FIELD OF THE INVENTION

The invention relates to compounds useful forthe treatment and/or care of the skin, hair, nails and/or mucous membranes. In particular, the compounds are useful for the treatment and/or prevention of skin aging and, in particular, for the treatment and/or prevention of skin wrinkles, the improvement or maintenance of skin firmness, the treatment and/or prevention of a sagging appearance of the skin, and/or the lifting of the skin. The invention extends to compositions comprising the compounds and methods of treatment using the compounds.

BACKGROUND OF THE INVENTION

The effects of aging play a major role in skin appearance. The most striking signs of facial aging include wrinkles and a sagging appearance of the face.

One of the most popular methods for reducing facial sagging is the face-lift. The facelift, also known as rhytidectomy, is a cosmetic surgical procedure for reducing the sagging or folds of skin on the cheeks and jawline as well as making other changes in the shape of the face that take place with age. During a face-lift, a flap of skin on each side of the face is pulled back, and tissues below the skin are surgically altered to return the contour of the face to a more youthful shape. Nevertheless, face-lifts can be associated with different complications and risks. Like any other type of surgery, a facelift poses a risk of bleeding, infection and an adverse reaction to anesthesia. Some other risks include hematoma, scarring, nerve injury, hair loss and skin loss. Moreover, the results of face-lifts are not permanent. With age, the facial skin may begin to droop again. In general, a face-lift can be expected to last 10 years.

Unsurprisingly, there is a growing interest in alternative and non-invasive methods to reduce face sagging and combat the effects of aging on skin. Skin microcurrent electrical stimulation (MES) is a facial aesthetic treatment which is growing in interest in the last years. MES is distinguished by the use of extremely small electrical currents (i.e. millionths of an amp, e.g. 300-500 pA) which are hardly perceptible, but mimic the body's own bio-electric currents. MES is used as cosmetic, non-therapeutic beauty treatment for improving skin rejuvenation. It is known as an effective, non-invasive, and inexpensive technique for fighting against skin aging appearance [Goldbert, A. et al. “Skin Rejuvenation with Non-lnvasive 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],

The uppermost layer of human skin is the epidermis, which is a stratified epithelium and is predominantly built by different layers of keratinocytes. Underlying the epidermis is the dermis which is composed of fibroblasts, blood and lymphatic vessels, nerve fibers and extracellular matrix (ECM). The extracellular matrix provides the necessary mechanical support for the skin. Collagen is the main structural component of the extracellular matrix. On a cellular level MES is known to stimulate the production of collagen type 1 in fibroblasts as well as promote fibroblast-induced contraction of collagen 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],

Muscleblind-like protein 1 (MBNL1) is a RNA-binding protein which is implicated in the differentiation and maintenance of the splicing pattern required for a healthy muscle function. It has been demonstrated that an increase of MBNL1 protein in fibroblast cells activates their trans-differentiation process to myofibroblast, a cell-type able to release a higher amount of extracellular matrix proteins, like collagen, elastin and fibronectin. Electrical stimulation has been demonstrated to induce myofibroblast appearance and function [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 are effective at upregulating the expression on MBNL1 in skin or muscle cells have been demonstrated as being useful in maintaining or improving skin firmness, preventing a sagging appearance of the skin and/or reducing facial asymmetry (WO 2020/161683 A1).

Although effective as a cosmetic treatment, using MES attracts some disadvantages. For instance, the intensity of electrical currents may depend on individual skin thickness Skin thickness is subjected to changes by age or external factors, and thus there is high intra- and inter-individual variability. In addition, skin health status can influence the intensity needed. For example, old skin or skin which which is deteriorated is less conductive (i.e. shows less transmission to microcurents) than healthy skin. In some cases, poor electrical contact between the electrode and the surface being treated results in the user feeling discomfort and pain, and in extreme cases can result in skin irritation. Some MES devices use electrodes and adhesive gels to improve the conductivity, but this is expensive and inconvenient on, e.g., the face because there is no allowance for movement of the electrodes once they have been positioned. Further, depending on the device, it can be difficult to precisely follow the outline of the surfaces of the body being treated and this is a problem as the stimuli should be able to address to a precise area. For example, some devices require the use of a mirror in order to be able to locate the wands of the device on the appropriate parts of the face and squeeze or lengthen the skin. Finally, some potential users have a negative preconception of MES treatment, i.e. prejudices against using electricity on their face, for example, as a daily beauty treatment.

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

SUMMARY OF THE INVENTION

In a first aspect, the invention provides a compound represented by formula (I): Ri-W _m -Xn-AAi-AA2-AA3-AA ₄ -Yo-Zp-R ₂ (I), a stereoisomer and/or cosmetically acceptable salt thereof, wherein: AAi is Leu, He or Vai;

AA ₂ is Pro Ala or Gly;

AA3 is Vai, He or Leu;

AA ₄ is Thr, Vai or no amino acid;

W, X, Y and Z are each independently any amino acid; m, n, p and q are each independently 0 or 1 ; m+n+p+q is less than or equal to 2;

R1 is selected from the group consisting of H, a polymer derived from polyethylene glycol, a non-cyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, aralkyl and R ₅ - CO-, wherein Rs is selected from the group consisting of H, a non-cyclic aliphatic group, alicyclyl, aryl, aralkyl, heterocyclyl and heteroarylalkyl;

R2 is selected from the group consisting of -NRsR4, -OR3, -SR3, wherein R3 and R4 are independently selected from a group consisting of H, a polymer derived from polyethylene glycol, a non-cyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl and aralkyl; and

R1 and R2 are not amino acids.

It has been found that compounds of the invention are effective in reducing the appearance of wrinkles in the skin, improving the firmness of skin, reducing a sagging appearance of the skin and in lifting the skin. By lifting the skin is meant tightening the skin. Lifting/tightening of skin provides skin with the appearance that it has moved from a lower to an upper position such that any downward gravitational movement of the skin, which increases by aging, is counteracted. Further, it has been found that compounds of the invention can act as an effective alternative to a commercially available microcurrent facial toning device for treating and/or preventing symptoms of skin aging. In particular, it has been found that compounds of the invention are effective in reducing the appearance of wrinkles in the skin, improving the firmness of skin, reducing a sagging appearance of the skin and in lifting the skin to a similar extent as a commercially available microcurrent facial toning device.

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

In another aspect, the invention provides the use of a compound of formula (I), its stereoisomers and/or its cosmetically acceptable salts, or a composition comprising a compound of formula (I), its stereoisomers and/or its cosmetically acceptable salts, for the treatment and/or care of the skin, hair, nails and/or mucous membranes. In particular, the invention provides the use 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, for the cosmetic, non-therapeutic treatment and/or care of the skin, hair, nails and/or mucous membranes. The cosmetic, non-therapeutic treatment and/or care can be: the prevention or the treatment of the symptoms of skin aging; the treatment and/or prevention of skin wrinkles; the improvement or maintenance of skin firmness; the treatment and/or prevention of a sagging appearance of the skin; and/or the lifting of the skin.

In another aspect, the invention provides a method of treatment and/or care of the skin, hair, nails and/or mucous membranes in a subject comprising administering an effective amount of a compound of formula (I), its stereoisomers and/or its cosmetically or pharmaceutically acceptable salts, or a composition comprising same, to the subject. In particular, the invention provides a method of cosmetic, non-therapeutic treatment and/or care of the skin, hair, nails and/or mucous membranes in a subject comprising administering a cosmetically effective amount of a compound of formula (I), its stereoisomers and/or its cosmetically acceptable salts, or a cosmetic composition comprising same, to the subject. Typically, the compound will be administered topically. The cosmetic, non-therapeutic treatment and/or care can be: the prevention or the treatment of the symptoms of skin aging; the treatment and/or prevention of skin wrinkles; the improvement or maintenance of skin firmness; the treatment and/or prevention of a sagging appearance of the skin; and/or the lifting of the skin.

DETAILED DESCRIPTION OF THE INVENTION

Definitions

In the context of this invention “skin” is understood to be the layers which comprise it, from the uppermost layer of the epidermis or stratum corneum to the lowermost layer or hypodermis, both inclusive. These layers are composed of different types of cells such as keratinocytes, fibroblasts, melanocytes, mast cells, neurones and/or adipocytes among others. The term “skin” also comprises the scalp. The term “skin” includes the skin of mammals and includes human skin. Likewise, the terms “hair, nails and mucous membranes” include the hair, nails and mucous membranes of mammals, for example humans.

The term “treatment”, as used herein and when it is not accompanied by the qualifications “cosmetic, non-therapeutic” refers to therapeutic methods including methods directed to the administration of a compound according to the invention to alleviate or eliminate a disease or disorder, or to reduce or eliminate one or more symptoms associated with said disease or disorder. The term “treatment”, when it is not accompanied by the qualifications “cosmetic, non-therapeutic”, also covers methods of therapy directed to alleviating or eliminating physiological consequences of the disease or disorder.

When the terms “treatment” and “care” are accompanied by the qualifications “cosmetic, non-therapeutic”, it means that the treatment or care has the aim of improving or maintaining the aesthetic appearance of the skin, hair, nails and/or mucous membranes. In particular, the treatment can have the aim of improving cosmetic properties of the skin, hair, nails and/or mucous membranes such as, for example and not restricted to, the level of hydration, elasticity, firmness, shine, tone or texture, which properties affect the aesthetic appearance of the skin, hair, nails and/or mucous membranes. The term “care” in the context of this specification refers to the maintenance of properties of the skin, hair, nails and/or mucous membranes. Said properties are subject to being improved or maintained by cosmetic treatment and/or care of the skin, hair, nails and/or mucous membranes both in healthy subjects as well as in those which present diseases and/or disorders of the skin, hair, nails and/or mucous membranes.

The term “prevention”, as used in this invention, refers to the ability of a compound of the invention to prevent, delay or hinder the appearance or development of a disease or disorder, or to prevent, delay or hinder the change in a cosmetic property of the skin, mucous membranes and/or hair. The term “prevention”, as used in this invention, is interchangeable with the term “inhibition”, i.e. it refers to the ability of a compound of the invention to inhibit the appearance or development of a disease or disorder, or to inhibit the change in a cosmetic property of the skin, hair, nails and/or mucous membranes.

In the context of this invention, the term “aging” refers to the changes experienced by the skin as the result of intrinsic aging process (i.e. chronoaging) or extrinsic skin aging process induced by environmental factors (i.e. through exposure to the sun (photoaging) or to environmental agents such as tobacco smoke, extreme climatic conditions of cold or wind, chemical contaminants or pollutants). In the context of the invention, aging includes all the external visible and/or perceptible changes through touch, such as and not restricted to, the development of discontinuities on the skin such as wrinkles, fine lines, expression lines, stretch marks, furrows, irregularities or roughness, increase in the size of pores, loss of hydration, loss of elasticity, loss of firmness, loss of smoothness, loss of the capacity to recover from deformation, loss of resilience, sagging of the skin such as sagging cheeks, the appearance of bags under the eyes or the appearance of a double chin, among others, changes to the color of the skin such as marks, reddening, bags or the appearance of hyperpigmented areas such as age spots or freckles among others, anomalous differentiation, hyperkeratinization, elastosis, keratosis, hair loss, orange-peel skin, loss of collagen structure and other histological changes of the stratum corneum, of the dermis, epidermis, vascular system (for example the appearance of spider veins or telangiectasias) or of those tissues close to the skin, among others. The term “photoaging” groups together the set of processes due to the prolonged exposure of the skin to ultraviolet radiation which result in the premature aging of the skin, and it presents the same physical characteristics as aging, such as and not restricted to, flaccidity, sagging, changes to the color or irregularities in the pigmentation, abnormal and/or excessive keratinization. The sum of various environmental factors such as exposure to tobacco smoke, exposure to pollution, and climatic conditions such as cold and/or wind also contribute to the aging of the skin.

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

Table 1 - Structures of the amino acid residues, their nomenclature in three-letter code and nomenclature for the amino acids in one letter code

Name Residue Symbol

Leucyl Isoleucyl -Leu- -lle-

L I

Alanyl Valyl

Threonyl

-Thr-

T

As used herein, the term “non-cyclic aliphatic group” includes linear (i.e. straight and unbranched) or branched, saturated or unsaturated hydrocarbyl groups such as alkyl, alkenyl and alkynyl. The non-cyclic aliphatic group may be substituted (mono- or poly- ) or unsubstituted.

As used herein, the term “alkyl” includes both saturated linear and branched alkyl groups, which may be substituted (mono- or poly-) or unsubstituted. The alkyl group is bound to the rest 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, yet more preferably 1 , 2, 3, 4, 5 or 6 carbon atoms. The term “alkyl” includes, for example, methyl, ethyl, isopropyl, isobutyl, te/Y-butyl, 2-methylbutyl, heptyl, 5-methylhexyl, 2-ethylhexyl, octyl, decyl, dodecyl, lauryl, hexadecyl, octadecyl and amyl.

As used herein, the term “alkenyl” refers to a group containing one or more double carbon-carbon bonds and which may be linear or branched and substituted (mono- or poly-) or unsubstituted. Preferably it has 1 , 2 or 3 double carbon-carbon bonds. If more than one double carbon-carbon bond is present, the double bonds may be conjugated or not 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, yet more preferably 2, 3, 4, 5 or 6 carbon atoms. The alkenyl group is bound to the rest of the molecule by a single bond. The term “alkenyl” includes, for example, vinyl (-CH2=CH ₂ ), allyl (-CH ₂ - CH=CH ₂ ), prenyl, oleyl, linoleyl groups and similar.

The term “alkynyl” refers to a group containing one or more triple carbon-carbon bonds and which may be linear or branched, and substituted (mono- or poly-) or unsubstituted. Preferably the alkynyl group has 1 , 2 or 3 triple carbon-carbon bonds. The triple bonds may be conjugated or not 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, yet more preferably 2, 3, 4, 5 or 6 carbon atoms. The alkynyl group is bound to the rest of the molecule by a single bond. The term “alkynyl” includes, for example and not restricted to, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, pentynyl, such as 1 -pentynyl, and similar. The alkynyl group can also contain one or more double carboncarbon bonds, and alkynyl groups include, for example and not restricted to, but-1-en-3- ynyl and pent-4-en-1-ynyl groups, and similar.

The term “alicyclyl” is used herein to cover, for example and not restricted to, aliphatic cyclic (alicyclic) groups such as cycloalkyl or cycloalkenyl or cycloalkynyl groups. The term "alicyclyl" refers to a monoradical that contains one or more rings of carbon atoms, the rings may be saturated (e.g., cyclohexyl) or unsaturated (e.g., cyclohexenyl) provided that they are not aromatic. More specifically alicylic groups contain three or more, from 3 to 24, from 3 to 12, or from 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 linked by a single bond or a linking group such as a methylene or other alkylene group. The alicyclic group may be substituted (mono- or poly-) or unsubstituted. In one embodiment, the alicyclyl group is a 6 to 12 membered ring system which consists of carbon atoms and optionally contains one or two double bonds.

The term “cycloalkyl” refers to a saturated mono- or polycyclic alkyl group which may be substituted (mono- or poly-) or unsubstituted. The cycloalkyl group has from 3 to 24, preferably from 3 to 16, more preferably from 3 to 14, even more preferably from 3 to 12, yet even more preferably 3, 4, 5 or 6 carbon atoms. The cycloalkyl group is bound to the rest of the molecule by a single bond. Cycloalkyl groups include, for example and not restricted to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, methyl cyclohexyl, dimethyl cyclohexyl, octahydroindene, decahydronaphthalene, dodecahydrophenalene and similar.

The term “cycloalkenyl” refers to a non-aromatic mono- or polycyclic alkenyl group which may be substituted (mono- or poly-) or unsubstituted. The cycloalkenyl group has from 5 to 24, preferably from 5 to 16, more preferably from 5 to 14, even more preferably from 5 to 12, yet more preferably 5 or 6 carbon atoms. The cycloalkenyl group is bound to the rest of the molecule by a single bond. Preferably the cycloalkenyl group contains 1 , 2 or 3 double carbon-carbon bonds. If more than one double carbon-carbon bond is present, the double bonds may be conjugated or not conjugated. Cycloalkenyl groups include, for example and not restricted to, the cyclopent-1 -en-1-yl group and similar. The term “cycloalkynyl” refers to a non-aromatic mono- or polycyclic alkynyl group which may be substituted (mono- or poly-) or unsubstituted. The cycloalkynyl group has from 8 to 24, preferably from 8 to 16, more preferably from 8 to 14, even more preferably from 8 to 12, yet even more preferably 8 or 9 carbon atoms and is bound to the rest of the molecule by a single bond. Preferably the cycloalkynyl group contains 1 , 2 or 3 triple carbon-carbon bonds, conjugated or not conjugated. Cycloalkynyl groups include, for example and not restricted to, the cyclooct-2-yn-1-yl group and similar. Cycloalkynyl groups can also contain one or more double carbon-carbon bonds, including, for example and not restricted to, the cyclooct-4-en-2-ynyl group and similar.

As used herein, the term “heterocyclyl” or “heterocyclic” refers to a hydrocarbon ring system of 3 to 10 members, wherein one or more of the atoms in the ring or rings is a heteroatom (i.e. not a carbon atom). Thus “heterocyclyl” or “heterocyclic” refers a cyclic group in which the ring atoms consist of carbon and one or more heteroatoms. To satisfy valence, the heteroatom may be bonded to H or substituent groups. Preferably from 1 , 2 or 3 of the ring carbon atoms are heteroatoms. Each heteroatom can be independently selected from the group consisting of O, N, S, P and B, or the group consisting of O, N, and S. The heterocyclyl group may be substituted (mono- or poly-) or unsubstituted. The heterocyclyl group may be a monocyclic, bicyclic, or tricyclic ring system and the rings may be, for example, fused or linked by a single bond or a linking group such as a methylene or other alkylene group. Nitrogen, carbon or sulfur atoms present in the heterocyclyl radical may be optionally oxidized and the nitrogen atom may be optionally quaternized. The heterocyclyl radical may be unsaturated or partially or fully saturated. The heterocyclyl radical may be aliphatic or aromatic. In one embodiment, the heterocyclyl is aliphatic (also known as heteroalicyclyl) and is a 3 to 10 membered ring system where the atoms of the ring or rings consist of carbon atoms and from 1 to 4, or 1 , 2 or 3 heteroatoms. In one embodiment, the heterocyclyl group is a 6 to 10 membered ring system where the atoms of the ring or rings consist of carbon atoms and from 1 to 4 heteroatoms and where the ring system optionally contains one or two double bonds. In one embodiment, the heterocyclyl is aromatic (also known as heteroaryl) and is a 6 to 10 membered ring system where the atoms of the ring or rings consist of carbon atoms and from 1 to 4, or 1 , 2 or 3 heteroatoms. The greatest preference is for the term heterocyclyl to refer to a ring of 5 or 6 members. Examples of saturated heteroalicyclyl groups are dioxane, piperidine, piperazine, pyrrolidine, morpholine and thiomorpholine. Examples of aromatic heterocyclyl groups are pyridine, pyrrol, furan, thiophene, benzofuran, imidazoline, quinolein, quinoline, pyridazine and naphthyridine. The term “aryl group” refers to an aromatic group which has from 6 to 30, preferably from 6 to 18, more preferably between 6 and 10, yet even more preferably 6 or 10 carbon atoms. The aryl group can comprise 1 , 2, 3 or 4 aromatic rings, which may be linked by a carbon-carbon bond or fused together and includes, for example and not restricted to, phenyl, naphthyl, diphenyl, indenyl, phenanthryl or antranyl among others. The aryl group may be substituted (mono- or poly-) or unsubstituted.

The term “aralkyl group” refers to an alkyl group substituted by an aromatic group, with from 7 to 24 carbon atoms and including, for example and not restricted to, -(CH2)i-6-phenyl, -(CH2)i-e-(1 -naphthyl), -(CH2)i-e-(2-naphthyl), -(CH2)i-e-CH(phenyl)2 and similar.

The term “heteroarylalkyl” refers to an alkyl group substituted by a heteroaryl (also known as 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 not restricted to, -(CH ₂ )i-6-imidazolyl, -(CH ₂ )i-6-triazolyl, -(CH ₂ )i-6-thienyl, -(CH ₂ )i-6-furyl, -(CH ₂ )i-6-pyrr olidinyl and similar.

As is understood in this technical field, there may be a certain degree of substitution of the aforementioned groups. In particular, there can be substitution in any of the groups identified above where it is explicitly stated. The substituted groups (radicals) referred to above are groups (or radicals) which are substituted in one or more positions available by one or more substituents. Preferably substitution is in the 1 , 2 or 3 positions, more preferably in the 1 or 2 positions, yet even more preferably in the 1 position. Suitable substituents include, for example and not restricted to: Ci-C ₄ alkyl; hydroxyl; Ci-C ₄ alkoxyl; amino; amino-Ci-C ₄ alkyl; Ci-C ₄ carbonyloxyl; Ci-C ₄ oxycarbonyl; halogen such as fluoride, chlorine, bromine and iodine; cyano; nitro; azide; Ci-C ₄ alkylsulfonyl; thiol; Ci-C ₄ alkylthio; aryloxy such as phenoxyl; -NRb(C=NRb)NRbR _c ; wherein Rb and R _c are independently selected from the group formed by H, Ci-C ₄ alkyl, C ₂ -C ₄ alkenyl, alkynyl, C3-C10 cycloalkyl, C ₆ -Ci ₈ aryl, C7-C17 aralkyl, heterocyclyl of 3-10 members or protective group of the amino group.

As will be undersood and, as indicated above, when it is stated herein that R is alkyl, alkenyl, alkynyl, alicyclyl, cycloalkyl, cycloalkenyl, cycloalkenyl, heterocyclyl, heterocyclic, heteroarylalkyl, aryl or aralkyl, etc, it is meant that R is such a group. For example, when it is stated R is alkyl, it is mean that R is an alkyl group.

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

Compounds of the invention

In a first aspect, the invention relates to a compound of formula (I) Ri-W _m -Xn-AAi-AA2-AA3-AA ₄ -Yo-Zp-R ₂ (I), a stereoisomer and/or cosmetically acceptable salt thereof, wherein:

AAi is Leu, He or Vai;

AA ₂ is Pro Ala or Gly;

AA ₃ is Vai, He or Leu;

AA ₄ is Thr, Vai or no amino acid;

W, X, Y and Z are each independently any amino acid; m, n, p and q are each independently 0 or 1 ; m+n+p+q is less than or equal to 2;

Ri is selected from the group consisting of H, a polymer derived from polyethylene glycol, a non-cyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, aralkyl and R ₅ - CO-, wherein R ₅ is selected from the group consisting of H, a non-cyclic aliphatic group, alicyclyl, aryl, aralkyl, heterocyclyl and heteroarylalkyl;

R ₂ is selected from the group consisting of -NR ₃ R ₄ , -OR ₃ , -SR ₃ , wherein R ₃ and R ₄ are independently selected from a group consisting of H, a polymer derived from polyethylene glycol, a non-cyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl and aralkyl; and

Ri and R ₂ are not amino acids.

The compound of formula (I) is a peptide which comprises 3, 4, 5 or 6 amino acids linked in a chain. Ri is bound to the amino terminal end (N-terminal) of the peptide and R ₂ is bound to the carboxy-termin al end (C-terminal) of the peptide. Ri can be selected from the group consisting of H, a polymer derived from polyethylene glycol with a molecular weight comprised between 200 and 35000 Daltons and Rs-CO-, wherein R5 is selected from the group consisting of C1-C24 alkyl, C2-C24 alkenyl, C2-C24 alkynyl, C3-C24 cycloalkyl, C5-C24 cycloalkenyl, C ₈ -C ₂ 4 cycloalkynyl, C ₆ -C ₃ o aryl, C7-C24 aralkyl, 3-10 membered heterocyclyl ring, and a heteroarylalkyl containing from 2 to 24 carbon atoms and from 1 to 3 heteroatoms, wherein the alkyl group has 1 to 6 carbon atoms.

R1 can be selected from the group consisting of H and R5-CO-, wherein Rs is selected from the group consisting of C1-C18 alkyl, C2-C24 alkenyl, C3-C24 cycloalkyl or the group consisting of C1-C16 alkyl, C2-C18 alkenyl, C3-C7 cycloalkyl. The Rs-CO- group includes alkanoyl groups such as acetyl (CH3-CO-, which is abbreviated herein as “Ac-”), myristoyl (CH ₃ -(CH ₂ )i2-CO-, which is abbreviated herein as “Myr-”) and palmitoyl (CH ₃ -(CH ₂ )i4-CO-, which is abbreviated herein as “Palm-”).

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

R1 can be selected from the group consisting of H and Rs-CO-, wherein R ₅ is selected from the group consisting of C1-C16 alkyl or C ₂ -Ci ₈ alkenyl.

R1 can be selected from the group consisting of H and R5-CO-, wherein R ₅ is C1-C15 alkyl.

R1 can be selected from the group consisting of H, acetyl and palmitoyl. Particularly, R1 is H.

R ₂ can be selected from the group consisting of -NR3R4, -OR ₃ , -SR ₃ , wherein R ₃ and R ₄ are independently selected from the group formed by H, a polymer derived from polyethylene glycol, C1-C24 alkyl, C2-C24 alkenyl, C2-C24 alkynyl, C3-C24 cycloalkyl, C5-C24 cycloalkenyl, C ₈ -C ₂ 4 cycloalkynyl, C ₆ -C ₃ o aryl, C7-C24 aralkyl, 3-10 membered heterocyclyl ring, and heteroarylalkyl containing from 2 to 24 carbon atoms and from 1 to 3 heteroatoms, wherein the alkyl group has 1 to 6 carbon atoms. Optionally, R ₃ and R ₄ can be joined by a saturated or unsaturated carbon-carbon bond, forming a ring with the nitrogen atom. R ₂ can be -NR3R4 or -OR3. R3 and R4 can be independently selected from the group consisting of H, a polymer derived from polyethylene glycol with a molecular weight comprised between 200 and 35000 Daltons, methyl, ethyl, hexyl, dodecyl and hexadecyl. Alternatively, R ₃ and R ₄ can be independently selected from the group consisting of H and C1-C16 alkyl. In one embodiment, R ₂ is not OR ₃ where R ₃ is a methyl group, i.e. R ₂ is not OCH3. In one embodiment R ₃ is H and R ₄ is selected from the group formed by H and C1-C16 alkyl, including methyl, ethyl, hexyl, dodecyl and hexadecyl.

R ₂ can be selected from the group consisting of -OH, -NH ₂ and -NHR4 where R4 is C1-C16 alkyl or C1-C3 alkyl or Ci-C ₂ alkyl.

R ₂ can be -OH or -NH ₂ . Particularly, R ₂ is OH.

R1 can be selected from the group consisting of H and R5-CO-, wherein R ₅ is selected from the group consisting of C1-C18 alkyl, C ₂ -C ₂ 4 alkenyl, C3-C ₂ 4 cycloalkyl; and R ₂ can be -NR3R4 or -OR3, wherein R ₃ and R ₄ are independently selected from the group consisting of H and C1-C16 alkyl. In this embodiment, R3 can be H and R4 can be selected from the group formed by H, C1-C16 alkyl, C1-C3 alkyl and Ci-C ₂ alkyl; for example, R ₂ can be selected from the group consisting of -OH and -NH ₂ .

R1 can be selected from the group consisting of H and acetyl, te/Y-butanoyl, prenyl, hexanoyl, 2-methylhexanoyl, cyclohexanecarboxyl, octanoyl, decanoyl, lauroyl, myristoyl, palmitoyl, stearoyl, oleoyl and linoleoyl; and R ₂ can be -NR ₃ R4 or -OR ₃ wherein R ₃ and R ₄ are independently selected from the group consisting of H and C1-C16 alkyl. In this embodiment, R ₃ can be H and R ₄ can selected from the group formed by H, C1-C16 alkyl, C1-C3 alkyl and Ci-C ₂ alkyl; for example, R ₂ can be selected from the group consisting of -OH and -NH ₂ .

R1 can be selected from the group consisting of H and R5-CO-, wherein R ₅ is selected from the group consisting of C1-C16 alkyl or C ₂ -Ci8 alkenyl; and R ₂ can be -NRsR4 or -ORs, wherein R ₃ and R ₄ are independently selected from the group consisting of H and C1-C16 alkyl. In this embodiment R ₃ can be H and R ₄ can be selected from the group formed by H, C1-C16 alkyl, C1-C3 alkyl and Ci-C ₂ alkyl; for example, R ₂ can be selected from the group consisting of -OH and -NH ₂ . Ri can be selected from the group consisting of H, acetyl, myristoyl or palmitoyl; and R2 can be -NR3R4 or -OR3, wherein R3 and R4 are independently selected from the group consisting of H and C1-C16 alkyl. In this embodiment R3 can be H and R4 can be selected from the group formed by H, C1-C16 alkyl, C1-C3 alkyl and C1-C2 alkyl; for example, R ₂ can be selected from the group consisting of -OH and -NH ₂ .

R1 can be selected from the group consisting of H and R5-CO-, wherein Rs is C1-C15 alkyl and R ₂ can be -NR3R4 or -OR ₃ , wherein R ₃ and R ₄ are independently selected from the group consisting of H and C1-C16 alkyl. In this embodiment R3 can be H and R4 can be selected from the group formed by H, C1-C16 alkyl, C1-C3 alkyl and C1-C2 alkyl; for example, R2 can be selected from the group consisting of -OH and -NH2.

R1 can be selected from the group consisting of H, acetyl and palmitoyl, and R ₂ can be -NR3R4 or -OR3, wherein R ₃ and R ₄ are independently selected from the group consisting of H and C1-C16 alkyl. In this embodiment R3 can be H and R4 can be selected from the group formed by H, C1-C16 alkyl, C1-C3 alkyl and C1-C2 alkyl; for example, R ₂ can be selected from the group consisting of -OH and -NH2.

R1 can be H and R2 can be -NR3R4 or -OR3, wherein R3 and R4 are independently selected from the group consisting of H and C1-C16 alkyl. In this embodiment R ₃ can be H and R ₄ can be selected from the group formed by H, C1-C16 alkyl, C1-C3 alkyl and C1-C2 alkyl; for example, R2 can be selected from the group consisting of -OH and -NH2.

R1 can be H and R ₂ can be -NR3R4 wherein R ₃ and R ₄ are independently selected from the group consisting of H and C1-C16 alkyl. In this embodiment R ₃ can be H and R ₄ can be selected from the group formed by H, C1-C16 alkyl, C1-C3 alkyl and C1-C2 alkyl; for example, R ₂ can be selected from the group consisting of -NH ₂ and -NHR ₄ where R ₄ is C1-C3 alkyl. R ₂ can be -NH ₂ .

R1 can be H and R2 can be -OH or -NH2. R1 can be acetyl and R2 can be -OH or -NH2. R1 can be acetyl and R ₂ can be -NH ₂ . R1 can be palmitoyl and R ₂ can be -OH.

The most preferred structures of the polymer derived from polyethylene glycol are the group (-CH2-CH2-O) _r H in which r is a number comprised between 4 and 795 and the group where s is a number comprised between 1 and 125.

The compound of formula (I) can carry at least one of the following conditions: Ri is not H; and R2 is not OH. That is, there is provided a compound of formula (I) where R1 is not H and/or R2 is not OH.

In the compound of formula (I): AA1 is selected from the group consisting of Leu, lie and Vai; AA ₂ is selected from the group consisting of Pro, Ala and Gly; AA ₃ is selected from the group consisting of Vai, He and Leu; and AA ₄ is selected from the group consisting of Thr, Vai and no amino acid. When AA ₄ is no amino acid, it means that an amino acid AA ₄ is not present in the compound.

AA1 can be selected from the group consisting of Leu and Vai, for example, where, in formula (I), AA1 is selected from the group consisting of Leu and Vai; AA ₂ is selected from the group consisting of Pro, Ala and Gly; AA ₃ is selected from the group consisting of Vai, He and Leu; and AA ₄ is selected from the group consisting of Thr, Vai and no amino acid.

AA1 can be Vai, for example, where, in formula (I), AA1 is Vai; AA ₂ is selected from the group consisting of Pro, Ala and Gly; AA ₃ is selected from the group consisting of Vai, lie and Leu; and AA ₄ is selected from the group consisting of Thr, Vai and no amino acid.

AA ₂ can be Pro, for example, where, in formula (I), AA1 is selected from the group consisting of Leu, lie and Vai; AA ₂ is Pro; AA ₃ is selected from the group consisting of Vai, lie and Leu; and AA ₄ is selected from the group consisting of Thr, Vai and no amino acid.

AA ₃ can be Vai or Leu, for example, where, in formula (I), AA1 is selected from the group consisting of Leu, lie and Vai; AA ₂ is selected from the group consisting of Pro, Ala and Gly; AA ₃ is selected from the group consisting of Vai and Leu; and AA ₄ is selected from the group consisting of Thr, Vai and no amino acid. AA ₃ can be Vai, for example, where, in formula (I), AAi is selected from the group consisting of Leu, He and Vai; AA2 is selected from the group consisting of Pro, Ala and Gly; AA3 is Vai; and AA4 is selected from the group consisting of Thr, Vai and no amino acid.

AA ₄ can be selected from the group consisting of Thr and Vai, for example, where, in formula (I), AA1 is selected from the group consisting of Leu, He and Vai; AA2 is selected from the group consisting of Pro, Ala and Gly; AA ₃ is selected from the group consisting of Vai, lie and Leu; and AA4 is selected from the group consisting of Thr and Vai.

AA4 can be selected from the group consisting of Thr and no amino acid, for example, where, in formula (I), AA1 is selected from the group consisting of Leu, lie and Vai; AA ₂ is selected from the group consisting of Pro, Ala and Gly; AA ₃ is selected from the group consisting of Vai, lie and Leu; and AA ₄ is selected from the group consisting of Thr and no amino acid.

The compound of formula (I) can carry the proviso that when there is no amino acid in the AA ₄ position, AA1 is Leu.

The compound of formula (I) can carry the proviso that when there is no amino acid in the AA ₄ position, AA ₂ is Pro.

The compound of formula (I) can carry the proviso that when there is no amino acid in the AA ₄ position, AA ₃ is Vai.

The compound of formula (I) can carry the proviso that it is not H-Lys-Leu-Pro-Val-Thr- OH or H-Leu-Pro-Val-Thr-Leu-Arg-OH.

The compound of formula (I) can carry the proviso that it is not H-Leu-Pro-lle-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.

In exemplary embodiments of the compound of formula (I):

AA1 is Leu; AA2 is Pro; AA ₃ is Vai; and AA4 is Thr;

AA1 is Leu; AA ₂ is Ala; AA ₃ is Vai; and AA ₄ is Thr;

AA1 is Leu; AA ₂ is Pro; AA ₃ is lie; and AA ₄ is Thr; AAi is Vai; AA2 is Pro; AA3 is Vai; and AA4 is Thr;

AA1 is Leu; AA2 is Gly; AA3 is Vai; and AA4 is Thr;

AA1 is Leu; AA2 is Pro; AA3 is Leu; and AA4 is Thr;

AA1 is Leu; AA ₂ is Pro; and AA ₃ is Vai; and AA1 is He; AA ₂ is Pro; AA ₃ is He; and AA ₄ is Thr.

In exemplary embodiments of the compound of formula (I):

AA1 is Leu; AA ₂ is Pro; AA ₃ is Vai; AA ₄ is Thr; R1 is H and R ₂ is OH or NH ₂ ;

AA1 is Leu; AA2 is Pro; AA3 is Vai; AA4 is Thr; R1 is H or Ac and R2 is NH2; and AA1 is Leu; AA2 is Pro; AA3 is Leu; AA4 is Thr; R1 is H and R2 is OH.

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

Table 2

Compounds of formula (I) include each of the amino acid sequences of Table 2 in which one of amino acids AA1 to AA4 is replaced by a replacement amino acid, wherein the replacement amino acid is selected from the alternative amino acids listed for the amino acid being replaced in formula (I) above. The replacement amino acid is different from the amino acid that is being replaced. The replacement amino acid can be no amino acid in the case of AA ₄ . Thus, for example, the invention provides for a compound of formula (I) corresponding to SEQ ID NO. 1 in which one of amino acids AAi to AA ₄ is replaced by an amino acid, wherein: when Leu (AAi) is replaced it is replaced by He or Vai; when Pro (AA2) is replaced it is replaced by Ala or Gly; when Vai (AA3) is replaced it is replaced by He or Leu; and when Thr (AA ₄ ) is replaced, it is replaced by Vai or no amino acid.

In the amino acid sequences of Table 2, R1 and R2 are H and OH, respectively. Compounds of the invention include each of the sequences of Table 2 with their N- and C- terminals modified by the other R1 and R ₂ groups, respectively, as defined herein for formula (I). For example, compounds of the invention include each of the sequences of Table 2 in which the N-terminal amino acid residue terminates with R1 as defined above for formula (I) where R1 is not H, and, alternatively or additionally, where the C-terminal amino acid residue optionally terminates with R2 as defined above for formula (I), where R ₂ is not OH.

Thus, in particular, the compound according to formula (I) can be any of the amino acid sequences SEQ ID NO. 1 to 10 and its stereoisomers, and/or its cosmetically acceptable salts, wherein optionally, said sequence has its N-terminal amino acid modified by R1 as defined above for formula (I), where R1 is not H, and, alternatively or additionally, said sequence has its C-terminal amino acid modified by R ₂ as defined above for formula (I), where R ₂ is not OH. The amino acid sequence can be SEQ ID NO. 1 .

The compounds of formula (I) can exist as stereoisomers or mixtures of stereoisomers; for example, the amino acids which comprise them can have the configuration L-, D-, or be racemic independently of each other. Therefore, it is possible to obtain isomeric mixtures as well as racemic mixtures or diastereomeric mixtures, or pure diastereomers or enantiomers, depending on the number of asymmetric carbons and on which isomers or isomeric mixtures are present. The preferred structures of the compounds of the invention are pure isomers, i.e., enantiomers or diastereomers. For example, when it is stated that AA2 can be Ala, it is understood that, unless otherwise specified, AA2 is selected from L-Ala, D-Ala or mixtures 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 compound of the invention by choosing the amino acid with the right configuration.

In the context of this invention, the term "amino acids” includes the amino acids encoded by the genetic code as well as non-encoded amino acids, whether they are natural or not. Examples of non-encoded amino acids are, without restriction, citrulline, ornithine, sarcosine, desmosine, norvaline, 4-aminobutyric acid, 2-aminobutyric acid, 2-aminoisobutyric acid, 6-aminohexanoyc acid, 1 -naphthylalanine, 2-naphthylalanine, 2-aminobenzoic acid, 4-aminobenzoic acid, 4-chlorophenylalanine, 2,3- diaminopropionic acid, 2,4-diaminobutyric acid, cycloserine, carnitine, cystine, penicillamine, pyroglutamic acid, thienylalanine, hydroxyproline, allo-isoleucine, allothreonine, isonipecotic acid, isoserine, phenylglycine, statin, B-alanine, norleucine, /V- methyl amino acids, a-amino acids and p-amino acids, among others, as well as their derivatives. A list of non-natural amino acids can be found in the article "Unusual amino acids in peptide synthesis" by D.C. Roberts and F. Vellaccio, in The Peptides, Vol. 5 (1983), Chapter VI, Gross E. and Meienhofer J., Eds., Academic Press, New York, USA or in the commercial catalogues of the companies specialized in the field.

When any of W, X, Y and/or Z are present, i.e. when at least one of n, m, p or q is not 0, it is understood that the nature of W, X, Y and/or Z does not hinder the activity of the compound of the invention, and, instead, contributes to it or has no effect on it. W, X, Y and Z can each be independently selected from the group consisting of Ala, Gly, Vai and He. W, X, Y and Z can each be independently selected from the group consisting of Ala, Vai and He. W, X, Y and Z can each be independently selected from the group consisting of Ala, Gly and Vai. W, X, Y and Z can each be indepently Ala or Gly . W, X, Y and Z can each be Ala.

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

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

Compounds of formula (I) include each of the compounds of Table 3 in which one of amino acids AAi to AA ₄ is replaced by a replacement amino acid, wherein the replacement amino acid is selected from the alternative amino acids listed for the amino acid being replaced in formula (I) above. The replacement amino acid is different from the amino acid that is being replaced. The replacement amino acid can be no amino acid in the case of AA ₄ . Thus, for example, the invention provides for a compound of formula (I) corresponding to PEP-1 in which one of amino acids AAi to AA ₄ is replaced by an amino acid, wherein: when Leu (AAi) is replaced it is replaced by He or Vai; when Pro (AA2) is replaced it is replaced by Ala or Gly; when Vai (AA3) is replaced it is replaced by He or Leu; and when Thr (AA ₄ ) is replaced, it is replaced by Vai or no amino acid. The compound according to formula (I) can 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) can be PEP-1.

The cosmetically or pharmaceutically acceptable salts of the compounds provided by the present invention are also found within the field of this invention. The term “cosmetically or pharmaceutically acceptable salt” means a salt recognized for its use in animals, for example, in mammals, and more specifically in human beings, and includes salts used to form base addition salts, either they are inorganic, for example and not restricted to, lithium, sodium, potassium, calcium, magnesium, manganese, copper, zinc or aluminium among others, or they are organic, for example and not restricted to, ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, arginine, lysine, histidine or piperazine among others, or acid addition salts, either they are organic, for example and not restricted to, acetate, citrate, lactate, malonate, maleate, tartrate, fumarate, benzoate, aspartate, glutamate, succinate, oleate, trifluoroacetate, oxalate, pamoate or gluconate among others, or inorganic, for example and not restricted to, chloride, sulfate, borate or carbonate, among others. The nature of the salt is not critical, provided that it is cosmetically or pharmaceutically acceptable. The cosmetically or pharmaceutically acceptable salts of the compounds of the invention can be obtained by the conventional methods, well known in the prior art [Berge S.M. et al., "Pharmaceutical Salts", (1977), J. Pharm. Sci., 66, 1-19],

The invention also provides for a combination comprising the compound of formula (I), its stereoisomers, and/or its cosmetically acceptable salts, in any of the embodiments described above, with: a Botulinum toxin; Ac-Glu-Glu-Met-Gln-Arg-Arg-NH ₂ (SEQ ID NO. 11); or H-Tyr-D-Ala-Gly-Phe-Leu-OH(SEQ ID NO. 12); or Ac-pAla-His-Ser-His-OH (SEQ ID NO. 13); or Ac-GIn-Glu-Met-Arg-Met-GIn-OH (SEQ ID NO. 14); or Ac-Asp-Val-Tyr- Lys-NH ₂ (SEQ ID NO. 15); or H-Ala-Leu-Lys-Pro-Asn-Thr-NH ₂ (SEQ ID NO. 16) and/or Ac-Arg-Arg-Gln-Met-Glu-Glu-NH ₂ (SEQ ID NO. 17); or Ac-Arg-Arg-D-GIn-Met-Glu-Glu- NH ₂ (SEQ ID NO. 18); or Ac-Arg-Arg-Gln-D-Met-Glu-Glu-NH ₂ (SEQ ID NO. 19); or Ac- Arg-Arg-D-Gln-D-Met-Glu-Glu-NH ₂ (SEQ ID NO. 20) or combinations thereof.

Preparation procedures of the compounds of the invention

Synthesis of the compounds of the 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], synthesis in solution, enzymatic synthesis [Kullmann “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 a bacterial strain, modified or unmodified by genetic engineering with the objective of producing the desired sequences, or by controlled hydrolysis of proteins with animal or plant origins, preferably plant, which results in free peptide fragments that contain the desired sequence.

For example, a method of obtaining the compounds of formula (I), their stereoisomers and mixtures thereof comprises the stages of:

-coupling of an amino acid, with the A/-terminal end protected and the C-terminal end free, with an amino acid with the A/-terminal end free and the C-terminal end protected or bound to a solid support;

-elimination of the protective group of the A/-terminal end;

-repetition of the coupling sequence and elimination of the protective group of the A/-terminal end until the desired peptide sequence is obtained;

-elimination of the protective group of the C-terminal end or cleavage of the solid support.

Preferably, the C-terminal end is bound to a solid support and the process is carried out in solid phase and, therefore, comprises the coupling of an amino acid with the A/-terminal end protected and the C-terminal end free, with an amino acid with the A/-terminal end free and the C-terminal end bound to a polymeric support; elimination of the protective group of the A/-terminal end; and repetition of this sequence as many times as is necessary to thus obtain the compound of desired length, finally followed by the cleavage of the synthesized compound from the original polymeric support.

The functional groups of the side chains of the amino acids are maintained conveniently protected with temporary or permanent protective groups throughout synthesis, and can be unprotected simultaneously or orthogonally to the process of cleavage of the peptide from the polymeric support. Alternatively, solid phase synthesis can be carried out using a convergent strategy coupling a peptide with the polymeric support or with a peptide or an amino acid previously bound to the polymeric support. Convergent synthesis strategies are widely known by persons skilled in the art and are described in Lloyd-Williams P. et al., “Convergent Solid-Phase Peptide Synthesis”, (1993), Tetrahedron, 49(48), 11065-11133.

The process can comprise the additional stages of deprotection of the A/-terminal and C-terminal ends and/or cleavage of the peptide from the polymeric support in an indiscriminate order, using standard procedures and conditions known in the prior art, after which the functional groups of these ends can be modified. The optional modification of the A/-terminal and C-terminal ends can be carried out with the peptide of formula (I) anchored to the polymeric support or once the peptide has been separated from the polymeric support.

Optionally, Ri can be introduced by the reaction of the /V-terminal end of the compound of the invention with a Ri-X compound through a nucleophilic substitution reaction, in the presence of an adequate base and solvent, wherein the fragments that have the functional groups not involved in the N-C bond formation are suitably protected with temporary or permanent protective groups. Ri is as defined above and X is a leaving group, for example and not restricted to, the tosyl group, the mesyl group and halogen groups among others.

Optionally and/or additionally, the R ₂ radicals can be introduced by the reaction of a compound HR ₂ with a complementary fragment which corresponds to the peptide of formula (I) in which R ₂ is -OH in the presence of an adequate solvent and a base such as /V,/V-diisopropylethylamine (DIEA) or trimethylamine, or an additive such as 1- hydroxy benzotriazole (HOBt) or 1 -hydroxyazabenzotriazole (HOAt), and a dehydrating agent such as a carbodiimide, a uronium salt, a phosphonium salt or amidinium salt, among others, or by prior formation of an acyl halide with, for example, thionyl chloride, and thereby obtaining a peptide according to the invention of formula (I), wherein the fragments that have the functional groups not involved in the N-C bond formation are suitably protected with temporary or permanent protective groups. Alternatively other R ₂ radicals may be introduced by simultaneous incorporation to the peptide cleavage process from the polymeric carrier. R2 is -OR3, -NR3R4 or -SR3, where R3 and R4 are as defined above.

A person skilled in the art would easily understand that the deprotection/cleavage steps of the C-terminal and A/-terminal ends and their subsequent derivatization can be performed in a different order, according to the processes known in the prior art.

The term “protective group” relates to a group which blocks an organic functional group and which can be removed in controlled conditions. The protective groups, their relative reactivities and the conditions in which they remain inert are known to the person skilled in the art.

Examples of representative protective groups for the amino group are amides, such as amide acetate, amide benzoate, amide pivalate; carbamates such as benzyloxycarbonyl (Cbz or Z), 2-chlorobenzyl (CIZ), para-nitrobenzyloxycarbonyl (pNZ), tert- butyloxycarbonyl (Boc), 2,2,2-trichloroethyloxycarbonyl (Troc), 2-(trimethylsilyl)ethyloxycarbonyl (Teoc), 9-fluorenylmethyloxycarbonyl (Fmoc) or allyloxycarbonyl (Alloc), trityl (Trt), methoxytrityl (Mtt), 2,4-dinitrophenyl (Dnp), A/-[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), among others, preferably Boc or Fmoc.

Examples of representative protective groups for the carboxyl group are esters, such as the te/Y-butyl ester (tBu), allyl ester (All), triphenylmethyl ester (Trt tester), cyclohexyl ester (cHx), benzyl ester (Bzl), o/Yho-nitrobenzyl ester, para-nitrobenzyl ester, para- methoxybenzyl ester, trimethylsilylethyl ester, 2-phenylisopropyl ester, fluorenylmethyl ester (Fm), 4-(/V-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbut yl]amino) benzyl ester (Dmab), among others; preferred protective groups of the invention are the All, tBu, cHex, Bzl and Trt esters.

The side chains of trifunctional amino acids can be protected during the synthetic process with temporary or permanent protective groups orthogonal to the protective groups of the A/-terminal and C-terminal ends.

The hydroxyl group of the tyrosine side chain can be protected with the 2- bromobenzyloxycarbonyl group (2-BrZ), tBu, All, Bzl or 2,6-dichlorobenzyl (2,6-diCIZ) among others. In a preferred embodiment, the protective group strategy used is the strategy wherein the amino groups are protected by Boc, the carboxyl groups are protected by Bzl, cHx or All esters and the tyrosine side chain is protected with 2-BrZ or Bzl. In another preferred embodiment, the protective group strategy used is the strategy wherein the amino groups are protected by Fmoc, the carboxyl groups are protected by tBu, All or Trt esters, the tyrosine side chain is protected by tBu.

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

Examples of these and other protective 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 “protective g rou ps” also includes the polymeric supports used in solid phase synthesis.

When synthesis takes place totally or partially in solid phase, the possible solid supports used in the process of the invention involve polystyrene support, polyethylene glycol grafted to polystyrene and similar, for example and not restricted to, p- methylbenzhydrylamine resins (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 resins [Barlos K. etal., “Darstellung geschutzter Peptid-Fragmente unter Einsatz substituierter Triphenylmethyl-Harze”, (1989), Tetrahedron Lett., 30, 3943-3946; Barlos K. et al., “Veresterung von partiell geschutzten Peptid-Fragmenten mit Harzen. Einsatz von 2-Chlorotritylchlorid zur Synthese von Leu1-Gastrin I”, (1989), Tetrahedron Lett., 30, 3947-3951], TentaGeF resins (Rapp Polymere GmbH), ChemMatrix ⁿ resins (Matrix Innovation, Inc) and similar, which may or may not include a labile linker, 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] and similar, which enable simultaneous deprotection and cleavage of the compound from the polymeric support.

Applications

The invention is based on the finding that compounds of formula (I) are useful in the treatment of the skin, hair, nails and/or mucous membranes, in particular the cosmetic, non-therapeutic treatment of the skin, hair, nails and/or mucous membranes. It has been found that compounds of formula (I) are useful in the prevention or treatment of the symptoms of skin aging, which symptoms include the presence of skin wrinkles, a loss of firmness and a sagging appearance of the skin. In particular, it has been found that compounds of the invention are effective in improving the firmness of the skin, reducing a sagging appearance of the skin, reducing the appearance of wrinkles in the skin and in lifting the skin. It has also been found that compounds of formula (I) are effective at upregulating the expression of musclebind-like protein 1 (MBNL-1) in skin and skeletal muscle cells. Further, it has also been found that compounds of formula (I) are effective in stimulating contraction of a collagen matrix containing fibroblast cells, i.e. a collagen matrix similar to the extracellular matrix in the dermis. Thus, the compounds of formula (I) are useful in the cosmetic, non-therapeutic treatment of the skin, hair, nails and/or mucous membranes.

The invention provides for the use of the compound of formula (I), a stereoisomer and/or cosmetically acceptable salt thereof, or a cosmetic composition comprising the compound of formula (I), a stereoisomer and/or a cosmetically acceptable salt thereof, in the treatment and/or care of the skin, hair, nails and/or mucous membranes. In particular, the treatment and/or care of the 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 this invention, skin includes the skin of the whole body including the skin of the face (including skin around the eyes), neckline, neck, decolletage, arms, hands, legs, feet, thighs, hips, buttocks, stomach and torso. The treatment and/or care of the skin can include: the treatment and/or prevention of the aging of the skin, the treatment and/or prevention of skin wrinkles; maintaining and improving skin firmness; the treatment and/or prevention of a sagging appearance of the skin; and/or having a lifting effect on the skin.

The treatment and/or care can involve the upregulation of the expression of MBNL-1 in skin (i.e. in skin cells, specifically in dermal fibroblast cells) and/or in muscles (i.e. in muscle cells, specifically skeletal muscle cells). It is believed that an increase of MBNL1 promotes human dermal fibroblast differentiation to myofibroblast, which improves collagen contraction. Besides an increase of MBNL-1 in muscle cells helps maintain facial skin muscle tone. As a result, skin sagginess is prevented.

The treatment and/or care can involve contraction of the extracellular matrix of the dermis. Fibroblasts which synthesise components of the extracellular matrix, induce contraction of the extracellular matrix. Compounds of formula (I) have been found to promote fibroblast-induced contraction of a fibroblast-containing collagen gel and thus are believed to be able to promote fibroblast-induced contraction of the extracellular matrix. 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 a sagging appearance of the skin and reduce or prevent the appearance of skin wrinkles.

The treatment and/or care can be the treatment and/or prevention of the aging of the skin. The treatment and/or prevention is skin aging includes the treatment (or alleviation) and/or the prevention of symptoms of skin aging. Symptoms of skin aging include the appearance of wrinkles and the loss of skin biomechanical properties such as firmness. A loss fo fimness can result in a sagging appearance of the skin. A loss of firmness can be due to a change in cell-matrix interactions in the extracellulr matrix of the dermis due to skin aging.

The treatment and/or care can be the treatment and/or prevention of skin wrinkles. Skin wrinkles include expression wrinkles, also commonly referred as expression lines.

The treatment and/or care can be the maintaining and/or improving skin firmness. The skin can be the skin of the face, in particular, the skin of the jawline.

The treatment and/or care can be the treatment and/or prevention of a sagging appearance of the skin. The treatment and/or care can be the lifting of the skin and can be, for example, the lifting of the eyebrows, the cheeks or the jawline.

The invention also extends to the use of a combination of the compound of formula (I) with a Botulinum toxin, Ac-Glu-Glu-Met-Gln-Arg-Arg-NH ₂ , H-Tyr-D-Ala-Gly-Phe-Leu-OH, Ac-pAla-His-Ser-His-OH, Ac-GIn-Glu-Met-Arg-Met-GIn-OH, Ac-Asp-Val-Tyr-Lys-NH2, H-Ala-Leu-Lys-Pro-Asn-Thr-NH ₂ and/or Ac-Arg-Arg-Gln-Met-Glu-Glu-NH _2] Ac-Arg-Arg- D-Gln-Met-Glu-Glu-NH ₂ , Ac-Arg-Arg-Gln-D-Met-Glu-Glu-NH ₂ and/or Ac-Arg-Arg-D-GIn- D-Met-Glu-Glu-NH ₂ in the treatment and/or care of the skin, hair, nails and/or mucous membranes as described above in relation to the applications (uses) of the compounds of formula (I). Ac-Glu-Glu-Met-Gln-Arg-Arg-NH ₂ is commercialized as Argireline® peptide by Lipotec SAU (The Lubrizol Corporation) and is known to imitate the cosmetic effects of Botulinum toxins on the skin in that it inhibits neuronal exocytosis.

The invention also provides a method of treatment and/or care of the skin, hair, nails and/or mucous membranes of a subject comprising administering a compound of formula (I), a stereoisomer and/or cosmetically or pharmaceutically acceptable salt thereof or a composition comprising the compound of the invention, a stereoisomer and/or a cosmetically or pharmaceutically acceptable salt thereof, to the subject. In particular, method is a cosmetic, non-therapeutic method of treatment and/or care of the skin, hair, nails and/or mucous membranes of a subject. The subject can be Caucasian. The method can be for the treatment and/or care of the skin, hair, nails and/or mucous membranes as described above in relation to the applications (uses) of the compound of formula (I). In particular, the method of treatment and/or care is that of the skin. The administration can be topical or, for example, transdermal. The compound of formula (I) may be present in a cosmetic composition such as the cosmetic composition as described herein. The method can involve administering the compound or administering the composition using microneedles.

The invention also extends to a method of treatment and/or care of the skin, hair, nails and/or mucous membranes of a subject comprising administering a combination of the compound of formula (I), a stereoisomer and/or cosmetically or pharmaceutically acceptable salt thereof with a Botulinum toxin, Ac-Glu-Glu-Met-Gln-Arg-Arg-NH ₂ , H-Tyr- D-Ala-Gly-Phe-Leu-OH; Ac-pAla-His-Ser-His-OH; or Ac-GIn-Glu-Met-Arg-Met-GIn-OH; or Ac-Asp-Val-Tyr-Lys-NH ₂ ; or H-Ala-Leu-Lys-Pro-Asn-Thr-NH ₂ and/or Ac-Arg-Arg-GIn- Met-Glu-Glu-NH2; orAc-Arg-Arg-D-Gln-Met-Glu-Glu-NH2; orAc-Arg-Arg-GIn-D-Met-Glu- GI11-NH2; and/or Ac-Arg-Arg-D-Gln-D-Met-Glu-Glu-NH2 to the subject. The method can be for the treatment and/or care of the skin, hair, nails and/or mucous membranes as described above in relation to the applications (uses) of the compound of formula (I). For example, the method of treatment can comprise administering a Botulinum toxin and a compound of formula (I), a stereoisomer and/or cosmetically or pharmaceutically acceptable salt thereof to the subject. For example, the method of treatment can comprise administering: Ac-Glu-Glu-Met-Gln-Arg-Arg-NH ₂ and a compound of the invention, a stereoisomer and/or cosmetically or pharmaceutically acceptable salt thereof, to the subject. Preferably, this method of treatment is a skin antiaging treatment.

The Botulinum toxin, Ac-Glu-Glu-Met-Gln-Arg-Arg-NH ₂ , H-Tyr-D-Ala-Gly-Phe-Leu-OH; Gln-D-Met-Glu-Glu-NH ₂ ; and the compound of formula (I) can be administered simultaneously or administered one after the other. When the Botulinum toxin and/or Ac- NH2; and the compound of formula (I) are administered at the same time, they can be administered as a separate dosage forms or as a part of a single composition. When the products are administered in separate dosage forms, the dosage forms can be in the same or different containers.

The above methods of treatment include the treatment and/or care of the skin, including: the treatment and/or prevention of the aging of the skin, the treatment and/or prevention of skin wrinkles; maintaining and improving skin firmness; the treatment and/or prevention of a sagging appearance ofthe skin; and/orthe lifting of the skin. In particular, the methods of treatment are cosmetic and non-therapeutic.

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

For the above described methods, topical or transdermal application can be carried out by iontophoresis, sonophoresis, electroporation, mechanical pressure, osmotic pressure gradient, occlusive cure, microinjections, by needle-free injections by means of pressure, by microelectric patches, face masks or any combination thereof.

For the above described methods, the frequency of application or administration can vary greatly, depending on the needs of each subject, with a recommendation of an application 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, even more preferably once a day. For example, the frequency of the administration according to the method of treatment and/or care of the skin, hair, nails and/or mucous membranes of a subject comprising administering a combination of the compound of formula (I), a stereoisomer and/or cosmetically or pharmaceutically acceptable salt thereof with a Botulinum toxi , Ac-Glu-Glu-Met-Gln-Arg-Arg-NH ₂ H-Tyr-D-Ala-Gly-Phe-Leu-OH, Ac- pAla-His-Ser-His-OH, Ac-GIn-Glu-Met-Arg-Met-GIn-OH, Ac-Asp-Val-Tyr-Lys-NH ₂ , H- Ala-Leu-Lys-Pro-Asn-Thr-NH2, Ac-Arg-Arg-Gln-Met-Glu-Glu-NH ₂ , Ac-Arg-Arg-D-GIn- Met-Glu-Glu-NH ₂ , Ac-Arg-Arg-Gln-D-Met-Glu-Glu-NH ₂ , and/or Ac-Arg-Arg-D-GIn-D-Met- Glu-Glu-NH ₂ to the subject, can vary widely, depending on the need of each subject. The method of the invention can comprise the administration of Botulinum toxin, followed by the administration of the compound of formula (I). For example, after the administration of the Botulinum toxin, the compound of formula (I) can be administered at least once a day for at least one week and/or the compound of formula (I) can be administered at least once a day until the next administration of Botulinum toxin.

Compositions of the invention

The compound of formula (I) can be administered by any means that causes contact between the compounds and the site of action in a subject’s body. The subject is preferably a mammal and, more preferably a human. The subject can be Caucasian.

Preferably the compound is contained a composition.

The invention provides a composition comprising a compound according to formula (I), a stereoisomer and/or a cosmetically or pharmaceutically acceptable salt thereof. In particular, the invention provides a cosmetic composition comprising a compound according to formula (I), a stereoisomer and/or a cosmetically acceptable salt thereof, together with at least one cosmetically acceptable excipient or adjuvant. These compositions can be prepared by conventional means known to persons skilled in the art [“Harry’s Cosmeticology”, Seventh edition, (1982), Wilkinson J.B., Moore R.J., ed. Longman House, Essex, GB],

The compounds of formula (I) have variable solubility in water, according to the nature of their amino acid sequence or any possible modifications in the A/-terminal and/or C-terminal ends. Therefore, the compounds of this invention can be incorporated into the compositions by aqueous solution, and those which are not soluble in water can be solubilized in cosmetically or pharmaceutically acceptable conventional solvents such as and not restricted to, ethanol, propanol, isopropanol, propylene glycol, glycerin, butylene glycol or polyethylene glycol or any combination thereof.

The cosmetically effective amount of the compounds of formula (I) which should be administered, as well as their dosage, will depend on numerous factors, including age, state 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 of the particular nature of the compounds to be used.

The terms “cosmetically effective amount” and “pharmaceutically effective amount” are understood to mean a non-toxic but sufficient amount of the compound or compounds of formula (I) 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 this invention at cosmetically or pharmaceutically effective concentrations to achieve the desired effect; for example in amounts with respect to the total weight of the composition of: from 0.00000001 % (in weight) to 20% (in weight); from 0.000001 % (in weight) to 15% (in weight), from 0.00001 % (in weight) to 10% (in weight); or from 0.0001 % (in weight) to 5% (in weight). The compounds of formula (I), their stereoisomers, mixtures thereof and/or their cosmetic or pharmaceutically acceptable salts, can also be incorporated into cosmetic or pharmaceutical delivery systems and/or sustained release systems.

The term “delivery system” relates to a diluent, adjuvant, excipient or carrier with which the compound of the invention is administered. These cosmetic or pharmaceutical carriers can be liquids, such as water, oils or surfactants, including those of petroleum, animal, plant or synthetic origin, for example and not restricted to, peanut oil, soybean oil, mineral oil, sesame oil, castor oil, polysorbates, sorbitan esters, ether sulfates, sulfates, betaines, glycosides, maltosides, fatty alcohols, nonoxynols, poloxamers, polyoxyethylenes, polyethylene glycols, dextrose, glycerol, digitonin and similar. A person skilled in the art knows the diluents, adjuvants or excipients which can be used in the different delivery systems in which the compound of the invention can be administered.

The term “sustained release” is used in a conventional sense relating to a delivery system of a compound which provides the gradual release of this compound during a period of time and preferably, although not necessarily, with relatively constant compound release levels over a period of time.

Examples of delivery or sustained release systems include, without restriction, liposomes, mixed liposomes, oleosomes, niosomes, ethosomes, milliparticles, microparticles, nanoparticles and solid lipid nanoparticles, nanostructured lipid carriers, sponges, cyclodextrins, vesicles, micelles, mixed micelles of surfactants, surfactantphospholipid mixed micelles, millispheres, microspheres and nanospheres, lipospheres, millicapsules, microcapsules and nanocapsules, as well as in microemulsions and nanoemulsions, which can be added to achieve a greater penetration of the active principle 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 an internal structure of reverse micelle and nanocapsules containing microemulsions.

In one embodiment, the 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.

The sustained release systems can be prepared by methods known in the prior art, and the compositions which contain them can be administered, for example, by topical or transdermal administration, including adhesive patches, non-adhesive patches, occlusive patches and microelectric patches, or by systemic administration, for example and not restricted to, oral or parenteral route, including nasal, rectal or subcutaneous implantation or injection, or direct implantation or injection into a specific body part, and preferably should release a relatively constant quantity of the compounds of the invention. The amount of compound contained in the sustained release system will depend, for example, on where the composition is to be administered, the kinetics and duration of the release of the compound of the invention, as well as the nature of the condition, disorder and/or disease to be treated and/or cared for.

The compounds of formula (I) can also be adsorbed on solid organic polymers or solid mineral supports such as and not restricted to, talc, bentonite, silica, starch or maltodextrin among others.

The compositions which contain the compound of formula (I), their stereoisomers, mixtures thereof and/or their cosmetically or pharmaceutically acceptable salts can also be incorporated into fabrics, non-woven fabrics and medical devices which are in direct contact with the skin, thus releasing the compounds of formula (I) whether by biodegradation of the binding system to the fabric, non-woven fabric or medical device, or by friction between them and the body, due to bodily moisture, the skin’s pH or body temperature. Furthermore, the compound of formula (I) can be incorporated into the fabrics and non-woven fabrics used to make garments that are in direct contact with the body.

Examples of fabrics, non-woven fabrics, garments, medical devices and means for immobilizing the compounds to them, among which are the delivery systems and/or the sustained release systems described above, can be found in literature and are known in antibacterial drug from a novel self-lubricating silicone biomaterial”, (2004), J. Cont. Release, 97(2), 313-320], The preferred fabrics, non-woven fabrics, garments and medical devices are bandages, gauzes, t-shirts, socks, tights, underwear, girdles, gloves, diapers, sanitary napkins, dressings, bedspreads, wipes, adhesive patches, nonadhesive patches, occlusive patches, microelectric patches and/or face masks.

The cosmetic or pharmaceutical compositions which contain the 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 ortransdermal application which optionally include cosmetically or pharmaceutically acceptable excipients necessary for formulating the desired administration form.

The compositions for topical or transdermal application can be produced in any solid, liquid or semisolid formulation, such as and not restricted to, creams, multiple emulsions such as and not restricted to, oil and/or silicone in water emulsions, water-in-oil 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, balsams, foams, lotions, gels, cream gels, hydroalcoholic solutions, hydroglycolic solutions, hydrogels, liniments, sera, soaps, shampoos, conditioners, serums, polysaccharide films, ointments, mousses, pomades, powders, bars, pencils and sprays or aerosols (sprays), including leave-on and rinse-off formulations. These topical or transdermal application formulations can be incorporated using techniques known by the person skilled in the art into different types of solid accessories for example and not restricted to, bandages, gauzes, t-shirts, socks, tights, underwear, girdles, gloves, diapers, sanitary napkins, dressings, bedspreads, wipes, adhesive patches, non-adhesive patches, occlusive patches, microelectric patches or face masks, or they can be incorporated into different make-up products such as makeup foundation, such as fluid foundations and compact foundations, make-up removal lotions, make-up removal milks, under-eye concealers, eye shadows, lipsticks, lip protectors, lip gloss and powders among others.

The cosmetic or pharmaceutical compositions of the invention may include agents which increase the percutaneous absorption of the compounds of the invention, for example and not restricted to, dimethylsulfoxide, dimethylacetamide, dimethylformamide, surfactants, azone (1-dodecylazacycloheptane-2-one), alcohol, urea, ethoxydiglycol, acetone, propylene glycol or polyethylene glycol, among others. Furthermore, the cosmetic or pharmaceutical compositions of this invention can be applied to local areas to be treated by means of iontophoresis, sonophoresis, electroporation, microelectric patches, mechanical pressure, osmotic pressure gradient, occlusive cure, microinjections or needle-free injections by means of pressure, such as injections by oxygen pressure, or any combination thereof, to achieve a greater penetration of the peptide of the invention. The application area will be determined by the nature of the condition, disorder and/or disease to be treated and/or cared for.

Furthermore, the 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 formulations for oral administration, preferably in the form of oral cosmetics or drugs, such as and not restricted to, capsules, including gelatin capsules, soft capsules, hard capsules, tablets, including sugar coated tablets, tablets, pills, powders, granules, chewing gum, solutions, suspensions, emulsions, syrups, elixirs, polysaccharide films, jellies or gelatins, and any other form known by the person skilled in the art. In a particular embodiment, the compounds of the invention can be incorporated into any form of functional food or fortified food, such as and not restricted to, dietary bars or compact or non-compact powders. These powders can be dissolved in water, soda, dairy products, soy derivatives or can be incorporated into dietary bars. The compounds of formula (I) can be formulated with common excipients and adjuvants for oral compositions or food supplements, for example and not restricted to, fat components, aqueous components, humectants, preservatives, texturizing agents, flavors, aromas, antioxidants and colorants common in the food industry.

Cosmetic or pharmaceutical compositions containing the compounds of formula (I), their stereoisomers, mixtures thereof and/or their cosmetically or pharmaceutically acceptable salts can also be administered, as well as by topical or transdermal route, by any other appropriate route, such as oral or parenteral route, for which they will include the pharmaceutically acceptable excipients necessary for the formulation of the desired administration form. In the context of this invention, the term “parenteral” includes nasal, auricular, ophthalmic, rectal, urethral, vaginal, subcutaneous, intradermal route, intravascular injections, such as intravenous, intramuscular, intraocular, intravitreous, intracorneal, intraspinal, intramedullary, intracranial, intracervical, intracerebral, intrameningeal, intraarticular, intrahepatic, intrathoracic, intratracheal, intrathecal and intraperitoneal, and any another similar injection or infusion technique. A person skilled in the art knows the different means by which the cosmetic or pharmaceutical compositions which contain the compounds of the invention can be administered.

Among the cosmetically or pharmaceutically acceptable adjuvants contained in the cosmetic or pharmaceutical compositions described herein are additional ingredients commonly used in cosmetic or pharmaceutical compositions, for example and not restricted to (i) anti-wrinkle agents, botox-like agents and/or anti-aging agents; (ii) firming agents, skin elasticity agents and/or restructuring agents; moisturizing agents; (iii) antiphotoaging agents, and/or blue-light protector agents; (iv) DNA protecting agents, DNA repair agents, and/or stem cell protecting agents; (v) free radical scavengers and/or antiglycation agents, detoxifying agents, antioxidant and/or anti-pollution agents; (vi) antiperspirant agents; (vii) melanin synthesis stimulating or inhibiting agents; (viii) whitening or depigmenting agents; (ix) propigmenting agents; (x) self-tanning agents; (xi) lipolytic agents or agents stimulating lipolysis, adipogenic agents, etc. Additional examples can be found in CTFA International Cosmetic Ingredient Dictionary & Handbook, 12th Edition (2008).

In one embodiment, the 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-agent, botox- like agent and/or anti-aging agent; (ii) firming agent, skin elasticity agent and/or restructuring agent; (iii) moisturizing agent; (iv) anti-photoaging agent, and/or blue-light protector agent; (v) DNA protecting agent, DNA repair agent, and/or stem cell protecting agent; (vi) free radical scavengers and/or anti-glycation agent, detoxifying agent, antioxidant and/or anti-pollution agents; and/or combinations thereof.

The anti-wrinkle agent, botox-like agent and/or anti-aging agent can be selected from the group consisting of Matrixyl® [INCI: Palmitoyl Pentapeptide-4], Matrixyl® 3000® [INCI: Palmitoyl Tetrapeptide-7, Palmitoyl Oligopeptide], Matrixyl® Synthe’6 [INCI: Glycerin, Water, Hydroxypropyl Cyclodextrin, Palmitoyl Tripeptide-38], Matrixyl® Morphomics™ [INCI: Pentylene Glycol, Caprylyl Glycol], Essenskin™ [INCI: calcium hydroxymethionine], Renovage [INCI: Teprenone], Dermaxyl® [INCI: Palmitoyl Oligopeptide], Calmosensine [INCI: Butylene Glycol, Acetyl Dipeptide-1 Cetyl Ester], Volulip [INCI: Cetearyl Ethylhexanoate, Sorbitan Isostearate, Portulaca Pilosa Extract, Sucrose Cocoate, Palmitoyl Tripeptide-38], Subliskin [INCI: Sinorhizobium Meliloti Ferment, Cetyl Hydroxyethyl Cellulose, Lecithin], Biopeptide CL [INCI: Palmitoyl Oligopeptide], Biopeptide EL [INCI: Palmitoyl Oligopeptide], Rigin [INCI: Palmitoyl Tetra peptide- 3], Biobustyl [INCI: Glyceryl Polymethacrylate, Rahnella/Soy Protein Ferment, Palmitoyl Oligopeptide], Dynalift [INCI: Sodium Polystyrene Sulfonate, Sorghum Bicolor Stalk Juice, Glycerin], Idealift [INCI: Acetyl Dipeptide-1 Cetyl Ester], Siegesbeckia [INCI: Siegesbeckia Orientales Extract], Ovaliss [INCI: Coco-glucoside, Caprylyl Glycol, Alcohol, Glaucine], Juvinity™ [INCI: Geranylgeranyisopropanol], Prolevis [INCI: Hydrolyzed Vegetable Protein], Idealift™ [INCI: Hydroxyethylcellulose, Acetyl Dipeptide-1 cetyl ester], Beautifeye™ [INCI: Albizia Julibrissin Bark Extract, Darutoside], Chromocare™ [INCI: Sigesbeckia Orientalis Extract, Rabdosia Rubescens Extract] or Resistem™ [INCI proposed: Globularia Cordifolia Ferment] marketed by Sederma/Croda. Vialox® [INCI: Pentapeptide-3], Syn®-Ake® [INCI: Dipeptide Diaminobutyroyl Benzylamide Diacetate], Syn®-Coll [INCI: Palmitoyl Tripeptide-5], Phytaluronate [INCI: Ceratonia Siliqua (Carob) Gum], Preregen® [INCI: Glycine soja (Soybean) Protein, Oxido Reductases], Pepha-Nutrix [INCI: Natural Nutrition Factors], Pepha-Tight [INCI: Algae Extract, Pullulan], Pentacare-NA [INCI: Hydrolyzed Wheat Gluten, Ceratonia Siliqua Gum], Syn®-Tacks [INCI: Glycerin, Palmitoyl Dipeptide-5 Diaminobutyloyl Hydroxythreonine, Palmitoyl Dipeptide-6 Diaminohydroxybutyrate], BeauActive MTP [INCI: Hydrolyzed milk protein], Syn®-TC [INCI: Tetradecyl Aminobutyroylvalylaminobutyric Urea Trifluoroacetat, Palmitoyl Tripeptide-5, Palmitoyl Dipeptide-5 Diaminobutyroyl Hydroxythreonine], Syn®-Hycan [INCI: Tetradecyl Aminobutyroylvalylaminobutyric Urea Trifluoroacetate], Syn®-Glycan [INCI: Tetradecyl Aminobutyroylvalyl-aminobutyric Urea Trifluoroacetate], Regu-Age [INCI: Hydrolyzed Rice Bran Protein, Oxido Reductases, Glycine Soja Protein], Pepha-Timp [INCI: Human oligopeptide-20], Pepha-Age [INCI: Dunaliella Salina Extract], Colhibin [INCI: Hydrolyzed Rice Protein], Elhibin [INCI: Glycine Soja Protein, Disodium cocoamphod iacetate] or All- Q™ Plus [INCI: Ubiquinone, Tocopheryl Acetate] marketed by Pentapharm/DSM; Myoxinol™ [INCI: Hydrolyzed Hibiscus esculentus Extract], Myoxinol™ LS 9736 [INCI: Hydrolyzed Hibiscus esculentus Extract, Dextrin], Syniorage™ [INCI: Acetyl Tetrape pt id e-11], Dermican™ [INCI: Acetyl Tetrapeptide-9], DN-AGE® LS [INCI: Cassia alata leaf Extract], Hyalufix GL [INCI: Alpinia Galanga Leaf Extract], Neurobiox [INCI: Achillea Millefolium Extract,], Deliner [INCI: Zea Mays (Corn) Kernel Extract], Lys'lastine V [INCI: Peucedanum Graveolens (Dill) Extract], Extraceilium [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], Extraceilium [INCI: Hydrolyzed Potato Protein], Marine Filling Spheres [INCI: Pentaerythrityl Tetraisostearate, Silica Dimethyl Silylate, Sodium Chondroitin Sulfate, Atelocollagen], Triactigen [INCI: Mannitol, Cyclodextrin, Yeast Extract, Disodium Succinate], Eterniskin [INCI: Grifola Frondosa Fruiting Body Extract, Maltodextrin], Ascotide [INCI: Ascorbyl Phosphate Succinoyl Pentapeptide-12], Hyalurosmooth [INCI: Cassia Angustifolia Seed Polysaccharide], Indinyl CA [INCI: Cassia Angustifolia Seed Polysaccharide], Arganyl [INCI: Argania Spinosa Leaf Extract], Sphingoceryl Veg [INCI: Phyto-ceramides], Vit-A-Like [INCI: Vigna Acontifolia Seed Extract], Peptiskin [INCI: Arginine/Lysine polypeptide], Prodejine [INCI: Mannitol, Cyclodextrin, Yeast Extract, Disodium Succinate], Aqu'activ [INCI: Behenyl Alcohol, Glyceryl Oleate, Cocamide MIPA, Calcium Citrate], Elestan [INCI: Glycerin, Manilkara Leaf Extract], Hibiscin HP [INCI: Hibiscus Esculentus Seed Extract], Collalift®18 [INCI: Khaya Senegalensis Bark], Collrepair™ DG [INCI: Hexylene Glycol, Niacin] or Litchiderm [INCI: Litchi Chinensis Pericarp Extract] marketed by Laboratoires Serobiologiques/Cognis/BASF; Argireline® [INCI: Acetyl Hexapeptide-8], SNAP-7 [INCI: Acetyl Heptapeptide-4], SNAP-8 [INCI: Acetyl Octapeptide-3], Leuphasyl® [INCI: Pentapeptide-18], Inyline® [INCI: Acetyl Hexapeptide-30], Aldenine® [INCI: Hydrolized Wheat Protein, Hydrolized Soy Protein, Tripeptide-1], Preventhelia® [INCI: Diaminopropionoyl Tripeptide-33], Decorinyl® [INCI: Tripeptide-10 Citrulline], Decorinol® [INCI: Tripeptide-9 Citrulline], Trylagen® [INCI: Pseudoalteromonas Ferment Extract, Hydrolyzed Wheat Protein, Hydrolyzed Soy Protein, Tripeptide-10 Citrulline, Tripeptide-1], Eyeseryl® [INCI: Acetyl Tetrapeptide-5], Peptide AC29 [INCI: Acetyl Tripeptide-30 Citrulline], Relistase® [INCI: Acetylarginyltriptophyl Diphenylglycine], Thermostressine® [INCI: Acetyl Tetrapeptide- 22], Lipochroman™ [INCI: Dimethylmethoxy Chromanol], Chromabright® [INCI: Dimethylmethoxy Chromanyl Palmitate], Antarcticine® [INCI: Pseudoalteromonas Ferment Extract], dGlyage® [INCI: Lysine HCI, Lecithin, Tripeptide-9 Citrulline], Vilastene™ [INCI: Lysine HCI, Lecithin, Tripeptide-10 Citrulline], Hyadisine® [INCI: Pseudoalteromonas Ferment Extract], Hyanify™ [INCI: Saccharide Isomerate], Diffuporine® [INCI: Acetyl Hexapeptide-37], Silusyne® [INCI: Soybean (Glycine Soja) Oil, Sorbitan Sesquioleate, Isohexadecane, Sodium Hyaluronate, Lauryldimonium Hydroxypropyl Hydrolized Soy Protein, Acetyl Hexapeptide-39], Adifyline® [INCI: Acetyl Hexapeptide-38], Delisens™ [INCI: Acetyl Hexapeptide-46], Telangyn™ [INCI: Acetyl Tetrapeptide-40], Reproage™ peptide [INCI: Acetyl Hexapeptide-8], Cellynkage™ marine ingredient [INCI: Saccharide Isomerate], Eyedeline™ marine ingredient [INCI: Plankton Extract], uplevity™ [INCI: Acetyl Tetrapeptide-2], Seacode™ marine ingredient [INCI: Pseudoalteromonas Ferment Extract] or Serilesine® peptide solution [INCI: Hexapeptide-10], Argireline® Amplified peptide [INCI: Acetyl Hexapeptide-8] marketed by Lipotec/Lubrizol; Sirtalice™ [INCI: Bacillus Ferment], Epitensive™ [INCI: Nicotiana Benthamiana Hexapeptide-40 SH-Oligopeptide-1 ], Scelleye™ [INCI: Nicotiana Benthamiana SH-Oligopeptide-2], Seadermium [INCI: Aqua, Glycerin, Bacillus Ferment], Pauseile [INCI: Aqua, Glycerin, Bacillus Ferment] or Neoclair pro [INCI: Aqua, Glycerin, Caprylyl Glycol, Acetyl Tetrapeptide-2] marketed by Lipotrue; Collaxyl® IS [INCI: Hexa peptide- 9], Laminixyl IS™ [INCI: Heptapeptide], Orsirtine™ GL [INCI: Oryza sativa (Rice) Extract], D’Orientine™ IS [INCI: Phoenix dactylifera (Date) Seed Extract], Phytoquintescine™ [INCI: Einkorn (Triticum monococcum) Extract], Quintescine™ IS [INCI: Dipeptide-4], Peptide Vinci 01 [INCI: Penta-decapeptide-1], Peptide Vinci 02™ [INCI: Hexapeptide-3], Aquarize IS™ [INCI: Hydrolyzed Rice Extract], Lanablue [INCI: Algae extract], Ederline™ [INCI: Pyrus Malus (Apple) Seed Extract], Dynachondrine™ ISR [INCI:Hydrolized Soy Protein], Prolixir S20™ [INCI: Dimer Tripeptide-43], Phytocohesine™ PSP [INCI: Sodium Beta-Sitosteryl Sulfate, Beta-Sitosterol], Perenityl™ IS [INCI: Pyrus Communis (Pear) Seed Extract], Caspaline 14™ [INCI:Hexapeptide-42], Peptide Q10™ [INCI:Pentapeptide-34 Trifluoroacetate], Survixyl IS™ [INCI: Pentapeptide-31 ], ChroNOgen™ [INCI: Tetrapeptide-26], Elixiance [INCI: Schinus Molle Extract], Harmoniance™ [INCI: Nelumbo Nucifera Flower Extract], Serenityl [INCI: Marsdenia Condurango Bark Extract], Natriance Wrinkle-less [INCI: Hydrolyzed Corn Protein], Phytoneomatrix [INCI: Hydrolyzed Soybean Extract], Prolixir ICE [INCI: Hydrolyzed Rice Protein], PhytoRNx Baobab™ [INCI: Hydrolyzed Adansonia Digitata Extract], Natriance Renovate Extract [INCI: Hydrolyzed Linseed Extract], Natriance Self-Hydrate Extract [INCI: Pisum Sativum Extract], Actopontine YST [INCI: Hydrolyzed Yeast Protein] or Telosense™ [proposed INCI: Hydrolized Soy Protein, Hydrolized Yeast Protein] marketed by Vincience/ISP/Ashland; BONT-L-Peptide [INCI: Palmitoyl Hexapeptide- 19], TIMP Peptide [INCI: Acetylhexapeptide-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 Acid/glycolic Acid Copolymer, Polyvinyl Alcohol, Copper Palmitoyl Heptapeptide-14, Heptapeptide-15 Palmitate] marketed by Infinitec Activos; EquiStat [INCI: Pyrus malus Fruit Extract, Glycine soja Seed Extract], Juvenesce [INCI: Ethoxydiglicol and Caprylic Trig lycerid, Retinol, Ursolic Acid, Phytonadione, llomastat], Ursolisome [INCI: Lecithin, Ursolic Acid, Atelocollagen, Xanthan Gum, Sodium chondroitin sulfate], Basaline [INCI: Hydrolyzed Malt Extract], Phytokine [INCI: Hydrolyzed Soy Protein], marketed by Coletica/Engelhard/BASF; Ameliox [INCI: Carnosine, Tocopherol, Silybum marianum Fruit Extract] or PhytoCellTec Malus Domestica [INCI: Malus domestica Fruit Cell Culture], Lipobelle Soyaglicane [INCI: Soy Isoflavones], RoyalEpigen P5 [INCI: Butyrospermum Parkii BUtter, Hydrogenated Lecithin, Maltodextrin, Pentapeptide-48, Phenethyl Alcohol, Ethylhexylglycerin, Glycerin, Aqua] or DermCom [INCI: Crocus Chrysanthus Bulb Extract, Acacia Senegal Gum, Aqua/Water] marketed by Mibelle Biochemistr;ActiMatrix [INCI: Peptide based mushroom Extract], Peptamide 6 [INCI: Hexapeptide-11 ] marketed by Active Organics/Arch; and combinations thereof.

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

The moisturizing agent can be selected from the group consisting of qua Shuttle [INCI: Sorbitol, Laminaria Digitata Extract, Diatomaceous Earth] marketed by Infinitec; AquaOsmoline™ [INCI: Ceratonia Siliqua (Carob) Seed Extract] marketed by Vincience/ISP/Ashland; Hydralphatine™ Asia [INCI: Hydrogenated Starch Hydrolysate, Panthenol, Bambusa Vulgaris Shoot Extract, Nelumbo Nucifera Flower Extract, Nymphaea Alba Root Extract] or Hydraporine™ [INCI: Betaine, Hydrogenated Lecithin, Honey, Pectin] marketed by Lucas Meyer Cosmetics/Unipex; PatcH2O™ [INCI: Trehalose, Urea, Serine, Glyceryl Polyacrylate, Algin, Sodium Hyaluronate, Pullulan], Aqu’activ™ [INCI: Behenyl Alcohol, Glyceryl Oleate, Cocamide MIPA], Irwinol® [INCI: Octyldodecanol, Irvingia Gabonensis Kernel Butter, Hydrogenated Coco-Glycerides], Lipodermol®) [INCI: Octyldodecanol, Arachidyl Propionate, Tocopheryl Acetate, Retinyl Palmitate, Ethyl Linoleate, Ethyl Linolenate] or Seanamin® SU [INCI: Sorbitol, Algae Extract, Chrondrus Crispus (Carrageenan), Fucus Vesiculosus Extract, Algin] marketed by L. Serobiologiques/Cognis/BASF; Snow Algae Powder [INCI: Coenochloris Signiensis Extract] marketed by Mibelle; Hyasol BT [INCI: Sodium Hyaluronate], Syn- Up™ [INCI: Benzylsulfonyl D-Seryl Homophenylalanine Amidinobenzamide Acetate] or Pentavitin® [INCI: Saccharide Isomerate] marketed by Pentapharm/DSM; Aqualance™ [INCI: Erythritol, Homarine HCI], Hydraprotectol™ [INCI: Glyceryl Polymethacrylate, Aleuritic Acid, Yeast Extract (Faex), Glycoprotein], Moist 24™ [INCI: Imperata Cylindrica Root Extract], Optim Hyal™ [INCI: Hydrolyzed Yeast Extract, Cetyl Hydroxyethylcellulose, Polyglucuronic Acid], Osmocide® 4 [INCI: Glycerin,

Aery lates/C 10-30 Alkyl Acrylate Crosspolymer] or Revidrate™ [INCI: Ethylhexyl

Palmitate, Sorbitan Oleate, Sorbitan Laureate, Myristyl Malate Phosphonic Acid] marketed by Sederma/Croda; Xpertmoist® molecular film [INCI: Glycerin,

Pseudoalteromonas Ferment Extract, Xanthan Gum, Proline, Alanine, Serine,

Ethylhexylglycerin, Caprylyl Glycol] or Actizyme GL advanced botanical ingredient [INCI: Glycerin, Mucor miehei extract, Aqua, Sodium Citrate, Potassium Sorbate, Sodium Benzoate, Phytic Acid] marketed by Lipotec/Lubrizol; and combinations thereof.

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

The DNA protecting agent, DNA repair agent, and/or stem cell protecting agent can be selected from the group consisting of; GP4G SP [INCI: Aqua, Glycerin, Aretmia Extract], Heliostatine [INCI: Aqua, Glycerin, Pisum Sativum Extract], Orsirtine [INCI: Aqua, Glycerin, Oryza Sativa Extract], Chronogen [INCI: Aqua, Butylene Glycol, Tetrapeptide (INCI proposed)], Survixyl IS [INCI: Water, Butylene Glycol, Pentapeptide-31] and Chrondricare [INCI: Aqua, Butylene Glycol Pentapeptide-28] marketed by Vincience/ISP/Ashland; Lanacityn® [INCI: Glycerin, Aqua, Alteromonas ferment extract, Chysanthellum indicum extract] or Melinoil [INCI: Isopropyl Palmitate, Lecithin, Aqua, Acetyl Hexapeptide-1] marketed by Atrium Innovations/Lucas Meyer Cosmetics; Repair Complex [INCI: Bifida Ferment Lysate] marketed by CLR; Phycojuvenine [INCI: Laminaria Digitata] marketed by Codif; Unirepair T-43 [INCI: Butylene Glycol, Acetyl Tyrosine, Proline, Hydrolyzed Vegetable Protein, Adenosine Triphosphate] marketed by Induchem; Dragosine [INCI: Carnosine] marketed by Symrise; DN-Age [INCI: Cassia Alata Leaf Extract] marketed by Laboratories Serobiologiques/Cognis/BASF; Helioguard [INCI: Porphyra Umbilicalis encapsulated into liposomes], PhytoCellTec Malus Domestica [INCI: PhytoCellTec Malus Domestica] or PhytoCellTec Argan [INCI: Argania Spinosa Sprout Cell Extraxt, Isomalt, Lecithin, Sodium Benzoate, Aqua] marketed by Mibelle Biochemistry; Pepha-Protect [INCI: Water Melon Extract] marketed by Pentapharm/DSM; Celligent [INCI: Helianthus Annuus Seed Oil, Ethyl Ferulate, Polyglyceryl-5 Trioleate, Rosmarinus Officinalis Leaf Extract, Aqua, Disodium Uridine Phosphate] or Defensil [INCI: Octyl Dodecanol, Echium Plantagineum Seed Oil, Cardiospermum Halicacabum Extract, Helianthus Annuus Seed Oil Unsaponifiables] marketed by Rahn; Venuceane [INCI: Thermus Thermophilus Ferment, Glycerin], UV- Soft [INCI: Yeast Extract], Renovage [INCI: Caprylic/Capric Triglyceride, Teprenone], Juvinity [INCI: Caprylic/Capric Triglyceride, Geranylgeranylpropanol (proposed)], Phytessence Holyherb [INCI: Butylene Glycol, Eriodictyon Californicum (Holyherb) Flower/Leaf/Stem Extract] or Resistem [INCI: Glycerin, Globularia Cordifolia Ferment] marketed by Sederma/Croda; Infraguard [INCI: Caesalpinia Spinosa Fruit Pod Extract, Propylene Glycol, Aqua, Helianthus Annuus Sprout Extract, Sodium Benzoate, Phenoxyethanol] marketed by Mibelle; Heliomoduline [INCI: Low molecular weight peptides from cottonseed] or Stem-C-Guard [Hydrolyzed Pea] marketed by Silab; and combinations thereof.

The reactive carbonyl species scavenger, free radical scavengers and/or anti-glycation agent, detoxifying agent, antioxidant and/or anti-pollution agent can be selected, for example and not restricted to, from the group formed by carnosine and its derivatives; GHK [INCI: Tripeptide-1] and its salts and/or derivatives or Quintescine IS [INCI: Dipeptide-4] marketed by Vincience/ISP/Ashland; Preregen [INCI: Glycine Soja (Soybean) Protein, Oxido Reductases], 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] marketed by Pentapharm/DSM; Preventhelia® [INCI: Diaminopropionoyl Tripeptide-33], Aldenine® [INCI: Hydrolized Wheat Protein, Hydrolized Soy Protein, Tripeptide 1], Lipochroman™ [INCI: Dimethylmethoxy Chromanol], Thermostressine® [INCI: Acetyl Tetrapeptide-22] Pollushield™ functional ingredient [INCI: Diisopropyl Adipate, Lecithin, Acrylic Acid/Acrylamidomethyl Propane Sulfonic Acid Copolymer, Dimethylmethoxy Chromanol, Xanthan Gum] or Bodyfensine® [INCI: Acetyl Dipeptide-3 Aminohexanoate] marketed by Lipotec/Lubrizol; unactyl [INCI: Mannitol, Pisum Sativum Extract, Histidine HCI, Arginine, Cyclodextrin, Dextrin, Yeast Extract, Acetyl Trysoine, Pyridoxine HCI, Khaya Senegalensis Bark Extract, Nicotinamide, Adenine Dinucleotide, Disodium Succinate, Aspartic Acid], Imidinyl [INCI: Tamarindus Indica Seed Polysaccharide], Phystrogene [INCI: Butylene Glycol, Malva Sylvestris (Mallow) Extract, Xanthan Gum] or Purisoft [INCI: Moringa Pterogysperma Seed Extract] marketed by Laboratoires Serobiologiques/Cognis/BASF; AquaCacteen [INCI: Glycerin, Opuntia Ficus Indica Stem Extract, Phenoxyethanol, Aqua], Trimoist (KMF) [INCI: Sodium Stearoyl Lactylate, Cetyl alcohol, Olus Vegetable oil, Tocopheryl acetate, Glycerin, Glycine soja sterol, Sodium lactate, Sodium barboxymethyl betaglucan, Carnosine, Lactic Acid], MelanoBronze [INCI: Vitex Agnus Castus Extract (Monk's pepper berries extract (phyto-endorphins)), Acetyl Tyrosine], CM-Glucan [INCI: Sodium Carobxymethyl Betaglucan, Phenoxyethanol, SunActin [INCI: Helianthus Annuus (Sunflower) Sprout Extract, Tocopherols, Glycerin, Lecithin, Phenoxyethanol, Aqua], GSP-T skin [INCI: Glycerin, Alcohol, Aqua, PEG-40 Hydrogenated Castor Oil, Vitis Vinifera (Grape) Seed Extract] or Detoxophane [INCI: Lepidium Sativum Sprout Extract, Lecithin, Phenoxyethanol, Glycerin, Water] marketed by Mibelle Biochemistry; Bacocalmine [INCI: PEG-8, Bacopa Monniera Extract, Water (Aqua), Hydroxyethylcellulose], Kombuchka [INCI: Saccharomyces/Xylinum Black Tea Ferment, Glycerin, Hydroxyethyl cellulose], Citystem [INCI: Glycerin, Marrubium Vulgare Extract] or Prodizia [INCI: Albizia Julibrissin Extract, Glycerin] marketed by Sederma/Croda; Extramel C [INCI: Hydroxypropyltrimonium Maltodextrin Crosspolymer, Cucumis Melo (Melon) Fruit Extract] marketed by Seppic; Defensine [INCI: Triticum Vulgare Germ Extract], Apolluskin® [INCI: Taraxacum officinale (Dandelion) Extract], Detoxyl® [INCI: Water, Butylene Glycol, Butyrospermum parkii (Shea Butter) Seedcake Extract] or Antiglyskin [INCI: Aqua, Helianthus Annuus Seed Extract] marketed by Silab; and combinations thereof. The compositions containing the compound of formula (I) and described herein may be for use in any of the applications or uses discussed above under the heading “Applications”.

The invention is illustrated by the following non-limiting examples.

EXAMPLES

General methods

Abbreviations

The abbreviations used for amino acids follow the 1983 IUPAC-IUB Joint Commission on Biochemical Nomenclature recommendations outlined in Eur. J. Biochem. (1984) 138:9-37.

(R), resin; 2-CITrt-(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, te/Y-butyloxycarbonyl; DCM, dichloromethane; DIEA, /V,/V-diisopropylethylamine; DIPCDI, /V,/V-diisopropylcarbodiimide; DMF, N,N- dimethylformamide; ESI-MS, electrospray ionization mass spectrometry; Fmoc, 9- flluorenylmethyloxycarbonyl; Gin, glutamine; Glu, glutamic acid; Gly, Glycine; His, histidine; HOBt, 1 -hydroxybenzotriazole; HPLC, high performance liquid chromatography; He, isoleucine; KOH, potassium hydroxide; Leu, leucine; Lys, lysine; MBHA, p-methylbenzhydrylamine; MeCN, acetonitrile; MeOH, methanol; Met, Methionine; Myr, myristoyl; Palm, palmitoyl; Pbf, 2, 2, 4,6,7- pentamethyldihydrobenzofuran-5-sulfonyl; Pro, proline; Ser, serine; tBu, te/Y-butyl; TFA, trifluoroacetic acid; Thr threonine; Trt, trithyl; Vai, valine.

Chemical Synthesis

All synthetic processes are carried out in polypropylene syringes fitted with porous polyethylene discs. The coupling protocol is carried out following the standard protocols founded in bibliography and the solvents and soluble reagents are removed by suction. The Fmoc group is removed with piperidine-DMF (2:8, v/v) (1 x 1 min, 1 x 5 min, 5 ml/g resin) [Lloyd-Williams P. etal. (1997) “Chemical Approaches to the Synthesis of Peptides and Proteins” CRC, Boca Raton (FL, USA)]. Washes between stages of deprotection, coupling and, again, deprotection, are carried out with DMF each time using 10 ml solvent/g resin (3 x 1 min after coupling, 5 x1 min after Fmoc removal). Coupling reactions are performed with 3 ml solvent/g resin. The control of the couplings is performed by carrying out the ninhydrin test [Kaiser E. et al., Anal. Biochem. (1970), 34: 595-598] or chloranil test [Christensen T., Acta Chem. Scand., (1979), 33B, 763-766], The coupling reactions are repeated as the desired peptide is synthesized. All synthetic reactions and washes are carried out at 25°C.

It is known by the skilled person that some amino acids are used with their functional groups in side chains protected. For instance, non-limiting examples of protecting groups are:

• tBu, te/Y-butyl for amino acid Thr

HPLC chromatographic analysis is carried out with Shimadzu equipment (Kyoto, Japan) using a reversed-phase column thermostatized at 30°C (50 x 4.6 mm, Kromasil C18, 3.5 pm, Akzo Nobel, Sweden). The elution is carried out using a gradient of acetonitrile (+0.07% TFA) in water (+0.1 % TFA) at a flow rate of 1 .6 mL/min and detection is carried out at 220 nm. The electrospray ionization mass spectrometry is carried out in a WATERS Alliance ZQ 2000 detector using a mixture of MeCN:H ₂ O 4:1 (+0.1 % TFA) as the mobile phase and a flow rate of 0.3 ml/min.

EXAMPLE 1

Obtaining Fmoc-W _m -X _n -AAi-AA ₂ -AA3.AA4-Y _o -Zp-PS-(R), wherein AAi is L-Leu; AA ₂ is L- Pro; AA ₃ is L-Val; AA ₄ is L-Thr and n, m, p and q are each 0.

Weights have been normalized. 1 equiv of Fmoc-L-Thr(tBu)-OH is dissolved in dry DCM and 0.8 equiv of DIEA added, prior to addition to 2-chlorotrityl resin. After 5 min, remaining 1 .7 equiv of DIEA are added and the mixture let stirred for additional 40 min. Capping of unreacted resin is achieved with methanol for 10 min. Resin is filtered and washed with DCM (3 x 1 min) and DMF (5 x 1 min).

Fmoc-Thr(tBu)-PS resin is treated with 5% piperidine in DCM/DMF 1 :1 for 10 min followed by 20% piperidine in DMF for 15 min in order to remove the Fmoc group. After washing of the resin as described in general methods, 2 equiv of Fmoc-L-Val-OH is incorporated onto the deprotected resin in the presence of 2.2 equiv of DIPCDI and 2 equiv of Oxyma using DMF as a solvent for 1 hour.

The resin is then washed as described in general methods and the deprotection treatment of the Fmoc group is repeated to couple the next amino acid: 2 equiv of Fmoc- L-Pro-OH; and subsequently 2 equiv of Fmoc-L-Leu-OH; are sequentially coupled in the presence of 2 equiv of Oxyma and 2.2 equiv of DIPCDI in each coupling step.

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

By following the described method it is possible to obtain different sequences changing the desired amino acids to be coupled.

EXAMPLE 2

General process for removal of Fmoc N-terminal protective group.

The N-terminal Fmoc group of the peptidyl resins obtained in Example 1 is deprotected as described in the general methods (20% piperidine in DMF, 1 x 1 min + 1 x 5 min). The peptidyl resins are washed with DMF (5 x 1 min), DCM (3 x 1 min), diethyl ether (3 x 1 min) and dried under vacuum.

EXAMPLE 3

Process for introducing the Ri palmitoyl group onto the peptidyl resins obtained in Example 2.

5 equiv of palmitic acid pre-dissolved in DMF (1 ml) is added respectively of each of the peptidyl resins obtained in Example 2, in the presence of Oxyma and DIPCDI. The mixture is allowed to react for 3 hours, after which the resin is washed with DMF (3 x 1 min), DCM (3 x 1 min), diethyl ether (3 x 1 min) and is dried under vacuum.

EXAMPLE 4

Process for introducing the Ri acetyl group onto the peptidyl resins obtained in Example 2

Each of the peptidyl resins obtained in Example 3 are treated with acetic anhydride in the presence of DIEA using DMF as a solvent. The mixture is allowed to react for 30 min, after which the resin is washed with DMF (3 x 1 min), DCM (3 x 1 min), diethyl ether (3 x 1 min) and is dried under vacuum.

EXAMPLE 5

Cleavage process from the polymeric support of the peptidyl resins obtained in Examples 2,3, and 4 .

Each of the dried peptidyl resins obtained in Examples 3, 4 and 5 are treated with 3 ml of TFA:H ₂ O (95:5, v/v) for 2 hours at room temperature under stirring. Then they are filtered through a polypropylene syringe fitted with porous polyethylene discs. The filtrate is collected onto cold diethyl ether, and washed 5 times with diethyl ether. The final precipitate is dried under vacuum.

HPLC analyses of the obtained peptides in gradients of MeCN (+0.07% TFA) in H ₂ O (+0.1 % TFA) show a purity exceeding 80% in all cases. The identity of the peptides obtained is confirmed by ESI-MS.

EXAMPLE 6

Musclebind like protein 1 (MBNL1) in Human skeletal muscle cells (hSKMC)

An increase of MBNL-1 in muscle cells helps maintaining the tone of facial skin muscles. Thus, compounds able to enhance MBNL-1 can be used as a good approach for cosmetic treatment of sagging facial appearance.

Methodology:

Cell culture and treatment

Human skeletal muscle cells (hSKMC) were cultured at 100,000 cells in T25 flasks with growth medium. After 4 days, cells reached around 80% of confluency and were seeded at 150,000 cells per well in 12-well plates in growth medium. Cells were incubated for 72 hours and then they were changed to differentiation medium and incubated during 48 hours. At the end of this period, cells were treated with defined peptides (0,5mg/ml) and with medium alone for control conditions during 48 hours in differentiation medium. Cells were also treated with 2mM of ketoprofen as a positive control.

Protein extraction and quantification

After the incubation period, cells were lysed and frozen at -80°C. For total protein quantification protein extract was measured by Bicinchoninic Acid (BCA) method. MBNL1 protein detection was performed by Homogeneous Time Resolved Fluorescence (HTRF) technology. Normalization of MBNL1 levels were performed by total protein quantification for each condition. Results are expressed as a relative MBNL1 protein level respect to control conditions. At least 3 replicates were carried out per condition.

Table 4 - MBNL1 expression in Human skeletal muscle cells (hSKMC)

EXAMPLE 7

Musclebind like protein 1 (MBNL1) in human dermal fibroblasts (HDF)

The aim of this study was to evaluate the increase of MBNL1 protein in human skin fibroblasts after electrical stimulation, mimicking a microcurrent-like treatment. Topical products able to increase MBNL1 protein amount in fibroblast cells, in a similar way to the microcurrent-like treatment, could induce the same antiaging benefits on the skin avoiding the side-effects of physical microcurrent treatment

Microcurrent stimulation assay:

Cells were seeded at 100.000 cells/well in 12-well plates over sterile glass slides and incubated at 37°C, 5% CO2 for 48 hours. After that, electrical stimulation was performed. Glass slides were transferred to 6-well plates and were electro-stimulated (1.5V) for 1 hour using a C-dish device (lonOptix) at room temperature. An identical 6-well plate with non-stimulated cells were incubated at room temperature for 1 hour. After electrostimulation, glass slides were transferred again to a 12-well plate and incubated at 37°C, 5% CO ₂ for 24 hours. Three different replicates were used for each condition.

Peptide treatment

Cells were seeded at 8.000 cells/well in 96-well plates and incubated at 37°C, 5%CO2 for 48 hours. After the incubation time, cells were treated with PEP-1 (H-Leu-Pro-Val- Thr-OH) at 0.01 mg/ml, 0.1 mg/ml and 0.5 mg/ml for 24 hours. Cells incubated with medium alone were used as a control. Three replicates were carried out for each condition.

MBNL1 immunofluorescence and quantification After 24 hours of incubation, cells were washed two times with phosphate buffered saline (PBS), fixed with 4% PFA (paraformaldehyde solution) for 15 minutes and washed again two times. After that, cells were permeabilized with 1 % X-Triton solution for 15 minutes and blocked with 5% bovine serum albumin (BSA) solution for 1 hour. Cells were incubated with 1/20 dilution of primary antibody against MBNL1 protein (Sigma) in 5% BSA solution for 2 hours. After the incubation time, cells were washed and incubated with 1/200 dilution of secondary antibody (AlexFluor 488) in 5% BSA solution for 1 hour. Finally, cells were washed 3 times and stained with 4',6-Diamidine-2'-phenylindole dihydrochloride (DAPI) mount solution for nuclei detection. MBNL1 protein quantification were measured as fluorescence intensity of MBNL1 normalized by the number of nuclei for each condition using a confocal microscope (Operetta® confocal microscope, PerkinElmer Inc) using Alexa 488 Green channel (Ex: 460-490nm/Em: 500-550nm). Results are expressed as an MBNL1 level that is relative to that of the control condition. At least, three independent experiments were analyzed in this assay.

Results were calculated using the following formula:

1 . Detection of MBNL1 protein after microcurrent stimulation

As shown Table 5, electrical stimulation (70 mV mm ^-1 ; <1 mA, 1.5V, 1 h) is able to increase MBNL1 protein compared to basal control (CTR; without MES) on human fibroblasts.

Table 5 - MBNL1 intensity in HDFa cells.

2. Detection of MBNL1 protein after peptide treatment As shown in Table 6, PEP-1 (H-Leu-Pro-Val-Thr-OH) increases MBNL1 protein compared with basal control (CTR; without MES) on human fibroblasts at tested conditions.Table 6 show that PEP-1 is able to induce MBNL1 protein expression at comparative levels to MES.

Table 6 - MBNL1 intensity in HDFa cells.

3. Comparative MBNL1 intensity in HDFa cells respect to electrical stimulation.

For comparative purposes, the effect of the peptide was compared with that of MES. The effect was calculated as follows:

% FI (peptide) — 100

Results are shown in Table 7. Table 7 - Comparative MBNL1 intensity in HDFa cells with respect to electrical stimulation. (mg/ml)

Control § - H 0.66 ± 4.10 i (Basal condition) The results show that PEP-1 has a significant effect on the levels of MBNL1 protein expression in fibroblast cells, similar to that of MES.

EXAMPLE 8

Effect of microcurrents and PEP-1 in collagen contraction assay

It is known that a remarkable change in the mechanical properties of the skin with aging is due to reduced contractile capacity as well as reduced migration activity of fibroblasts. Healthy fibroblasts induce contraction of the collagen network through physical interactions with collagen fibers. The collagen network is essential for maintaining the firmness of the skin. The collagen contraction assay is a well-known experimental approach to measuring the cell-induced contraction of the extracellular matrix. In this assay, the capacity of fibroblasts, embedded in a collagen-based gel, to reduce the gel diameter is evaluated.

By improving the contractile forces, the mechanical tension can be improved, which can be associated to “lifting” effect at the scale of fibroblasts.

Microcurrent system:

The microcurrent system was built by coupling gold electrodes (in order to avoid medium oxidation leading to cell death when current goes through) to opposite sides of 60 mm Petri dishes (separated by 4 cm). When a voltage is applied, an electric field generates between opposite positive and negative poles and current passes through the culture. During the stimulation time (2 hours), each of the 60 mm Petri dishes is connected to a voltage source that allows regulating the amount of current that passes through each of them. For these experiments, a 40 pA/petri current (which corresponds to aprox. 67 mV/mm) was used.

Preparation and expansion of cell culture:

Human dermal fibroblast (HDF) cell culture and expansion: Cells were thawed in T75 flasks and the growth medium was changed every 2 days of cell culture. After 7 days, cells were expanded to obtain a total amount of 7x10 ⁶ cells to be used in the experiments.

Peptide treatment and 3D collagen gel:

Once finished the expansion, cultures are trypsinized and seeded at 3x10 ⁵ cells 1 60 mm Petri up to a total of 10 dishes per replicate. These ten dishes correspond to one experiment (ControlZ-MES vs +MES) at a specific concentration. Peptide treatment was performed at 0.01 mg/ml.

After an overnight (OZN)incubation to allow cell attachment, each Petri dish is treated at the corresponding concentration with 4 ml of specific medium for a total of 24 hours in both conditions (without MES and with MES). Peptide treatment on the dishes that are not stimulated with microcurrent is initiated 2 hours in advance, and their passage into 3D cultures occurs at the same time as the microcurrent stimulation of the other dishes. In the case of the microcurrent-stimulated dishes, medium is replaced by 2.5 ml of fresh medium prior to stimulation giving to a total of 22 hours of treatment with peptides only, and 2 hours of treatment with peptides and electrostimulation.

Each 3D culture is prepared by mixing collagen solution with the culture medium corresponding to each of the conditions (without peptide or with peptide). This way, the complete peptide treatment duration comprises 48 hours: 24 hours of 2D stimulation and 24 hours of 3D stimulation. 3D cultures in collagen type I hydrogels require of the following elements: (i) the fabrication of a stock of neutralized rat tail collagen type I, and (ii) a cell suspension at a specific cell concentration. Plaques are located at 37°C for 45 minutes. After the incubation, cultures are separated and detached from the walls of the wells to allow contraction. Acellular controls are also separated. 0.5 ml of each warm medium is added on top of each well. Images of collagen gel diameter are taken of each well at 24 hours post detachment and analyzed by Imaged.

- Image quantification

Hydrogel contraction is considered as deformation experienced as surface area variation:

AArea (at

- An initial area is stablished. At t=O, all the hydrogels present the conformation delimited by the culture platform. In this case, a 24-well plate. Area t=0 gel 1 .86 cm ² (Area of a well in a 24-well plate)

- Quantification of Area at t=x; Ax. In this case, t=24 h

The image is introduced in Imaged.

The scale is configured based on the diameter of the well (d=1 .54 cm ² ). The diameter is simulated in imaged and configured at 1.54 units

The perimeter of the hydrogel is surrounded, and the area is calculated per image - The average between replicates of each condition is calculated.

- Area deformation is calculated based on formula in Aarea and data transformed to absolute %.

The results are shown below in Table 8.

Table 8

TABLE 5

¹ Stadistical calculations were performed with unpaired t-test: **p<0.01 ; ***p<0.001 ; ns: non-significant

The results show that PEP-1 promotes collagen contraction to a similar extent to MES.

EXAMPLE 9

Determination of myofibroblast marker EDA-Fn by immunofluorescence

EDA-Fn is an isoform of fibronectin, which serves as marker for the presence of myofibroblasts.

- Cell recovering and seeding

After the experimental protocol described in EXAMPLE 8, recovery of the cells was performed by the extraction of cells from the 3D culture and their reseeding on glass coverslips. To recover cells, the collagen hydrogel was digested in agitation at 37°C with a collagenase solution. After the digestion, cycles of centrifugation and washing were performed to eliminate collagen debris. Then, cells were seeded on coverslips in replicated as in the conditions of the 3D cultures of EXAMPLE 8. For future fluorescence analysis, cells were seeded on glass coverslips previously coated with collagen at a density of 3x10 ⁵ fibroblasts/cm ² , let attach overnight and fixed with 4% PFA.

- EDA-Fn Immunofluorescence

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

Calculations were performed for 4 replicates.

Table 9 - Fold induction of EDA-Fn as myofibroblast

TABLE 6

Stadistical calculations were performed with unpaired t-test: **p<0.01 , ****p<0.0001 .

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

EXAMPLE 10

Preparation of a light cream comprising 2 wt.% PEP-1 peptide solution

In a suitable vessel, weight the ingredients of phase A are weighted: water [INCI: WATER (AQUA)].

Next, phase A1 ingredients: Phenoxyethanol [INCI: PHENOXYETHANOL], Disodium EDTA [INCI: DISODIUM EDTA], Potassium sorbate [INCI: POTASSIUM SORBATE] and Zemea® [INCI: PROPANEDIOL], are added to phase A and mixed until homogeneous. Then phase B1 : Carbopol® Ultrez 21 polymer [INCI: ACRYLATES/C10-30 ALKYL ACRYLATE CROSSPOLYMER] is added to the previous mixture under stirring. Once dispersed, phase B2: Xanthan gum [INCI: XANTHAN GUM], is added to the previous mixture and mixed until homogeneous.

Phase C: Schercemol™ 1818 Ester [INCI: ISOSTEARYL ISOSTEARATE] is subsequently added to the vessel and mixed until completely incorporated in the mixture. Finally, Phase D: PEP-1 peptide solution [INCI: AQUA, CAPRYLYL GLYCOL & TETRAPEPTIDE-1 ] is added and mixed with moderate stirring until homogeneous. pH is adjusted to 6.0 - 6.5 with phase E ingredients: Sodium Hydroxide 20% w/w [INCI: WATER (AQUA); SODIUM HYDROXIDE])

Phase INGREDIENT (INCI name) % Weight

A WATER (AQUA) 83.50

A1 PHENOXYETHANOL 0.35

A1 DISSODIUM EDTA 0.20

A1 POTASSIUM SORBATE 0.10

A1 PROPANEDIOL 10.00

ACRYLATES/C 10-30 ALKYL ACRYLATE

B1 0.65

CROSSPOLYMER

B2 XANTHAN GUM 0.20

C ISOSTEARYL ISOSTEARATE 2.00

D [AQUA, CAPRYLYL GLYCOL & TETRAPEPTIDE-1] 2.00

E [WATER (AQUA), SODIUM HYDROXIDE] 1 .00

Table 10

Example 11

In vivo study for jawline firmness assessment in Caucasian volunteers. The study was carried out for 28 days. Forty-six (46) volunteers aged between 40 and 65 years old were included in the study and were divided into two groups. The first group included 36 volunteers (31 women and 5 men) which applied twice a day for 28 days the composition described in Example 5 on half face and placebo cream having the same ingredients except PEP-1 on the other half. The second group of 10 volunteers (9 women and 1 man) used a microcurrent device (Nuface®) with an activator gel without active ingredients once a day. 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 volunteers.

Subjects served as their own reference and results obtained at 28 days were compared with those obtained at initial time. Furthermore, results obtained with volunteers using the microcurrent device were compared with those obtained with the volunteers applying placebo and active cream.

The efficacy of the product was assessed by the RO parameter measured with Cutometer® (Courage & Khazaka) at initial time and after 28 days of product application. RO parameter is defined as the maximum amplitude after applying suction on the skin using a negative pressure. The higher the resistance of the skin to negative pressure, the firmer. For this reason, a decrease of RO parameter means an increase of skin firmness. RO measurements were acquired in two adjacent points in volunteer’s jawline obtaining a mean value for each timepoint of the test.

Jawline firmness was assessed by the mean variation of RO parameter. Results are shown in Table 11 .

Table 1 1 - RO mean variation of active and placebo creams after 28 days of product application. * p <0.05, Is p<0.1 calculated using paired t-student test. The results shown in Table 1 1 demonstrate that after 28 days of application of the composition of Example 5 there is a significant decrease in the RO parameter, the decrease being greater and more significant than that observed for placebo cream. According to the results, firmness improves after 28 days of product application and provides a similar variation to that achieved with the microcurrent device.

EXAMPLE 12

In vivo study for the assessment of the eyebrow lifting effect in Caucasian volunteers.

The study was carried out for 28 days. Forty-six (46) volunteers aged between 40 and 65 years old were included in the study and were divided into two groups. The first group included 36 volunteers (31 women and 5 men) which applied the composition described in Example 5 on half face and placebo (same composition without peptide) on the other half, twice a day for 28 days. The second group of 10 volunteers (9 women and 1 man) used a microcurrent device (Nuface®) with an activator gel without active ingredients once a day. 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.

Subjects served as their own reference and results obtained at 28 days were compared with those obtained at initial time. Furthermore, results obtained with volunteers using the microcurrent device were compared with those obtained with the volunteers applying placebo and active cream.

Volunteers’ facial images were acquired at initial time and after 28 days of product application. The efficacy of the product was assessed by the measurement of a diagonal distance between eyelashes and eyebrows obtained from image analysis with FrameScan® software. The diagonal distance was calculated by drawing a horizontal line between a point at the start of the eyelashes and a point at the end of eyelashes (the eyelashes’ line). Then, an additional line was drawn from the middle zone of the lips to the upper arch of the eyebrow diagonally, crossing it by the exact middle point of the eyelashes’ line previously drawn. The eyebrow lifting measurement corresponds to the distance from the middle point of the eyelashes’ line to the end of the eyebrow arch.

The eyebrow lifting effect was assessed by the mean variation of the diagonal distance as can be seen in the results shown in Table 12.

Table 12 - Diagonal distance mean variation of active and placebo creams after 28 days of product application and comparison versus microcurrent device.

The results shown in Table 12 demonstrate that after 28 days of application of the composition of Example 10 there is a significant increase in the diagonal distance respect to placebo cream and the same is observed with the microcurrent device. Furthermore, comparison of active cream versus placebo cream shows a significant effect. According to the results, eyebrow lifting increases after 28 days of product application obtaining a similar variation to that achieved with the microcurrent device.

EXAMPLE 13

In vivo study for the assessment of the antiwrinkle efficacy of the peptide of the invention in Caucasian volunteers.

The study was carried out for 7 days. Forty-five (45) volunteers aged between 40 and 65 years old were included in the study and were divided into two groups. The first group included 36 volunteers (31 women and 5 men) which applied the composition described in Example 10 on half face and placebo cream on the other half twice a day for 7 days. The second group of 9 volunteers (8 women and 1 man) used a microcurrent device (Nuface®) with an activator gel without active ingredients once a day. 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.

Subjects served as their own reference and results obtained at 7 days were compared with those obtained at initial time. Furthermore, results obtained with volunteers using the microcurrents device were compared with those obtained with the volunteers applying placebo and active cream. Volunteers’ images of crow feet area were acquired at initial time and 7 days of product application. The efficacy of the product was assessed by the coefficient of visibility obtained from image analysis with FrameScan® software. Coefficient of visibility is defined as the occupancy rate of the wrinkles multiplied by the contrast wrinkle/skin and finally multiplied by 100.

Antiwrinkle efficacy was assessed by the mean variation of coefficient of visibility which is used for evaluating wrinkle visibility. Results are shown in Table 13.

Table 13 - Coefficient of visibility mean variation of active and placebo creams after 7 days of product application and comparison versus placebo cream. * p <0.05, l.s. p<0.1 calculated using paired t-student test.

The results shown in Table 13 demonstrate that after 7 days of application of the composition of Example 10 there is a significant variation in the coefficient of visibility respect to placebo cream and the same is observed with the microcurrents device. Furthermore, comparison of active cream versus placebo cream shows a low significant effect. According to the results, wrinkle visibility decreases after 7 days of product application observing results that mimic the microcurrents device effect. EXAMPLE 14

Preparation of a Gel-cream comprising peptide PEP-1.

In a suitable vessel, the ingredients of phase A: water [INCI: WATER (AQUA)], Zemea™ [INCI: PROPANEDIOL], Phenoxetol® [INCI: PHENOXYETHANOL], Dissolvine® NA2 [INCI: DISODIUM EDTA] and Potassium Sorbate Granular [POTASSIUM SORBATE] are dispersed.

Phase A1 ingredient: Carbopol® Ultrez 21 Polymer [INCI: ACRYLATES/ C10/30 ALKYL ACRYLATE CROSSPOLYMER] is added to the previous mixture under stirring. Once dispersed, phase A2: Xanthan Gum [INCI: XANTHAN GUM] is introduced to the previous mixture and stirred until complete dispersion.

In a separate vessel, phase B ingredients: Schercemol™ 1818 Ester [INCI: ISOSTEARYL ISOSTEARATE], is weighed.

The emulsion is made by adding slowly phase B into phase A under conditions of fast stirring with a turbine.

Phase C: Peptide PEP-1 solution [INCI: WATER (AQUA); CAPRYLYL GLYCOL; Peptide PEP-1 is added to the previous mixture. pH is adjusted to 6.0 - 6.5 with phase D ingredient: Sodium Hydroxide 20% w/w [INCI: WATER (AQUA); SODIUM HYDROXIDE])

Phase INGREDIENT (INCI name) % weight

"A WATER 83.54

A PROPANEDIOL 10.00

A PHENOXYETHANOL 0.35

A DISODIUM EDTA 0.20

A POTASSIUM SORBATE 0.10

ACRYLATES/ C10/30 ALKYL ACRYLATE

A1 0.65

CROSSPOLYMER

A2 XANTHAN GUM 0.20

B ISOSTEARYL ISOSTEARATE 2.00 [WATER (AQUA); CAPRYLYL GLYCOL; PEPTIDE

C 2.00

PEP-1 ]

0.96

D [WATER (AQUA); SODIUM HYDROXIDE]

Table 14

A gel-cream comprising other peptides of the invention can be prepared by substituting PEP-1 for other peptides disclosed herein.

EXAMPLE 15

Preparation of a lotion comprising 2% of peptide PEP-1

In a suitable vessel, the ingredients of phase A1 : water [INCI: WATER (AQUA)], Zemea™ [INCI: PROPANEDIOL], glycerin [INCI: GLYCERIN], potassium sorbate [INCI: POTASSIUM SORBATE] and Dissolvine® NA2 [INCI: DISODIUM EDTA] are dissolved.

Phase A2 ingredient: Carbopol® Ultrez 30 Polymer [INCI: CARBOMER] is added in the previous mixture. Once dispersed, phase A3: xanthan gum [INCI: XANTHAN GUM] is introduced. Then the mixture is heated at 70-75°C.

In a separate vessel, phase B ingredients: Fancor® Meadowfoam seed oil [INCI: LIMNANTHES ALBA (MEADOWFOAM) SEED OIL], Kodasil 600 IDD Gel [INCI: ISODODECANE; VINYL DIMETHICONE/LAURYL DIMETHICONE CROSSPOLYMER; DIMETHICONE; LAURYL DIMETHICONE], Astro-sil 2C 350 [INCI: DIMETHICONE], Schercemol™ CATC ester [INCI: COCOYL ADIPIC ACID/TRIMETHYLOLPROPANE COPOLYMER; TRIMETHYLOLPROPANE], Schercemol™ DIS ester [INCI: DIISOPROPYL SEBACATE], Tocopheryl Acetate [INCI: TOCOPHERYL ACETATE] and Phenoxetol™ [INCI: PHENOXYETHANOL] are mixed and the resulting mixture is heated at 70-75°C.

The emulsion is made by adding slowly phase B into phase A under conditions of fast stirring with a turbine.

Once the mixture is cooled to 40°C, the components of phase C: Novemer™ EC-2 polymer [INCI: WATER (AQUA); SODIUM ACRYLATES/BEHENETH-25 METHACRYLATE CROSSPOLYMER; HYDROGENATED POLYDECENE, LAURYL GLUCOSIDE], SA-SB-300 (7%) [INCI: SILICA; DIMETHICONE], Fragrance [INCI: FRAGANCE (PARFUM)], and peptide PEP-1 solution [INCI: WATER (AQUA);

CAPRYLYL GLYCOL; peptide PEP-1) are added to the previous mixture. pH is adjusted to 6.0 - 6.5 with phase D ingredient sodium hydroxide 20% w/w [INCI: WATER (AQUA); SODIUM HYDROXIDE])

Phase INGREDIENT (INCI name) % weight

A1 WATER 63.60

A1 PROPANEDIOL 10.00

A1 GLYCERIN 5.00

A1 POTASSIUM SORBATE 0.10

A1 DISODIUM EDTA 0.20

A2 CARBOMER 0.30

A3 XANTHAN GUM 0.20

B LIMNANTHES ALBA (MEADOWFOAM) SEED OIL 5.00

[ISODODECANE; VINYL DIMETHICONE/LAURYL

B DIMETHICONE CROSSPOLYMER; DIMETHICONE; 3.00

LAURYL DIMETHICONE]

B DIMETHICONE 3.00

[COCOYL ADIPIC ACID/TRIMETHYLOLPROPANE

B 2.00

COPOLYMER; TRIMETHYLOLPROPANE]

B DIISOPROPYL SEBACATE 2.00

B TOCOPHERYL ACETATE 0.50

B PHENOXYETHANOL 0.50

[WATER (AQUA); SODIUM

ACRYLATES/BEHENETH-25 METHACRYLATE

C 1.50

CROSSPOLYMER; HYDROGENATED

POLYDECENE, LAURYL GLUCOSIDE]

C [SILICA; DIMETHICONE] 1.00

[WATER (AQUA); CAPRYLYL GLYCOL; Peptide

C 2.00

PEP-1]

C FRAGANCE (PARFUM) 0.10 q.s.

D [WATER (AQUA); SODIUM HYDROXIDE]

Table 15 A lotion comprising other peptides of the invention can be prepared by substituting PEP- 1 for other peptides disclosed herein.

EXAMPLE 16

Preparation of a fluid emulsion comprising 2% of peptide PEP-1

In a suitable vessel, the ingredients of phase A1 : water [INCI: WATER (AQUA)], Zemea™ [INCI: PROPANEDIOL], glycerin [INCI: GLYCERIN], Genencare™ OSMS BA [INCI: BETAINE], Dissolvine® NA2 [INCI: DISODIUM EDTA], potassium sorbate [INCI: POTASSIUM SORBATE] are dissolved.

Phase A2: Carbopol® ultrez 10 polymer [INCI: CARBOMER] is added to the previous mixture. Once dispersed, phase A3: Cola®Fax CPE-K [INCI: POTASSIUM CETYL PHOSPHATE] is added. The resulting mixture is heated at 70-75°C.

In another vessel, the components of phase B: Massocare® HD [INCI: ISOHEXADECANE], Lincol BAS [INCI: C12-15 ALKYL BENZOATE], Gandak C [INCI: CETYL ALCOHOL], Sorbital T 20 P [INCI: POLYSORBATE 20], 2-phenoxyethanol [INCI: PHENOXYETHANOL], Vegetable stearic acid 50/50 [INCI: STEARIC ACID; PALMITIC ACID] are mixed and heated at 70-75°C. Phase B is slowly introduced over phase A under conditions of intense stirring with a turbine.

The mixture is cooled at 40°C, and phase C: BRB CM 56-S [INCI: CYCLOMETHICONE], peptide PEP-1 solution [INCI: WATER (AQUA); CAPRYLYL GLYCOL; peptide PEP-1], Fragrance [INCI: FRAGRANCE (PARFUM)] is added. The pH is adjusted to 6.0-6.5 with the ingredient of phase D: Sodium Hydroxide 20% w/w [INCI: WATER (AQUA); SODIUM HYDROXIDE],

Phase INGREDIENT (INCI name) % weight

A1 WATER 71.2

A1 PROPANEDIOL 10

A1 GLYCERIN 3

A1 BETAINE 3

A1 DISODIUM EDTA 0.2

A1 POTASSIUM SORBATE 0.1

A2 CARBOMER 0.4 A3 POTASSIUM CETYL PHOSPHATE 0.4

B ISOHEXADECANE 2

B C12-15 ALKYL BENZOATE 2

B CETYL ALCOHOL 1.8

B POLYSORBATE 20 0.8

B PHENOXYETHANOL 0.5

B [STEARIC ACID; PALMITIC ACID] 0.5

C CYCLOMETHICONE 2

C [WATER (AQUA); CAPRYLYL GLYCOL; PEP-1] 2

C FRAGRANCE (PARFUM) 0.1

D [WATER (AQUA); SODIUM HYDROXIDE] q.s.

Table 16

A fluid emulsion comprising other peptides of the invention can be prepared by substituting PEP-1 for other peptides disclosed herein.

EXAMPLE 17

Effect of comparative peptides not encompassed by the present invention in collagen contraction. The capacity of different peptides (not according to the invention) to stimulate collagen contraction was conducted using the same procedure as in Example 8.

Table 17

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

EXAMPLE 18

In vivo study for the assessment of the eyebrow lifting effect for comparative peptide Ac- Asp-Val-Tyr-Lvs-NH2. A study was carried out for 28 days for determining the lifting effect of Ac-Asp-Val-Tyr- Lys-NH ₂ (not according to the invention). Forty-two (42) Caucasian female volunteers, aged between 35 and 58 years-old showing skin wrinkledness on the crow’s feet area are included. Subjects apply a cream comprising Ac-Asp-Val-Tyr-Lys-NH ₂ on one side of the face (left or right) and a placebo cream having the same composition except peptide. Both creams were applied for 28 days twice a day (morning and evening). The subjects served as their own reference and results obtained at time 28 days are compared with those obtained at initial time and between treatments. The eyebrow lifting effect was determined as disclosed in Example 12.

Table 18

The results are shown in Table 18 and demonstrate that peptide Ac-Asp-Val-Tyr-Lys- NH ₂ did not have a lifting effect.

Various aspects and embodiments of the present invention are defined by the following numbered clauses:

1 . A compound of formula (I)

Ri- W _m -Xn-AAi-AA2-AA3-AA ₄ -Yo-Zp-R ₂ (I), a stereoisomer and/or cosmetically acceptable salt thereof, wherein:

AAi is Leu, He or Vai;

AA ₂ is Pro, Ala or Gly;

AA ₃ is Vai, He or Leu;

AA ₄ is Thr, Vai or is no amino acid;

W, X, Y and Z are each independently any amino acid; m, n, p and q are each independently 0 or 1 ; m+n+p+q is less than or equal to 2; Ri is selected from the group consisting of H, a polymer derived from polyethylene glycol, a non-cyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, aralkyl and Rs- CO-, wherein Rs is selected from the group consisting of H, a non-cyclic aliphatic group, alicyclyl, aryl, aralkyl, heterocyclyl and heteroarylalkyl;

R ₂ is selected from the group consisting of -NR ₃ R ₄ , -OR ₃ , -SR ₃ , wherein R ₃ and R ₄ are independently selected from a group consisting of H, a polymer derived from polyethylene glycol, a non-cyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl and aralkyl; and

Ri and R ₂ are not amino acids.

2. A compound according to clause 1 , wherein AAi is Leu or Vai, and, preferably, AAi is Leu.

3. A compound according to clause 1 or claim 2, wherein AA ₂ is Pro.

4. A compound according to any one of the preceding clauses, wherein AA ₃ is Vai or Leu, and, preferably, AA ₃ is Vai.

5. A compound according to any one of the preceding clauses, wherein AA ₄ is Thr or Vai.

6. A compound according to any one of clauses 1 to 4, wherein AA ₄ is Thr or no amino acid.

7. A compound according to clause 6, wherein AA ₄ is no amino acid and AAi is Leu and/or AA ₂ is Pro and/or AA ₃ is Vai.

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

9. A compound according to any one of the preceding clauses wherein, when present, each of X W, X, Y and Z is independently selected from the group consisting of Ala, Vai and He.

10. A compound according to clause 9 wherein AA ₃ is Vai. 11 . A compound according to clause 1 , wherein the compound is:

Ri-Leu-Pro-Val-Thr-R2;

Ri-Leu-Ala-Val-Thr-R2;

Ri-Leu-Pro-lle-Thr-R ₂ ;

Ri-Val-Pro-Val-Thr-R ₂ ;

Ri-Leu-Gly-Val-Thr-R ₂ ;

Ri-Leu-Pro-Leu-Thr-R2;

Ri-Ala-Leu-Pro-Val-Thr-R ₂ ;

Ri-Leu-Pro-Val-R2; or

R1-lle-Pro-lle-Thr-R ₂ .

12. A compound according to any one of the preceding clauses, wherein Ri is selected from the group consisting of H and R ₅ -CO-, wherein R ₅ is selected from the group consisting of C1-C18 alkyl, C2-C24 alkenyl, C3-C24 cycloalkyl; and R ₂ is -NR3R4 or -OR ₃ wherein R3 and R4 are independently selected from the group consisting of H and C1-C16 alkyl.

13. A compound according to clause 1 , wherein the compound is: H-Leu-Pro-Val-Thr-OH;

H-Leu-Pro-Val-Thr-NH ₂ ;

Palm-Leu-Pro- Val-Thr-OH;

Ac-Leu-Pro-Val-Thr-OH;

Ac-Leu-Pro-Val-Thr-NH ₂ ;

H-Leu-Ala-Val-Thr-OH;

H-Leu-Pro-lle-Thr-OH;

H-Val-Pro-Val-Thr-OH;

H-Leu-Gly-Val-Thr-OH;

H-Leu-Pro-Leu-Thr-OH;

H-Ala-Leu-Pro-Val-Thr-OH;

H-Leu-Pro-Val-OH; or

H-lle-Pro-lle-Thr-OH.

14. A compound according to anyone of the preceding clauses, wherein the compound is not H-Lys-Leu-Pro-Val-Thr-OH or H-Leu-Pro-Val-Thr-Leu-Arg-OH. 15. A compound according to anyone of the preceding clauses, wherein the compound is not H-Leu-Pro-lle-Thr-OH, H-Leu-Pro-Leu-Thr-OH or H-Leu-Pro-Val-Thr-Gly- OH.

16. A composition comprising a cosmetically effective quantity of a compound of formula (I) according to any one of clauses 1 to 15, a stereoisomer and/or cosmetically acceptable salt thereof, and at least one cosmetically acceptable excipient or adjuvant.

17. Use of a compound according to any one of clauses 1 to 15, a stereoisomer and/or a cosmetically acceptable salt thereof, for the cosmetic, non-therapeutic treatment and/or care of the skin, hair, nails and/or mucous membranes.

18. The use according to clause 17, wherein the cosmetic, non-therapeutic treatment and/or care is: the treatment and/or prevention of skin aging; the reduction and/or prevention of skin wrinkles; the improvement or maintenance of skin firmness; the treatment and/or prevention of sagging appearance of the skin; and/or the lifting of the skin.

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