Compounds useful for treating and / or caring for skin, hair, nails and / or mucous membranes

Abstract

The present invention relates to a compound of formula (I) R1-Wm-Xn-AA1-AA2-AA3-AA4-Yo-Zp-R2, stereoisomers and / or cosmetically acceptable salts thereof, in which: AA1 is Leu, Ile or Val; aA2 is Pro, Ala or Gly; aA3 is Val, Ile or Leu; aA4 is Thr, Val or a non-amino acid. The compounds are useful for treating and / or preventing symptoms of skin aging, and in particular for treating and / or preventing skin wrinkles, improving or maintaining skin compactness, treating and / or preventing the appearance of skin sagging, and / or lifting skin.

Description

TECHNICAL FIELD

[0001] The present invention relates to compounds that can be used for treating and / or caring for the skin, hair, nails, and / or mucous membranes. Specifically, the compounds can be used for treating and / or preventing skin aging, and in particular for treating and / or preventing skin wrinkles, improving or maintaining skin firmness, treating and / or preventing the appearance of skin sagging, and / or lifting the skin. The present invention extends to compositions containing the compounds and methods of treatment using the compounds. BACKGROUND ART

[0002] The effects of aging play a major role in the appearance of the skin. The most obvious signs of facial aging include facial wrinkles and the appearance of sagging.

[0003] One of the most popular methods for reducing facial sagging is a facelift. A facelift, also known as rhytidectomy, is a cosmetic surgical procedure designed to reduce skin sagging or folds on the cheeks and jaw, as well as other changes in the facial shape that occur with aging. During a facelift, flaps of skin on both sides of the face are pulled back, and the tissue under the skin is surgically altered to restore the facial contour to a more youthful shape. However, a facelift can carry different complications and risks. Like any other type of surgery, a facelift carries the risk of bleeding, infection, and adverse reactions to anesthesia. Some other risks include hematoma, scarring, nerve damage, hair loss, and skin sloughing. Moreover, the effects of a facelift are not permanent. As a person ages, the facial skin may sag again. Generally, a single facelift is expected to last for 10 years.

[0004] Surprisingly, there is a growing interest in alternative and non-invasive methods for reducing facial sagging and counteracting the effects of aging on the skin. Microcurrent electrical stimulation (MES) of the skin is a facial beauty treatment that has gained increasing attention in recent years. MES is characterized by the use of extremely small currents (i.e., one millionth of an ampere, e.g., 300 μA - 500 μA), which are barely perceptible but mimic the body's own bioelectric currents. MES is used as a cosmetic, non-therapeutic beauty treatment for improving skin rejuvenation. It is known to be an effective, non-invasive, and inexpensive technique for counteracting 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 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].

[0005] The outermost layer of human skin is the epidermis, which is a stratified epithelium and is mainly constructed by different layers of keratinocytes. Below the epidermis is the dermis, which consists 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 I collagen in fibroblasts and to promote fibroblast-induced collagen contraction, which improves the appearance of the skin [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] Muscleblind-like protein 1 (MBNL1) is an RNA-binding protein that is involved in the differentiation and maintenance of splicing patterns required for healthy muscle function. Studies have shown that an increase in MBNL1 protein in fibroblasts activates their trans-differentiation process into myofibroblasts, a cell type that is capable of releasing large amounts of extracellular matrix proteins such as collagen, elastin, and fibronectin. Electrical stimulation has been shown to induce the appearance 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 that effectively upregulate MBNL1 expression in skin or muscle cells have been shown to be useful for maintaining or improving skin firmness, preventing the appearance of skin sagging, and / or reducing facial asymmetry (WO 2020 / 161683A1).

[0007] Although effective as a cosmetic treatment, the use of MES has several drawbacks. For example, the current intensity can depend on the individual skin thickness, which varies with age or external factors, and thus there are large differences within and between individuals. In addition, the skin health status affects the required intensity. For example, older or degenerated skin has lower electrical conductivity (i.e., exhibits poor microcurrent transmission) than healthy skin. In some cases, poor electrical contact between the electrodes and the surface to be treated can cause discomfort and pain to the user, and in extreme cases, skin allergies. Some MES devices use electrodes and adhesive gels to improve conductivity, but this is both expensive and inconvenient (e.g., for use on the face). This is because once the electrodes are in place, they are not allowed to move. In addition, due to the differences in devices, it is difficult to accurately track the contour of the body surface being treated. Moreover, since the stimulation should be able to be localized to a precise area, this is a problem. For example, some devices require the use of a mirror in order to position the device rod properly on the face, squeezing or stretching the skin. Finally, some potential users have a negative bias towards MES treatment, for example, towards using electricity for daily cosmetic treatment on the face.

[0008] There is a need to provide alternative methods for alleviating or preventing signs of the skin, for example, for reducing skin wrinkles, improving skin firmness, and reducing the appearance of skin sagging. There is a need to provide a method that overcomes the problems associated with known methods such as facelifts or MES. There is a need to find new active compounds that can alleviate or prevent signs of skin aging. Summary of the Invention

[0009] In a first aspect, the present invention provides a compound represented by formula (I):

[0010] R1-W m -X n -AA1-AA2-AA3-AA4-Y o -Z p -R2 (I),

[0011] its stereoisomers and / or cosmetically acceptable salts, wherein:

[0012] AA1 is Leu, Ile or Val;

[0013] AA2 is Pro, Ala or Gly;

[0014] AA3 is Val, Ile or Leu;

[0015] AA4 is Thr, Val or a non-amino acid;

[0016] W, X, Y and Z are each independently any amino acid;

[0017] m, n, p, and q are each independently 0 or 1;

[0018] m + n + p + q is less than or equal to 2;

[0019] R1 is selected from the group consisting of: H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, a cycloaliphatic group, a heterocyclic group, a heteroarylalkyl group, an aryl group, an aralkyl group, and R5-CO-, where R5 is selected from the group consisting of: H, an acyclic aliphatic group, a cycloaliphatic group, an aryl group, an aralkyl group, a heterocyclic group, and a heteroarylalkyl group;

[0020] 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, a cycloaliphatic group, a heterocyclic group, a heteroarylalkyl group, an aryl group, and an aralkyl group; and

[0021] R1 and R2 are not amino acids.

[0022] It has been found that the compounds of the present invention are effective in reducing the appearance of wrinkles in the skin, improving the firmness of the skin, reducing the appearance of skin sagging, and lifting the skin. Lifting the skin means tightening the skin. The lifting / tightening of the skin provides an appearance such that the skin has moved from a lower position to a higher position, thereby counteracting any downward gravitational movement of the skin that increases due to aging. In addition, it has been found that the compounds of the present invention can be an effective alternative to commercially available microcurrent facial conditioning devices for treating and / or preventing symptoms of skin aging. Specifically, it has been found that the compounds of the present invention are effective in reducing the appearance of wrinkles in the skin, improving the firmness of the skin, reducing the appearance of skin sagging, and lifting the skin to a similar extent as commercially available microcurrent facial conditioning devices.

[0023] In another aspect, the present invention provides a cosmetic composition comprising a compound of formula (I), its stereoisomers, and / or its cosmetically acceptable salts, and at least one cosmetically acceptable excipient or adjuvant.

[0024] On the other hand, the present invention provides a compound of formula (I), its stereoisomers and / or its cosmetically acceptable salts; or the use of a composition comprising a compound of formula (I), its stereoisomers and / or its cosmetically acceptable salts for the treatment and / or care of skin, hair, nails and / or mucous membranes. Specifically, the present invention provides a compound of formula (I), its stereoisomers and / or its cosmetically acceptable salts; or the use of a cosmetic composition comprising a compound of formula (I), its stereoisomers and / or its cosmetically acceptable salts 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 can be: preventing or treating the symptoms of skin aging; treating and / or preventing skin wrinkles; improving or maintaining skin firmness; treating and / or preventing the appearance of skin sagging; and / or lifting the skin.

[0025] On the other hand, 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 stereoisomers and / or its cosmetically or pharmaceutically acceptable salts; or a composition comprising the compound of formula (I), its stereoisomers and / or its cosmetically or pharmaceutically acceptable salts. Specifically, the present invention provides a method for the 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 stereoisomers and / or its cosmetically acceptable salts; or a cosmetic composition comprising a compound of formula (I), its stereoisomers and / or its cosmetically acceptable salts. Generally, the compound will be administered topically. The cosmetic, non-therapeutic treatment and / or care can be: preventing or treating the symptoms of skin aging; treating and / or preventing skin wrinkles; improving or maintaining skin firmness; treating and / or preventing the appearance of skin sagging; and / or lifting the skin. Detailed Description

[0026] Definition

[0027] In the context of the present invention, "skin" should be understood to include the skin, the layers from the uppermost or stratum corneum of the epidermis to the lowermost or hypodermis (including both). These layers are composed of different types of cells, such as keratinocytes, fibroblasts, melanocytes, mast cells, neurons and / or adipocytes, etc. The term "skin" also includes the scalp. The term "skin" includes the skin of mammals and includes human skin. Similarly, the terms "hair, nails and mucous membranes" include the hair, nails and mucous membranes of mammals (e.g., humans).

[0028] As used herein, the term "treatment", when not accompanied by the qualifying conditions "cosmetic, non-therapeutic", refers to a therapeutic method that includes methods involving the administration of a compound according to the present invention to alleviate or eliminate a disease or disorder, or to reduce or eliminate one or more symptoms associated with the disease or disorder. The term "treatment", when not accompanied by the qualifying conditions "cosmetic, non-therapeutic", also encompasses therapeutic methods involving alleviating or eliminating the physiological consequences of a disease or disorder.

[0029] When the terms "treatment" and "care" are accompanied by the qualifying conditions "cosmetic, non-therapeutic", they mean that the purpose of the treatment or care is to improve or maintain the aesthetic appearance of the skin, hair, nails and / or mucous membranes. Specifically, the purpose of the treatment is to improve the cosmetic properties of the skin, hair, nails and / or mucous membranes, such as, for example and without limitation, the hydration level, elasticity, firmness, gloss, tone or texture, which affect the aesthetic appearance of the skin, hair, nails and / or mucous membranes. The term "care" in the context of the present specification refers to maintaining the properties of the skin, hair, nails and / or mucous membranes. The properties are improved or maintained by performing cosmetic treatment and / or care on the skin, hair, nails and / or mucous membranes of both healthy subjects and subjects presenting with diseases and / or disorders of the skin, hair, nails and / or mucous membranes.

[0030] As used in the present invention, the term "prevention" refers to the ability of the compounds of the present invention to prevent, delay or impede the appearance or development of a disease or disorder, or to prevent, delay or impede changes in the cosmetic properties of the skin, mucous membranes and / or hair. As used in the present invention, the term "prevention" may be interchanged with the term "inhibition", that is, it 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.

[0031] In the context of the present invention, the term "aging" refers to the changes that the skin undergoes due to the intrinsic aging process (i.e., chronological aging) or the extrinsic skin aging process induced by environmental factors (i.e., through exposure to the sun (photoaging) or environmental agents such as tobacco smoke, extreme climatic conditions of cold or strong wind, chemical pollutants or contaminants). In the context of the present invention, aging includes all externally visible and / or perceptible by touch changes, such as and not limited to: discontinuous development of the skin, such as wrinkles, fine lines, expression lines, stretch marks, furrows, irregularities or roughness; enlarged pores, loss of hydration, loss of elasticity, loss of firmness, loss of smoothness, loss of the ability to recover from deformation, loss of resilence; skin sagging, such as cheek sagging, appearance of eye bags under the eyes or appearance of a double chin, etc.; skin color changes, such as the appearance of blotches, flushing, eye bags or hyperpigmentation areas, such as age spots or freckles, etc.; abnormal differentiation, hyperkeratosis, elastosis, keratosis, hair loss, cellulite, loss of collagen structure and other histological changes in the stratum corneum, dermis, epidermis, vascular system (e.g., appearance of spider veins or telangiectasias) or those tissues close to the skin. The term "photoaging" is grouped together with a set of methods due to the long-term exposure of the skin to ultraviolet radiation that causes permanent aging of the skin, and it presents the same physical characteristics as aging, such as and not limited to laxity, sagging, color changes or irregular, abnormal and / or excessive pigmentation. The sum of various environmental factors, such as exposure to tobacco smoke, exposure to pollution and climatic conditions (such as cold and / or strong wind) also causes skin aging.

[0032] In this specification, the abbreviations used for amino acids follow the rules specified by the IUPAC-IUB Commission of Biochemical Nomenclature in Eur. J. Biochem., (1984), 138, 9 - 37. Thus, for example, Gly represents NH2-CH2-COOH, Gly- represents NH2-CH2-CO-, -Gly represents -NH-CH2-COOH, and -Gly- represents -NH-CH2-CO-. Thus, the hyphen representing the peptide bond, when located to the right of the symbol, eliminates the OH in the 1-carboxyl group of the amino acid (here represented in the conventional non-ionized form), and when located to the left of the symbol, eliminates the H in the 2-amino group of the amino acid; both modifications can be applied to the same symbol (see Table 1).

[0033]

[0034] As used herein, the term "acyclic aliphatic group" includes straight-chain (i.e., linear and unbranched) or branched, saturated or unsaturated hydrocarbon groups, such as alkyl, alkenyl, and alkynyl groups. The acyclic aliphatic group may be substituted (mono- or poly-) or unsubstituted.

[0035] As used herein, the term "alkyl" includes saturated straight-chain and branched alkyl groups, which may be substituted (mono- or poly-) or unsubstituted. The alkyl group is bonded to the remainder of the molecule by a single bond. The alkyl group has from 1 to 24, preferably from 1 to 16, more preferably from 1 to 14, even more preferably from 1 to 12, still 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 pentyl.

[0036] As used herein, the term "alkenyl" refers to a group containing one or more carbon-carbon double bonds and may be straight-chain or branched and substituted (mono- or poly-) or unsubstituted. Preferably, it has 1, 2, or 3 carbon-carbon double bonds. If there is more than one carbon-carbon double bond, the double bonds may be conjugated or non-conjugated. Preferably, the alkenyl group has from 2 to 24, preferably from 2 to 16, more preferably from 2 to 14, even more preferably from 2 to 12, still more preferably 2, 3, 4, 5, or 6 carbon atoms. The alkenyl group is bonded to the remainder of the molecule by a single bond. The term "alkenyl" includes, for example, vinyl (-CH2=CH2), allyl (-CH2-CH=CH2), isoprenyl, oleyl, linoleyl groups, and the like.

[0037] The term "alkynyl" refers to a group containing one or more carbon-carbon triple bonds and may be straight-chain or branched and substituted (mono- or poly-) or unsubstituted. Preferably, the alkynyl group has 1, 2, or 3 carbon-carbon triple bonds. The triple bonds may be conjugated or non-conjugated. The alkynyl group has from 2 to 24, preferably from 2 to 16, more preferably from 2 to 14, even more preferably from 2 to 12, still more preferably 2, 3, 4, 5, or 6 carbon atoms. The alkynyl group is bonded to the remainder of the molecule by a single bond. The term "alkynyl" includes, for example, and is not limited to, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, pentynyl, such as 1-pentynyl, and the like. The alkynyl group may also contain one or more carbon-carbon double bonds, and the alkynyl group includes, for example, and is not limited to, but-1-en-3-ynyl group and pent-4-en-1-ynyl group, and the like.

[0038] The term "alicyclic group" is used herein to encompass, for example and without limitation, aliphatic cyclic (alicyclic) groups, such as cycloalkyl or cycloalkenyl or cycloalkynyl groups. The term "alicyclic group" refers to a monovalent group containing one or more rings of carbon atoms, which rings may be saturated (e.g., cyclohexyl) or unsaturated (e.g., cyclohexenyl), provided that they are not aromatic. More specifically, an alicyclic group contains three or more, 3 to 24, 3 to 12 or 6 to 12 ring carbon atoms. The alicyclic group may be a monocyclic, bicyclic or tricyclic ring system, and the rings may be, for example, fused or may be linked by a linking group such as a single bond or a methylene or other alkylene group. The alicyclic group may be substituted (mono- or poly-) or unsubstituted. In one embodiment, the alicyclic group is a 6- to 12-membered ring system composed of carbon atoms and optionally containing one or two double bonds.

[0039] The term "cycloalkyl" refers to a saturated monocyclic or polycyclic alkyl group which may be substituted (mono- or poly-) or unsubstituted. The cycloalkyl group has 3 to 24, preferably 3 to 16, more preferably 3 to 14, even more preferably 3 to 12, and still even more preferably 3, 4, 5 or 6 carbon atoms. The cycloalkyl group is bonded to the remainder of the molecule by a single bond. The cycloalkyl group includes, for example and without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, methylcyclohexyl, dimethylcyclohexyl, octahydroindene, decahydronaphthalene, dodecahydrophenalene, etc.

[0040] The term "cycloalkenyl" refers to a non-aromatic monocyclic or polycyclic alkenyl group which may be substituted (mono- or poly-) or unsubstituted. The cycloalkenyl group has 5 to 24, preferably 5 to 16, more preferably 5 to 14, even more preferably 5 to 12, and still more preferably 5 or 6 carbon atoms. The cycloalkenyl group is bonded to the remainder of the molecule by a single bond. Preferably, the cycloalkenyl group contains 1, 2 or 3 carbon-carbon double bonds. If there is more than one carbon-carbon double bond, the double bonds may be conjugated or non-conjugated. The cycloalkenyl group includes, for example and without limitation, cyclopent-1-en-1-yl group, etc.

[0041] The term "cycloalkynyl" refers to a non-aromatic monocyclic or polycyclic alkynyl group which may be substituted (mono- or poly-) or unsubstituted. The cycloalkynyl group has 8 to 24, preferably 8 to 16, more preferably 8 to 14, even more preferably 8 to 12, and still even more preferably 8 or 9 carbon atoms, and is bonded to the remainder of the molecule by a single bond. Preferably, the cycloalkynyl group contains 1, 2 or 3 carbon-carbon triple bonds, which carbon-carbon triple bonds may be conjugated or non-conjugated. The cycloalkynyl group includes, for example and without limitation, cyclooct-2-yn-1-yl group, etc. The cycloalkynyl group may also contain one or more carbon-carbon double bonds, which one or more carbon-carbon double bonds include, for example and without limitation, cyclooct-4-en-2-ynyl group, etc.

[0042] As used herein, the term "heterocyclic group" or "heterocyclic" refers to a hydrocarbon ring system having from 3 to 10 members, wherein one or more of the atoms in one or more of the rings are heteroatoms (i.e., not carbon atoms). Thus, "heterocyclic group" or "heterocyclic" refers to a cyclic group in which the ring atoms are composed of carbon and one or more heteroatoms. To satisfy valency, the heteroatoms may be bonded to H or a substituent group. Preferably, 1, 2, or 3 of the ring carbon atoms are heteroatoms. Each heteroatom may independently be selected from the group consisting of O, N, S, P, and B or from the group consisting of O, N, and S. The heterocyclic group may be substituted (mono- or poly-) or unsubstituted. The heterocyclic group may be a monocyclic, bicyclic, or tricyclic ring system, and the rings may be, for example, fused or may be linked by a linker such as a methylene or other alkylene group. The nitrogen, carbon, or sulfur atoms present in the heterocyclic group may optionally be oxidized, and the nitrogen atoms may optionally be quaternized. The heterocyclic group may be unsaturated or partially or fully saturated. The heterocyclic group may be aliphatic or aromatic. In one embodiment, the heterocyclic group is aliphatic (also referred to as heterocycloalkyl) and is a 3- to 10-membered ring system in which one or more of the ring atoms are composed of carbon atoms and 1 to 4, or 1, 2, or 3 heteroatoms. In one embodiment, the heterocyclic group is a 6- to 10-membered ring system in which one or more of the ring atoms are composed of carbon atoms and 1 to 4 heteroatoms, and wherein the ring system optionally contains one or two double bonds. In one embodiment, the heterocyclic group is aromatic (also referred to as heteroaryl) and is a 6- to 10-membered ring system in which one or more of the ring atoms are composed of carbon atoms and 1 to 4, or 1, 2, or 3 heteroatoms. Most preferably, the term heterocyclic group refers to a 5- or 6-membered ring. Examples of saturated heterocycloalkyl groups are dioxane, piperidine, piperazine, pyrrolidine, morpholine, and thiomorpholine. Examples of aromatic heterocyclic groups are pyridine, pyrrole, furan, thiophene, benzofuran, imidazoline, quinolein, quinoline, pyridazine, and naphthyridine.

[0043] The term "aryl group" refers to an aromatic group having from 6 to 30, preferably from 6 to 18, more preferably between 6 and 10, and even more preferably 6 or 10 carbon atoms. The aryl group may include 1, 2, 3, or 4 aromatic rings, which may be linked by carbon-carbon bonds or may be fused together, and includes, for example and without limitation, phenyl, naphthyl, diphenyl, indenyl, phenanthryl, or anthryl, etc. The aryl group may be substituted (mono- or poly-) or unsubstituted.

[0044] The term "aralkyl group" refers to an alkyl group substituted by an aromatic group, which has from 7 to 24 carbon atoms and includes, for example and without limitation: -(CH2)1-6 -phenyl, -(CH2) 1-6 -(1-naphthyl), -(CH2) 1-6 -(2-naphthyl), -(CH2) 1-6 -CH(phenyl)2, etc.

[0045] The term "heteroarylalkyl" refers to an alkyl group substituted with a heteroaryl group (also known as an aromatic heterocyclic group) as defined above, the alkyl group having from 1 to 6 carbon atoms and the heteroaryl group having from 2 to 24 carbon atoms and from 1 to 3 heteroatoms. Heteroarylalkyl groups include, for example and without limitation, -(CH2) 1-6 -imidazolyl, -(CH2) 1-6 -triazolyl, -(CH2) 1-6 -thienyl, -(CH2) 1-6 -furyl, -(CH2) 1-6 -pyrrolidinyl group, etc.

[0046] As understood in the art, the above groups may have a certain degree of substitution. Specifically, substitution may be present in any of the groups explicitly set forth above. The above-mentioned substituted groups (radicals) are groups (or radicals) substituted with one or more substituents in one or more available positions. Preferably, the substitution is in 1, 2 or 3 positions, more preferably in 1 or 2 positions, and even more preferably in 1 position. Suitable substituents include, for example and without limitation: C1-C4 alkyl; hydroxy; C1-C4 alkoxy; amino; amino-C1-C4 alkyl; C1-C4 carbonyloxy; C1-C4 oxycarbonyl; halogens such as fluoride, chlorine, bromine and iodine; cyano; nitro; azide; C1-C4 alkylsulfonyl; thiol; C1-C4 alkylthio; aryloxy such as phenoxy; -NR b (C=NR b )NR b R c ; where R b and R c are independently selected from the group consisting of: H, C1-C4 alkyl, C2-C4 alkenyl, alkynyl, C3-C 10 cycloalkyl, C6-C 18 aryl, C7-C 17 aralkyl, 3- to 10-membered heterocyclic group or a protecting group for an amino group.

[0047] As will be understood and as stated above, when R is stated herein to be an alkyl, alkenyl, alkynyl, alicyclic, cycloalkyl, cycloalkenyl, cycloalkenyl, heterocyclic, heterocycle, heteroarylalkyl, aryl or aralkyl, etc., it is meant that R is such a group. For example, when it is mentioned that R is alkyl, it is meant that R is an alkyl group.

[0048] As used herein, the term "comprising" or "including" (which is inclusive or open-ended and does not exclude additional unrecited elements or method steps) is intended to cover, in the alternative embodiments, the phrases "consisting essentially of" and "consisting of", where "consisting of" excludes any element or step not specified and "consisting essentially of" allows for 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.

[0049] Compounds of the present invention

[0050] In a first aspect, the present invention relates to a compound of formula (I):

[0051] R1-W m -X n -AA1-AA2-AA3-AA4-Y o -Z p -R2 (I),

[0052] its stereoisomers and / or pharmaceutically acceptable salts, wherein:

[0053] AA1 is Leu, Ile or Val;

[0054] AA2 is Pro, Ala or Gly;

[0055] AA3 is Val, Ile or Leu;

[0056] AA4 is Thr, Val or a non-amino acid;

[0057] W, X, Y and Z are each independently any amino acid;

[0058] m, n, p and q are each independently 0 or 1;

[0059] m + n + p + q is less than or equal to 2;

[0060] R1 is selected from the group consisting of: H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, an alicyclic group, a heterocyclic group, a heteroarylalkyl group, an aryl group, an aralkyl group and R5-CO-, where R5 is selected from the group consisting of: H, an acyclic aliphatic group, an alicyclic group, an aryl group, an aralkyl group, a heterocyclic group and a heteroarylalkyl group;

[0061] 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, an alicyclic group, a heterocyclic group, a heteroarylalkyl group, an aryl group and an aralkyl group; and

[0062] R1 and R2 are not amino acids.

[0063] The compound of formula (I) is a peptide comprising 3, 4, 5 or 6 amino acids linked in a chain. R1 is bound to the amino terminus (N-terminus) of the peptide and R2 is bound to the carboxyl terminus (C-terminus) of the peptide.

[0064] R1 may be selected from the group consisting of: H, a polymer derived from polyethylene glycol having a molecular weight between 200 daltons and 35,000 daltons, and R5-CO-, where R5 is selected from the group consisting of: 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 aralkyl, 3- to 10-membered heterocyclic ring, and heteroarylalkyl containing 2 to 24 carbon atoms and 1 to 3 heteroatoms, where the alkyl group has 1 to 6 carbon atoms.

[0065] R1 may be selected from the group consisting of: H and R5-CO-, where R5 is selected from the group consisting of: C1-C 18 alkyl, C2-C 24 alkenyl, C3-C 24 cycloalkyl or the group consisting of: C1-C 16 alkyl, C2-C 18 alkenyl, C3-C7 cycloalkyl. The R5-CO- group includes alkanoyl groups such as acetyl (CH3-CO-, which is abbreviated as "Ac-" herein), myristoyl (CH3-(CH2) 12 -CO-, which is abbreviated as "Myr-" herein) and palmitoyl (CH3-(CH2) 14 -CO-, which is abbreviated as "Palm-" herein).

[0066] R1 may be selected from the group consisting of: H and acetyl, tert-butyryl, isoprenyl, hexanoyl, 2-methylhexanoyl, cyclohexanecarboxyl, octanoyl, decanoyl, lauroyl, myristoyl, palmitoyl, stearoyl, oleoyl, and linoleoyl.

[0067] R1 may be selected from the group consisting of: H and R5-CO-, where R5 is selected from the group consisting of: C1-C 16 alkyl or C2-C 18 alkenyl.

[0068] R1 can be selected from the group consisting of: H and R5-CO-, wherein R5 is C1-C 15 alkyl.

[0069] R1 can be selected from the group consisting of H, acetyl and palmitoyl. Specifically, R1 is H.

[0070] R2 may be selected from the group consisting of: -NR3R4, -OR3, -SR3, wherein R3 and R4 are independently selected from the group consisting of: H, polymers 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 24 Aralkyl, 3-10 membered heterocyclyl ring and heteroarylalkyl containing 2 to 24 carbon atoms and 1 to 3 heteroatoms, wherein the alkyl group has 1 to 6 carbon atoms. Optionally, R3 and R4 can be bound by a saturated or unsaturated carbon-carbon bond to form a ring having a nitrogen atom.

[0071] R2 may be -NR3R4 or -OR3. R3 and R4 may be independently selected from the group consisting of: H, polymers derived from polyethylene glycol including molecular weights between 200 and 35,000, methyl, ethyl, hexyl, dodecyl and hexadecyl. Alternatively, R3 and R4 may 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 selected from H and C1-C 16 The group formed by the alkyl group includes methyl, ethyl, hexyl, dodecyl and hexadecyl.

[0072] R2 can be selected from the group consisting of: -OH, -NH2 and -NHR4, wherein R4 is C1-C 16 Alkyl or C1-C3 alkyl or C1-C2 alkyl.

[0073] R2 can be -OH or -NH2. Specifically, R2 is OH.

[0074] R1 may be selected from the group consisting of: H and R5-CO-, wherein R5 is selected from the group consisting of: C1-C 18 Alkyl, C2-C 24 Alkenyl, C3-C24 cycloalkyl; and R2 may be -NR3R4 or -OR3, where R3 and R4 are independently selected from the group consisting of: H and C1-C 16 alkyl. In this embodiment, R3 may be H, and R4 may be selected from the group consisting of H, C1-C 16 alkyl, C1-C3 alkyl, and C1-C2 alkyl; for example, R2 may be selected from the group consisting of: -OH and -NH2.

[0075] R1 may be selected from the group consisting of: H and acetyl, tert-butyryl, isoprenyl, hexanoyl, 2-methylhexanoyl, cyclohexanecarboxyl, octanoyl, decanoyl, lauroyl, myristoyl, palmitoyl, stearoyl, oleoyl, and linoleoyl; and R2 may be -NR3R4 or -OR3, where R3 and R4 are independently selected from the group consisting of: H and C1-C 16 alkyl. In this embodiment, R3 may be H, and R4 may be selected from the group consisting of H, C1-C 16 alkyl, C1-C3 alkyl, and C1-C2 alkyl; for example, R2 may be selected from the group consisting of: -OH and -NH2.

[0076] R1 may be selected from the group consisting of: H and R5-CO-, where R5 is selected from the group consisting of C1-C 16 alkyl or C2-C 18 alkenyl; and R2 may be -NR3R4 or -OR3, where R3 and R4 are independently selected from the group consisting of: H and C1-C 16 alkyl. In this embodiment, R3 may be H, and R4 may be selected from the group consisting of H, C1-C 16 alkyl, C1-C3 alkyl, and C1-C2 alkyl; for example, R2 may be selected from the group consisting of: -OH and -NH2.

[0077] R1 may be selected from the group consisting of: H, acetyl, myristoyl, and palmitoyl; and R2 may be -NR3R4 or -OR3, where R3 and R4 are independently selected from the group consisting of: H and C1-C 16 alkyl. In this embodiment, R3 may be H, and R4 may be selected from the group consisting of H, C1-C 16 alkyl, C1-C3 alkyl, and C1-C2 alkyl; for example, R2 may be selected from the group consisting of: -OH and -NH2.

[0078] R1 may be optionally selected from the group consisting of: H and R5-CO-, where R5 is C1-C 15alkyl, and R2 may be -NR3R4 or -OR3, where R3 and R4 are independently selected from the group consisting of: H and C1-C 16 alkyl. In this embodiment, R3 may be H, and R4 may be selected from the group consisting of H, C1-C 16 alkyl, the group formed by C1-C3 alkyl and C1-C2 alkyl; for example, R2 may be selected from the group consisting of: -OH and -NH2.

[0079] R1 may be selected from the group consisting of: H, acetyl, and palmitoyl; and R2 may be -NR3R4 or -OR3, where R3 and R4 are independently selected from the group consisting of: H and C1-C 16 alkyl. In this embodiment, R3 may be H, and R4 may be selected from the group consisting of H, C1-C 16 alkyl, the group formed by C1-C3 alkyl and C1-C2 alkyl; for example, R2 may be selected from the group consisting of: -OH and -NH2.

[0080] R1 may be H; and R2 may be -NR3R4 or -OR3, where R3 and R4 are independently selected from the group consisting of: H and C1-C 16 alkyl. In this embodiment, R3 may be H, and R4 may be selected from the group consisting of H, C1-C 16 alkyl, the group formed by C1-C3 alkyl and C1-C2 alkyl; for example, R2 may be selected from the group consisting of: -OH and -NH2.

[0081] R1 may be H; and R2 may be -NR3R4, where R3 and R4 are independently selected from the group consisting of: H and C1-C 16 alkyl. In this embodiment, R3 may be H, and R4 may be selected from the group consisting of H, C1-C 16 alkyl, the group formed by C1-C3 alkyl and C1-C2 alkyl; for example, R2 may be selected from the group consisting of: -NH2 and -NHR4, where R4 is C1-C3 alkyl. R2 may be -NH2.

[0082] R1 may be H and R2 may be -OH or -NH2. R1 may be acetyl and R2 may be -OH or -NH2. R1 may be acetyl and R2 may be -NH2. R1 may be palmitoyl and R2 may be -OH.

[0083] The most preferred structure of the polymer derived from polyethylene glycol is: the group (-CH2-CH2-O) r -H, where r is a number between 4 and 795; and the group

[0084]

[0085] where s is a number between 1 and 125.

[0086] 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, a compound of formula (I) is provided in which R1 is not H and / or R2 is not OH.

[0087] 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 non - amino acid. When AA4 is a non - amino acid, this means that amino acid AA4 is absent in the compound.

[0088] AA1 may 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 non - amino acid.

[0089] AA1 may 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 non - amino acid.

[0090] AA2 may 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;

[0091] and AA4 is selected from the group consisting of Thr, Val, and non - amino acid.

[0092] AA3 may 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 non - amino acid.

[0093] 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 non - amino acids.

[0094] AA4 can be optionally 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.

[0095] AA4 can be optionally selected from the group consisting of: Thr and non - amino acids. 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 non - amino acids.

[0096] The compound of formula (I) can have the following condition: when there is no amino acid at the AA4 position, AA1 is Leu.

[0097] The compound of formula (I) can have the following condition: when there is no amino acid at the AA4 position, AA2 is Pro.

[0098] The compound of formula (I) can have the following condition: when there is no amino acid at the AA4 position, AA3 is Val.

[0099] The compound of formula (I) can have the following condition: it is not H - Lys - Leu - Pro - Val - Thr - OH or H - Leu - Pro - Val - Thr - Leu - Arg - OH.

[0100] The compound of formula (I) can have the following condition: 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.

[0101] In an exemplary embodiment of the compound of formula (I):

[0102] AA1 is Leu; AA2 is Pro; AA3 is Val; and AA4 is Thr;

[0103] AA1 is Leu; AA2 is Ala; AA3 is Val; and AA4 is Thr;

[0104] AA1 is Leu; AA2 is Pro; AA3 is Ile; and AA4 is Thr;

[0105] AA1 is Val; AA2 is Pro; AA3 is Val; and AA4 is Thr;

[0106] AA1 is Leu; AA2 is Gly; AA3 is Val; and AA4 is Thr;

[0107] AA1 is Leu; AA2 is Pro; AA3 is Leu; and AA4 is Thr;

[0108] AA1 is Leu; AA2 is Pro; and AA3 is Val; and

[0109] AA1 is Ile; AA2 is Pro; AA3 is Ile; and AA4 is Thr.

[0110] In an exemplary embodiment of the compound of formula (I):

[0111] AA1 is Leu; AA2 is Pro; AA3 is Val; AA4 is Thr; R1 is H and R2 is OH or NH2;

[0112] AA1 is Leu; AA2 is Pro; AA3 is Val; AA4 is Thr; R1 is H or Ac and R2 is NH2; and

[0113] AA1 is Leu; AA2 is Pro; AA3 is Leu; AA4 is Thr; R1 is H and R2 is OH.

[0114] The compound of formula (I) may be selected from the amino acid sequences listed in Table 2, in which their sequence identifiers, their stereoisomers and / or their cosmetically or pharmaceutically acceptable salts are detailed.

[0115] Table 2

[0116] Sequence Identifier Leu-Pro-Val-Thr SEQ ID NO.1 Leu-Ala-Val-Thr SEQ ID NO.2 Leu-Pro-Ile-Thr SEQ ID NO.3 Val-Pro-Val-Thr SEQ ID NO.4 Leu-Gly-Val-Thr SEQ ID NO.5 Leu-Pro-Leu-Thr SEQ ID NO.6 Ala-Leu-Pro-Val-Thr SEQ ID NO.7 Leu-Pro-Val SEQ ID NO.8 Ile-Pro-Ile-Thr SEQ ID NO.9 Leu-Ala-Val-Thr SEQ ID NO.10

[0117] The compounds of formula (I) comprise each of the amino acid sequences in Table 2, wherein one of amino acids AA1 to AA4 is replaced by a replacement amino acid, and the replacement amino acid is selected from the replacement amino acids of the amino acids replaced in formula (I) listed above. The replacement amino acid is different from the replaced amino acid. In the case of AA4, the replacement amino acid may be a non-amino acid. Thus, for example, the present invention provides a compound of formula (I) corresponding to SEQ ID NO.1, wherein one of amino acids AA1 to AA4 is replaced by an amino acid, wherein: when Leu (AA1) is replaced, it is replaced by Ile or Val; when Pro (AA2) is replaced, it is replaced by Ala or Gly; when Val (AA3) is replaced, it is replaced by Ile or Leu; and when Thr (AA4) is replaced, it is replaced by Val or a non-amino acid.

[0118] In the amino acid sequences of Table 2, R1 and R2 are H and OH, respectively. The compounds of the present invention comprise each of the sequences in Table 2, the N-terminus and C-terminus of which are modified by additional R1 and R2 groups, respectively, as defined herein for formula (I). For example, the compounds of the present invention comprise each of the sequences in Table 2, wherein the N-terminal amino acid residue terminates in R1 as defined above for formula (1), wherein R1 is not H, and alternatively or additionally wherein the C-terminal amino acid residue optionally terminates in R2 as defined above for formula (1), wherein R2 is not OH.

[0119] Thus, specifically, the compounds according to formula (I) can be any one of the amino acid sequences SEQ ID NO.1 to SEQ ID NO.10 and their stereoisomers and / or their cosmetically acceptable salts, wherein optionally, the N-terminal amino acid of the sequence is modified by R1 as defined above for formula (I), wherein R1 is not H, and alternatively or additionally, the C-terminal amino acid of the sequence is modified by R2 as defined above for formula (I), wherein R2 is not OH. The amino acid sequence can be SEQ ID NO.1.

[0120] Compounds of formula (I) may exist as stereoisomers or mixtures of stereoisomers; for example, the amino acids comprising them may have the L-configuration, the D-configuration, or may be racemic independently of each other. Thus, it is possible to obtain mixtures of isomers as well as racemic mixtures or mixtures of diastereoisomers or pure diastereoisomers or enantiomers, depending on the number of asymmetric carbons and which isomers or mixtures of isomers are present. Preferred structures of the compounds of the invention are pure isomers, i.e. enantiomers or diastereoisomers. For example, when it is stated that AA2 may be Ala, it is to be understood that, unless otherwise indicated, AA2 is selected from L-Ala, D-Ala or a mixture of both (racemic or non-racemic). The preparation procedures described in this document enable the person skilled in the art to obtain each of the stereoisomers of the compounds of the invention by selecting amino acids with the correct configuration.

[0121] In the context of the present invention, the term "amino acid" includes amino acids encoded by the genetic code as well as non-coded amino acids, whether natural or non-natural. Examples of non-coded amino acids are, 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, alloisoleucine, allothreonine, pipecolic acid, isoserine, phenylglycine, statine, β-alanine, norleucine, N-methyl amino acids, α-amino acids and β-amino acids, etc. and derivatives thereof. A list of non-natural amino acids can be found in D.C. Roberts and F. Vellaccio, "Unusual amino acids in peptide synthesis" in Peptides, Volume 5 (1983), Chapter VI, Gross E. and Meienhofer J., Academic Press, New York, USA or in the commercial catalogues of companies specialising in this field.

[0122] 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 should be understood that the nature of W, X, Y, and / or Z does not prevent the activity of the compounds of the present invention, but rather contributes to or does not contribute to their action. W, X, Y, and Z can independently be selected from the group consisting of: Ala, Gly, Val, and Ile. W, X, Y, and Z can independently be selected from the group consisting of: Ala, Val, and Ile. W, X, Y, and Z can independently be selected from the group consisting of: Ala, Gly, and Val. Each of W, X, Y, and Z can independently be Ala or Gly. Each of W, X, Y, and Z can be Ala.

[0123] Each of m, n, p, and q can be 0, i.e., the compound of formula (I) is a peptide comprising 3 or 4 amino acids (e.g., AA1 - AA2 - AA3 - AA4 or AA1 - AA2 - AA3) linked in a chain. The sum of m, n, p, and q can be 1, i.e., the compound of formula (I) is a peptide comprising alternatively 4 or 5 amino acids linked in a chain. Alternatively, the sum of m, n, p, and q can be 2, i.e., the compound of formula (I) is a peptide comprising 5 or 6 amino acids linked in a chain.

[0124] Specifically, the compounds of formula (I) can be selected from the group consisting of: the compounds listed in Table 3, their stereoisomers, and / or their cosmetically acceptable salts.

[0125] Table 3

[0126]

[0127]

[0128] The compounds of formula (I) include each of the compounds in Table 3, wherein one of the amino acids AA1 to AA4 is replaced by a replacement amino acid, wherein the replacement amino acid is selected from the replacement amino acids of the amino acids listed as being 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 a non - amino acid. Thus, for example, the present invention provides compounds of formula (I) corresponding to PEP - 1, wherein one of the amino acids AA1 to AA4 is replaced by an amino acid, wherein: when Leu (AA1) is replaced, it is replaced by Ile or Val; when Pro (AA2) is replaced, it is replaced by Ala or Gly; when Val (AA3) is replaced, it is replaced by Ile or Leu; and when Thr (AA4) is replaced, it is replaced by Val or a non - amino acid.

[0129] The compound according to formula (I) may be selected from any of PEP-1 to PEP-13, its stereoisomers and / or its cosmetically or pharmaceutically acceptable salts. The compound of formula (I) may be PEP-1.

[0130] Cosmetically or pharmaceutically acceptable salts of the compounds provided by the present invention are also found within the scope of the present invention. The term "cosmetically or pharmaceutically acceptable salts" refers to salts that are approved for use in animals (e.g., mammals), more specifically, salts that can be used in humans, and includes: salts formed for: base addition salts, the base addition salts being inorganic, such as and not limited to lithium, sodium, potassium, calcium, magnesium, manganese, copper, zinc or aluminum, etc., or the base addition salts being organic, such as and not limited to ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, arginine, lysine, histidine or piperazine, etc.; or acid addition salts, the acid addition salts being organic, such as and not limited to acetate, citrate, lactate, malonate, maleate, tartrate, fumarate, benzoate, aspartate, glutamate, succinate, oleate, trifluoroacetate, oxalate, pamoate or gluconate, etc., or being inorganic, such as and not limited to chloride, sulfate, borate or carbonate, etc. 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 S.M. et al., "Pharmaceutical Salts", (1977), Journal of Pharmaceutical Sciences, 66, 1-19].

[0131] The present invention also provides a combination comprising a compound of formula (I) according to any one of the above embodiments, its stereoisomers and / or its cosmetically acceptable salts with the following substances: botulinum toxin; Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 (SEQ ID NO.11); or H-Tyr-D-Ala-Gly-Phe-Leu-OH (SEQ ID NO.12); or Ac-βAla-His-Ser-His-OH (SEQ ID NO.13); or Ac-Gln-Glu-Met-Arg-Met-Gln-OH (SEQ ID NO.14); or Ac-Asp-Val-Tyr-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 a combination thereof.

[0132] Preparation procedures of the compounds of the present invention

[0133] The synthesis of the compounds of the present invention, their stereoisomers, mixtures thereof and / or their cosmetically or pharmaceutically acceptable salts can be carried out according to conventional methods known in the prior art, such as solid-phase peptide synthesis methods [Stewart J.M. and 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 syntheses of opioid peptides", (1980), J. Biol. Chem., 255(17), 8234-8238] or any combination thereof. The compounds can also be obtained by fermentation of bacterial strains, modified or unmodified by genetic engineering aimed at producing the desired sequence, or by controlled hydrolysis of proteins of animal or plant origin, preferably plant origin, which hydrolysis yields free peptide fragments containing the desired sequence.

[0134] For example, a method for obtaining a compound of formula (I), its stereoisomers and mixtures thereof comprises the following steps:

[0135] - 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 protected or solid-phase carrier-bound C-terminus;

[0136] - removing the protecting group at the N-terminus;

[0137] - repeating the coupling sequence and removing the protecting group at the N-terminus until the desired peptide sequence is obtained;

[0138] - removing the protecting group at the C-terminus or cleaving the solid-phase carrier.

[0139] Preferably, the C-terminus is attached to a solid support and the method is carried out in the solid phase. Thus, the method comprises: 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 attached to a polymeric support; removing the protecting group from the N-terminus; and repeating the sequence as many times as desired to obtain a compound of the desired length, and finally cleaving the synthesized compound from the original polymeric support.

[0140] The functional groups of the side chains of the amino acids are kept sufficiently protected throughout the synthesis using temporary or permanent protecting groups and can be deprotected simultaneously or orthogonally to the process of cleaving the peptide from the polymeric support.

[0141] Alternatively, solid-phase synthesis can be carried out using a convergent strategy that couples a peptide having a polymeric support with a previously attached peptide or amino acid to the polymeric support. 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.

[0142] The method may include using standard procedures and conditions known in the art to carry out other steps of deprotecting the N-terminus and C-terminus and / or cleaving the peptide from the polymeric support in any order, and the functional groups of these termini may be modified after these other steps. Optional modifications to the N-terminus and C-terminus can be carried out using the peptide of formula (I) anchored to the polymeric support or when the peptide has been separated from the polymeric support.

[0143] Optionally, R1 can be introduced by reacting the N-terminus of the compound of the present invention with an R1-X compound by a nucleophilic substitution reaction in the presence of a suitable base and solvent, wherein the fragment having a functional group not involved in N-C bond formation is appropriately protected using temporary or permanent protecting groups. R1 is as defined above and X is a leaving group such as, for example and without limitation, p-toluenesulfonyl, methanesulfonyl, and halogen groups, etc.

[0144] Optionally and / or additionally, the R2 group can be introduced by reacting the compound HR2 with a complementary fragment of the peptide of formula (I) in which R2 is -OH in the presence of a suitable solvent and a 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, a urea salt, a phosphonium salt or an amidinium salt, etc., or by pre-forming an acyl halide with thionyl chloride, for example, and thus obtaining a peptide of formula (I) according to the invention, wherein the fragment having a functional group not involved in N-C bond formation is appropriately protected with a temporary or permanent protecting group. Alternatively, other R2 groups can be introduced by incorporating them simultaneously into the peptide cleavage process from a polymer support. R2 is -OR3, -NR3R4 or -SR3, where R3 and R4 are as defined above.

[0145] Those skilled in the art will readily understand that the C-terminal and N-terminal deprotection / cleavage steps and their subsequent derivatization can be carried out in a different order according to methods known in the prior art.

[0146] The term "protecting group" refers to a group that blocks an organic functional group and can be removed under controlled conditions. Protecting groups, their relative reactivity, and the conditions under which they remain inert are known to those skilled in the art.

[0147] Examples of representative protecting groups for amino groups are amides such as amidoacetate, amidobenzoate, amido pivalate; carbamates such as benzyloxycarbonyl (Cbz or Z), 2-chlorobenzyloxycarbonyl (CIZ), p-nitrobenzyloxycarbonyl (pNZ), tert-butoxycarbonyl (Boc), 2,2,2-trichloroethoxycarbonyl (Troc), 2-(trimethylsilyl)ethoxycarbonyl (Teoc), 9-fluorenylmethoxycarbonyl (Fmoc) or allyloxycarbonyl (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-dioxo-cyclohexylidene)-3-methylbutyl (ivDde), 1-(1-adamantyl)-1-methylethoxycarbonyl (Adpoc), etc., preferably Boc or Fmoc.

[0148] Examples of representative protecting groups for carboxyl groups are esters such as tert-butyl ester (tBu), allyl ester (All), trityl ester (Trt ester), cyclohexyl ester (cHx), benzyl ester (Bzl), o-nitrobenzyl ester, p-nitrobenzyl ester, p-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), etc.; preferred protecting groups of the present invention are All, tBu, cHex, Bzl and Trt esters.

[0149] The side chains of trifunctional amino acids can be protected during the synthesis process with temporary or permanent protecting groups orthogonal to the protecting groups at the N-terminus and C-terminus.

[0150] The hydroxyl group of the tyrosine side chain can be protected with 2-bromobenzyloxycarbonyl group (2-BrZ), tBu, All, Bzl or 2,6-dichlorobenzyl (2,6-diClZ), etc. In a preferred embodiment, the protecting group strategy used is one in which the amino group is protected by Boc, the carboxyl group is protected by Bzl, cHx or All ester and the tyrosine side chain is protected by 2-BrZ or Bzl. In another preferred embodiment, the protecting group strategy adopted is one in which the amino group is protected by Fmoc, the carboxyl group is protected by tBu, All or Trt ester and the tyrosine side chain is protected by tBu.

[0151] The amino group of the tryptophan side chain can be protected, for example, by formyl (For) or Boc. In one embodiment, the amino group is protected by Fmoc, and the tryptophan side chain can be in the following situations: unprotected, i.e., the amino acid is incorporated in the form of Fmoc-Trp-OH; protected by Boc, i.e., the amino acid is incorporated in the form of Fmoc-Trp(Boc)-OH; or protected by For, i.e., the amino acid is incorporated as Fmoc-Trp(For)-OH. In one embodiment, the amino group is protected by Boc, and the tryptophan side chain can be protected by For, i.e., the amino acid is incorporated in the form of Boc-Trp(For)-OH.

[0152] Examples of these and other protecting groups, their introduction and removal can be found in the literature [Atherton B. and Sheppard R.C., "Solid Phase Peptide Synthesis: A practical approach", (1989), IRL Oxford University Press]. The term "protecting group" also includes the polymer supports used in solid phase synthesis.

[0153] When the synthesis occurs completely or partially in the solid phase, the possible solid-phase carriers used in the method of the present invention relate to polystyrene carriers, polyethylene glycol grafted to polystyrene, etc., for example and without limitation: 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., "Darstellung geschützter Peptid-Fragmente unter Einsatz substituierter Triphenylmethyl-Harze", (1989), Tetrahedron Lett., 30, 3943-3946; Barlos K. et al., "Veresterung von partiell geschützten Peptid-Fragmenten mit Harzen. Einsatz von 2-Chlorotritylchlorid zur Synthese von Leu1-Gastrin I", (1989), Tetrahedron Lett., 30, 3947-3951]; TentaGel β resin (Rapp Polymere GmbH); ChemMatrix βResins (Matrix Innovation, Inc), etc., which may or may not contain labile linkers such as 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 S.S., "p-Alkoxybenzyl Alcohol Resin and p-Alkoxybenzyloxycarbonylhydrazide Resin for Solid Phase Synthesis of Protected Peptide Fragments", (1973), J. Am. Chem. Soc., 95, 1328-1333], etc., which enable the simultaneous deprotection and cleavage of compounds from the polymer support.

[0154] Application

[0155] The present invention is based on the following discovery: Compounds of formula (I) can be used for the treatment of skin, hair, nails and / or mucous membranes, in particular for cosmetic, non-therapeutic treatment of skin, hair, nails and / or mucous membranes. It has been found that compounds of formula (I) can be used for the prevention or treatment of symptoms of skin aging, which include the presence of skin wrinkles, loss of firmness and the appearance of skin sagging. Specifically, it has been found that the compounds of the present invention effectively improve the firmness of the skin, reduce the appearance of skin sagging, reduce the appearance of wrinkles in the skin and lift the skin. It has also been found that compounds of formula (I) effectively up-regulate the expression of muscleblind-like protein 1 (MBNL-1) in skin and skeletal muscle cells. In addition, it has also been found that compounds of formula (I) are effective in stimulating the contraction of a collagen matrix containing fibroblasts (i.e., a collagen matrix similar to the extracellular matrix in the dermis). Therefore, compounds of formula (I) can be used for cosmetic, non-therapeutic treatment of skin, hair, nails and / or mucous membranes.

[0156] The present invention provides the use of a compound of formula (I), its stereoisomers and / or cosmetically acceptable salts; or 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. Specifically, the treatment and / or care of skin, hair, nails and / or mucous membranes is cosmetic and non-therapeutic. The treatment and / or care can be the treatment and / or care of the skin. In the context of the present invention, the skin includes the skin of the entire body, including the skin of the face (including the skin around the eyes), the décolletage, the neck, the chest, the arms, the hands, the legs, the feet, the thighs, the hips, the buttocks, the stomach and the trunk. The treatment and / or care of the skin may include: treating and / or preventing skin aging, treating and / or preventing skin wrinkles; maintaining and improving skin firmness; treating and / or preventing the appearance of skin sagging; and / or having a lifting effect on the skin.

[0157] The treatment and / or care may involve up-regulation of MBNL-1 expression in the skin (i.e., skin cells, in particular dermal fibroblasts) and / or muscle (i.e., muscle cells, in particular skeletal muscle cells). It is believed that the increase in MBNL1 promotes the differentiation of human dermal fibroblasts into myofibroblasts, which improves collagen contraction. In addition, the increase in MBNL-1 in muscle cells helps to maintain facial skin muscle tone. Therefore, skin sagging can be prevented.

[0158] Treatment and / or care may involve contraction of the extracellular matrix of the dermis. Fibroblasts that synthesize extracellular matrix components induce contraction of the extracellular matrix. It has been found that the compounds of formula (I) promote the contraction of fibroblast-containing collagen gels induced by fibroblasts, and are therefore considered to be able to promote the contraction of the extracellular matrix induced by fibroblasts. It is believed that this ability contributes to the ability of the compounds of formula (I) to, for example, maintain or improve skin firmness, treat or prevent the appearance of skin sagging, and reduce or prevent the appearance of skin wrinkles.

[0159] Treatment and / or care may be treatment and / or prevention of skin aging. Treatment and / or prevention of skin aging includes treating (or alleviating) and / or preventing the symptoms of skin aging. The symptoms of skin aging include the appearance of wrinkles and the loss of skin biomechanical properties (such as firmness). Loss of firmness can lead to the appearance of skin sagging. The loss of firmness may be due to changes in cell-matrix interactions in the dermal extracellular matrix caused by skin aging.

[0160] Treatment and / or care may be treatment and / or prevention of skin wrinkles. Skin wrinkles include expression wrinkles, which are commonly also referred to as expression lines.

[0161] Treatment and / or care may be maintenance and / or improvement of skin firmness. The skin may be facial skin, particularly the skin of the jaw.

[0162] Treatment and / or care may be treatment and / or prevention of the appearance of skin sagging.

[0163] Treatment and / or care may be lifting the skin, and may be, for example, lifting the eyebrows, cheeks or jaw.

[0164] The invention also extends to the use of a compound of formula (I) in combination with 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-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 for the application (use) of the compound of formula (I). Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 is commercialized as a peptide by Lipotec SAU (The Lubrizol Corporation) and is considered to mimic the cosmetic effects of botulinum toxin on the skin since it can inhibit neuronal exocytosis.

[0165] The invention also 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 a compound of formula (I), its stereoisomers and / or cosmetically or pharmaceutically acceptable salts; or a composition comprising a compound of the invention, its stereoisomers and / or cosmetically or pharmaceutically acceptable salts. Specifically, 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 can be a Caucasian. The method can be used for treating and / or caring for the skin, hair, nails and / or mucous membranes as described above for the application (use) of the compound of formula (I). Specifically, the method of treatment and / or care is a method for treating and / or caring for the skin. The administration can be topical or, for example, transdermal. The compound of formula (I) can be present in a cosmetic composition, such as the cosmetic compositions described herein. The method can involve the use of microneedles to administer the compound or the composition.

[0166] The present invention also extends to 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 a compound of formula (I), its stereoisomers and / or cosmetically or pharmaceutically acceptable salts in combination with botulinum toxin Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2, H-Tyr-D-Ala-Gly-Phe-Leu-OH; Ac-βAla-His-Ser-His-OH; or 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 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; and / or Ac-Arg-Arg-D-Gln-D-Met-Glu-Glu-NH2. The method can be used for treating and / or caring for the skin, hair, nails and / or mucous membranes as described above for the uses of the compound of formula (I). For example, the treatment method can comprise administering botulinum toxin and a compound of formula (I), its stereoisomers and / or cosmetically or pharmaceutically acceptable salts to the subject. For example, the treatment method can comprise administering to the subject: Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 and a compound of the present invention, its stereoisomers and / or cosmetically or pharmaceutically acceptable salts. Preferably, the treatment method is a skin anti-aging treatment.

[0167] 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 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) can be administered simultaneously or one after another. When 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; 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 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) 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 form, the dosage forms can be in the same or different containers.

[0168] The above-mentioned treatment methods include treating and / or caring for the skin, including: treating and / or preventing skin aging, treating and / or preventing skin wrinkles; maintaining and improving skin firmness; treating and / or preventing the appearance of skin sagging; and / or lifting the skin. Specifically, the treatment method is cosmetic and non-therapeutic.

[0169] On the other hand, the present invention provides a compound of formula (I), its stereoisomers and / or pharmaceutically acceptable salts for use as a medicament; or a pharmaceutical composition comprising a compound of formula (I), its stereoisomers and / or pharmaceutically acceptable salts. Specifically, the present invention provides a compound of formula (I), its stereoisomers and / or pharmaceutically acceptable salts for treating or preventing a disease or disorder; or a pharmaceutical composition comprising a compound of formula (I), its stereoisomers and / or pharmaceutically acceptable salts. On the other hand, the present invention provides the use of a compound of formula (I), its stereoisomers and / or pharmaceutically acceptable salts for manufacturing a medicament for treating or preventing a disease or disorder. On the other hand, the present invention provides a method for treating or preventing a disease or disorder in a subject, which method comprises administering to the subject a therapeutically effective amount of a compound of formula (I) or a pharmaceutical composition comprising the compound of formula (I).

[0170] For the methods described above, topical or transdermal administration can be carried out by iontophoresis, sonophoresis, electroporation, mechanical pressure, osmotic gradient, dressing care, microinjection, needleless injection by means of pressure, through a microelectronic patch, a facial mask or any combination thereof.

[0171] For the methods described above, the frequency of application or administration may vary widely depending on the needs of each subject, where the application is recommended from once a month to ten times a day, preferably from once a week to four times a day, more preferably from three times a week to twice a day, and even more preferably once a day. For example, the frequency of administration of methods for treating and / or caring for the skin, hair, nails, and / or mucous membranes of a subject, including the following, can vary widely: administering to a subject a compound of formula (I), its stereoisomers and / or cosmetically or pharmaceutically acceptable salts in combination with 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, 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 Ac-Arg-Arg-D-Gln-D-Met-Glu-Glu-NH2, depending on the needs of each subject. The methods of the present invention may include administering botulinum toxin and then administering a compound of formula (I). For example, after administering botulinum toxin, the compound of formula (I) may be administered at least once a day for at least one week and / or the compound of formula (I) may be administered at least once a day until the next administration of botulinum toxin.

[0172] Compositions of the present invention

[0173] The compound of formula (I) can be administered by any means that causes contact between the compound and the site of action in the subject. The subject is preferably a mammal, and more preferably a human. The subject can be a Caucasian. Preferably, the compound is included in a composition.

[0174] The present invention provides a composition comprising a compound according to formula (I), its stereoisomers and / or cosmetically or pharmaceutically acceptable salts. Specifically, the present invention provides a cosmetic composition comprising a compound according to formula (I), its stereoisomers and / or cosmetically acceptable salts, and at least one cosmetically acceptable excipient or adjuvant. These compositions can be prepared by conventional methods known to those skilled in the art [“Harry’s Cosmeticology”, 7th Edition, (1982), edited by Wilkinson J.B., Moore R.J., Longman House, Essex, GB].

[0175] Depending on the nature of its amino acid sequence or any possible modification at the N-terminus and / or C-terminus, the compound of formula (I) has variable solubility in water. Thus, the compounds of the present invention can be incorporated into the composition via an aqueous solution, and those insoluble in water can be dissolved in conventional cosmetically or pharmaceutically acceptable solvents such as, and not limited to, ethanol, propanol, isopropanol, propylene glycol, glycerol, butylene glycol or polyethylene glycol, or any combination thereof.

[0176] The cosmetically effective amount of the compound of formula (I) to be administered and its dosage will depend on a variety of factors, including age, the condition of the patient, the nature or severity of the condition, disorder or disease to be treated and / or cared for, the route and frequency of administration, and the specific nature of the compound to be used.

[0177] The terms “cosmetically effective amount” and “pharmaceutically effective amount” should be understood to mean an amount of one or more compounds of formula (I) that is non-toxic but sufficient to provide the desired effect. The terms “pharmaceutically effective” and “therapeutically effective” are used interchangeably herein. The compounds of formula (I) are used in the cosmetic or pharmaceutical compositions of the present invention at a cosmetically or pharmaceutically effective concentration to achieve the desired effect; for example, the amount used relative to the total weight of the composition is: 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).

[0178] The compound of formula (I), its stereoisomers, its mixtures and / or its cosmetically or pharmaceutically acceptable salts can also be incorporated into cosmetic or drug delivery systems and / or sustained release systems.

[0179] The term "delivery system" refers to a diluent, adjuvant, excipient or carrier administered together with the compounds of the present invention. These cosmetic or pharmaceutical carriers can be liquids such as water, oils, or surfactants, including those of petroleum, animal, vegetable, or synthetic origin, such as and without limitation, peanut oil, soybean oil, mineral oil, sesame oil, castor oil, polysorbates, sorbitan esters, ether sulfates, sulfates, betaines, glucosides, maltosides, fatty alcohols, nonoxynols, poloxamers, polyethylene oxides, polyethylene glycols, dextrans, glycerol, digitonin, etc. Those skilled in the art are aware of the diluents, adjuvants or excipients that can be used in the different delivery systems in which the compounds of the present invention can be administered.

[0180] The term "sustained release" is used in its conventional meaning for a delivery system of a compound that provides a gradual release of this compound over a period of time and preferably, but not necessarily, has a relatively constant level of compound release over a period of time.

[0181] Examples of delivery or sustained release systems include but are not limited to liposomes, mixed liposomes, oleosomes, niosomes, ethosomes, millimetric particles, microparticles, nanoparticles and solid lipid nanoparticles, nanostructured lipid carriers, sponges, cyclodextrins, vesicles, micelles, mixed micelles of surfactants, surfactant-phospholipid mixed micelles, millimetric spheres, microspheres and nanospheres, lipid spheres, millimetric capsules, microcapsules and nanocapsules, and microemulsions and nanoemulsions, which can be added to achieve greater permeability 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, more preferably water-in-oil microemulsions with a reversed micelle internal structure and nanocapsules containing microemulsions.

[0182] 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 creams, emulsions, gels, liposomes, nanoparticles and ointments.

[0183] Sustained release systems can be prepared by methods known in the prior art, and compositions containing sustained release systems can be administered, for example, by topical or transdermal administration, including adhesive patches, non-adhesive patches, occlusive patches and microelectronic patches; or by systemic administration, such as and without limitation, oral or parenteral routes, including nasal, rectal or subcutaneous implantation or injection, or direct implantation or injection into a specific body site, and preferably should release a relatively constant amount of the compounds of the present invention. The amount of the compound contained in the sustained release system will depend, for example, on where the composition will be administered, the kinetics and duration of the release of the compounds of the present invention, and the nature of the condition, disorder and / or disease to be treated and / or cared for.

[0184] The compounds of formula (I) can also be adsorbed on solid organic polymers or solid mineral carriers, such as, but not limited to, talc, bentonite, silica, starch or maltodextrin, etc.

[0185] Compositions containing the compounds of formula (I), their stereoisomers, mixtures thereof and / or their cosmetically or pharmaceutically acceptable salts can also be incorporated into fabrics, nonwovens and medical devices that come into direct contact with the skin, so that due to body humidity, skin pH or body temperature, the compounds of formula (I) are released by biodegradation of the binding system into the fabric, nonwoven or medical device, or by friction between it and the body. In addition, the compounds of formula (I) can be incorporated into fabrics and nonwovens used for manufacturing clothing that comes into direct contact with the body.

[0186] Examples of fabrics, nonwovens, clothing, medical devices and devices for fixing the compounds thereto (which are the delivery systems and / or sustained release systems described above) can be found in the literature and are known in the prior art [Schaab C.K. (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., Vol. 33, edited by Hipler U.C. and Elsner P., S.Karger AG, Basel, Switzerland; Malcolm R.K. 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 fabrics, nonwovens, clothing and medical devices are bandages, gauzes, T-shirts, socks, tights, underwear, corsets, gloves, diapers, sanitary napkins, dressings, sheets, wipes, adhesive patches, non-adhesive patches, occlusive patches, microcurrent patches and / or face masks.

[0187] Cosmetic or pharmaceutical compositions containing a compound of formula (I), its stereoisomers, mixtures thereof and / or its cosmetically or pharmaceutically acceptable salts can be used in different types of compositions for topical or transdermal application, which optionally contain cosmetically or pharmaceutically acceptable excipients necessary for formulating the required administration form.

[0188] Compositions for topical or transdermal application can be prepared in any solid, liquid or semi-solid formulation form, such as and not limited to creams, multiple emulsions (such as and not limited to water-in-oil and / or silicone emulsions, oil-in-water and / or silicone emulsions, water / oil / water or water / silicone / water type emulsions and oil / water / oil or silicone / water / silicone type emulsions), anhydrous compositions, aqueous dispersions, oils, milks, balms, foams, lotions, gels, cream gels, hydroalcoholic solutions, hydroglycolic solutions, hydrogels, liniments, serums, polysaccharide films, ointments, mousses, hair oils, powders, sticks, pens and sprays or aerosols (sprays), including wash-free and rinse formulations. These topical or transdermal application formulations can be incorporated into different types of solid excipients using techniques known to those skilled in the art, such as and not limited to bandages, gauzes, t-shirts, socks, tights, underwear, belts, gloves, diapers, sanitary napkins, dressings, bedspreads, rags, adhesive patches, non-adhesive patches, occlusive patches, microcurrent patches or face masks, or they can be incorporated into different cosmetic products, such as cosmetic foundations (such as liquid foundations and powder compacts), makeup removers, makeup remover milks, eye concealers, eyeshadows, lipsticks, lip balms, lip glosses and lip powders, etc.

[0189] The cosmetic or pharmaceutical compositions of the present invention may contain agents that increase the transdermal absorption of the compounds of the present invention, such as and not limited to dimethyl sulfoxide, dimethylacetamide, dimethylformamide, surfactants, azone (1-dodecylazacycloheptan-2-one), alcohols, ureas, ethoxydiglycol, acetone, propylene glycol or polyethylene glycol, etc. In addition, the cosmetic or pharmaceutical compositions of the present invention can be applied to local areas treated by iontophoresis, sonophoresis, electroporation, microcurrent patches, mechanical pressure, osmotic gradient, occlusive healing, microinjection or needleless injection by pressure (such as injection by oxygen pressure) or any combination thereof to achieve greater penetration of the peptides of the present invention. The application area will be determined by the nature of the condition, disorder and / or disease to be treated and / or cared for.

[0190] In addition, compositions containing the compounds of formula (I), their stereoisomers, mixtures thereof and / or their cosmetically or pharmaceutically acceptable salts can be used in different types of oral formulations, preferably in the form of oral cosmetics or pharmaceuticals, such as and without limitation: capsules, including gelatin capsules, soft capsules, hard capsules; tablets, including sugar-coated tablets, tablets, pills, powders, granules, chewing gums; solutions; suspensions; emulsions; syrups; elixirs; polysaccharide films; gels or gelatin; 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 food or fortified food, such as and without limitation, dietary bars or compressed or non-compressed powders. These powders can be dissolved in water, soda water, dairy products, soy derivatives or incorporated into diet bars. The compounds of formula (I) can be formulated with common excipients and adjuvants for oral compositions or food supplements, such as and without limitation, fatty components, aqueous components, humectants, preservatives, thickeners, flavoring agents, fragrances, antioxidants and colorants common in the food industry.

[0191] In addition to topical or transdermal administration, the cosmetic or pharmaceutical compositions containing the compounds of formula (I), their stereoisomers, mixtures thereof and / or their cosmetically or pharmaceutically acceptable salts can be administered by any other suitable route, such as oral or parenteral routes, and for this purpose these compositions will contain the pharmaceutically acceptable excipients necessary for formulating the desired form of administration. In the context of the present invention, the term "parenteral" includes nasal, ear, eye, rectal, urethral, vaginal, subcutaneous, intradermal routes, intravascular injection, such as intravenous, intramuscular, intraocular, intravitreal, intracorneal, intraspinal, intramedullary, intracranial, endocervical, intracerebral, intrathecal, intra-articular, intrahepatic, intrathoracic, intratracheal, intrathecal and intraperitoneal, and any other similar injection or infusion techniques. Different devices for administering the cosmetic or pharmaceutical compositions containing the compounds of the present invention are known to those skilled in the art.

[0192] 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, such as, but not limited to, (i) anti-wrinkle agents, botulinum-like agents, and / or anti-aging agents; (ii) firming agents, skin elasticity agents, and / or restructuring agents; humectants; (iii) anti-photoaging agents and / or blue light protectants; (iv) DNA protectants, DNA repair agents, and / or stem cell protectants; (v) free radical scavengers and / or anti-glycation agents, detoxifying agents, antioxidants, and / or anti-pollution agents; (vi) antiperspirants; (vii) melanin synthesis stimulants or inhibitors; (viii) skin lightening agents or depigmenting agents; (ix) pigmenting agents; (x) self-tanning agents; (xi) lipolytic agents or agents that stimulate lipolysis, adipogenic agents, etc. Additional examples can be found in the CTFA International Cosmetic Ingredient Dictionary & Handbook, 12th Edition (2008).

[0193] 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 selected from the group consisting of: (i) anti-wrinkle agents, botulinum-like agents, and / or anti-aging agents; (ii) firming agents, skin elasticity agents, and / or restructuring agents; (iii) humectants; (iv) anti-photoaging agents and / or blue light protectants; (v) DNA protectants, DNA repair agents, and / or stem cell protectants; (vi) free radical scavengers and / or anti-glycation agents, detoxifying agents, antioxidants, and / or anti-pollution agents; and / or combinations thereof.

[0194] The anti-wrinkle agents, botulinum-like agents, and / or anti-aging agents may be selected from the group consisting of those sold by Sederma / Croda [INCI: Palmitoyl Pentapeptide-4], [INCI: Palmitoyl Tetrapeptide-7, Palmitoyl Oligopeptide], Synthe’6 [INCI: Glycerin, Water, Hydroxypropyl Cyclodextrin, Palmitoyl Tripeptide-38], Morphomics TM [INCI: Pentylene Glycol, Caprylyl Glycol], Essenskin TM [INCI: Calcium Hydroxymethionine], Renovage [INCI: Teprenone], [INCI: Palmitoyl oligopeptide], Calmosensine [INCI: Butylene glycol, Acetyl dipeptide-1 cetyl ester], Volulip [INCI: Cetearyl ethylhexanoate, Sorbitan isostearate, Portulaca Pilosa extract, Sucrose cocoate, Palmitoyl tripeptide-38], Subliskin [INCI: Sinorhizobium Meliloti fermentation product, Cetyl hydroxyethylcellulose, Lecithin], Biopeptide CL [INCI: Palmitoyl oligopeptide], Biopeptide EL [INCI: Palmitoyl oligopeptide], Rigin [INCI: Palmitoyl tetrapeptide-3], Biobustyl [INCI: Glycerin polymethacrylate, Lactobacillus rahniel / soy protein fermentation product, Palmitoyl oligopeptide], Dynalift [INCI: Sodium polystyrene sulfonate, Sorghum Bicolor stem juice, Glycerin], Idealift [INCI: Acetyl dipeptide-1 cetyl ester], Siegesbeckia [INCI: Siegesbeckia Orientales extract], Juvinity TM [INCI: Geranylgeranyl isopropanol], Prolevis [INCI: Hydrolyzed plant protein], Idealift TM [INCI: Hydroxyethyl cellulose, Acetyl dipeptide-1 cetyl ester], Beautifeye R [INCI: Albizia Julibrissin bark extract, Darutoside], Chromocare TM [INCI: Siegesbeckia Orientalis extract, Rabdosia Rubescens extract] or Resistem TM [Proposed INCI: Globularia Cordifolia fermentation product]. Sold by Pentapharm / DSM [INCI: Pentapeptide-3], [INCI: Dipeptide Diaminobutyroyl benzylamide diacetate], [INCI: Palmitoyl tripeptide-5], Phytaluronate [INCI: Ceratonia Siliqua (carob) gum], [INCI: Glycine soja (Soybean) Protein, Oxidoreductase], Pepha-Nutrix [INCI: Natural Nutrient Factor], Pepha-Tight [INCI: Algae Extract, Pullulan], Pentacare-NA [INCI: Hydrolyzed Wheat Gluten, Ceratonia Siliqua Gum], [INCI: Glycerin, Palmitoyl Dipeptide-5 Diaminobutyroyl Hydroxythreonine, Palmitoyl Dipeptide-6 Diaminohydroxybutyrate], BeauActive MTP [INCI: Hydrolyzed Milk Protein], [INCI: Tetradecylaminobutyroylvalylaminobutyryl Urea Trifluoroacetate, Palmitoyl Tripeptide-5, Palmitoyl Dipeptide-5 Diaminobutyroyl Hydroxythreonine], [INCI: Tetradecylaminobutyroylvalylaminobutyryl Urea Trifluoroacetate], [INCI: Tetradecylaminobutyroylvalylaminobutyryl 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, Cocoyl Amphodiacetate Disodium] or All-Q TM Plus [INCI: Coenzyme Q10, Tocopheryl Acetate]; Myoxinol sold by Laboratoires Sérobiologiques / Cognis / BASF TM [INCI: Hydrolyzed Hibiscus esculentus Extract], Myoxinol TM LS 9736 [INCI: Hydrolyzed Hibiscus esculentus Extract, Dextrin], Syniorage TM [INCI: Acetyl Tetrapeptide-11], Dermican TM [INCI: Acetyl Tetrapeptide-9], LS [INCI: Cassia alata Leaf Extract], Hyalufix GL [INCI: Alpinia Galanga Leaf Extract], Neurobiox [INCI: Achillea Millefolium Extract], Deliner [INCI: Zea Mays (Corn) Kernel Extract], Lys'lastine V [INCI: Peucedanum Graveolens (Dill) Extract], Extracellium [INCI: Hydrolyzed Potato Protein], Proteasyl TP LS 8657 [INCI: Pisum Sativum Extract], Flavagrum PEG [INCI: PEG-6 Isostearate, Hesperetin Laurate], Micromerol [INCI: Pyrus Malus Fruit Extract], Extracellium [INCI: Hydrolyzed Potato Protein], MarineFilling Spheres [INCI: Pentaerythrityl Tetraisostearate, Dimethylsilylated Silica, Sodium Chondroitin Sulfate, Telopeptide-Free Collagen], Triactigen [INCI: Mannitol, Cyclodextrin, Yeast Extract, Disodium Succinate], Eterniskin [INCI: Grifola Frondosa Fruitbody Extract, Maltodextrin], Ascotide [INCI: Ascorbyl Phosphate Succinyl Pentapeptide-12], Hyalurosmooth [INCI: Cassia Angustifolia Seed Polysaccharide], Indinyl CA [INCI: Cassia Angustifolia Seed Polysaccharide], Arganyl [INCI: Argania Spinosa Leaf Extract], Sphingoceryl Veg [INCI: Phytoceramide], 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, Cocamidopropyl MIPA, Calcium Citrate], Elestan [INCI: Glycerin, Manilkara Leaf Extract], Hibiscin HP [INCI: Hibiscus Esculentus Seed Extract], 18 [INCI: Khaya Senegalensis Bark], Collrepair TM DG [INCI: Hexylene Glycol, Niacin] or Litchiderm [INCI: Litchi Chinensis Pericarp Extract]; sold by Lipotec / Lubrizol [INCI: Acetyl Hexapeptide-8], SNAP-7 [INCI: Acetyl Heptapeptide-4], SNAP-8 [INCI: Acetyl Octapeptide-3], [INCI: Pentapeptide-18], [INCI: Acetyl Hexapeptide-30], [INCI: Hydrolyzed Wheat Protein, Hydrolyzed Soy Protein, Tripeptide-1], [INCI: Diaminopropionyl Tripeptide-33], [INCI: Tripeptide-10 Citrulline], [INCI: Tripeptide-9 Citrulline], [INCI: Pseudoalteromonas Ferment Extract, Hydrolyzed Wheat Protein, Hydrolyzed Soy Protein, Tripeptide-10 Citrulline, Tripeptide-1], [INCI: Acetyl Tetrapeptide-5], Peptide AC29 [INCI: Acetyl Tripeptide-30 Citrulline], [INCI: Acetyl Arginyl Tryptophyl Diphenylglycine], [INCI: Acetyl Tetrapeptide-22], Lipochroman TM [INCI: Dimethylmethoxy Chromanol], [INCI: Dimethylmethoxy Chroman Palmitate], [INCI: Pseudoalteromonas Ferment Extract], [INCI: Lysine HCl, Lecithin, Tripeptide-9 Citrulline], Vilastene TM [INCI: Lysine HCl, Lecithin, Tripeptide-10 Citrulline], [INCI: Pseudoalteromonas Ferment Extract], Hyanify TM [INCI: Carbohydrate Isomers], [INCI: Acetyl Hexapeptide-37], [INCI: Soybean (Glycine Soja) Oil, Sorbitan Sesquioleate, Isocetane, Sodium Hyaluronate, Lauryl Dimethyl Ammonium Hydroxypropyl Hydrolyzed Soy Protein, Acetyl Hexapeptide-39] [INCI: Acetyl Hexapeptide-38], Delisens TM [INCI: Acetyl Hexapeptide-46], Telangyn TM [INCI: Acetyl Tetrapeptide-40], Reproage TM Peptide [INCI: Acetyl Hexapeptide-8], Cellynkage TM Marine ingredient [INCI: Carbohydrate Isomerate], Eyedeline TM Marine ingredient [INCI: Plankton Extract], uplevity TM [INCI: Acetyl Tetrapeptide-2], Seacode TM Marine ingredient [INCI: Pseudoalteromonas Ferment Extract] or Peptide solution [INCI: Hexapeptide-10], Amplified peptide [INCI: Acetyl Hexapeptide-8]; Sirtalice sold by Lipotrue TM [INCI: Bacillus Ferment], Epitensive TM [INCI: Nicotiana Benthamiana Hexapeptide-40SH-Oligopeptide-1], Scelleye TM [INCI: Nicotiana Benthamiana SH-Oligopeptide-2], Seadermium [INCI: Contains water, glycerin, Bacillus Ferment], Pauseile [INCI: Contains water, glycerin, Bacillus Ferment] or Neoclair pro [INCI: Contains water, glycerin, caprylyl glycol, Acetyl Tetrapeptide-2]; Sold by Vincience / ISP / Ashland IS [INCI: Hexapeptide-9], LaminixylIS TM [INCI: Heptapeptide], Orsirtine TM GL [INCI: Oryza sativa (Rice) Extract], D’Orientine TM IS [INCI: Phoenix dactylifera (Date) Seed Extract], PhytoquintescineTM [INCI: Einkorn (Triticum monococcum) Extract], Quintescine TM IS [INCI: Dipeptide-4], Peptide Vinci 01 [INCI: Pentadecapeptide-1], Peptide Vinci 02 TM [INCI: Hexapeptide-3], AquarizeIS TM [INCI: Hydrolyzed Rice Extract], Lanablue [INCI: Algae Extract], Ederline R [INCI: Apple (Pyrus Malus) Seed Extract], Dynachondrine R ISR [INCI: Hydrolyzed Soy Protein], Prolixir S20 R [INCI: Dimeric Tripeptide-43], Phytocohesine TM PSP [INCI: Sodium β-Sitosterol Sulfate, β-Sitosterol], Perenityl TM IS [INCI: Pear (Pyrus Communis) Seed Extract], Caspaline 14 TM [INCI: Hexapeptide-42], Peptide Q10 TM [INCI: Pentapeptide-34 Trifluoroacetate], Survixyl IS TM [INCI: Pentapeptide-31], ChroNOgen TM [INCI: Tetrapeptide-26], Elixiance [INCI: Schinus Molle Extract], Harmoniance TM [INCI: Lotus (Nelumbo Nucifera) Flower Extract], Serenityl [INCI: Marsdenia Condurango Bark Extract], Natriance Wrinkle-less [INCI: Hydrolyzed Corn Protein], Phytoneomatrix [INCI: Hydrolyzed Soy Extract], Prolixir ICE [INCI: Hydrolyzed Rice Protein], PhytoRNxBaobab TM[INCI: Hydrolyzed Baobab (Adansonia Digitata) Extract], Natriance Renovate Extract [INCI: Hydrolyzed Flaxseed Extract], Natriance Self-Hydrate Extract [INCI: Pea (Pisum Sativum) Extract], Actopontine YST [INCI: Hydrolyzed Yeast Protein] or Telosense TM[Proposed INCI: Hydrolyzed Soy Protein, Hydrolyzed Yeast Protein]; BONT-L-Peptide [INCI: Palmitoyl Hexapeptide-19], TIMP Peptide [INCI: Acetyl Hexapeptide-20], ECM 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 / Glycolic Copolymer, Polyvinyl Alcohol, Copper Palmitoyl Heptapeptide-14, Heptapeptide-15 Palmitate], sold by Infinitec Activos; EquiStat [INCI: Apple (Pyrus malus) Fruit Extract, Wild Soybean (Glycine soja) Seed Extract], Juvenesce [INCI: Ethoxydiglycol and Triglycerol Caprylate, Retinol, Ursolic Acid, Phytomenadione, Ilomastat], Ursolisome [INCI: Lecithin, Ursolic Acid, Telopeptide-Free Collagen, Xanthan Gum, Sodium Chondroitin Sulfate], Basaline [INCI: Hydrolyzed Malt Extract], Phytokine [INCI: Hydrolyzed Soy Protein], sold by Coletica / Engelhard / BASF; Ameliox [INCI: Carnosine, Tocopherol, Milk Thistle (Silybum marianum) Fruit Extract] or PhytoCellTec Malus Domestica [INCI: Apple (Malus domestica) Fruit Cell Culture], Lipobelle Soyaglicane [INCI: Soy Isoflavones], RoyalEpigen P5 [INCI: Shea Butter (Butyrospermum Parkii), Hydrogenated Lecithin, Maltodextrin, Pentapeptide-48, Phenethyl Alcohol, Ethylhexylglycerin, Glycerin, Aqua], or DermCom [INCI: Crocus Chrysanthus Bulb Extract, Acacia Senegal Gum, Aqua], sold by Mibelle Biochemistr; ActiMatrix [INCI: Peptide-Based Mushroom Extract], Peptamide 6 [INCI: Hexapeptide-11], sold by Active Organics / Arch; and combinations thereof.

[0195] The firming agent, skin elasticity agent, and / or restructuring agent may be optionally selected from the group consisting of: Argassential sold by BASF [INCI: C10-16 alkyl glucoside, dioctyl ether, glycerol] or Replexium BC [INCI: isosorbide dimethyl ether, polysorbate 20, water-containing, acetyl tetrapeptide-11, acetyl tetrapeptide-9]; Prolevis sold by Sederma / Croda [INCI: hydrolyzed vegetable protein] or Poretect [INCI: caprylic / capric triglyceride, sorbitan trioleate, Apium Graveolens seed extract, Linum Usitatissimum seed extract]; Actifirm Ultra Advanced plant ingredients sold by Lipotec / Lubrizol [INCI: Centella Asiatica extract, Rosmarinus Officinalis leaf extract, dipropylene glycol, alcohol, Echinacea Angustifolia leaf extract] or Actifcol Advanced plant ingredients [INCI: water-containing, glycerol, sodium citrate, Lentinus Edodes extract, potassium sorbate, sodium benzoate, phytic acid]; Densorphin sold by Mibelle TM [INCI: Vitex Agnus Castus extract, water-containing, maltodextrin] or PhytoCellTec TM [INCI: isomalt, water-containing, Saponaria Pumila callus extract, lecithin]; and combinations thereof.

[0196] The humectant may be optionally selected from the group consisting of: qua Shuttle sold by Infinitec [INCI:

[0197] sorbitol, Laminaria Digitata extract, diatomaceous earth]; Aqua-Osmoline sold by Vincience / ISP / Ashland TM [INCI: Ceratonia Siliqua (carob) seed extract]; Hydralphatine sold by Lucas Meyer Cosmetics / Unipex TMAsia [INCI: Hydrolyzed Starch, Panthenol, Bambusa Vulgaris Shoot Extract, Nelumbo Nucifera Flower Extract, Nymphaea Alba Root Extract] or Hydraporine TM [INCI: Betaine, Hydrogenated Lecithin, Honey, Pectin]; PatcH2O sold by L.Serobiologiques / Cognis / BASF TM [INCI: Trehalose, Urea, Serine, Glyceropolyacrylate, Algin, Sodium Hyaluronate, Pullulan], Aqu’activ TM [INCI: Behenyl Alcohol, Glyceryl Oleate, Cocamide MIPA], [INCI: Octyldodecanol, Irvingia Gabonensis Kernel Butter, Hydrogenated Coconut Glycerides], )[INCI: Octyldodecanol, Phenylpropanol Propionate, Tocopheryl Acetate, Retinyl Palmitate, Ethyl Linoleate, Ethyl Linolenate] or SU [INCI: Sorbitol, Algae Extract, Chrondrus Crispus (Carrageenan), Fucus Vesiculosus Extract, Algin]; Snow Algae Powder sold by Mibelle [INCI: Coenochloris Signiensis Extract]; Hyasol BT sold by Pentapharm / DSM [INCI: Sodium Hyaluronate], Syn-Up TM [INCI: Benzylsulfonyl D-Seryl-Homo-Phenylalanine Amidinobenzylamide Acetate] or [INCI: Carbohydrate Isomerate]; Aqualance sold by Sederma / Croda TM [INCI: Erythritol, Lobeline Hydrochloride], Hydraprotectol TM [INCI: Glyceropolymethacrylate, Aleuritic Acid, Yeast Extract (Faex), Glycoprotein], Moist 24 TM [INCI: Imperata Cylindrica Root Extract], Optim Hyal TM [INCI: Hydrolyzed Yeast Extract, Cetyl Hydroxyethylcellulose, Polyglucuronic Acid], 4 [INCI: Glycerin, Acrylate / Acrylic C10-30 Alkyl Ester Crosslinked Polymer] or Revidrate TM[INCI: Ethylhexyl Palmitate, Sorbitan Oleate, Sorbitan Laurate, Myristyl Malate Phosphate]; Sold by Lipotec / Lubrizol Molecular film [INCI: Glycerin, Pseudoalteromonas Ferment Extract, Xanthan Gum, Proline, Alanine, Serine, Ethylhexylglycerin, Octyldecanol] or Actizyme GL advanced plant ingredient [INCI: Glycerin, Mucor miehei Extract, Aqueous, Sodium Citrate, Potassium Sorbate, Sodium Benzoate, Phytate]; and combinations thereof.

[0198] The anti-photoaging agent and / or blue light protection agent can be optionally selected from the group consisting of: Algaktiv Genofix CPD sold by Greenaltech [INCI: Plankton Extract, Aqueous, Lecithin]; Blumilight sold by Ashland TM Biofunctional [Proposed INCI: Water / Aqueous (and) Butylene Glycol (and) Theobroma Cacao (Cocoa Tree) Seed Extract]; Lys’Sun sold by BASF [INCI: Hamamelis Virginiana Leaf Extract, Aqueous, Pentylene Glycol, Octyldecanol, Xanthan Gum]; Vitachelox sold by Indena [INCI: Vitis Vinifera Seed Extract, Camellia Sinensis Leaf Extract, Quercus Robur Wood Extract]; L-VCG sold by Freshine Bio-technology [INCI: Ascorbyl Glucoside]; Sold by Lipotec / Lubrizol Blue component [INCI: Glycerin, Aqua, Hydrolyzed Pea Protein, Glucose, Sodium Chloride]; Lightwaves Defense sold by Naolys [JS+M] [INCI: Jasminum Sambac Leaf Cell Extract]; Blue Oleoactif sold by Oleos-Hallstar [INCI: Glycine Soja Oil, Polyglycerin-3 Diisostearate, Oryza Sativa Germ Extract, Oryza Sativa Extract]; Majestem sold by Sederma [INCI: Glycerin, Leontopodium Alpinum Callus Extract, Xanthan Gum] or Senestem [INCI: Glycerin, Plantago Lanceolata Leaf Extract, Xanthan Gum]; Blueshield sold by Solabia [INCI: Glycerin, Capsicum Annuum Fruit Extract, Xanthan Gum]; and combinations thereof.

[0199] The DNA protectant, DNA repair agent, and / or stem cell protectant may be selected from the group consisting of GP4G SP sold by Vincience / ISP / Ashland [INCI: Aqua, Glycerin, Artemia 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]; sold by Atrium Innovations / Lucas Meyer Cosmetics [INCI: Glycerin, Aqua, Alteromonas Ferment Extract, Chysanthellum indicum Extract] or Melinoil [INCI: Isopropyl Palmitate, Lecithin, Aqua, Acetyl Hexapeptide-1]; Repair Complex sold by CLR [INCI: Bifida Ferment Lysate]; Phycojuvenine sold by Codif [INCI: Laminaria Digitata]; Unirepair T-43 sold by Induchem [INCI: Butylene Glycol, Acetyl Tyrosine, Proline, Hydrolyzed Vegetable Protein, Adenosine Triphosphate]; Dragosine sold by Symrise [INCI: Carnosine]; DN-Age sold by Laboratories Serobiologiques / Cognis / BASF [INCI: Cassia Alata Leaf Extract]; Helioguard sold by Mibelle Biochemistry [INCI: Porphyra Umbilicalis Encapsulated in Liposomes], PhytoCellTec Malus Domestica [INCI: PhytoCellTec Malus Domestica] or PhytoCellTec Argan [INCI: Argania Spinosa Bud Cell Extract, Erythritol, Lecithin, Sodium Benzoate, Aqua]; Pepha-Protect sold by Pentapharm / DSM [INCI: Watermelon Extract]; Celligent sold by Rahn [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 sold by Sederma / Croda [INCI: Thermus Thermophilus fermentation product, glycerin], UV-Soft [INCI: yeast extract], Renovage [INCI: caprylic / capric triglyceride, teprenone], Juvinity [INCI: caprylic / capric triglyceride, geranylgeranyl alcohol (proposed)], Phytessence Holyherb [INCI: butylene glycol, Eriodictyon Californicum (yerba santa) flower / leaf / stem extract] or Resistem [INCI: glycerin, Globularia Cordifolia fermentation product]; Infraguard sold by Mibelle [INCI: Caesalpinia spinosa fruit pod extract, propylene glycol, water-containing, Helianthus Annuus bud extract, sodium benzoate, phenoxyethanol]; Heliomoduline sold by Silab [INCI: low molecular weight peptides from cotton seeds] or Stem-C-Guard [hydrolyzed peas]; and combinations thereof.

[0200] Reactive carbonyl species scavengers, free radical scavengers and / or anti-glycation agents, detoxifying agents, antioxidants and / or anti-pollution agents may be selected from, for example but not limited to, the group consisting of: carnosine and its derivatives; GHK [INCI: tripeptide-1] and its salts and / or derivatives or Quintescine IS [INCI: dipeptide-4] sold 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, glycerin, water] or Dismutin-BT [INCI: highly purified SOD from a natural yeast strain of Saccharomyces cerevisiae] sold by Pentapharm / DSM; [INCI: diaminopropionyl tripeptide-33], [INCI: Hydrolyzed Wheat Protein, Hydrolyzed Soy Protein, Tripeptide 1], Lipochroman TM [INCI: Dimethylmethoxy Chromanol], [INCI: Acetyl Tetrapeptide-22], Pollushield R Functional ingredients [INCI: Diisopropyl Adipate, Lecithin, Acrylic Acid / Acrylamidomethylpropanesulfonic Acid Copolymer, Dimethylmethoxy Chromanol, Xanthan Gum] or [INCI: Acetyl Dipeptide-3 Aminohexanoate]; unactyl sold by Laboratoires Sérobiologiques / Cognis / BASF [INCI: Mannitol, Extract of Pisum Sativum, Histidine Hydrochloride, Arginine, Cyclodextrin, Dextrin, Yeast Extract, Acetyl Tyrosine, Pyridoxine Hydrochloride, Extract of Khaya Senegalensis Bark, Niacinamide, Adenosine Diphosphate, Disodium Succinate, Aspartic Acid], Imidinyl [INCI: Tamarindus Indica Seed Polysaccharide], Phystrogene [INCI: Butylene Glycol, Extract of Malva Sylvestris (Mallow), Xanthan Gum] or Purisoft [INCI: Extract of Moringa Pterogysperma Seeds]; AquaCacteen sold by Mibelle Biochemistry [INCI: Glycerol, Extract of Opuntia Ficus Indica Stem, Phenoxyethanol, Aqueous], Trimoist (KMF) [INCI: Sodium Stearoyl Lactylate, Cetyl Alcohol, Olus Vegetable Oil, Tocopheryl Acetate, Glycerol, Glycine Soja Sterols, Sodium Lactate, Sodium Carboxymethyl β-Glucan, Carnosine, Lactic Acid], MelanoBronze [INCI: Extract of Vitex Agnus Castus (Extract of Monk's pepper berries (Phytoendorphins)), Acetyl Tyrosine], CM-Glucan [INCI: Sodium Carboxymethyl β-Glucan, Phenoxyethanol, SunActin [INCI: Extract of Helianthus Annuus (Sunflower) Buds, Tocopherol, Glycerol, Lecithin, Phenoxyethanol, Aqueous], GSP-T skin [INCI: Glycerol, Alcohol, Aqueous, PEG-40 Hydrogenated Castor Oil, Extract of Vitis Vinifera (Grape) Seeds] or Detoxophane [INCI: Extract of Lepidium Sativum Buds, Lecithin, Phenoxyethanol, Glycerol, Water];Bacocalmine sold by Sederma / Croda [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]; Extramel C sold by Seppic [INCI: hydroxypropyltrimonium chloride maltodextrin cross-linked polymer, Cucumis Melo (melon) fruit extract]; Defensine sold by Silab [INCI: Triticum Vulgare germ extract]; [INCI: Taraxacum officinale (dandelion) extract], [INCI: water, butylene glycol, Butyrospermum parkii (shea butter) seed cake extract] or Antiglyskin [INCI: aqua, Helianthus Annuus seed extract]; and combinations thereof.

[0201] The compositions containing the compounds of formula (I) described herein can be used for any application or use discussed under the above title "Applications".

[0202] The present invention is illustrated by the following non-limiting examples.

[0203] Examples

[0204] General methods

[0205] Abbreviations

[0206] 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.

[0207] (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-butoxycarbonyl; DCM, dichloromethane; DIEA, N,N′-diisopropylethylamine; DIPCDI, N,N′-diisopropylcarbodiimide; DMF, N,N-dimethylformamide; ESI-MS, electrospray ionization mass spectrometry; Fmoc, 9-fluorenylmethoxycarbonyl; 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-methyldiphenylmethylamine; 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.

[0208] Chemical synthesis

[0209] All synthetic procedures were carried out in polypropylene syringes fitted with porous polyethylene disks. The coupling protocol was carried out according to the standard protocol established in the reference, and the solvents and soluble reagents were removed by aspiration. The Fmoc group was removed with 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)]. The washes between the deprotection, coupling and further deprotection steps were carried out with DMF, using 10 ml of solvent / g resin each time (3×1 min after coupling, 5×1 min after removal of Fmoc). The coupling reaction was carried out with 3 ml of solvent / g resin. The control of the coupling was carried out by performing: the ninhydrin test [Kaiser E. et al., Anal. Biochem. (1970), 34:595 - 598] or the tetrachlorobenzoquinone test [Christensen T., Acta Chem. Scand. (1979), 33B, 763 - 766]. The coupling reaction was repeated when the desired peptide was synthesized. All synthetic reactions and washes were carried out at 25 °C.

[0210] It is known to those skilled in the art that some amino acids are used together with their protected functional groups in the side chain. For example, non-limiting examples of protecting groups are:

[0211] ● tBu, the tert-butyl group of the amino acid threonine

[0212] HPLC chromatographic analysis was carried out using a reversed-phase column maintained at 30 °C (50 mm × 4.6 mm, Kromasil C18, 3.5 μm, Akzo Nobel, Sweden) with a Shimadzu device (Kyoto, Japan). Elution was carried out using a gradient of water (+0.1% TFA) containing acetonitrile (+0.07% TFA) at a flow rate of 1.6 mL / min and detection was carried out at 220 nm. Electrospray ionization mass spectrometry was carried out in a WATERS Alliance ZQ 2000 detector using a mixture of MeCN:H2O 4:1 (+0.1% TFA) as the mobile phase and a flow rate of 0.3 ml / min.

[0213] Example 1

[0214] Obtain Fmoc-W m -Xn -AA1-AA2-AA 3- AA4-Y o -Z p -PS-(R), where 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.

[0215] The weight has been standardized. 1 equivalent of Fmoc-L-Thr(tBu)-OH was dissolved in dry DCM and 0.8 equivalent of DIEA was added, then it was added to 2-chlorotrityl resin. After 5 minutes, the remaining 1.7 equivalents of DIEA were added and the mixture was stirred for another 40 minutes. The unreacted resin was capped with methanol for 10 minutes. The resin was filtered and washed with DCM (3×1 minute) and DMF (5×1 minute).

[0216] The Fmoc-Thr(tBu)-PS resin was treated with a 1:1 solution of 5% piperidine in DCM / DMF for 10 minutes, then with a 20% piperidine solution in DMF for 15 minutes to remove the Fmoc group. After washing the resin as described in the general method, 2 equivalents of Fmoc-L-Val-OH were incorporated onto the deprotected resin using DMF as a solvent in the presence of 2.2 equivalents of DIPCDI and 2 equivalents of Oxyma for 1 hour.

[0217] Then, as described in the general method, the resin was washed and the deprotection treatment of the Fmoc group was repeated to couple the next amino acids: 2 equivalents of Fmoc-L-Pro-OH; and subsequently 2 equivalents of Fmoc-L-Leu-OH; in each coupling step, they were coupled sequentially in the presence of 2 equivalents of Oxyma and 2.2 equivalents of DIPCDI.

[0218] After synthesis, the peptidyl resin was washed with DMF and DCM (3×1 minute).

[0219] By following the described method, it is possible to obtain different sequences of the desired amino acids to be coupled.

[0220] Example 2

[0221] General method for removing the Fmoc N-terminal protecting group.

[0222] As described in the general method (20% piperidine in DMF, 1×1 minute + 1×5 minutes), the N-terminal Fmoc group of the peptidyl resin obtained in Example 1 was deprotected. The peptidyl resin was washed with DMF (5×1 minute), DCM (3×1 minute), diethyl ether (3×1 minute), and dried under vacuum.

[0223] Example 3

[0224] Method for introducing an R1 palmitoyl group into the peptidyl resin obtained in Example 2.

[0225] In the presence of Oxyma and DIPCDI, 5 equivalents of palmitic acid (1 ml) pre-dissolved in DMF were added to each peptidyl resin in the peptidyl resin obtained in Example 2. The mixture was allowed to react for 3 hours, and then the resin was washed with DMF (3 × 1 minute), DCM (3 × 1 minute), and diethyl ether (3 × 1 minute), and dried under vacuum.

[0226] Example 4

[0227] Method for introducing an R1 acetyl group into the peptidyl resin obtained in Example 2.

[0228] In the presence of DIEA, using DMF as a solvent, each peptidyl resin in the peptidyl resin obtained in Example 3 was treated with acetic anhydride. The mixture was allowed to react for 30 minutes, and then the resin was washed with DMF (3 × 1 minute), DCM (3 × 1 minute), and diethyl ether (3 × 1 minute), and dried under vacuum.

[0229] Example 5

[0230] Method for cleaving the polymer support of the peptidyl resins obtained in Examples 2, 3, and 4.

[0231] Each peptidyl resin in the dry peptidyl resins obtained in Example 3, Example 4, and Example 5 was treated with 3 ml of TFA:H2O (95:5, v / v) for 2 hours at room temperature under stirring. Then it was filtered through a polypropylene syringe equipped with a porous polyethylene plate. The filtrate was collected onto cold diethyl ether and washed 5 times with diethyl ether. The final precipitate was dried under vacuum.

[0232] HPLC analysis of the obtained peptides in H2O (+0.1% TFA) containing MeCN (+0.07% TFA) with a certain gradient showed a purity exceeding 80% in all cases. The identity of the obtained peptides was confirmed by ESI-MS.

[0233] Example 6

[0234] Muscleblind-like protein 1 (MBNL1) in human skeletal muscle cells (hSKMC)

[0235] The increase of MBNL-1 in muscle cells contributes to maintaining the tension of facial skin muscles. Therefore, compounds capable of enhancing MBNL-1 can be used as a good method for cosmetic treatment of sagging faces.

[0236] Methods :

[0237] Cell culture and treatment

[0238] Human skeletal muscle cells (hSKMC) were cultured with 100,000 cells in a T25 culture flask with growth medium. After 4 days, the cells reached approximately 80% confluence and were seeded at 150,000 cells / well in the growth medium of a 12-well plate. The cells were incubated for 72 hours and then switched to differentiation medium and incubated for 48 hours. At the end of this period, during the 48 hours in differentiation medium, the cells were treated with the defined peptide (0.5 mg / ml) and with medium only as a control condition. The cells were also treated with 2 mM ketoprofen as a positive control.

[0239] Protein extraction and quantification

[0240] After the incubation period, the cells were lysed and frozen at -80 °C. For total protein quantification, the protein extracts were measured by the Bicinchoninic Acid (BCA) method. MBNL1 protein detection was performed by homogeneous time-resolved fluorescence (HTRF) technology. The MBNL1 levels were normalized by total protein quantification under each condition. The results were expressed as relative MBNL1 protein levels relative to the control condition. Each condition was performed with at least 3 replicates.

[0241] Table 4 - MBNL1 expression in human skeletal muscle cells (hSKMC)

[0242] ID Peptide % MBNL1 compared to basal control PEP-1 H-Leu-Pro-Val-Thr-OH 213.0 PEP-2 <![CDATA[H-Leu-Pro-Val-Thr-NH2]]> 183.2 PEP-3 Palm-Leu-Pro-Val-Thr-OH 160.4 PEP-4 Ac-Leu-Pro-Val-Thr-OH 131.3 PEP-5 <![CDATA[Ac-Leu-Pro-Val-Thr-NH2]]> 213.7 PEP-6 H-Leu-Ala-Val-Thr-OH 157.0 PEP-7 H-Leu-Pro-Ile-Thr-OH 156.3 PEP-8 H-Val-Pro-Val-Thr-OH 131.3 PEP-9 H-Leu-Gly-Val-Thr-OH 122.4 PEP-10 H-Leu-Pro-Leu-Thr-OH 222.0 PEP-11 H-Ala-Leu-Pro-Val-Thr-OH 259.0 PEP-12 H-Leu-Pro-Val-OH 177.8 PEP-13 H-Ile-Pro-Ile-Thr-OH 133.3

[0243] Example 7

[0244] Muscleblind-like protein 1 (MBNL1) in human dermal fibroblasts (HDF)

[0245] The aim of this study was to evaluate the increase in MBNL1 protein in human skin fibroblasts after electrical stimulation (simulated microcurrent-like treatment). A topical product that can increase the amount of MBNL1 protein in fibroblasts in a manner similar to microcurrent-like treatment may induce the same anti-aging benefits on the skin, thus avoiding the side effects of physical microcurrent treatment.

[0246] Microcurrent stimulation assay :

[0247] Cells were seeded at 100,000 cells / well in a 12-well plate on sterilized coverslips and incubated at 37 °C, 5% CO2 for 48 hours. After that, electrical stimulation was performed. The coverslips were transferred to a 6-well plate and electrically stimulated (1.5 V) for 1 hour at room temperature using a C-chamber device (IonOptix). The same 6-well plate with unstimulated cells was incubated at room temperature for 1 hour. After electrical stimulation, the coverslips were transferred back to the 12-well plate and incubated at 37 °C, 5% CO2 for 24 hours. Three different replicates were used for each condition.

[0248] Peptide treatment

[0249] 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, the cells were treated with 0.01 mg / ml, 0.1 mg / ml, and 0.5 mg / ml of PEP-1 (H-Leu-Pro-Val-Thr-OH) for 24 hours. Cells incubated with only medium were used as controls. Three replicates were performed for each condition.

[0250] MBNL1 immunofluorescence and quantification

[0251] After 24 hours of incubation, the cells were washed twice with phosphate-buffered saline (PBS), fixed with 4% PFA (paraformaldehyde solution) for 15 minutes and washed twice again. After that, the cells were permeabilized with 1% X-Triton solution for 15 minutes and blocked with 5% bovine serum albumin (BSA) solution for 1 hour. The cells were incubated with a primary antibody against MBNL1 protein (Sigma) diluted 1 / 20 in 5% BSA solution for 2 hours. After the incubation period, the cells were washed and incubated with a secondary antibody (AlexFluor 488) diluted 1 / 200 in 5% BSA solution for 1 hour. Finally, the cells were washed 3 times and stained with 4',6-diamidino-2'-phenylindole dihydrochloride (DAPI) mounting solution for nuclear detection. Using a confocal microscope ( Confocal microscope, PerkinElmer Inc), using the Alexa 488 green channel (Ex: 460 nm - 490 nm / Em: 500 nm - 550 nm), the quantification of MBNL1 protein was measured, i.e., the fluorescence intensity of MBNL1 normalized by the number of cell nuclei under each condition. The results were expressed as the MBNL1 level relative to the control condition. At least three independent experiments were analyzed in this assay.

[0252] The results were calculated using the following formula:

[0253]

[0254] 1. Detection of MBNL1 protein after microcurrent stimulation

[0255] As shown in Table 5, compared with the basal control (CTR; without MES), electrical stimulation (70 mV·mm -1 ; <1 mA, 1.5 V, 1 h) was able to increase MBNL1 protein on human fibroblasts.

[0256] Table 5 - MBNL1 intensity in HDFa cells .

[0257]

[0258] 2. Detection of MBNL1 protein after peptide treatment

[0259] As shown in Table 6, under the test conditions, compared with the basal control (CTR; without MES), PEP-1 (H-Leu-Pro-Val-Thr-OH) increased MBNL1 protein in human fibroblasts. Table 6 shows that PEP-1 was able to induce MBNL1 protein expression at a level comparable to that of MES.

[0260] Table 6 - MBNL1 intensity in HDFa cells .

[0261]

[0262] 3. Comparative MBNL1 intensity in HDFa cells relative to electrical stimulation .

[0263] For comparison purposes, the effect of the peptide was compared with the effect of MES. The effect was calculated as follows:

[0264]

[0265] The results are shown in Table 7.

[0266] Table 7 - Comparative MBNL1 intensity in HDFa cells relative to electrical stimulation .

[0267]

[0268] The results showed that PEP-1 had a significant effect on the expression level of MBNL1 protein in fibroblasts, similar to the effect of MES.

[0269] Example 8

[0270] ​

[0271] Well-known significant changes in the mechanical properties of the skin with aging are due to the reduced contractility and reduced migratory activity of fibroblasts. Healthy fibroblasts induce the 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 method for measuring cell-induced extracellular matrix contraction. In this assay, the ability of fibroblasts embedded in a collagen-based gel to reduce the gel diameter is evaluated.

[0272] By improving contractility, mechanical tension can be improved, which can be related to a "lifting" effect on the fibroblast scale.

[0273] Microcurrent system:

[0274] The microcurrent system was constructed by coupling gold electrodes to opposite sides (4 cm apart) of a 60 mm culture dish (to avoid cell death due to medium oxidation when current passes through). When a voltage is applied, an electric field is generated between the opposite positive and negative electrodes, and current passes through the culture. During the stimulation time (2 hours), each 60 mm culture dish was connected to a voltage source that allowed adjustment of the amount of current passing through each dish. For these experiments, a current of 40 μA / dish (corresponding to approximately 67 mV / mm) was used.

[0275] Preparation and expansion of cell cultures:

[0276] Human dermal fibroblast (HDF) cell culture and expansion: The cells were thawed in a T75 culture flask, and the growth medium was changed every 2 days for cell culture. After 7 days, the cells were expanded to obtain a total of 7×10 6 cells for use in the experiments.

[0277] Peptide treatment and 3D collagen gel:

[0278] Once the expansion was completed, the cultures were trypsinized and seeded at 3×10 5 cells / 60 mm culture dish until a total of 10 dishes were used for each repeat. These ten dishes corresponded to one experiment at a specific concentration (control / -MES vs +MES). Peptide treatment was carried out at 0.01 mg / ml.

[0279] After overnight (O / N) incubation to allow cell attachment, each culture dish was treated with 4 ml of a specific medium at the corresponding concentration for a total of 24 hours under two conditions (without MES and with MES). Peptide treatment on the culture dishes not stimulated with microcurrent started 2 hours earlier, and their entry into the 3D culture occurred simultaneously with the microcurrent stimulation of the other culture dishes. In the case of the culture dishes stimulated with microcurrent, the medium was replaced with 2.5 ml of fresh medium before stimulation, resulting in a total of 22 hours of peptide treatment only, and 2 hours of peptide treatment and electrical stimulation.

[0280] Each 3D culture was prepared by mixing a collagen solution with a culture medium corresponding to each condition (without peptide or with peptide). In this way, the complete peptide treatment duration 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 a neutralized type I rat tail collagen stock solution, and (ii) a cell suspension at a specific cell concentration. The plates were placed at 37 °C for 45 minutes. After incubation, the cultures were separated and detached from the walls of the wells to allow them to contract. The cell-free controls were also separated. 0.5 ml of each warm culture medium was added on top of each well. Images of the collagen gel diameter of each well were taken 24 hours after separation and analyzed using ImageJ.

[0281] - Image quantification

[0282] Hydrogel shrinkage was considered as the deformation experienced with the change in surface area:

[0283]

[0284] - The initial area was stable. At t = 0, all hydrogels presented the conformation defined by the culture platform. In this case, 24-well plates were used. Area at t = 0 gel → 1.86 cm 2 (Well area of 24-well plate)

[0285] - Quantification of the area at t = x; Ax. In this case, t = 24 h

[0286] The images were imported into ImageJ.

[0287] The scale was configured based on the diameter of the well (d = 1.54 cm 2 ) and the diameter was simulated and configured as 1.54 units in ImageJ.

[0288] Around the perimeter of the hydrogel, and the area was calculated based on the image.

[0289] - Calculate the average between replicates for each condition.

[0290] - Calculate the area deformation based on the formula for Δ area and convert the data to absolute %.

[0291] The results are shown in Table 8 below.

[0292] ​

[0293]

[0294] ​

[0295] 1 Statistical calculations were performed using unpaired t-tests: **p < 0.01; ***p < 0.001; ns: not significant

[0296] The results showed that PEP-1 promoted collagen contraction to a similar extent as MES.

[0297] ​

[0298] ​

[0299] EDA-Fn is an isoform of fibronectin that serves as a marker for the presence of myofibroblasts.

[0300] - Cell recovery and seeding

[0301] After following the experimental protocol described in Example 8, cell recovery was performed by extracting cells from the 3D culture and re-seeding them on glass coverslips. To recover the cells, the collagen hydrogel was digested with a collagenase solution under agitation at 37 °C. After digestion, a cycle of centrifugation and washing was performed to remove collagen fragments. Then, the cells were re-seeded on the coverslips according to the conditions of the 3D culture of Example 8. For future fluorescence analysis, the cells were seeded at a density of 3 × 10 5 fibroblasts / cm 2 on glass coverslips pre-coated with collagen, allowed to attach overnight and fixed with 4% PFA.

[0302] - EDA-Fn immunofluorescence

[0303] EDA-Fn immunofluorescence was performed using glass coverslips, a marker of 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 coverslips were permeabilized with a PBS solution of 0.5% Triton X-100 for 10 minutes at room temperature. Then, a blocking solution (PBS solution of 4% BSA) was added for 2 hours. After that, the cells were washed (3 times) in PBS and incubated with a primary antibody solution (Abcam IST-9, EDA-FN) in the dark for 2 hours, and the primary antibody solution was used at 1 / 500 in a PBS solution of 4% BSA. Then, the cells were washed (3 times) in PBS and incubated with a secondary antibody solution (Alexa Fluor 488) in the dark for 1 hour, and the secondary antibody solution was used at 1 / 500 in a PBS solution of 4% BSA. Then, the cells were washed again in PBS and DAPI staining was added to stain the cell nuclei. The glass coverslips were fixed on slides for analysis. Finally, the green fluorescence intensity under each condition was quantified in an Operetta (PerkinElmer) and normalized by the number of cell nuclei. The CTR condition (without electrical stimulation) was normalized to 100 and compared with the CTR MES and peptide treatment conditions using the following formula:

[0304]

[0305] Calculations were performed for 4 replicates.

[0306] ​

[0307]

[0308] ​

[0309] Statistical calculations were performed using an unpaired t-test: **p < 0.01, ****p < 0.0001.

[0310] The results showed that PEP-1 was able to increase the presence of myofibroblasts.

[0311] ​

[0312] Preparation of a light cream containing 2% by weight of PEP-1 peptide solution

[0313] In a suitable container, weigh the components of Phase A: Water [INCI: Aqua (Water)].

[0314] Next, weigh the components of Phase A1: Phenoxyethanol [INCI: Phenoxyethanol], Disodium EDTA [INCI: Disodium EDTA], Potassium Sorbate [INCI: Potassium Sorbate] and [INCI: Propylene Glycol] is added to Phase A and mixed until homogeneous.

[0315] Then Phase B1: Ultrez 21 Polymer [INCI: Acrylate / C10-30 Alkyl Acrylate Crosspolymer] is added to the previous mixture with agitation. Once dispersed, Phase B2: Xanthan Gum [INCI: Xanthan Gum] is added to the previous mixture and mixed until homogeneous.

[0316] Subsequently, Phase C: Schercemol R 1818 Ester [INCI: Isostearyl Isostearate] is added to the container and mixed until completely incorporated into the mixture. Finally, Phase D: PEP-1 Peptide Solution [INCI: Aqua, Caprylyl Glycol & Tetrapeptide-1] is added and mixed until homogeneous with moderate agitation.

[0317] The pH is adjusted to 6.0 - 6.5 using the following Phase E components: Sodium Hydroxide 20% w / w [INCI: Water (aqua); Sodium Hydroxide]

[0318]

[0319]

[0320] Table 10

[0321] Example 11

[0322] In vivo study of jaw firmness assessment in Caucasian volunteers .

[0323] This study lasted for 28 days. Forty-six (46) volunteers between the ages of 40 and 65 were included in this study and divided into two groups. The first group consisted of 36 volunteers (31 females and 5 males), to whom the composition described in Example 5 was applied to one half of the face, and a placebo cream having the same composition except for PEP-1 was applied to the other half of the face, twice daily for 28 days. The second group of 10 volunteers (9 females and 1 male) used a microcurrent device once a day and an activator gel without active ingredients. The volunteers using the microcurrent device were trained on how to apply the activator gel and how to use the device to standardize its application among the volunteers.

[0324] The subjects served as their own reference, comparing the results obtained at 28 days with the results obtained at the initial time. In addition, the results obtained by the volunteers using the microcurrent device were compared with the results obtained by the volunteers applying the placebo and the active cream.

[0325] The efficacy of the product was evaluated by the R0 parameter measured at the initial time and 28 days after application of the product (Courage&Khazaka). The R0 parameter is defined as the maximum amplitude after applying suction on the skin using negative pressure. The higher the skin's resistance to negative pressure, the firmer the skin. For this reason, a decrease in the R0 parameter means an increase in skin firmness. R0 measurements were obtained at two adjacent points in the mandible of the volunteers, and thus the average value at each time point of the test was obtained.

[0326] The firmness of the jaw was evaluated by the average change in the R0 parameter. The results are shown in Table 11 .

[0327]

[0328] Table 11 - Average change in R0 of the active cream and placebo cream 28 days after application of the product. *p < 0.05 and ls p < 0.1 were calculated using the paired Student's t - test.

[0329] The results shown in Table 11 indicate that 28 days after application of the composition of Example 5, the R0 parameter decreased significantly, and this decrease was greater and more significant than that observed for the placebo cream. Based on these results, the firmness 28 days after application of the product was improved and provided a change similar to that achieved by the microcurrent device.

[0330] Example 12

[0331] In vivo study to evaluate the eyebrow lifting effect in Caucasian volunteers .

[0332] This study lasted for 28 days. Forty - six (46) volunteers aged between 40 and 65 years were included in this study and divided into two groups. The first group consisted of 36 volunteers (31 females and 5 males). The composition described in Example 5 was applied to one half of the face, and a placebo (the same composition without peptides) was applied to the other half of the face, twice a day for 28 days. The second group of 10 volunteers (9 females and 1 male) used a microcurrent device and an activator gel without active ingredients once a day. The volunteers using the microcurrent device were trained on how to apply the activator gel and how to use the device to standardize its application among them.

[0333] The subjects served as their own reference, comparing the results obtained at 28 days with those obtained at the initial time. In addition, the results obtained by the volunteers using the microcurrent device were compared with those obtained by the volunteers applying the placebo and the active cream.

[0334] Facial images of volunteers were collected at the initial time and 28 days after applying the product. The efficacy of the product was evaluated by measuring the diagonal distance between the eyelashes and eyebrows, which was obtained by image analysis using software. The diagonal distance was calculated by drawing a horizontal line (eyelash line) between the point at the start of the eyelashes and the point at the end of the eyelashes. Then, an additional line was diagonally drawn from the middle area of the lips to the upper dental arch of the eyebrows, intersecting at the exact midpoint of the previously drawn eyelash line. The eyebrow lift measurement corresponded to the distance from the midpoint of the eyelash line to the end of the eyebrow arch.

[0335] As can be seen from the results shown in Table 12, the eyebrow lifting effect was evaluated by the average change in the diagonal distance 。

[0336]

[0337] Table 12 - Average change in diagonal distance of the active cream and placebo cream 28 days after applying the product and comparison with the microcurrent device.

[0338] The results shown in Table 12 indicate that 28 days after applying the composition of Example 10, the diagonal distance increased significantly compared to the placebo cream, and this was observed with the microcurrent device. In addition, the comparison between the active cream and the placebo cream showed a significant effect. According to the results, the eyebrow lift increased 28 days after applying the product, obtaining similar changes to those achieved with the microcurrent device.

[0339] Example 13

[0340] In vivo study to evaluate the anti-wrinkle efficacy of the peptides of the present invention in Caucasian volunteers 。

[0341] This study was conducted for 7 days. Forty-five (45) volunteers aged between 40 and 65 years were included in this study and divided into two groups. The first group included 36 volunteers (31 females and 5 males), and the composition described in Example 10 was applied to one half of the face, and the placebo cream was applied to the other half of the face, twice a day for 7 days. The second group of 9 volunteers (8 females and 1 male) used the microcurrent device and an activator gel without active ingredients once a day. The volunteers using the microcurrent device were trained on how to apply the activator gel and how to use the device to standardize its application among them.

[0342] The subjects served as their own reference, comparing the results obtained at 7 days with the results obtained at the initial time. In addition, the results obtained by the volunteers using the microcurrent device were compared with the results obtained by the volunteers applying the placebo and active creams.

[0343] Images of the crow's feet area of volunteers were collected at the initial time and 7 days after applying the product. The efficacy of the product was evaluated by the visibility coefficient obtained through image analysis using software. The visibility coefficient is defined as the occupancy of wrinkles multiplied by the contrast of wrinkles / skin and finally multiplied by 100.

[0344] The anti-wrinkle efficacy was evaluated by the average change in the visibility coefficient used to evaluate the visibility of wrinkles.

[0345] The results are shown in Table 13 .

[0346]

[0347] Table 13 - Average change in the visibility coefficient of the active cream and the placebo cream 7 days after applying the product and comparison with the placebo cream. *p < 0.05 and l.s.p < 0.1 were calculated using the paired Student's t-test.

[0348] The results shown in Table 13 indicate that there was a significant change in the visibility coefficient relative to the placebo cream 7 days after applying the composition of Example 10, and this was observed using the microcurrent device. In addition, the comparison between the active cream and the placebo cream showed a low significant effect. Based on this result, the wrinkle visibility decreased 7 days after applying the product, and the result of simulating the effect of the microcurrent device was observed.

[0349] Example 14

[0350] Preparation of a gel cream containing the peptide PEP-1.

[0351] In a suitable container, disperse the components of Phase A: water [INCI: Aqua (Water)], Zemea R [INCI: Propylene Glycol], [INCI: Phenoxyethanol], NA2 [INCI: Disodium EDTA] and potassium sorbate granules [Potassium Sorbate].

[0352] For Phase A1 components: Ultrez 21 polymer [INCI: Acrylates / Acrylamide copolymer] is 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.

[0353] In a separate container, weigh the components of Phase B: Schercemol TM 1818 ester [INCI: Isostearyl Isostearate].

[0354] An emulsion is prepared by slowly adding Phase B to Phase A under the condition of rapid stirring with a turbine.

[0355] Phase C: Peptide PEP-1 solution [INCI: Water (aqua); Caprylyl Glycol; Peptide PEP-1 was added to the previous mixture.

[0356] Adjust the pH to 6.0 - 6.5 using the following Phase D components: Sodium Hydroxide 20% w / w [INCI: Water (aqua); Sodium Hydroxide])

[0357]

[0358] Table 14

[0359] Gel-creams containing other peptides of the present invention can be prepared by replacing other peptides disclosed herein with PEP-1.

[0360] Example 15

[0361] Preparation of a lotion containing 2% peptide PEP-1

[0362] In a suitable container, dissolve the components of Phase A1: Water [INCI: Water (aqua)], Zemea TM [INCI: Propylene Glycol], Glycerin [INCI: Glycerin], Potassium Sorbate [INCI: Potassium Sorbate] and NA2 [INCI: Disodium EDTA].

[0363] Add the components of Phase A2: Ultrez 30 Polymer [INCI: Carbomer] to the previous mixture. Once dispersed, introduce Phase A3: Xanthan Gum [INCI: Xanthan Gum]. Then heat the mixture at 70°C to 75°C.

[0364] In a separate container, mix the components of Phase B: Lumialis Officinalis Seed Oil [INCI: Limnanthes Alba (Meadowfoam) Seed Oil], Kodasil 600IDD Gel [INCI: Isododecane; Vinyl Dimethicone / Methicone Silsesquioxane Crosspolymer; Dimethicone; Lauryl Dimethicone], Astro-sil 2C 350 [INCI: Dimethicone], Schercemol TM CATC Ester [INCI: Capryloyl Adipic Acid / Trimethylolpropane Copolymer; Trimethylolpropane], Schercemol R DIS Ester [INCI: Diisopropyl Sebacate], Tocopheryl Acetate [INCI: Tocopheryl Acetate] and Phenoxetol R [INCI: Phenoxyethanol], and heat the resulting mixture at 70°C to 75°C.

[0365] An emulsion is prepared by slowly adding Phase B to Phase A under conditions of rapid agitation with a turbine.

[0366] Once the mixture has cooled to 40 °C, the components of Phase C: Novemer TM EC-2 polymer [INCI: Water (aqua); Sodium acrylate / ceteth-25 methacrylate crosspolymer; Hydrogenated polydecene, lauryl glucoside], SA-SB-300 (7%) [INCI: Silica; Polydimethylsiloxane], fragrance [INCI: Fragrance (parfum)] and peptide PEP-1 solution [INCI: Water (aqua); Caprylyl glycol; Peptide PEP-1] are added to the previous mixture.

[0367] The pH was adjusted to 6.0 - 6.5 using the following Phase D ingredients: sodium hydroxide 20% w / w [INCI: Water (aqua); Sodium Hydroxide])

[0368]

[0369]

[0370] Table 15

[0371] Lotions containing other peptides of the present invention can be prepared by replacing PEP-1 with other peptides disclosed herein.

[0372] Example 16

[0373] Preparation of a fluid emulsion containing 2% peptide PEP-1

[0374] In a suitable container, the components of Phase A1: water [INCI: Water (aqua)], Zemea TM [INCI: Propylene glycol], glycerin [INCI: Glycerin], Genencare TM OSMS BA [INCI: Betaine], NA2 [INCI: Disodium EDTA], potassium sorbate [INCI: Potassium sorbate] are dissolved.

[0375] Phase A2: ultrez 10 polymer [INCI: Carbomer] is added to the previous mixture. Once dispersed, Phase A3 is added: Fax CPE-K [INCI: Potassium cetyl phosphate]. The resulting mixture is heated at 70 °C - 75 °C.

[0376] In another container, the components of Phase B: HD [INCI: Isododecane], Lincol BAS [INCI: C12-15 Alkyl Benzoate], Gandak C [INCI: Cetyl Alcohol], Sorbitan T 20P [INCI: Polysorbate 20], 2-Phenoxyethanol [INCI: Phenoxyethanol], Vegetable Stearic Acid 50 / 50 [INCI: Stearic Acid; Palmitic Acid] are mixed and heated at 70°C - 75°C. Phase B is slowly introduced onto Phase A under the condition of intensive agitation with a turbine.

[0377] The mixture is cooled to 40°C and Phase C is added: BRB CM 56-S [INCI: Cyclomethicone], Peptide PEP-1 Solution [INCI: Aqua (Water); Caprylyl Glycol; Peptide PEP-1], Fragrance [INCI: Parfum (Fragrance)]. The pH is adjusted to 6.0 - 6.5 using the following components of Phase D: Sodium Hydroxide 20% w / w [INCI: Aqua (Water); Sodium Hydroxide].

[0378]

[0379]

[0380] Table 16

[0381] Fluid emulsions containing other peptides of the present invention can be prepared by replacing PEP-1 with other peptides disclosed herein.

[0382] Example 17

[0383] Effect of a comparative peptide not covered by the present invention on collagen contraction.

[0384] The ability of different peptides (not according to the present invention) to stimulate collagen contraction was carried out using the same procedure as in Example 8 Ability 。

[0385] Mean value Base control (without MES) 100 Positive control (with MES) 159.7 <![CDATA[Ac-Arg-Arg-D-Gln-Met-Glu-Glu-NH2(0.01mg / ml)]]> 82.5 <![CDATA[Ac-Asp-Val-Tyr-Lys-NH2(0.01mg / ml)]]> 91.6 <![CDATA[H-Ala-Leu-Lys-Pro-Asn-Thr-NH2(0.01mg / ml)]]> 101.4

[0386] Table 17

[0387] The results are shown in Table 17. None of the peptides were able to promote collagen contraction.

[0388] Example 18

[0389] In vivo study to evaluate the eyebrow lifting effect of the comparative peptide Ac-Asp-Val-Tyr-Lys-NH2 。

[0390] A 28-day study was conducted to determine the lifting effect of Ac-Asp-Val-Tyr-Lys-NH2 (not according to the present invention). It included 42 white female volunteers aged between 35 and 58 years, all having skin wrinkles in the crow's feet area. The subjects applied a cream containing Ac-Asp-Val-Tyr-Lys-NH2 on one side of the face (left or right), and a placebo cream having the same composition except for the peptide. The two creams were applied for 28 days, twice a day (in the morning and evening). The subjects served as their own reference, and the results obtained after 28 days were compared with those obtained at the initial time and during the treatment. The eyebrow lifting effect was determined as disclosed in Example 12.

[0391]

[0392] Table 18

[0393] The results are shown in Table 18 and indicate that the peptide Ac-Asp-Val-Tyr-Lys-NH2 does not have a lifting effect.

[0394] The various aspects and embodiments of the present invention are defined by the following numbered clauses:

[0395] 1. A compound of formula (I):

[0396] R1-W m -X n -AA1-AA2-AA3-AA4-Y o -Z p -R2 (I),

[0397] its stereoisomers and / or cosmetically acceptable salts, wherein:

[0398] AA1 is Leu, Ile or Val;

[0399] AA2 is Pro, Ala or Gly;

[0400] AA3 is Val, Ile or Leu;

[0401] AA4 is Thr, Val or a non-amino acid;

[0402] W, X, Y and Z are each independently any amino acid;

[0403] m, n, p and q are each independently 0 or 1;

[0404] m + n + p + q is less than or equal to 2;

[0405] R1 is selected from the group consisting of: H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, an alicyclic group, a heterocyclic group, a heteroarylalkyl group, an aryl group, an aralkyl group, and R5-CO-, where R5 is selected from the group consisting of: H, an acyclic aliphatic group, an alicyclic group, an aryl group, an aralkyl group, a heterocyclic group, and a heteroarylalkyl group;

[0406] R2 is selected from the group consisting of: -NR3R4, -OR3, -SR3, where R3 and

[0407] R4 are independently selected from the group consisting of: H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, an alicyclic group, a heterocyclic group, a heteroarylalkyl group, an aryl group, and an aralkyl group; and

[0408] R1 and R2 are not amino acids.

[0409] 2. The compound according to clause 1, wherein AA1 is Leu or Val, and preferably,

[0410] AA1 is Leu.

[0411] 3. The compound according to clause 1 or claim 2, wherein AA2 is Pro.

[0412] 4. The compound according to any one of the foregoing clauses, wherein AA3 is Val or Leu, and

[0413] preferably, AA3 is Val.

[0414] 5. The compound according to any one of the foregoing clauses, wherein AA4 is Thr or Val.

[0415] 6. The compound according to any one of clauses 1 to 4, wherein AA4 is Thr or a non-amino acid.

[0416] 7. The compound according to clause 6, wherein AA4 is a non-amino acid and AA1 is Leu and / or AA2 is Pro and / or AA3 is Val.

[0417] 8. The compound according to any one of the foregoing clauses, wherein m + n + p + q is 0 or 1.

[0418] 9. The compound according to any one of the foregoing clauses, wherein, when present, each of X, W, X, Y, and Z is independently selected from the group consisting of Ala, Val, and Ile.

[0419] 10. The compound according to clause 9, wherein AA3 is Val.

[0420] 11. The compound according to clause 1, wherein the compound is:

[0421] R1 - Leu - Pro - Val - Thr - R2;

[0422] R1 - Leu - Ala - Val - Thr - R2;

[0423] R1 - Leu - Pro - Ile - Thr - R2;

[0424] R1 - Val - Pro - Val - Thr - R2;

[0425] R1 - Leu - Gly - Val - Thr - R2;

[0426] R1 - Leu - Pro - Leu - Thr - R2;

[0427] R1 - Ala - Leu - Pro - Val - Thr - R2;

[0428] R1 - Leu - Pro - Val - R2; or

[0429] R1 - Ile - Pro - Ile - Thr - R2.

[0430] 12. A compound according to any one of the preceding clauses, wherein R1 is optionally selected from the group consisting of: H and R5 - CO -, where R5 is selected from the group consisting of: C1 - C 18 alkyl,

[0431] C2 - C 24 alkenyl, C3 - C 24 cycloalkyl; and R2 is - NR3R4 or - OR3, where R3 and R4 are independently selected from the group consisting of: H and C1 - C 16 alkyl.

[0432] 13. A compound according to clause 1, wherein the compound is:

[0433] H - Leu - Pro - Val - Thr - OH;

[0434] H - Leu - Pro - Val - Thr - NH2;

[0435] Palm - Leu - Pro - Val - Thr - OH;

[0436] Ac - Leu - Pro - Val - Thr - OH;

[0437] Ac - Leu - Pro - Val - Thr - NH2;

[0438] H-Leu-Ala-Val-Thr-OH;

[0439] H-Leu-Pro-Ile-Thr-OH;

[0440] H-Val-Pro-Val-Thr-OH;

[0441] H-Leu-Gly-Val-Thr-OH;

[0442] H-Leu-Pro-Leu-Thr-OH;

[0443] H-Ala-Leu-Pro-Val-Thr-OH;

[0444] H-Leu-Pro-Val-OH; or

[0445] H-Ile-Pro-Ile-Thr-OH.

[0446] 14. A compound according to any one of the preceding clauses, wherein the compound is not H-Lys-

[0447] Leu-Pro-Val-Thr-OH or H-Leu-Pro-Val-Thr-Leu-Arg-OH.

[0448] 15. A compound according to any one of the preceding clauses, wherein the compound is not H-Leu-

[0449] Pro-Ile-Thr-OH, H-Leu-Pro-Leu-Thr-OH or H-Leu-Pro-Val-Thr-Gly-

[0450] OH.

[0451] 16. A composition comprising a cosmetically effective amount of a compound of formula (I) according to any one of clauses 1 to 15, its stereoisomers and / or cosmetically acceptable salts, and at least one cosmetically acceptable excipient or adjuvant.

[0452] 17. Use of a compound according to any one of clauses 1 to 15, its stereoisomers and / or cosmetically acceptable salts for the cosmetic, non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes.

[0453] 18. Use according to clause 17, wherein the cosmetic, non-therapeutic treatment and / or care is: treating and / or preventing skin aging; reducing and / or preventing skin wrinkles; improving or maintaining skin firmness; treating and / or preventing the appearance of skin sagging; and / or lifting the skin.

[0454] 19. A method for the cosmetic, non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes of a subject, said method comprising administering a cosmetically effective amount of a compound according to any one of clauses 1 to 15.

Claims

1. A compound of formula (I): R1-W m -X n -AA1-AA2-AA3-AA4-Y o -Z p -R2(I), Its stereoisomers and / or pharmaceutically acceptable salts, wherein: AA1 is Leu, Ile or Val; AA2 is Pro, Ala or Gly; AA3 is Val, Ile or Leu; AA4 is Thr, Val or a non - 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, a cycloaliphatic group, a heterocyclic group, a heteroarylalkyl group, an aryl group, an aralkyl group and R5 - CO -, where R5 is selected from the group consisting of: H, an acyclic aliphatic group, a cycloaliphatic group, an aryl group, an aralkyl group, a heterocyclic group and a heteroarylalkyl group; 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, a cycloaliphatic group, a heterocyclic group, a heteroarylalkyl group, an aryl group and an aralkyl group; and R1 and R2 are not amino acids; Provided that 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. The compound according to claim 1, wherein AA1 is Leu or Val, and preferably, AA1 is Leu.

3. The compound according to claim 1 or claim 2, wherein AA2 is Pro.

4. The compound according to any one of the preceding claims, wherein AA3 is Val or Leu, and preferably, AA3 is Val.

5. The compound according to any one of the preceding claims, wherein AA4 is Thr or Val.

6. The compound according to any one of claims 1 to 4, wherein AA4 is Thr or a non - amino acid.

7. The compound according to claim 6, wherein AA4 is a non - amino acid and AA1 is Leu and / or AA2 is Pro and / or AA3 is Val.

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

9. The compound according to claim 1, wherein the compound is: R1 - Leu - Pro - Val - Thr - R2; R1 - Leu - Ala - Val - Thr - R2; R1 - Val - Pro - Val - Thr - R2; R1 - Leu - Gly - Val - Thr - R2; R1 - Ala - Leu - Pro - Val - Thr - R2; R1 - Leu - Pro - Val - R2; or R1 - Ile - Pro - Ile - Thr - R2.

10. A compound according to any one of the preceding claims, wherein R1 is selected from the group consisting of H and R5-CO-, where R5 is selected from the group consisting of C1-C 18 alkyl, C2-C 24 alkenyl, C3-C 24 cycloalkyl; and R2 is -NR3R4 or -OR3, where R3 and R4 are independently selected from the group consisting of H and C1-C 16 alkyl.

11. The compound according to claim 1, wherein the 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-Val-Pro-Val-Thr-OH; H-Leu-Gly-Val-Thr-OH; H-Ala-Leu-Pro-Val-Thr-OH; H-Leu-Pro-Val-OH; or H-Ile-Pro-Ile-Thr-OH.

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

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

14. Use according to claim 13, wherein the cosmetic, non-therapeutic treatment and / or care is: treating and / or preventing skin aging; reducing and / or preventing skin wrinkles; improving or maintaining skin firmness; treating and / or preventing the appearance of skin sagging; and / or lifting the skin.

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

Images