky A., "The practice of Peptide Synthesis", (1994), Springer Verlag, Berlin; Lloyd-Williams P. et al., "Chemical Approaches to the Synthesis of Peptides and Proteins", (1997), CRC, Boca Raton, FL, USA], solution synthesis, enzymatic synthesis [Kullmann W., "Proteases as catalysts for enzymic synthesis of opioids"]. The compounds of the present invention can be obtained according to conventional methods known in the prior art, such as "The Synthesis of Peptides of the Present Invention," (1980), J. Biol. Chem., 255(17), 8234-8238], or any combination thereof. The compounds of the present invention can also be obtained by fermentation of bacterial strains that have been modified or not by genetic engineering to produce the desired sequence, or by controlled hydrolysis of proteins of animal or plant origin, preferably plant origin, which result in free peptide fragments containing the desired sequence.

[0091] For example, methods for obtaining compounds of formula (I), their stereoisomers and mixtures thereof include: - coupling an amino acid having a protected N-terminus and a free C-terminus with an amino acid having a free N-terminus and a C-terminus that is protected or bound to a solid support, - removing the N-terminal protecting group, - repeating the coupling procedure and removing the N-terminal protecting group until the desired peptide sequence is obtained; - removing the protecting group at the C-terminus or cleaving the solid support.

[0092] Preferably, the C-terminus is attached to a solid support, and the process is carried out in the solid phase and therefore involves coupling an N-terminally protected, C-terminally free amino acid with an N-terminally free, C-terminally attached amino acid attached to a polymeric support, removing the N-terminal protecting group, and repeating this procedure as many times as necessary to obtain a compound of the desired length, followed finally by cleavage of the synthesized compound from the original polymeric support.

[0093] The functional groups of the side chains of the amino acids are conveniently protected by temporary or permanent protecting groups maintained throughout the synthesis and can be deprotected simultaneously or orthogonally with the process of cleavage of the peptide from the polymer support.

[0094] Alternatively, solid-phase synthesis can be carried out using a convergent strategy in which a polymer support is coupled to a peptide, or a peptide or amino acid pre-bound to a polymer support is coupled to a peptide. Convergent synthesis strategies are well known to those skilled in the art and are described in Lloyd-Williams P. et al., "Convergent Solid-Phase Peptide Synthesis", (1993), Tetrahedron, 49(48), 11065-11133.

[0095] The above process may include additional steps of deprotecting the N- and C-termini and / or cleaving the peptide from the polymer support in any order, using standard procedures and conditions known in the art, after which the functional groups at these termini may be modified. Any modifications of the N- and C-termini may be carried out with the peptide of formula (I) attached to the polymer support or once the peptide has been separated from the polymer support.

[0096] Optionally, R1 can be introduced by reacting the N-terminus of the compound of the present invention with an R1-X compound by nucleophilic substitution in the presence of a suitable base and solvent, where the functional groups of the fragments not involved in the N-C bond formation are appropriately protected by temporary or permanent protecting groups, where R1 is as defined above and X is a leaving group, such as, but not limited to, tosyl, mesyl, and halogen, among others.

[0097] Optionally and / or additionally, the R radical can be introduced by reaction of the compound HR with a complementary fragment corresponding to the peptide of formula (I) (wherein R is -OH) in the presence of a suitable solvent and base, such as N,N-diisopropylethylamine (DIEA) or trimethylamine, or an additive, such as 1-hydroxybenzotriazole (HOBt) or 1-hydroxyazabenzotriazole (HOAt), and a dehydrating agent, such as a carbodiimide, uronium salt, phosphonium salt, or amidinium salt, among others, or by prior formation of an acyl halide, for example, with thionyl chloride, to obtain the peptide according to the invention of formula (I), where the fragment containing functional groups not involved in N-C bond formation is appropriately protected by a temporary or permanent protecting group. Alternatively, other R radicals can be introduced by simultaneous incorporation into the peptide cleavage process from the polymer support. R is -OR, -NRR, or -SR (wherein R and R are as defined above).

[0098] Those skilled in the art will readily understand that the C-terminal and N-terminal deprotection / cleavage steps and their subsequent derivatization can be performed in different orders according to methods known in the prior art.

[0099] The term "protecting group" refers to a group that blocks an organic functionality and can be removed under controlled conditions. Protecting groups, their relative reactivities and the conditions under which they remain inert are known to those skilled in the art.

[0100] Representative examples of protecting groups for amino groups include amides such as acetate amide, benzoate amide, and pivalate amide; benzyloxycarbonyl (Cbz or Z), 2-chlorobenzyl (ClZ), para-nitrobenzyloxycarbonyl (pNZ), tert-butyloxycarbonyl (Boc), 2,2,2-trichloroethyloxycarbonyl (Troc), 2-(trimethylsilyl)ethyloxycarbonyl (Teoc), 9-fluorenylmethyloxycarbonyl (Fmoc), or allyloxycarbonyl (Cbz or Z). Carbamates such as dimethylcarbonyl (Alloc), trityl (Trt), methoxytrityl (Mtt), 2,4-dinitrophenyl (Dnp), N-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl (Dde), 1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl (ivDde), 1-(1-adamantyl)-1-methylethoxycarbonyl (Adpoc), among others, are preferably Boc or Fmoc.

[0101] Representative examples of protecting groups for carboxyl groups are esters such as tert-butyl ester (tBu), allyl ester (All), triphenylmethyl ester (Trt ester), cyclohexyl ester (cHx), benzyl ester (Bzl), ortho-nitrobenzyl ester, para-nitrobenzyl ester, para-methoxybenzyl ester, trimethylsilylethyl ester, 2-phenylisopropyl ester, fluorenylmethyl ester (Fm), 4-(N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino)benzyl ester (Dmab), among others; preferred protecting groups of the present invention are All, tBu, cHex, Bzl and Trt ester.

[0102] The side chains of the trifunctional amino acid may be protected during the synthesis process by temporary or permanent protecting groups that are orthogonal to the N- and C-terminal protecting groups.

[0103] The hydroxyl group of the tyrosine side chain can be protected with, among others, 2-bromobenzyloxycarbonyl group (2-BrZ), tBu, All, Bzl, or 2,6-dichlorobenzyl (2,6-diClZ). In a preferred embodiment, the protecting group strategy used is one in which the amino group is protected with Boc, the carboxyl group is protected with an ester of Bzl, cHx, or All, and the tyrosine side chain is protected with 2-BrZ or Bzl. In another preferred embodiment, the protecting group strategy used is one in which the amino group is protected with Fmoc, the carboxyl group is protected with a tBu, All, or Trt ester, and the tyrosine side chain is protected with tBu.

[0104] The amino group of the tryptophan side chain can be protected, for example, with a formyl group (For) or Boc. In one embodiment, when the amino group is protected with Fmoc, the tryptophan side chain can be unprotected, i.e., the amino acid is incorporated as Fmoc-Trp-OH, protected with Boc, i.e., the amino acid is incorporated as Fmoc-Trp(Boc)-OH, or protected with For, i.e., the amino acid is incorporated as Fmoc-Trp(For)-OH. In one embodiment, the amino group is protected with Boc and the tryptophan side chain can be protected with For, i.e., the amino acid is incorporated as Boc-Trp(For)-OH.

[0105] Examples of these and other protecting groups, their introduction and removal can be found in the literature [Atherton B. and Sheppard RC, "Solid Phase Peptide Synthesis: A practical approach", (1989), IRL Oxford University Press]. The term "protecting group" also includes polymer supports used in solid phase synthesis.

[0106] When the synthesis is carried out wholly or partly in the solid phase, possible solid supports that can be used in the process of the present invention include polystyrene supports, polyethylene glycol grafted to polystyrene, and similar supports, such as, but not limited to, p-methylbenzhydrylamine resin (MBHA) [Matsueda G.R. et al., "A p-methylbenzhydrylamine resin for improved solid-phase synthesis of peptide amides", (1981), Peptides, 2, 45-50], 2-chlorotrityl resin [Barlos K. et al., "Improved synthesis of peptide fragments under triphenylmethyl-harze", (1989), Tetrahedron Lett., 30, 3943-3946; Barlos K. et al., "Improved synthesis of peptide fragments under triphenylmethyl-harze", (1989), Tetrahedron Lett., 30, 3943-3946]. zur Synthese von Leu1-Gastrin I”, (1989), Tetrahedron Lett., 30, 3947-3951], TentaGel® resin (Rapp Polymere GmbH), ChemMatrix® resin (Matrix Innovation, Inc.) and similar supports, which may be used with 5-(4-aminomethyl-3,5-dimethoxyphenoxy) valeric acid (PAL) [Albericio F. et al., “Preparation and application of the 5-(4-(9-fluorenylmethyloxycarbonyl)aminomethyl-3,5-dimethoxy-phenoxy)valeric acid (PAL) handle for the solid-phase synthesis of C-terminal peptide amides under mild conditions”, (1990), J. Org. Chem.,55,3730-3743], 2-[4-aminomethyl-(2,4-dimethoxyphenyl)]phenoxyacetic acid (AM) [Rink H., "Solid-phase synthesis of protected peptide fragments using a trialkoxy-diphenyl-methylester resin", (1987), Tetrahedron Lett.,28,3787-3790], [Wang SS, "p-Alkoxybenzyl Alcohol Resin and p-Alkoxybenzyloxycarbonylhydrazide Resin for Solid Phase Synthesis of Protected Peptide Fragments", (1973), J. Am. Chem. Soc.,95,1328-1333], and the like, which linker allows for simultaneous deprotection and cleavage of the compound from the polymer support.

[0107] Purpose The present invention is based on the discovery that compounds of formula (I) are useful for treating skin, hair, nails, and / or mucous membranes, particularly for non-therapeutic cosmetic treatment of skin, hair, nails, and / or mucous membranes. Compounds of formula (I) have been found to be useful for preventing or treating symptoms of skin aging, including the presence of wrinkles, loss of skin firmness, and the appearance of sagging skin. In particular, compounds of the present invention have been found to be effective in improving skin firmness, reducing the appearance of sagging skin, reducing the appearance of wrinkles, and lifting skin. Compounds of formula (I) have also been found to be effective in upregulating the expression of muscle bind-like protein 1 (MBNL-1) in skin and skeletal muscle cells. Furthermore, compounds of formula (I) have also been found to be effective in stimulating the contraction of a collagen matrix containing fibroblasts, i.e., a collagen matrix similar to the extracellular matrix in the dermis. The compounds of formula (I) are therefore useful in the cosmetic, non-therapeutic treatment of skin, hair, nails, and / or mucous membranes.

[0108] The present invention provides the use of a compound of formula (I), its stereoisomers and / or cosmetically acceptable salts, or the use of a cosmetic composition comprising a compound of formula (I), its stereoisomers and / or cosmetically acceptable salts, in the treatment and / or care of skin, hair, nails, and / or mucous membranes. In particular, the treatment and / or care of skin, hair, nails, and / or mucous membranes is cosmetic and non-therapeutic. The treatment and / or care may be skin treatment and / or care. In the context of the present invention, skin includes skin of the entire body, including the face (including the skin around the eyes), nape, neck, décolletage, arms, hands, legs, feet, thighs, waist, buttocks, abdomen, and trunk. Skin treatment and / or care may include the treatment and / or prevention of skin aging, the treatment and / or prevention of skin wrinkles, the maintenance and improvement of skin firmness, the treatment and / or prevention of the appearance of sagging skin, and / or having a lifting effect on the skin.

[0109] Treatment and / or care may include upregulating MBNL-1 expression in skin (i.e., skin cells, specifically dermal fibroblasts) and / or muscle (i.e., muscle cells, specifically skeletal muscle cells). Increased MBNL1 is thought to promote the differentiation of human dermal fibroblasts into myofibroblasts and improve collagen contraction. In addition, increased MBNL-1 in muscle cells helps maintain muscle tone in facial skin. As a result, sagging skin is prevented.

[0110] Treatment and / or care can involve the contraction of the extracellular matrix of the dermis.Fibroblasts, which synthesize components of the extracellular matrix, induce the contraction of the extracellular matrix.The compound of formula (I) has been found to promote the fibroblast-induced contraction of fibroblast-containing collagen gel, and is therefore believed to be able to promote the fibroblast-induced contraction of the extracellular matrix.This ability is believed to contribute to the ability of the compound of formula (I), for example, to maintain or improve skin firmness, treat or prevent the appearance of sagging skin, and reduce or prevent the appearance of wrinkles on the skin.

[0111] The treatment and / or care may be the treatment and / or prevention of skin aging. The treatment and / or prevention of skin aging includes the treatment (i.e., alleviation) and / or prevention of symptoms of skin aging. Symptoms of skin aging include the appearance of wrinkles and a decrease in biomechanical properties of the skin, such as firmness. Loss of firmness may result in the appearance of sagging skin. Loss of firmness may be due to changes in cell-matrix interactions in the extracellular matrix of the dermis due to skin aging.

[0112] The treatment and / or care may be the treatment and / or prevention of skin wrinkles, including expression wrinkles, also commonly called expression lines.

[0113] The treatment and / or care may be maintaining and / or improving the firmness of the skin. The skin may be facial skin, in particular the skin of the jaw line.

[0114] The treatment and / or care may be the treatment and / or prevention of the appearance of sagging skin.

[0115] The treatment and / or care may be a skin lifting, for example a brow, cheek or jawline lifting.

[0116] The present invention also relates to a method for treating a botulinum toxin comprising administering to a patient a therapeutically effective amount of a compound of formula (I) in combination with a botulinum toxin, Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2, H-Tyr-D-Ala-Gly-Phe-Leu-OH, Ac-βAla-His-Ser-His-OH, Ac-Gln-Glu-Met-Arg-Met-Gln-OH, Ac-Asp-Val-Tyr-Lys-NH2, H-Ala-Leu-Lys-Pro-Asn-Thr-NH2 and / or Ac-Arg The present invention also extends to the use of a compound of formula (I) in combination with Ac-Arg-Gln-Met-Glu-Glu-NH2, Ac-Arg-Arg-D-Gln-Met-Glu-Glu-NH2, Ac-Arg-Arg-Gln-D-Met-Glu-Glu-NH2 and / or Ac-Arg-Arg-D-Gln-D-Met-Glu-Glu-NH2 in the treatment and / or care of the skin, hair, nails and / or mucous membranes as described above in connection with the application (use) of the compound of formula (I). Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 is commercialized as Argireline® peptide by Lipotec SAU (The Lubrizol Corporation) and is known to mimic the cosmetic effect of botulinum toxin on the skin in that it inhibits neuronal exocytosis.

[0117] The present invention also provides a method for treating and / or caring for the skin, hair, nails, and / or mucous membranes of a subject, comprising administering to the subject a compound of Formula (I), its stereoisomers, and / or cosmetically or pharmaceutically acceptable salts, or a composition comprising a compound of the present invention, its stereoisomers, and / or its cosmetically or pharmaceutically acceptable salts. In particular, the method is a cosmetic, non-therapeutic method for treating and / or caring for the skin, hair, nails, and / or mucous membranes of a subject. The subject may be Caucasian. The method may be for treating and / or caring for the skin, hair, nails, and / or mucous membranes, as described above with respect to the application (use) of a compound of Formula (I). In particular, the method of treatment and / or care is skin treatment and / or care. Administration may be topical or, for example, transdermal. The compound of Formula (I) may be present in a cosmetic composition, such as the cosmetic compositions described herein. The method may comprise administering the compound or administering the composition using a microneedle.

[0118] The present invention also extends to a method of treating and / or caring for the skin, hair, nails and / or mucous membranes of a subject, comprising combining a compound of formula (I), a stereoisomer and / or a cosmetically or pharmaceutically acceptable salt thereof with a botulinum toxin, Ac-Glu-Glu-Met-Gln-Arg-Arg-NH, H-Tyr-D-Ala-Gly-Phe-Leu-OH, Ac-βAla-His-Ser-His-OH, Ac-Glu-Glu-Met-Arg-Met-Gln-OH or Ac-As The method comprises administering to a subject p-Val-Tyr-Lys-NH2, or H-Ala-Leu-Lys-Pro-Asn-Thr-NH2 and / or Ac-Arg-Arg-Gln-Met-Glu-Glu-NH2, or Ac-Arg-Arg-D-Gln-Met-Glu-Glu-NH2, or Ac-Arg-Arg-Gln-D-Met-Glu-Glu-NH2, or Ac-Arg-Arg-Gln-D-Met-Glu-Glu-NH2, and / or a combination thereof with Ac-Arg-Arg-D-Gln-D-Met-Glu-Glu-NH2. The method may be for treating and / or caring for the skin, hair, nails, and / or mucous membranes, as described above with respect to the application (use) of a compound of formula (I). For example, the method of treatment may comprise administering to a subject a botulinum toxin and a compound of formula (I), its stereoisomer, and / or a cosmetically or pharmaceutically acceptable salt thereof. For example, a method of treatment can comprise administering to a subject the compound of the invention, its stereoisomers and / or cosmetically or pharmaceutically acceptable salts thereof, Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2, and the compounds of the invention. Preferably, the method of treatment is a preventive treatment of skin aging.

[0119] Botulinum toxin, Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2, H-Tyr-D-Ala-Gly-Phe-Leu-OH, Ac-βAla-His-Ser-His-OH, Ac-Gln-Glu-Met-Arg-Met-Gln-OH, or Ac-Asp-Val-Tyr-Lys-NH2, or H-Ala-Leu-Lys-Pro-Asn-Thr-NH2 and / or or Ac-Arg-Arg-Gln-Met-Glu-Glu-NH2, or Ac-Arg-Arg-D-Gln-Met-Glu-Glu-NH2, Ac-Arg-Arg-Gln-D-Met-Glu-Glu-NH2, and / or Ac-Arg-Arg-D-Gln-D-Met-Glu-Glu-NH2 and the compound of formula (I) may be administered simultaneously or one after the other. Botulinum toxin and / or Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2, H-Tyr-D-Ala-Gly-Phe-Leu-OH, Ac-βAla-His-Ser-His-OH, A c-Gln-Glu-Met-Arg-Met-Gln-OH, or Ac-Asp-Val-Tyr-Lys-NH2, or H-Ala-Leu-Lys-Pro-Asn-Thr-NH2 and / or Ac-Ar When g-Arg-Gln-Met-Glu-Glu-NH2, or Ac-Arg-Arg-D-Gln-Met-Glu-Glu-NH2, Ac-Arg-Arg-Gln-D-Met-Glu-Glu-NH2, and / or Ac-Arg-Arg-D-Gln-D-Met-Glu-Glu-NH2 and the compound of formula (I) are administered simultaneously, they can be administered as separate dosage forms or as part of a single composition. When the products are administered in separate dosage forms, the dosage forms can be in the same or different containers.

[0120] The above treatment methods include skin treatment and / or care, such as treatment and / or prevention of skin aging, treatment and / or prevention of skin wrinkles, maintenance and improvement of skin firmness, treatment and / or prevention of the appearance of sagging skin, and / or skin lifting, etc. In particular, the treatment methods are cosmetic and non-therapeutic.

[0121] In another aspect, the present invention provides a compound of formula (I), its stereoisomer and / or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising them, for use as a medicament. In particular, the present invention provides a compound of formula (I), its stereoisomer and / or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising them, for use in the treatment or prevention of a disease or disorder. In another aspect, the present invention provides the use of a compound of formula (I), its stereoisomer and / or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for treating or preventing a disease or disorder. In another aspect, the present invention provides a method for treating or preventing a disease or disorder in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or a pharmaceutical composition comprising same.

[0122] For the above methods, topical or transdermal application may be performed by iontophoresis, sonophoresis, electroporation, mechanical pressure, osmotic gradient, occlusive therapy, microinjection, needle-free injection by pressure, microelectrical patch, face mask, or any combination thereof.

[0123] For the above methods, the frequency of application or administration can vary widely depending on the needs of each subject, but recommended applications are once a month to 10 times a day, preferably once a week to 4 times a day, more preferably 3 times a week to 2 times a day, and even more preferably once a day. For example, a compound of formula (I), its stereoisomer and / or a cosmetically or pharmaceutically acceptable salt thereof, in combination with botulinum toxin, Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2H-Tyr-D-Ala-Gly-Phe-Leu-OH, Ac-βAla-His-Ser-His-OH, Ac-Gln-Glu-Met-Arg-Met-Gln-OH, Ac-Asp-Val-Tyr-Lys-NH2, H-Ala-Leu-Lys-Pro-Asn-Thr-NH2, The frequency of administration according to the method for treating and / or caring for a subject's skin, hair, nails, and / or mucous membranes, which comprises administering to the subject Ac-Arg-Arg-Gln-Met-Glu-Glu-NH2, Ac-Arg-Arg-D-Gln-Met-Glu-Glu-NH2, Ac-Arg-Arg-Gln-D-Met-Glu-Glu-NH2, and / or a combination thereof, can vary widely depending on the needs of each subject. The method of the invention can include administration of a botulinum toxin followed by administration of a compound of formula (I). For example, after administration of the botulinum toxin, the compound of formula (I) can be administered at least once daily for at least one week, and / or the compound of formula (I) can be administered at least once daily until the next administration of the botulinum toxin.

[0124] Compositions of the Invention The compound of formula (I) can be administered by any means that brings the compound into contact with the site of action in the subject's body.The subject is preferably a mammal, more preferably a human.The subject may be Caucasian.Preferably, the compound is contained in a composition.

[0125] The present invention provides compositions comprising a compound according to formula (I), its stereoisomers and / or cosmetically or pharmaceutically acceptable salts. In particular, the present invention provides cosmetic compositions comprising a compound according to formula (I), its stereoisomers and / or cosmetically acceptable salts, together with at least one cosmetically acceptable excipient or adjuvant. These compositions can be prepared by conventional means known to those skilled in the art ("Harry's Cosmeticology", Seventh edition, (1982), Wilkinson JB, Moore RJ, ed. Longman House, Essex, GB).

[0126] The compounds of formula (I) have varying degrees of solubility in water depending on the nature of their amino acid sequence or any possible modifications at the N-terminus and / or C-terminus. Thus, the compounds of the present invention can be incorporated into compositions by aqueous solution, and compounds that are not water-soluble can be solubilized in conventional cosmetically or pharmaceutically acceptable solvents, including but not limited to ethanol, propanol, isopropanol, propylene glycol, glycerin, butylene glycol, or polyethylene glycol, or any combination thereof.

[0127] The cosmetically effective amount of a compound of formula (I) to be administered, as well as the dosage of the compound, will depend on a number of factors, including the age and condition of the patient, the nature or severity of the condition, the disorder or disease being treated and / or cared for, the route and frequency of administration, and the particular nature of the compound used.

[0128] The terms "cosmetically effective amount" and "pharmaceutically effective amount" are understood to mean a non-toxic but sufficient amount of a compound of formula (I) to provide the desired effect. The terms "pharmaceutically effective" and "therapeutically effective" are used interchangeably herein. The compound of formula (I) is used in the cosmetic or pharmaceutical composition of the present invention at a cosmetically or pharmaceutically effective concentration to achieve the desired effect, for example, in an amount of 0.00000001% (by weight) to 20% (by weight), 0.000001% (by weight) to 15% (by weight), 0.00001% (by weight) to 10% (by weight), or 0.0001% (by weight) to 5% (by weight) relative to the total weight of the composition.

[0129] The compounds of formula (I), their stereoisomers, mixtures thereof and / or cosmetically or pharmaceutically acceptable salts thereof may also be incorporated into cosmetic or pharmaceutical delivery and / or sustained release systems.

[0130] The term "delivery system" refers to a diluent, adjuvant, excipient, or carrier that is administered with the compound of the present invention. These cosmetic or pharmaceutical carriers are liquids such as water, oil, or surfactants, including those of petroleum, animal, vegetable, or synthetic origin, such as, but not limited to, peanut oil, soybean oil, mineral oil, sesame oil, castor oil, polysorbate, sorbitan ester, ether sulfate, sulfate, betaine, glycoside, maltoside, fatty alcohol, nonoxynol, poloxamer, polyoxyethylene, polyethylene glycol, dextrose, glycerol, digitonin, and the like. Those skilled in the art will be familiar with the diluents, adjuvants, or excipients that can be used in various delivery systems that can administer the compound of the present invention.

[0131] The term "sustained release" is used in its conventional sense to refer to a compound delivery system that provides for gradual release of the compound over a period of time, preferably, but not necessarily, at a relatively constant level of compound release over a period of time.

[0132] Examples of delivery or sustained-release systems include, but are not limited to, liposomes, mixed liposomes, oleosomes, niosomes, ethosomes, milliparticles, microparticles, nanoparticles and solid lipid nanoparticles, nanostructured lipid carriers, sponges, cyclodextrins, vesicles, micelles, surfactant mixed micelles, surfactant-phospholipid mixed micelles, millispheres, microspheres and nanospheres, lipospheres, millicapsules, microcapsules and nanocapsules, and microemulsions and nanoemulsions, which can be added to achieve better penetration of the active ingredient and / or improve its pharmacokinetic and pharmacodynamic properties. Preferred delivery or sustained-release systems are liposomes, surfactant-phospholipid mixed micelles, microemulsions, and more preferably, water-in-oil microemulsions with a reverse micelle internal structure and nanocapsules containing microemulsions.

[0133] In one embodiment, the present invention provides a cosmetic or pharmaceutical composition comprising a compound of formula (I) and a cosmetically or pharmaceutically acceptable carrier selected from the group consisting of a cream, an emulsion, a gel, a liposome, a nanoparticle, and an ointment.

[0134] Sustained-release systems can be prepared by methods known in the art, and compositions containing the systems can be administered, for example, by topical or transdermal administration, including adhesive patches, non-adhesive patches, occlusive patches, and microelectric patches, or by systemic administration (e.g., but not limited to, oral routes, or parenteral routes, including nasal, rectal, or subcutaneous implantation or injection, or direct implantation or injection into a particular body part), and should preferably release a relatively constant amount of the compound of the invention. The amount of compound contained in a sustained-release system depends, for example, on the location where the composition is administered, the kinetics and duration of release of the compound of the invention, and the nature of the condition, disorder, and / or disease being treated and / or cared for.

[0135] The compounds of formula (I) may also be adsorbed onto a solid organic polymer or a solid inorganic support such as, but not limited to, talc, bentonite, silica, starch or maltodextrin, among others.

[0136] Compositions containing the compound of formula (I), its stereoisomers, mixtures thereof, and / or cosmetically or pharmaceutically acceptable salts thereof can be incorporated into fabrics, nonwovens, and medical devices that come into direct contact with the skin, thereby releasing the compound of formula (I), whether by biodegradation of the binding system to the fabric, nonwoven, or medical device due to body moisture, skin pH, or body temperature, or by friction between the fabric, nonwoven, or medical device. Furthermore, the compound of formula (I) can be incorporated into textiles and nonwovens used to make clothing that comes into direct contact with the body.

[0137] Examples of textiles, nonwovens, clothing, medical devices and means for immobilizing compounds thereon, among others, are the delivery systems and / or sustained release systems mentioned above, which can be found in the literature and are known in the prior art [Schaab CK (1986) HAPPI May 1986; Nelson G., "Application of microencapsulation in textiles", (2002), Int. J. Pharm., 242 (1-2), 55-62; "Biofunctional Textiles and the Skin" (2006) Curr. Probl. Dermatol. v. 33, Hipler UC and Elsner P., eds. S. Karger AG, Basel, Switzerland; Malcolm RK et al., "Controlled release of a model antibacterial drug from a novel self-lubricating silicone"]. "biomaterial", (2004), J. Cont. Release, 97(2), 313-320]. Preferred textiles, nonwovens, garments, and medical devices are bandages, gauze, T-shirts, socks, tights, underwear, girdles, gloves, diapers, sanitary napkins, bandages, bedspreads, wipes, adhesive patches, non-adhesive patches, occlusive patches, microelectric patches, and / or face masks.

[0138] Cosmetic or pharmaceutical compositions containing the compound of formula (I), its stereoisomers, mixtures thereof and / or its cosmetically or pharmaceutically acceptable salts may be used in a variety of different types of compositions for topical or transdermal application, which compositions optionally contain cosmetically or pharmaceutically acceptable excipients necessary for the formulation of the desired dosage form.

[0139] Compositions for topical or transdermal application can be made into any solid, liquid, or semi-solid formulation, for example, but not limited to, creams, multiple emulsions, including but not limited to, oil-in-water and / or silicone-in-water emulsions, water-in-oil and / or water-in-silicone emulsions, water / oil / water or water / silicone / water emulsions, and oil / water / oil or silicone / water / silicone emulsions, anhydrous compositions, aqueous dispersions, oils, milks, balsams, foams, lotions, gels, cream gels, hydroalcoholic solutions, hydroglycolic solutions, hydrogels, liniments, serums, soaps, shampoos, conditioners, serums, polysaccharide films, ointments, mousses, pomades, powders, bars, pencils, and sprays or aerosols (sprays), including leave-on and rinse-off formulations. These topical or transdermal formulations can be incorporated using techniques known to those skilled in the art into various types of solid accessories, including, but not limited to, bandages, gauze, T-shirts, socks, tights, underwear, girdles, gloves, diapers, sanitary napkins, bandages, bedspreads, wipes, adhesive patches, non-adhesive patches, occlusive patches, micro-electric patches, or face masks, or into various makeup products, such as makeup foundations, including liquid foundations and compact foundations, makeup remover lotions, makeup remover emulsions, dark circle concealers, eye shadows, lipsticks, lip protectors, lip glosses, and powders, among others.

[0140] The cosmetic or pharmaceutical composition of the present invention may contain an agent that increases the percutaneous absorption of the compound of the present invention, for example, but not limited to, dimethyl sulfoxide, dimethylacetamide, dimethylformamide, surfactants, Azone (1-dodecylazacycloheptan-2-one), alcohol, urea, ethoxydiglycol, acetone, propylene glycol, or polyethylene glycol, among others. Furthermore, the cosmetic or pharmaceutical composition of the present invention may be applied to the localized area to be treated by iontophoresis, sonophoresis, electroporation, microelectric patching, mechanical pressure, osmotic gradient, occlusive cure, microinjection, or needleless injection with pressure, such as oxygen pressure injection, or any combination thereof, to achieve better penetration of the peptide of the present invention. The area of ​​application is determined by the nature of the condition, disorder, and / or disease to be treated and / or cared for.

[0141] Furthermore, compositions containing the compound of formula (I), its stereoisomers, mixtures thereof, and / or cosmetically or pharmaceutically acceptable salts thereof can be used in various types of preparations for oral administration, preferably in the form of oral cosmetics or drugs, such as, but not limited to, capsules, including gelatin capsules, soft capsules, and hard capsules, tablets, including dragees, tablets, pills, powders, granules, chewing gum, solutions, suspensions, emulsions, syrups, elixirs, polysaccharide films, jellies, or gelatins, and any other forms known to those skilled in the art. In certain embodiments, the compounds of the present invention can be incorporated into any form of functional or fortified food, including, but not limited to, dietary bars or compacted or non-compacted powders. These powders can be dissolved in water, soda, dairy products, soy derivatives, or incorporated into dietary bars. The compounds of formula (I) can be formulated with common excipients and adjuvants for oral compositions or dietary supplements, including, but not limited to, fatty components, aqueous components, humectants, preservatives, texturizing agents, flavors, aromas, antioxidants, and colorants common in the food industry.

[0142] Cosmetic or pharmaceutical compositions containing a compound of formula (I), its stereoisomers, mixtures thereof, and / or cosmetically or pharmaceutically acceptable salts thereof can be administered by any other suitable route, such as oral or parenteral, as well as topical or transdermal routes, and therefore the compositions contain pharmaceutically acceptable excipients necessary for the formulation of the desired dosage form. In the context of the present invention, the term "parenteral" includes intravascular injections such as nasal, auricular, ocular, rectal, urethral, ​​vaginal, subcutaneous, intradermal, intravenous, intramuscular, intraocular, intravitreal, intracorneal, intraspinal, intramedullary, intracranial, intracervical, intracerebral, intrameningeal, intraarticular, intrahepatic, intrathoracic, intratracheal, intrathecal, and intraperitoneal, as well as any other similar injection or infusion techniques. Those skilled in the art are aware of the various means by which cosmetic or pharmaceutical compositions containing the compounds of the present invention can be administered.

[0143] Among the cosmetically or pharmaceutically acceptable adjuvants contained in the cosmetic or pharmaceutical compositions described herein are additional ingredients commonly used in cosmetic or pharmaceutical compositions, including, but not limited to, (i) anti-wrinkle agents, Botox-like agents, and / or anti-aging agents; (ii) firming agents, skin elasticity agents, and / or restructuring agents; moisturizing agents; (iii) anti-photoaging agents and / or blue light protection agents; (iv) DNA protection agents, DNA repair agents, and / or stem cell protection agents; (v) free radical scavengers and / or anti-glycation agents, detoxifying agents, antioxidants, and / or anti-pollution agents; (vi) antiperspirants; (vii) melanin synthesis stimulators or inhibitors; (viii) skin lightening or depigmenting agents; (ix) propigmenting agents; (x) self-tanning agents; and (xi) lipolytic agents or lipolytic stimulators, adipogenic agents. Additional examples can be found in the CTFA International Cosmetic Ingredient Dictionary & Handbook, 12th Edition (2008).

[0144] In one embodiment, the present invention provides a cosmetic or pharmaceutical composition comprising a compound of formula (I) and a pharmaceutically or cosmetically effective amount of an adjuvant, wherein the adjuvant is selected from the group consisting of: (i) anti-wrinkle, Botox-like, and / or anti-aging agents; (ii) firming, skin elasticity, and / or restructuring agents; (iii) moisturizing agents; (iv) anti-photoaging and / or blue light protection agents; (v) DNA protection agents, DNA repair agents, and / or stem cell protection agents; (vi) free radical scavengers, and / or anti-glycation agents, detoxifying agents, antioxidants, and / or anti-pollution agents; and / or combinations thereof.

[0145] Anti-wrinkle, Botox-like, and / or anti-aging agents include Matrixyl® [INCI: Palmitoyl Pentapeptide-4], Matrixyl® 3000® [INCI: Palmitoyl Tetrapeptide-7, Palmitoyl Oligopeptide], Matrixyl® Synthe'6 [INCI: Glycerin, Water, Hydroxypropyl Cyclodextrin, Palmitoyl Tripeptide-38], Matrixyl® Morphomics™ [INCI: Pentylene Glycol, Caprylyl Glycol], Essenskin™ [INCI: Hydroxymethionine Calcium], Renovage [INCI: Teprenone], Dermaxyl® [INCI: Palmitoyl Oligopeptide], Calmosensine [INCI: Butylene Glycol, Acetyl Dipeptide-1 Cetyl Ester], Volulip [INCI: Cetearyl Ethylhexanoate, Sorbitan Isostearate, Portulaca Pilosa Extract, Sucrose Palmitate, Palmitoyl Tripeptide-38], Subliskin [INCI: Sinorhizobium Meliloti Ferment, Cetyl Hydroxyethylcellulose, Lecithin], Biopeptide CL [INCI: Palmitoyl Oligopeptide], Biopeptide EL [INCI: Palmitoyl Oligopeptide], Rigin [INCI: Palmitoyl Tetrapeptide-3], Biobustyl [INCI: Glyceryl Polymethacrylate, Rahnella / Soy Protein Ferment, Palmitoyl Oligopeptide], Dynalift [INCI: Sodium Polystyrene Sulfonate, Sorghum Bicolor Stem Juice, Glycerin], Idealift [INCI: Acetyl Dipeptide-1 Cetyl Ester], Siegesbeckia [INCI: SiegesbeckiaOrientales extract], Ovaliss [INCI: Coco-glucoside, Caprylyl glycol, Alcohol, Glaucine], Juvinity™ [INCI: Geranylgerani-isopropanol], Prolevis [INCI: Hydrolyzed Vegetable Protein], Idealift™ [INCI: Hydroxyethylcellulose, Acetyl Dipeptide-1 Cetyl Ester], Beautifeye™ [INCI: Albizia Julibrissin Bark Extract, Darutoside], Chromocare™ [INCI: Sigesbeckia Orientalis Extract, Rabdosia Rubescens Extract], or Resistem [proposed INCI: Globularia Cordifolia Ferment]. Vialox® [INCI: Pentapeptide-3], Syn®-Ake® [INCI: Dipeptide diaminobutyroyl benzylamide diacetate], Syn®-Coll [INCI: Palmitoyl tripeptide-5], Phytaluronate [INCI: Ceratonia siliqua (carob) gum], Preregen® [INCI: Glycine], marketed by Pentapharm / DSM soja (soybean) protein, oxidoreductase enzymes], Pepha-Nutrix [INCI: Natural Nutritional Factors], Pepha-Tight [INCI: Algae extract, pullulan], Pentacare-NA [INCI: Hydrolyzed wheat gluten, carob gum], Syn®-Tacks [INCI: Glycerin, Palmitoyl Dipeptide-5 Diaminobutyroyl Hydroxythreonine, Palmitoyl Dipeptide-6 Diaminohydroxybutyrate], BeauActiveMTP [INCI: Hydrolyzed Milk Protein], Syn®-TC [INCI: Tetradecylaminobutyroylvalylaminobutyric Urea Trifluoroacetate, Palmitoyl Tripeptide-5, Palmitoyl Dipeptide-5 Diaminobutyroyl Hydroxythreonine], Syn®-Hycan [INCI: Tetradecylaminobutyroylvalylaminobutyric Urea Trifluoroacetate], Syn®-Glycan [INCI: Tetradecylaminobutyroylvalylaminobutyric Urea Trifluoroacetate], Regu-Age [INCI: Hydrolyzed Rice Bran Protein, Oxidoreductase, Glycine Soja Protein], Pepha-Timp [INCI: Human Oligopeptide-20], Pepha-Age [INCI: Dunaliella Salina Extract], Colhibin [INCI: Hydrolyzed Rice Protein], Elhibin [INCI: Glycine Soja protein, disodium cocoamphodiacetate], or All-Q™ Plus [INCI: ubiquinone, tocopheryl acetate]; Myoxinol™ [INCI: hydrolyzed Hibiscus esculentus extract], Myoxinol™ LS 9736 [INCI: hydrolyzed Hibiscus esculentus extract, dextrin], Syniorage™ [INCI: acetyl tetrapeptide-11], Dermican™ [INCI: acetyl tetrapeptide-9], DN-AGE® LS [INCI: Cassia alata leaf extract], Hyalufix GL [INCI: Alpinia Galanga leaf extract], Neurobiox [INCI: Achillea Millefolium extract], Deliner [INCI: Zea Mays (corn) seed extract], Lys'lastine, marketed by Laboratoires Serobiologiques / Cognis / BASF V [INCI: Peucedanum Graveolens (Dill) Extract], Extracellium [INCI: Hydrolyzed Potato Protein], Proteasyl TP LS 8657 [INCI: Pisum Sativum Extract], FlavagrumPEG [INCI: PEG-6 Isostearate, Hesperetin Laurate], Micromerol [INCI: Pyrus Malus Fruit Extract], Extracellium [INCI: Hydrolyzed Potato Protein], Marine Filling Spheres [INCI: Pentaerythrityl Tetraisostearate, Silica Dimethyl Silylate, Sodium Chondroitin Sulfate, Atelocollagen], Triactigen [INCI: Mannitol, Cyclodextrin, Yeast Extract, Disodium Succinate], Eterniskin [INCI: Grifola Frondosa Fruiting Body Extract, Maltodextrin], Ascotide [INCI: Ascorbyl Succinoyl Pentapeptide-12 Phosphate], Hyalurosmooth [INCI: Cassia Angustifolia Seed Polysaccharide], Indinyl CA [INCI: Cassia Angustifolia Seed Polysaccharide], Arganyl [INCI: Argania Spinosa Leaf Extract], Sphingoceryl Veg [INCI: Plant Ceramides], Vit-A-Like [INCI: Vigna Acontifolia Seed Extract], Peptiskin [INCI: Arginine / Lysine Polypeptide], Prodejine [INCI: Mannitol, Cyclodextrin, Yeast Extract, Disodium Succinate], Aqu'activ [INCI: Behenyl Alcohol, Glyceryl Oleate, Cocamide MIPA, Calcium Citrate], Elestan [INCI: Glycerin, Manilkara Leaf Extract], Hibiscin HP [INCI: Hibiscus Esculentus Seed Extract], Collalift® 18 [INCI: Khaya Senegalensis Peel], Collrepair™ DG [INCI: Hexylene Glycol, Niacin], or Litchiderm [INCI: Litchi ChinensisPericarp extract]; Argireline® [INCI: Acetyl hexapeptide-8], SNAP-7 [INCI: Acetyl heptapeptide-4], SNAP-8 [INCI: Acetyl octapeptide-3], Leuphasyl® [INCI: Pentapeptide-18], Inyline® [INCI: Acetyl hexapeptide-30], Aldenine® [INCI: Hydrolyzed wheat protein, hydrolyzed soy protein, tripeptide-1], marketed by Lipotec / Lubrizol , Preventhelia® [INCI: Diaminopropionoyl Tripeptide-33], Decorinyl® [INCI: Tripeptide-10 Citrulline], Decorinol® [INCI: Tripeptide-9 Citrulline], Trylagen® [INCI: Pseudoalteromonas Ferment Extract, Hydrolyzed Wheat Protein, Hydrolyzed Soy Protein, Tripeptide-10 Citrulline, Tripeptide-1], Eyeseryl® [INCI: Acetyl Tetrapeptide-5], Peptide AC29 [INCI: Acetyl Tripeptide-30 Citrulline], Relistase® [INCI: Acetylarginyltryptophyldiphenylglycine], Thermostressine® [INCI: Acetyl Tetrapeptide-22], Lipochroman™ [INCI: Dimethylmethoxychromanol], Chromabright® [INCI: Dimethylmethoxychromanylpalmitate], Antarcticine® [INCI: Pseudoalteromonas spp. Ferment Extract], dGlyage® [INCI: Lysine HCl, Lecithin, Tripeptide-9 Citrulline], Vilastene™ [INCI: Lysine HCl, Lecithin, Tripeptide-10 Citrulline], Hyadisine® [INCI: Pseudoalteromonas Ferment Extract], Hyanify™ [INCI: Saccharide Isomerates], Diffuporine® [INCI: Acetyl Hexapeptide-37], Silusyne® [INCI: Soy (GlycineSoja (Soybean) Oil, Sorbitan Sesquioleate, Isohexadecane, Sodium Hyaluronate, Lauryldimonium Hydroxypropyl Hydrolyzed Soy Protein, Acetyl Hexapeptide-39, Adifyline® [INCI: Acetyl Hexapeptide-38], Delisens™ [INCI: Acetyl Hexapeptide-46], Telangyn™ [INCI: Acetyl Tetrapeptide-40], Reproage™ Peptide [INCI: Acetyl Hexapeptide-8], Cellynkage™ Marine Ingredients [INCI: Saccharide Isomerates], Eyedeline (Trademark) Marine Ingredients [INCI: Plankton Extract], uplevity™ [INCI: Acetyl Tetrapeptide-2], Seacode™ Marine Ingredients [INCI: Pseudoalteromonas Ferment Extract], or Serilesine® Peptide Solution [INCI: Hexapeptide-10], Argireline® Amplified Peptide [INCI: Acetyl Hexapeptide-8]; commercially available from Lipotrue, Sirtalice™ [INCI: Bacillus Ferment], Epitensive™ [INCI: Nicotiana benthamiana Hexapeptide-40 SH-Oligopeptide-1], Scelleye™ [INCI: Nicotiana benthamiana SH-Oligopeptide-2], Seadermium [INCI: Aqua, Glycerin, Bacillus Ferment], Pauseil e [INCI: Aqua, Glycerin, Bacillus Ferment], or Neoclair pro [INCI: Aqua, Glycerin, Caprylyl Glycol, Acetyl Tetrapeptide-2]; Collaxyl® IS [INCI: Hexapeptide-9], Laminixyl IS™ [INCI: Heptapeptide], Orsirtine™ GL [INCI: Oryza sativa (Rice) Extract], D'Orientine™ IS [INCI: Phoenix dactylifera (Date Palm) Seed Extract], Phytoquintescine™ [INCI: Einkorn (Einkorn) Extract], Quintescine™ IS [INCI: Dipeptide-4], Peptide Vinci 01 [INCI: Pentadecapeptide-1], Peptide Vinci, marketed by Vincience / ISP / Ashland 02™ [INCI: Hexapeptide-3], Aquarize IS™ [INCI: Hydrolyzed rice extract], Lanablue [INCI: Algae extract], Ederline™ [INCI: Pyrus Malus (apple) seed extract], Dynachondrine™ ISR [INCI: Hydrolyzed soy protein], Prolixir S20™ [INCI: Dimeric tripeptide-43], Phytocohesine™ PSP [INCI: Sodium beta-sitosteryl sulfate, beta-sitosterol], Perenityl™ IS [INCI: Pyrus Communis (pear) seed extract], Caspaline 14™ [INCI: Hexapeptide-42], Peptide Q10™ [INCI: Pentapeptide-34 trifluoroacetate], Survixyl IS™ [INCI: Pentapeptide-31], ChroNOgen™ [INCI: Tetrapeptide-26], Elixiance [INCI: Schinus Molle Extract], Harmoniance™ [INCI: Nelumbo Nucifera Flower Extract], Serenityl [INCI: Marsdenia Condurango Peel Extract], NatrianceWrinkle-less [INCI: Hydrolyzed Corn Protein], Phytoneomatrix [INCI: Hydrolyzed Soybean Extract], Prolixir ICE [INCI: Hydrolyzed Rice Protein], PhytoRNx Baobab™ [INCI: Hydrolyzed Adansonia Digitata Extract], Natriance Renovate Extract [INCI: Hydrolyzed Flaxseed Extract], Natriance Self-Hydrate Extract [INCI: Pisum Sativum Extract], Actopontine YST [INCI: Hydrolyzed Yeast Protein], or Telosense™ [Suggested INCI: Hydrolyzed Soybean Protein, Hydrolyzed Yeast Protein]; BONT-L-Peptide [INCI: Palmitoyl Hexapeptide-19], TIMP Peptide [INCI: Acetyl Hexapeptide-20], ECM, marketed by Infinitec Activos Moduline [INCI: Palmitoyl Tripeptide-28], Renaissance [INCI: Hydrolyzed Wheat Protein, Palmitoyl Decapeptide-21, Decapeptide-22, Oligopeptide-78, Zinc Palmitoyl Nonapeptide-14], or X50 Antiaging [INCI: Lactic Acid / Glycolic Acid Copolymer, Polyvinyl Alcohol, Copper Palmitoyl Heptapeptide-14, Heptapeptide-15 Palmitate]; EquiStat [INCI: Pyrus malus fruit extract, Glycine soja (Glycine max) palmitate], marketed by Coletica / Engelhard / BASF; soja seed extract], Juvenesce [INCI: Ethoxydiglycol and Caprylic Triglyceride, Retinol, Ursolic Acid, Phytonadione, Ilomastat], Ursolisome [INCI: Lecithin, Ursolic Acid, Atelocollagen, Xanthan Gum, Sodium Chondroitin Sulfate], Basaline [INCI: Hydrolyzed Malt Extract], Phytokine [INCI: Hydrolyzed Soy Protein]; Ameliox [INCI: Carnosine, Tocopherol, Silybum marianum Fruit Extract], or PhytoCellTec Malus Domestica [INCI: Malusdomestica fruit cell culture], Lipobelle Soyaglicane [INCI: Soy Isoflavones], RoyalEpigen P5 [INCI: Butyrospermum Parkii Butter, Hydrogenated Lecithin, Maltodextrin, Pentapeptide-48, Phenethyl Alcohol, Ethylhexylglycerin, Glycerin, Aqua], or DermCom [INCI: Crocus Chrysanthus Bulb Extract, Gum Arabic, Aqua / Water]; ActiMatrix [INCI: Peptide-Based Mushroom Extract], Peptamide 6 [INCI: Hexapeptide-11], marketed by Active Organics / Arch; and combinations thereof.

[0146] The firming, skin elasticity, and / or restructuring agents may be Argassential [INCI: C10-16 Alkyl Glucoside, Dicaprylyl Ether, Glycerin] or Replexium BC [INCI: Dimethyl Isosorbide, Polysorbate 20, Aqua, Acetyl Tetrapeptide-11, Acetyl Tetrapeptide-9] marketed by BASF; Prolevis [INCI: Hydrolyzed Vegetable Protein] or Poretect [INCI: Caprylic / Capric Triglyceride, Sorbitan Trioleate, Apium Graveolens Seed Extract, Linum Usitatissimum Seed Extract] marketed by Sederma / Croda; Actifirm Ultra Advanced Botanicals [INCI: Centella Asiatica Extract, Rosmarinus Officinalis Leaf Extract, Dipropylene Glycol, Alcohol, Echinacea] marketed by Lipotec / Lubrizol. Angustifolia Leaf Extract] or Actifcol Advanced Botanical Ingredients [INCI: Aqua, Glycerin, Sodium Citrate, Lentinus Edodes Extract, Potassium Sorbate, Sodium Benzoate, Phytic Acid]; Densorphin™ [INCI: Vitex Agnus Castus Extract, Aqua, Maltodextrin] or PhytoCellTec™ nunatak® [INCI: Isomalt, Aqua, Saponaria Pumila Callus Culture Extract, Lecithin] sold by Mibelle; and combinations thereof.

[0147] Moisturizers include qua Shuttle [INCI: Sorbitol, Laminaria Digitata extract, Diatomaceous Earth] marketed by Infinitec; Aqua-Osmoline™ [INCI: Ceratonia Siliqua (Carob) Seed Extract] marketed by Vincience / ISP / Ashland; and Hydralphatine™ Asia [INCI: Hydrogenated Starch Hydrolysate, Panthenol, Bambusa Vulgaris Shoot Extract, Nelumbo Nucifera Flower Extract, Nymphaea Alba root extract], or Hydraporine™ [INCI: betaine, hydrogenated lecithin, honey, pectin]; PatcH2O™ [INCI: trehalose, urea, serine, glycerol polyacrylate, algin, sodium hyaluronate, pullulan], Aqu'activ™ [INCI: behenyl alcohol, glyceryl oleate, cocamide MIPA], Irwinol® [INCI: octyldodecanol, Irvingia gabonensis kernel butter, hydrogenated coco-glycerides], Lipodermol® [INCI: octyldodecanol, arachidyl propionate, tocopheryl acetate, retinyl palmitate, ethyl linoleate, ethyl linolenate], or Seanamin® SU, marketed by L.Serobiologiques / Cognis / BASF. [INCI: Sorbitol, Algae Extract, Chrondrus Crispus (Carrageenan), Fucus Vesiculosus Extract, Algin]; Snow and Ice Algae Powder [INCI: Coenochloris Signiensis Extract], marketed by Mibelle; Hyasol BT [INCI: Sodium Hyaluronate], Syn-Up™ [INCI: Benzylsulfonyl D-Seryl Homophenylalanine Amidinobenzamide Acetate], or Pentavitin® [INCI: Saccharide Isomerate], marketed by Pentapharm / DSM;Aqualance™ [INCI: Erythritol, Homarine HCl], Hydraprotectol™ [INCI: Glyceryl Polymethacrylate, Aromatic Acid, Yeast Extract (Faex), Glycoproteins], Moist 24™ [INCI: Imperata Cylindrica Root Extract], Optima™, marketed by Sederma / Croda Hyal™ [INCI: Hydrolyzed Yeast Extract, Cetyl Hydroxyethylcellulose, Polyglucuronic Acid], Osmocide® 4 [INCI: Glycerin, Acrylic Acid / C10-30 Alkyl Acrylate Crosspolymer], or Revidrate™ [INCI: Ethylhexyl Palmitate, Sorbitan Oleate, Sorbitan Laureate, Myristylphosphonic Malate]; Xpertmoist® Molecular Film [INCI: Glycerin, Pseudoalteromonas Ferment Extract, Xanthan Gum, Proline, Alanine, Serine, Ethylhexylglycerin, Caprylyl Glycol], or Actizyme GL Advanced Botanical Ingredients [INCI: Glycerin, Mucor miehei Extract, Aqua, Sodium Citrate, Potassium Sorbate, Sodium Benzoate, Phytic Acid], marketed by Lipotec / Lubrizol; and combinations thereof.

[0148] Anti-photoaging and / or blue light protection agents include Algaktiv Genofix CPD (INCI: Plankton extract, aqua, lecithin) marketed by Greenaltech; Blumilight™ Biofunctional (proposed INCI: Water / aqua (and) butylene glycol (and) Theobroma Cacao (cocoa) (seed extract)) marketed by Ashland; Lys'Sun (INCI: Hamamelis Virginiana leaf extract, aqua, pentylene glycol, caprylyl glycol, xanthan gum) marketed by BASF; Vitachelox (INCI: Vitis Vinifera seed extract, Camellia Sinensis leaf extract, Quercus Robur wood extract) marketed by Indena; Freshine L-VCG [INCI: Ascorbyl Glucoside] marketed by Bio-technology; Lumicease Blue Ingredients [INCI: Glycerin, Aqua, Hydrolyzed Pea Protein, Glucose, Sodium Chloride] marketed by Lipotec / Lubrizol; Lightwaves Defense [JS+M] [INCI: Jasminum Sambac Leaf Cell Extract] marketed by Naolys; Blue Oleoactif [INCI: Glycine Soja Oil, Polyglyceryl-3 Diisostearate, Oryza Sativa Germ Extract, Oryza Sativa Extract] marketed by Oleos-Hallstar; Majestem [INCI: Glycerin, Leontopodium Alpinum Callus Culture Extract, Xanthan Gum] or Senestem [INCI: Glycerin, Plantago sativa L. Extract] marketed by Sederma Lanceolata leaf extract, xanthan gum]; Blueshield [INCI: Glycerin, Capsicum Annuum fruit extract, xanthan gum], marketed by Solabia; and combinations thereof.

[0149] DNA protectants, DNA repair agents, and / or stem cell protectants include GP4G SP [INCI: Aqua, Glycerin, Aretmia extract], Heliostatine [INCI: Aqua, Glycerin, Pisum Sativum extract], Orsirtine [INCI: Aqua, Glycerin, Oryza Sativa extract], Chronogen [INCI: Aqua, Butylene Glycol, Tetrapeptide (proposed INCI)], Survixyl IS [INCI: Water, Butylene Glycol, Pentapeptide-31], and Chrondricare [INCI: Aqua, Butylene Glycol, Pentapeptide-28] marketed by Vincience / ISP / Ashland; Lanacityn® [INCI: Glycerin, Aqua, Alteromonas ferment extract, Chysanthellum spp.] marketed by Atrium Innovations / Lucas Meyer Cosmetics; indicum extract] or Melinoil [INCI: Isopropyl palmitate, lecithin, aqua, acetyl hexapeptide-1]; Repair Complex [INCI: Bifida ferment lysate] marketed by CLR; Phycojuvenine [INCI: Laminaria Digitata] marketed by Codif; Unirepair T-43 [INCI: Butylene glycol, acetyl tyrosine, proline, hydrolyzed vegetable protein, adenosine triphosphate] marketed by Induchem; Dragosine [INCI: Carnosine] marketed by Symrise; DN-Age [INCI: Cassia Alata leaf extract] marketed by Laboratories Serobiologiques / Cognis / BASF;Helioguard [INCI: Liposome-Encapsulated Porphyra Umbilicalis], PhytoCellTec Malus Domestica [INCI: PhytoCellTec Malus Domestica], or PhytoCellTec Argan [INCI: Argania Spinosa Sprout Cell Extract, Isomalt, Lecithin, Sodium Benzoate, Aqua], marketed by Mibelle Biochemistry; Pepha-Protect [INCI: Watermelon Extract], marketed by Pentapharm / DSM; Celligent [INCI: Helianthus Annuus Seed Oil, Ethyl Ferulate, Polyglyceryl-5 Trioleate, Rosmarinus Officinalis Leaf Extract, Aqua, Disodium Uridine Phosphate], or Defensil [INCI: Octyldodecanol, Echium Plantagineum Seed Oil, Cardiospermum Halicacabum Extract, Helianthus Annuus Seed Oil Unsaponifiables]; Venuceane [INCI: Thermus Thermophilus Ferment, Glycerin], UV-Soft [INCI: Yeast Extract], Renovage [INCI: Caprylic / Capric Triglyceride, Teprenone], Juvinity [INCI: Caprylic / Capric Triglyceride, Geranylgeranylpropanol (suggested)], Phytessence Holyherb [INCI: Butylene Glycol, Eriodictyon Californicum (Holyherb) Flower / Leaf / Stem Extract], or Resistem [INCI: Glycerin, Globularia Cordifolia Ferment], marketed by Sederma / Croda; Infraguard [INCI: Caesalpinia Spinosa Fruit Pod Extract, Propylene Glycol, Aqua, Helianthus Annuus Bud Extract, Sodium Benzoate, Phenoxyethanol], marketed by Mibelle;Heliomoduline (INCI: low molecular weight peptide from cotton) or Stem-C-Guard (hydrolyzed peas), marketed by Silab; and combinations thereof.

[0150] Reactive carbonyl species scavengers, free radical scavengers, and / or anti-glycation agents, detoxifying agents, antioxidants, and / or anti-pollution agents include, but are not limited to, carnosine and its derivatives; GHK [INCI: Tripeptide-1] and its salts and / or derivatives, or Quintescine IS [INCI: Dipeptide-4], marketed by Vincience / ISP / Ashland; Preregen [INCI: Glycine Soja (Soybean) Protein, Oxidoreductase], Edelweiss GC [INCI: Leontopodium Alpinum Extract], Lipogard [INCI: Squalane, Ubiquinone], Nectapure [INCI: Buddleja Davidii Extract, Thymus Vulgaris Extract], Alpaflor Nectapure [INCI: Buddleja Davidii Extract, Thymus Vulgaris Extract], Vulgaris extract, glycerin, water], or Dismutin-BT [INCI: highly purified SOD from a wild yeast strain of Saccharomyces cerevisiae]; Preventhelia® [INCI: diaminopropionoyl tripeptide-33], Aldenine® [INCI: hydrolyzed wheat protein, hydrolyzed soy protein, tripeptide 1], Lipochroman™ [INCI: dimethylmethoxychromanol], Thermostressine® [INCI: acetyl tetrapeptide-22], Pollushield™ functional ingredients [INCI: diisopropyl adipate, lecithin, acrylic acid / acrylamidomethylpropanesulfonic acid copolymer, dimethylmethoxychromanol, xanthan gum], or Bodyfensine® [INCI: aminohexanoic acid acetyl dipeptide-3], marketed by Lipotec / Lubrizol;unactyl [INCI: Mannitol, Pisum Sativum extract, Histidine HCl, Arginine, Cyclodextrin, Dextrin, Yeast extract, Acetyltrypsin, Pyridoxine HCl, Khaya Senegalensis peel extract, Nicotinamide, Adenine dinucleotide, Disodium succinate, Aspartic acid], Imidinyl [INCI: Tamarindus Indica seed polysaccharide], Phystrogene [INCI: Butylene glycol, Malva Sylvestris (mallow) extract, Xanthan gum], or Purisoft [INCI: Moringa Pterogysperma seed extract], marketed by Laboratoires Serobiologiques / Cognis / BASF; AquaCacteen [INCI: Glycerin, Opuntia Ficus Indica Stem Extract, Phenoxyethanol, Aqua], Trimoist (KMF) [INCI: Sodium Stearoyl Lactylate, Cetyl Alcohol, Olus Vegetable Oil, Tocopheryl Acetate, Glycerin, Glycine Soja Sterol, Sodium Lactate, Barboxymethyl Beta-Glucan Sodium, Carnosine, Lactic Acid], MelanoBronze [INCI: Vitex Agnus Castus Extract (Monk Pepper Fruit Extract (Phytoendorphin)), Acetyl Tyrosine], CM-Glucan [INCI: Carboxymethyl Beta-Glucan Sodium, Phenoxyethanol], SunActin [INCI: Helianthus Annuus (Sunflower) Sprout Extract], Tocopherol, Glycerin, Lecithin, Phenoxyethanol, Aqua], GSP-T Skin [INCI: Glycerin, Alcohol, Aqua, PEG-40 Hydrogenated Castor Oil, Vitis Vinifera (Grape) Seed Extract], or Detoxophane [INCI: Lepidium Sativum Bud Extract, Lecithin, Phenoxyethanol, Glycerin, Water];Bacocalmine [INCI: PEG-8, Bacopa Monniera extract, water (aqua), hydroxyethylcellulose], Kombuchka [INCI: Saccharomyces / Xylinum black tea ferment, glycerin, hydroxyethylcellulose], Citystem [INCI: Glycerin, Marrubium Vulgare extract], or Prodizia [INCI: Albizia Julibrissin extract, glycerin] marketed by Sederma / Croda; Extramel C [INCI: Hydroxypropyltrimonium maltodextrin crosspolymer, Cucumis Melo (melon)] fruit extract marketed by Seppic; Defensine [INCI: Triticum Vulgare germ extract], Apolluskin® [INCI: Taraxacum officinale (dandelion) extract], Detoxyl® [INCI: Water, butylene glycol, Butyrospermum parkii (Shea) butter, thyme] marketed by Silab. parkii (Shea Butter) Seed Cake Extract], or Antiglyskin [INCI: Aqua, Helianthus Annuus Seed Extract; and combinations thereof.

[0151] The compositions containing compounds of formula (I) and described herein may be for use in any of the applications or uses discussed above under the heading "Applications."

[0152] The invention is illustrated by the following non-limiting examples. [Example]

[0153] General method Abbreviation The abbreviations used for amino acids follow the recommendations of the 1983 IUPAC-IUB Joint Commission on Biochemical Nomenclature, as outlined in Eur. J. Biochem. (1984) 138:9-37.

[0154] (R), resin; 2-ClTrt-(R), 2-chlorotrityl resin; Ac, acetyl; AcOH, acetic acid; Ala, alanine; AM, 2-[4-aminomethyl-(2,4-dimethoxyphenyl)]phenoxyacetic acid; Arg, arginine; Asn, asparagine; Asp, aspartic acid; Boc, tert-butyloxycarbonyl; DCM, dichloromethane; DIEA, N,N'-diisopropylethylamine; DIPCDI, N,N'-diisopropylcarbodiimide; DMF, N,N-dimethylformamide; ESI-MS, electrospray ionization mass spectrometry; Fmoc, 9-fluorenylmethyloxycarbonyl; Gln, glutamine; Glu , glutamic acid; Gly, glycine; His, histidine; HOBt, 1-hydroxybenzotriazole; HPLC, high-performance liquid chromatography; Ile, isoleucine; KOH, potassium hydroxide; Leu, leucine; Lys, lysine; MBHA, p-methylbenzhydrylamine; MeCN, acetonitrile; MeOH, methanol; Met, methionine; Myr, myristoyl; Palm, palmitoyl; Pbf, 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl; Pro, proline; Ser, serine; tBu, tert-butyl; TFA, trifluoroacetic acid; Thr, threonine; Trt, trityl; Val, valine.

[0155] chemical synthesis All synthetic processes are carried out in polypropylene syringes fitted with porous polyethylene discs. Coupling procedures are carried out according to standard procedures based on literature references, and solvents and soluble reagents are removed by aspiration. The Fmoc group is removed using piperidine-DMF (2:8, v / v) (1 × 1 min, 1 × 5 min, 5 mL / g resin) ((Lloyd-Williams P. et al. (1997) "Chemical Approaches to the Synthesis of Peptides and Proteins", CRC, Boca Raton, FL, USA)). Washing between the deprotection, coupling and deprotection steps is carried out with DMF using 10 mL of solvent / g resin each time (3 × 1 min after coupling, 5 × 1 min after Fmoc removal). The coupling reaction is carried out using 3 mL of solvent / g resin. Coupling control is performed using the ninhydrin test [Kaiser E. et al., Anal. Biochem. (1970), 34:595-598] or the chloranil test [Christensen T., Acta Chem. Scand., (1979), 33B, 763-766]. The coupling reaction is repeated while synthesizing the desired peptide. All synthesis reactions and washings are carried out at 25°C.

[0156] Those skilled in the art will recognize that some amino acids are used with their side chain functional groups protected. For example, non-limiting examples of protecting groups include: For the amino acid Thr, tBu, tert-butyl

[0157] HPLC chromatography analysis was performed on a Shimadzu apparatus (Kyoto, Japan) using a reversed-phase column (50 × 4.6 mm, Kromasil C18, 3.5 μm, Akzo Nobel, Sweden) thermostated at 30 °C. Elution was performed using a gradient of acetonitrile (+0.07% TFA) in water (+0.1% TFA) at a flow rate of 1.6 mL / min, with detection at 220 nm. Electrospray ionization mass spectrometry was performed on a WATERS Alliance ZQ 2000 detector using MeCN:HO 4:1 (+0.1% TFA) as the mobile phase at a flow rate of 0.3 mL / min.

[0158] Example 1 Fmoc-W m -X n -AA1-AA2-AA 3- AA4-Y o -Z p -PS-(R) (wherein AA1 is L-Leu, AA2 is L-Pro, AA3 is L-Val, AA4 is L-Thr, and n, m, p, and q are each 0).

[0159] Weights were normalized. 1 equivalent of Fmoc-L-Thr(tBu)-OH was dissolved in dry DCM, and 0.8 equivalents of DIEA was added, followed by the addition of 2-chlorotrityl resin. After 5 minutes, the remaining 1.7 equivalents of DIEA were added, and the mixture was allowed to stir for an additional 40 minutes. Capping of unreacted resin was achieved with methanol for 10 minutes. The resin was filtered and washed with DCM (3 x 1 minute) and DMF (5 x 1 minute).

[0160] To remove the Fmoc group, Fmoc-Thr(tBu)-PS resin is treated with 5% piperidine in DCM / DMF 1:1 for 10 min, followed by 20% piperidine in DMF for 15 min. After washing the resin as described in General Methods, 2 equivalents of Fmoc-L-Val-OH are incorporated onto the deprotected resin in the presence of 2.2 equivalents of DIPCDI and 2 equivalents of Oxyma using DMF as solvent for 1 h.

[0161] The resin is then washed as described in the general methods and the Fmoc group deprotection procedure is repeated to couple the next amino acid (2 equivalents of Fmoc-L-Pro-OH followed by 2 equivalents of Fmoc-L-Leu-OH), coupled sequentially in the presence of 2 equivalents of Oxyma and 2.2 equivalents of DIPCDI at each coupling step.

[0162] After synthesis, the peptidyl resin is washed with DMF and DCM (3 x 1 min).

[0163] By following the method described, it is possible to obtain different sequences that vary the desired amino acids to be coupled.

[0164] Example 2 General method for removal of the Fmoc N-terminal protecting group. The N-terminal Fmoc group of the peptidyl resin obtained in Example 1 is deprotected as described in the general method (20% piperidine in DMF, 1 x 1 min + 1 x 5 min). The peptidyl resin is washed with DMF (5 x 1 min), DCM (3 x 1 min), diethyl ether (3 x 1 min) and dried under vacuum.

[0165] Example 3 A method for introducing an R1 palmitoyl group into the peptidyl resin obtained in Example 2. Five equivalents of palmitic acid, predissolved in DMF (1 mL), are added to each peptidyl resin obtained in Example 2 in the presence of Oxyma and DIPCDI. The mixture is reacted for 3 hours, after which the resin is washed with DMF (3 x 1 min), DCM (3 x 1 min), diethyl ether (3 x 1 min) and dried under vacuum.

[0166] Example 4 Method for introducing an R1 acetyl group into the peptidyl resin obtained in Example 2 Each of the peptidyl resins obtained in Example 3 is treated with acetic anhydride in the presence of DIEA using DMF as the solvent. The mixture is allowed to react for 30 minutes, after which the resin is washed with DMF (3 x 1 minute), DCM (3 x 1 minute), diethyl ether (3 x 1 minute) and dried under vacuum.

[0167] Example 5 Methods for cleaving the peptidyl resins obtained in Examples 2, 3, and 4 from the polymer support. Each of the dried peptidyl resins obtained in Examples 3, 4, and 5 is treated with 3 mL of TFA:HO (95:5, v / v) for 2 hours at room temperature under stirring. They are then filtered through a polypropylene syringe fitted with a porous polyethylene disk. The filtrate is collected on cold diethyl ether and washed five times with diethyl ether. The final precipitate is dried under vacuum.

[0168] HPLC analysis of the peptides obtained with a gradient of H2O (+0.1% TFA) containing MeCN (+0.07% TFA) shows a purity of more than 80% in all cases. The identity of the peptides obtained is confirmed by ESI-MS.

[0169] Example 6 Muscle-bound-like protein 1 (MBNL1) in human skeletal muscle cells (hSKMC) Increased MBNL-1 in muscle cells helps maintain muscle tone in facial skin, and compounds that can enhance MBNL-1 could therefore be used as a good approach to cosmetically treating the appearance of facial sagging.

[0170] method: Cell culture and treatment Human skeletal muscle cells (hSKMCs) were cultured at 100,000 cells per well in a T25 flask containing growth medium. After 4 days, cells reached approximately 80% confluency and were seeded at 150,000 cells per well in growth medium into 12-well plates. Cells were incubated for 72 hours, then switched to differentiation medium and incubated for 48 hours. At the end of this period, cells were treated with the specified peptides (0.5 mg / mL) for 48 hours in differentiation medium, or with medium alone for control conditions. Cells were also treated with 2 mM ketoprofen as a positive control.

[0171] Protein extraction and quantification After the incubation period, cells were lysed and frozen at -80°C. Protein extracts were measured by the bicinchoninic acid (BCA) method for total protein quantification. MBNL1 protein detection was performed by homogeneous time-resolved fluorescence (HTRF) method. Correction of MBNL1 levels was performed by quantifying total protein for each condition. Results are expressed as relative MBNL1 protein levels to the control condition. At least three replicates were performed for each condition.

[0172] [Table 4]

[0173] Example 7 Muscle-binding-like protein 1 (MBNL1) in human dermal fibroblasts (HDFs) The purpose of this study was to evaluate the increase in MBNL1 protein in human skin fibroblasts after electrical stimulation mimicking a microcurrent-like treatment. Topical products capable of increasing MBNL1 protein levels in fibroblasts could induce the same anti-aging effects on skin as microcurrent-like treatments, while avoiding the side effects of physical microcurrent treatments.

[0174] Microcurrent stimulation assay: Cells were seeded at 100,000 cells / well in 12-well plates on sterile glass slides and incubated at 37°C and 5% CO2 for 48 hours. Electrical stimulation was then performed. The slides were transferred to 6-well plates and electrically stimulated (1.5 V) for 1 hour at room temperature using a C-dish apparatus (IonOptix). An identical 6-well plate containing unstimulated cells was incubated at room temperature for 1 hour. After electrical stimulation, the slides were again transferred to 12-well plates and incubated at 37°C and 5% CO2 for 24 hours. Three different replicates were used for each condition.

[0175] Peptide treatment Cells were seeded at 8,000 cells / well in a 96-well plate and incubated at 37°C, 5% CO2 for 48 hours. After the incubation period, cells were treated with 0.01 mg / mL, 0.1 mg / mL, or 0.5 mg / mL of PEP-1 (H-Leu-Pro-Val-Thr-OH) for 24 hours. Cells incubated with medium alone served as a control. Three replicates were performed for each condition.

[0176] MBNL1 immunofluorescence and quantification After 24 hours of incubation, the cells were washed twice with phosphate-buffered saline (PBS), fixed with 4% paraformaldehyde (PFA) for 15 minutes, and washed twice again. The cells were then permeabilized with 1% X-Triton® solution for 15 minutes and blocked with 5% bovine serum albumin (BSA) for 1 hour. The cells were then incubated with a 1 / 20 dilution of primary antibody against MBNL1 protein (Sigma) in 5% BSA for 2 hours. After the incubation period, the cells were washed and incubated with a 1 / 200 dilution of secondary antibody (AlexFluor 488) in 5% BSA for 1 hour. Finally, the cells were washed three times and stained with 4',6-diamidine-2'-phenylindole dihydrochloride (DAPI) mounting solution for nuclear detection. MBNL1 protein quantification was measured as the fluorescence intensity of MBNL1 corrected by the number of nuclei for each condition using a confocal microscope (Operetta® Confocal Microscope, PerkinElmer Inc.) using the Alexa 488 Green channel (Ex: 460-490 nm / Em: 500-550 nm). Results are expressed as MBNL1 levels relative to the MBNL1 levels in the control condition. At least three independent experiments were analyzed in this assay.

[0177] The results were calculated using the following formula:

[0178]

number

[0179] 1. Detection of MBNL1 protein after microcurrent stimulation As shown in Table 5, electrical stimulation (70 mV mm -1 ; <1 mA, 1.5 V, 1 h) can increase MBNL1 protein in human fibroblasts compared to the basal control (CTR; no MES).

[0180] [Table 5]

[0181] 2. Detection of MBNL1 protein after peptide treatment As shown in Table 6, PEP-1 (H-Leu-Pro-Val-Thr-OH) increases MBNL1 protein in human fibroblasts under the conditions tested compared to the basal control (CTR; no MES). Table 6 shows that PEP-1 can induce MBNL1 protein expression at a level comparable to MES.

[0182] [Table 6]

[0183] 3. Comparison of MBNL1 intensity in HDFa cells in response to electrical stimulation. For comparison, the effect of the peptide was compared with that of MES. The effect was calculated as follows:

[0184]

number

[0185] The results are shown in Table 7.

[0186] [Table 7]

[0187] The results show that PEP-1, like MES, has a pronounced effect on the level of MBNL1 protein expression in fibroblasts.

[0188] Example 8 Effects of microcurrent and PEP-1 on collagen contraction assay The significant changes in the mechanical properties of skin with aging are known to be due to a decrease in the contractile capacity and migratory activity of fibroblasts. Healthy fibroblasts induce contraction of the collagen network through physical interactions with collagen fibers. The collagen network is essential for maintaining skin firmness. The collagen contraction assay is a well-known experimental approach for measuring cell-induced contraction of the extracellular matrix. This assay evaluates the ability of fibroblasts embedded in a collagen-based gel to reduce the gel diameter.

[0189] By improving contractile force, mechanical tension can be improved and may be associated with a "lifting" effect on the scale of the fibroblasts.

[0190] Microcurrent Systems: The microcurrent system was constructed by attaching gold electrodes (to avoid oxidation of the medium, which would result in cell death when current was passed) to opposite sides of 60 mm Petri dishes (4 cm apart). When a voltage was applied, an electric field was generated between the opposing positive and negative electrodes, causing a current to pass through the culture. During the stimulation period (2 hours), each of the 60 mm Petri dishes was connected to a voltage source, allowing for adjustment of the amount of current passing through each. In these experiments, a current of 40 μA / Petri (corresponding to approximately 67 mV / mm) was used.

[0191] Cell culture preparation and growth: Culture and expansion of human dermal fibroblasts (HDFs): Cells were thawed in T75 flasks and the growth medium was changed every 2 days of cell culture. After 7 days, cells were expanded to a total of 7 x 10 6 The cells used in the experiments were obtained.

[0192] Peptide treatment and 3D collagen gel: Once growth was complete, the cultures were trypsinized and 3 × 10 5 Cells were seeded per 60 mm Petri dish, up to a total of 10 dishes per replicate. These 10 dishes correspond to one experiment at a particular concentration (control / -MES vs +MES). Peptide treatment was performed at 0.01 mg / mL.

[0193] After overnight incubation to allow cells to attach, each Petri dish was treated with 4 mL of the specified medium at the corresponding concentration for both conditions (without MES and with MES) for a total of 24 hours. Peptide treatment on dishes not stimulated with microcurrent began 2 hours before passage into 3D culture, coinciding with microcurrent stimulation of the other dishes. For dishes stimulated with microcurrent, the medium was replaced with 2.5 mL of fresh medium before stimulation and treated with peptide alone for a total of 22 hours, followed by peptide and electrical stimulation for 2 hours.

[0194] Each 3D culture was prepared by mixing the collagen solution with the corresponding culture medium for each condition (without or with peptide). Thus, the complete peptide treatment period included 48 hours (24 hours of 2D stimulation and 24 hours of 3D stimulation). 3D culture in type I collagen hydrogel required the following elements: (i) preparation of neutralized rat tail type I collagen stock and (ii) a cell suspension at a specific cell concentration. Plaques were placed at 37°C for 45 minutes. After incubation, the cultures were detached, detached from the well walls, and allowed to shrink. A cell-free control was also separated. 0.5 mL of the respective warm medium was added to the top of each well. Images of the collagen gel diameter were taken from each well 24 hours after detachment and analyzed using ImageJ.

[0195] -Image quantification The contraction of the hydrogel can be thought of as a deformation experienced as a change in surface area.

[0196]

number

[0197] Import the images into ImageJ.

[0198] The scale is the diameter of the well (d = 1.54 cm 2 ) The diameter was simulated in ImageJ and is constructed to be 1.54 units.

[0199] The perimeter of the hydrogel is circled and the area is calculated for each image. - Calculate the average across replicates for each condition. - Area deformation is calculated based on the Δ area formula and data converted to absolute %.

[0200] The results are shown in Table 8 below.

[0201] [Table 8] 1 Statistical calculations were performed using unpaired t-tests. ** p<0.01, *** p<0.001, ns: no significant difference

[0202] The results show that PEP-1 stimulates collagen contraction to the same extent as MES.

[0203] Example 9 Immunofluorescence determination of myofibroblast marker EDA-Fn EDA-Fn is an isoform of fibronectin that serves as a marker for the presence of myofibroblasts.

[0204] - Cell harvesting and seeding Following the experimental protocol described in Example 8, cells were harvested by extracting them from the 3D culture and reseeding them on glass coverslips. To harvest the cells, collagen hydrogels were digested with collagenase solution at 37°C with stirring. After digestion, cycles of centrifugation and washing were performed to remove collagen residues. The cells were then seeded on glass coverslips in duplicate as in the 3D culture conditions of Example 8. For subsequent fluorescence analysis, the cells were harvested at 3 × 10 5 fibroblasts / cm 2 The cells were seeded onto collagen-precoated coverslips at a density of 1000 μg / cm, allowed to attach overnight, and fixed in 4% PFA.

[0205] -EDA-Fn immunofluorescence Coverslips were used for EDA-Fn immunofluorescence, a marker for myofibroblasts. EDA-Fn immunofluorescence was performed in control samples (with or without MES) and after peptide treatment (PEP-1 0.01 mg / mL). Briefly, cells attached to the coverslips were permeabilized with 0.5% Triton® X-100 in PBS for 10 minutes at room temperature. Blocking solution (4% BSA in PBS) was then added for 2 hours. Cells were then washed three times in PBS and incubated with primary antibody solution (Abcam IST-9, EDA-FN) using 1 / 500 dilution of 4% BSA in PBS for 2 hours in the dark. Cells were then washed three times in PBS and incubated with secondary antibody solution (Alexa Fluor 488) using 1 / 500 dilution of 4% BSA in PBS for 1 hour in the dark. Cells were then washed again in PBS, and DAPI stain was added to stain the nuclei. Coverslips were mounted on glass slides for analysis. Finally, green fluorescence intensity was quantified for each condition using Operetta (PerkinElmer) and corrected for the number of nuclei. The CTR condition (no electrical stimulation) was corrected by 100 and compared to the CTR MES and peptide-treated conditions using the following formula:

[0206]

number

[0207] Calculations were performed for four replicate experiments.

[0208] [Table 9] Statistical calculations were performed using unpaired t-tests: ** p<0.01, **** p<0.0001.

[0209] The results demonstrate that PEP-1 was able to increase the presence of myofibroblasts.

[0210] Example 10 Preparation of a light cream containing 2 wt% PEP-1 peptide solution In a suitable container, weigh out the ingredients of Phase A: Water [INCI: Water (Aqua)].

[0211] Next, add Phase A1 ingredients: Phenoxyethanol [INCI: Phenoxyethanol], Disodium EDTA [INCI: Disodium EDTA], Potassium Sorbate [INCI: Potassium Sorbate] and Zemea® [INCI: Propanediol] to Phase A and mix until homogeneous.

[0212] Next, add Phase B1: Carbopol® Ultrez 21 polymer (INCI: Acrylates / C10-30 Alkyl Acrylate Crosspolymer) to the previous mixture with stirring. Once dispersed, add Phase B2: Xanthan Gum [INCI: Xanthan Gum] to the previous mixture and stir until homogeneous.

[0213] Next, add Phase C: Schercemol™ 1818 ester [INCI: Isostearyl isostearate] to the vessel and mix until fully incorporated into the mixture. Finally, add Phase D: PEP-1 peptide solution [INCI: Water, Caprylyl Glycol and Tetrapeptide-1] and mix with gentle stirring until homogenous.

[0214] Adjust pH to 6.0-6.5 with Phase E ingredients: Sodium hydroxide 20% w / w [INCI: Water (Aqua), Sodium Hydroxide].

[0215] [Table 10]

[0216] Example 11 In vivo study to assess jawline firmness in Caucasian volunteers. The study was conducted for 28 days. 46 volunteers, aged 40-65 years, were included in the study and divided into two groups. Group 1 included 36 volunteers (31 women and 5 men) who applied the composition described in Example 5 twice daily to half of their faces for 28 days, and a placebo cream containing the same ingredients except for PEP-1 to the other half. Group 2 included 10 volunteers (9 women and 1 man) who used a microcurrent device (Nuface®) once daily with an activator gel containing no active ingredients. Volunteers using the microcurrent device were trained on how to apply the activator gel and how to use the device to standardize application across volunteers.

[0217] Subjects served as their own references, and the results obtained at 28 days were compared with those obtained at the initial time point. Furthermore, the results obtained in volunteers using the microcurrent device were compared with those obtained in volunteers who applied the placebo and active cream.

[0218] The effectiveness of the product was evaluated by the R0 parameter measured with a Cutometer® (Courage & Khazaka) at the beginning and 28 days after product application. The R0 parameter is defined as the maximum width after applying suction to the skin using negative pressure. The higher the resistance of the skin to negative pressure, the firmer it is. Thus, a decrease in the R0 parameter indicates an increase in skin firmness. R0 measurements were taken at two adjacent points on the volunteer's jawline, and an average value was obtained for each time point of the study.

[0219] Jawline firmness was assessed by the mean variation of the R0 parameter, and the results are shown in Table 11.

[0220] [Table 11]

[0221] The results, shown in Table 11, demonstrate that after 28 days of application of the composition of Example 5, there was a significant decrease in the R parameter, which was greater and more significant than that observed for the placebo cream. The results show that firmness improved after 28 days of product application, providing changes similar to those achieved with microcurrent.

[0222] Example 12 In vivo study to evaluate brow lift efficacy in Caucasian volunteers. The study was conducted for 28 days. 46 volunteers, aged 40-65 years, were included in the study and divided into two groups. Group 1 included 36 volunteers (31 women and 5 men) who applied the composition described in Example 5 to one half of their face twice daily for 28 days, and a placebo (the same composition without the peptide) to the other half. Group 2 included 10 volunteers (9 women and 1 man) who used a microcurrent device (Nuface®) once daily with an activator gel containing no active ingredients. Volunteers using the microcurrent device were trained on how to apply the activator gel and how to use the device to standardize application across volunteers.

[0223] Subjects served as their own references, and the results obtained at 28 days were compared with those obtained at the initial time point. Furthermore, the results obtained in volunteers using the microcurrent device were compared with those obtained in volunteers who applied the placebo and active cream.

[0224] The images of the volunteer's face were taken at the first application and 28 days after application.The effectiveness of the product was evaluated by measuring the diagonal distance between the eyelashes and eyebrows, which was obtained from image analysis using FrameScan® software.The diagonal distance was calculated by drawing a horizontal line (lash line) between the start point of the eyelashes and the end point of the eyelashes.An additional line was then drawn diagonally from the central zone of the lips to the upper arch of the eyebrow, intersecting the exact midpoint of the previously drawn lash line.The brow lift measurement corresponds to the distance from the midpoint of the lash line to the end of the brow arch.

[0225] The brow lift effect was assessed by the mean change in diagonal distance, as seen in the results shown in Table 12.

[0226] [Table 12]

[0227] The results shown in Table 12 demonstrate that after 28 days of application of the composition of Example 10, there was a significant increase in diagonal distance compared to the placebo cream, and the same was observed with the microcurrent device. Furthermore, a comparison of the active cream versus the placebo cream shows a significant effect. The results show that brow lift increased after 28 days of product application, with a similar variation to that achieved with the microcurrent device.

[0228] Example 13 In vivo study to evaluate the anti-wrinkle effect of the peptides of the invention in Caucasian volunteers. The study lasted for 7 days. 45 volunteers, aged 40-65 years, were included in the study and divided into two groups. Group 1 included 36 volunteers (31 women and 5 men) who applied the composition described in Example 10 to one half of their face twice daily for 7 days, and a placebo cream to the other half. Group 2 included 9 volunteers (8 women and 1 man) who used a microcurrent device (Nuface®) once daily with an activator gel containing no active ingredients. Volunteers using the microcurrent device were trained on how to apply the activator gel and how to use the device to standardize application across volunteers.

[0229] Subjects served as their own references, and the results obtained at 7 days were compared with those obtained at the initial time point. Furthermore, the results obtained in volunteers using the microcurrent device were compared with those obtained in volunteers who applied the placebo and active cream.

[0230] Images of the fine wrinkle area of ​​the volunteers' crow's feet were taken on the first and seventh day after product application. Product effectiveness was assessed by the visibility index obtained from image analysis using FrameScan® software. The visibility index is defined as the wrinkle occupancy multiplied by the wrinkle / skin contrast, finally multiplied by 100.

[0231] The anti-wrinkle effect was evaluated by the mean variation of the visibility index, which is used to evaluate the visibility of wrinkles. The results are shown in Table 13.

[0232] [Table 13]

[0233] The results shown in Table 13 demonstrate that after 7 days of application of the composition of Example 10, there is a significant change in the visibility index compared to the placebo cream, and the same is observed with the microcurrent device. Furthermore, a comparison of the active cream versus the placebo cream shows a low significant effect. According to the results, the visibility of wrinkles is reduced after 7 days of application of the product, a result that mimics the effect of the microcurrent device.

[0234] Example 14 Preparation of a gel cream containing peptide PEP-1. In a suitable container, disperse the ingredients of Phase A: water [INCI: Water (AQUA)], Zemea™ [INCI: Propanediol], Phenoxetol® [INCI: Phenoxyethanol], Dissolvine® NA2 [INCI: Disodium EDTA], and potassium sorbate granules [potassium sorbate].

[0235] Phase A1 ingredients: Carbopol® Ultrez 21 Polymer (INCI: (Acrylates / C10 / 30 Alkyl Acrylate) Crosspolymer) are added to the previous mixture with stirring. Once dispersed, Phase A2: Xanthan Gum (INCI: Xanthan Gum) is introduced into the previous mixture and stirred until completely dispersed.

[0236] In a separate container, weigh out the ingredients for Phase B: Schercemol™ 1818 Ester (INCI: Isostearyl Isostearate).

[0237] The emulsion is made by slowly adding Phase B to Phase A under high speed turbine agitation.

[0238] Phase C: Peptide PEP-1 Solution [INCI: Water (Aqua), Caprylyl Glycol, Peptide PEP-1] is added to the previous mixture.

[0239] Adjust pH to 6.0-6.5 with Phase D ingredients: Sodium hydroxide 20% w / w [INCI: Water (Aqua), Sodium Hydroxide].

[0240] [Table 14]

[0241] Gel creams containing other peptides of the present invention can be prepared by substituting PEP-1 with other peptides disclosed herein.

[0242] Example 15 Preparation of a lotion containing 2% of the peptide PEP-1. In a suitable container, dissolve the ingredients of Phase A1: water [INCI: Water (AQUA)], Zemea™ [INCI: Propanediol], glycerin [INCI: Glycerin], potassium sorbate [INCI: Potassium sorbate], and Dissolvine® NA2 [INCI: Disodium EDTA].

[0243] Phase A2 components: Carbopol® Ultrez 30 Polymer [INCI: Carbomer] are added to the previous mixture. Once dispersed, Phase A3: Xanthan Gum [INCI: Xanthan Gum] is introduced. The mixture is then heated to 70-75°C.

[0244] In a separate container, combine the Phase B ingredients: Fancor® Meadowfoam Seed Oil [INCI: Limnanthes Alba (Meadowfoam) Seed Oil], Kodasil 600 IDD Gel [INCI: Isododecane; Vinyl Dimethicone / Lauryl Dimethicone Crosspolymer; Dimethicone; Lauryl Dimethicone], Astro-sil 2C 350 [INCI: Dimethicone], Schercemol™ CATC Ester [INCI: Cocoyl Adipate / Trimethylolpropane Copolymer; Trimethylolpropane], Schercemol™ DIS Ester [INCI: Diisopropyl Sebacate], Tocopheryl Acetate [INCI: Tocopheryl Acetate], and Phenocetol™ [INCI: Phenoxyethanol] and heat the resulting mixture to 70-75°C.

[0245] The emulsion is made by slowly adding Phase B to Phase A under high speed turbine agitation.

[0246] Once the mixture has cooled to 40°C, the ingredients of Phase C: Novemer™ EC-2 polymer [INCI: Water (Aqua); Sodium Acrylate / Beheneth-25 Methacrylate Crosspolymer; Hydrogenated Polydecene, Lauryl Glucoside], SA-SB-300 (7%) [INCI: Silica; Dimethicone], Fragrance [INCI: Fragrance (Parfum)], and Peptide PEP-1 Solution [INCI: Water (Aqua), Caprylyl Glycol, Peptide PEP-1] are added to the previous mixture.

[0247] Adjust the pH to 6.0-6.5 with Phase D ingredients sodium hydroxide 20% w / w [INCI: Water (Aqua), Sodium Hydroxide].

[0248] [Table 15]

[0249] Lotions containing other peptides of the present invention can be prepared by substituting other peptides disclosed herein for PEP-1.

[0250] Example 16 Preparation of a fluid emulsion containing 2% peptide PEP-1 In a suitable container, dissolve the ingredients of Phase A1: Water [INCI: Water (Aqua)], Zemea™ [INCI: Propanediol], Glycerin [INCI: Glycerin], Genencare™ OSMS BA [INCI: Betaine], Dissolvine® NA2 [INCI: Disodium EDTA], Potassium Sorbate [INCI: Potassium Sorbate].

[0251] Phase A2: Carbopol® ultrez 10 polymer (INCI: Carbomer) is added to the previous mixture. Once dispersed, Phase A3: Cola® Fax CPE-K (INCI: Potassium Cetyl Phosphate) is added. The resulting mixture is heated to 70-75°C.

[0252] In a separate vessel, mix the ingredients of phase B: Massocare® HD (INCI: Isohexadecane), Lincoln BAS (INCI: C12-15 Alkyl Benzoate), Gandak C (INCI: Cetyl Alcohol), Sorbital T 20 P (INCI: Polysorbate 20), 2-Phenoxyethanol (INCI: Phenoxyethanol), Vegetable Stearic Acid 50 / 50 (INCI: Stearic Acid, Palmitic Acid) and heat to 70-75°C. Phase B is slowly introduced into phase A under vigorous turbine stirring.

[0253] Cool the mixture to 40 °C and add Phase C: BRB CM 56-S (INCI: Cyclomethicone), Peptide PEP-1 Solution (INCI: Water (Aqua), Caprylyl Glycol, Peptide PEP-1), and Fragrance (INCI: Fragrance (Parfum)). Adjust the pH to 6.0-6.5 with Phase D ingredients: Sodium Hydroxide 20 w / w% [INCI: Water (Aqua); Sodium Hydroxide].

[0254] [Table 16]

[0255] Fluid emulsions containing other peptides of the present invention can be prepared by substituting other peptides disclosed herein for PEP-1.

[0256] Example 17 Effect of a comparison peptide not encompassed by the present invention on collagen contraction. The ability of different peptides (not according to the invention) to stimulate collagen contraction was carried out using the same procedure as in Example 8.

[0257] [Table 17]

[0258] The results are shown in Table 17. None of the peptides were able to stimulate collagen contraction.

[0259] Example 18 In vivo study to evaluate the brow lifting effect of the comparative peptide Ac-Asp-Val-Tyr-Lys-NH2. A 28-day study was conducted to assess the lifting effect of Ac-Asp-Val-Tyr-Lys-NH2. Forty-two Caucasian female volunteers, aged 35 to 58 years, exhibiting skin wrinkles in the crow's feet area were included. Subjects applied a cream containing Ac-Asp-Val-Tyr-Lys-NH2 and a placebo cream with the same composition, except for the peptide, to one side of their face (left or right). Both creams were applied twice daily (morning and evening) for 28 days. Subjects served as their own baseline, and the results obtained on day 28 were compared with those obtained initially and during treatment. The brow lifting effect was assessed as described in Example 12.

[0260] [Table 18]

[0261] The results are shown in Table 18 and demonstrate that the peptide Ac-Asp-Val-Tyr-Lys-NH2 had no lifting effect.

[0262] Various aspects and embodiments of the present invention are defined by the following numbered clauses: 1. Formula (I): R1-W m -X n -AA1-AA2-AA3-AA4-Y o -Z p -R2(I) Stereoisomers and / or cosmetically acceptable salts thereof, wherein: AA1 is Leu, Ile, or Val, AA2 is Pro, Ala, or Gly; AA3 is Val, Ile, or Leu; AA4 is Thr, Val or no amino acid; W, X, Y, and Z are each independently any amino acid; m, n, p, and q are each independently 0 or 1; m+n+p+q is less than or equal to 2, R1 is selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, an alicyclyl, a heterocyclyl, a heteroarylalkyl, an aryl, an aralkyl, and R5-CO-, and R5 is selected from the group consisting of H, an acyclic aliphatic group, an alicyclyl, an aryl, an aralkyl, a heterocyclyl, and a heteroarylalkyl; R2 is selected from the group consisting of -NR3R4, -OR3, -SR3, and R3 and R4 are independently selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, and aralkyl; R1 and R2 are compounds that are not amino acids. 2. The compound according to paragraph 1, wherein AA1 is Leu or Val, preferably AA1 is Leu. 3. The compound according to paragraph 1 or 2, wherein AA2 is Pro. 4. The compound according to any one of paragraphs 1 to 3, wherein AA3 is Val or Leu, preferably AA3 is Val. 5. The compound according to any one of paragraphs 1 to 4, wherein AA4 is Thr or Val. 6. The compound according to any one of items 1 to 4, wherein AA4 is Thr or no amino acid. 7. The compound according to paragraph 6, wherein AA4 is no amino acid, AA1 is Leu, and / or AA2 is Pro, and / or AA3 is Val. 8. The compound according to any one of items 1 to 7, wherein m+n+p+q is 0 or 1. 9. The compound of any one of clauses 1-8, wherein, if present, each of XW, X, Y and Z is independently selected from the group consisting of Ala, Val and Ile. 10. The compound according to paragraph 9, wherein AA3 is Val. 11. The compound is R1-Leu-Pro-Val-Thr-R2, R1-Leu-Ala-Val-Thr-R2, R1-Leu-Pro-Ile-Thr-R2, R1-Val-Pro-Val-Thr-R2, R1-Leu-Gly-Val-Thr-R2, R1-Leu-Pro-Leu-Thr-R2, R1-Ala-Leu-Pro-Val-Thr-R2, R1-Leu-Pro-Val-R2, or The compound according to claim 1, wherein R1-Ile-Pro-Ile-Thr-R2. 12. R1 is selected from the group consisting of H and R5-CO-, and R5 is C1-C 18 Alkyl, C2-C 24 Alkenyl, C3-C 24 cycloalkyl, R2 is —NR3R4 or —OR3, and R3 and R4 are independently selected from the group consisting of H and C1-C 16 12. The compound according to any one of items 1 to 11, wherein the compound is selected from the group consisting of alkyl. 13. A compound is H-Leu-Pro-Val-Thr-OH, H-Leu-Pro-Val-Thr-NH2, Palm-Leu-Pro-Val-Thr-OH, Ac-Leu-Pro-Val-Thr-OH, Ac-Leu-Pro-Val-Thr-NH2, H-Leu-Ala-Val-Thr-OH, H-Leu-Pro-Ile-Thr-OH, H-Val-Pro-Val-Thr-OH, H-Leu-Gly-Val-Thr-OH, H-Leu-Pro-Leu-Thr-OH, H-Ala-Leu-Pro-Val-Thr-OH, H-Leu-Pro-Val-OH, or 2. The compound according to claim 1, wherein the compound is H-Ile-Pro-Ile-Thr-OH. 14. The compound according to any one of items 1 to 13, wherein the compound is not H-Lys-Leu-Pro-Val-Thr-OH or H-Leu-Pro-Val-Thr-Leu-Arg-OH. 15. The compound according to any one of clauses 1 to 14, wherein the compound is not H-Leu-Pro-Ile-Thr-OH, H-Leu-Pro-Leu-Thr-OH or H-Leu-Pro-Val-Thr-Gly-OH. 16. A composition comprising a cosmetically effective amount of a compound of formula (I), its stereoisomer and / or cosmetically acceptable salt as defined in any one of items 1 to 15, and at least one cosmetically acceptable excipient or adjuvant. 17. Use of a compound according to any one of claims 1 to 15, a stereoisomer thereof and / or a cosmetically acceptable salt thereof for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes. 18. Use according to item 17, wherein the cosmetic non-therapeutic treatment and / or care is treatment and / or prevention of symptoms of skin ageing, reduction and / or prevention of skin wrinkles, improvement or maintenance of skin firmness, treatment and / or prevention of the appearance of sagging skin and / or skin lifting. 19. A method for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails, and / or mucous membranes of a subject, comprising administering a cosmetically effective amount of a compound according to any one of claims 1 to 15.

Claims

1. Formula (I): R １ -W ｍ -X ｎ -AA １ -AA ２ -AA ３ -AA ４ -Y ｏ -Z ｐ -R ２ Compound (I), Stereoisomers and / or cosmetically acceptable salts thereof, wherein: A.A. １ is Leu, He or Val, A.A. ２ is Pro, Ala or Gly, A.A. ３ is Val, He, or Leu, A.A. ４ is Thr, Val or no amino acid, W, X, Y, and Z are each independently any amino acid; m, n, p, and q each independently represent 0 or 1; m+n+p+q is equal to or less than 2; R １ is H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, aralkyl, and R ５ -CO-, and R ５ is selected from the group consisting of H, an acyclic aliphatic group, alicyclyl, aryl, aralkyl, heterocyclyl, and heteroarylalkyl; R ２ is -NR ３ R ４ , -OR ３ , -SR ３ and R ３ and R ４ are independently selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, and aralkyl; R １ and R ２ is not an amino acid, However, the compound of formula (I) is not H-Leu-Pro-Ile-Thr-OH, H-Leu-Pro-Leu-Thr-OH, H-Leu-Pro-Val-Thr-Gly-OH, H-Lys-Leu-Pro-Val-Thr-OH or H-Leu-Pro-Val-Thr-Leu-Arg-OH.

2. A.A. １ is Leu or Val, preferably AA １ The compound of claim 1 , wherein is Leu.

3. A.A. ２ 3. The compound of claim 1 or claim 2, wherein is Pro.

4. A.A. ３ is Val or Leu, preferably AA ３ The compound according to any one of claims 1 to 3, wherein is Val.

5. A.A. ４ The compound according to any one of claims 1 to 4, wherein is Thr or Val.

6. A.A. ４ is Thr or no amino acid.

7. A.A. ４ is free of amino acids, and AA １ is Leu and / or AA ２ is Pro and / or AA ３ The compound of claim 6, wherein is Val.

8. The compound according to any one of claims 1 to 7, wherein m+n+p+q is 0 or 1.

9. The compound is R １ -Leu-Pro-Val-Thr-R ２ 、 R １ -Leu-al��Thr-R ２ 、 R １ -Val-Pro-Val-Thr-R ２ 、 R １ -Leu-Gly-Val-Thr-R ２ 、 R １ -Alpha -Black -Yellow -Yellow -Black -Yellow ２ 、 R １ -Leu-Pro-Val-R ２ , or R1-Ile-Pro-Ile-Thr-R ２ 2. The compound of claim 1, wherein:

10. R １ But H and R ５ -CO-, and R ５ is C １ ~C １８ Alkyl, C ２ ~C ２４ Alkenyl, C ３ ~C ２４ cycloalkyl; R ２ is -NR ３ R ４ Or -OR ３ and R ３ and R ４ are independently H and C １ ~C １６ The compound of any one of claims 1 to 9, wherein the compound is selected from the group consisting of alkyl.

11. The compound is H-Leu-Pro-Val-Thr-OH, White House ２ 、 Palm-Leu-Pro-Val-Thr-OH, Ac-Leu-Pro-Val-Thr-OH, Ac-Leu-Pro-Val-Thr-NH ２ 、 H-Leu-Ala-Val-Thr-OH, H-Val-Pro-Val-Thr-OH, H-Leu-Gly-Val-Thr-OH, H-Ala-Leu-Pro-Val-Thr-OH, H-Leu-Pro-Val-OH, or The compound of claim 1 , which is H-Ile-Pro-Ile-Thr-OH.

12. A composition comprising a cosmetically effective amount of a compound of formula (I) according to any one of claims 1 to 11, its stereoisomer and / or cosmetically acceptable salt, and at least one cosmetically acceptable excipient or adjuvant.

13. Use of a compound, its stereoisomer and / or cosmetically acceptable salt according to any one of claims 1 to 11 for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes.

14. 14. The use according to claim 13, wherein the cosmetic non-therapeutic treatment and / or care is the treatment and / or prevention of symptoms of skin ageing, the reduction and / or prevention of skin wrinkles, the improvement or maintenance of skin firmness, the treatment and / or prevention of the appearance of sagging skin and / or skin lifting.

15. 12. A method for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails, and / or mucous membranes of a subject, comprising administering a cosmetically effective amount of a compound according to any one of claims 1 to 11.

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