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

Abstract

To provide a compound of a formula (I), R1-Wm-Xn-AAi-AA2-AA3-AA4-AA5-AA6-Yp-Zq-Ra, a stereoisomer and / or cosmetically acceptable salt thereof; where AA1 is Asp, Gly, Asn, Gln, Ala, or no amino acid, AA2 is Val, Ile, Leu, or Ala, AA3 is Tyr, Phe, Trp, Lys, Arg, or His, AA4 is Lys, Arg, His, Pro, or Val, AA5 is Asn, Asp, Gln, or no amino acid, and AA6 is Thr, Ala, Ser, or no amino acid.SOLUTION: Compounds are useful for the treatment and / or prevention of the symptoms of skin aging and, in particular, for the treatment and / or prevention of skin wrinkles, the treatment and / or prevention of a sagging appearance of the skin, and / or the reduction and / or prevention of facial asymmetry.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to compounds useful for treating and / or caring for skin, hair, nails and / or mucous membranes.In particular, the compounds are useful for preventing skin aging, in particular for treating and / or preventing wrinkles in the skin, treating and / or preventing the appearance of sagging skin, and / or reducing and / or preventing facial asymmetry.The present invention extends to compositions comprising the compounds, and to treatment methods using the compounds. [Background technology]

[0002] The effects of aging play a major role in the appearance of skin. The most noticeable sign of facial aging is the appearance of facial wrinkles and sagging. With age, the epidermis and connective tissue of the skin weaken, facial muscles lose firmness, the epidermis begins to loosen and sag, the natural folds of skin in the cheek, neck, and chin areas change, and facial fat is redistributed and reduced.

[0003] In particular, loss of facial muscle firmness is associated with muscle aging, a well-known process that begins when humans reach around age 40 and accelerates in later years. The resulting loss of muscle mass (muscle tone) can give the face a loose, saggy appearance. There is loss of jawline definition and loss of facial definition.

[0004] Different methods have been proposed to improve facial muscle firmness. One of the most common methods to reduce facial sagging is the facelift. A facelift, also known as rhytidectomy, is a cosmetic surgery to reduce sagging skin or folds in the cheeks and jawline, as well as other changes in the shape of the face that accompany aging. During a facelift, flaps of skin on each side of the face are pulled back and the tissues underneath the skin are surgically remodeled to return the facial contours to a more youthful shape. Nevertheless, facelifts may be associated with different complications and risks. As with any other type of surgery, facelifts carry the risk of bleeding, infection, and adverse reactions to anesthesia. Some other risks include hematomas, scarring, nerve damage, hair loss, and skin loss, among others. Furthermore, the results of a facelift are not permanent. With age, the skin of the face may begin to sag again. In general, a facelift can be expected to last 10 years.

[0005] Not surprisingly, there is growing interest in alternative, non-invasive methods to reduce facial sagging. One of the most promising is electrical stimulation. Electronic muscle stimulation (EMS) has been used as an alternative intervention to improve muscle recovery, improving muscle structure and function in multiple biomedical fields. [Kern, H. et al "Electrical stimulation counteracts muscle decline in seniors", (2014), Frontiers in Aging Neuroscience, Vol 6 (189), pp. 11-11]. There are four main types of treatments, which differ in the type of electrical current used: Galvanic treatments, Neuromuscular Electrical Stimulation (NMES) (also known as Faradic treatments), Microcurrent Electrical Neuromuscular Stimulation (MENS), and Radiofrequency treatments.

[0006] MENS is distinguished by the use of very small currents (i.e., millionths of an ampere, e.g., 300-500 μA) that are barely perceptible but mimic the body's own bioelectric currents. MENS is therefore designed for cosmetic non-therapeutic cosmetic procedures to improve skin rejuvenation, not for medical use, but as an effective, non-invasive and inexpensive technique to combat the appearance of skin aging [Goldbert, A. et al. "Skin Rejuvenation with Non-Invasive Pulsed Electric Fields", (2015), Nature Scientific Reports, Vol 5(10187), pp.1-18; Seniee, F. et al. "Consider of Micro-Current's effect to "Facial Wrinkle Trend, Randomized Clinical Trial Study", (2012), Life Science Journal Vol 9(3), pp.1184-1189]. By stimulating skin cells in a specific way, wrinkles and sagging skin can be reduced.

[0007] At the cellular level, MENS is also known to stimulate the production of collagen and elastin. Collagen is the most abundant protein in the connective tissue of the skin, forming a mesh-like structure that helps support the growth of new cells while providing the necessary flexibility. One of the well-known characteristics of aging is sagging skin. Increasing collagen synthesis is thought to be beneficial in reducing the signs of aging. Collagen synthesis declines with age, reducing skin firmness and contributing to the appearance of wrinkles in older people [Varani, J. et al. "Decreased Collagen Production in Skin and Skin Tightness"]. 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. Thus, MENS may improve the firmness and tone of facial skin.

[0008] Nevertheless, there are some drawbacks to treatments using MENS. For example, the intensity level of the current may depend on the individual's skin thickness. In general, as health deteriorates or physical condition changes, the microcurrents flowing through the human body become weaker. Skin thickness depends on age or changes in external factors, leading to greater intra- and inter-individual variability. In some cases, poor electrical contact between the electrodes and the surface being treated can cause discomfort and pain for the user, and in extreme cases, skin irritation. Some MENS devices use electrodes and adhesive gels to improve conductivity, which is expensive and inconvenient, for example on the face, as there is no room to move once the electrodes are in place. Furthermore, some devices can be difficult to precisely follow the contours of the body surface being treated, which is problematic because stimulation needs to be able to address precise areas. For example, some devices require the use of a mirror in order to position the wand of the device on the appropriate part of the face and squeeze or stretch the skin. Finally, some potential users have negative preconceptions about MENS treatments, i.e., a prejudice against using electricity on the face, for example, as a daily cosmetic treatment.

[0009] There is a need to provide alternative methods for reducing or preventing signs of skin aging, for example, to improve skin tone and firmness and / or to reduce the appearance of sagging skin.There is a need to provide methods that overcome the problems associated with known methods such as facelift or MENS.There is a need to find new active compounds that can reduce or prevent signs of skin aging.In particular, there is a need to find new active compounds that can prevent or reduce the appearance of skin wrinkles and / or facial sagging. The present invention seeks to meet some or all of these needs and to solve some or all of the problems identified above. [Prior art documents] [Non-patent literature]

[0010] [Non-Patent Document 1] Kern, H. et al “Electrical stimulation counteracts muscle decline in seniors”, (2014), Frontiers in Aging Neuroscience, Vol 6(189), pp.11-11 [Non-Patent Document 2] Goldbert, A. et al. “Skin Rejuvenation with Non-Invasive Pulsed Electric Fields”, (2015), Nature Scientific Reports, Vol 5(10187), pp.1-18 [Non-Patent Document 3] Seniee, F. et al. "Consider of Micro-Current's effect to variation of Facial Wrinkle trend,Randomized Clinical Trial Study", (2012), Life Science Journal Vol 9(3), pp.1184-1189 [Non-Patent Document 4] 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 Summary of the Invention [Means for solving the problem]

[0011] In a first aspect, the present invention provides a compound represented by formula (I): R1-W m -X n -AA1-AA2-AA3-AA4-AA5-AA6-Y p -Z q -R2(I) and / or a cosmetically acceptable salt thereof, wherein AA1 is Asp, Glu, Asn, Gln, Ala, Gly, or no amino acid; AA2 is Val, Ile, Leu, or Ala; AA3 is Tyr, Phe, Trp, Lys, Arg, or His; AA4 is Lys, Arg, His, Pro, or Val; AA5 is Asn, Asp, Gln, or no amino acid; AA6 is Thr, Ala, Ser, or no amino acid. W, X, Y and Z are each independently any amino acid; m, n, p and q are each independently 0 or 1; m+n+p+q is less than or equal to 2, R1 is selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, aralkyl, and R5-CO-, where R5 is selected from the group consisting of H, an acyclic aliphatic group, alicyclyl, aryl, aralkyl, heterocyclyl, and heteroarylalkyl, R2 is selected from the group consisting of -NR3R4, -OR3, -SR3, where R3 and R4 are independently selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, and aralkyl; R1 and R2 are not amino acids.

[0012] In particular, the present invention provides compounds represented by formula (I), where when AA5 is Asn, Asp, or Gln, AA1 is Ala, Gly, or no amino acid, AA2 is Val, Ile, or Leu, AA3 is Lys, Arg, or His, AA4 is Pro or Val, and AA6 is Thr, Ala, Ser, or no amino acid, with the proviso that AA1 is different from AA6. Optionally, or in addition, the present invention provides compounds represented by formula (I), where when AA5 is no amino acid, AA1 is Asp, Glu, Asn, or Gln, AA2 is Val, Ile, Leu, or Ala, AA3 is Tyr, Phe, or Trp, AA4 is Lys, Arg, or His, and AA6 is no amino acid.

[0013] The compounds of the present invention have been found to be effective in upregulating the expression of muscle blind-like 1 (MBNL1). MBNL1 is a highly conserved RNA-binding protein, which plays a key role in the process of muscle differentiation and maintenance. Increased MBNL1 protein in fibroblasts activates the process of transdifferentiation into myofibroblasts, a cell type that can release large amounts of extracellular matrix proteins such as collagen, elastin, and fibronectin. This increase in myofibroblasts leads to increased collagen in the skin, resulting in a firming effect on the skin. Thus, the compounds of the present invention are useful in reducing and / or preventing problems associated with the loss of muscle mass (muscle tone) due to muscle aging, such as the appearance of facial sagging. Furthermore, the compounds of the present invention can be used in cosmetic procedures that exert a skin lifting effect through a chemical mechanism, similar to the effect of physical procedures such as electrical stimulation microcurrent, but without the inconvenience of the latter. Furthermore, the compounds of the present invention have been found to be effective in inhibiting noradrenaline release in the skin and increasing the amount of lipids in adipocytes. These further indicate their usefulness as skin anti-aging agents.

[0014] In another aspect, the present invention provides a cosmetic composition comprising a compound of formula (I), its stereoisomers and / or its cosmetically acceptable salts, together with at least one cosmetically acceptable excipient or adjuvant.

[0015] In another aspect, the present invention provides the use of a compound of formula (I), its stereoisomers and / or its cosmetically acceptable salts, or the use of a composition comprising a compound of formula (I), its stereoisomers and / or its cosmetically acceptable salts, for the treatment and / or care of skin, hair, nails and / or mucous membranes. The present invention provides the use of a compound of formula (I), its stereoisomers and / or its cosmetically acceptable salts, or the use of a cosmetic composition comprising a compound of formula (I), its stereoisomers and / or its cosmetically acceptable salts, for the cosmetic non-therapeutic treatment and / or care of skin, hair, nails and / or mucous membranes. The cosmetic non-therapeutic treatment and / or care may be the prevention or treatment of symptoms of skin aging, the treatment and / or prevention of skin wrinkles, the stimulation of collagen synthesis and / or the prevention of collagen loss, the improvement or maintenance of skin firmness, the treatment and / or prevention of the appearance of sagging skin, the treatment or prevention of facial asymmetries, the increase in volume of adipose tissue, and / or the prevention and / or reduction of the effects of adipose tissue loss.

[0016] In another aspect, the present invention provides a method for treating and / or caring for the skin, hair, nails and / or mucous membranes of a subject, comprising administering to the subject an effective amount of a compound of formula (I), its stereoisomer and / or its cosmetically or pharma- ceutically acceptable salt, or a composition comprising them. In particular, the present invention provides a method for cosmetic non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes of a subject, comprising administering to the subject a cosmetically effective amount of a compound of formula (I), its stereoisomer and / or its cosmetically acceptable salt, or a cosmetic composition comprising them. Typically, the compound is administered topically. The cosmetic non-therapeutic treatment and / or care can be the prevention or treatment of symptoms of skin aging, the treatment and / or prevention of skin wrinkles, the stimulation of collagen synthesis and / or the prevention of collagen loss, the improvement or maintenance of skin firmness, the treatment and / or prevention of the appearance of sagging skin, and / or the treatment or prevention of facial asymmetry, the increase in volume of adipose tissue, and / or the prevention and / or reduction of the effects of adipose tissue loss.

[0017] In another aspect, the present invention provides a kit for use in the cosmetic non-therapeutic treatment and / or care of the skin, comprising: (i) a composition comprising a botulinum toxin; (ii) optionally a composition comprising Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2; and (iii) a cosmetic composition comprising a compound of formula (I). In an embodiment of the present invention, for example, the following items are provided: (Item 1) A compound of formula (I), R1-W m -X n -AA1-AA2-AA3-AA4-AA5-AA6-Y p -Z q -R2(I) Stereoisomers and / or cosmetically acceptable salts thereof, wherein AA1 is Asp, Glu, Asn, Gln, Ala, Gly, or no amino acid; AA2 is Val, Ile, Leu, or Ala; AA3 is Tyr, Phe, Trp, Lys, Arg, or His; AA4 is Lys, Arg, His, Pro, or Val; AA5 is Asn, Asp, Gln, or no amino acid; AA6 is Thr, Ala, Ser, or no amino acid; W, X, Y and Z are each independently any amino acid; m, n, p and q are each independently 0 or 1; m+n+p+q is less than or equal to 2, R1 is selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, aralkyl, and R5-CO-, where R5 is selected from the group consisting of H, an acyclic aliphatic group, alicyclyl, aryl, aralkyl, heterocyclyl, and heteroarylalkyl; R2 is selected from the group consisting of -NR3R4, -OR3, -SR3, and R3 and R4 are independently selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, and aralkyl; The compound, its stereoisomers and / or cosmetically acceptable salts, wherein R1 and R2 are not amino acids. (Item 2) if AA5 is no amino acid, then AA1 is Asp, Glu, Asn, or Gln, AA2 is Val, Ile, Leu, or Ala, AA3 is Tyr, Phe, or Trp, AA4 is Lys, Arg, or His, and AA6 is no amino acid; and / or 2. The compound according to item 1, wherein if AA5 is Asn, Asp, or Gln, then AA1 is Ala, Gly, or no amino acid, AA2 is Val, Ile, or Leu, AA3 is Lys, Arg, or His, AA4 is Pro or Val, and AA6 is Thr, Ala, Ser, or no amino acid, and AA1 is different from AA6. (Item 3) 3. The compound according to item 2, wherein AA1 is Asp, Glu, Asn, or Gln, AA2 is Val, Ile, Leu, or Ala, AA3 is Tyr, Phe, or Trp, AA4 is Lys, Arg, or His, AA5 is no amino acid, and AA6 is no amino acid. (Item 4) The compound according to item 3, wherein (i) AA1 is Asp, Glu, or Asn, or (ii) AA1 is Asp or Glu. (Item 5) The compound according to item 3 or 4, wherein AA2 is Val or Ile. (Item 6) The compound according to any one of items 3 to 5, wherein AA3 is Tyr or Phe. (Item 7) 7. The compound according to any one of items 3 to 6, wherein AA4 is Lys or Arg. (Item 8) The compound according to any one of items 3 to 7, wherein AA1 is Asp, AA2 is Val, AA3 is Tyr, and AA4 is Lys. (Item 9) The compound according to item 2, wherein AA1 is Ala, Gly, or no amino acid, AA2 is Val, Ile, or Leu, AA3 is Lys, Arg, or His, AA4 is Pro or Val, AA5 is Asn, Asp, or Gln, and AA6 is Thr, Ala, Ser, or no amino acid, and AA1 is different from AA6. (Item 10) 10. The compound according to item 9, wherein AA1 is Ala or Gly. (Item 11) The compound according to item 9 or 10, wherein AA2 is Leu or Ile. (Item 12) The compound according to any one of items 9 to 11, wherein AA3 is Lys or Arg. (Item 13) The compound according to any one of items 9 to 12, wherein AA5 is Asn or Asp. (Item 14) 14. The compound according to any one of items 9 to 13, wherein (i) AA6 is Thr, Ala, or Ser, or (ii) AA6 is Thr or Ala. (Item 15) The compound according to any one of items 9 to 14, wherein AA1 is Ala, AA2 is Leu, AA3 is Lys, AA4 is Pro, AA5 is Asn, and AA6 is Thr. (Item 16) The compound according to any one of items 1 to 15, wherein m+n+p+q is 0 or 1. (Item 17) The compound according to any one of items 2 to 15, wherein m+n+p+q is 0 or 1. (Item 18) The compound is R1-Asp-Val-Tyr-Lys-R2, R1-Glu-Val-Tyr-Lys-R2, R1-Asp-Ile-Tyr-Lys-R2, R1-Asp-Ile-Phe-Lys-R2, R1-Asp-Val-Tyr-Arg-R2, R1-Asn-Val-Tyr-Lys-R2, R1-Asp-Leu-Tyr-Lys-R2, R1-Ala-Asp-Val-Tyr-Lys-R2, R1-Asp-Val-Tyr-Lys-Ala-R2, R1-Glu-Ile-Tyr-Lys-R2, R1-Glu-Ile-Tyr-Arg-R2, R1-Glu-Ile-Phe-Arg-R2, R1-Ala-Leu-Arg-Pro-Asn-Thr-R2, R1-Ala-Leu-Lys-Val-Asn-Thr-R2, R1-Leu-Lys-Pro-Asn-Thr-R2, R1-Ala-Leu-Lys-Pro-Asn-R2, R1-Gly-Ile-Lys-Pro-Asn-Thr-R2, R1-Ala-Ile-Arg-Pro-Asn-Thr-R2, R1-Gly-Val-Arg-Pro-Asn-Thr-R2, or The compound according to item 1, wherein R1-Ala-Leu-Lys-Pro-Gln-Thr-R2. (Item 19) R1 is H and R5-CO- (wherein R5 is C1-C 18 Alkyl, C2-C 24 Alkenyl, C3-C 24cycloalkyl; R2 is selected from the group consisting of -NR3R4 or -OR3 (wherein R3 and R4 are independently selected from H and C1-C 16 19. The compound according to any one of items 1 to 18, wherein the aryl group is selected from the group consisting of alkyl. (Item 20) The compound is Ac-W m -X n -Asp-Val-Tyr-Lys-Y p -Z q -NH2(IV), HW m -X n -Ala-Leu-Lys-Pro-Asn-Thr-Y p -Z q -NH2(V), Ac-Asp-Val-Tyr-Lys-NH2 (PEP1), or The compound according to item 1, which is H-Ala-Leu-Lys-Pro-Asn-Thr-NH2 (PEP2). (Item 21) The compound is Palm-Asp-Val-Tyr-Lys-NH2(PEP3), Ac-Asp-Val-Tyr-Lys-OH(PEP4), H-Asp-Val-Tyr-Lys-NH2(PEP5), Ac-Glu-Val-Tyr-Lys-NH2(PEP7), Ac-Asp-Ile-Tyr-Lys-NH2(PEP8), Ac-Asp-Val-Phe-Lys-NH2(PEP9), Ac-Asp-Val-Tyr-Arg-NH2(PEP10), Ac-Asn-Val-Tyr-Lys-NH2(PEP11), Ac-Asp-Leu-Tyr-Lys-NH2(PEP12), Palm-Glu-Val-Tyr-Lys-NH2(PEP13), Ac-Ala-Asp-Val-Tyr-Lys-NH2(PEP14), Ac-Asp-Val-Tyr-Lys-Ala-NH2(PEP15), Ac-Glu-Ile-Tyr-Lys-NH2(PEP20), Ac-Glu-Ile-Tyr-Arg-NH2(PEP23), Ac-Glu-Ile-Phe-Arg-NH2(PEP24), Ac-Ala-Leu-Lys-Pro-Asn-Thr-OH(PEP27), H-Ala-Leu-Arg-Pro-Asn-Thr-NH2(PEP30), H-Ala-Leu-Lys-Val-Asn-Thr-NH2(PEP31), H-Leu-Lys-Pro-Asn-Thr-NH2(PEP40), H-Ala-Leu-Lys-Pro-Asn-NH2(PEP41), H-Gly-Ile-Lys-Pro-Asn-Thr-NH2(PEP42), H-Ala-Ile-Arg-Pro-Asn-Thr-NH2(PEP44), H-Gly-Val-Arg-Pro-Asn-Thr-NH2 (PEP46), or 2. The compound according to item 1, which is H-Ala-Leu-Lys-Pro-Gln-Thr-NH2 (PEP50). (Item 22) 22. A combination of a compound according to any one of items 1 to 21, or a stereoisomer and / or a cosmetically acceptable salt thereof, with a botulinum toxin and / or a peptide of the sequence Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2. (Item 23) A composition comprising a cosmetically effective amount of a compound of formula (I) according to any one of items 1 to 21, a stereoisomer thereof and / or a cosmetically acceptable salt thereof, or a combination according to item 22, and at least one cosmetically acceptable excipient or adjuvant. (Item 24) 22. Use of a compound according to any one of items 1 to 21, its stereoisomers and / or cosmetically acceptable salts for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes. (Item 25) Use according to item 24, wherein said cosmetic non-therapeutic treatment and / or care is treatment and / or prevention of skin aging, reduction and / or prevention of skin wrinkles, stimulation of collagen synthesis and / or prevention of collagen loss, improvement or maintenance of skin firmness, treatment and / or prevention of the appearance of sagging skin, reduction and / or prevention of facial asymmetries, increase in the volume of adipose tissue, prevention and / or alleviation of adipose tissue loss and / or reduction of skin roughness and / or improvement of skin smoothness. (Item 26) A method for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes of a subject, comprising administering to said subject a cosmetically effective amount of a compound according to any one of items 1 to 21, 24. A method comprising administering to the subject a combination according to item 22 or a composition according to item 23. (Item 27) The method according to item 26, wherein said non-therapeutic cosmetic treatment and / or care is treatment and / or prevention of skin aging, reduction and / or prevention of skin wrinkles, stimulation of collagen synthesis and / or prevention of collagen loss, improvement or maintenance of skin firmness, treatment and / or prevention of the appearance of sagging skin, reduction and / or prevention of facial asymmetry and / or increase in adipose tissue volume, prevention and / or reduction of adipose tissue loss and / or reduction of skin roughness and / or improvement of skin smoothness. [Brief description of the drawings]

[0018] [Figure 1]Figure 1 shows the percentage of MBNL1 protein present in human skeletal muscle cells (based on the total protein content of human skeletal muscle cells) measured using time-resolved fluorescence energy transfer assay.Measurements are performed on samples of human skeletal muscle cells treated with compounds of the present invention and on control samples of human skeletal muscle cells not treated with compounds of the present invention (Example 7).Abbreviations: BC=basal control. [Diagram 2] 1 shows the level of MBNL1 protein present in human dermal fibroblasts, measured using an immunofluorescence assay. Measurements are performed on samples of human dermal fibroblasts treated with the compounds of the present invention, and on control samples of human dermal fibroblasts not treated with the compounds of the present invention (Example 8). Abbreviations: BC=basal control. [Diagram 3] Figure 1 shows the level of muscle mass loss in human skeletal muscle cells measured using an immunofluorescence assay. Measurements are performed on samples of human skeletal muscle cells treated with a compound of the invention and on control samples of human skeletal muscle cells not treated with a compound of the invention (Example 9). Abbreviations: BC = basal control. [Figure 4] Figure 1 shows the percentage of muscle mass loss in human skeletal muscle cells measured using an immunofluorescence assay. Measurements are performed on samples of human skeletal muscle cells treated with tumor necrosis factor alpha (TNFα) and either (i) treated with a compound of the invention or (ii) not treated with a compound of the invention. Results are also compared to human skeletal muscle cells not treated with TNFα or a compound of the invention (Example 10). Abbreviations: BC+TNF=basal control with 20 mg / ml TNFα, BC=basal control. [Diagram 5] Figure 11 shows the level of collagen type I on human dermal fibroblasts as determined by alpha-ELISA assay (Example 11). Measurements are performed on samples of human dermal fibroblasts treated with compounds of the invention and on basal control samples not treated with compounds of the invention. Abbreviations: COL% = percentage of collagen type I, BC = basal control. [Figure 6]Figure 1 shows the noradrenaline release level of human neuroblastoma cell line SS determined using immunofluorescence assay.Measurements are performed on human neuroblastoma cell line treated with the compound of the present invention and on samples of basal control not treated with the compound of the present invention (Example 12).Abbreviations: NA=noradrenaline, BC=basal control. [Figure 7] Figure 1 shows the level of lipid accumulation in human subcutaneous preadipocytes as determined by fluorescent staining. Measurements were performed on samples of co-cultures of young and old preadipocytes treated or not with compounds of the invention. Results are also compared with cultures of old preadipocytes. Abbreviations: LA% = percentage of lipid accumulation, CC = co-culture control, YC = young control, OC = old control. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] definition In the context of the present invention, "skin" is understood to mean the multiple layers that compose it, from the top layer or stratum corneum to the bottom layer or subcutaneous tissue, including both the top layer or stratum corneum and the bottom layer or subcutaneous tissue. These layers are composed of different types of cells, such as keratinocytes, fibroblasts, melanocytes, mast cells, neurons and / or adipocytes, among others. The term "skin" also includes the scalp. The term "skin" includes mammalian skin, including human skin. Similarly, the term "hair, nails and mucous membranes" includes mammalian, e.g. human, hair, nails and mucous membranes.

[0020] As used herein, the term "treatment" without the proviso "cosmetic non-therapeutic" refers to therapeutic methods including methods directed to administering a compound according to the present invention to reduce or eliminate a disease or disorder, or to reduce or eliminate one or more symptoms associated with a disease or disorder. The term "treatment" without the proviso "cosmetic non-therapeutic" also encompasses therapeutic methods aimed at reducing or eliminating the physiological consequences of a disease or disorder.

[0021] When the terms "treatment" and "care" are accompanied by the proviso "cosmetic non-therapeutic", it means that the treatment or care is aimed at improving or maintaining the aesthetic appearance of the skin, hair, nails and / or mucous membranes. In particular, the treatment has the objective of improving the cosmetic properties of the skin, hair, nails and / or mucous membranes, such as but not limited to the level of moisture, elasticity, firmness, luster, color 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 the properties of the skin, hair, nails and / or mucous membranes, which properties will be improved or maintained by cosmetic treatment and / or care of the skin, hair, nails and / or mucous membranes, both in healthy subjects and in subjects exhibiting diseases and / or disorders of the skin, hair, nails and / or mucous membranes.

[0022] The term "prevention" as used in the present invention refers to the ability of the compounds of the present invention to prevent, delay, or hinder the appearance or development of a disease or disorder, or to prevent, delay, or hinder the change in the cosmetic properties of the skin, mucous membrane, and / or hair. The term "prevention" as used in the present invention is interchangeable with the term "inhibition", i.e., refers to the ability of the compounds of the present invention to inhibit the appearance or development of a disease or disorder, or to inhibit the change in the cosmetic properties of the skin, hair, nails, and / or mucous membrane.

[0023] In the context of the present invention, the term "aging" refers to the changes that the skin undergoes as a result of the intrinsic aging process (i.e. chronoaging) or as a result of the extrinsic skin aging process induced by environmental factors (i.e. exposure to the sun (photoaging) or environmental factors such as cigarette smoke, extreme weather conditions such as cold or wind, chemical pollutants or pollutants). In the context of the present invention, ageing includes all externally and / or tactilely perceptible changes such as, for example but not limited to, the development of discontinuities on the skin such as wrinkles, fine lines, expression lines, stretch marks, deep wrinkles, unevenness or roughness, an increase in pore size, decreased moisture, decreased elasticity, decreased firmness, decreased smoothness, decreased ability to recover from deformations, decreased resilience, sagging skin such as sagging cheeks, the appearance of dark circles, among others, or the appearance of a double chin, changes in skin color such as age spots, redness, dark circles, or the appearance of hyperpigmented areas such as age spots or freckles, among others, abnormal differentiation, hyperkeratinization, elastosis, keratosis, hair loss, orange peel skin, decreased collagen structure, and other histological changes in the stratum corneum, dermis, epidermis, vasculature (e.g. the appearance of spider veins or telangiectasias), or in tissues close to the skin, among others. The term "photoaging" refers to a collection of processes resulting from prolonged exposure of the skin to ultraviolet light that results in premature aging of the skin, which exhibits the same physical characteristics as aging, including, but not limited to, laxity, sagging, changes in color or irregular pigmentation, and abnormal and / or excessive keratinization. The sum of various environmental factors, such as exposure to tobacco smoke, exposure to pollution, and climatic conditions, such as cold and / or wind, also contribute to skin aging.

[0024] In this specification, the abbreviations used for amino acids follow the rules of the IUPAC-IUB Commission on Biochemical Nomenclature, as set forth in Eur.J.Biochem.,(1984),138,9-37. Thus, for example, Gly represents NH2-CH2-COOH, Gly- represents NH2-CH2-CO-, -Gly represents -NH-CH2-COOH, and -Gly- represents -NH-CH2-CO-. Thus, when the hyphen representing the peptide bond is located on the right side of the symbol, it eliminates the OH (here represented in the conventional non-ionized form) in the 1-carboxyl group of the amino acid, and when it is located on the left side of the symbol, it eliminates the H in the 2-amino group of the amino acid, and both modifications can be applied to the same symbol (see Table 1). [Table 1]

[0025] As used herein, the term "acyclic aliphatic group" includes linear (i.e., straight and unbranched) or branched, saturated or unsaturated hydrocarbyl groups such as alkyl, alkenyl, and alkynyl. Acyclic aliphatic groups can be substituted (mono- or poly) or unsubstituted.

[0026] As used herein, the term "alkyl" includes both saturated, straight and branched chain alkyl groups, and the groups may be substituted (mono or poly) or unsubstituted. The alkyl group is attached to the remainder of the molecule by a single bond. The alkyl group has 1 to 24, preferably 1 to 16, more preferably 1 to 14, even more preferably 1 to 12, and even more preferably 1, 2, 3, 4, 5, or 6 carbon atoms. The term "alkyl" includes, for example, methyl, ethyl, isopropyl, isobutyl, tert-butyl, 2-methylbutyl, heptyl, 5-methylhexyl, 2-ethylhexyl, octyl, decyl, dodecyl, lauryl, hexadecyl, octadecyl, and amyl.

[0027] As used herein, the term "alkenyl" refers to a group containing one or more carbon-carbon double bonds, which may be linear or branched, substituted (mono- or poly) or unsubstituted. Preferably, an alkenyl has one, two, or three carbon-carbon double bonds. When more than one carbon-carbon double bond is present, the double bonds may be conjugated or unconjugated. Preferably, an alkenyl group has 2-24, preferably 2-16, more preferably 2-14, even more preferably 2-12, even more preferably 2, 3, 4, 5, or 6 carbon atoms. An alkenyl group is attached to the remainder of the molecule by a single bond. The term "alkenyl" includes, for example, vinyl (-CH2=CH2), allyl (-CH2-CH=CH2), prenyl, oleyl, linoleyl groups, and the like.

[0028] The term "alkynyl" refers to a group containing one or more carbon-carbon triple bonds, which may be linear or branched, substituted (mono- or poly) or unsubstituted. Preferably, an alkynyl group has one, two or three carbon-carbon triple bonds. The double bonds may be conjugated or unconjugated. An alkynyl group has 2-24, preferably 2-16, more preferably 2-14, even more preferably 2-12, and even more preferably 2, 3, 4, 5 or 6 carbon atoms. An alkynyl group is attached to the remainder of the molecule by a single bond. The term "alkynyl" includes, for example, but is not limited to, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, pentynyl, such as 1-pentynyl, and the like. Alkynyl groups can also contain one or more carbon-carbon double bonds and include, but are not limited to, for example, but-1-en-3-ynyl and pent-4-en-1-ynyl groups, and the like.

[0029] The term "alicyclyl" is used herein to include aliphatic cyclic (alicyclic) groups, such as, for example, but not limited to, cycloalkyl or cycloalkenyl or cycloalkynyl groups. The term "alicyclyl" refers to a monoradical containing one or more carbon atom rings, which may be saturated (e.g., cyclohexyl) or unsaturated (e.g., cyclohexenyl), provided that they are not aromatic. More specifically, an alicyclyl group contains 3 or more, 3-24, 3-12, or 6-12 ring carbon atoms. An alicyclic group may be a monocyclic, bicyclic, or tricyclic ring system, and the rings may be fused or linked by a linking group, such as, for example, a single bond or a methylene group or other alkylene group. An alicyclic group may be substituted (mono- or poly) or unsubstituted. In one embodiment, an alicyclyl group is a 6-12 membered ring system consisting of carbon atoms and optionally containing one or two double bonds.

[0030] The term "cycloalkyl" refers to a saturated monocyclic or polycyclic alkyl group that may be substituted (mono- or poly) or unsubstituted. Cycloalkyl groups have 3 to 24, preferably 3 to 16, more preferably 3 to 14, even more preferably 3 to 12, and even more preferably 3, 4, 5, or 6 carbon atoms. Cycloalkyl groups are attached to the remainder of the molecule by a single bond. Cycloalkyl groups include, but are not limited to, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, methylcyclohexyl, dimethylcyclohexyl, octahydroindene, decahydronaphthalene, dodecahydrophenalene, and similar groups.

[0031] The term "cycloalkenyl" refers to a non-aromatic monocyclic or polycyclic alkenyl group that may be substituted (mono- or poly) or unsubstituted. Cycloalkenyl groups have 5 to 24, preferably 5 to 16, more preferably 5 to 14, even more preferably 5 to 12, and even more preferably 5 or 6 carbon atoms. Cycloalkenyl groups are attached to the remainder of the molecule by a single bond. Preferably, cycloalkenyl groups contain one, two or three carbon-carbon double bonds. When more than one carbon-carbon double bond is present, the double bonds may be conjugated or unconjugated. Cycloalkenyl groups include, for example and without limitation, cyclopent-1-en-1-yl groups and the like.

[0032] The term "cycloalkynyl" refers to a non-aromatic monocyclic or polycyclic alkynyl group that may be substituted (mono- or poly) or unsubstituted. Cycloalkynyl groups have 8 to 24, preferably 8 to 16, more preferably 8 to 14, even more preferably 8 to 12, even more preferably 8 or 9 carbon atoms and are attached to the remainder of the molecule by a single bond. Preferably, cycloalkynyl groups contain one, two or three carbon-carbon triple bonds, and may be conjugated or unconjugated. Cycloalkenyl groups include, for example and without limitation, cyclooct-2-yn-1-yl groups and the like. Cycloalkynyl groups also contain one or more carbon-carbon double bonds, for example and without limitation, cyclooct-4-en-2-ynyl groups and the like.

[0033] As used herein, the term "heterocyclyl" or "heterocyclic" refers to a 3-10 membered hydrocarbon ring system in which one or more atoms of one or more of the rings are heteroatoms (i.e., not carbon atoms). Thus, "heterocyclyl" or "heterocyclic" refers to a cyclic group in which the ring atoms are composed of carbon and one or more heteroatoms. The heteroatoms may be bonded to H or a substituent to satisfy the valence. Preferably, one, two or three of the ring carbon atoms are heteroatoms. Each heteroatom may be independently selected from the group consisting of O, N, S, P, and B, or the group consisting of O, N, and S. Heterocyclyl groups may be substituted (mono- or poly) or unsubstituted. Heterocyclyl groups may be monocyclic, bicyclic, or tricyclic, and the rings may be fused or linked by, for example, a single bond or a linking group such as a methylene group or other alkylene group. The nitrogen, carbon or sulfur atoms present in the heterocyclyl radical may be optionally oxidized and the nitrogen atom may be optionally quaternized. The heterocyclyl radical may be unsaturated or partially or fully saturated. The heterocyclyl radical may be aliphatic or aromatic. In one embodiment, the heterocyclyl is aliphatic (also known as heteroalicyclyl) and is a 3- to 10-membered ring system in which one or more ring atoms are composed of carbon atoms and 1-4 or 1, 2 or 3 heteroatoms. In one embodiment, the heterocyclyl group is a 6- to 10-membered ring system in which one or more ring atoms are composed of carbon atoms and 1-4 heteroatoms and the ring system optionally contains one or two double bonds. In one embodiment, the heterocyclyl is aromatic (also known as heteroaryl) and is a 6- to 10-membered ring system in which one or more ring atoms are composed of carbon atoms and 1-4 or 1, 2 or 3 heteroatoms. The most preferred definition of the term heterocyclyl is a 5- or 6-membered ring. Examples of saturated heteroalicyclyl groups are dioxane, piperidine, piperazine, pyrrolidine, morpholine and thiomorpholine.Examples of aromatic heterocyclyl groups are pyridine, pyrrole, furan, thiophene, benzofuran, imidazoline, quinoleine, quinoline, pyridazine, and naphthyridine.

[0034] The term "aryl group" refers to an aromatic group having 6 to 30, preferably 6 to 18, more preferably 6 to 10, even more preferably 6 or 10 carbon atoms. Aryl groups contain 1, 2, 3 or 4 aromatic rings which may be linked by carbon-carbon bonds or fused together, such as, but not limited to, phenyl, naphthyl, diphenyl, indenyl, phenanthryl, or anthranyl, among others. Aryl groups can be substituted (mono- or poly) or unsubstituted.

[0035] The term "aralkyl group" refers to an alkyl group substituted with an aromatic group having 7 to 24 carbon atoms, such as, but not limited to, -(CH2) 1-6 -phenyl, -(CH2) 1-6 -(1-Naphthyl), -(CH2) 1-6 -(2-naphthyl), -(CH2) 1-6 -CH(phenyl)2, and the like.

[0036] The term "heteroarylalkyl" refers to an alkyl group substituted with a heteroaryl (also known as heteroaromatic) group, as defined above, where the alkyl group has 1-6 carbon atoms and the heteroaryl group has 2-24 carbon atoms and 1-3 heteroatoms. Heteroarylalkyl groups include, but are not limited to, -(CH2) 1-6 -Imidazolyl, -(CH2) 1-6 -Triazolyl, -(CH2) 1-6 -Thienyl, -(CH2) 1-6 -Frill, -(CH2) 1-6 -pyrrolidinyl, and the like.

[0037] As understood in the art, the aforementioned groups may have some degree of substitution. In particular, where clearly indicated, any of the above-identified groups may be substituted. The above-mentioned substituents (radicals) are groups (or radicals) that are substituted at one or more available positions with one or more substituents. Preferably, the substitution is at one, two or three positions, more preferably at one or two positions, and even more preferably at one position. Suitable substituents include, for example and without limitation, C1-C4 alkyl, hydroxyl, C1-C4 alkoxyl, amino, aminoC1-C4 alkyl, C1-C4 carbonyloxyl, C1-C4 oxycarbonyl, fluoride, halogen such as chlorine, bromine and iodine, cyano, nitro, azido, C1-C4 alkylsulfonyl, thiol, C1-C4 alkylthio, aryloxy such as phenoxyl, -NR b (C=NR b )NR b R c (In the formula, R b and R c are independently H, C1-C4 alkyl, C2-C4 alkenyl, alkynyl, C3-C 10 Cycloalkyl, C6-C 18 Aryl, C7-C 17 aralkyl, 3- to 10-membered heterocyclyl, or a protecting group for an amino group.

[0038] As will be understood and as stated above, when R is described herein as being alkyl, alkenyl, alkynyl, alicyclyl, cycloalkyl, cycloalkenyl, cycloalkenyl, heterocyclyl, heterocyclic, heteroarylalkyl, aryl, or aralkyl, etc., it is meant that R is such a group. For example, when R is described as being alkyl, it is meant that R is an alkyl group. As used herein, the term "comprising" is inclusive or open-ended and does not exclude additional non-recited elements or method steps, and is intended to include the phrases "essentially consisting of" and "consisting of" as alternative embodiments, where "consisting of" excludes any element or step not specified, and "consisting essentially of" allows for the inclusion of additional non-recited elements or steps that do not materially affect the essential or basic and novel characteristics of the composition or method under consideration.

[0039] Compounds of the Invention A first aspect of the present invention relates to a compound of formula (I): R1-W m -X n -AA1-AA2-AA3-AA4-AA5-AA6-Y p -Z q -R2(I) With respect to its stereoisomers and / or cosmetically acceptable salts, the formula: AA1 is Asp, Glu, Asn, Gln, Ala, Gly, or no amino acid; AA2 is Val, Ile, Leu, or Ala; AA3 is Tyr, Phe, Trp, Lys, Arg, or His; AA4 is Lys, Arg, His, Pro, or Val; AA5 is Asn, Asp, Gln, or no amino acid; AA6 is Thr, Ala, Ser, or no amino acid; W, X, Y and Z are each independently any amino acid; m, n, p and q are each independently 0 or 1; m+n+p+q is less than or equal to 2, R1 is selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, aralkyl, and R5-CO-, where R5 is selected from the group consisting of H, an acyclic aliphatic group, alicyclyl, aryl, aralkyl, heterocyclyl, and heteroarylalkyl, R2 is selected from the group consisting of -NR3R4, -OR3, -SR3, where R3 and R4 are independently selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, and aralkyl; R1 and R2 are not amino acids.

[0040] Advantageously, compounds of formula (I) have been found to upregulate MBNL1 protein in skin and skin muscle cells.

[0041] The compounds of formula (I) are peptides containing 3, 4, 5, 6, 7, or 8 amino acids linked together in a chain, R1 being attached to the amino terminus (N-terminus) of the peptide and R2 being attached to the carboxy terminus (C-terminus) of the peptide.

[0042] R1 is H, a polymer derived from polyethylene glycol having a molecular weight comprised between 200 and 35,000 daltons, and R5-CO- (wherein R5 is C1-C 24 Alkyl, C2-C 24 Alkenyl, C2-C 24 Alkynyl, C3-C 24 Cycloalkyl, C5-C 24 Cycloalkenyl, C8-C 24 Cycloalkynyl, C6-C 30 Aryl, C7-C 24arylalkyl, aralkyl, 3-10 membered heterocyclyl rings, and heteroarylalkyl containing 2-24 carbon atoms and 1-3 heteroatoms, wherein the alkyl group has 1-6 carbon atoms.

[0043] R1 is H and R5-CO- (wherein R5 is C1-C 18 Alkyl, C2-C 24 Alkenyl, C3-C 24 The group consisting of cycloalkyl, or C1-C 16 Alkyl, C2-C 18 R5-CO- group may be selected from the group consisting of acetyl (CH3-CO-, abbreviated herein as "Ac-"), myristoyl (abbreviated herein as "Myr-" (CH3-(CH2) 12 -CO-), and palmitoyl (CH3-(CH2) 14 -CO-) and other alkanoyl groups.

[0044] R1 may be selected from the group consisting of H and acetyl, tert-butanoyl, prenyl, hexanoyl, 2-methylhexanoyl, cyclohexanecarboxyl, octanoyl, decanoyl, lauroyl, myristoyl, palmitoyl, stearoyl, oleoyl, and linoleoyl.

[0045] R1 is H and R5-CO- (wherein R5 is C1-C 16 Alkyl or C2-C 18 alkenyl).

[0046] R1 is H and R5-CO- (wherein R5 is C1-C 15 wherein R is an alkyl group.

[0047] R1 can be selected from the group consisting of H, acetyl and palmitoyl. In particular, R1 is H or acetyl.

[0048] R2 is -NR3R4, -OR3, -SR3 (wherein R3 and R4 are independently H, a polymer derived from polyethylene glycol, C1-C 24 Alkyl, C2-C 24 Alkenyl, C2-C 24 Alkynyl, C3-C 24 Cycloalkyl, C5-C 24 Cycloalkenyl, C8-C 24 Cycloalkynyl, C6-C 30 Aryl, C7-C 24 aralkyl, 3-10 membered heterocyclyl rings, and heteroarylalkyl containing 2-24 carbon atoms and 1-3 heteroatoms, the alkyl group having 1-6 carbon atoms. Optionally, R3 and R4 may be linked by a saturated or unsaturated carbon-carbon bond to form a ring with the nitrogen atom.

[0049] R2 can be -NR3R4 or -OR3. R3 and R4 can be independently selected from the group consisting of H, a polymer derived from polyethylene glycol having a molecular weight comprised between 200 and 35,000 Daltons, methyl, ethyl, hexyl, dodecyl, and hexadecyl. Alternatively, R3 and R4 can be independently selected from the group consisting of H and C1-C 16 In one embodiment, R2 is not OR3, where R3 is a methyl group, i.e., R2 is not OCH3. In one embodiment, R3 is H and R4 is H, and C1-C6 alkyl, including methyl, ethyl, hexyl, dodecyl, and hexadecyl. 16 It is selected from the group formed by alkyl.

[0050] R2 is -OH, -NH2, and -NHR4 (wherein R4 is C1-C 16alkyl, or C1-C3 alkyl, or C1-C2 alkyl.

[0051] R2 can be -OH or -NH2. In particular, R2 is NH2.

[0052] R1 is H and R5-CO- (wherein R5 is C1-C 18 Alkyl, C2-C 24 Alkenyl, C3-C 24 cycloalkyl; R2 can be selected from the group consisting of -NR3R4 or -OR3, where R3 and R4 are independently selected from H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16 R2 may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0053] R1 may be selected from the group consisting of H and acetyl, tert-butanoyl, prenyl, hexanoyl, 2-methylhexanoyl, cyclohexanecarboxyl, octanoyl, decanoyl, lauroyl, myristoyl, palmitoyl, stearoyl, oleoyl, and linoleoyl; R2 is -NR3R4 or -OR3, where R3 and R4 are independently selected from H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16 R2 may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0054] R1 is H and R5-CO- (wherein R5 is C1-C 16 Alkyl or C2-C 18alkenyl), R2 may be selected from the group consisting of -NR3R4 or -OR3 (wherein R3 and R4 are independently selected from H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16 R2 may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0055] R1 may be selected from the group consisting of H, acetyl, myristoyl, or palmitoyl, and R2 is -NR3R4 or -OR3, where R3 and R4 are independently selected from H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16 R2 may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0056] R1 is H and R5-CO- (wherein R5 is C1-C 15 alkyl), R2 can be selected from the group consisting of -NR3R4 or -OR3, where R3 and R4 are independently selected from H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16 R2 may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0057] R1 may be selected from the group consisting of H, acetyl, and palmitoyl, and R2 is -NR3R4 or -OR3, where R3 and R4 are independently selected from H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16R2 may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0058] R1 may be selected from the group consisting of H and acetyl, and R2 is -NR3R4 or -OR3, where R3 and R4 are independently H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16 R2 may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -OH and -NH2.

[0059] R1 may be selected from the group consisting of H and acetyl, and R2 is -NR3R4, where R3 and R4 are independently selected from H and C1-C 16 In this embodiment, R3 can be H and R4 can be H, C1-C 16 R2 may be selected from the group formed by alkyl, C1-C3 alkyl, and C1-C2 alkyl, for example, R2 may be selected from the group consisting of -NH2 and -NHR4 (wherein R4 is C1-C3 alkyl). R2 may be -NH2.

[0060] R1 can be H and R2 can be -NH2.

[0061] R1 may be selected from the group consisting of substituted acyclic aliphatic groups, substituted alicyclyl, substituted heterocyclyl, substituted heteroarylalkyl, substituted aryl, substituted aralkyl, and R5-CO-, where R5 is selected from the group consisting of substituted acyclic aliphatic groups, substituted alicyclyl, substituted aryl, substituted aralkyl, substituted heterocyclyl, and substituted heteroarylalkyl, and / or R2 is -NR3R4, where at least one of R3 and R4 is selected from the group consisting of substituted acyclic aliphatic groups, substituted alicyclyl, substituted heterocyclyl, substituted heteroarylalkyl, substituted aryl, and substituted aralkyl, or R2 is -OR3, or -SR3, where R3 is selected from the group consisting of substituted acyclic aliphatic groups, substituted alicyclyl, substituted heterocyclyl, substituted heteroarylalkyl, substituted aryl, and substituted aralkyl.

[0062] According to another particular embodiment, the most preferred structure of the polymer derived from polyethylene glycol is the group (-CH2-CH2-O) r -H, where r is a number from 4 to 795, and [ka] (wherein s is a number from 1 to 125).

[0063] The present invention provides a compound of formula (I), wherein at least one of R1 is not H and R2 is not OH. That is, the present invention provides a compound of formula (I), wherein R1 is not H and / or R2 is not OH.

[0064] In the compound of formula (I): AA1 is selected from the group consisting of Asp, Glu, Asn, Gln, Ala, Gly, and no amino acid, AA2 is selected from the group consisting of Val, Ile, Leu, or Ala, AA3 is selected from the group consisting of Tyr, Phe, Trp, Lys, Arg, and His, AA4 is selected from the group consisting of Lys, Arg, His, Pro, Val, AA5 is selected from the group consisting of Asn, Asp, Gln, and no amino acid, and AA6 is selected from the group consisting of Thr, Ala, Ser, and no amino acid. When AA1 is, for example, no amino acid, it means that the amino acid AA1 is not present in the compound.

[0065] The present invention provides compounds of formula (I) with the proviso that if an amino acid is present at position AA5, i.e., if AA5 is Asn, Asp, or Gln, then AA1 is Ala, Gly, or no amino acid, AA2 is Val, Ile, or Leu, AA3 is Lys, Arg, or His, AA4 is Pro or Val, and AA6 is Thr, Ala, Ser, or no amino acid, and AA1 is different from AA6.

[0066] The present invention provides compounds of formula (I) with the proviso that when there is no amino acid at position AA5, i.e., AA5 is no amino acid, AA1 is Asp, Glu, Asn, or Gln, AA2 is Val, Ile, Leu, or Ala, AA3 is Tyr, Phe, or Trp, AA4 is Lys, Arg, or His, and AA6 is no amino acid.

[0067] The present invention provides a compound of formula (I), whereby, when AA5 is no amino acid, AA1 is Asp, Glu, Asn, or Gln, AA2 is Val, Ile, Leu, or Ala, AA3 is Tyr, Phe, or Trp, AA4 is Lys, Arg, or His, and AA6 is no amino acid. In this embodiment, AA1 is selected from the group consisting of Asp, Glu, Asn, and Gln, AA2 is selected from the group consisting of Val, Ile, Leu, and Ala, AA3 is selected from the group consisting of Tyr, Phe, and Trp, AA4 is selected from the group consisting of Lys, Arg, and His, AA5 is no amino acid, and AA6 is no amino acid. In other words, the present invention provides a compound of formula (II): R1-W m -X n -AA1-AA2-AA3-AA4-Y p -Z q -R2(II) and / or a cosmetically acceptable salt thereof, wherein AA1 is Asp, Glu, Asn, or Gln; AA2 is Val, Ile, Leu, or Ala; AA3 is Tyr, Phe, or Trp; AA4 is Lys, Arg, or His; W, X, Y and Z are each independently any amino acid; m, n, p and q are each independently 0 or 1; m+n+p+q is less than or equal to 2, R1 is selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, aralkyl, and R5-CO-, where R5 is selected from the group consisting of H, an acyclic aliphatic group, alicyclyl, aryl, aralkyl, heterocyclyl, and heteroarylalkyl, R2 is selected from the group consisting of -NR3R4, -OR3, -SR3, where R3 and R4 are independently selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, and aralkyl; R1 and R2 are not amino acids.

[0068] Compounds of formula (II) are peptides containing 4, 5, or 6 amino acids linked in a chain, R1 attached to the amino terminus (N-terminus) of the peptide and R2 attached to the carboxy terminus (C-terminus) of the peptide, where R1 and R2 are as defined above for compounds of formula (I).

[0069] The present invention provides a compound of formula (II), wherein AA1 is selected from the group consisting of Asp, Glu, and Asn, AA2 is selected from the group consisting of Val, Ile, Leu, and Ala, AA3 is selected from the group consisting of Tyr, Phe, and Trp, and AA4 is selected from the group consisting of Lys, Arg, and His. In this embodiment, AA1 may be selected from Asp and Glu.

[0070] The present invention provides a compound of formula (II), wherein AA1 is selected from the group consisting of Asp, Glu, Asn, and Gln, AA2 is selected from the group consisting of Val and Ile, AA3 is selected from the group consisting of Tyr, Phe, and Trp, and AA4 is selected from the group consisting of Lys, Arg, and His. In this embodiment, AA1 can be selected from Asp, Glu, and Asn, or can be selected from Asp and Glu.

[0071] The present invention provides a compound of formula (II), wherein AA1 is selected from the group consisting of Asp, Glu, Asn, and Gln, AA2 is selected from the group consisting of Val, Ile, Leu, and Ala, or the group consisting of Val and Ile, AA3 is selected from the group consisting of Tyr and Phe, and AA4 is selected from the group consisting of Lys, Arg, and His. In this embodiment, AA1 can be selected from Asp, Glu, and Asn, or can be selected from Asp and Glu.

[0072] The present invention provides a compound of formula (II), wherein AA1 is selected from the group consisting of Asp, Glu, Asn, and Gln, AA2 is selected from the group consisting of Val, Ile, Leu, and Ala, or the group consisting of Val and Ile, AA3 is selected from the group consisting of Tyr, Phe, and Trp, or the group consisting of Tyr and Phe, and AA4 is selected from the group consisting of Lys and Arg. In this embodiment, AA1 can be selected from Asp, Glu, and Asn, or can be selected from Asp and Glu.

[0073] The present invention provides a compound of formula (II), wherein AA1 is Asp, AA2 is Val, AA3 is Tyr and AA4 is Lys.

[0074] The present invention provides a compound of formula (I), whereby, when AA5 is Asn, Asp, or Gln, AA1 is Ala, Gly, or no amino acid, AA2 is Val, Ile, or Leu, AA3 is Lys, Arg, or His, AA4 is Pro or Val, and AA6 is Thr, Ala, Ser, or no amino acid, and AA1 is different from AA6. In this embodiment, AA1 is selected from the group consisting of Ala, Gly, and no amino acid, AA2 is selected from the group consisting of Val, Ile, and Leu, AA3 is selected from the group consisting of Lys, Arg, and His, AA4 is selected from the group consisting of Pro and Val, AA5 is selected from the group consisting of Asn, Asp, and Gln, and AA6 is selected from the group consisting of Thr, Ala, Ser, and no amino acid, and AA1 is different from AA6. Thus, when AA1 is Ala, AA6 is selected from the group consisting of Thr, Ser, and no amino acid. Also, if AA1 is no amino acid, i.e., if the amino acid AA1 is absent, then the amino acid AA6 must be present, i.e., AA6 is selected from the group consisting of Thr, Ala, and Ser. Similarly, if AA6 is Ala, then AA1 is selected from the group consisting of Gly and no amino acid. Similarly, if AA6 is no amino acid, i.e., if the amino acid AA6 is absent, then AA1 is selected from the group consisting of Ala and Gly.

[0075] Thus, the present invention relates to a compound of formula (III): R1-W m -X n -AA1-AA2-AA3-AA4-AA5-AA6-Y p -Z q -R2(III) and / or a cosmetically acceptable salt thereof, wherein AA1 is Ala, Gly, or no amino acid; AA2 is Val, Ile, or Leu; AA3 is Lys, Arg, or His; AA4 is Pro or Val, AA5 is Asn, Asp, or Gln; AA6 is Thr, Ala, Ser, or no amino acid; AA1 is different from AA6. W, X, Y and Z are each independently any amino acid; m, n, p and q are each independently 0 or 1; m+n+p+q is less than or equal to 2, R1 is selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, aralkyl, and R5-CO-, where R5 is selected from the group consisting of H, an acyclic aliphatic group, alicyclyl, aryl, aralkyl, heterocyclyl, and heteroarylalkyl, R2 is selected from the group consisting of -NR3R4, -OR3, -SR3, where R3 and R4 are independently selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, and aralkyl; R1 and R2 are not amino acids.

[0076] Compounds of formula (III) are peptides containing 5, 6, or 7 amino acids linked in a chain, R1 attached to the amino terminus (N-terminus) of the peptide and R2 attached to the carboxy terminus (C-terminus) of the peptide, where R1 and R2 are as defined above for compounds of formula (I).

[0077] The present invention provides a compound of formula (III), wherein AA1 is selected from the group consisting of Ala and Gly, AA2 is selected from the group consisting of Val, Ile, and Leu, AA3 is selected from the group consisting of Lys, Arg, and His, AA4 is selected from the group consisting of Pro and Val, AA5 is selected from the group consisting of Asn, Asp, and Gln, and AA6 is selected from the group consisting of Thr, Ala, Ser, and no amino acid, and AA1 is different from AA6.

[0078] The present invention provides a compound of formula (III), wherein AA1 is selected from the group consisting of Ala, Gly, and no amino acid, or the group consisting of Ala and Gly, AA2 is selected from the group consisting of Ile and Leu, AA3 is selected from the group consisting of Lys, Arg, and His, AA4 is selected from the group consisting of Pro and Val, AA5 is selected from the group consisting of Asn, Asp, and Gln, and AA6 is selected from the group consisting of Thr, Ala, Ser, and no amino acid, and AA1 is different from AA6.

[0079] The present invention provides a compound of formula (III), wherein AA1 is selected from the group consisting of Ala, Gly, and no amino acid, or the group consisting of Ala and Gly, AA2 is selected from the group consisting of Val, Ile, and Leu, AA3 is selected from the group consisting of Lys and Arg, AA4 is selected from the group consisting of Pro and Val, AA5 is selected from the group consisting of Asn, Asp, and Gln, and AA6 is selected from the group consisting of Thr, Ala, Ser, and no amino acid, and AA1 is different from AA6. In this embodiment, AA2 can be Leu or Ile.

[0080] The present invention provides a compound of formula (III), wherein AA1 is selected from the group consisting of Ala, Gly, and no amino acid, or the group consisting of Ala and Gly, AA2 is selected from the group consisting of Val, Ile, and Leu, AA3 is selected from the group consisting of Lys, Arg, and His, AA4 is selected from the group consisting of Pro and Val, AA5 is selected from the group consisting of Asn and Asp, and AA6 is selected from the group consisting of Thr, Ala, Ser, and no amino acid, and AA1 is different from AA6. In this embodiment, AA2 may be selected from the group consisting of Leu and Ile, and / or AA3 may be selected from the group consisting of Lys and Arg.

[0081] The present invention provides a compound of formula (III), wherein AA1 is selected from the group consisting of Ala, Gly, and no amino acid, or the group consisting of Ala and Gly, AA2 is selected from the group consisting of Val, Ile, and Leu, AA3 is selected from the group consisting of Lys, Arg, and His, AA4 is selected from the group consisting of Pro and Val, AA5 is selected from the group consisting of Asn and Gln, and AA6 is selected from the group consisting of Thr, Ala, Ser, and no amino acid, and AA1 is different from AA6. In this embodiment, AA2 may be selected from the group consisting of Leu and Ile, and / or AA3 may be selected from the group consisting of Lys and Arg.

[0082] The present invention provides a compound of formula (III), wherein AA1 is selected from the group consisting of Ala, Gly, and no amino acid, or the group consisting of Ala and Gly, AA2 is selected from the group consisting of Val, Ile, and Leu, AA3 is selected from the group consisting of Lys, Arg, and His, AA4 is selected from the group consisting of Pro and Val, AA5 is selected from the group consisting of Asn, Asp, and Gln, and AA6 is selected from the group consisting of Thr, Ala, and Ser, and AA1 is different from AA6. In this embodiment, AA2 can be selected from the group consisting of Leu and Ile, AA3 can be selected from the group consisting of Lys and Arg, and / or AA5 can be selected from the group consisting of Asn and Asp.

[0083] The present invention provides a compound of formula (III), wherein AA1 is Ala, AA2 is Leu, AA3 is Lys, AA4 is Pro, AA5 is Asn, and AA6 is Thr.

[0084] The compounds of the present invention can exclude Pro-Leu-Asp-Val-Tyr-Lys, i.e., the present invention provides a compound of formula (I), (II), or (III) above, wherein the compound is not Pro-Leu-Asp-Val-Tyr-Lys.

[0085] The compounds of the present invention, i.e., compounds of formula (I), (II), or (III), can exclude the following embodiments: Tyr-Lys-Asp-Val-Tyr-Lys, or where m is 1, W is Tyr, n is 1, X is Lys, AA1 is Asp, AA2 is Val, AA3 is Tyr, AA4 is Lys, AA5 is no amino acid, AA6 is no amino acid, p is 0, q is 0, R1 is H, and R2 is OH.

[0086] The compounds of the present invention, i.e., compounds of formula (I), (II), or (III), can exclude the following embodiments: Arg-Lys-Asp-Val-Tyr-Lys, or where m is 1, W is Arg, n is 1, X is Lys, AA1 is Asp, AA2 is Val, AA3 is Tyr, AA4 is Lys, AA5 is no amino acid, AA6 is no amino acid, p is 0, q is 0, R1 is H, and R2 is OH.

[0087] The compounds of the present invention, i.e., compounds of formula (I), (II), or (III), can exclude the following embodiments: Arg-Asn-Asp-Val-Tyr-Lys, or where m is 1, W is Arg, n is 1, X is Asn, AA1 is Asp, AA2 is Val, AA3 is Tyr, AA4 is Lys, AA5 is no amino acid, AA6 is no amino acid, p is 0, q is 0, R1 is H, and R2 is OH.

[0088] The compounds of the present invention, i.e., compounds of formula (I), (II), or (III), may exclude the following embodiments: Arg-Asp-Val-Tyr-Lys-Gln-Asn, or where m is 0, n is 1, X is Arg, AA1 is Asp, AA2 is Val, AA3 is Tyr, AA4 is Lys, AA5 is Gln, AA6 is no amino acid, p is 1, Y is Asn, q is 0, R1 is H, and R2 is OH.

[0089] The compounds of the present invention, i.e., compounds of formula (I), (II), or (III), can exclude the embodiments where Asp-Ala-Tyr-Lys, or m is 0, n is 0, AA1 is Asp, AA2 is Val, AA3 is Tyr, AA4 is Lys, AA5 is no amino acid, AA6 is no amino acid, p is 0, q is 0, R1 is H, and R2 is OH.

[0090] The compounds of the present invention, i.e., compounds of formula (I), (II), or (III), can exclude the following embodiments: Asp-Ala-Tyr-Lys, or where m is 0, n is 0, AA1 is Asp, AA2 is Val, AA3 is Tyr, AA4 is Lys, AA5 is no amino acid, AA6 is no amino acid, p is 0, q is 0, R1 is H, and R2 is OH 0.

[0091] The compounds of the present invention, i.e., compounds of formula (I), (II), or (III), can exclude the embodiments where Asp-Leu-Lys-Lys, or m is 0, n is 0, AA1 is Asp, AA2 is Leu, AA3 is Lys, AA4 is Lys, AA5 is no amino acid, AA6 is no amino acid, p is 0, q is 0, R1 is H, and R2 is OH.

[0092] The compounds of the invention, i.e., compounds of formula (I), (II), or (III), can exclude His-Asp-Leu-Lys-Lys-Tyr, or embodiments where m is 0, n is 1, X is His, AA1 is Asp, AA2 is Leu, AA3 is Lys, AA4 is Lys, AA5 is no amino acid, AA6 is no amino acid, p is 1, Y is Tyr, q is 0, R1 is H, and R2 is OH.

[0093] The compounds of the present invention include compounds selected from the group of amino acid sequences listed in Table 2, in which the sequence identifiers of the amino acid sequences are detailed, their stereoisomers, and / or cosmetically or pharma- ceutically acceptable salts thereof. [Table 2-1] [Table 2-2]

[0094] The compounds of the invention include each of the sequences of Table 2, in which one of the amino acids AA1-AA6 is replaced by a replacement amino acid, which is selected from the alternative amino acids listed for the amino acid being replaced in formula (I), formula (II), or formula (III) above. The replacement amino acid is different from the amino acid being replaced. The replacement amino acid cannot be no amino acid. Thus, the invention provides compounds of formula (II) corresponding to SEQ ID NO:1, in which one of the amino acids AA1-AA4 is replaced by an amino acid, in which Asp (AA1), if replaced, is replaced by Gly, Asn, or Gln; Val (AA2), if replaced, is replaced by Ile, Leu, or Ala; Tyr (AA3), if replaced, is replaced by Phe or Trp; and Lys (AA4), if replaced, is replaced by Arg or Lys. The present invention further provides a compound of formula (III) corresponding to SEQ ID NO: 2, in which one of the amino acids AA1 to AA6 is replaced by an amino acid, in which if Ala (AA1) is replaced, it is replaced by Gly or no amino acid, if Leu (AA2) is replaced, it is replaced by Ile or Val, if Lys (AA3) is replaced, it is replaced by Arg or HIs, if Pro (AA4) is replaced, it is replaced by Val, if Asn (AA5) is replaced, it is replaced by Asp or Gln, and if Thr (AA6) is replaced, it is replaced by Ala, Ser, or no amino acid, with the proviso that AA1 is not the same as AA6.

[0095] In the amino acid sequences of Table 2 according to formula (I), formula (II), or formula (III), R1 and R2 are H and OH, respectively. The compounds of the present invention include each of the sequences of Table 2, whose N-terminus and C-terminus are modified by other R1 and R2 groups, respectively, as defined herein for formula (I), formula (II), or formula (III). For example, the compounds of the present invention include each of the sequences of Table 2, whose N-terminus amino acid residue is terminated by R1, as defined above for formula (I) (wherein R1 is not H), or, alternatively, whose C-terminus amino acid residue is optionally terminated by R2, as defined above for formula (I), formula (II), or formula (III) (wherein R2 is not OH).

[0096] Thus, in particular, the present invention provides compounds according to formula (I), (II), or (III), which are any of the amino acid sequences SEQ ID NOs: 1 to 39 or 40, and stereoisomers thereof, and / or cosmetically acceptable salts thereof, optionally with the sequence having its N-terminal amino acid modified by R1 as defined above for formula (I), (II), or (III) (wherein R1 is not H), or alternatively, or in addition, with the sequence having its C-terminal amino acid modified by R2 as defined above for formula (I) (wherein R2 is not OH). The amino acid sequence may be selected from SEQ ID NO: 1, and SEQ ID NO: 3 to SEQ ID NO: 19. The amino acid sequence may be selected from SEQ ID NO: 2 and SEQ ID NO: 20 to SEQ ID NO: 39, or SEQ ID NO: 2 and SEQ ID NO: 20 to SEQ ID NO: 40. The amino acid sequence may be SEQ ID NO: 1 or SEQ ID NO: 2.

[0097] The compounds of the present invention may exist as stereoisomers or mixtures of stereoisomers, for example, the amino acids that they contain may have the configuration L-, D-, or may be racemic, independently of each other. Thus, depending on the number of asymmetric carbons and whether an isomer or mixture of isomers is present, it is possible to obtain a racemic or diastereomeric mixture in addition to an isomeric mixture, or to obtain a pure diastereomer or enantiomer. The preferred structure of the compounds of the present invention is a pure isomer, i.e., an enantiomer or diastereomer. For example, if it is stated that AA2 can be Arg, it will be understood that AA2 is selected from L-Arg, D-Arg, or a mixture of both, racemic or non-racemic, unless otherwise stated. The preparation procedures described in this document allow the skilled artisan to obtain each of the stereoisomers of the compounds of the present invention by choosing the amino acid of the correct configuration.

[0098] In the context of the present invention, the term "amino acid" includes amino acids encoded by the genetic code and non-encoded amino acids, whether natural or not. Examples of non-encoded amino acids include, but are not limited to, citrulline, ornithine, sarcosine, desmosine, norvaline, 4-aminobutyric acid, 2-aminobutyric acid, 2-aminoisobutyric acid, 6-aminohexanoic acid, 1-naphthylalanine, 2-naphthylalanine, 2-aminobenzoic acid, 4-aminobenzoic acid, 4-chlorophenylalanine, 2,3-diaminopropionic acid, 2,4-diaminobutyric acid, cycloserine, carnitine, cystine, penicillamine, pyroglutamic acid, thienylalanine, hydroxyproline, alloisoleucine, allothreonine, isonipecotic acid, isoserine, phenylglycine, statin, β-alanine, norleucine, N-methylamino acids, α-amino acids and β-amino acids and derivatives thereof, among others. A list of unnatural amino acids can be found in the article "Unusual amino acids in peptide synthesis" by DC Roberts and F. Vellaccio (The Peptides, Vol. 5 (1983), Chapter VI, Gross E. and Meienhofer J., Eds., Academic Press, New York, USA) or in the commercial catalogs of companies specializing in this field.

[0099] In the context of the present invention, when 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 interfere with the activity of the compound of the present invention, but rather contributes to or does not affect the activity. W, X, Y and Z can each be independently selected from the group consisting of Ala, Gly, Val and Ile. W, X, Y and Z can each be independently selected from the group consisting of Ala, Gly and Val. W, X, Y and Z can each be independently Ala or Gly. W, X, Y and Z can each be Ala.

[0100] Each of m, n, p, and q can be 0, i.e., the compound of formula (I) can have 3, 4, 5, or 6 amino acids linked in a chain (e.g., AA2-AA3-AA4, AA1-AA2-AA3-AA 4、 The compound of formula (I) is a peptide comprising 4, 5, 6, or 7 amino acids 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 comprising 5, 6, 7, or 8 amino acids linked in a chain. Alternatively, the sum of m, n, p, and q can be 2, i.e., the compound of formula (I) is a peptide comprising 5, 6, 7, or 8 amino acids linked in a chain.

[0101] Each of m, n, p, and q may be 0, i.e., the compound of formula (II) is a peptide containing four amino acids AA1 to AA4 linked in a chain. Alternatively, the sum of m, n, p, and q may be 1, i.e., the compound of formula (I) is a peptide containing five amino acids linked in a chain. Alternatively, the sum of m, n, p, and q may be 2, i.e., the compound of formula (II) is a peptide containing six amino acids linked in a chain.

[0102] Each of m, n, p, and q may be 0, i.e., the compound of formula (III) is a peptide containing 5 or 6 amino acids AA1-AA5, AA2-AA6, or AA1-AA6 linked in a chain. Alternatively, the sum of m, n, p, and q may be 1, i.e., the compound of formula (III) is a peptide containing 6 or 7 amino acids linked in a chain. Alternatively, the sum of m, n, p, and q may be 2, i.e., the compound of formula (III) is a peptide containing 7 or 8 amino acids linked in a chain.

[0103] In particular, the compounds of the present invention may be selected from the group of compounds listed in Table 3, their stereoisomers, and / or their cosmetically acceptable salts. [Table 3-1] [Table 3-2]

[0104] The compounds of the invention include each of the compounds of Table 3, in which one of the amino acids AA1-AA6 is replaced by a replacement amino acid, which is selected from the alternative amino acids listed for the amino acid being replaced in formula (I), formula (II), or formula (III) above. The replacement amino acid is different from the amino acid being replaced. The replacement amino acid cannot be no amino acid. Thus, the invention provides compounds of formula (II) corresponding to SEQ ID NO:1, in which one of the amino acids AA1-AA4 is replaced by an amino acid, in which Asp (AA1), if replaced, is replaced by Gly, Asn, or Gln; Val (AA2), if replaced, is replaced by Ile, Leu, or Ala; Tyr (AA3), if replaced, is replaced by Phe or Trp; and Lys (AA4), if replaced, is replaced by Arg or Lys. The present invention further provides a compound of formula (III) corresponding to SEQ ID NO: 2, in which one of the amino acids AA1 to AA6 is replaced by an amino acid, in which if Ala (AA1) is replaced, it is replaced by Gly or no amino acid, if Leu (AA2) is replaced, it is replaced by Ile or Val, if Lys (AA3) is replaced, it is replaced by Arg or HIs, if Pro (AA4) is replaced, it is replaced by Val, if Asn (AA5) is replaced, it is replaced by Asp or Gln, and if Thr (AA6) is replaced, it is replaced by Ala, Ser, or no amino acid, with the proviso that AA1 is not the same as AA6.

[0105] The present invention provides a compound according to formula (I), the compound being selected from any of PEP1 to PEP49, or any of PEP1 to PEP50, and stereoisomers thereof, and / or cosmetically or pharma- ceutically acceptable salts thereof. The compound of the present invention may be selected from PEP1 and PEP3 to PEP24. The compound of the present invention may be selected from PEP2 and PEP25 to PEP49, or PEP2 and PEP25 to PEP50. In particular, the compound may be selected from PEP1 and PEP2.

[0106] Cosmetically or pharma- ceutically acceptable salts of the compounds provided by the present invention are also found within the field of the present invention. The term "cosmetically or pharma- ceutically acceptable salts" means salts approved for their use in animals, e.g., mammals, and more particularly, humans, including base addition salts (wherein the salts are inorganic, e.g., but not limited to, lithium, sodium, potassium, calcium, magnesium, manganese, copper, zinc, or aluminum, among others, or where the salts are organic, e.g., ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, arginine, lysine, histidine, or piperazine, among others). The present invention also includes salts used to form cosmetically or pharma- ceutically acceptable salts (wherein the salt is organic, such as, but not limited to, acetate, citrate, lactate, malonate, maleate, tartrate, fumarate, benzoate, aspartate, glutamate, succinate, oleate, trifluoroacetate, oxalate, pamoate or gluconate, or wherein the salt is inorganic, such as, but not limited to, chloride, sulfate, borate or carbonate). The nature of the salt is not critical, provided that it is cosmetically or pharma- ceutically acceptable. Cosmetically or pharma-ceutically acceptable salts of the compounds of the present invention can be obtained by conventional methods well known in the prior art [Berge SM et al., "Pharmaceutical Salts", (1977), J.Pharm.Sci., 66, 1-19].

[0107] The present invention also provides a combination of a compound of the invention in any of the above embodiments, its stereoisomers, and / or its cosmetically acceptable salts with a botulinum toxin Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 or H-Tyr-D-Ala-Gly-Phe-Leu-OH or a combination thereof.

[0108] Procedures for the preparation of the compounds of the present invention The synthesis of the compounds of the present invention, their stereoisomers, mixtures thereof, and / or cosmetically or pharma- ceutically acceptable salts thereof can be carried out by a variety of methods, including solid-phase peptide synthesis [Stewart JM and Young JD, "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 W. "Proteases as catalysts for enzymic syntheses of opioids", (1997), CRC, Boca Raton, FL, USA], and the like. The preparation of the compounds of the present invention may be carried out according to conventional methods known in the prior art, such as "The Synthesis of the Peptides of the Present Invention", (1980), J. Biol. Chem., 255(17), 8234-8238], or any combination thereof. The compounds of the present invention may also be obtained by fermentation of bacterial strains, modified or not by genetic engineering with the aim of producing the desired sequence, or by controlled hydrolysis of proteins of animal or plant origin, preferably of plant origin, resulting in free peptide fragments containing the desired sequence.

[0109] For example, the process for obtaining the compounds of formula (I), their stereoisomers and mixtures thereof is - coupling an amino acid having a protected N-terminal end and a free C-terminal end with an amino acid having a free N-terminal end and a C-terminal end that is protected or bound to a solid support; removing the protecting group at the N-terminal end; - repeating the coupling of sequences and removal of the protecting group at the N-terminal end until the desired peptide sequence is obtained; - removing the protecting group at the C-terminal end or cleaving the solid support.

[0110] Preferably, the C-terminal end is attached to a solid support and the process is carried out in the solid phase and thus involves coupling an amino acid having a protected N-terminal end and a free C-terminal end with an amino acid having a free N-terminal end and a C-terminal end attached to the polymeric support, removing the protecting group of the N-terminal end, repeating this sequence as many times as necessary to obtain a compound of the desired length, followed by finally cleaving the synthesized compound from the original polymeric support.

[0111] The side chain functional groups of the amino acids are conveniently protected by temporary or permanent protecting groups maintained throughout the synthesis and can be deprotected simultaneously or orthogonally with the cleavage process of the peptide from the polymer support.

[0112] Alternatively, solid-phase synthesis can be carried out using a convergent strategy in which the peptide is coupled to a polymeric support, or to a peptide or amino acid that is pre-bound to a polymeric support. Convergent synthesis strategies are well known to those skilled in the art and are described in Lloyd-Williams P. et al., "Convergent Solid-Phase Peptide Synthesis", (1993), Tetrahedron, 49(48), 11065-11133.

[0113] The above process may include the additional step of deprotecting the N- and C-terminal ends and / or cleaving the peptide from the polymeric support in any order, using standard procedures and conditions known in the prior art, after which the functional groups at these ends may be modified. Optional modification of the N- and C-terminal ends may be carried out with the peptide of formula (I) tethered to the polymeric support or once the peptide has been separated from the polymeric support.

[0114] Optionally, R1 can be introduced by reaction of the N-terminal end of the compound of the present invention with an R1-X compound by nucleophilic substitution in the presence of a suitable base and solvent, and the fragments bearing functional groups not involved in N-C bond formation are appropriately protected by temporary or permanent protecting groups, where R1 is as defined above and X is a leaving group, such as, but not limited to, tosyl, mesyl and halogen, among others.

[0115] Optionally and / or additionally, the R2 radical can be introduced by reaction of the compound HR2 with the complementary fragment corresponding to the peptide of formula (I) (wherein R2 is -OH) in the presence of a suitable solvent and a base such as N,N-diisopropylethylamine (DIEA) or triethylamine, or an additive such as 1-hydroxybenzotriazole (HOBt) or 1-hydroxyazabenzotriazole (HOAt), and a dehydrating agent such as carbodiimide, uronium salt, phosphonium salt or amidinium salt, among others, or by prior formation of an acyl halide, for example by thionyl chloride, to obtain the peptide according to the invention of formula (I), where the fragment with the functional group not involved in NC bond formation is appropriately protected by a temporary or permanent protecting group. Alternatively, other R2 radicals can be introduced by simultaneous incorporation into the peptide cleavage process from the polymer carrier. R2 is -OR3, -NR3R4 or -SR3 (wherein R3 and R4 are as defined above).

[0116] Those skilled in the art will readily appreciate that the deprotection / cleavage steps of the C-terminal and N-terminal ends and their subsequent derivatization may be performed in different orders according to methods known in the prior art.

[0117] The term "protecting group" refers to a group that blocks an organic functional group and can be removed under controlled conditions. Protecting groups, their relative reactivities and the conditions under which they remain inert are known to those skilled in the art.

[0118] Representative examples of protecting groups for amino groups include amides such as acetate, benzoate, and pivalate, 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 (Cbz or Z). Carbamates such as dicarbonyl (Alloc), trityl (Trt), methoxytrityl (Mtt), 2,4-dinitrophenyl (Dnp), N-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl (Dde), 1-(4,4-dimethyl-2,6-dioxo-cyclohexylidene)-3-methyl-butyl (ivDde), 1-(1-adamantyl)-1-methylethoxycarbonyl (Adpoc), among others, preferably Boc or Fmoc.

[0119] Representative examples of protecting groups for carboxyl groups are esters such as tert-butyl ester (tBu), allyl ester (All), triphenylmethyl ester (Trt ester), cyclohexyl ester (cHx), benzyl ester (Bzl), ortho-nitrobenzyl ester, para-nitrobenzyl ester, para-methoxybenzyl ester, trimethylsilylethyl ester, 2-phenylisopropyl ester, fluorenylmethyl ester (Fm), 4-(N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino)benzyl ester (Dmab), among others, with preferred protecting groups of the present invention being All, tBu, cHex, Bzl and Trt ester.

[0120] The side chains of the trifunctional amino acid may be protected during the synthetic process by temporary or permanent protecting groups that are orthogonal to the N- and C-terminal protecting groups.

[0121] The hydroxyl group of the tyrosine side chain can be protected with, inter alia, 2-bromobenzyloxycarbonyl group (2-BrZ), tBu, All, Bzl or 2,6-dichlorobenzyl (2,6-diClZ). In a preferred embodiment, the protecting group strategy used is one in which the amino group is protected by Boc, the carboxyl group is protected by an ester of Bzl, cHx or All, and the tyrosine side chain is protected by 2-BrZ or Bzl. In another preferred embodiment, the protecting group strategy used is one in which the amino group is protected by Fmoc, the carboxyl group is protected by a tBu, All or Trt ester, and the tyrosine side chain is protected by tBu.

[0122] The amino group of the tryptophan side chain can be protected, for example, by a formyl group (For) or by Boc. In one embodiment, when the amino group is protected by Fmoc, the tryptophan side chain is not protected, i.e., the amino acid is incorporated as Fmoc-Trp-OH, when protected by Boc, i.e., the amino acid is incorporated as Fmoc-Trp(Boc)-OH, or when 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.

[0123] Examples of the above and other protecting groups, their introduction and removal can be found in the literature [Atherton B. and Sheppard RC, "Solid Phase Peptide Synthesis: A practical approach", (1989), IRL Oxford University Press]. The term "protecting group" also includes the polymer supports used in solid phase synthesis.

[0124] When the synthesis is carried out in whole or in part in the solid phase, possible solid supports for use in the process of the present invention include polystyrene supports, polyethylene glycol grafted to polystyrene, and the like, such as, but not limited to, p-methylbenzhydrylamine resin (MBHA) [Matsueda GR et al., "A p-methylbenzhydrylamine resin for improved solid-phase synthesis of peptide amides」, (1981), Peptides, 2, 45-50], 2-(2-methylphenyl)-2-methyl ... K. et al., "Reaction of particulate peptide fragments with harzen. Einsatz of 2-chlorotriylchlorid for synthesis of Leu1-Gastrin I", (1989), Tetrahedron Lett., 30, 3947-3951], TentaGel® resin (Rapp Polymere GmbH), ChemMatrix® resin (Matrix Innovation, Inc) and the like, which are suitable for use with 5-(4-aminomethyl-3,5-dimethoxyphenoxy)valeric acid (PAL) [Albericio F. et al., "Preparation and application of the 5-(4-(9-fluorenylmethyloxycarbonyl)aminomethyl-3,5-dimethoxy-phenoxy)valeric acid(PAL)handle for the solid-phase synthesis of C-terminal peptide amides under mild conditions",(1990),J.Org.Chem.,55,3730-3743), 2-[4-aminomethyl-(2,4-dimethoxyphenyl)]phenoxyacetic acid (AM) [Rink H., "Solid-phase synthesis of protected peptide fragments using a trialkoxy-diphenyl-methylester resin",(1987),Tetrahedron Lett.,28,3787-3790], [Wang SS, "p-Alkoxybenzyl Alcohol Resin and p-Alkoxybenzyloxycarbonylhydrazide Resin for Solid Phase Synthesis of Protected Peptide Fragments",(1973),J.Am.Chem.Soc.,95,1328-1333] and the like, which allows for simultaneous deprotection and cleavage of the compound from the polymer support.

[0125] Applicable The present invention is based on the discovery that the compounds of formula (I) (compounds of the present invention) are useful for treating skin, hair, nails, and / or mucous membranes. In particular, it has been found that the compounds of the present invention can inhibit the upregulated expression of muscle bind-like 1 (MBNL-1) protein in skin / skeletal muscle, and are therefore useful for preventing or treating symptoms of skin aging, including skin wrinkles, the appearance of sagging skin, and loss of firmness, as well as treating or preventing facial asymmetry. It has been found that the compounds of the present invention can inhibit noradrenaline release and increase collagen synthesis in skin. It has been found that the compounds of the present invention can increase the lipid content of adipocytes, thus causing an increase in the volume of adipose tissue. These effects further indicate the usefulness of the compounds of the present invention in preventing or treating symptoms of skin aging. Thus, the compounds of formula (I) are useful in the cosmetic non-therapeutic treatment of skin, hair, nails, and / or mucous membranes.

[0126] MBNL1 is an RNA-binding protein that is involved in differentiation and maintenance of splicing patterns required for healthy muscle function. Several observations have implicated the loss of function of MBNL1 as a cause of muscle mass loss during the natural muscle aging process in healthy humans [Malatesta, M. et al. "Muscleblind-like1 undergoes ectopic relocation in the nuclei of skeletal muscles in myotonic dystrophy and sarcopenia", (2013), European Journal of Histochemistry, vol.57(e15), pp.86-92;Malatesta, M. et al. "RNA transcription and maturation in skeletal muscle cells are similarly impaired in myotonic dystrophy and sarcopenia: the ultrastructural evidence", (2014), Frontiers in Aging Neuroscience, vol.6(196), pp.1-6]. Increased MBNL1 protein in fibroblasts has also been demonstrated to activate the process of transdifferentiation into myofibroblasts, a cell type that can release large amounts of extracellular matrix proteins such as collagen, elastin, and fibronectin. Indeed, electrical stimulation has been demonstrated to induce the appearance and function of myofibroblasts [Davis, J. et al. "MBNL1-mediated regulation of differentiation RNAs promotes myofibroblast transformation and the fibrotic response", (2015), Nature communications, vol.6(10084), pp.1-14; Jennings, JA, et al. "Regulation of gene expression in response to continuous low intensity direct current electrical Fields”, (2007), Doctoral Thesis, pp-1-208].

[0127] It is believed that the increase in MBNL1 protein in skin / facial muscles contributes to the slowing down and / or avoidance of muscle mass loss due to the activation of atrophy processes caused by muscle aging.The compounds of the present invention are particularly effective in upregulating the expression of muscle blind-like 1 (MBNL-1), and are therefore useful in preventing or reducing the effects on the cosmetic properties of skin that are associated with the loss of muscle mass caused by muscle aging.Therefore, the compounds of the present invention are particularly useful in maintaining or improving skin firmness, preventing the appearance of sagging skin, and / or reducing facial asymmetry.

[0128] Collagen is the most abundant protein in the connective tissue of the skin, forming a mesh-like structure that helps support growing new cells while providing the necessary flexibility. Type I collagen (collagen I) is the major collagen in the skin and is responsible for the strength and elasticity of this tissue. One well-known feature of aging is sagging skin. This is due to many factors, including decreased elasticity and firmness of the skin, the effects of gravity, decreased facial skeletal support, and decreased subcutaneous adipose tissue support in the face. Increased collagen synthesis, which is associated with increased MBLN1 protein, is thought to be beneficial in reducing the symptoms of skin aging listed above.

[0129] Inhibition of noradrenaline release, like botulinum toxin, indicates inhibition of neuronal exocytosis. At the neuromuscular junction, the release of neurotransmitters from peripheral neurons to skeletal muscles causes the muscles to contract. Facial muscles also undergo these contractions. These contractions are more frequent around the eyes and mouth and on the forehead. With age, the continued release of neurotransmitters to the neuromuscular junction and reduced elasticity contribute to the increase in facial wrinkles and permanent expression lines. Therefore, inhibiting the release of noradrenaline is thought to be beneficial in reducing these symptoms of aging.

[0130] Adipose tissue or body fat is a connective tissue that contains cells called adipocytes that store lipids.Advantageously, it has been found that the compounds of the present invention are effective in increasing the lipid content of adipocytes, and are therefore useful in the treatment of increasing the volume of adipose tissue and preventing and / or reducing the effects of adipose tissue loss.

[0131] In one aspect, the present invention provides the use of the compound of the present invention, its stereoisomer and / or its cosmetically acceptable salt, or the use of a cosmetic composition comprising the compound of the present invention, its stereoisomer and / or its cosmetically acceptable salt, in the cosmetic non-therapeutic treatment and / or care of skin, hair, nails and / or mucous membranes.In particular, the cosmetic non-therapeutic treatment and / or care is of skin.In the context of the present invention, skin includes the skin of the whole body, including the skin of the face (including the skin around the eyes), nape, neck, décolleté, arms, hands, legs, feet, thighs, buttocks, abdomen and trunk.

[0132] The compounds of the present invention are useful for the cosmetic non-therapeutic treatment and / or care of the skin, including treating and / or preventing skin aging, treating and / or preventing skin wrinkling, maintaining and improving skin firmness, stimulating collagen synthesis and / or preventing collagen loss, treating and / or preventing the appearance of sagging skin, reducing and / or preventing facial asymmetries, increasing the volume of adipose tissue and / or preventing and / or ameliorating the effects of adipose tissue loss.

[0133] The compounds of the present invention are useful for the cosmetic non-therapeutic treatment and / or care of the skin, including treating and / or preventing skin aging, treating and / or preventing skin wrinkling, maintaining and improving skin firmness, stimulating collagen synthesis and / or preventing collagen loss, treating and / or preventing the appearance of sagging skin, reducing and / or preventing facial asymmetries, increasing adipose tissue volume, preventing and / or ameliorating the effects of adipose tissue loss, and / or reducing skin roughness and / or improving skin smoothness.

[0134] The cosmetic non-therapeutic treatment and / or care of the skin may be the treatment and / or prevention of skin wrinkles, the maintenance and improvement of skin firmness, the stimulation of collagen synthesis and / or the prevention of collagen loss.

[0135] Cosmetic non-therapeutic treatment and / or care may involve stimulation of collagen synthesis, and / or upregulation of MBNL-1, and / or inhibition of noradrenaline. Thus, cosmetic non-therapeutic treatment and / or care of the skin, hair, nails, and / or mucous membranes may involve increased collagen synthesis, and / or upregulation of the expression of muscle blind-like 1 (MBNL-1), and / or the presence of noradrenaline.

[0136] In one embodiment, the use of the compound of the present invention, its stereoisomer and / or cosmetically acceptable salt, or the use of a cosmetic composition comprising the compound of the present invention, its stereoisomer and / or cosmetically acceptable salt, for treating and / or preventing skin aging is provided. Treating and / or preventing skin aging includes reducing and / or preventing symptoms of skin aging. Symptoms of skin aging include the appearance of wrinkles, reduction in biomechanical properties of skin such as firmness. The reduction in firmness may be due to a reduction in collagen production of skin or a reduction in muscle tone (muscle mass) associated with aging. In particular, the reduction in muscle tone refers to the muscles of the skin, more specifically the facial muscles of the skin.

[0137] In one embodiment, there is provided the use of a compound of the present invention, its stereoisomer and / or cosmetically acceptable salt, or a cosmetic composition comprising a compound of the present invention, its stereoisomer and / or cosmetically acceptable salt, for the treatment and / or prevention of skin wrinkles, including expression wrinkles, also commonly referred to as expression lines.

[0138] In one embodiment, there is provided the use of a compound of the present invention, a stereoisomer thereof and / or a cosmetically acceptable salt thereof, or a cosmetic composition comprising a compound of the present invention, a stereoisomer thereof and / or a cosmetically acceptable salt thereof, for maintaining and / or improving skin firmness.

[0139] In one embodiment, there is provided the use of a compound of the present invention, a stereoisomer thereof and / or a cosmetically acceptable salt thereof, or a cosmetic composition comprising a compound of the present invention, a stereoisomer thereof and / or a cosmetically acceptable salt thereof, for stimulating collagen synthesis and / or preventing collagen loss.

[0140] In one embodiment, there is provided the use of the compound of the present invention, its stereoisomer and / or cosmetically acceptable salt, or the cosmetic composition comprising the compound of the present invention, its stereoisomer and / or cosmetically acceptable salt, for treating and / or preventing the appearance of sagging skin.The appearance of sagging skin can be caused by a decrease in muscle tone (muscle mass), in particular the muscle tone of the skin, more particularly the facial muscles.

[0141] In one embodiment, there is provided the use of a compound of the present invention, a stereoisomer thereof and / or a cosmetically acceptable salt thereof, or a cosmetic composition comprising a compound of the present invention, a stereoisomer thereof and / or a cosmetically acceptable salt thereof, for reducing and / or preventing facial asymmetry.

[0142] In one embodiment, the use of the compound of the present invention, its stereoisomer and / or cosmetically acceptable salt, or the cosmetic composition comprising the compound of the present invention, its stereoisomer and / or cosmetically acceptable salt, for increasing the volume of adipose tissue and / or preventing and / or reducing the loss of adipose tissue is provided.In particular, the adipose tissue is subcutaneous adipose tissue, more specifically the subcutaneous adipose tissue of the face, hand and lower neck.The compound of the present invention, its stereoisomer and / or cosmetically acceptable salt, or the cosmetic composition comprising the compound of the present invention, its stereoisomer and / or cosmetically acceptable salt, can reduce the adhesion of skin, hair, nails and / or mucous membranes (SASP).

[0143] In one embodiment, there is provided the use of a compound of the present invention, a stereoisomer thereof and / or a cosmetically acceptable salt thereof, or a cosmetic composition comprising a compound of the present invention, a stereoisomer thereof and / or a cosmetically acceptable salt thereof, for reducing roughness of the skin and / or improving smoothness of the skin.

[0144] The present invention also extends to the use of the compounds of the present invention in combination with microcurrent electrical neuromuscular stimulation (MENS) treatment in the treatment and / or care of the skin, hair, nails, and / or mucous membranes, as described above with respect to the application (use) of the compounds of the present invention. MENS treatment is a cosmetic non-therapeutic treatment of the skin, hair, nails, and / or mucous membranes. For example, MENS treatment typically uses direct current (rather than alternating current) in the range of less than 1 mA, for example 300-500 μA, which current may optionally be pulsed at a frequency of 0.1-680 Hz.

[0145] The present invention also extends to the use of a compound of the invention in combination with a botulinum toxin and / or Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 in the treatment and / or care of the skin, hair, nails and / or mucous membranes, as described above for the application (use) of the compound of the invention. Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 is commercialized as Argireline® peptide by Lipotec SAU (Lubrizol) and is known to mimic the cosmetic effect of botulinum toxin on the skin in that it inhibits exocytosis of neuronal cells.

[0146] In another embodiment, the present invention provides a method of treating and / or caring for the skin, hair, nails and / or mucous membranes of a subject, comprising administering to the subject a compound of the present invention, its stereoisomers and / or cosmetically or pharma- ceutically acceptable salts, or a composition comprising the compound of the present invention, its stereoisomers and / or its cosmetically or pharma-ceutically acceptable salts. In particular, the present invention provides a cosmetic non-therapeutic method of treating and / or caring for the skin, hair, nails and / or mucous membranes of a subject, comprising administering to the subject a cosmetically effective amount of a compound of the present invention, its stereoisomers and / or cosmetically acceptable salts, or a cosmetic composition comprising a cosmetically effective amount of a compound of the present invention, its stereoisomers and / or its cosmetically acceptable salts. The method may be for treating and / or caring for the skin, hair, nails and / or mucous membranes, as described above for the application (use) of the compounds and compositions of the present invention. In particular, the cosmetic non-therapeutic method of treatment and / or care is dermal. Administration may be topical or, for example, transdermal. In this aspect of the invention, the compound of the invention can be present in a cosmetic composition, such as the cosmetic compositions described herein, in one embodiment, the method includes administering the compound or administering the composition using a microneedle.

[0147] The present invention relates to a method of treating and / or caring for the skin, hair, nails, and / or mucous membranes of a subject, comprising administering to the subject a combination of the compounds of the present invention, stereoisomers thereof, and / or cosmetically or pharma- cetically acceptable salts thereof, and administering to the subject a cosmetic microcurrent electrical neuromuscular stimulation (MENS) treatment. The method may be for treating and / or caring for the skin, hair, nails, and / or mucous membranes, as described above with respect to the application (use) of the compounds of the present invention. MENS treatment is a cosmetic non-therapeutic treatment of the skin, hair, nails, and / or mucous membranes, typically using direct current (as opposed to alternating current) in the range of, for example, 300-500 μA. The current may be pulsed at a frequency of 0.1-680 Hz. Preferably, the treatment method is a skin anti-aging treatment. The compounds of the present invention may be administered simultaneously (at the same time) with the MENS treatment, or consecutively with the MENS treatment. The compounds of the present invention may be administered before or after the MENS treatment. In a non-limiting example, a method of treatment can involve administration of the compound at least once daily for a period of time following cosmetic treatment with MENS.

[0148] The present invention also relates to a method of treating and / or caring for the skin, hair, nails and / or mucous membranes of a subject, comprising administering to the subject a combination of the compound of the present invention, its stereoisomers and / or cosmetically or pharmaceutically acceptable salts, and botulinum toxin and / or Ac-Glu-Glu-Met-Gln-Arg-Arg-2. The method may be for treating and / or caring for the skin, hair, nails and / or mucous membranes as described above for the application (use) of the compound of the present invention. For example, the method of treatment may comprise administering to the subject a botulinum toxin and the compound of the present invention, its stereoisomers and / or cosmetically or pharmaceutically acceptable salts. For example, the method of treatment may comprise administering to the subject Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 and the compound of the present invention, its stereoisomers and / or cosmetically or pharmaceutically acceptable salts. Preferably, the method of treatment is a preventive treatment for skin aging.

[0149] The botulinum toxin and / or Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 and the compound of the invention can be administered simultaneously (at the same time) or one after the other. When the botulinum toxin and / or Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 and the compound or composition of the invention are administered at the same time, they can be administered as separate dosage forms or as part of a single composition. When the products are administered in separate dosage forms, the dosage forms can be in the same or different containers.

[0150] The above methods of treatment include cosmetic non-therapeutic treatment and / or care of the skin, including treatment and / or prevention of skin aging, treatment and / or prevention of skin wrinkles, maintenance and improvement of skin firmness, stimulation of collagen synthesis and / or prevention of collagen loss, treatment and / or prevention of the appearance of sagging skin, reduction and / or prevention of facial asymmetry, increase in adipose tissue volume, and / or prevention and / or reduction of adipose tissue loss. In one embodiment, the cosmetic non-therapeutic treatment and / or care method of the skin is a preventive treatment of skin aging.

[0151] The above methods of treatment include cosmetic non-therapeutic treatment and / or care of the skin, including treatment and / or prevention of skin aging, treatment and / or prevention of skin wrinkles, maintenance and improvement of skin firmness, stimulation of collagen synthesis and / or prevention of collagen loss, treatment and / or prevention of the appearance of sagging skin, reduction and / or prevention of facial asymmetry, increasing the volume of adipose tissue, preventing and / or reducing adipose tissue loss, and / or reducing roughness of the skin and / or improving skin smoothness. In one embodiment, the cosmetic non-therapeutic treatment and / or care method of the skin is a preventive treatment of skin aging.

[0152] In another aspect, the present invention provides a compound of formula (I), its stereoisomer and / or its pharmaceutically acceptable salt, or a pharmaceutical composition comprising them, for use as a medicament. In particular, the present invention provides a compound of formula (I), its stereoisomer and / or its pharmaceutically acceptable salt, or a pharmaceutical composition comprising them, for use in treating or preventing a disease or disorder. In another aspect, the present invention provides the use of a compound of formula (I), its stereoisomer and / or its pharmaceutically acceptable salt, for the manufacture of a medicament for treating or preventing a disease or disorder. In another aspect, the present invention provides a method for treating or preventing a disease or disorder in a subject, comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or a pharmaceutical composition comprising it.

[0153] For the above methods of the present invention, topical or transdermal application may be performed by iontophoresis, sonophoresis, electroporation, mechanical pressure, osmotic gradients, occlusion therapy, microinjection, needle-free injection by pressure, microelectrical patches, face masks or any combination thereof.

[0154] For the above-mentioned methods of the invention, the frequency of application or administration can vary widely depending on the needs of each subject, but the recommended application is once a month to 10 times a day, preferably once a week to 4 times a day, more preferably three times a week to twice a day, and even more preferably once a day. For example, the frequency of administration of a method of treating and / or caring for the skin, hair, nails, and / or mucous membranes of a subject, comprising administering to the subject a combination of a compound of the invention, a stereoisomer thereof, and / or a cosmetically or pharma- ceutically acceptable salt thereof, and a botulinum toxin and / or Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2, can vary widely depending on the needs of each subject. In one embodiment, the method of the invention includes administration of a botulinum toxin, followed by administration of a compound or composition of the invention. In certain embodiments, after administration of the botulinum toxin, the compound or composition of the invention is administered at least once a day for at least one week. More specifically, the compound or composition of the invention is administered at least once a day until the next administration of the botulinum toxin.

[0155] Compositions of the Invention The compounds of the present invention may be administered for application in the form of a composition containing the compound by any means which results in contact between the compound and the site of action in the body of a subject, preferably a mammal, preferably a human.

[0156] In another aspect, the present invention provides compositions comprising a compound according to formula (I), its stereoisomers and / or cosmetically or pharma- ceutically acceptable salts.

[0157] In particular, the present invention provides cosmetic compositions comprising a compound according to formula (I), its stereoisomers and / or cosmetically acceptable salts, together with at least one cosmetically acceptable excipient or adjuvant. These compositions may be prepared by conventional means known to those skilled in the art ["Harry's Cosmeticology", Seventh edition, (1982), Wilkinson JB, Moore RJ, ed. Longman House, Essex, GB].

[0158] The compound of the present invention has variable solubility in water according to the nature of its amino acid sequence or any possible modification at N-terminus and / or C-terminus.Therefore, the compound of the present invention can be incorporated into the composition by aqueous solution, and the compound that is not water-soluble can be solubilized in conventional cosmetically or pharmaceutical acceptable solvent, including but not limited to ethanol, propanol, isopropanol, propylene glycol, glycerin, butylene glycol or polyethylene glycol or any combination thereof.

[0159] The cosmetically effective amount of a compound of the present invention to be administered, as well as the dosage of the compound, will depend on a number of factors, including the age, condition of the patient, the nature or severity of the condition, the disorder or disease being treated and / or cared for, the route and frequency of administration, and the particular nature of the compound used.

[0160] The terms "cosmetically effective amount" and "pharmaceutical effective amount" are understood to mean a non-toxic but sufficient amount of the compound(s) of the present invention to provide the desired effect. The terms "pharmaceutical effective" and "therapeutically effective" are used interchangeably herein. The compounds of the present invention are used in the cosmetic or pharmaceutical compositions of the present invention at a cosmetically or pharmaceutical effective concentration to achieve the desired effect, for example, in an amount of 0.00000001% (wt) to 20% (wt), 0.000001% (wt) to 15% (wt), 0.00001% (wt) to 10% (wt), or 0.0001% (wt) to 5% (wt) relative to the total weight of the composition.

[0161] The compounds of formula (I), their stereoisomers, mixtures thereof and / or their cosmetically or pharma- ceutically acceptable salts may also be incorporated into cosmetic or pharmaceutical delivery and / or sustained release systems.

[0162] The term "delivery system" refers to diluent, adjuvant, excipient or carrier that is administered with the compound of the present invention.These cosmetic or pharmaceutical carriers are liquids such as water, oil or surfactants, including those of petroleum, animal, vegetable or synthetic origin, and include, but are not limited to, peanut oil, soybean oil, mineral oil, sesame oil, castor oil, polysorbate, sorbitan ester, ether sulfate, sulfate, betaine, glycoside, maltoside, fatty alcohol, nonoxynol, poloxamer, polyoxyethylene, polyethylene glycol, dextrose, glycerol, digitonin and the like.Those skilled in the art will know the diluent, adjuvant or excipient that can be used in various delivery systems that can administer the compound of the present invention.

[0163] The term "sustained release" is used in its conventional sense in reference to a compound delivery system that provides for gradual release of the compound over a period of time, preferably, but not necessarily, at a relatively constant compound release level over a period of time.

[0164] Examples of delivery or sustained release systems include, but are not limited to, liposomes, mixed liposomes, oleosomes, niosomes, ethosomes, milliparticles, microparticles, nanoparticles and solid lipid nanoparticles, nanostructured lipid carriers, sponges, cyclodextrins, vesicles, micelles, surfactant mixed micelles, surfactant-phospholipid mixed micelles, millispheres, microspheres and nanospheres, lipospheres, millicapsules, microcapsules and nanocapsules, and microemulsions and nanoemulsions, which can be added to achieve better penetration of the active ingredient and / or improve its pharmacokinetic and pharmacodynamic properties. Preferred delivery or sustained release systems are liposomes, surfactant-phospholipid mixed micelles, microemulsions, more preferably water-in-oil microemulsions with reverse micelle internal structure and nanocapsules containing microemulsions.

[0165] In one embodiment, the present invention provides a cosmetic or pharmaceutical composition comprising a compound of formula (I) and a cosmetically or pharma- ceutically acceptable carrier selected from the group consisting of creams, emulsions, gels, liposomes, nanoparticles, and ointments.

[0166] Sustained release systems can be prepared by methods known in the prior art, and compositions containing the systems can be administered, for example, by topical or transdermal administration, including adhesive patches, non-adhesive patches, occlusive patches and microelectric patches, or by systemic administration (for example, but not limited to, oral routes, or parenteral routes, including nasal, rectal or subcutaneous implantation or injection, or direct implantation or injection into a particular body part), and should preferably release a relatively constant amount of the compound of the invention. The amount of compound contained in a sustained release system depends, for example, on the location where the composition is administered, the kinetics and duration of release of the compound of the invention, and the nature of the condition, disorder and / or disease being treated and / or cared for.

[0167] The compounds of the present invention may also be adsorbed onto solid organic polymers or solid inorganic supports such as, but not limited to, talc, bentonite, silica, starch or maltodextrin, among others.

[0168] The composition containing the compound of formula (I), its stereoisomers, their mixtures, and / or their cosmetically or pharma- ceutically acceptable salts can be incorporated into fabrics, nonwovens, and medical devices that come into direct contact with the skin, and thus release the compound of the present invention, whether by the moisture of the body, the pH of the skin, or by body temperature, by biodegradation of the binding system to the fabric, nonwoven, or medical device, or by friction between the fabric, nonwoven, or medical device and the body.Furthermore, the compound of the present invention can be incorporated into fabrics and nonwovens that are used to make clothing that comes into direct contact with the body.

[0169] Examples of fabrics, nonwovens, clothing, medical devices and means for immobilizing compounds thereon are among others the delivery systems and / or sustained release systems mentioned above, which can be found in the literature and are known in the prior art [Schaab CK (1986) HAPPI May 1986; Nelson G., "Application of microencapsulation in textiles", (2002), Int. J. Pharm., 242(1-2), 55-62; "Biofunctional Textiles and the Skin" (2006) Curr. Probl. Dermatol. v. 33, Hipler UC and Elsner P., eds. S. Karger AG, Basel, Switzerland; Malcolm RK et al., "Controlled release of a model antibacterial drug from a novel self-lubricating silicone "biomaterial", (2004), J. Cont. Release, 97(2), 313-320]. Preferred fabrics, nonwovens, garments and medical devices are bandages, gauzes, t-shirts, socks, tights, underwear, girdles, gloves, diapers, sanitary napkins, dressings, bed covers, wipes, adhesive patches, non-adhesive patches, occlusive patches, micro-electrical patches and / or face masks.

[0170] The cosmetic or pharmaceutical compositions containing the compounds of the present invention, their stereoisomers, mixtures thereof and / or their cosmetically or pharma- ceutically acceptable salts may be used in a variety of different types of compositions for topical or transdermal application, which compositions optionally contain cosmetically or pharma- ceutically acceptable excipients necessary for the formulation of the desired administration form.

[0171] Compositions for topical or transdermal application can be made into any solid, liquid, or semi-solid formulation, for example, but not limited to, creams, multiple emulsions, including but not limited to, oil-in-water and / or silicone-in-water emulsions, water-in-oil and / or water-in-silicone emulsions, water / oil / water or water / silicone / water emulsions, and oil / water / oil or silicone / water / silicone emulsions, anhydrous compositions, aqueous dispersions, oils, milks, balsams, foams, lotions, gels, cream gels, hydroalcoholic solutions, hydroglycolic solutions, hydrogels, liniments, serums, soaps, shampoos, conditioners, serums, polysaccharide films, ointments, mousses, pomades, powders, bars, pencils, and sprays or aerosols (sprays), including leave-on and rinse-off formulations. These topical or transdermal formulations can be incorporated using techniques known to those skilled in the art into various types of solid equipment, including, but not limited to, bandages, gauze, T-shirts, socks, tights, underwear, girdles, gloves, diapers, sanitary napkins, bandages, bed covers, wipes, adhesive patches, non-adhesive patches, occlusive patches, micro-electrical patches or face masks, or into various makeup products, such as makeup foundations, including liquid foundations and compact foundations, makeup remover lotions, makeup remover emulsions, dark circle concealers, eye shadows, lipsticks, lip protectors, lip glosses and powders, among others.

[0172] The cosmetic or pharmaceutical composition of the present invention may include an agent that increases the percutaneous absorption of the compound of the present invention, such as, but not limited to, dimethylsulfoxide, dimethylacetamide, dimethylformamide, surfactants, azone (1-dodecylazacycloheptan-2-one), alcohol, urea, ethoxydiglycol, acetone, propylene glycol, or polyethylene glycol, among others. Furthermore, the cosmetic or pharmaceutical composition of the present invention may be applied to the local area to be treated by iontophoresis, sonophoresis, electroporation, microelectric patch, mechanical pressure, osmotic gradient, occlusive cure, microinjection or needleless injection by pressure such as injection by oxygen pressure, or any combination thereof, to achieve better penetration of the peptide of the present invention. The area of ​​application is determined by the nature of the condition, disorder, and / or disease to be treated and / or cared for.

[0173] Furthermore, the compositions containing the compounds of formula (I), their stereoisomers, mixtures thereof and / or their cosmetically or pharma- ceutically acceptable salts can be used in various types of preparations for oral administration, preferably in the form of oral cosmetics or drugs, such as, but not limited to, capsules, including gelatin capsules, soft capsules, 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 forms known to those skilled in the art. In certain embodiments, the compounds of the present invention can be incorporated into any form of functional or enriched food, including, but not limited to, dietary bars or compact or non-compact powders. These powders can be dissolved in water, soda, dairy products, soybean derivatives, or incorporated into dietary bars. The compounds of the present invention can be formulated with common excipients and adjuvants for oral compositions or dietary supplements, including, but not limited to, fatty components, aqueous components, humectants, preservatives, texturizing agents, flavors, aromas, antioxidants and colorants common in the food industry.

[0174] Cosmetic or pharmaceutical compositions containing the compounds of formula (I), their stereoisomers, their mixtures and / or their cosmetically or pharma- ceutically acceptable salts can be administered by any other suitable route, such as oral or parenteral, as well as by topical or transdermal route, and therefore the compositions contain pharma- ceutically acceptable excipients necessary for the formulation of the desired dosage form.In the context of the present invention, the term "parenteral" includes intravascular injections such as nasal, auricular, ocular, rectal, urethral, ​​vaginal, subcutaneous, intradermal routes, intravenous, intramuscular, intraocular, intravitreal, intracorneal, intraspinal, intramedullary, intracranial, intracervical, intracerebral, intrameningeal, intraarticular, intrahepatic, intrathoracic, intratracheal, intrathecal and intraperitoneal, as well as any other similar injection or infusion technique.Those skilled in the art are aware of the various means by which cosmetic or pharmaceutical compositions containing the compounds of the present invention can be administered.

[0175] Among the cosmetically or pharma- ceutical acceptable adjuvants contained in the cosmetic or pharmaceutical compositions according to the present invention are additional ingredients commonly used in cosmetic or pharmaceutical compositions, such as, but not limited to, anti-wrinkle agents, Botox-like agents, and / or anti-aging agents, (ii) firming agents, skin elasticity agents, and / or restructuring agents, moisturizing agents, (iv) photoaging prevention agents and / or blue light protection agents, DNA protection agents, DNA repair agents, and / or stem cell protection agents, free radical scavengers and / or anti-glycation agents, detoxifying agents, antioxidants and / or anti-pollution agents, antiperspirants, stimulators or inhibitors of melanin synthesis, skin whitening or depigmenting agents, pigmentation agents, self-tanning agents, lipolytic agents or agents stimulating lipolysis, adipogenic agents, etc. Additional examples can be found in the CTFA International Cosmetic Ingredient Dictionary & Handbook, 12th Edition (2008).

[0176] In one embodiment, the present invention provides a cosmetic or pharmaceutical composition comprising a compound of formula (I) and a pharma- ceutical or cosmetically effective amount of an adjuvant selected from the group consisting of: (i) anti-wrinkle, Botox-like, and / or anti-aging agents, (ii) firming, skin elasticity, and / or restructuring agents, (iii) moisturizing agents, (iv) photoaging prevention and / or blue light protection agents, (v) DNA protection agents, DNA repair agents, and / or stem cell protection agents, (vi) free radical scavengers and / or anti-glycation agents, detoxifying agents, antioxidants and / or anti-pollution agents, and / or combinations thereof.

[0177] In certain embodiments, the anti-wrinkle, Botox-like, and / or anti-aging agent is 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® 1000® (INCI: Palmitoyl Pentapeptide-4), Matrixyl® 2000® (INCI: Palmitoyl Tetrapeptide-7, Palmitoyl Oligopeptide), Matrixyl® Synthe'6 (INCI: Glycerin, Water, Hydroxypropyl Cyclodextrin, Palmitoyl Tripeptide-38), Matrixyl® 1000® (INCI: Palmitoyl Pentapeptide-4), Matrixyl® 1000® (INCI: Palmitoyl Tetrap ... ) 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 Hydroxyethylcellulose, Lecithin), Biopeptide CL (INCI: Palmitoyl Oligopeptide), Biopeptide EL (INCI: Palmitoyl Oligopeptide), Rigin (INCI: Palmitoyl Tetrapeptide-3), Biobustyl (INCI: Glyceryl Polymethacrylate, Rahnella / Soy Protein Ferment, Palmitoyl Oligopeptide), Dynalift (INCI: Sodium Polystyrene Sulfonate, Sorghum Bicolor Stalk Juice, Glycerin), Idealift (INCI: Acetyl Dipeptide-1 Cetyl Ester), Siegesbeckia (INCI: SiegesbeckiaOrientales Extract), Ovaliss (INCI: Coco-glucoside, Caprylyl Glycol, Alcohol, Glaucine), Juvinity™ (INCI: Geranylgerani Isopropanol), Prolevis (INCI: Hydrolyzed Vegetable Protein), Idealift™ (INCI: Hydroxyethylcellulose, Acetyl Dipeptide-1 Cetyl Ester), Beautifeye™ (INCI: Albizia Julibrissin Bark Extract, Darutoside), Chromocare™ (INCI: Sigesbeckia Orientalis Extract, Rabdosia Rubescens Extract) or Resistem™ (Suggested INCI: Globularia Cordifolia Cordifolia fermentate), 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, oxidoreductase), Pepha-Nutrix (INCI: Natural nutritional factors), Pepha-Tight (INCI: Algae extract, pullulan), Pentacare-NA (INCI: Hydrolyzed wheat gluten, Ceratonia siliqua (carob) gum ... Siliqua Gum), Syn®-Tac (INCI: Glycerin, Palmitoyl Dipeptide-5 Diaminobutyloyl Hydroxythreonine, Palmitoyl Dipeptide-6 Diaminohydroxybutyrate), BeauActive MTP (INCI: Hydrolyzed Milk Protein), Syn®-TC (INCI: Tetradecyl Aminobutyroylvalylaminobutyric Urea Trifluoroacetate)Trifluoroacetat), Palmitoyl Tripeptide-5, Palmitoyl Dipeptide-5 Diaminobutyroyl Hydroxythreonine), Syn®-Hycan (INCI: Tetradecyl Aminobutyroyl Valyl Aminobutyric Urea Trifluoroacetate), Syn®-Glycan (INCI: Tetradecyl Aminobutyroyl Valyl-Aminobutyric Urea Trifluoroacetate), Regu-Age (INCI: Hydrolyzed Rice Bran Protein, Oxidoreductase, Glycine Soja Protein), Pepha-Timp (INCI: Human Oligopeptide-20), Pepha-Age (INCI: Dunaliella Salina Extract), Colhibin (INCI: Hydrolyzed Rice Protein), Elhibin (INCI: Glycine Soja Protein), soja protein, disodium cocoamphodiacetate), or All-Q™ Plus (INCI: ubiquinone, tocopheryl acetate), Myoxinol™ (INCI: hydrolyzed okra (hibiscus esculentus) extract, Myoxinol™ LS 9736 (INCI: hydrolyzed okra (hibiscus esculentus) extract, dextrin), Syniorage™ (INCI: acetyl tetrapeptide-11), Dermican™ (INCI: acetyl tetrapeptide-9), DN-AGE® LS (INCI: Cassia alata leaf extract), Hyalufix GL (INCI: Alpinia galanga leaf extract), Neurobiox (INCI: Achillea millefolium extract), sold by Laboratoires Serobiologiques / Cognis / BASF. Millefolium Extract), Deliner (INCI: Zea May (Corn) Kernel Extract), Lys'lastine V (INCI: Peucedanum Graveolens (Dill) Extract), Extracellium (INCI: Hydrolyzed Potato Protein), Proteasyl TP LS 8657 (INCI: PisumSativum Extract), Flavagrum PEG (INCI: PEG-6 Isostearate, Hesperetin Laurate), Micromerol (INCI: Pyrus Malus Fruit Extract), Extracellium (INCI: Hydrolyzed Potato Protein), Marine Filling Spheres (INCI: Pentaerythrityl Tetraisostearate, Silica Dimethylsilylate, Sodium Chondroitin Sulfate, Atelocollagen), Triactigen (INCI: Mannitol, Cyclodextrin, Yeast Extract, Disodium Succinate), Eterniskin (INCI: Maitake (Grifola Frondosa) Fruiting Body Extract, Maltodextrin), Ascotide (INCI: Ascorbyl Phosphate Succinoyl Pentapeptide-12), Hyalurosmooth (INCI: Senna (Cassia Angustifolia) Seed Polysaccharide), Indinyl CA (INCI: Senna (Cassia Angustifolia seed polysaccharides), Arganyl (INCI: Argania spinosa leaf extract), Sphingoceryl Veg (INCI: Phytoceramides), 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: LitchiChinensis (Acetyl Hexapeptide-8) Peel Extract), Argireline® (INCI: Acetyl Heptapeptide-4), SNAP-8 (INCI: Acetyl Octapeptide-3), Leuphasyl® (INCI: Pentapeptide-18), Inyline® (INCI: Acetyl Heptapeptide-30), Aldenine® (INCI: Hydrolized Wheat Protein, Hydrolyzed Soy Protein, Tripeptide-1) sold by Lipotec / Lubrizol , Preventhelia® (INCI: Diaminopropionoyl Tripeptide-33), Decorinyl® (INCI: Tripeptide-10 Citrulline), Decorinol® (INCI: Tripeptide-9 Citrulline), Trylagen® (INCI: Pseudoalteromonas Ferment Extract, Hydrolyzed Wheat Protein, Hydrolyzed Soy Protein, Tripeptide-10 Citrulline, Tripeptide-1), Eyeseryl® (INCI: Acetyl Tetrapeptide-5), PeptideAC29 (INCI: Acetyl Tripeptide-30 Citrulline), Relistase® (INCI: Acetyl Arginyl Tryptophyl Diphenylglycine), Thermostressine® (INCI: Acetyl Tetrapeptide-22), Lipochroman™ (INCI: Dimethyl Methoxychromanol), Chromabright® (INCI: Dimethyl Methoxychromanyl Palmitate), Antarcticine®: Pseudoalteromonas Ferment Extract ), dGlyage® (INCI: Lysine HCl, Lecithin, Tripeptide-9 Citrulline), Vilastene™ (INCI: Lysine HCl, Lecithin, Tripeptide-10 Citrulline), Hyadisine® (INCI: Pseudoalteromonas Ferment Extract), Hyanify™ (INCI: Saccharide Isomerates), Diffuporine® (INCI: Acetyl Hexapeptide-37), Silusyne® (INCI: Soy (Glycine soja) Oil, Sorbitan Sesquioleate, Isohexadecane, Sodium Hyaluronate, Lauryldimonium Hydroxypropyl Hydrolyzed Soy Protein, Acetyl Hexapeptide-39), Adifyline® (INCI: Acetyl Hexapeptide-38), Delisens™ (INCI: Acetyl Hexapeptide-46), Telangyn™ (INCI: Acetyl Tetrapeptide-40), Reproage™ Peptides (INCI: Acetyl Hexapeptide-8), Cellynkage™ Marine Proteins (INCI: Saccharide isomerates), Eyedeline™ Marine Formula (INCI: Plankton extract), uplevity™ (INCI: Acetyl tetrapeptide-2), Seacode™ Marine Formula (INCI: Pseudoalteromonas ferment extract), or Serilesine® Peptide Solution (INCI: Hexapeptide-10), Sirtalice™ (INCI: Bacillus ferment), sold by Lipotrue, Epitensive™ (INCI: Nicotiana benthamiana hexapeptide-40 SH-oligopeptide-1), Scelleye™ (INCI: Nicotiana benthamiana 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), Collaxyl® IS (INCI: Hexapeptide-9), Laminixyl IS™ (INCI: Heptapeptide), Orsirtine™ GL (INCI: Oryza sativa (rice) extract), D'Orientine™ IS (INCI: phoenix dactylifera (date palm) seed extract), Phytoquintescine™ (INCI: Triticum aestivum L.) sold by Vincience / ISP / Ashland. 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: Apple (PyrusMalus (Apple) Seed Extract), Dynachondrine™ ISR (INCI: Hydrolyzed Soy Protein), Prolixir S20™ (INCI: Dimer Tripeptide-43), Phytocohesine™ PSP (INCI: Beta-Sitosteryl Sodium 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 Communis (Pear) Seed Extract) Molle Extract), Harmoniance™ (INCI: Lotus (Nelumbo Nucifera) Flower Extract), Serenityl (INCI: Condurango (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 African Baobab (Adansonia Digitata) Extract), Natriance Repair Extract (INCI: Hydrolyzed Flaxseed Extract), Natriance Self-Hydrating Extract (INCI: Pea (Pisum Sativum) Extract), Actopontine YST (INCI: Hydrolyzed Yeast Protein), or Telosense™ (Indicated INCI: Hydrolyzed Soybean Protein, Hydrolyzed Yeast Protein), Infinitec BONT-L-Peptide (INCI: Palmitoyl Hexapeptide-19), TIMP Peptides (INCI: Acetyl Hexapeptide-20), ECM Moduline (INCI: Palmitoyl Tripeptide-28), Renaissance (INCI: Hydrolyzed Wheat Protein, Palmitoyl Decapeptide-21, Decapeptide-22, Oligopeptide-78, Zinc Palmitoyl Nonapeptide-14) sold by Activos, or X50 Anti-Aging Agent (INCI: Lactic / Glycolic Acid Copolymer, Polyvinyl Alcohol, Copper Palmitoyl Heptapeptide-14, Heptapeptide-15 Palmitate) sold by Coletica / Engelhard / BASF, EquiStat (INCI: Apple (Pyrus Malus) Fruit Extract, Wild Soybean (Glycine Soja) Fruit Extract, Glycine Soja) sold by Coletica / Engelhard / BASF,soja seed extract), Juvenesce (INCI: Ethoxydiglycol and Caprylic Triglyceride, Retinol, Ursolic Acid, Phytonadione, Ilomastat), Ursolisome (INCI: Lecithin, Ursolic Acid, Atelocollagen, Xanthan Gum, Sodium Chondroitin Sulfate), Basaline (INCI: Hydrolyzed Malt Extract), Phytokine (INCI: Hydrolyzed Soy Protein), Ameliox (INCI: Carnosine, Tocopherol, Milk Thistle (Silybum marianum) Fruit Extract) or PhytoCellTec Malus Domestica (INCI: Apple (Malus domestica) Fruit Cell Culture), Lipobelle Soyaglicane (INCI: Soy Isoflavones), RoyalEpigen P5 (INCI: Shea Butter (Butyrospermum Parkii Butter, Hydrogenated Lecithin, Maltodextrin, Pentapeptide-48, Phenethyl Alcohol, Ethylhexylglycerin, Glycerin, Aqua), or DermCom (INCI: Crocus Chrysanthus Bulb Extract, Acacia Senegal Gum, Aqua / Water), ActiMatrix (INCI: Peptide-Based Mushroom Extract) sold by Active Organics / Arch, Peptamide 6 (INCI: Hexapeptide-11), and combinations thereof.

[0178] In another embodiment, the firming, skin elasticity and / or restructuring agent is 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 Tetrapeptide-11, Acetyl Tetrapeptide-9) sold by BASF, Prolevis (INCI: Hydrolyzed Vegetable Protein) or Poretect (INCI: Caprylic / Capric Triglyceride, Sorbitan Trioleate, Celery (Apium Graveolens) Seed Extract, Linum Usitatissimum Seed Extract) sold by Sederma / Croda, Actifirm Ultra Advanced botanical ingredient (INCI: Centella Asiatica Extract, Rosmarinus Officinalis Leaf Extract, Dipropylene Glycol, Alcohol, Echinacea Anguilla Root Extract) sold by Lipotec / Lubrizol. Angustifolia leaf extract) or Actifcol Advanced botanical ingredient (INCI: Aqua, Glycerin, Sodium Citrate, Lentinus Edodes extract, Potassium Sorbate, Sodium Benzoate, Phytic Acid), Densorphin™ sold by Mibelle (INCI: Vitex Agnus Castus extract, Aqua, Maltodextrin) or PhytoCellTec™ nunatak® (INCI: Isomalt, Aqua, Saponaria Pumila callus culture extract, Lecithin), and combinations thereof.

[0179] In another embodiment, the moisturizer is selected from the group consisting of qua Shuttle (INCI: Sorbitol, Laminaria Digitata extract, Diatomaceous Earth) sold by Infinitec, Aqua-Osmoline™ (INCI: Ceratonia Siliqua (Carob) seed extract) sold by Vincience / ISP / Ashland, Hydralphatine™ Asia (INCI: Hydrogenated Starch Hydrolysate, Panthenol, Bambusa Vulgaris Shoot Extract, Nelumbo Nucifera Flower Extract, Nymphaea Alba Root Extract) sold by Lucas Meyer Cosmetics / Unipex, or Hydraporine™ (INCI: Betaine, Hydrogenated Lecithin, Honey, Pectin), L.PatcH2O™ (INCI: Trehalose, Urea, Serine, Glyceryl Polyacrylate, Algin, Sodium Hyaluronate, Pullulan), Aqu'activ™ (INCI: Behenyl Alcohol, Glyceryl Oleate, Cocamide MIPA), Irwinol® (INCI: Octyldodecanol, African Mango (Irvingia Gabonensis) Kernel Butter, Hydrogenated Cocoglycerides), 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), snow algae powder sold by Mibelle (INCI: Coenochloris Signiensis extract), Hyasol BT (INCI: Sodium hyaluronate) sold by Pentapharm / DSM, Syn-Up™ (INCI: Benzylsulfonyl D-seryl homophenylalanine amidinobenzamide acetate), or Pentavitin® (INCI: Saccharide isomerate), Aqualance™ (INCI: Erythritol, Homarine HCl), Hydraprotectol™ (INCI: Glyceryl Polymethacrylate, Aryl Acid, Yeast Extract (Faex), Glycoproteins), Moist 24™ (INCI: Imperata Cylindrica Root Extract), Optimum™ (INCI: Imperata Cylindrica Root Extract), sold by Sederma / Croda Hyal™ (INCI: Hydrolyzed Yeast Extract, Cetyl Hydroxyethylcellulose, Polyglucuronic Acid), Osmocide® 4 (INCI: Glycerin, Acrylates / C10-30 Alkyl Acrylate Crosspolymer), or Revidrate™ (INCI: Ethylhexyl Palmitate, Sorbitan Oleate, Sorbitan Laureate, Myristyl Phosphonic Malate), Xpertmoist® Molecular Film sold by Lipotec / Lubrizol (INCI: Glycerin, Pseudoalteromonas Ferment Extract, Xanthan Gum, Proline, Alanine, Serine, Ethylhexylglycerin, Caprylyl Glycol) or Actizyme GL Advanced Botanical Ingredients (INCI: Glycerin, Mucor miehei) miehei) extract, aqua, sodium citrate, potassium sorbate, sodium benzoate, phytic acid), and combinations thereof.

[0180] In another embodiment, the photoprotective and / or blue light protection agent is selected from the group consisting of Algaktiv Genofix CPD (INCI: Plankton Extract, Aqua, Lecithin) sold by Greenaltech, Blumilight™ Biofunctional (Indicated INCI: Water / Aqua (and) Butylene Glycol (and) Theobroma cacao (cocoa) seed extract) sold by Ashland, Lys'Sun (INCI: Hamamelis Virginiana Leaf Extract, Aqua, Pentylene Glycol, Caprylyl Glycol, Xanthan Gum) sold by BASF, Vitachelox (INCI: Vitis Vinifera Seed Extract, Camellia Sinensis Leaf Extract, Quercus Robur Wood Extract) sold by Indena, Freshine L-VCG (INCI: Ascorbyl Glucoside) sold by Bio-technology, Lumicease blue ingredient (INCI: Glycerin, Aqua, Hydrolyzed Pea Protein, Glucose, Sodium Chloride) sold by Lipotec / Lubrizol, Lightwaves Defense (JS+M) (INCI: Jasminum Sambac Leaf Cell Extract) sold by Naolys, Blue Oleoactif (INCI: Glycine soja Oil, Polyglyceryl-3 Diisostearate, Oryza sativa Germ Extract, Oryza sativa Extract) sold by Oleos-Hallstar, Majestem (INCI: Glycerin, Leontopodium Alpinum Callus Culture Extract, Xanthan Gum) or Senestem (INCI: Glycerin, Plantago lanceolata) sold by Sederma. lanceolata) leaf extract, xanthan gum), Blueshield (INCI: Glycerin, Capsicum anguicida) sold by SolabiaAnnuum) fruit extract, xanthan gum, and combinations thereof.

[0181] In another embodiment, the DNA protection agent, DNA repair agent, and / or stem cell protection agent is 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 (referred to as INCI)), Survixyl IS (INCI: Water, Butylene glycol, Pentapeptide-31), and Chrondricare (INCI: Aqua, Butylene glycol Pentapeptide-28), sold by Vincience / ISP / Ashland, Lanacityn® (INCI: Glycerin, Aqua, Alteromonas ferment extract, Chysanthellum indicum extract, and others sold by Atrium Innovations / Lucas Meyer Cosmetics. indicum extract) or Melinoil (INCI: Isopropyl palmitate, Lecithin, Aqua, Acetyl hexapeptide-1), Repair Complex (INCI: Bifida ferment lysate) sold by CLR, Phycojuvenine (INCI: Oweed (Laminaria Digitata)) sold by Codif, Unirepair T-43 (INCI: Butylene glycol, Acetyl tyrosine, Proline, Hydrolyzed vegetable protein, Adenosine triphosphate) sold by Induchem, Dragosine (INCI: Carnosine) sold by Symrise, DN-Age (INCI: Cassia Alata leaf extract) sold by Laboratories Serobiologiques / Cognis / BASF, Helioguard (INCI: Porphyra umbilicalis encapsulated in liposomes) sold by Mibelle Biochemistry Umbilicalis), PhytoCellTec Malus domesticaDomestica) (INCI: PhytoCellTec Malus Domestica) or PhytoCellTec Argan (INCI: Argania spinosa bud cell extract, isomalt, lecithin, sodium benzoate, aqua), Pepha-Protect (INCI: Watermelon extract) sold by Pentapharm / DSM, Celligent (INCI: Sunflower (Helianthus Annuus) seed oil, ethyl ferulate, polyglyceryl-5 trioleate, rosemary (Rosmarinus Officinalis) leaf extract, aqua, disodium uridine phosphate) or Defensil (INCI: Octyldodecanol, Echium Plantagineum seed oil, Cardiospermum Halicacabum extract, Sunflower (Helianthus Annuus seed oil unsaponifiables), Venuceane (INCI: Thermus Thermophilus ferment, glycerin) sold by Sederma / Croda, UV-Soft (INCI: Yeast extract), Renovage (INCI: Caprylic / capric triglyceride, Teprenone), Juvinity (INCI: Caprylic / capric triglyceride, Geranylgeranylpropanol (presented)), Phytessence Holyherb (INCI: Butylene glycol, Eriodictyon Californicum (Holy Herb) flower / leaf / stem extract), or Resistem (INCI: Glycerin, Globularia Cordifolia ferment), Infraguard (INCI: Caesalpinia Spinosa Fruit Pod Extract, Propylene Glycol, Aqua, Sunflower (HelianthusAnnuus (Sprout Extract, Sodium Benzoate, Phenoxyethanol), Heliomoduline (INCI: Low Molecular Weight Peptide from Cotton Seed) or Stem-C-Guard (Hydrolyzed Pea) sold by Silab, and combinations thereof.

[0182] In another embodiment, the reactive carbonyl species scavenger, free radical scavenger and / or anti-glycation agent, detoxifier, antioxidant and / or anti-pollutant agent may be, for example and without limitation, Carnosine and its derivatives, GHK (INCI: Tripeptide-1), and its salts and / or derivatives or Quintescine IS (INCI: Dipeptide-4) sold by Vincience / ISP / Ashland, Preregen (INCI: Glycine soja (soybean) protein, oxidoreductases) sold by Pentapharm / DSM, Edelweiss GC (INCI: Leontopodium Alpinum extract), Lipogard (INCI: Squalane, Ubiquinone), Nectapure (INCI: Buddleja Davidii extract, Thymus vulgaris extract), Thymus truncatula (INCI: Thymus truncatula ... Vulgaris Extract), Alpaflor Nectapure (INCI: Buddleja Davidii Extract, Thymus Vulgaris Extract, Glycerin, Water), or Dismutin-BT (INCI: Saccharomyces cerevisiae Extract, ... cerevisiae), Preventhelia® (INCI: diaminopropionoyl tripeptide-33), Aldenine® (INCI: hydrolyzed wheat protein, hydrolyzed soy protein, tripeptide 1), Lipochroman™ (INCI: dimethylmethoxychromanol), Thermostressine® (INCI: acetyl tetrapeptide-22), Pollushield™ functional ingredients (INCI: diisopropyl adipate, lecithin, acrylic acid / acrylamidomethylpropanesulfonic acid copolymer, dimethylmethoxychromanol, xanthan gum), or Bodyfensine® (INCI: aminohexanoic acid acetyl dipeptide-3), sold by Laboratoiresunactyl (INCI: Mannitol, Pisum Sativum Extract, Histidine HCl, Arginine, Cyclodextrin, Dextrin, Yeast Extract, Acetyl Trisoine, Pyridoxine HCl, 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) sold by Serobiologiques / Cognis / BASF, AquaCacteen (INCI: Glycerin, Opuntia Ficus Indica (Stalk) Extract, Phenoxyethanol, Aqua), Trimoist (KMF) (INCI: Sodium Stearoyl Lactylate, Cetyl Alcohol, Olus Vegetable Oil, Tocopheryl Acetate, Glycerin, Glycine soja (Glycine soja) Sterols, Sodium Lactate, Sodium Barboxymethyl Beta Glucan, Carnosine, Lactic Acid), MelanoBronze (INCI: Vitex Agnus Castus (Carrot) Berry Extract (Phytoendorphin), Acetyl Tyrosine), CM-Glucan (INCI: Carobxymethyl Beta Glucan Sodium, Phenoxyethanol), SunActin (INCI: Helianthus Annuus (Sunflower) Sprout Extract, Tocopherol, Glycerin, Lecithin, Phenoxyethanol, Aqua), GSP-T skin (INCI: Glycerin, Alcohol, Aqua, PEG-40 Hydrogenated Castor Oil, Vitis Vinifera (Grape) Seed Extract), or Detoxophane (INCI: LepidiumSativum (Sativum) Sprout Extract, Lecithin, Phenoxyethanol, Glycerin, Water), Bacocalmine (INCI: PEG-8, Bacopa monniera Extract, Water (Aqua), Hydroxyethylcellulose), Kombuchka (INCI: Saccharomyces / Xylinum Black Tea Ferment, Glycerin, Hydroxyethylcellulose), Citystem (INCI: Glycerin, Marrubium Vulgare Extract), or Prodizia (INCI: Albizia Julibrissin Extract, Glycerin), Extramel C (INCI: Hydroxypropyltrimonium Maltodextrin Crosspolymer, Cucumis Melo (Melon) Fruit Extract), sold by Seppic, Defensine (INCI: Triticum Vulgare (Triticum) Fruit Extract), sold by Silab Vulgare Germ Extract), Apolluskin® (INCI: Taraxacum officinale (Dandelion) Extract), Detoxyl® (INCI: Water, Butylene Glycol, Butyrospermum parkii (Shea Butter) Seed Cake Extract), or Antiglyskin (INCI: Aqua, Helianthus Annuus Seed Extract), and combinations thereof.

[0183] The compositions of the present invention may be for use in any of the applications or uses discussed above under the heading "Applications."

[0184] In another aspect, the present invention relates to a kit for use in a cosmetic, non-therapeutic treatment method for the treatment and / or care of the skin, comprising: (i) a composition comprising a botulinum toxin; (ii) optionally a composition comprising Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2; and (iii) a cosmetic composition comprising a compound of formula (I), (II), or (III).

[0185] (i) the composition comprising botulinum toxin, (ii) the composition comprising Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2 (if present), and (iii) the composition comprising the compound of the present invention according to the first aspect may be in the same or separate containers. In one embodiment, the kit may further comprise a means for applying the composition to the skin. For example, the kit may comprise a means such as a syringe or a microneedle.

[0186] The invention is illustrated by the following non-limiting examples. EXAMPLES

[0187] Common methods Abbreviation The abbreviations used for amino acids follow the recommendations of the 1983 IUPAC-IUB Joint Commission on Biochemical Nomenclature, as outlined in Eur. J. Biochem. (1984) 138:9-37.

[0188] (R), resin; 2-ClTrt-(R), 2-chlorotrityl resin; Ac, acetyl; AcOH, acetic acid; Ala, alanine; AM, 2-[4-aminomethyl-(2,4-dimethoxyphenyl)]phenoxyacetic acid; Arg, arginine; Asn, asparagine; Asp, aspartic acid; Boc, tert-butyloxycarbonyl; DCM, dichloromethane; DIEA, N,N'-diisopropylethylamine; DIPCDI, N,N'-diisopropylcarbodiimide; DMF, N,N-dimethylformamide; ESI-MS, electrospray ionization mass spectrometry; Fmoc, 9-fluorenylmethyloxycarbonyl; Gln, glutamine; Glu , glutamic acid; Gly, glycine; His, histidine; HOBt, 1-hydroxybenzotriazole; HPLC, high performance liquid chromatography; Ile, isoleucine; KOH, potassium hydroxide; Leu, leucine; Lys, lysine; MBHA, p-methylbenzhydrylamine; MeCN, acetonitrile; MeOH, methanol; Met, methionine; Myr, myristoyl; Palm, palmitoyl; Pbf, 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl; Pro, proline; Ser, serine; tBu, tert-butyl; TFA, trifluoroacetic acid; Thr, threonine; Trt, trityl; Val, valine.

[0189] chemical synthesis All synthesis processes are carried out in polypropylene syringes fitted with porous polyethylene disks. The coupling procedures are carried out according to standard procedures based on literature references, and the solvents and soluble reagents are removed by aspiration. The Fmoc group is removed with piperidine-DMF (2:8, v / v) (1×1 min, 1×5 min, 5 mL / g resin) [Lloyd-Williams P. et al. (1997) "Chemical Approaches to the Synthesis of Peptides and Proteins" CRC, Boca Raton (FL, USA)]. Washing between the deprotection, coupling and deprotection steps is carried out with DMF (3×1 min) using 10 mL solvent / g resin each time. The coupling reactions are carried out with 3 mL solvent / g resin. The coupling is controlled by carrying out the ninhydrin test (Kaiser E. et al., Anal. Biochem. (1970), 34:595-598] or the chloranil test [Christensen T., Acta Chem. Scand., (1979), 33B, 763-766]. The coupling reaction is repeated synthesizing the desired peptide. All synthesis reactions and washings are carried out at 25°C.

[0190] Those skilled in the art will recognize that some amino acids are used with their side chain functional groups protected. For example, non-limiting examples of protecting groups are: For the amino acid Glu, tBu, tert-butyl, and For the amino acid Arg, Pbf, 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl, and For the amino acid Gln, it is Trt, trityl.

[0191] HPLC chromatographic analysis is performed on a Shimadzu instrument (Kyoto, Japan) using a reversed-phase column (50×4.6 mm, Kromasil C18, 3.5 μm, Akzo Nobel, Sweden) thermostatized at 30° C. Elution is performed using a gradient of acetonitrile (+0.07% TFA) in water (+0.1% TFA) at a flow rate of 1.6 mL / min, with detection at 220 nm. Electrospray ionization mass spectrometry is performed on a WATERS Alliance ZQ 2000 detector at a flow rate of 0.3 mL / min using a 4:1 mixture of MeCN:H2O (+0.1% TFA) as the mobile phase.

[0192] Example 1 Fmoc-W m -X n -AA1-AA2-AA 3- AA4-Y p -Z q -AM-MBHA-(R), where AA1 is L-Asp, AA2 is L-Val, AA3 is L-Tyr, AA4 is L-Lys, and n, m, p, and q are each 0. Weights were normalized. To remove the Fmoc group, Fmoc-AM-pMBHA resin is treated with piperidine:DMF according to the general protocol described. 5 equivalents of Fmoc-L-Lys(Boc)-OH are incorporated into the deprotected resin in the presence of 5.5 equivalents of DIPCDI and 5 equivalents of HOBt using DMF as solvent for 1 hour.

[0193] The resin is then washed as described in the general methods, the Fmoc group deprotection treatment is repeated and the next amino acid is coupled: 5 equivalents of Fmoc-L-Tyr(tBu)-OH, then 5 equivalents of Fmoc-L-Val-OH, 5 equivalents of Fmoc-L-Asp(tBu)-OH) in the presence of 5 equivalents of HOBt and 5.5 equivalents of DIPCDI in each coupling step.

[0194] After synthesis, the peptidyl-resin is washed with DCM (3 x 1 min).

[0195] By following the method described it is possible to obtain different sequences which vary the desired amino acids to be coupled.

[0196] Example 2 Fmoc-W m -X n -AA1-AA2-AA 3- AA4-AA5-AA 6- -Y p -Z q -AM-MBHA-(R), where AA1 is L-Ala, AA2 is L-Leu, AA3 is L-Lys, AA4 is L-Pro, AA5 is L-Asn, AA6 is L-Thr, and n, m, p, and q are each 0. Weights were normalized. To remove the Fmoc group, Fmoc-AM-pMBHA resin is treated with piperidine:DMF according to the general protocol described. 5 equivalents of Fmoc-L-Thr(tBu)-OH are incorporated into the deprotected resin in the presence of 5.5 equivalents of DIPCDI and 5 equivalents of HOBt using DMF as solvent for 1 hour.

[0197] The resin is then washed as described in the general methods, the Fmoc group deprotection treatment is repeated and the next amino acid is coupled: 5 equivalents of Fmoc-L-Asn(Trt)-OH, then 5 equivalents of Fmoc-L-Pro-OH, 5 equivalents of Fmoc-L-Lys(Boc)-OH, 5 equivalents of Fmoc-L-Leu-OH and finally 5 equivalents of Fmoc-L-Ala-OH in the presence of 5 equivalents of HOBt and 5.5 equivalents of DIPCDI in each coupling step.

[0198] After synthesis, the peptidyl-resin is washed with DCM (3 x 1 min).

[0199] By following the method described it is possible to obtain different sequences which vary the desired amino acids to be coupled.

[0200] Example 3 General method for removal of the Fmoc N-terminal protecting group. The N-terminal Fmoc group of the peptidyl resin obtained in Example 1 or 2 is deprotected as described in the general method (20% piperidine in DMF, 1×1 min+1×5 min). The peptidyl resin is washed with DMF (5×1 min), DCM (3×1 min), diethyl ether (3×1 min) and dried in vacuum.

[0201] Example 4 A method for introducing an R1 palmitoyl group into the peptidyl resin obtained in Example 3. Five equivalents of palmitic acid, predissolved in DMF (1 ml), are added to each of the peptidyl resins obtained in Example 3, respectively, in the presence of HOBt and DIPCDI. The mixtures are allowed to react for 3 hours, after which the resins are washed with DMF (3 x 1 min), DCM (3 x 1 min), diethyl ether (3 x 1 min) and dried in vacuum.

[0202] Example 5 A method for introducing an R1 acetyl group into the peptidyl resin obtained in Example 3. Each of the peptidyl resins obtained in Example 3 is treated with acetic anhydride in the presence of DIEA using DMF as the solvent. The mixture is allowed to react for 30 minutes, after which the resin is washed with DMF (3×1 min), DCM (3×1 min), diethyl ether (3×1 min) and dried under vacuum.

[0203] Example 6 Methods for cleaving the peptidyl-resins obtained in Examples 3, 4 and 5 from the polymeric support. Each of the dried peptidyl resins obtained in Examples 3, 4, and 5 is treated with 3 ml of TFA:H2O (95:5, v / v) for 2 hours at room temperature under stirring. They are then filtered through a polypropylene syringe fitted with a porous polyethylene disk. The filtrate is collected on cold diethyl ether and washed five times with diethyl ether. The final precipitate is dried under vacuum.

[0204] General formula R1-W m -X n -AA1-AA2-AA3- AA4-Y p -Z q -OH, R1-W m -X n -AA1-AA2-AA 3- AA4-NH 2、 R1-W m -X n -AA1-AA2-AA 3- AA4-AA5-AA6-Y p -Z q -OH, or R1-W m -X n -AA1-AA2-AA 3- AA4-AA5-AA6-Y p -Z q Peptides with -NH2, where R1 is H, acetyl or palmitoyl, are obtained according to this method.

[0205] HPLC analysis of the peptides obtained in a gradient of H2O (+0.1% TFA) containing MeCN (+0.07% TFA) shows a purity of more than 80% in all cases. The identity of the peptides obtained is confirmed by ESI-MS.

[0206] Example 7 In vitro quantification of muscle-bound-like protein 1 (MBNL1) in human skeletal muscle cells by time-resolved fluorescence resonance energy transfer. Aging is associated with loss of muscle mass. Reduced function of muscle-binding-like protein 1 (MBNL1) is associated with the loss of muscle mass associated with the aging process in facial muscles.

[0207] MBNL1 induction by the peptides of the present invention is assessed by time-resolved fluorescence resonance energy transfer (TR-FRET) assay. The aim of this study is to investigate the ability of peptide candidates to increase MBNL1 in human skeletal muscle cells (hSkMc).

[0208] hSkMc (Innoprot) was cultured in skeletal muscle cell growth medium (Promocell) at 1.5x10 4Cells are seeded in 12-well plates at a density of 10 ...

[0209] Measurement of MBNL1 protein levels is performed using the Human MBNL1 Assay Kit (Cisbio) according to the manufacturer's protocol. Briefly, the kit is used to perform TR-FRET for MBNL1 quantification. Protein is detected with the antibody included in the kit and quantified by fluorimetry. Quantification is performed using a microplate reader (ClarioStar, BMG) set at 665 nm and 620 nm.

[0210] The total protein concentration of the cell lysates is determined using the Pierce BCA Protein Assay Kit (Thermo Scientific) according to the manufacturer's protocol. Briefly, after adding Working Reagent to the samples and standards, the samples are incubated. The color change is then measured at 562 nm using an absorbance microplate reader (Clariostar, BMG). The total protein amount is used to normalize the levels of MBNL1 protein concentration obtained by the TR-FRET test of the samples.

[0211] The results demonstrate that the peptides of the present invention, PEP1 (Ac-Asp-Val-Tyr-Lys-NH2) and PEP2 (H-Ala-Leu-Lys-Pro-Asn-Thr-NH2), increase MBNL1 levels when compared to basal controls (Figure 1). Enhancing MBNL1 protein is believed to slow the loss of muscle mass during aging, thus avoiding the appearance of sagging facial skin in the elderly.

[0212] Example 8 In vitro quantification of muscle-binding-like protein 1 (MBNL1) in human dermal fibroblasts by immunofluorescence. Increased collagen synthesis is thought to be beneficial in reducing the signs of aging. Muscle-binding-like protein 1 (MBNL1) in fibroblasts activates transdifferentiation into myofibroblasts. These cells can release large amounts of extracellular matrix proteins, such as collagen, elastin, or fibronectin, to prevent the appearance of wrinkles.

[0213] MBNL1 induction by the peptides of the present invention is evaluated by immunofluorescence assay.The aim of this study is to investigate the ability of peptide candidates to increase MBNL1 in human dermal fibroblasts (HDFs).

[0214] HDFs (Cascade) were cultured at 8x10 in fibroblast growth medium (Promocell). 3Cells are seeded in 96-well plates at a density of 1000 cells / well. After 48 h of incubation, the medium is removed and fresh medium containing 1, 0.5, and 0.01 mg / ml of the test item is added. Treatment is continued for 24 h, with untreated cells used as basal controls. After 24 h of treatment, immunofluorescence is performed. Cells are fixed with 4% paraformaldehyde (Sigma) for 15 min, permeabilized with 1% Triton X-100 (Sigma) for 15 min, and then blocked with 5% bovine serum albumin (Sigma). The primary antibody anti-MBNL1 rabbit (Sigma) is then added and incubated for 2 h. The secondary antibody Alexa Fluor 488 goat anti-rabbit IgG (Life Technologies) is then added and incubated for 1 h. To stain the nuclei, Hoechst (Life Technologies) is used. Technologies) and incubate for 10 minutes. Finally, the fluorescence intensity and nucleus number of MBNL1 cell nuclei are measured by Operetta (Perkin Elmer). Fluorescence is normalized by cell nuclei and the results are expressed relative to the co-basal control. The results are shown in Figure 2.

[0215] The results demonstrate that the peptides of the invention PEP1 (Ac-Asp-Val-Tyr-Lys-NH2) and PEP2 (H-Ala-Leu-Lys-Pro-Asn-Thr-NH2) increase MBNL1 levels when compared to basal controls.

[0216] Example 9 In vitro prevention of muscle mass loss induced in human skeletal muscle cells by immunofluorescence. Loss of muscle mass is associated with aging in facial muscles. It has been suggested that decreased function of muscle-binding-like protein 1 (MBNL1) in muscle cells may be associated with the loss of muscle mass with aging. It has been reported in the literature that myotube diameters of muscle cells less than 20 μm are an indicator of decreased muscle mass.

[0217] Myosin heavy chain (MHyC) is used as a morphological marker of differentiated myotubes, allowing the measurement of diameter and therefore the extent of mass loss.Tumor necrosis factor alpha (TNF-α) has been described in the literature as a muscle mass loss inducer.

[0218] Prevention of muscle mass loss by peptides of the invention is assessed by immunofluorescence assay. The aim of this study is to investigate the ability of peptide candidates to prevent muscle mass loss in the presence of TNF-α in human skeletal cells (hSKMCs).

[0219] hSkMc (Tebu-Bio) was cultured at 1.5x10 in skeletal muscle cell growth medium (Promocell). 4 Cells are seeded in 96-well plates at a density of 1000 cells / well. After 24 hours of incubation, the medium is replaced with skeletal muscle cell differentiation medium (Promocell) and the cells are allowed to differentiate for 6 days. After this, fresh differentiation medium containing 0.5 mg / ml of the test item and 20 ng / ml of TNFα (Sigma) is added. Treatment is continued for 48 hours, with untreated cells used as basal control and 20 ng / ml of TNFα treated cells used as muscle mass reduction control. After 48 hours of treatment, immunofluorescence is performed. Cells are fixed with 4% paraformaldehyde (Sigma) for 15 minutes, permeabilized with 1% Triton X-100 (Sigma) for 15 minutes, and then blocked with 5% bovine serum albumin (Sigma). Primary antibody anti-MHyC mouse (1:100, in vitro) is then added and incubated for 2 hours. Afterwards, the secondary antibody Alexa Fluor 488 goat anti-mouse IgG (1:250, Life Technologies) is added and incubated for 1 h. Finally, the diameter of the myotubes is determined by imaging the MHyC staining with Operetta (Perkin Elmer). The percentage of mass loss is calculated automatically with Harmony (Perkin Elmer) software by classifying the myotubes by diameter using an atrophy threshold of 20 μm. The results are shown in Figure 4 and are normalized to TNF-α.

[0220] The results demonstrate that the peptides of the invention PEP1 and PEP2 prevent mass loss when compared to TNF-α treatment.

[0221] Example 10 In vitro attenuation of the effects of muscle mass loss induced in human skeletal muscle cells by immunofluorescence. The muscle mass loss correction by the peptides of the present invention is evaluated by immunofluorescence assay. The aim of this study is to investigate the ability of peptide candidates to correct the loss of muscle mass after treatment with TNF-α in human skeletal muscle cells (hSKMCs). Myosin heavy chain (MHyC) is used as a morphological marker of differentiated myotubes, which allows the measurement of the diameter and therefore the extent of mass loss. Tumor necrosis factor alpha (TNF-α) has been described in the literature as a muscle mass loss inducer.

[0222] hSkMc (Tebu-Bio) was cultured at 1.5x10 in skeletal muscle cell growth medium (Promocell). 4Cells are seeded in 96-well plates at a density of 10 ... Cells are fixed with 4% paraformaldehyde (Sigma) for 15 min, permeabilized with 1% Triton X-100 (Sigma) for 15 min, and then blocked with 5% bovine serum albumin (Sigma). Primary antibody anti-MHyC mouse (1:100, Vitro) is then added and incubated overnight at 4 °C. Secondary antibody Alexa Fluor 488 goat anti-mouse IgG (1:250, Life Technologies) is then added and incubated for 1 h. Finally, myotube diameters are measured using Operetta (Perkin Mass loss is determined by imaging of MHyC staining by Perkin Elmer). The percentage of mass loss is calculated automatically using Harmony (Perkin Elmer) software by classifying myotubes by diameter using a mass loss threshold of 20 μm. The results shown in Figure 4 are normalized to mass loss controls.

[0223] The results demonstrate that the peptides of the invention PEP1 and PEP2 correct (ie, reduce) the mass loss when compared to basal controls treated with TNF-α.

[0224] Example 11 In vitro study of type I collagen synthesis in human dermal fibroblasts by AlphaLISA. Collagen induction by the peptides of the invention is evaluated in the AlphaLISA assay. The aim of this study is to investigate the ability of the product to induce collagen type I synthesis in human dermal fibroblasts (HDFa) isolated from adult skin.

[0225] HDFa (Promocell) were cultured at 1x10 in fibroblast growth medium supplemented with C-39016 (Promocell). 5 Cells are seeded into 48-well plates at a density of 10x. After 24 h of incubation, fresh medium supplemented with low serum growth supplement (Gibco) containing 0.5 μg / ml of the test item is added. Treatment is continued for 48 h, with untreated cells used as basal controls. After 48 h of treatment, cell supernatants are collected. A protease inhibitor cocktail (Sigma) is added to each supernatant, which is then stored at -80 °C until analyzed with AlphaLISA using the AlphaLISA COL1A1 detection kit (PerkinElmer) according to the manufacturer's instructions. Briefly, donor and acceptor beads in the presence of collagen type I are close enough to generate a luminescent signal that is directly proportional to the amount of collagen type I present in each condition tested. The color produced by this reaction is measured with a microtiter plate reader, and the concentration of collagen type I is determined using linear regression of the standard curve. Results of collagen synthesis versus untreated cells are shown in Figure 5.

[0226] The results demonstrate that the peptides of the invention enhance the production of type I collagen relative to basal conditions in HDFa at the concentrations tested.

[0227] Example 12 Inhibition of noradrenaline release from human neuroblastoma cells. The aim of this study was to evaluate the efficacy of the peptides of the present invention in inhibiting neuronal exocytosis by measuring the levels of noradrenaline (NA) release in a human neuroblastoma cell line (SH-SY5Y cells) by enzyme-linked immunosorbent assay (ELISA).

[0228] SH-SY5Y (ECACC) cells were cultured at 1 × 10 6 The cells are seeded in 12-well plates at a density of 10 ... The resulting supernatants are used for quantification of NA by ELISA using a noradrenaline ELISA kit (IBL International) according to the manufacturer's instructions. In brief, a direct sandwich ELISA is performed using plates pre-coated with anti-NA antibodies. The color obtained after substrate addition is directly proportional to the amount of NA present in each condition tested. The absorbance at 405 nm is read in a microplate absorbance reader (Clariostar, BMG). The percentage of NA release for each condition is calculated relative to the basal control. The results of the percentage of NA release relative to untreated cells (basal control) are shown in Figure 6.

[0229] The results demonstrate that the peptide of the present invention inhibits NA release against basal condition in SH-SY5Y at the test concentration.Increased exocytosis release at neuromuscular junction is associated with aging and the increase in facial wrinkles and expression lines.The peptide of the present invention reduces exocytosis level, thus reducing NA release in SH-SY5Y.

[0230] Example 13 In vitro lipid accumulation in human subcutaneous preadipocytes. The aim of this study is to investigate the ability of peptide candidates to induce lipid accumulation in human subcutaneous adipocytes and thus prevent adipocyte senescence. Measurement of lipid accumulation in co-cultures of young and old adipocytes indirectly evaluates the inhibition of the senescence-associated secretory phenotype (SASP). In the pool of old adipocytes, there are more senescent cells. When co-cultured with young cells, the observed lipid accumulation is below the theoretically expected level due to the senescence-inducing effect of SASP on young adipocytes.

[0231] The induction of lipid accumulation by the peptides of the present invention is evaluated by Adipored® assay reagent and lipid fluorescence staining. Human subcutaneous preadipocytes (26 and 60 year old donors, Cell Applications) cells were cultured in 96-well plates at 4x10 3 Cells were co-cultured in human preadipocyte growth medium (Sigma) at a density of 8×10 cells / well. Monocultures of each age were 3 Cells / well are seeded at a density of 10 ... The results of the percentage of lipid content relative to untreated cells (basal control) are shown in FIG.

[0232] The results demonstrate that the peptides PEP1 and PEP2 of the invention increase lipid accumulation in adipocytes when compared to basal and aged controls.

[0233] Example 14 Preparation of a cream containing peptide PEP1 (Ac-Asp-Val-Tyr-Lys-NH2) solution In a suitable container, dissolve Phase A ingredients: Water (INCI: Water (Aqua)), Zemea™ (INCI: Propanediol), Hydrolite® 5 (INCI: Pentylene Glycol), Phenoxetol™ (INCI: Phenoxyethanol), and Dissolvine® NA2 (INCI: Disodium EDTA).

[0234] Phase A1 ingredients: Carbopol® Ultrez 10 Polymer (INCI: Carbomer) are added to the previous mixture. Once dispersed, Phase A2: Cola® Fax CPE-K (INCI: Potassium Cetyl Phosphate) is introduced. The mixture is then heated up to 70-75°C.

[0235] In a separate container, mix the ingredients for Phase B: Schercemol™ DIS Ester (INCI: Diisopropyl Sebacate), Phytocream® 2000 (INCI: Glyceryl Stearate, Cetearyl Alcohol, Potassium Palmitoyl Hydrolyzed Wheat Protein), Massocare® EC (INCI: Ethylhexyl Cocoate), Astro-sil 2C 350 (INCI: Dimethicone), and Tocopheryl Acetate (INCI: Tocopheryl Acetate) and heat the resulting mixture to 70-75°C.

[0236] The emulsion is made by slowly adding phase B to phase A under high speed turbine agitation.

[0237] Once the mixture has cooled to 40°C, the components of Phase C: Novemer™ EC-1 polymer (INCI: Mineral Oil (Paraffinum Liquidum), Water (Aqua), Acrylates / Acrylamide Crosspolymer, Polysorbate 85) are added to the previous mixture with stirring and mixed until dispersed.

[0238] Phase D: Add peptide PEP1 solution (INCI: Glycerin, Water (Aqua), Peptide PEP1) to the previous mixture.

[0239] Phase E: Fragrance (INCI: Fragrance (Parfum)) is added.

[0240] Adjust the pH to 6.0-6.5 with Phase F ingredients: Sodium hydroxide 20% w / w (INCI: Water (Aqua), Sodium Hydroxide). [Table 4]

[0241] Preparation of a cream containing peptide PEP2 (H-Ala-Leu-Lys-Pro-Asn-Thr-NH2) solution In a suitable container, dissolve Phase A ingredients: Water (INCI: Water (Aqua)), Zemea™ (INCI: Propanediol), Hydrolite® 5 (INCI: Pentylene Glycol), Phenoxetol™ (INCI: Phenoxyethanol), and Dissolvine® NA2 (INCI: Disodium EDTA).

[0242] Phase A1 ingredients: Carbopol® Ultrez 10 Polymer (INCI: Carbomer) are added to the previous mixture. Once dispersed, Phase A2: Cola® Fax CPE-K (INCI: Potassium Cetyl Phosphate) is introduced. The mixture is then heated up to 70-75°C.

[0243] In a separate container, mix the ingredients for Phase B: Schercemol™ DIS Ester (INCI: Diisopropyl Sebacate), Phytocream® 2000 (INCI: Glyceryl Stearate, Cetearyl Alcohol, Potassium Palmitoyl Hydrolyzed Wheat Protein), Massocare® EC (INCI: Ethylhexyl Cocoate), Astro-sil 2C 350 (INCI: Dimethicone), and Tocopheryl Acetate (INCI: Tocopheryl Acetate) and heat the resulting mixture to 70-75°C.

[0244] The emulsion is made by slowly adding phase B to phase A under high speed turbine agitation.

[0245] Once the mixture has cooled to 40°C, the components of Phase C: Novemer™ EC-1 polymer (INCI: Mineral Oil (Paraffinum Liquidum), Water (Aqua), Acrylates / Acrylamide Crosspolymer, Polysorbate 85) are added to the previous mixture with stirring and mixed until dispersed.

[0246] Phase D: Peptide PEP2 solution (INCI: Glycerin, Water (Aqua), Peptide PEP2) is added to the previous mixture.

[0247] Phase E: Fragrance (INCI: Fragrance (Parfum)) is added.

[0248] Adjust the pH to 6.0-6.5 with Phase F ingredients: Sodium hydroxide 20% w / w (INCI: Water (aqua), Sodium hydroxide). [Table 5]

[0249] Example 15 Preparation of a cream containing peptide PEP1 (Ac-Asp-Val-Tyr-Lys-NH2) solution. In a suitable container, disperse the Phase A ingredients: Water (INCI: Water (Aqua)), Zemea™ (INCI: Propanediol), Phenoxetol® (INCI: Phenoxyethanol), Dissolvine® NA2 (INCI: Disodium EDTA), and Potassium Sorbate Granules (Potassium Sorbate).

[0250] Phase A1 ingredients: Carbopol® Ultrez 21 Polymer (INCI: Acrylates / C10 / 30 Alkyl Acrylates Crosspolymer) are added to the previous mixture with stirring. Once dispersed, Phase A2: Xanthan Gum (INCI: Xanthan Gum) is introduced to the previous mixture and stirred until completely dispersed.

[0251] In a separate container, weigh out the ingredients for Phase B: Schercemol™ 1818 Ester (INCI: Isostearyl Isostearate).

[0252] The emulsion is made by slowly adding phase B to phase A under high speed turbine agitation.

[0253] Phase C: Add Peptide PEP1 solution (INCI: Water (Aqua), Caprylyl Glycol, Peptide PEP1) to the previous mixture.

[0254] Adjust the pH to 6.0-6.5 with Phase D ingredients: Sodium Hydroxide 20% w / w [INCI: Water (AQUA), Sodium Hydroxide]. [Table 6]

[0255] In this example, by substituting PEP2 for PEP1, a gel cream containing the peptide PEP2 (H-Ala-Leu-Lys-Pro-Asn-Thr-NH2) can be obtained.

[0256] Example 16 Preparation of gel containing 2% peptide PEP1 (Ac-Asp-Val-Tyr-Lys-NH2) solution In a suitable container, dissolve Phase A ingredients: Water (INCI: Water (Aqua)), Zemea™ (INCI: Propanediol), Glucam™ E-20 Humectant (INCI: Methyl Gluceth-20), Dissolvine® NA2 (INCI: Disodium EDTA), Phenoxetol® (INCI: Phenoxyethanol).

[0257] Phase A1: Add Carbopol® ultrez 10 polymer (INCI: Carbomer) to the previous mixture and mix until completely dispersed.

[0258] Phase B: Peptide PEP-23 solution (INCI: Water (Aqua), Caprylyl Glycol, PEP-23) is added to the previous mixture and mixed.

[0259] Phase C: EUMULGIN® CO 40 (INCI: PEG-40 Hydrogenated Castor Oil), Fragrance (INCI: Fragrance (Parfum)) are added to the previous mixture and mixed.

[0260] Ingredients for phase D: Sodium hydroxide 20% w / w (INCI: Water (aqua), Sodium hydroxide) to adjust pH to 6.0-6.5. [Table 7]

[0261] In this example, by substituting PEP2 for PEP1, a gel containing the peptide PEP2 (H-Ala-Leu-Lys-Pro-Asn-Thr-NH2) can be obtained.

[0262] Example 17 Preparation of lotion containing 2% peptide PEP1 (Ac-Asp-Val-Tyr-Lys-NH2) solution In a suitable container, dissolve Phase A1 ingredients: Water (INCI: Water (Aqua)), Zemea™ (INCI: Propanediol), Glycerin (INCI: Glycerin), Potassium Sorbate (INCI: Potassium Sorbate), and Dissolvine® NA2 (INCI: Disodium EDTA).

[0263] The ingredients of phase A2: Carbopol® Ultrez 30 Polymer (INCI: Carbomer) are added to the previous mixture. Once dispersed, phase A3: Xanthan Gum (INCI: Xanthan Gum) is introduced. The mixture is then heated to 70-75°C.

[0264] In a separate container, mix the ingredients for Phase B: Fancor® Meadowfoam Seed Oil (INCI: LIMNATHES 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 Esters (INCI: Cocoyl Adipic Acid / Trimethylolpropane Copolymer, Trimethylolpropane), Schercemol™ DIS Esters (INCI: Diisopropyl Sebacate), Tocopheryl Acetate (INCI: Tocopheryl Acetate), and Phenoxetol™ (INCI: Phenoxyethanol) and heat the resulting mixture to 70-75°C.

[0265] The emulsion is made by slowly adding phase B to phase A under high speed turbine agitation.

[0266] Once the mixture has cooled to 40°C, the components of Phase C: Novemer™ EC-2 Polymer (INCI: Water (Aqua), Sodium Acrylate / Beheneth-25 Methacrylate Crosspolymer, Hydrogenated Polydecene, Lauryl Glucoside), SA-SB-300 (7%) (INCI: Silica, Dimethicone), Fragrance (INCI: Fragrance (Parfum)), and Peptide PEP1 Solution (INCI: Water (Aqua), Caprylyl Glycol, Peptide PEP1) are added to the previous mixture.

[0267] Adjust the pH to 6.0-6.5 with Phase D ingredients: Sodium hydroxide 20% w / w (INCI: Water (Aqua), Sodium Hydroxide). [Table 8]

[0268] In this example, PEP1 is replaced by PEP2, resulting in a lotion containing the peptide PEP2 (H-Ala-Leu-Lys-Pro-Asn-Thr-NH2).

[0269] Example 18 Preparation of a fluid emulsion containing 2% peptide PEP1 (Ac-Asp-Val-Tyr-Lys-NH2) solution In a suitable container, dissolve the ingredients of Phase A1: Water (INCI: Water (Aqua)), Zemea™ (INCI: Propanediol), Glycerin (INCI: Glycerin), Genencare™ OSMS BA (INCI: Betaine), Dissolvine® NA2 (INCI: Disodium EDTA), Potassium Sorbate (INCI: Potassium Sorbate).

[0270] Phase A2: Carbopol® ultrez 10 polymer (INCI: Carbomer) is added to the previous mixture. Once dispersed, Phase A3: Cola® Fax CPE-K (INCI: Potassium Cetyl Phosphate) is added. The resulting mixture is heated to 70-75°C.

[0271] In a separate vessel, mix the components of phase B: Massocare® HD (INCI: Isohexadecane), Lincoln BAS (INCI: C12-15 alkyl benzoate), Gandak C (INCI: Cetyl alcohol), Sorbital T 20 P (INCI: Polysorbate 20), 2-phenoxyethanol (INCI: Phenoxyethanol), Vegetable stearic acid 50 / 50 (INCI: Stearic acid, Palmitic acid) and heat to 70-75°C. Phase B is slowly introduced into phase A under conditions of vigorous turbine stirring.

[0272] Cool the mixture at 40 °C and add Phase C: BRB CM 56-S (INCI: Cyclomethicone), Peptide PEP1 solution (INCI: Water (Aqua), Caprylyl Glycol, Peptide PEP1), fragrance (INCI: Fragrance (Parfum)). Phase D ingredients: Adjust pH to 6.0-6.5 with Sodium Hydroxide 20% w / w (INCI: Water (Aqua), Sodium Hydroxide). [Table 9]

[0273] In this example, PEP1 is replaced with PEP2, resulting in a fluid emulsion containing the peptide PEP2 (H-Ala-Leu-Lys-Pro-Asn-Thr-NH2).

[0274] Example 19 In vitro quantification of muscle-bound-like protein 1 (MBNL1) in human skeletal muscle cells by time-resolved fluorescence resonance energy transfer. Different peptides of the invention are tested at 0.5 mg / mL as disclosed in Example 7. The results are shown in Table 10 and demonstrate that all peptides increase MBNL1 levels when compared to the basal control. [Table 10]

[0275] Example 20 In vitro quantification of muscle-bound-like protein 1 (MBNL1) in human skeletal muscle cells by time-resolved fluorescence resonance energy transfer. The assay is carried out as disclosed in Example 7, except that hSkMc from TEBU-BIO (Barcelona, ​​Spain) is used. The different peptides of the invention are tested at a concentration of 0.5 mg / ml.

[0276] The results are shown in Table 11 and demonstrate that all peptides increase MBNL1 levels when compared to basal controls. [Table 11]

[0277] Example 21 In vivo study with a composition containing PEP1 for the evaluation of the anti-wrinkle and smoothing effectiveness of long-term application in female volunteers with Caucasian skin type. The study will be carried out for 28 days. Forty-two (42) Caucasian female volunteers, aged between 35 and 58 years, showing skin wrinkles in the area of ​​crow's feet, will be included. The subjects will apply to one side of the face (left or right) a cream containing PEP1 (active cream) and a placebo cream (placebo cream) having the same composition except for PEP1. Both creams will be applied twice a day (morning and evening) for 28 days. The subjects will act as the reference and will compare the results obtained on the 28th day with those obtained initially and during the treatment (active vs. placebo).

[0278] The anti-wrinkle effectiveness of cream in crow's feet area is evaluated by determining the maximum depth of the maximum wrinkle, and the image of the crow's feet area of ​​volunteers is measured with a 3D microtopography imaging system.Volunteers are instructed to keep smiling, and the maximum depth of the maximum wrinkle is taken at the initial time and 28 days after application of the product.The results of wrinkle reduction after treatment are shown in Table 12. [Table 12]

[0279] The results show that after 28 days of application of the cream, the maximum depth of the largest wrinkle is reduced compared to the initial time, the reduction being much higher for the active cream than for the placebo cream.

[0280] The smoothing effectiveness of the cream is evaluated by determining the arithmetic roughness (Sa). Images of the volunteers' cheeks are taken with a 3D microtopography imaging system. Measurements of the arithmetic roughness (Sa) are taken initially and 28 days after application of the cream. The results of roughness reduction after treatment are shown in Table 13. [Table 13]

[0281] The results show that there is a reduction in arithmetic roughness (Sa) after treatment with the active cream, whereas this effect is negligible for the placebo cream. A reduction in roughness means that the skin is smoother.

[0282] Various aspects and embodiments of the present invention are defined by the following numbered clauses.

[0283] 1. A compound of formula (I), R1-W m -X n -AA1-AA2-AA3-AA4-AA5-AA6-Y p -Z q -R2(I) Stereoisomers and / or cosmetically acceptable salts thereof, wherein AA1 is Asp, Glu, Asn, Gln, Ala, Gly, or no amino acid; AA2 is Val, Ile, Leu, or Ala; AA3 is Tyr, Phe, Trp, Lys, Arg, or His; AA4 is Lys, Arg, His, Pro, or Val; AA5 is Asn, Asp, Gln, or no amino acid; AA6 is Thr, Ala, Ser, or no amino acid; W, X, Y and Z are each independently any amino acid; m, n, p and q are each independently 0 or 1; m+n+p+q is less than or equal to 2, R1 is selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, aralkyl, and R5-CO-, where R5 is selected from the group consisting of H, an acyclic aliphatic group, alicyclyl, aryl, aralkyl, heterocyclyl, and heteroarylalkyl; R2 is selected from the group consisting of -NR3R4, -OR3, -SR3, and R3 and R4 are independently selected from the group consisting of H, a polymer derived from polyethylene glycol, an acyclic aliphatic group, alicyclyl, heterocyclyl, heteroarylalkyl, aryl, and aralkyl; R1 and R2 are compounds, stereoisomers and / or cosmetically acceptable salts thereof that are not amino acids.

[0284] 2. The compound according to clause 1, wherein if AA5 is no amino acid, then AA1 is Asp, Glu, Asn, or Gln, AA2 is Val, Ile, Leu, or Ala, AA3 is Tyr, Phe, or Trp, AA4 is Lys, Arg, or His, and AA6 is no amino acid.

[0285] 3. The compound according to clause 2, wherein AA1 is Asp, Glu, Asn, or Gln, AA2 is Val, Ile, Leu, or Ala, AA3 is Tyr, Phe, or Trp, AA4 is Lys, Arg, or His, AA5 is no amino acid, and AA6 is no amino acid.

[0286] 4. The compound according to clause 3, wherein (I) AA1 is Asp, Glu, or Asn, or (II) AA1 is Asp or Glu.

[0287] 5. The compound according to clause 3 or clause 4, wherein AA2 is Val or Ile.

[0288] 6. The compound according to any one of clauses 3 to 5, wherein AA3 is Tyr or Phe.

[0289] 7. The compound according to any one of clauses 3 to 6, wherein AA4 is Lys or Arg.

[0290] 8. The compound according to any one of clauses 3 to 7, wherein AA1 is Asp, AA2 is Val, AA3 is Tyr and AA4 is Lys.

[0291] 9. R1 is H and R5-CO- (wherein R5 is C1-C 18 Alkyl, C2-C 24 Alkenyl, C3-C 24 cycloalkyl; R2 is selected from the group consisting of -NR3R4 or -OR3 (wherein R3 and R4 are independently selected from H and C1-C 16 9. The compound according to any one of clauses 1 to 8, wherein the compound is selected from the group consisting of alkyl.

[0292] 10. A compound, Ac-W m -X n -Asp-Val-Tyr-Lys-Y p -Z q -NH2(IV), HW m -X n -Ala-Leu-Lys-Pro-Asn-Thr-Y p -Z q -NH2(V), Ac-Asp-Val-Tyr-Lys-NH2 (PEP1), or The compound described in clause 1, which is H-Ala-Leu-Lys-Pro-Asn-Thr-NH2 (PEP2).

[0293] 11. A combination of a compound according to any one of items 1 to 10 or a stereoisomer and / or a cosmetically acceptable salt thereof and with a botulinum toxin and / or a peptide of the sequence Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2.

[0294] 12. A composition comprising a cosmetically effective amount of a compound of formula (I) as defined in any one of clauses 1 to 11, a stereoisomer thereof and / or a cosmetically acceptable salt thereof, or a combination as defined in clause 10, and at least one cosmetically acceptable excipient or adjuvant.

[0295] 13. Use of a compound according to any one of claims 1 to 10, its stereoisomers and / or cosmetically acceptable salts for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes.

[0296] 14. The use according to clause 13, 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 stimulation of collagen synthesis and / or the prevention of collagen loss, the improvement or maintenance of skin firmness, the treatment and / or prevention of the appearance of sagging skin, the reduction and / or prevention of facial asymmetries, the increase in the volume of adipose tissue and / or the prevention and / or reduction of adipose tissue loss.

[0297] 15. A method for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes of a subject, comprising administering to the subject a cosmetically effective amount of a compound according to any one of clauses 1 to 10, a combination according to clause 11 or a composition according to clause 13.

[0298] 16. The method according to clause 15, wherein the non-therapeutic cosmetic treatment and / or care is the treatment and / or prevention of skin aging, the reduction and / or prevention of skin wrinkles, the stimulation of collagen synthesis and / or the prevention of collagen loss, the improvement or maintenance of skin firmness, the treatment and / or prevention of the appearance of sagging skin, the reduction and / or prevention of facial asymmetry and / or the increase in the volume of adipose tissue and / or the prevention and / or reduction of adipose tissue loss.

[0299] 17. The compound according to clause 1, wherein if AA5 is Asn, Asp, or Gln, then AA1 is Ala, Gly, or no amino acid, AA2 is Val, Ile, or Leu, AA3 is Lys, Arg, or His, AA4 is Pro or Val, and AA6 is Thr, Ala, Ser, or no amino acid, and AA1 is different from AA6.

[0300] 18. The compound according to clause 17, wherein AA1 is Ala, Gly, or no amino acid, AA2 is Val, Ile, or Leu, AA3 is Lys, Arg, or His, AA4 is Pro or Val, AA5 is Asn, Asp, or Gln, and AA6 is Thr, Ala, Ser, or no amino acid, and AA1 is different from AA6.

[0301] 19. The compound according to clause 18, wherein AA1 is Ala or Gly.

[0302] 20. The compound according to clause 18 or clause 19, wherein AA2 is Leu or Ile.

[0303] 21. The compound according to any one of clauses 18-20, wherein AA3 is Lys or Arg.

[0304] 22. The compound according to any one of clauses 18-21, wherein AA5 is Asn or Asp.

[0305] 23. The compound according to any one of clauses 18 to 22, wherein (i) AA6 is Thr, Ala, or Ser, or (ii) AA6 is Thr or Ala.

[0306] 24. The compound according to any one of clauses 18-23, wherein AA1 is Ala, AA2 is Leu, AA3 is Lys, AA4 is Pro, AA5 is Asn and AA6 is Thr.

[0307] 25. R1 is H and R5-CO- (wherein R5 is C1-C 18 Alkyl, C2-C 24 Alkenyl, C3-C 24 cycloalkyl; R2 is selected from the group consisting of -NR3R4 or -OR3, where R3 and R4 are independently selected from H and C1-C 16 24. The compound according to any one of clauses 17 to 23, wherein the aryl group is selected from the group consisting of alkyl.

[0308] 26. A combination of a compound according to any one of items 17 to 25 or a stereoisomer and / or a cosmetically acceptable salt thereof and with a botulinum toxin and / or a peptide of the sequence Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2.

[0309] 27. A composition comprising a cosmetically effective amount of a compound of formula (I) as defined in any one of clauses 17 to 25, a stereoisomer thereof and / or a cosmetically acceptable salt thereof, or a combination as defined in clause 26, and at least one cosmetically acceptable excipient or adjuvant.

[0310] 28. Use of a compound according to any one of clauses 17 to 25, its stereoisomers and / or cosmetically acceptable salts for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes.

[0311] 29. Use according to clause 28, wherein the cosmetic non-therapeutic treatment and / or care is the treatment and / or prevention of skin aging, reduction and / or prevention of skin wrinkles, stimulation of collagen synthesis and / or prevention of collagen loss, improvement or maintenance of skin firmness, treatment and / or prevention of the appearance of sagging skin, reduction and / or prevention of facial asymmetries, increase in the volume of adipose tissue and / or prevention and / or reduction of adipose tissue loss.

[0312] 30. A method for the cosmetic non-therapeutic treatment and / or care of the skin, hair, nails and / or mucous membranes of a subject, comprising administering to the subject a cosmetically effective amount of a compound according to any one of clauses 17 to 23, a combination according to clause 26 or a composition according to clause 27.

[0313] 31. Use according to clause 30, wherein the non-therapeutic cosmetic treatment and / or care is the treatment and / or prevention of skin aging, the reduction and / or prevention of skin wrinkles, the stimulation of collagen synthesis and / or the prevention of collagen loss, the improvement or maintenance of skin firmness, the treatment and / or prevention of the appearance of sagging skin, the reduction and / or prevention of facial asymmetries and / or the increase in the volume of adipose tissue and / or the prevention and / or reduction of adipose tissue loss.

Claims

[Claim 1] The invention described in this specification.

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