Novel cosmetic and / or dermatological ingredient for improving the condition, appearance and / or comfort of the skin and / or mucous membranes and / or skin appendages

Abstract

The present invention relates to a cosmetic or dermatological ingredient or a cosmetic or dermatological composition comprising the peptide of sequence SEQ ID N ° 1 and / or a derivative thereof and / or a salt thereof, and to the uses thereof for improving the condition and / or appearance and / or comfort of healthy skin and / or healthy mucous membranes and / or healthy skin appendages.

Description

[0001] New cosmetic and / or dermatological ingredient to improve the condition, appearance and / or comfort of the skin and / or mucous membranes and / or hair

[0002] Technical Field

[0003] The present invention relates to a new cosmetic and / or dermatological ingredient containing the SEQ ID No. 1 sequence peptide and / or its derivatives and / or its salts, its uses for its cosmetic and / or dermatological properties as well as its applications in cosmetic and / or dermatological compositions.

[0004] Previous technique

[0005] Collagen is a structural component of all organs and tissues in mammals. Synthesized by fibroblasts, this protein, a constituent of the extracellular matrix (ECM), is present in large quantities in vertebrate tissues. It is a large family comprising 29 different types. Among the various types of collagen, type I and type III collagens are found in many human tissues, particularly the skin, specifically in the dermis. Type I collagen is the predominant collagen in the skin. Type III collagen, also present in the dermis, is also found in muscles and blood vessels. Both type I and type III collagens are fibrillar collagens. They are initially synthesized as procollagen, which undergoes extracellular transformation into mature collagen.This collagen then assembles into fibrils, organized into a network, and then stabilized by covalent cross-linking bonds.

[0006] Collagen plays a crucial role in the architecture and biomechanical properties of the skin. It is also involved in regulating its own biosynthesis, as well as that of cofactors involved in its assembly, maturation, and stabilization. Under the influence of aging and / or intrinsic and / or extrinsic factors such as oxidative stress, pollution, UV radiation, an unbalanced diet, hormonal imbalances, and chronic inflammation, collagen fibers are degraded, notably through the activation of metalloproteinases (MMPs). Furthermore, collagen synthesis by skin fibroblasts decreases, and the newly synthesized fibers are of lower quality, less well-organized, and less dense. This alters the architecture of the dermis, and therefore of the skin and mucous membranes.This results in visible effects considered unsightly, including loss of firmness, loss of elasticity, loss of density, thinning of the skin, particularly the dermis, and the appearance of wrinkles. Furthermore, collagen plays a role in anchoring hair and skin appendages (hair, skin, and nails) to the dermis. A healthy dermis also contributes to the structure and function of the hair follicle. Therefore, a decrease in collagen leads to a loss of anchorage for hair and skin appendages, particularly hair, resulting in increased hair loss, as well as a reduction in the growth and quality of keratin fibers, especially in hair.

[0007] The decrease in the synthesis and / or quality of collagen fibers also leads to a decrease in skin renewal and reconstruction, particularly when the skin has been damaged, for example by aggressive agents, including mechanical trauma, or by diseases such as chickenpox, acne, and / or burns. These so-called scarred areas then display marks often considered unsightly, such as stretched scars, including white, dystrophic, atrophic, and / or keloid scars.

[0008] Collagen is therefore the target of many cosmetic and dermatological ingredients aimed at increasing its synthesis and / or improving the quality of collagen fibers.

[0009] There is a constant need for an active ingredient capable of both repairing damaged collagen and increasing collagen production. There is also a need for a cosmetic active ingredient capable of comprehensively and effectively improving the condition of the skin, mucous membranes, and hair / nails.

[0010] So-called CHP (collagen hybridizing peptide) peptides capable of hybridizing degraded or partially degraded collagen have already been described as a cosmetic active ingredient and are characterized by the repetition of a GPP or GPO motif, O designating hydroxyproline.

[0011] The applicant identified that a specific CHP-type peptide with SEQ ID No. 1 sequence: (GPP)4-GFOGER-(GPP)4, in which O designates hydroxyproline, preferably (2S,4R)-4-hydroxyproline (4Hyp), advantageously in the form of the following acetylated and amidated derivative with general formula 2: CH3-C(=O)-(GPP)4-GFOGER-(GPP)4-NH2, made it possible, surprisingly and particularly unexpectedly, to meet this need, not only by the ability of this peptide to stimulate collagen synthesis but also by its ability to repair damaged collagen and more generally, by its complementary properties allowing to improve overall the condition, appearance and / or comfort of the skin, mucous membranes and / or hair.

[0012] The peptide sequence of the invention contains the SEQ ID No. 3 peptide sequence: GFOGER. This is a collagen sequence motif that recognizes certain transmembrane integrins of the extracellular matrix, such as O2-1 integrins, which are cellular receptors involved in cell adhesion, migration, and signaling. Biomimetic collagen peptides therefore commonly incorporate this motif, particularly for the production of cell culture biomaterials. Patent application W02023060218A1 thus generally describes CHP peptide sequences with the general formula: (Gly-XY) a.bin which Gly denotes glycine, X and / or Y denotes a proline, a modified proline or a hydroxyproline and in which a is 3 and b is 20. This patent application explicitly mentions the peptides of sequence SEQ ID No. 4 (GPP)3-GFOGER-(GPP)3 otherwise designated (Gly-Pro-Pro)3 - Gly- Phe - Hyp - Gly- Glu- Arg -(Gly-Pro-Pro)3 and SEQ ID No. 5 (GPP)5-GFOGER-(GPP)5 otherwise designated (Gly-Pro-Pro)s - Gly- Phe -Hyp - Gly- Glu- Arg - (Gly-Pro-Pro)5. However, this patent application does not disclose the specific peptide according to the invention and does not suggest its specific and very complete properties as discovered by the applicant in the context of the present invention and which other peptides explicitly described in the prior art do not have or have at a significantly lesser level as demonstrated in Example 2.

[0013] Thus, the new peptide according to the invention is particularly distinguished from other CHP peptides described in the prior art by its level of performance on these properties but also by its multiple other complementary properties allowing to completely improve the condition, appearance and / or comfort of the skin, mucous membranes and / or hair.

[0014] The present invention thus relates to a new cosmetic or dermatological ingredient comprising the peptide of sequence SEQ ID No. 1, and / or one of its derivatives and / or one of its salts, advantageously comprising the derivative of the peptide of SEQ ID No. 1 of general formula 2:

[0015] CH3- C(=O)-(Gly-Pro-Pro)4 - Gly- Phe -Hyp - Gly- Glu- Arg -(Gly-Pro-Pro)4 - NH2(2). in which Hyp designates hydroxyproline, preferentially (2S,4R)-4-hydroxyproline (4- Hyp).

[0016] Thus advantageously the peptide of sequence SEQ ID No. 1 of the cosmetic or dermatological ingredient according to the present invention is in the form of the derivative of general formula (2):

[0017] CH3- C(=O)-(Gly-Pro-Pro)4 - Gly- Phe -Hyp - Gly- Glu- Arg -(Gly-Pro-Pro)4 - NH2(2).

[0018] The present invention also relates to a cosmetic or dermatological composition comprising the peptide of sequence SEQ ID No. 1, and / or one of its derivatives and / or one of its salts, advantageously the derivative of the peptide of SEQ ID No. 1 of general formula 2: CH3-C(=O)-(Gly-Pro-Pro)4 - Gly- Phe -Hyp - Gly- Glu- Arg -(Gly-Pro-Pro)4 - NH2(2), said cosmetic or dermatological composition further comprising a suitable cosmetic and / or dermatological vehicle.

[0019] Thus advantageously the peptide of sequence SEQ ID No. 1 of the cosmetic or dermatological composition according to the present invention is in the form of the derivative of general formula 2.

[0020] The present invention also relates to the non-therapeutic cosmetic use of SEQ ID No. 1 peptide and / or one of its derivatives and / or one of its salts, advantageously the derivative of SEQ ID No. 1 peptide with general formula 2: CH3-C(=O)-(Gly-Pro-Pro)4-Gly-Phe-Hyp-Gly-Glu-Arg-(Gly-Pro-Pro)4-NH2(2), in which Hyp designates hydroxyproline, preferably (2S,4R)-4-hydroxyproline (4-Hyp), and / or a cosmetic ingredient comprising it according to the present invention and / or a cosmetic composition comprising it according to the present invention to improve the condition and / or appearance and / or comfort of healthy skin and / or healthy mucous membranes and / or healthy hair and nails, in particular to prevent and / or reduce the signs of aging of healthy skin and / or healthy mucous membranes, and / or to improve the architecture of the healthy skin and / or healthy mucous membranes, in particular regenerating healthy skin and / or healthy mucous membranes,and / or to increase the thickness of healthy skin and / or healthy mucous membranes, and / or to prevent the thinning of healthy skin and / or healthy mucous membranes, in particular to prevent thin healthy skin and / or thin healthy mucous membranes, and / or to strengthen the skin and / or mucous membrane barrier, and / or to prevent and / or treat unsightly marks on healthy skin and / or healthy mucous membranes, in particular to prevent and / or treat unsightly non-pathological scars, and / or reduce their visibility, and / or to improve and / or maintain the biomechanical properties of healthy skin and / or healthy mucous membranes, in particular firmness, density, elasticity, suppleness, and / or tone, and / or to soothe healthy skin, in particular a healthy scalp, and / or healthy mucous membranes, in particular sensitive skin, in particular a sensitive scalp, and / or sensitive mucous membranes, and / or to improve and / or maintain healthy hair, nails, and / or skin appendages.in particular to improve and / or maintain the growth of skin appendages, especially keratin fibers, and / or the quality of the keratinous material produced in skin appendages, especially keratin fibers, and / or to prevent and / or reduce the loss of skin appendages, especially hair.

[0021] The present invention therefore relates to the non-therapeutic cosmetic use of the SEQ ID No. 1 peptide, and / or one of its derivatives, advantageously the derivative of the SEQ ID No. 1 peptide of general formula 2, and / or one of its salts, and / or a cosmetic ingredient comprising it according to the present invention and / or a cosmetic composition comprising it according to the present invention to prevent and / or reduce the signs of aging of healthy skin and / or healthy mucous membranes, and / or to improve the architecture of healthy skin and / or healthy mucous membranes, preferably to regenerate healthy skin and / or healthy mucous membranes, and / or to improve and / or maintain the biomechanical properties of healthy skin and / or healthy mucous membranes.

[0022] Furthermore, the present invention also relates to the non-therapeutic cosmetic use of the SEQ ID No. 1 peptide and / or one of its derivatives and / or one of its salts, advantageously the derivative of the SEQ ID No. 1 peptide with general formula 2:

[0023] CH3-C(=O)-(Gly-Pro-Pro)4-Gly-Phe-Hyp-Gly-Glu-Arg-(Gly-Pro-Pro)4-NH2(2), where Hyp denotes hydroxyproline, preferably (2S,4R)-4-hydroxyproline (4-Hyp), and / or a cosmetic ingredient comprising it according to the present invention and / or a cosmetic composition comprising it according to the present invention to increase the amount of collagen, in particular to increase the synthesis of type I collagen, type III collagen and / or procollagen I, and / or the quantity and / or quality of collagen fibers and / or decrease the amount of damaged collagen in healthy skin and / or healthy mucous membranes, and / or to increase the proliferation and / or migration of keratinocytes in healthy skin and / or healthy mucous membranes, and / or to increase the thickness of healthy skin and / or healthy mucous membranes, in particular the dermis and epidermis, and / or to decrease the amount of interleukin 8 and / or 6 in healthy skin and / or healthy mucous membranes,and / or to reduce forehead and crow's feet wrinkles in healthy skin, and / or to reduce glycation in healthy skin and / or mucous membranes, and / or to increase the amount of leptin in healthy skin and / or mucous membranes, particularly its expression, and / or to increase the amount of talin in healthy skin and / or mucous membranes, particularly its expression, and / or to increase the amount of hyaluronic acid in the dermis of healthy skin and / or mucous membranes, particularly its production, and / or to increase the tone of healthy skin and mucous membranes.

[0024] Furthermore, the present invention also relates to a non-therapeutic cosmetic care and / or treatment method comprising the topical application to at least one area of ​​healthy skin and / or healthy mucous membrane and / or healthy hair appendage of the SEQ ID No. 1 peptide and / or one of its derivatives, advantageously the derivative of the SEQ ID No. 1 peptide of general formula 2, and / or one of its salts and / or a cosmetic ingredient comprising it according to the invention and / or a cosmetic composition comprising it according to the invention, to improve the condition and / or appearance and / or comfort of the area of ​​healthy skin and / or healthy mucous membrane and / or healthy hair appendage.

[0025] The present invention also relates to the SEQ ID No. 1 peptide and / or one of its derivatives, advantageously the derivative of the SEQ ID No. 1 peptide of general formula 2, and / or one of its salts, for its use by topical application:

[0026] - to repair the skin and / or mucous membranes, in particular to repair wounds and / or other superficial injuries of the skin and / or mucous membranes such as canker sores, and / or to improve healing, in particular for the treatment and / or prevention of scars, especially pathological scars, and / or

[0027] - to prevent and / or treat skin inflammations, particularly of the scalp, and / or mucous membrane inflammations, such as dermatitis and erythema, especially sunburn and / or diaper rash, and / or gingivitis, and / or

[0028] - to prevent and / or treat acne, and / or

[0029] - to prevent and / or treat alopecia, and / or

[0030] - to prevent and / or treat elastosis, particularly solar elastosis.

[0031] The peptide according to the invention has the advantage of being a cosmetically acceptable active ingredient that does not irritate the skin and exhibits high chemical stability. It does not cause allergies. This peptide can be produced on an industrial scale.

[0032] The peptide according to the invention is the SEQ ID No. 1 peptide, which comprises 30 amino acids: SEQ ID No. 1: GPP-GPP-GPP-GPP-GFOGER-GPP-GPP-GPP-GPP

[0033] O denoting proline modified in the form of hydroxyproline, preferentially (2S,4R)-4-hydroxyproline (4-Hyp).

[0034] The peptide according to the invention contains 30 amino acids and therefore has the general formula 1: (Gly-Pro-Pro)4- Gly- Phe -Hyp - Gly- Glu- Arg -(Gly-Pro-Pro)4 (1)

[0035] This peptide has a molecular weight of 2688g / mol and a thermal disassembly temperature of 32°C. The thermal disassembly temperature corresponds to the temperature at which this triple-helix-organized peptide becomes unstable and appears as disordered peptide chains and can be measured by circular dichroism, as described in the publication by Ahmad et al., J. Nucl. Med. 2025, Feb 2025.

[0036] The amino acids constituting the peptide according to the invention can be in their L, D, or DL ​​forms. Preferably, they are all in the L configuration. According to one embodiment of the invention, the peptide according to the invention is in the form of one of its derivatives in which the last proline of the GPP motif is modified to the form of hydroxyproline, preferably (2S,4R)-4-hydroxyproline (4-Hyp). Thus, according to this embodiment of the invention, the peptide derivative is:

[0037] SEQ ID No. 2: GPO- GPO- GPO- GPO-GFOGER- GPO- GPO- GPO- GPO

[0038] O denoting proline modified in the form of hydroxyproline, preferably (2S,4R)-4- hydroxyproline(4- Hyp).

[0039] This same peptide can also be written under the general formula 3: (Gly-Pro-Hyp)4- Gly- Phe-Hyp- Gly- Glu- Arg-(Gly-Pro-Hyp)4(3)

[0040] Advantageously, the peptide according to the invention is in the form of derivatives comprising a modification of the amino acid at the N- and / or C-terminal position by the addition of a functional group, for example, coupled with a hydrophilic or hydrophobic penetrating agent, a stabilizing agent, or a protecting group, according to conventional methods known to those skilled in the art, in particular by acylation of the terminal -NH2 group, or amidation or alkylation of the terminal -COOH group to form an amide or an ester. This may, in particular, involve grafting onto the free terminal -NH2 group an acyl group comprising 2 to 24 carbon atoms, saturated or unsaturated, linear or branched, and which may also contain -OH, -SH, COOH, or CONH2 groups.It may also involve a modification of the terminal free COOH group into an amide group (-CONH2) or the grafting of this terminal free -COOH group by an alkyl or alkoxy group, said group comprising 1 to 24 carbon atoms, saturated or unsaturated, linear or branched and possibly also containing -OH, -SH, COOH or CONH2 groups.

[0041] According to one embodiment of the invention, the term "peptide derivative" means the peptide which has an N-terminal amino acid modification with a linear or branched C2-C24 acyl group, saturated or unsaturated, substituted or unsubstituted, preferably the peptide which has an N-terminal amino acid modification with an acetyl group.

[0042] In this particular embodiment, the peptide derivative according to the invention of SEQ ID No. 1 has the following general formula 4:

[0043] CH3-C(=O)-(Gly-Pro-Pro)4- Gly- Phe -Hyp - Gly- Glu- Arg -(Gly-Pro-Pro)4(4) and that of SEQ ID N°2 has the following general formula 5:

[0044] CH3-C(=O)-(Gly-Pro- Hyp)4- Gly- Phe -Hyp - Gly- Glu- Arg -(Gly-Pro- Hyp)4(5) in which Hyp denotes hydroxyproline, preferentially (2S,4R)-4-hydroxyproline (4-Hyp).

[0045] According to another embodiment of the invention, the term "peptide derivative" means the peptide which has a modification of the C-terminal amino acid with a C1-C24 amide or C1-C24 ester function, said function being linear or branched, saturated or unsaturated, substituted or unsubstituted, or with a primary amide function, preferably a primary (-NH2) amide.

[0046] Thus advantageously, the carboxylic group -COOH at the C-terminal end of the peptide according to the invention is transformed into an amide group -CONH2.

[0047] In this particular embodiment, the peptide derivative according to the invention of SEQ ID No. 1 has the following general formula 6:

[0048] (Gly-Pro-Pro)4 - Gly- Phe -Hyp - Gly- Glu- Arg -(Gly-Pro-Pro)4- NH2 (6) and that of SEQ ID N°2 has the following general formula 7:

[0049] (Gly-Pro-Hyp)4- Gly- Phe -Hyp - Gly- Glu- Arg -(Gly-Pro-Hyp)4- NH2 (7) in which Hyp denotes hydroxyproline, preferentially (2S,4R)-4-hydroxyproline (4-Hyp).

[0050] In a third embodiment, the peptide according to the invention is acetylated at its N-terminus and amidated at its C-terminus and corresponds to the derivative of SEQ ID No. 1 with the formula:

[0051] CH3-C(=O)-GPP-GPP-GPP-GPP-GFOGER-GPP-GPP-GPP-GPP-NH2.

[0052] O in the GFOGER motif designating proline modified as hydroxyproline, preferentially (2S,4R)-4-hydroxyproline (4-Hyp).

[0053] This same peptide can also be written according to the general formula 2:

[0054] CH3-C(=O)- (Gly-Pro-Pro)4- Gly- Phe -Hyp - Gly- Glu- Arg -(Gly-Pro-Pro)4 - NH2(2) in which Hyp denotes hydroxyproline, preferentially (2S,4R)-4-hydroxyproline (4- Hyp).

[0055] Thus this peptide has an amide group -CONH2 in place of the carboxylic group -COOH at the C-terminal end of the peptide and an acetyl group CH3-C(=O) on the N-terminal amine of the peptide.

[0056] This preferred derivative of the peptide according to the invention is described in Example 1a) and has a molecular weight of 2729.06 g / mol and a thermal disassembly temperature of 32°C. According to a variant of the invention, the peptide is in the form of the derivative of SEQ ID No. 2 and further comprises a modification of the amino acid at the N and / or C terminal position by the addition of a functional group as previously described.

[0057] In particular, the SEQ ID No. 2 derivative has an amide group -CONH2 in place of the carboxyl group -COOH at the C-terminal end of the peptide and an acetyl group CH3-C(=O) on the N-terminal amine of the peptide. Such a peptide is written as:

[0058] CH3-C(=O)- GPO- GPO- GPO- GPO-GFOGER- GPO- GPO- GPO- GPO-NH2.

[0059] O in the GPO and GFOGER motifs denoting proline modified as hydroxyproline, preferentially (2S,4R)-4-hydroxyproline (4-Hyp).

[0060] This same peptide can also be written according to the following general formula 8:

[0061] CH3-C(=O)- (Gly-Pro- Hyp)4- Gly- Phe -Hyp - Gly- Glu- Arg -(Gly-Pro- Hyp)4- NH2(8) in which Hyp denotes hydroxyproline, preferentially (2S,4R)-4-hydroxyproline (4- Hyp).

[0062] The derivatives of the peptide according to the invention are cosmetically and / or dermatologically acceptable, in particular topically acceptable.

[0063] According to the invention, "salts" refers to the peptide formed by the reaction of the peptide with an acid or a base, resulting in the formation of a salt. The peptide then carries a positive charge due to the protonation of its amino groups, while the counter-ion from the acid or base provides a negative charge. Peptide salts according to the invention include acetate, hydrochlorate, sulfate, phosphate, and trifluoroacetate; preferably, acetate or hydrochlorate.

[0064] The salts of the peptide according to the invention are cosmetically and / or dermatologically acceptable, in particular topically acceptable.

[0065] The term “peptide according to the invention” means the peptide of SEQ ID No. 1 and / or its derivatives and / or its salts as described above.

[0066] In one embodiment, the peptide according to the invention is exactly that of SEQ ID No. 1.

[0067] In a preferred embodiment, the peptide according to the invention is the derivative of the SEQ ID No. 1 peptide in the N-terminally acetylated and C-terminally amidated form of the formula:

[0068] CH3- C(=O)- GPP-GPP-GPP-GPP-GFOGER- GPP-GPP-GPP-GPP-NH2, O in the GPO motif designates proline modified as hydroxyproline, preferentially (2S,4R)-4-hydroxyproline (4-Hyp). This peptide corresponds to the peptide with general formula 2:

[0069] CH3- C(=O)- (Gly-Pro-Pro)4 - Gly- Phe -Hyp - Gly- Glu- Arg -(Gly-Pro-Pro)4 - NH2(2) in which Hyp denotes hydroxyproline, preferentially (2S,4R)-4-hydroxyproline (4- Hyp).

[0070] Preferably, the salts and derivatives of the peptide according to the invention do not contain a Gly-Gly-Gly- group in the N terminal and biotin, of formula C10H16N2O3S and corresponding to 5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoic acid. (CAS 58-85-5).

[0071] Thus, the peptide according to the invention, the cosmetic ingredient, and the cosmetic and / or dermatological compositions according to the invention do not include the following SEQ ID No. 6 peptide: Biotin - GGG-GPP-GPP-GPP-GPP-GFOGER- GPP-GPP-GPP-GPP-NH2

[0072] O in the GFOGER motif designating proline modified as hydroxyproline, preferentially (2S,4R)-4-hydroxyproline (4-Hyp).

[0073] The peptide according to the invention, its derivatives and its salts, can be obtained by chemical synthesis or by biotechnological synthesis using a microorganism produced naturally or by recombinant technologies with methods well known to those skilled in the art.

[0074] According to one embodiment, the peptide according to the invention can be obtained by chemical synthesis using conventional techniques. The techniques for the chemical synthesis of peptides are known to those skilled in the art, and examples include the techniques described in JM Stewart and JD Young, *Solid Phase Peptide Synthesis*, 2 nd editions, Pierce Chemical Company, Rockford, Illinois (1984), or M. Bodanzsky and A. Bodanzsky, The practice of peptide synthesis, Springer Verlag. New York (1984) as well as that described in the publication LL Bennink et al, Visualizing collagen proteolysis by peptide hybridization: From 3D cell culture to in vivo imaging, Biomaterials 183(2018)67-76.

[0075] Thus, according to one embodiment of the present invention, the peptide is chemically synthesized in the solid and / or liquid phase, where the amino acids are sequentially coupled via peptide bonds. The steps include protecting the amino acid functional groups to prevent undesired reactions, coupling the amino acids, and final deprotection to release the synthesized peptide. In a particular embodiment, the peptide according to the invention shall have a purity level of at least 50%, preferably at least 70%, advantageously at least 80%, preferably at least 90%, and even more preferably at least 95% (w / w).

[0076] According to another alternative method, the peptide according to the invention can be obtained by biotechnological synthesis, in particular from a recombinant bacterial or yeast strain, i.e. genetically modified to produce the peptide according to the invention.

[0077] The bacterial strain is preferentially Escherichia coii, the yeast strain is preferentially chosen from Pichia and Saccharomyces, in particular Pichia pastoris and Saccharomyces cerevisiae.

[0078] The production of the peptide by a yeast strain classically involves the following steps, which are well known to those skilled in the art:

[0079] - transformation of yeast using a peptide expression system according to the invention coupled to export signal sequences, typically of plasmid type;

[0080] - culture of the transgenic yeast on a culture medium;

[0081] - batch and / or fed-batch fermentation;

[0082] - recovery of fermentation must and removal of yeast biomass, for example by centrifugation and filtration or tangential microfiltration;

[0083] - Concentration and / or purification of the peptide.

[0084] According to an alternative embodiment of the present invention, the peptide is used in the form of a lysate or fermentation filtrate of microorganism by producing, preferably from a recombinant bacterium or yeast, more preferably chosen from the recombinant bacterium Escherichia coii, or recombinant yeasts of the Genus Pichia or Saccharomyces, even more preferably from the yeast Pichia pastoris or the yeast Saccharomyces cerevisiae, in particular genetically modified to produce this sequence, said fermentation filtrate being preferably enriched in peptide according to the invention.

[0085] According to an alternative embodiment of the present invention, the peptide is used in a purified form from a lysate or fermentation filtrate by the usual peptide purification techniques, in particular selected from membrane filtration, chromatography, precipitation and / or immunoprecipitation.

[0086] According to the invention, a "recombinant bacterium" or "recombinant yeast" is defined as a bacterium or yeast whose cells have been genetically modified to express the peptide according to the invention. According to the invention, a "lysate" of a bacterium or yeast is defined as a preparation from the cells, in the fermentation medium or after separation from the fermentation medium by centrifugation and / or filtration. This lysate is obtained after partial or total degradation or rupture of the plasma membrane and / or cell wall to partially or totally release their contents. This process can be carried out by mechanical, chemical, or enzymatic methods well known to those skilled in the art, and may be followed by partial or total purification of the peptide of interest.

[0087] According to the invention, a "fermentation filtrate" is defined as the solution obtained after culturing the recombinant bacteria or yeast in a fermentation medium, and after a step of separating and removing the yeast or bacterial cells by filtration. The separation and / or removal step may include and / or be preceded by centrifugation.

[0088] According to an alternative embodiment of the invention, the peptide according to the invention, one of its salts or one of its derivatives is contained in a fermentation filtrate, preferably in an amount of at least equal to or greater than 0.0001% by weight of dry matter relative to the total weight of the filtrate, preferably between 0.001% and 10%, more preferably between 0.01% and 5%, by weight of dry matter relative to the total weight of the filtrate.

[0089] The N-terminal amino acid can be modified with a linear or branched C2-C24 acyl group, saturated or unsaturated, substituted or unsubstituted, preferentially at C2 i.e. an acetyl group (CH3-C(=O)).

[0090] The C-terminal amino acid may be modified with a C1-C24 amide function or a Ci-C24 ester function, said function being linear or branched, saturated or unsaturated, substituted or unsubstituted, or with a primary amide function, preferably with a primary amide function (-NH2 in place of the -OH of the terminal carboxylic acid).

[0091] It is possible to prepare the synthetic peptide, the fermentation lysates or filtrates, the purified peptide according to the invention in powder form by drying (spray drying, lyophilization, etc.) with or without a drying support such as mannitol, maltodextrin, cyclodextrin, according to the classic formulation techniques known to those skilled in the art, preferably the drying support is mannitol.

[0092] It is also possible to prepare the synthetic peptide, the fermentation lysates or filtrates, and the purified peptide according to the invention as a liquid solution in water, glycerol, and polyols such as diols (propanediol, butanediol, pentanediol, hexanediol, etc.) alone or in mixtures, using conventional dissolution and formulation techniques known to those skilled in the art. Advantageously, the peptide is purified as a liquid solution in water and glycerol, preferably containing at least 50%, and preferably 80%, glycerol by weight of dry matter relative to the total weight of the liquid solution.

[0093] According to a preferred embodiment of the invention, the peptide is used at a temperature close to or above its thermal disassembly temperature. Thus, the use of the peptide according to the invention is perfectly suited for use on the skin, mucous membranes, and hair at their natural temperatures, in the form of a powdered cosmetic or dermatological ingredient or in the form of a cosmetic or dermatological composition.

[0094] The peptide according to the invention can be used alone, as a cosmetic or dermatological ingredient and / or in a cosmetic or dermatological composition.

[0095] The present invention relates to a cosmetic or dermatological ingredient comprising the peptide according to the invention previously described (peptide of sequence SEQ ID No. 1 and / or one of its derivatives and / or one of its salts).

[0096] According to the invention, a "cosmetic or dermatological ingredient" is defined as the peptide alone (peptide with sequence ID No. 1 and / or one of its derivatives and / or one of its salts) or in combination with a cosmetic or dermatological vehicle suitable for topical application, intended to be incorporated into a cosmetic or dermatological composition. Cosmetic ingredients are defined in particular by the International Nomenclature of Cosmetic Ingredients (INCI). According to the invention, the cosmetic or dermatological ingredient is active, that is to say, it is intended to provide cosmetic or dermatological efficacy in the cosmetic or dermatological composition.

[0097] For the purposes of this invention, the term "suitable cosmetic / or dermatological vehicle" means that its composition or components are suitable for use in contact with human skin, mucous membranes and / or hair, without undue toxicity, incompatibility, instability, allergic response, or their equivalents.

[0098] Preferably, the cosmetic or dermatological ingredient comprises the peptide of SEQ ID No. 1, possibly in the form of one of its salts and / or one of its derivatives, advantageously the derivative of general formula 2, in a content greater than or equal to 0.0001% by weight, preferably between 0.0001% and 10% by weight, more preferably between 0.005% and 1% by weight, even more preferably between 0.01% and 0.25% by weight, again preferentially between 0.01% and 0.1% by weight, again advantageously about 0.02% by weight (i.e. 200 ppm), of dry matter in relation to the total weight of the cosmetic ingredient.

[0099] Thus the cosmetic or dermatological ingredient may be used in a cosmetic or dermatological composition, preferably in a content between 0.001% and 10% by weight, advantageously between 0.01% and 5% by weight, in particular between 0.1% and 3% by weight, of dry matter in relation to the total weight of the composition.

[0100] Thus, the peptide according to the invention, particularly in the form of a powdered cosmetic or dermatological ingredient, is preferably used in the cosmetic or dermatological composition according to the invention in a content between lxl0' 6 % and 0.1% by weight, preferably of lxl0' 5 % to lxl0' 2 % by weight, still advantageously 5xl0' 5 % to 2xl0' 3 %, in particular lxl0' 4 % to lxl0' 3 %, advantageously 2xl0' 4 % by weight of dry matter relative to the total weight of the composition.

[0101] The cosmetic or dermatological ingredient according to the invention may be in powder or liquid form.

[0102] In a preferred embodiment, the cosmetic or dermatological ingredient is in powder form, obtained in particular after the drying step, preferably by freeze-drying or spray-drying, the peptide being mixed with an inert support, conventionally a spray-drying support such as mannitol, maltodextrin, or cyclodextrin. Preferably, the drying support is maltodextrin or mannitol, and again, preferably mannitol. Thus, in one embodiment, the cosmetic or dermatological ingredient according to the invention is in powder form further containing mannitol. In another particular embodiment, the ingredient according to the invention in powder form consists of a mixture of the peptide according to the invention and the drying support such as mannitol, maltodextrin, or cyclodextrin, preferably a mixture of the peptide according to the invention and mannitol.

[0103] Preferably, the ingredient according to the invention in powder form has a peptide content according to the invention (peptide of sequence SEQ ID No. 1 and / or one of its derivatives and / or one of its salts) of between 0.01% and 0.25% by weight, preferably between 0.01% and 0.1% by weight, preferably 0.02% by weight of dry matter, relative to the total weight of the ingredient, preferably the ingredient according to the invention in powder form further comprising a drying agent, preferably mannitol. In a particular embodiment, the cosmetic or dermatological ingredient according to the invention is in powder form and contains 99.98% by weight of mannitol and 0.02% by weight of the peptide according to the invention, advantageously the peptide of general formula 2, by dry matter relative to the total weight of the ingredient, in particular as described in Example 10c).

[0104] According to an alternative embodiment, the cosmetic or dermatological ingredient is in liquid form, the peptide being solubilized and / or diluted in a solvent, particularly a polar solvent, such as water, an alcohol, and / or a polyol such as glycerol, propanediol, a glycol such as pentylene glycol and / or butylene glycol and / or hexylene glycol, in particular 1,2-hexylene glycol (or 1,2-hexanediol) and / or caprylyl glycol, or a mixture thereof. In particular, it may be a mixture of water, glycerol, and hexylene glycol such as 1,2-hexylene glycol. The peptide may also be contained in the production lysate or fermentate, particularly as an aqueous solution, and may be used directly as a cosmetic or dermatological ingredient or in concentrated form.Preferably, the ingredient according to the invention in liquid form contains a peptide content according to the invention of between 0.005% and 0.1% by weight, preferably 0.02% by weight, of dry matter relative to the total weight of the ingredient.

[0105] For the purposes of the present invention, "topical route" means the application of the peptide according to the invention, preferably in the form of a cosmetic or dermatological ingredient and / or the cosmetic or dermatological composition according to the invention, to the surface of the skin, in particular the scalp and / or mucous membranes, and / or hair, preferably the hair, in particular by direct application or by spraying.

[0106] The peptide according to the invention, its salts and derivatives are topically acceptable.

[0107] For the purposes of the present invention, "topically acceptable" means an ingredient suitable for topical application, non-toxic, non-irritating to the skin and / or mucous membranes and / or hair, which does not induce an allergic response and is not chemically unstable.

[0108] For the purposes of this invention, "cosmetically acceptable" means a cosmetic ingredient that is non-toxic, non-irritating to the skin and / or mucous membranes and / or hair, does not induce an allergic response, and is chemically stable. For the purposes of this invention, "dermatologically acceptable" means a dermatological ingredient that is non-toxic, non-irritating to the skin and / or mucous membranes and / or hair, does not induce an allergic response, and is chemically stable.

[0109] The peptide according to the invention, its salts and derivatives are particularly suitable for application on the skin, mucous membranes and hair.

[0110] For the purposes of this invention, "skin" means the skin of all or part of the body, particularly human skin, including the scalp, selected from the face, hands, arms, décolletage, legs, neck, back, shoulders, abdomen, wrists, forearms, ankles, thighs, nape of the neck, scalp, joint and / or armpit creases, and labial mucous membranes, preferably the face, particularly the area around the eyes and / or mouth and the forehead. In particular, skin is that which may be exposed to aggressive agents, especially those likely to degrade collagen fibers, including areas exposed to aggressive environmental or chemical agents, friction, and / or maceration. This includes, more specifically, the face, particularly the area around the lips and / or eyes and the forehead, the scalp, hands, neck, décolletage, joint creases, and / or armpits.

[0111] For the purposes of the present invention, "mucous membrane(s)" means the ocular, nasal, vaginal, anal and / or oral mucosa, in particular the oral and labial mucosa, preferably the labial, ocular and / or nasal mucosa.

[0112] For the purposes of the present invention, "phaneres" means nails and "keratin fibers".

[0113] The term “keratin fibers” refers to hair, eyelashes, eyebrows, body hair, particularly beard and / or mustache hair, preferentially hair.

[0114] For the purposes of this invention, "cosmetic" means a non-pharmaceutical, non-therapeutic use that is not intended for the prevention and / or treatment of skin, mucous membranes, and / or hair and nails that have been diagnosed as pathological by a specialist in the field, such as a dermatologist. It therefore refers to use on healthy skin, mucous membranes, and / or hair and nails.

[0115] The term "improve" a parameter means a significant increase in the measured value of that parameter after treatment with the peptide according to the invention compared to the value of that parameter obtained without treatment with that peptide.

[0116] The term "maintaining" a parameter means preventing and / or stopping the decrease in the value of the parameter measured after treatment with the peptide according to the invention by comparison with the value of the decrease in this parameter obtained without treatment with this peptide, particularly under the effect of aggressive agent(s).

[0117] According to the present invention, "aggressive agents" means environmental agents such as pollutants, climatic factors (such as wind, cold, heat), UV exposure, biological factors, including emotional factors such as stress, dietary and / or hormonal imbalances, and / or chemical agents (for example, heavy metals, detergents, compounds contained in cosmetic treatments such as perfumes, preservatives, alcohols, pH, AHAs or dermatological such as acid vitamin A), and / or aggressive conditions including perspiration and mechanical aggressions such as hair removal, shaving, friction, and even water, particularly hard water.

[0118] The term "healthy skin and / or healthy mucous membranes and / or healthy skin appendages" means all or part of an area of ​​healthy skin and / or healthy mucous membranes and / or healthy skin appendages, particularly human skin, to which the peptide according to the invention is applied and which is deemed "non-pathological" by a dermatologist, i.e., not exhibiting cancer, infection, pathological scarring, skin disease or condition such as candidiasis, impetigo, psoriasis, eczema, acne, ichthyosis, gingivitis or dermatitis, particularly atopic dermatitis, or wounds, particularly diabetic lesions or injuries or canker sores or ulcerations or burns and / or other dermatoses, or aphthous ulcers or inflammation or irritation such as erythema, particularly solar erythema and / or diaper rash, elastosis, particularly solar elastosis, or hives or allergies such as contact allergy,or alopecia or pathologies associated with glycation and / or wound healing, or pathologies associated with a decrease in the quantity and / or quality of collagen and / or leptin and / or talin. It is therefore not a case of inflamed, atopic, reactive, damaged and / or irritated skin or mucous membranes.

[0119] Preferably, the application of the peptide according to the invention is by topical route, advantageously on specific parts and / or areas of the body chosen from among the scalp, the face, in particular the contour of the lips and / or eyes as well as the forehead, hands, arms, décolleté, legs, neck, back, shoulders, belly, wrists, forearms, ankles, thighs, nape of the neck, joint folds, and / or armpits, labial mucous membranes.

[0120] The peptide according to the invention, optionally in the form of its salts and / or derivatives, advantageously in the form of the derivative with general formula 2, is useful and therefore can be used, alone and / or as a cosmetic ingredient and / or in a cosmetic composition, to improve the condition and / or appearance and / or comfort of healthy skin and / or healthy mucous membranes and / or healthy hair and nails, and preferably for:

[0121] - to prevent and / or reduce the signs of aging of healthy skin and / or healthy mucous membranes, and / or

[0122] - to improve the architecture of healthy skin and / or healthy mucous membranes, in particular to regenerate healthy skin and / or healthy mucous membranes, and / or to increase the thickness of healthy skin and / or healthy mucous membranes, and / or to prevent the thinning of healthy skin and / or healthy mucous membranes, in particular to prevent thin healthy skin and / or thin healthy mucous membranes, and / or to strengthen the skin and / or mucous membrane barrier, and / or

[0123] - to prevent and / or treat unsightly marks on healthy skin and / or mucous membranes, in particular to prevent and / or treat unsightly non-pathological scars, and / or reduce their visibility, and / or

[0124] - to improve and / or maintain the biomechanical properties of healthy skin and / or healthy mucous membranes, in particular firmness, density, elasticity, suppleness and / or tone, and / or

[0125] - to soothe healthy skin, particularly a healthy scalp, and / or healthy mucous membranes, particularly sensitive skin, including a sensitive scalp, and / or sensitive mucous membranes, and / or

[0126] - to improve and / or maintain healthy hair and skin appendages, in particular to improve and / or maintain the growth of hair and skin appendages, especially keratin fibers, and / or the quality of the keratin material produced at the level of the hair and skin appendages, especially keratin fibers, and / or to prevent and / or reduce the loss of hair and skin appendages, especially keratin fibers, preferentially hair.

[0127] The applicant has indeed discovered that the peptide according to the invention, and in particular the peptide of general formula 2, allows:

[0128] - to increase the amount of collagen, preferentially collagen synthesis, in particular the synthesis of type I and III collagens, and procollagen I (examples 3 and 4) and / or the quantity and quality of collagen fibers, notably by decreasing the amount of damaged collagen (examples 2 and 12) in the skin and / or mucous membranes,

[0129] - to increase the proliferation and / or migration of keratinocytes in the skin and / or mucous membranes, particularly when the epidermis is weakened (example 5), - to increase the thickness of the skin and / or mucous membranes, including the total thickness of the skin (example 13) but also specifically the thickness of the epidermis (example 15),

[0130] - to decrease the amount of interleukin 8 and / or 6 in the skin and / or mucous membranes (example 7),

[0131] - to reduce forehead wrinkles and crow's feet (examples 13 and 14),

[0132] - to reduce glycation in the skin and / or mucous membranes (example 6),

[0133] - to increase the amount of leptin in the skin and / or mucous membranes, in particular its expression (example 8),

[0134] - to increase the amount of talin in the skin and / or mucous membranes, in particular its expression (example 9),

[0135] - to increase the amount of hyaluronic acid in the dermis of the skin and / or mucous membranes, in particular its production (example 12),

[0136] - to increase the tone of the skin and mucous membranes (example 13), and can therefore be used for these properties in the skin and mucous membranes.

[0137] The peptide according to the invention allows for a very comprehensive "improvement of collagen fibers," that is, by increasing their quality and / or quantity and / or preventing their degradation. Indeed, it increases the amount of collagen in the skin and mucous membranes, notably by stimulating collagen synthesis, particularly of procollagen I and type I and III collagens, as demonstrated in Example 3 on monolayer fibroblasts and Example 4 on the dermis. Furthermore, the peptide according to the invention is capable of binding to damaged collagen and reducing the amount of damaged collagen present in the skin, as demonstrated in Examples 2 and 12. Thus, the peptide allows both the repair of damaged collagen fibers and the stimulation of the production of new collagen fibers.

[0138] The peptide according to the invention reduces glycation in the skin and / or mucous membranes, that is, the phenomenon by which sugars bind to proteins, particularly elastin and collagen, leading to a loss of their properties, specifically a loss of elasticity, suppleness, and firmness, and increased rigidity. This property is demonstrated in particular by the inhibition of the formation of advanced glycation end products (AGEs) in Example 6. The peptide according to the invention, in particular the derivative with general formula 2, increases leptin expression, specifically gene expression (Example 8). Leptin is a particularly interesting target for cosmetic and / or dermatological applications because subcutaneous adipocytes interact with dermal fibroblasts by increasing the production of collagen and hyaluronic acid via the secretion of adiponectin and leptin (Ezure and Amano (BioFactors 31 (2007) 229-236)).Thus, maintaining a significant level of leptin even in the event of skin stress allows for the maintenance of a quality dermis.

[0139] Furthermore, the applicant has shown that the peptide according to the invention, in particular the derivative with general formula 2, stimulates the expression of talin, specifically its protein expression (Example 9). This cytoplasmic protein links integrins to cytoskeletal actin, anchoring cells to the extracellular matrix. When the extracellular matrix interacts with an integrin, talin is activated, leading to the activation of integrins by altering their conformation. This increases the affinity of integrins for the extracellular matrix and strengthens the mechanical forces between the matrix and the cytoskeleton, contributing to intracellular mechanical signaling.Thus, the increase in talin expression testifies to and reinforces the interaction of integrins with the extracellular matrix and therefore promotes the processes of cell migration, tissue remodeling, proliferation and differentiation and generally contributes to cell communication with the matrix.

[0140] Furthermore, the peptide according to the invention has the advantage of acting very comprehensively on the different compartments of the skin and mucous membranes:

[0141] - on the epidermis by stimulating the proliferation and migration of keratinocytes as well as by inhibiting interleukin 8,

[0142] - on the dermis by improving collagen, particularly its quality and / or quantity, anti-glycation activity, inhibition of interleukin 6, stimulation of talin expression and stimulation of hyaluronic acid production,

[0143] - on the hypodermis via the maintenance of leptin expression.

[0144] These effects are not achieved with prior art peptides or with the GFOGER sequence (SEQ ID No. 3) alone, as the examples demonstrate. These properties thus contribute to improving the overall condition of the skin and / or mucous membranes, and therefore to anchoring the hair follicles, particularly the hair follicle, in the dermis and hypodermis, ensuring that the hair follicle is well-nourished and thus functions properly, producing high-quality keratin fibers, especially hair.

[0145] Thus, the peptide according to the invention is generally useful for preventing the appearance and / or reducing unsightly, unpleasant and / or uncomfortable manifestations in healthy skin, mucous membranes and / or hair, visible and / or felt due to a change in the state of healthy skin and / or mucous membranes and / or hair, due to:

[0146] - a decrease in the amount of collagen, particularly its synthesis, especially type I and / or type III, and / or procollagen I, and / or a decrease in the quality and / or quantity of collagen fibers, particularly an increase in damaged collagen in healthy skin and / or healthy mucous membranes, and / or

[0147] - a decrease in the proliferation and / or migration of keratinocytes in healthy skin and / or healthy mucous membranes, and / or

[0148] - a decrease in the thickness of healthy skin and / or healthy mucous membranes, particularly the dermis and epidermis, and / or

[0149] - an increase in the level of interleukin 8 and / or 6 in healthy skin and / or healthy mucous membranes, and / or

[0150] - the appearance of unsightly marks and / or signs of aging on healthy skin and / or healthy mucous membranes, and / or

[0151] - an increase in glycation in healthy skin and / or healthy mucous membranes, and / or

[0152] - a decrease in the amount of talin, in particular its expression, in healthy skin and / or healthy mucous membranes, and / or

[0153] - a decrease in the amount of leptin, in particular its expression, in healthy skin and / or healthy mucous membranes, and / or

[0154] - a decrease in the amount of hyaluronic acid, particularly its production, in the dermis of healthy skin and / or healthy mucous membranes, and / or

[0155] - a decrease in the tone of healthy skin and / or healthy mucous membranes.

[0156] The peptide according to the invention, optionally in the form of a cosmetic ingredient and / or a cosmetic composition, in particular the derivative of general formula 2, is useful for preventing and / or reducing the signs of aging of healthy skin and / or healthy mucous membranes. "Preventing and / or reducing the signs of aging" means delaying and / or preventing the appearance and / or reducing the amount and / or extent of signs of aging of healthy skin and / or healthy mucous membranes, whether natural and / or induced by aggressive agents (in particular photoinduced).The term “signs of healthy skin aging” refers to all unsightly manifestations of healthy skin due to skin aging and includes the reduction of the biomechanical properties of healthy skin and / or healthy mucous membranes, in particular firmness and tone and / or architecture of healthy skin and / or healthy mucous membranes due to natural or aggressive aging (in particular photoinduced), in particular the reduction of the thickness of healthy skin.

[0157] Preferably, the signs of skin aging are the appearance of marked microrelief of the skin, the formation and / or presence of fine lines, fine wrinkles and / or wrinkles, including frown lines and crow's feet, especially under the eyes and around the lips, sagging of the skin, roughness of the skin and / or withering of the skin and / or a lack of firmness, elasticity and / or tone of the skin.

[0158] The peptide according to the invention, in particular the derivative of general formula 2, has demonstrated its properties to prevent and / or reduce the signs of aging in that it binds to damaged collagen and reduces its quantity (examples 2 and 12), stimulates the synthesis of type I collagen, type III collagen and procollagen I (examples 3 and 4), reduces glycation (example 6), increases the expression of leptin (example 8) and talin (example 9), increases the production of hyaluronic acid in the dermis (example 12) and increases the thickness of the epidermis (examples 5 and 15).

[0159] These signs of skin aging can be measured by clinical tests, particularly on crow's feet and forehead wrinkles and on skin tone, as described in examples 13 and 14.

[0160] The peptide according to the invention, possibly in the form of its salts and / or derivatives, in particular the derivative of general formula 2, can therefore be used to prevent and / or stop natural and / or aggressive aging (in particular photoinduced) and / or to rejuvenate healthy skin and / or healthy mucous membranes, giving them a younger and smoother appearance, in particular by reducing wrinkles, advantageously forehead wrinkles and / or crow's feet.

[0161] The cosmetic ingredient according to the invention is particularly useful as an "anti-aging ingredient" in that it prevents and / or reduces the signs of aging in healthy skin and / or mucous membranes. The peptide according to the invention, optionally in the form of a cosmetic ingredient and / or cosmetic composition, in particular the derivative of general formula 2, is also useful for improving the architecture of healthy skin and / or mucous membranes, in particular for regenerating healthy skin and / or mucous membranes, and / or increasing the thickness of healthy skin and / or mucous membranes, and / or preventing the thinning of healthy skin and / or mucous membranes, in particular for preventing thin healthy skin and / or mucous membranes, and / or strengthening the skin and / or mucous membrane barrier.

[0162] The peptide according to the invention, in particular the derivative with general formula 2, improves the architecture of healthy skin and mucous membranes through its properties on their different compartments:

[0163] - at the level of the epidermis, the peptide increases the proliferation and migration of keratinocytes and the thickness of the epidermis (examples 5 and 15),

[0164] - at the level of the dermis, the peptide binds to damaged collagen and reduces it (examples 2 and 12), increases the synthesis of procollagen I (example 3) and type I and III collagens (examples 3 and 4), has an anti-glycation effect (example 6) and increases the production of hyaluronic acid (example 12) as well as the expression of talin (example 9),

[0165] - at the level of the hypodermis by maintaining leptin expression (example 8) without overstimulating it

[0166] For the purposes of the present invention, "thickness of healthy skin and / or healthy mucous membranes" means the total height of healthy skin and / or healthy mucous membranes, in particular the epidermis, dermis and / or hypodermis, preferably the dermis.

[0167] The applicant has indeed shown that the peptide according to the invention makes it possible to improve the quantity of collagen, in particular the synthesis, and / or the quality of skin collagen, in particular to reduce damaged collagen (example 3, 4 and 12) but also to increase the production of hyaluronic acid in the dermis (example 12), to increase the expression of talin (example 9) and to maintain the expression of leptin (example 8), which contribute to the thickness of the dermis and its functions.

[0168] The thicknesses of the epidermis and / or dermis can, for example, be measured in vivo using ultrasound imaging as performed in Example 13, and the thickness of the epidermis can also be measured in vitro as described in Examples 5 and 15.

[0169] The peptide according to the invention, through its properties on keratinocyte migration and proliferation, particularly improves the skin and / or mucous membrane barrier (Example 5). The peptide according to the invention is particularly useful for regenerating healthy skin and / or mucous membranes, especially for stimulating epidermal renewal, particularly in pre-treatment and / or post-treatment aesthetic procedures, especially laser treatments.

[0170] The peptide according to the invention, possibly in the form of a cosmetic ingredient and / or cosmetic composition, in particular the derivative of general formula 2, is also useful for preventing and / or treating unsightly marks on healthy skin and / or healthy mucous membranes, in particular for preventing and / or treating unsightly non-pathological scars, and / or for reducing the visibility of unsightly non-pathological scars.

[0171] The term "preventing and / or treating unsightly marks on healthy skin and / or mucous membranes" means preventing the appearance and / or improving the appearance and / or look of unsightly marks on healthy skin and / or mucous membranes, including non-pathological scarring, particularly stretched scars, including stretch marks, white, dystrophic, atrophic and keloid scars, particularly scars due to injuries, acne, pimples, chickenpox and / or burns, as well as other marks such as tattoos, laser treatment marks and / or imperfections, particularly to make them less visible.The properties of the peptide according to the invention for improving the dermis (examples 2, 3, 4, 12) show that the peptide according to the invention is particularly useful for the prevention and / or treatment of unsightly cutaneous and / or mucosal marks in which the dermis has areas of depression or sagging.

[0172] The peptide according to the invention also makes it possible to prevent and / or treat unsightly marks on healthy skin and / or healthy mucous membranes by its properties on the proliferation and migration of keratinocytes (example 5), anti-glycation (example 6), regeneration via the expression of talin (example 9) and by increasing the thickness of the epidermis (examples 13 and 15) and of the skin (example 13).

[0173] The peptide according to the invention can in particular be used on healthy skin and / or healthy mucous membranes, in pretreatment and / or posttreatment of healthy skin and / or healthy mucous membranes to prevent and / or reduce unsightly marks on healthy skin and / or healthy mucous membranes due to tattoos and / or laser treatments.

[0174] The peptide according to the invention, possibly in the form of a cosmetic ingredient and / or cosmetic composition, in particular the derivative of general formula 2, is also useful for improving the biomechanical properties of healthy skin and / or healthy mucous membranes.

[0175] For the purposes of this invention, "biomechanical properties of healthy skin and / or healthy mucous membranes" means the suppleness, firmness, elasticity, tone and / or density, and more preferably the firmness and / or tone of healthy skin and / or healthy mucous membranes.

[0176] For the purposes of this invention, "firmness of healthy skin and / or mucous membranes" means the ability of healthy skin and / or mucous membranes to resist deformation. Firmness can, for example, be measured using conventional techniques known to those skilled in the art. As an in vivo example, firmness can be measured using devices such as an indentometer and a cutometer®. As an in vitro example, firmness can be assessed by measuring collagen synthesis and / or the level of damaged collagen. Another in vitro example is measuring the binding and enhancement of collagen, particularly collagen damaged by the peptide according to the invention, as described in Examples 2, 3, 4, 8, and 12.

[0177] For the purposes of this invention, "tonicity of healthy skin and / or healthy mucous membranes" refers to the skin's resistance to deformation and corresponds to the R6 parameter measured according to the method described in Chen et al., Cosmetics 2024, 11, 205. The R6 value increases with age, reflecting a loss of tonicity. Tonicity can, for example, be measured in vivo using a Cutometer® as described in Example 13.

[0178] For the purposes of this invention, "density (of the dermis) of healthy skin and / or healthy mucous membranes" refers to the content, organization, and compaction of the structural components of the extracellular matrix, such as collagen fibers, preferably type I or III collagen fibers, elastin, glycosaminoglycans (GAGs), preferably hyaluronic acid, and proteoglycans synthesized by fibroblasts. Density can be measured, for example, in vivo and ex vivo (biopsy) using conventional methods, including ultrasound or confocal microscopy.

[0179] The peptide according to the invention, optionally in the form of its salts and / or derivatives, is useful and can therefore be used to improve and / or maintain the biomechanical properties of healthy skin and / or mucous membranes, in particular by maintaining, improving, and / or increasing collagen, preferably collagen fibers, preferably type I and III collagen (Examples 3, 4, and 12), and by maintaining and / or increasing hyaluronic acid production in the dermis (Example 12). The applicant has shown that the peptide according to the invention is useful as an anti-glycation agent (Example 6), which contributes to maintaining the biomechanical properties of healthy skin and / or mucous membranes.

[0180] The stimulation of leptin by the peptide according to the invention as demonstrated in Example 8 also contributes to good dermal quality and therefore to the biomechanical properties of healthy skin and / or healthy mucous membranes.

[0181] The peptide according to the invention, possibly in the form of a cosmetic ingredient and / or cosmetic composition, in particular the derivative of general formula 2, is also useful for soothing healthy skin and / or healthy mucous membranes.

[0182] The term "soothing healthy skin and / or healthy mucous membranes" refers to the ability to prevent and / or limit signs of discomfort in healthy skin and / or healthy mucous membranes, particularly when they have been exposed to aggressive agents, and / or to reduce these signs of discomfort.

[0183] Signs of discomfort include dryness of healthy skin and / or mucous membranes, loss of evenness of skin tone of healthy skin and / or mucous membranes, including the appearance of redness, sensations of tightness, overheating, heat, tingling, prickling, tension, a rough appearance of healthy skin and / or mucous membranes and / or a loss of softness to the touch of healthy skin and / or mucous membranes.

[0184] The applicant has indeed shown that the peptide according to the invention has the property of decreasing the amount of interleukins 8 and 6 in the skin and / or mucous membranes, in particular secreted under the effect of inflammatory stress as demonstrated in example 7 and reduces glycation in the skin and / or mucous membranes (example 6), which contributes to creating an inflammatory context and is therefore useful for soothing healthy skin and / or healthy mucous membranes.

[0185] The peptide according to the invention has the advantage of respecting the skin and mucous membrane microbiota. Indeed, the applicant evaluated the effects of using the peptide at different dosages (5 pM, 1 pM, and 0.1 pM) on various bacterial strains, particularly staphylococci such as S. aureus, S. epidermidis, S. hominis, S. accolens, and S. acnes, but also lactobacilli such as *S. crispatus*, micrococcus such as *M. iuteus*, and Acinobacter such as *A. iwoffiii*, and demonstrated that the peptide according to the invention does not decrease bacterial viability and therefore helps maintain the balance of the skin microbiome. The peptide according to the invention, possibly in the form of a cosmetic ingredient and / or a cosmetic composition, particularly the derivative with general formula 2, is also useful for improving and / or maintaining healthy hair, nails, and skin appendages.

[0186] According to the present invention, "improving and / or maintaining healthy hair follicles" means improving and / or maintaining the growth of healthy hair follicles, particularly keratin fibers, preferably hair, as well as the quality of the keratin produced in healthy hair follicles, particularly healthy keratin fibers, preferably healthy hair, and / or preventing and / or reducing the loss of healthy hair follicles, particularly keratin fibers, preferably hair. Through its properties on the architecture of the scalp skin and the reduction of pro-inflammatory stress in the scalp skin, the peptide according to the invention improves the anchoring, structure, and / or function of the hair follicle in order to limit hair loss, promote growth, and increase the diameter, density, and / or strength of the keratin fibers produced, particularly hair.

[0187] The peptide of SEQ ID No. 1, possibly in the form of one of its salts and / or one of its derivatives, advantageously the derivative of general formula 2, possibly in the form of the cosmetic or dermatological ingredient according to the invention, is intended to be used in the form of cosmetic or dermatological compositions.

[0188] The present invention therefore also relates to cosmetic and / or dermatological compositions which contain the peptide according to the invention.

[0189] The cosmetic or dermatological compositions according to the invention further contain any suitable cosmetic and / or dermatological solvent and / or any suitable cosmetic and / or dermatological vehicle and / or any suitable cosmetic and / or dermatological excipient, possibly in combination with other compounds of interest.They may, in particular, contain a cosmetically or dermatologically suitable excipient and / or a cosmetically or dermatologically suitable vehicle selected from surfactants, preservatives, buffering agents, swelling agents, chelating agents, biocidal agents, denaturants, opacifying agents, pH adjusters, reducing agents, stabilizing agents, emulsifiers, thickeners, gelling agents, film-forming polymers, solvents, fillers, bactericides, odor absorbers, mattifying agents, conditioning agents, texturizing agents, gloss-enhancing agents, pigments, colorants, perfumes and chemical or mineral sunscreens, trace elements, essential oils, sweeteners, and flavor modifiers. These combinations are also covered by the present invention.The CTFA Cosmetic Ingredient Handbook, Second Edition (1992) describes various cosmetic and dermatological ingredients commonly used in the cosmetic and dermatological industry, which are particularly suited for topical administration.

[0190] Advantageously, the excipient(s) and / or vehicle(s) are chosen from the group comprising polyglycerols, esters, polymers and cellulose derivatives, lanolin derivatives, phospholipids, lactoferrins, lactoperoxidases, sucrose-based stabilizers, vitamin E and its derivatives, xanthan gums, natural and synthetic waxes, vegetable oils, triglycerides, unsaponifiables, phytosterols, silicones, protein hydrolysates, betaines, aminoxides, plant extracts, sucrose esters, titanium dioxide, glycines, and parabens, and preferably from the group consisting of steareth-2, steareth-21, glycol-15 stearyl ether, cetearyl alcohol, phenoxyethanol, and methylparaben, ethylparaben, propylparaben, butylparaben, butylene glycol, caprylyl glycol, natural tocopherols, glycerin, dihydroxycetyl sodium phosphate,isopropyl hydroxycetyl ether, glycol stearate, triisononanoine, octyl cocoate, polyacrylamide, isoparaffin, laureth-7, a carbomer, propylene glycol, hexylene glycol, glycerol, bisabolol, a dimethicone, sodium hydroxide, PEG-30 dipolyhydroxysterate, caprylic / capric triglycerides, cetearyl octanoate, dibutyl adipate, grapeseed oil, jojoba oil, magnesium sulfate, EDTA, a cyclomethicone, xanthan gum, citric acid, sodium lauryl sulfate, waxes and mineral oils, isostearyl isostearate, propylene glycol dipelargonate, propylene glycol isostearate, PEG 8, beeswax, hydrogenated palm kernel oil glycerides, lanolin oil, sesame oil, cetyl lactate, lanolin alcohol, castor oil, titanium dioxide, lactose, sucrose, low-density polyethylene, isotonic saline solution, and mixtures thereof.

[0191] The cosmetic or dermatological ingredient and the cosmetic or dermatological composition can be presented in all the galenic forms classically used for topical application such as liquid or solid forms or even in the form of a pressurized liquid.They may in particular be formulated as a solution, aqueous or oily, a cream or aqueous gel or an oily gel, in particular in a jar or tube, in particular a shower gel, a shampoo, a milk, an emulsion, a hydrogel, a microemulsion or a nanoemulsion, in particular oil-in-water or water-in-oil or multiple or silicone, a serum, a lotion, in particular in a glass bottle, a plastic bottle or a dosing bottle or in an aerosol, an ampoule, a liquid soap, a paste, a dermatological bar, an ointment, a foam, an aerosol, a mask, a patch, an anhydrous product, preferably liquid, pasty or solid, for example in the form of a stick or in powders, in particular makeup.In particular, the composition is presented in the form of a serum, lotion, cream, milk, ointment, paste, mousse, emulsion, hydrogel, shower gel, mask, stick, patch, or makeup powder, advantageously as a cream or lotion. Preferably, the composition is presented in the form of a cream, lotion for the skin and / or hair, or shampoo, conditioner, rinse-off or leave-on.

[0192] The peptide according to the present invention has the advantage of not irritating and / or stripping the skin, mucous membranes and hair, thus maintaining the microbiota and is particularly suitable for the care and / or treatment of sensitive and / or irritated skin and / or mucous membranes.

[0193] In the case of administration via the mucosal route, the cosmetic or dermatological composition according to the invention and / or the peptide according to the invention, possibly in the form of a cosmetic or dermatological ingredient, may be in the form of eye drops, in particular ophthalmic eye drops, a lotion, an aerosol, a gel, in particular an oral gel or a mucoadhesive composition,

[0194] The cosmetic or dermatological composition according to the invention may further comprise other cosmetic or dermatological ingredients active in the treatment of the skin and / or mucous membranes and / or hair, in particular those inducing a complementary or synergistic effect with the peptide according to the invention. These may include, in particular, the following cosmetic and / or dermatological ingredients:

[0195] - ingredients that help prevent and / or combat the signs of aging of the skin and / or mucous membranes;

[0196] - depigmenting agents and / or agents active on pigment spots;

[0197] - ingredients that improve skin firmness and / or elasticity;

[0198] - metalloproteinase (MMP) inhibitor ingredients;

[0199] - ingredients for treating sensitive skin and / or mucous membranes;

[0200] - active ingredients on the scalp, anti-dandruff and / or active ingredients said to be anti-hair loss and / or stimulating hair growth;

[0201] - the active ingredients on the microbial flora;

[0202] - the active ingredients on the barrier function;

[0203] - photoprotective ingredients, UVA and / or UVB filters and / or protection against pollution. Among the agents used to prevent and / or combat the signs of aging, we can mention the mixture of Acetyl Tetrapeptide-11 and Acetyl Tetrapeptide-9 described in patent application FR3076722A1 and marketed by the applicant under the name Replexium™, resveratrol, retinol, vitamin C, an agent stimulating fibronectin synthesis, in particular a maize extract, such an extract being marketed by the applicant under the name Deliner™; an agent stimulating laminin synthesis, in particular a biotechnologically modified malt extract, such an extract being marketed by the applicant under the name Basaline™; and a lipid synthesis stimulating agent such as a biotechnologically modified potato extract (soas tuberosum) marketed by the applicant under the name Lipidessence™;an agent stimulating the expression and / or activity of Hyaluronan synthase 2 (HAS2) such as the plant extracts described in patent application FR2 893 252 Al and in particular an aqueous extract of Galanga A / pinia ga / anga) marketed under the name Hyalufix™ by the applicant; an agent stimulating the synthesis of lysyl oxidase like (LOXL) such as those described in patent application FR2855968, and in particular a dill extract marketed under the name Lys'lastine™ by the applicant.;

[0204] For depigmenting agents, we can mention niacinamide or vitamin B3 and derivatives.

[0205] Among the active ingredients for improving skin firmness are the synthetic tetrapeptide marketed as Dermican™, an extract of Hibiscus Abe / moscus as described in the applicant's patent application filed under number FR0654316 and marketed as Linefactor™, a fibroblast growth-stimulating agent, for example, a fermented soy extract containing peptides, known as Phytokine™, marketed by the applicant and also described in patent application EP1119344 B1 (Laboratoires Expanscience), a purified pea extract marketed as Proteasyl™, an extract of Manilkara multinervis marketed as Elestan™, an extract of Khaya senega / ensis marketed as Collalift™18, an extract of Argan pulp marketed as Argassential™, and an extract of Schizandra chinensis, marketed under the name Sqisandryl™ by the plaintiff,The peptide from SEQ ID No. 9: TVFDGVLRPGQL described in patent application FR3141066A1, an extract of NepheHum lappaceum marketed by the applicant under the name Nephoria™ and described in patent application FR3065876A1, as well as a mixture of palmitoyl tripeptide-1 and palmitoyl tetrapeptide-7 marketed under the name Matrixyl™ 3000 by Sederma. Among the metalloproteinase-inhibiting ingredients, one could mention those specifically inhibiting MMPs 1, 2, 3, and 9, such as retinoids and derivatives, oligopeptides and lipopeptides, lipoamino acids, and the malt extract marketed by BASF Beauty Care Solutions France under the trade name Collalift®.

[0206] Among the active ingredients for sensitive skin are: deoiled, ungerminated Moringa oleifera seed protein extract marketed under the trade name Purisoft®; a Cestrum latifolium plant extract marketed under the name Symbiocell™; a butter extracted from the fruit of the Irvingia gabonensis tree marketed under the name Irwinol™; an Eperua falcata root extract marketed under the name Eperuline™; and a peptide from SEQ ID No. 10: N-acetyl-L-Tyrosyl-L-Prolyl-L-Phenylalanyllin-L-

[0207] Phenylalaninamide (INCI: Acetyl Tetrapeptide 15) marketed under the name Skinasensyl™, an extract of Inonotus obliquas marketed under the name Inolixir™ by the applicant.

[0208] Among the active ingredients on the scalp and / or keratin fibers, we can mention an extract of Cassia aiata leaves marketed under the name DN-Age™ as an antioxidant active ingredient for hair care; sarcosine marketed under the name Scalposine™ by the applicant and described in patent application FR3101776A1; the peptide marketed by the applicant under the name PeptAide™ 4.0 described in patent application FR3114744A1; an extract of Hippophae rhamnoides described in patent application FR3117372A1; an extract of Nepheiium iappaceum marketed by the applicant under the name Rambuvital™ and described in patent application FR3076734; and an extract of Siybum marianum to improve keratin fibers described in patent application FR3142088A1 and marketed under the name Kerasylium™.

[0209] Among the anti-hair loss ingredients are a combination of sulfopeptides, amino acids, aminosaccharides, B vitamins, zinc, and / or extracts of Panax ginseng and Artium majus marketed under the name Trichogen™ LS 8960 by the applicant, and / or a hair-protecting agent such as an extract of Litchi chinensis pericarp marketed under the name Litchiderm™ by the applicant, and / or a soothing and anti-itch active ingredient such as rapeseed phytosterols marketed under the name Phytosoothe™ LS9766 by the applicant, and / or an active ingredient to strengthen the hair follicle such as an extract of Nepheiium iappaceum, and / or minodoxil, valproic acid as marketed by Amorepacific, and / or stemoxidine, and / or aminoxil, and / or Hairgenyl as marketed by Silab, and / or Rednensyl. as marketed by Givaudan-Induchem and / or Anagain as marketed by Mibelle and / or Baïcapil as marketed by Provital,anti-dandruff active ingredients such as zinc pyrithione and / or octopirox and / or ketoconazole glycolipids extracted from yeast marketed by BASF under the name BioToLife and / or hexamidine diisethionate marketed under the name El esta b™ HP 100 and / or the complex containing an extract of Piper nigrum berries, an extract of Inga aiba bark and sodium lauroyl lactylate marketed under the name Sanicapyl by the applicant, and / or anti-dandruff active ingredients such as piroctone olamine, particularly when combined with salicylic acid.

[0210] These combinations of active ingredients with the peptide according to the invention are likely to strengthen the hair follicle and thus help to reduce the loss of keratin fibers, preferentially of hair.

[0211] The peptide according to the present invention may also be used in combination with ingredients active on the cutaneous and / or mucosal microbial flora and / or active on the skin barrier function, in particular moisturizing and / or soothing agents, including an oligosaccharide obtained by enzymatic synthesis marketed by Solabia under the name BioEcolia™ or an alpha-glucohydrate complex marketed by the same company under the name Ecoskin™, an extract of Alisma plantago-aquatica, an extract of Argania spinosa (Lipofructyl™ Argan), a mixture of ceramides (Sphingoceryl™ VEG), purifying extracts of Boido (Beta pur™), products based on inulin or fructooligosaccharides, extracts of bifidobacteria, an extract of Pueraria iobata root marketed under the name Inhipase™ by the applicant,a beta-glucan derivative from baker's yeast marketed by Mibelle under the name CM-Glucan Forte™ and / or an extract of Mirabilis jaiapa marketed under the name Pacifeel™ by Sederma, a polysaccharide extracted from Cassia angustifoiia seeds marketed under the name Hyalurosmooth™ by the applicant, or an agent selected from one of the combinations containing pullulan, sodium hyaluronate and sodium alginate marketed under the name PatcH2O™ by the applicant and described in patent application FR2994387A1, a pericarp extract of Litchi chinensis marketed under the name Litchiderm™ by the applicant, a natural honey extract marketed by the applicant under the name Melhydran™, a flax extract marketed under the name Oligolin™ by the applicant, a yeast extract modified by biotechnology and marketed by the applicant under the name Relipidium™ and described in patent application FR3055799,an extract of Nepheiium iappaceum marketed by the applicant under the name Nephydrat™ and described in patent application FR3069779A1;

[0212] Among the photoprotective active ingredients or UVA and / or UVB filters usable according to the present invention in combination with the peptide according to the invention, we may mention photoprotective agents active in UV-A and / or UV-B, such as para-aminobenzoic acid derivatives, in particular "UVINUL P25" by BASF, salicylic derivatives, in particular homosalate alone or in combination with titanium oxides, dibenzoylmethane derivatives, cinnamic derivatives, diphenyl acrylate derivatives, including Octocrylene sold in particular under the trade name "UVINUL N539" by BASF, benzophenone derivatives, in particular Benzophenone-1 sold in particular under the trade name "UVINUL 400" by BASF, benzylidene camphor derivatives, benzimidazole derivatives, triazine derivatives, including Ethylhexyl triazone sold in particular under the trade name "UVINUL T150" by BASF, benzotriazole derivatives, anthranilic derivatives,Imidazoline derivatives, benzalmalonate derivatives, 4,4-diarylbutadiene derivatives, and mixtures thereof.

[0213] Among the protective agents against pollution, we can mention an extract of leaves of A' rgania spinosa marketed under the name Arganyl™ by the applicant or an extract of seeds of Moringa oleifera marketed under the name Purisoft™ by the applicant or an extract of root of Eperua falcata marketed under the name Eperuline™ by the applicant.

[0214] The peptide according to the invention is particularly suitable for use on all types of skin, mucous membranes and / or skin appendages, including Caucasian, Asian, African and in particular on all skin types.

[0215] It is particularly suitable for masking the first unsightly signs of aging in healthy skin, especially the first expression lines and / or for so-called mature skin, i.e. men or women aged at least 50, especially menopausal women.

[0216] The peptide according to the invention, optionally in the form of its salts and / or derivatives, preferably the derivative with general formula 2, is particularly suitable for the care of sensitive and / or sensitized, fragile, weakened, and / or atopic-prone skin and / or mucous membranes. The peptide according to the invention is thus particularly useful for treating the unsightly and / or unpleasant and / or uncomfortable manifestations of sensitive and / or sensitized, fragile, weakened, and / or atopic-prone skin and / or mucous membranes.

[0217] In general, "sensitive skin and / or mucous membranes" can be defined as healthy skin and / or healthy mucous membranes which, by nature, tolerate very few aggressive agents.

[0218] Sensitive and sensitized skin are not pathological, unlike allergic skin. However, they can react to aggressive agents and / or conditions with unsightly, unpleasant, and / or uncomfortable cutaneous and / or mucosal manifestations such as dryness, uneven skin tone, redness, tightness, tingling, prickling, stinging, tension, heat, or burning, a rough texture, and / or loss of softness to the touch. Therefore, the "sensitive skin" characteristic can be assessed by the individual themselves through subjective skin sensations or by a dermatologist through objective skin reactions.

[0219] Unsightly, unpleasant, and / or uncomfortable symptoms can be generalized to the entire body, but most of the time they can be located in well-defined areas such as the scalp, the face (particularly around the lips and / or eyes) as well as the forehead, skin folds, the buttocks in infants, etc. These areas can therefore be sensitive areas of skin and / or mucous membranes.

[0220] Similarly, "sensitized skin and / or mucous membranes" are healthy skin and / or mucous membranes made sensitive momentarily and therefore not pathological as such.

[0221] "Fragile or weakened skin and / or mucous membranes (i.e., temporarily fragile)" refers to healthy skin and / or mucous membranes whose barrier function is compromised. This condition can be related to the individual's health and / or age, with the elderly and infants, for example, having fragile skin. It can also result from chemical or physical aggressions such as abrasion, friction, cuts, tattoos, and laser treatments.

[0222] "Atopic-prone skin and / or mucous membranes" refers to healthy skin and / or mucous membranes that are extremely fragile and / or weakened, with increased permeability due to a compromised barrier function. This skin is genetically predisposed to develop, under the influence of multiple intrinsic and extrinsic factors, into the pathological condition of atopic dermatitis. Therefore, the "atopic-prone skin" characteristic can be assessed by the individual themselves through subjective skin sensations or by a dermatologist through objective skin reactions.

[0223] The uncomfortable, unpleasant, and / or unsightly manifestations of sensitized, fragile, and / or weakened skin and / or mucous membranes are the same as those experienced by sensitive skin and / or mucous membranes, without these manifestations and / or skin conditions being indicative of the prevention and / or treatment of a pathology. The peptide according to the invention is useful for soothing such unsightly, unpleasant, and / or uncomfortable manifestations of sensitive skin and / or mucous membranes, thus providing genuine comfort to sensitive skin and / or mucous membranes.

[0224] The peptide according to the invention, preferably the derivative of general formula 2, is also suitable for the care of normal, oily, dry, blemished skin and in particular acne-prone and acne-prone skin.

[0225] The present invention also relates to a non-therapeutic cosmetic care and / or treatment method comprising the topical application, in particular daily, to at least one area of ​​healthy skin and / or healthy mucous membrane and / or healthy hair, of the peptide according to the invention, and / or of a cosmetic ingredient comprising it according to the invention and / or of a cosmetic composition comprising it according to the invention to improve the condition and / or appearance and / or comfort of the area of ​​healthy skin, and / or healthy mucous membrane and / or healthy hair, in particular hair.

[0226] The method according to the present invention may include the preliminary step of identifying the area of ​​healthy skin and / or healthy mucous membrane and / or healthy hair and nails whose condition and / or appearance and / or comfort is to be or is to be improved, in particular an area of ​​healthy skin and / or healthy mucous membrane and / or healthy hair and nails on which it is desired to increase the amount of collagen, in particular collagen synthesis, especially type I and III collagens, and procollagen I, and / or the quantity and / or quality of collagen fibers and / or decrease the amount of damaged collagen, and / or increase the proliferation and / or migration of keratinocytes, and / or increase the thickness, in particular of the dermis and epidermis, and / or decrease the amount of interleukin 8 and / or 6, and / or decrease wrinkles, in particular of the forehead and crow's feet, and / or decrease glycation, and / or increase leptin expression,and / or increase talin expression, and / or increase hyaluronic acid production in the dermis, and / or increase skin tone.

[0227] Advantageously, the invention also relates to a cosmetic treatment method for improving the condition and / or appearance and / or comfort of healthy skin and / or healthy mucous membranes and / or healthy hair and nails of an individual who needs / desires it, comprising the steps:

[0228] - Identification on the individual of an area of ​​healthy skin and / or healthy mucous membranes and / or healthy hair and nails, the condition and / or appearance and / or comfort of which should be or is desired to be improved, in particular an area of ​​healthy skin and / or healthy mucous membranes and / or healthy hair and nails on which / in which one wishes to increase the amount of collagen, in particular increasing collagen synthesis, especially type I, type III, and / or procollagen I collagen, and / or the quantity and / or quality of collagen fibers and / or decreasing the amount of damaged collagen, and / or increasing the proliferation and / or migration of keratinocytes, and / or increasing the thickness, particularly of the dermis and epidermis, and / or decreasing the amount of interleukin 8 and / or 6, and / or reducing forehead and crow's feet wrinkles, and / or decreasing glycation, and / or increasing leptin expression, and / or increasing the expression of the taline,and / or increase hyaluronic acid production in the dermis and / or increase firmness, and,

[0229] - topical application to this area of ​​healthy skin and / or healthy mucous membranes and / or healthy hair and nails, of the peptide according to the invention, preferably of the derivative of general formula 2 and / or of the cosmetic ingredient and / or of a cosmetic composition containing it in an effective quantity to improve the condition and / or appearance and / or comfort of healthy skin and / or healthy mucous membranes and / or healthy hair and nails, in particular in a peptide content according to the invention between lxl0' 6 % and 0.1% by weight, preferably of lxl0' 5 % to lxl0' 2 % by weight, still advantageously 5xl0' 5 % to 2xl0' 3 %, preferably lxl0' 4 % to lxl0' 3 %, in particular 2xl0' 4 % by weight of dry matter relative to the total weight of the composition.

[0230] Advantageously, the peptide according to the invention, preferably in the form of the cosmetic composition, is applied daily to the healthy skin, healthy mucous membranes and / or healthy hair to be treated, preferably twice a day, for a period of at least 28 days, preferably for 56 days.

[0231] The present invention also relates to the SEQ ID No. 1 peptide and / or one of its salts and / or one of its derivatives, according to the present invention, alone or in the form of a dermatological ingredient according to the invention and / or a dermatological composition according to the invention, for its use by topical application:

[0232] - to repair the skin and / or mucous membranes, in particular to repair wounds and / or other superficial injuries such as canker sores, and / or to improve healing and / or for the treatment and / or prevention of scars, particularly pathological scars, and / or

[0233] - to prevent and / or treat skin inflammations, particularly of the scalp, and / or mucous membrane inflammations, such as dermatitis and erythema, especially sunburn, diaper rash, and / or gingivitis and / or - to prevent and / or treat alopecia and / or

[0234] - to prevent and / or treat elastosis, particularly solar elastosis and / or

[0235] - to prevent and / or treat acne.

[0236] Indeed, the peptide reduces glycation in the skin and mucous membranes (example 6) and has the property of decreasing the synthesis of interleukins, particularly II-8 and II-6 (example 7). This helps to reduce and / or prevent inflammation in the skin and / or mucous membranes, as well as all pathologies with a cutaneous and / or mucosal inflammatory component, such as dermatitis and erythema, especially sunburn, diaper rash, and / or gingivitis and acne. This reduction and / or prevention of inflammation, particularly in the scalp, helps to limit hair loss, and therefore the peptide can be used to prevent and / or treat alopecia, especially that caused by and / or accompanied by scalp inflammation.

[0237] By its properties to stimulate the proliferation and migration of keratinocytes (example 5) and to stimulate the expression of talin (example 9), the peptide according to the invention is particularly useful for repairing skin and / or mucous membranes.

[0238] The SEQ ID No. 1 peptide, possibly in the form of its salts and derivatives according to the present invention, is particularly suitable for use alone or as a dermatological ingredient and / or dermatological composition in the treatment and / or care of skin, particularly scalp and / or mucous membranes, that is inflamed, atopic, reactive, damaged and / or irritated.

[0239] The term "reactive skin and / or mucous membranes" refers to skin and / or mucous membranes whose tolerance threshold has decreased and which react excessively. This includes skin and / or mucous membranes described as intolerant, irritable, or allergic.

[0240] The term “atopic skin and / or mucous membrane” refers to skin and / or mucous membrane affected by the pathology of atopic dermatitis.

[0241] The characteristics "reactive skin and / or mucous membrane" and "atopic skin and / or mucous membrane" can be assessed by the dermatologist with objective skin reactions.

[0242] The dermatological composition preferably contains the peptide according to the invention in a peptide content between lxl0' 6 % and 0.1% by weight, preferably of lxlO' 5 % to lxlO' 2 % by weight, still advantageously 5xl0' 5 % to 2xl0' 3 %, in particular lxlO' 4 % to lxlO' 3 %, advantageously 2xl0' 4 % by weight of dry matter relative to the total weight of the composition.

[0243] Other purposes, features and advantages of the invention will become clear to those skilled in the art upon reading the explanatory description, which refers to examples given only by way of illustration and which shall in no way limit the scope of the invention.

[0244] The examples form an integral part of the present invention and any feature which appears new compared with any prior art from the description taken as a whole, including the examples, forms an integral part of the invention in its function and in its generality.

[0245] Thus, each example has a general scope.

[0246] On the other hand, in the examples, and unless otherwise indicated, temperature is expressed in degrees Celsius, percentages in w / w and pressure is atmospheric pressure.

[0247] EXAMPLES

[0248] Example 1: Synthesis of the peptide according to the invention, i) Synthesis of the SEP IP No. 1 peptide derivative with an acetyl function at the N-terminus and an amide function at the C-terminus of general formula 2:

[0249] The peptide according to the invention was obtained by solid-phase chemical synthesis at a purity of 97.1% determined by HPLC-UV. The identity of the peptide according to the invention was confirmed by spectroscopy (LC-ESI-MS for Liquid Chromatography-Electrospray Ionization-Mass Spectrometry) by the mass spectrum of the peptide showing a peak of m / z 1365.4 [M+2H]2+.

[0250] The peptide is the preferred derivative with general formula 2:

[0251] CH3-C(=O)- GPP-GPP-GPP-GPP-GFOGER- GPP-GPP-GPP-GPP-NH2.

[0252] The amino acid O of the GFO motif designates proline modified in the form of (2S,4R)-4-hydroxyproline (4-Hyp).

[0253] Such a peptide is written as:

[0254] CH3- C(=O)- (Gly-Pro-Pro)4 - Gly- Phe -Hyp - Gly- Glu- Arg -(Gly-Pro-Pro)4 - NH2lb) Synthesis of the SEO IP peptide derivative No. 1

[0255] The peptide according to the invention was obtained by solid-phase chemical synthesis at a purity of 97.5% determined by HPLC-UV. The identity of the peptide according to the invention was confirmed by spectroscopy (LC-ESI-MS for Liquid Chromatography-Electrospray Ionization-Mass Spectrometry) by the mass spectrum of the peptide showing a peak of m / z 1344.9 [M+2H]2+.

[0256] The peptide is that of SEQ ID No. 1: GPP-GPP-GPP-GPP-GFOGER- GPP-GPP-GPP-GPP. The amino acid O of the GFO motif designates proline modified into (2S,4R)-4-hydroxyproline (4-Hyp). Such a peptide corresponds to that of the general formula 1: (Gly-Pro-Pro)4-Gly-Phe-Hyp-Gly-Glu-Arg-(Gly-Pro-Pro)4 (l)

[0257] Example 2: Evaluation of the ability of the peptide according to the invention to bind to denatured collagen (gelatin)

[0258] Principle: The test used is that described in the publication Bennick et al, 2018 (Biomaterials, Volume 183, November 2018, Pages 67-76) in which the concentrations of the different gelatin solutions, EDC (l-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride) / NHS (N-hydroxysulfosuccinimide) were modified and a bovine serum albumin (BSA - Bovine Serum Albumin) solution was used to saturate the nonspecific binding sites.

[0259] This test involves coating a plate with a solution of denatured collagen (porcine gelatin), then adding the peptides to be tested, which have been previously grafted with a fluorescent probe (carboxyfluorescein) coupled to a spacer (GGG). Several rinses are then performed, and finally, the residual fluorescence is measured. The higher the fluorescence, the more the tested product has bound and been fixed to the denatured collagen (gelatin).

[0260] Protocol

[0261] A gelatin solution (Sigma, G2500) was prepared at 100 pg / ml (w / v) in phosphate-buffered saline (PBS) at 60 °C. ImM magnesium chloride and ImM calcium chloride were added after the gelatin had dissolved. 600 µL of this mixture was loaded into each well and incubated at room temperature for 1 h to allow gelation. The thin gelatin hydrogel films were then crosslinked with 120 µL of a 2-(N-morpholino)ethanosulfonic acid (MES) buffered solution (pH 5.5, 100 µL / well) containing 60 mM NHS and 150 mM EDC, for 1 h at room temperature. The crosslinked gelatin films were washed three times with 1 mL of TBST2 (Tris BupH® buffered saline, Thermo Scientific, containing ImM manganese chloride). 1.2 mL of 1% (w / v) BSA solution prepared in TBST2 was added to each well, and the plate was incubated for 30 minutes at room temperature.Each well was then rinsed three times with 1 mL of TBST2. The peptides to be tested were obtained by chemical synthesis. The peptide according to the invention was obtained according to example (a). A 400 pL solution of PBS (phosphate-buffered saline) containing each peptide N-terminally grafted with carboxyfluorescein (CF) coupled with a spacer (GGG) (except for GFOGER (SEQ ID No. 3)) at a concentration of 20 pM was then added to each well and left for 24 hours at 32°C and protected from light to allow product fixation. The solutions containing the different peptides to be tested were applied directly to each well at room temperature without preconditioning. After this period, each well was washed three times with 1 mL of TBST2 at room temperature and then 0.5 mL of TBST2 was added to each well for fluorescence reading (ex: 493 nm, em: 517 nm) measured with a microplate reader (VARIOSKAN LUX).One well / condition was created, and fluorescence readings were taken from each well (n=27). Statistical analysis of the data was performed using SigmaPlot software (version 12.5), according to the Mann-Whitney U test, and the significance level was set at 5% (p<0.05). Results are presented as mean ± SEM (standard error of the mean). Fluorescence is expressed in arbitrary units.

[0262] Results :

[0263] Table 1 - Gelatin binding test (denatured collagen)

[0264] Conclusion: The peptide with sequence (GPP)4-GFOGER-(GPP)4-NH2 (SEQ ID No. 1) shows a superior ability to bind to denatured collagen (p<0.001) compared to the GFOGER sequence alone (SEQ ID No. 3) and compared to (GPP)5-GFOGER-(GPP)5-NH2 (SEQ ID No. 5) (p<0.001) and (GPP)3-GFOGER-(GPP)3-NH2 (SEQ ID No. 4) (p<0.05). Thus, the peptide according to the invention has the property of binding more strongly than the GFOGER sequence (SEQ ID No. 3) alone and the peptides explicitly described in the prior art.

[0265] This test thus contributes to demonstrating that the peptide according to the invention is useful for preventing and / or reducing the signs of aging in healthy skin and / or mucous membranes, improving the architecture of healthy skin and / or mucous membranes, preventing and / or treating unsightly marks on healthy skin and / or mucous membranes, improving and / or maintaining the biomechanical properties of healthy skin and / or mucous membranes, and / or improving and / or maintaining healthy hair, nails, and skin appendages by enhancing their anchoring in a higher-quality dermis. (This test demonstrates the activity of the peptide according to the invention.) according to the invention on stimulation l and I on monolayer fibroblasts. The aim of this test was to evaluate the efficacy of the peptide according to the invention by comparison to the peptide sequence "GFOGER" (SEQ ID No. 3) on the synthesis of procollagen I (Pro-Col I) and collagen I on monolayer fibroblasts.

[0266] Protocol:

[0267] Normal human fibroblasts from a 19-year-old breast donor were seeded in 96-well plates for 4 days at 37°C, 5% CO2, with culture medium. The peptide obtained according to example (a) was solubilized to 100 pM in water, and this solution was then diluted to 20 pM in the culture medium and applied to the cells at 5 pM. The synthetic peptide with the sequence GFOGER was applied directly to the cells at a concentration of 5 pM from a 100 pM aqueous stock solution.

[0268] The cells were treated for 6 hours with the GFOGER peptide (SEQ ID No. 3) or the peptide according to example a) at 5 pM, then the culture medium was renewed.

[0269] An untreated condition (NT) with the culture medium allows measurement of the basal production of procollagen I and collagen I.

[0270] Collagen I and Pro-Col I synthesis were measured after 48 hours of incubation at 37°C and 5% CO2. The supernatants were used to measure Pro-Col I (Human Pro-Collagen I C-Terminal Propeptide (PICP) ELISA kit, Abeam). A standard lysis reagent was then added to measure the DNA content without solubilizing the Collagen I deposited at the bottom of the wells. The amount of DNA in the wells was measured using ThermoFisher Scientific's Quant-iT PicoGreen reagents, and Collagen I was measured using DELFIA TRF technology (Rewity).

[0271] The corrected fluorescence is adjusted for the DNA concentration in each well to obtain a stimulation ratio for each well. The percentage of stimulation of collagen I or pro-col I synthesis is then determined by adjusting the stimulation ratio of the active treatment with the untreated condition. Results are presented as mean ± SEM (standard error of the mean). Statistical analysis of the data was performed using SigmaPlot software (version 12.5), and the significance level was set at 5% (p < 0.05).

[0272] Results: Table 3.1 - Synthesis of Pro-Col I on monolayer fibroblasts

[0273] Conclusion: The peptide according to the invention induced a significant increase in the synthesis of procollagen I and collagen I, unlike the GFOGER peptide (SEQ ID No. 3). This demonstrates the ability of the peptide according to the invention to stimulate the synthesis of collagen I and procollagen I, and therefore the dermis, thereby preventing and / or reducing the signs of aging in healthy skin and / or mucous membranes, improving the architecture of healthy skin and / or mucous membranes, preventing and / or treating unsightly marks on healthy skin and / or mucous membranes, particularly those due to depression and / or sagging of the dermis, improving and / or maintaining the biomechanical properties of healthy skin and / or mucous membranes, and / or improving and / or maintaining healthy hair, nails, and skin appendages by enhancing their anchoring in a higher-quality dermis.

[0274] Example 4: Evaluation of the activity of the peptide according to the invention on the stimulation of collagen I and III synthesis in the dermis

[0275] Principle: The objective of the study was to evaluate the efficacy of the peptide according to the invention on the synthesis of collagen I and III in a reconstructed dermis model.

[0276] Protocol: Reconstructed human dermis matured for 28 days was obtained after seeding fibroblasts from a donor (18-year-old woman) onto an acellular matrix made of collagen, chitosan, and glucosaminoglycan (GAG) (Mimedisc®) and cultured in a specific cell growth medium, DMEM (Dulbecco's Modified Eagle Medium) / F12, containing 10% fetal bovine serum (v / v) and antibiotics. The culture medium was renewed every two days, and the following conditions were tested (3 reconstructed dermis / condition):

[0277] - An untreated control (NT) group consisted of reconstructed dermis cultures maintained in the aforementioned medium without any further treatment.

[0278] - For treatments with the active ingredient: the peptide obtained according to example a) is solubilized to 100 pM in water, then this peptide stock solution is diluted to 20 pM in water before being applied to the reconstructed dermis at a concentration of 0.4 pM. Treatments with the peptide were performed every 2 days, from day 7 to day 28.

[0279] Collagen I and III expression in reconstructed human dermis was assessed by immunostaining and quantified by image analysis. 10 µm tissue cryosections were fixed with acetone at -20°C for 10 minutes and then treated with 2% (v / v) sheep serum for 2 hours at room temperature. After washing, the sections were incubated with anti-collagen I (Invitrogen) and anti-collagen III (Novotec) antibodies for 2 hours at room temperature. Secondary antibodies were then applied (Thermofisher). Finally, the slides were mounted with a specific medium (VECTASHIELD antifade) containing DAPI (4',6-diamidino-2-phenylindole) for nuclear staining and then analyzed by fluorescence microscopy (LEICA SP8).

[0280] Collagen I and collagen III expression was quantified by image analysis using FIJI software (Image J2, open source). Results are presented as mean ± SEM (standard error of the mean). A total of 9 images were acquired per condition (3 reconstructed dermis / condition and 3 images / reconstructed dermis).

[0281] Statistical analysis of the data was performed using SigmaPlot software (version 12.5). A two-tailed test was used to compare the post-treatment data with the untreated control. The significance level was set at 5% (p<0.05).

[0282] Results :

[0283] Table 4 - Synthesis of collagen I and III on reconstructed dermis

[0284] Conclusion: The peptide according to the invention significantly stimulated the synthesis of collagen I and III. This demonstrates the property of the peptide according to the invention to stimulate the synthesis of type I and III collagen and therefore to improve the dermis and thus prevent and / or reduce the signs of aging of healthy skin and / or healthy mucous membranes, improve the architecture of healthy skin and / or healthy mucous membranes, prevent and / or treat unsightly marks of healthy skin and / or healthy mucous membranes, in particular those due to depression and / or sagging of the dermis, improve and / or maintain the biomechanical properties of healthy skin and / or healthy mucous membranes, and / or improve and / or maintain healthy hair and nails.

[0285] Example 5: Evaluation of the activity of the peptide according to the invention on the proliferation and migration of keratinocytes in the neo-epidermis

[0286] Principle: The objective of the study was to evaluate the activity of the peptide according to the invention on the proliferation and migration of keratinocytes in the neo-epidermis and thus on wound healing using human skin excipients maintained in survival. The first step allows for the reproduction of topical application of the products after the creation of lesions on the excipients. The second, histological phase allows for the evaluation of the general morphology of the neo-epidermis that forms to close the wound, as well as the measurement of its length.

[0287] Protocol:

[0288] A 0.8 mL aliquot of an aqueous peptide stock solution obtained according to example (a) at 100 pM is diluted in 99.2 mL of saline in Dulbecco's phosphate buffer (DPBS). The resulting solution has a molarity of 0.8 pM. This is the concentration tested for the peptide.

[0289] Rectangular excipients were prepared from abdominoplasty tissue from a 49-year-old woman with phototype II (according to the Fitzpatrick skin type classification). The excipients were maintained in culture medium suitable for explant culture at 37°C in a humid atmosphere with 5% CO2. At baseline (day 0.00), two lesions per excipient were created using a 3.5 mm diameter biopsy punch, deep enough to remove the epidermis and the superficial dermis. The lesions were made immediately before product application.

[0290] At 0.8 pM peptide solution (J2, J5, J7), the peptide solution was applied topically at a rate of 3 pL per expiant and spread using a small spatula (3 expiants per condition). The culture medium was halved on J2, J5, and J7. Injured expiants who did not receive the peptide solution (untreated controls, "NT") were used for analysis of the results on J5 and J8.

[0291] At 0.08, 0.5, and 0.8, the excipients were collected and placed in a buffered formaldehyde solution. 24 h later, the samples were dehydrated and embedded in paraffin. 5 µm thick sections were prepared with a microtome and then mounted on histological glass slides.

[0292] The appearance of the synthesized neo-epidermis was assessed by microscopic observation of skin sections after Masson's trichrome staining (Leica DMLB microscope coupled with an Olympus DP scanning device). Four images per expiant were analyzed using dedicated software (CellSens Software).

[0293] The parameters evaluated are as follows:

[0294] A. Analysis of the general morphology of the neo-epidermis formed following the lesion according to the following criteria

[0295] - The number of cell layers (correlated with good proliferation) is evaluated based on the average number of cell layers of the synthesized neo-epidermis.

[0296] - The length of the synthesized neo-epidermis (correlated with good migration) is noted on a scale of 0 to 5.

[0297] - for each criterion, the higher the score, the more the analyzed parameter is increased or improved.

[0298] A score higher than the score of the untreated control (NT) at the same observation time shows a healing activity of the peptide according to the tested invention.

[0299] B. The length of the formed neo-epidermis (expressed in pm) was measured by image analysis.

[0300] The statistical analysis of the data was carried out according to the student test, n=12 (3 expiants / condition; 4 images / explant).

[0301] Results

[0302] The morphological analysis and measurement of the length of the formed neo-epidermis are summarized in the tables below. Table 5.1 - Qualitative morphological analysis of neo-epidermis formed on the injured area

[0303] Table 5.2 - Mean measurement of the length of the newly formed neo-epidermis (n=12 measurements per condition)

[0304] Conclusion: The peptide according to the invention rapidly increases the proliferation and migration of keratinocytes in the neo-epidermis, which generally contributes to epidermal renewal and regeneration, maintaining its good condition and repairing it in depth when damaged. This test further demonstrates that the peptide according to the invention, through its healing activity, repairs damaged epidermis in both length and thickness, thus preventing the formation of unsightly scars. This therefore demonstrates that the peptide according to the invention is useful for preventing and / or reducing the signs of aging in healthy skin and / or mucous membranes, improving the architecture of healthy skin and / or mucous membranes, in particular regenerating them and increasing their thickness, and preventing and / or treating unsightly marks on healthy skin and / or mucous membranes.

[0305] Example 6: Evaluation of the anti-alvation activity of the peptide according to the invention

[0306] Principle: The objective of the study was to evaluate the anti-glycation activity of the peptide according to the invention in a model composed of explants of devitalized whole human skin.

[0307] Protocol: Whole-skin excipients, 5 mm in diameter, were used as substrates for the glycation reaction. The skin was obtained from an abdominal plastic surgery procedure performed on a 43-year-old woman. These excipients were first subjected to four successive freeze / thaw cycles to eliminate any trace of enzymes that could interfere with the glycation reaction. They were then incubated for 14 days at 45°C in the absence or presence of 60 mM ribose, and in the absence (control NT) or presence of the peptide obtained according to example 1a) at different doses, while being protected from the atmosphere and light. The untreated control NT represents the result of the experiment conducted with 60 mM ribose but without the addition of the tested peptide. The peptide obtained according to example a) is solubilized to 100 pM in water and then diluted in the expiant incubation buffer (PBS buffer) to the desired concentration. Three expiants are tested per condition.

[0308] At the end of the incubation stage, the glycated proteins of the skin expiants were quantified using a colorimetric method (Kobayashi K and Igimi H, Biol. Pharm. Bull, 19 (4) 487-490 (1996)).

[0309] The statistical analysis of the data was performed using a one-way ANOVA (analysis of variance) test followed by a Holm-Sidak test. The significance level was set at 5% (p<0.05).

[0310] Results :

[0311] Table 6 - Inhibition of glycation on devitalized skin expiants

[0312] Conclusion: The peptide according to the invention significantly inhibits the glycation reaction. This demonstrates that the peptide according to the invention is useful for preventing and / or reducing the signs of aging of healthy skin and / or mucous membranes, improving the architecture of healthy skin and / or mucous membranes, in particular regenerating them, preventing and / or treating unsightly marks on healthy skin and / or mucous membranes, improving and / or maintaining the biomechanical properties of healthy skin and / or mucous membranes, soothing healthy skin and / or mucous membranes, and / or improving and / or maintaining healthy hair, nails, and skin.

[0313] Example 7: Evaluation of the anti-inflammatory activity of the peptide according to the invention

[0314] Principle: The objective was to evaluate the anti-inflammatory activity of the peptide according to the invention by measuring the inhibition of interleukin IL-8 synthesis, induced by the application of a pro-inflammatory cocktail on keratinocytes and the inhibition of interleukin IL-6 synthesis induced by UVA irradiation on fibroblasts in irradiated collagen lattice.

[0315] 7.1: IL-8 keratinocyte test:

[0316] Protocol: Normal human keratinocytes from the abdomen of a 64-year-old woman were seeded in 96-well plates and incubated at 37°C and 5% CO2 for 3 days. The cells were first incubated or not for 24 hours with the peptide diluted in a nutrient-free standard medium, and then for 24 hours with a pro-inflammatory cocktail (PIC) composed of TNFα, IFNγ, and Poly I:C sufficient to significantly stimulate IL-8 release from keratinocytes in a nutrient-free standard medium. The condition without peptide and without PIC is denoted as "NT", the condition without peptide and with pro-inflammatory cocktail as "CIC", and the condition with peptide and with pro-inflammatory cocktail as "CIC+Peptide." The peptide obtained according to example a) is solubilized to 100 pM in water, then this stock solution of peptide is diluted to 20 pM in a nutrient-free medium, and then applied to the cells at 0.1 pM.After two 24-hour incubations, the supernatant is removed and analyzed using Rewity's AlphaLisa IL8 technology. The percentage of IL-8 inhibition (NT) is determined by first subtracting the baseline IL-8 concentration following treatment with the pro-inflammatory cocktail (CPI).

[0317] The statistical analysis of the data was carried out using the Student's t-test or a One Way ANOVA - Dunnett's and the number of replicates (n) per condition is indicated in the table.

[0318] IL-8 keratinocyte results:

[0319] Table 7.1 - IL-8 synthesis inhibition assay on keratinocytes

[0320] Conclusion: The peptide according to the invention significantly inhibited IL-8 synthesis induced by the pro-inflammatory cocktail on keratinocytes by 31.1%, indicating a soothing effect on the skin, particularly the scalp, and / or mucous membranes, especially sensitive skin and / or mucous membranes. This reduction in pro-inflammatory stress also improves the structure and / or function of the hair follicle to limit hair loss and increase the diameter, density, and / or strength of the hair fibers produced.

[0321] 7.2: IL-6 fibroblast test

[0322] Protocol: A cell suspension of human dermal fibroblasts from the abdomen of a 46-year-old Caucasian woman was mixed with a type I collagen solution (as described by R.L. Ehrmann et al., J. Natl. Cancer Inst. 1956, 16, 1375) to obtain a gel containing 200,000 fibroblasts / ml and 0.45 mg / mL of type I collagen. The peptide (as described in example 1a) was solubilized to 100 pM in water, and this peptide stock solution was then diluted to 50 pM in water. This solution was then added to the collagen solution at a concentration of 5 pM, if desired. For the peptide-free condition, an equivalent volume of water was added. The mixture was then irradiated with UVA at 2 J / cm². 2 for the stressed control (“UVA”) and the peptide being tested. The collagen gels were then incubated for 4 days at 37°C, with 5% CO2 and 95% humidity. The release of IL-6 into the supernatant was quantified by an ELISA assay (R&D systems).

[0323] The condition without peptide and without UVA is designated by "NT", the condition without peptide and with UVA is designated by "UVA", and the condition with peptide and with UVA is designated by "with UVA+ Peptide".

[0324] Each condition was tested in quadruplets, and the results are expressed as a percentage relative to the control with UVA stress (UVA) and presented as mean ± standard error of the mean (SEM). Statistical evaluations were based on Student's t-test according to the recommendations of the SigmaPlot software.

[0325] IL-6 fibroblast results:

[0326] Table 7.2 - IL-6 synthesis inhibition test on fibroblasts

[0327] Conclusion: The peptide according to the invention significantly inhibits UVA-induced IL-6 synthesis in fibroblasts by 28%, demonstrating its usefulness in soothing the skin, including the scalp and / or mucous membranes, particularly sensitive skin and / or mucous membranes. This pro-inflammatory stress-reduction effect also improves the structure and / or function of the hair follicle to limit hair loss and increase the diameter, density, and / or strength of the hair fibers produced. The peptide according to the invention is therefore also useful for improving and / or maintaining healthy hair and nails.

[0328] Example 8: Evaluation of the activity of the peptide according to the invention on leptin expression

[0329] The effect of the peptide is evaluated on an ex vivo model of vascularized human adipose tissue subjected to stress by the cytokine TNFa and on which the expression of the leptin gene is measured by the quantitative reverse transcription PCR (polymerase chain reaction) technique known as RT-qPCR.

[0330] Protocol:

[0331] This 0.8 pM aqueous peptide solution is prepared and then diluted to 0.08 pM in a basal medium (=EGM Endothelial cell Growth Medium) supplemented with 2% (v / v) FBS (fetal calf serum), 22.5 pg / mL heparin and 1 pg / mL ascorbic acid) with or without the addition of TNFα (stress-free control) in a dose sufficient to induce inflammatory stress which results in a significant decrease in leptin.

[0332] Vascularized models of human subcutaneous adipose tissue were generated from fresh liposuction material obtained from a donor (65-year-old woman). Centrifugation was then performed to separate the adipose tissue fractions and cells. The cellular fraction, containing a population of highly proliferative stem cells, was purified, and the adipose tissue fraction was mechanically dissociated using a medical device to reduce its size and obtain lobular structures. Finally, the cell and tissue fractions (adipose cell preparation) were mixed and incubated at 37°C, 5% CO2 in an optimized medium (EGM Plus - Lonza) for 2 weeks prior to processing.

[0333] On day 0 (J0), 50 mg of adipocyte preparation was encapsulated in LMT agarose and then loaded into each well of a 24-well plate; 1 mL of basal medium containing or not (NT) TNF-α and the α peptide was added. The medium (containing the products to be tested) was renewed every 2–3 days for 10 days. The number of replicates per condition was set at n=5.

[0334] At day 10, cell viability was checked using a commercially available XTT test kit (Roche), following the manufacturer's instructions.

[0335] On day 10, total RNA was extracted from 3 or 4 replicates for each group using a commercially available RNA extraction kit (Zymoclean Gel RNA Recovery kit, Ozyme), following the manufacturer's instructions. A reverse transcription-polymerase chain reaction (RT-qPCR) assay was performed on each duplicate replica (8 values ​​per condition). Leptin gene expression was analyzed by real-time PCR using the StepOne Plus system from Applied Biosystems in all replicas. The primer sequences used for leptin detection were: hLeptin Fw 5'-AGGGAGACCGAGCGCTTTC-3' SEQ ID #7 and hLeptin Rv 5'-TGCATCTCCACACACCAAACC-3' SEQ ID #9.

[0336] Statistical analysis of the data was performed using SigmaPlot software (version 12.5). A Student's t-test or Mann-Whitney U test was used to compare the post-treatment data with the stressed control (TNFα). The significance level was set at 5% (p < 0.05). The number of assays per condition is shown in Table 8.

[0337] Results

[0338] Cell viability was monitored across all experimental conditions, and treatment with the peptide had no impact on this parameter. Results are presented as mean percentages relative to the control with TNFα stress ± standard error of the mean (SEM).

[0339] Table 8 - Average leptin expression

[0340] According to the results presented in Table 8, the addition of TNFα leads to a significant decrease in basal leptin expression. The peptide according to the invention, at a concentration of 0.08 pM, restored leptin expression to a level similar to the basal level prior to TNFα stress, increasing its expression by 485% compared to TNFα.

[0341] This test therefore demonstrates that the peptide has the ability to maintain a significant level of leptin, despite inflammatory skin stress and therefore contributes to the production of collagen and hyaluronic acid and thus to a quality dermis, promoting the anchoring of the hair follicle and contributing to the limitation of hair loss.

[0342] This therefore demonstrates that the peptide according to the invention is useful for preventing and / or reducing the signs of aging of healthy skin and / or healthy mucous membranes, improving the architecture of healthy skin and / or healthy mucous membranes, in particular increasing their thickness, and / or improving and / or maintaining the biomechanical properties of healthy skin and / or healthy mucous membranes, and / or improving and / or maintaining healthy hair and nails.

[0343] Example 9: Evaluation of the effect of the peptide according to the invention on talin expression

[0344] Protocol:

[0345] Normal human fibroblasts obtained from a breast sample of a 19-year-old woman were seeded into 12-well plates and incubated at 37°C and 5% CO2 for 3 days.

[0346] The plaques were then irradiated or not (unstressed control) with UVA at a dose of 10 J / cm² 2Then, the products to be tested (peptide Ia) or GFOGER (SEQ ID No. 3) were applied or not (stressed control, referred to as "UVA"). After 6 hours of incubation, the medium was replaced with culture medium without the product to be tested (GFM Fibroblast Growth Medium complete) and then again with culture medium without the active ingredient the following morning. 48 hours after the start of the experiment, the cells were harvested and then lysed using a specific lysis buffer (CelLytic™, Sigma). The protein concentration was determined by the bicinchoninate assay (BCA Protein Assay), and then all samples were adjusted to the same protein concentration and loaded in equal amounts into each capillary.

[0347] Talin was identified using a capillary electrophoresis-based protein analysis system (Sally Sue instrument, ProteinSimple, San Jose, California, USA), using primary anti-talin antibodies (Cell Signaling), then revealed by a horseradish peroxidase (HRP) conjugated secondary antibody and a chemiluminescent substrate.

[0348] The chemiluminescent signal obtained was detected and quantified using Compass software version 5.0.1 (ProteinSimple), on six to eight replicates (n=6-8).

[0349] Talin expression levels were expressed as a mean percentage ± SEM (standard error of the mean) with n=6-8, relative to the UVA-stressed control. The talin level in this condition is considered the reference level, set at 100%.

[0350] Statistical analyses were performed using SigmaPlot software (version 12.5) (Systat Software Inc., San Jose, California, USA).

[0351] The statistical comparison between the conditions was carried out using a Student's t-test, with a significance threshold set at 5% (p < 0.05).

[0352] Result :

[0353] Table 9: Stimulation of talin expression by GFOGER (SEQ IDN°3) and by the peptide according to the invention on fibroblasts after UVA stress.

[0354] Following UVA irradiation, a decrease in talin expression was observed compared to the untreated, unirradiated control (unstressed control). The peptide according to the invention significantly increased talin expression by 202% (p < 0.001) compared to the untreated (UVA) irradiated control. In contrast, the GFOGER peptide (SEQ ID No. 3) showed no activity on talin expression. This test demonstrates that the peptide according to the invention increases talin expression, thereby enhancing the activation and signaling activity of integrins, thus improving their ability to establish optimal connections between cells and the extracellular matrix and contributing to skin regeneration, particularly when the skin is subjected to damage.

[0355] This therefore demonstrates that the peptide according to the invention is useful for preventing and / or reducing the signs of aging of healthy skin and / or healthy mucous membranes, improving the architecture of healthy skin and / or healthy mucous membranes, in particular regenerating them and increasing their thickness, and / or preventing and / or treating unsightly marks on healthy skin and / or healthy mucous membranes.

[0356] Example 10: cosmetic ingredient

[0357] The cosmetic ingredient is prepared by diluting and mixing the peptide obtained in example a) in powders or liquids to obtain the following compositions (in % w / w): a.

[0358] • Peptide (la) 0.25%

[0359] • Mannitol qsp 100%

[0360] • Peptide (la) 0.1%

[0361] • Maltodextrin q.s. 100%

[0362] • Peptide (la) 0.02%

[0363] • Mannitol qsp 100% • Peptide la) 0.01%

[0364] • Maltodextrin q.s. 100%

[0365] • Peptide (la) 0.005%

[0366] • 1,2-Hexandiol 1%

[0367] • Glycerin 50%

[0368] • Water qsp 100%

[0369] Example 11: Cosmetic composition

[0370] The cosmetic ingredient in Example 10 is formulated as the following gel-cream type cosmetic composition (Table 11):

[0371] The formulation was carried out in a conventional cold process.

[0372] Such a composition therefore contains 0.8 pM or 2 ppm by mass of the peptide obtained according to example a).

[0373] Example 12: Evaluation of the effect of the peptide according to the invention on damaged collagen in biopsies

[0374] -Protocol:

[0375] Punch biopsies were obtained from 5 healthy female volunteers (aged 60 to 70 years, Fitzpatrick skin type II) with thin skin on the inner forearm. All procedures involving an interventional study on human volunteers were approved by an ethics committee. Each volunteer applied the composition described in Example 11 and the placebo composition (the composition of Example 11 in which the cosmetic ingredient is replaced by water) to each forearm twice daily, using gentle massage (randomized and double-blind study).Before starting treatment (J0) and after 8 weeks of treatment (J56), punch biopsies (4 mm wide and 0.7 mm deep) were made on each arm, then frozen and stored at -80°C. The biopsies were then embedded in a cryogenic fixation medium (OCT Optimal Cutting Temperature compound) and 10 µm skin sections were made.

[0376] -Immunostaining of damaged collagen:

[0377] Damaged collagen expression in skin biopsies was assessed by immunostaining and quantification. Serial 10 µm tissue cryosections were fixed with acetone at -20°C for 10 minutes and blocked with 2% (v / v) sheep serum for 2 hours at room temperature. After washing, the cryosections were incubated with a fluorescein-conjugated damaged collagen hybridizing peptide (F-CHP, 3Helix) for 16 hours at 4°C. Following a wash step with PBS buffer, the slides were mounted with VECTASHIELD antifade medium containing DAPI for nuclear staining and analyzed by fluorescence microscopy (LEICA SP8).

[0378] Damaged collagen was quantified by estimating its distribution in the region of interest (part of the dermis) using ImageJ software. The results are expressed as a percentage change from baseline (J0) in the percentage of damaged collagen surface area in the dermis.

[0379] -Immunostaining of hyaluronic acid:

[0380] Hyaluronic acid is detected via immunolabeling of the HABP (hyaluronic acid binding protein) which is specifically bound to hyaluronic acid.

[0381] HABP expression in skin biopsies was assessed by immunostaining and quantification. 10 µm tissue cryosections were fixed with 4% (w / v) paraformaldehyde at room temperature for 20 minutes and blocked with 2% (v / v) sheep serum for 2 hours at room temperature. After washing, the cryosections were incubated with an HABP antibody (conjugated with biotin) for 16 hours at 4°C. Streptavidin Alexa 488 secondary antibodies were then applied. Finally, the slides were mounted with VECTASHIELD antifade medium containing DAPI for nuclear staining and analyzed by fluorescence microscopy (LEICA SP8). Hyaluronic acid was quantified by estimating its intensity in the superficial dermis (depth of 35 pm from the dermo-epidermal junction (DEJ) not included in the quantification) and deep dermis (depth of 35 pm to 115 pm from the DEJ) using ImageJ software.Results are expressed as the percentage change from baseline (J0) in the percentage of HABP intensity in each dermal compartment. Damaged collagen and HABP expression were quantified by fluorescence imaging using FIJI software (Image J2, open source). Results are presented as mean ± SEM (standard error of the mean). Statistical analysis was performed using SigmaPlot software (version 12.5). A two-tailed test was used to compare post-treatment data with baseline and with the placebo composition. The significance level was set at 5% (p < 0.05).

[0382] Results obtained with the composition according to the invention:

[0383] Number of images analyzed for each condition: 30 for JO and J56

[0384] Table 12 - Variation in damaged collagen and hyaluronic acid content after 56 days of treatment on human volunteers with the composition of ex 11

[0385] After 56 days, the damaged collagen content of the skin treated with the composition containing the peptide according to the invention was reduced by 41% (p<0.01) compared to the content at JO and by 25% compared to the content of the placebo composition (p<0.01).

[0386] After 56 days, the hyaluronic acid content of the skin treated with the composition according to the invention was increased by 60% (p<0.001) and 75% (p<0.001) in the superficial and deep dermis respectively vs JO and by 32% (p<0.05) and 42% (p<0.01) vs placebo composition.

[0387] The peptide according to the invention therefore makes it possible to reduce the amount of damaged collagen present in the skin and to increase the amount of hyaluronic acid in the different layers of the dermis and thus to improve the condition of the skin, its appearance and its comfort.

[0388] This therefore demonstrates that the peptide according to the invention is useful for preventing and / or reducing the signs of aging of healthy skin and / or healthy mucous membranes, improving the architecture of healthy skin and / or healthy mucous membranes, in particular increasing their thickness, and / or preventing and / or treating unsightly marks on healthy skin and / or healthy mucous membranes, in particular when these marks are due to or accompanied by a depression of the dermis, for improving and / or maintaining the biomechanical properties of healthy skin and / or healthy mucous membranes and / or for improving and / or maintaining healthy skin appendages.

[0389] Example 13: Clinical tests of the peptide according to the invention on forehead wrinkles, skin tone and thickness

[0390] Protocol:

[0391] Two groups of women aged 42 to 70 applied either the composition of Example 11 or the placebo composition (the same as Example 11 but with the cosmetic ingredient replaced by water) to half of their face twice a day for two months. The maximum depth of the forehead wrinkle was assessed using fringe projection (AEVA), skin tone was measured with a cutometer (Cutometer dual MPA 580), and total skin thickness (epidermis + dermis) was estimated using an ultrasound device (DUB Skin Scanner). The efficacy of the peptide-containing composition was compared with that of the placebo gel-cream.

[0392] Measurements of the maximum and mean depth of forehead wrinkles were taken at baseline (EO), after one month of application (D28), and finally after two months of application (D56). The peptide's efficacy on the mean and maximum depth of forehead wrinkles was determined by comparing the percentage change after 28 and 56 days of application, relative to EO, of the peptide-containing composition according to the invention with that of the placebo composition. Values ​​are expressed as averages across the analyzed volunteers. Cutometry measurements (parameter R6) were taken at baseline (EO) and after two months of application (D56). Parameter R6 corresponds to the evaluation of skin tone and may be correlated with skin resistance following deformation. This parameter increases with aging (Chen et al., Cosmetics 2024, 11, 205).The peptide's efficacy on skin tone was determined by comparing the percentage change after 56 days of application, relative to baseline (day 0), of the composition of Example 11 with that of the placebo composition. A decrease in the change of parameter R6 corresponds to an improvement in skin tone. Values ​​are expressed as averages across the analyzed volunteers.

[0393] Total skin thickness measurements were taken at baseline (Day 0), after one month of application (Day 28), and finally after two months of application (Day 56). The peptide's efficacy on skin thickness was determined by comparing the percentage change after 28 and 56 days of application, relative to Day 0, between the composition of Example 11 and the placebo composition. Values ​​are expressed as the average across the analyzed volunteers. Statistical analyses were performed after verifying the normality of the distribution of values ​​(Shapiro-Wilk test) using an unpaired comparison (Student's t-test or Mann-Whitney U test). The significance level was set at 5% (p < 0.05).

[0394] Results :

[0395] The number of volunteers (n) is designated for the placebo composition (placebo) and for the composition according to the invention of exile (Compo Pept).

[0396] Table 13 - Variation in maximum and mean depths of forehead wrinkles and skin thickness after 28 and 56 days of treatment on human volunteers with the composition of ex 10

[0397] After 28 and 56 days, the maximum depth of forehead wrinkles treated with the composition of Example 11 was reduced by 21% (p<0.05) and 27% (p<0.1), respectively, compared to the placebo composition. After 28 and 56 days, the average depth of forehead wrinkles treated with the peptide-containing composition was reduced by 13% (p<0.05) and 21% (p<0.05), respectively, compared to the placebo. The peptide according to the invention therefore reduces the average and maximum depth of forehead wrinkles.

[0398] After 56 days, the change in parameter R6 measured on skin treated with the composition of Example 11 was reduced by 10% (p<0.05) compared to placebo (with n=32 for placebo and n=33 for the composition of Example 11, and a statistical analysis (p<0.05)). The peptide according to the invention therefore improves skin tone. After 28 and 56 days, the average thickness of skin treated with the composition of Example 11 was increased by 5% (p<0.05) and 6% (p<0.05), respectively, compared to the placebo composition. The peptide according to the invention therefore increases skin thickness.

[0399] This therefore demonstrates that the peptide according to the invention is useful for preventing and / or reducing the signs of aging of healthy skin and / or healthy mucous membranes, improving the architecture of healthy skin and / or healthy mucous membranes, in particular increasing their thickness, and / or preventing and / or treating unsightly marks on healthy skin and / or healthy mucous membranes, particularly when these marks are due to or accompanied by a depression of the dermis, to improve and / or maintain the biomechanical properties of healthy skin and / or healthy mucous membranes.

[0400] Example 14: Clinical tests of the peptide according to the invention on crow's feet wrinkles

[0401] Protocol

[0402] A group of women aged 55 to 71 years applied either the composition described in Example 11 or the placebo composition (the composition of Example 11 in which the cosmetic ingredient according to the invention was replaced by water) to half of their face, twice a day for one month. The depth of crow's feet was assessed by image analysis (Colorface®) at baseline (D0) and after one month of application (D28). The peptide's efficacy on the depth of crow's feet was determined by comparing the percentage change after 28 days of application, compared to D0, of the formulation containing the peptide with that of the placebo composition. Values ​​are expressed as the average across the analyzed volunteers. Statistical analysis was performed after verifying the normality of the distribution of values ​​(Shapiro-Wilk test) using paired comparisons (Student's t-test or Mann-Whitney U test).The significance threshold is 5% (p<0.05).

[0403] Results :

[0404] The number of volunteers (n) was 24 for the placebo composition (placebo) and for the composition according to the invention of exile.

[0405] After 28 days, the depth of crow's feet wrinkles treated with the composition according to the invention was reduced by 10% (p<0.01) compared to placebo.

[0406] This demonstrates that the peptide according to the invention is useful for preventing and / or reducing the signs of aging in healthy skin and / or healthy mucous membranes. Example 15: Evaluation of the effect of the peptide according to the invention on epidermal thickness

[0407] Protocol:

[0408] Reconstructed skin is created using cells from the foreskin of a 3-year-old Asian donor. Four samples for each condition are cultured in a microfluidic device with a flow rate of 1 pL per minute.

[0409] The dermis is obtained after 4 days of culture in a fibrin gel, followed by keratinocyte seeding and a 48-hour proliferation phase before the models are transferred to the air-liquid phase for 14 days. During the last 7 days, an aging cocktail (here, cortisol, but alternatively, a mixture of pro-inflammatory compounds described in Example 7 could be used) is added to the culture medium via systemic application, except for the unstressed control. Also, from day 7 of air-liquid culture until day 14 of air-liquid culture (when culture is stopped), for each condition, 10 pL of the product to be tested is applied topically daily. The product tested was PBS buffer for the untreated stressed control or the peptide obtained according to Example 1a) diluted to a concentration of 0.4 pM in PBS buffer.The skins are then collected and prepared for microscopic analysis.

[0410] Results :

[0411] Application of the aging-inducing cocktail to reconstructed skin resulted in a 25% decrease in epidermal thickness (p<0.01) compared to that of unstressed control skin. In contrast, the epidermal thickness of stressed skin to which the peptide was applied was not significantly different from that of unstressed control skin.

[0412] Thus, the peptide according to the invention made it possible to maintain the thickness of the epidermis in a model of reconstructed skin stressed by an aging cocktail.

[0413] This therefore demonstrates that the peptide according to the invention is useful for preventing and / or reducing the signs of aging of healthy skin and / or healthy mucous membranes, improving the architecture of healthy skin and / or healthy mucous membranes, in particular increasing their thickness, and / or preventing and / or treating unsightly marks on healthy skin and / or healthy mucous membranes.

Claims

1. CLAIMS 1. Cosmetic or dermatological ingredient comprising the peptide of sequence SEQ ID No. 1 and / or one of its derivatives and / or one of its salts.

2. Cosmetic or dermatological ingredient according to claim 1, wherein the peptide is in the form of the derivative of general formula 2: CH3- C(=O)- (Gly-Pro-Pro)4 - Gly- Phe -Hyp - Gly- Glu- Arg -(Gly-Pro-Pro)4 - NH2(2) 3. Cosmetic or dermatological ingredient according to any one of the preceding claims wherein the peptide is present in a content greater than or equal to 0.0001% by weight, preferably between 0.0001% and 10% by weight, more preferably between 0.005% and 1% by weight, even more preferably between 0.01% and 0.25% by weight, again preferably between 0.01% and 0.1% by weight, of dry matter relative to the total weight of the cosmetic ingredient.

4. Cosmetic or dermatological ingredient according to any one of the preceding claims, characterized in that it is in powder form or in liquid form, preferably in powder form further containing a drying support, more preferably in powder form further containing mannitol.

5. Cosmetic or dermatological composition comprising the peptide as defined in any one of claims 1 or 2 and further comprising a suitable cosmetic and / or dermatological vehicle.

6. Cosmetic or dermatological composition according to the preceding claim in which the peptide is present in a content between lxl0' 6 % and 0.1% by weight, preferably of lxl0' 5 % to lxl0' 2 % by weight, still advantageously 5xl0' 5 % to 2xl0' 3 %, in particular lxl0' 4 % to lxl0' 3%, by weight of dry matter relative to the total weight of the composition.

7. Non-therapeutic cosmetic use of a peptide of SEQ sequence ID No. 1 and / or of one of its derivatives and / or of one of its salts and / or of a cosmetic ingredient comprising it according to any one of claims 1 to 4 and / or of a cosmetic composition comprising it according to any one of claims 5 or 6, to improve the condition and / or appearance and / or comfort of healthy skin and / or healthy mucous membranes and / or healthy hair, preferably to prevent and / or reduce the signs of aging of healthy skin and / or healthy mucous membranes and / or to improve the architecture of healthy skin and / or healthy mucous membranes and / or to improve the biomechanical properties of healthy skin and / or healthy mucous membranes.

8. Non-therapeutic cosmetic use according to claim 7, wherein the peptide is in the form of the derivative with general formula 2: CH3- C(=O)- (Gly-Pro-Pro)4 - Gly- Phe -Hyp - Gly- Glu- Arg -(Gly-Pro-Pro)4 - NH2(2) 9. Non-therapeutic cosmetic use according to any one of claims 7 or 8 for: - to prevent and / or reduce the signs of aging of healthy skin and / or healthy mucous membranes, and / or - to improve the architecture of healthy skin and / or healthy mucous membranes, in particular to regenerate healthy skin and / or healthy mucous membranes, and / or to increase the thickness of healthy skin and / or healthy mucous membranes, and / or to prevent the thinning of healthy skin and / or healthy mucous membranes, in particular to prevent thin healthy skin and / or thin healthy mucous membranes, and / or to strengthen the skin and / or mucous membrane barrier, and / or - to prevent and / or treat unsightly marks on healthy skin and / or mucous membranes, in particular to prevent and / or treat unsightly non-pathological scars, and / or reduce their visibility, and / or - to improve and / or maintain the biomechanical properties of healthy skin and / or healthy mucous membranes, in particular firmness, density, elasticity, suppleness, and / or tone, and / or - to soothe healthy skin, especially a healthy scalp, and / or healthy mucous membranes, especially sensitive skin, especially a sensitive scalp, and / or sensitive mucous membranes and / or - to improve and / or maintain healthy hair and skin appendages, in particular to improve and / or maintain the growth of hair and skin appendages, especially keratin fibers, and / or the quality of the keratin material produced at the level of the hair and skin appendages, especially keratin fibers, and / or to prevent and / or reduce the loss of hair and skin appendages, especially hair.

10. Non-therapeutic cosmetic use according to any one of claims 7 to 9 for: - to increase the amount of collagen, preferentially the synthesis of type I collagen, type III collagen and / or procollagen I, the quantity and / or quality of collagen fibers, and / or to decrease the amount of damaged collagen in healthy skin and / or healthy mucous membranes, and / or - increase the proliferation and / or migration of keratinocytes in healthy skin and / or healthy mucous membranes, and / or - to increase the thickness of healthy skin and / or healthy mucous membranes, particularly the dermis and epidermis, and / or - decrease the amount of interleukin 8 and / or 6 in healthy skin and / or healthy mucous membranes, and / or - reduce forehead and crow's feet wrinkles in healthy skin, and / or - to reduce glycation in healthy skin and / or healthy mucous membranes, and / or - increase the amount of leptin in healthy skin and / or healthy mucous membranes, and / or - increase the amount of talin in healthy skin and / or healthy mucous membranes, and / or - to increase the amount of hyaluronic acid in the dermis of healthy skin and / or healthy mucous membranes, and / or - to increase the tone of healthy skin and / or healthy mucous membranes.

11. Non-therapeutic cosmetic use according to any one of claims 7 to 10, characterized in that it is intended for sensitive skin.

12. Non-therapeutic cosmetic use according to any one of claims 7 to 11, characterized in that it is a topical use.

13. Non-therapeutic cosmetic use according to any one of claims 7 to 12 including topical application to at least one area of ​​healthy skin and / or healthy mucous membrane and / or healthy hair selected from the scalp, face in particular the contour of the lips and / or eyes as well as the forehead, hands, arms, décolleté, legs, neck, back, shoulders, belly, wrists, forearms, ankles, thighs, nape of the neck, joint folds and / or armpits, labial mucous membranes, hair, eyelashes, eyebrows and / or head hair.

14. A non-therapeutic cosmetic care and / or treatment method comprising the topical application to at least one area of ​​healthy skin and / or healthy mucous membranes and / or healthy hair and nails of the SEQ ID No. 1 peptide and / or one of its derivatives and / or one of its salts and / or a cosmetic ingredient comprising it according to any one of claims 1 to 4 and / or a cosmetic composition comprising it according to any one of claims 5 or 6, to improve the condition and / or appearance and / or comfort of the area of ​​healthy skin and / or healthy mucous membranes and / or healthy hair and nails.

15. A non-therapeutic cosmetic treatment method according to claim 14, characterized in that it comprises the preliminary step of identifying an area of ​​healthy skin and / or healthy mucous membrane and / or healthy hair and / or nails whose condition and / or appearance and / or the comfort must be where one wishes to improve, in particular an area of ​​healthy skin and / or healthy mucous membrane and / or healthy hair on which and / or in which one wishes to increase the amount of collagen, preferentially the synthesis of type I, type III, and procollagen I collagens, the quantity and / or quality of collagen fibers and / or decrease the amount of damaged collagen, and / or increase the proliferation and / or migration of keratinocytes, and / or increase the thickness, in particular of the dermis and epidermis, and / or decrease the amount of interleukin 8 and / or 6, and / or decrease forehead and crow's feet wrinkles, and / or decrease glycation, and / or increase leptin expression, and / or increase talin expression, and / or increase hyaluronic acid production in the dermis and / or increase tone.

16. A non-therapeutic cosmetic treatment method according to any one of claims 14 or 15, wherein the peptide is in the form of the derivative of formula 2: CH3- C(=O)-(Gly-Pro-Pro)4 - Gly- Phe -Hyp - Gly- Glu- Arg -(Gly-Pro-Pro)4- NH2.

17. Peptide of SEQ ID No. 1 and / or one of its salts and / or one of its derivatives, for use by topical application: - to repair the skin and / or mucous membranes, in particular to repair wounds and / or other superficial injuries of the skin and / or mucous membranes such as canker sores, and / or to improve healing, in particular for the treatment and / or prevention of scars, especially pathological scars, and / or - to prevent and / or treat skin inflammations, particularly of the scalp, and / or mucous membrane inflammations, such as dermatitis and erythema, especially sunburn and / or diaper rash, and / or gingivitis, and / or - to prevent and / or treat acne, and / or - to prevent and / or treat alopecia, and / or - to prevent and / or treat elastosis, particularly solar elastosis.

18. Peptide for its use according to the preceding claim characterized in that it is in the form of a dermatological ingredient according to any one of claims 1 to 4 and / or in the form of a dermatological composition according to any one of claims 5 or 6.

19. Peptide for its use according to any one of claims 17 or 18, for its use in the treatment and / or care of inflamed, atopic, reactive, damaged and / or irritated skin, in particular scalp, and / or mucous membranes.

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