Novel cosmetic and / or dermatological ingredient for improving the condition, appearance and / or comfort of the skin and / or mucous membranes and / or hair and nails
The SEQ ID No. 1 peptide stimulates collagen synthesis and repairs damage, addressing collagen degradation issues in cosmetic and dermatological applications, enhancing skin and hair health.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2025-09-05
- Publication Date
- 2026-03-12
AI Technical Summary
There is a need for a cosmetic and dermatological ingredient that can repair damaged collagen, stimulate collagen production, and improve the overall condition, appearance, and comfort of the skin, mucous membranes, and hair, addressing issues such as loss of firmness, elasticity, and increased hair loss due to collagen degradation caused by aging and external factors.
A specific CHP-type peptide with the SEQ ID No. 1 sequence (GPP)4-GFPGER-(GPP)4, which stimulates collagen synthesis and repairs damaged collagen, is used in cosmetic and dermatological compositions.
The peptide effectively improves the condition and appearance of healthy skin, mucous membranes, and hair by increasing collagen synthesis, enhancing biomechanical properties, and reducing signs of aging, while being cosmetically acceptable and non-irritating.
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Abstract
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 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 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 follicles) to the dermis. A healthy dermis contributes to the health and proper functioning 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 stimulating 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-GFPGER-(GPP)4 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. 12:GFPGER peptide sequence, which is analogous to the SEQ ID No. 3:GFOGER sequence, with hydroxyproline O replaced by proline. The SEQ ID No. 3 sequence is a collagen recognition motif for certain transmembrane integrins of the extracellular matrix, such as O2-I integrins, which are cellular receptors involved in cell adhesion, migration, and signaling. Biomimetic collagen peptides therefore classically incorporate this motif, particularly for the production of cell culture biomaterials.
[0013] Patent application W02023060218A1 thus described in general terms CHP peptide sequences of general formula: (Gly-XY) a.bin which Gly denotes glycine, X and / or Y denotes proline, modified proline or 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)s. 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.
[0014] 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 and / or appearance and / or comfort of the skin, mucous membranes and / or hair.
[0015] 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.
[0016] 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 and further comprising a suitable cosmetic and / or dermatological vehicle.
[0017] 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 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, 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 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 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 skin appendages, in particular to improve and / or maintain the growth of hair appendages, in particular keratin fibers, and / or the quality of the keratinous material produced in the hair appendages, in particular keratin fibers, and / or to prevent and / or reduce hair loss, in particular hair loss.
[0018] The present invention therefore 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 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.
[0019] Furthermore, 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, 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 collagen synthesis, in particular type I collagen, and / or the amount and / or quality of collagen fibers, and / or 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 increase the thickness of healthy skin and / or healthy mucous membranes, in particular the dermis and / or epidermis, and / or decrease glycation in healthy skin and / or healthy mucous membranes, and / or maintain the quality of the hypodermis.and / or to increase the amount of FabP4 protein, particularly its gene expression, in healthy skin and / or healthy mucous membranes, and / or to increase the amount of talin, particularly its protein expression, in healthy skin and / or healthy mucous membranes.
[0020] 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 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.
[0021] The present invention also relates to the SEQ ID No. 1 peptide and / or one of its derivatives and / or one of its salts, for use by topical application:
[0022] - 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
[0023] - 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
[0024] - to prevent and / or treat acne, and / or
[0025] - to prevent and / or treat alopecia, and / or
[0026] - to prevent and / or treat elastosis, particularly solar elastosis.
[0027] 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.
[0028] 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-GFPGER-GPP-GPP-GPP-GPP
[0029] The peptide according to the invention therefore has the general formula 1: (Gly-Pro-Pro)4 - Gly- Phe -Pro - Gly- Glu- Arg -(Gly-Pro-Pro)4 (1)
[0030] This peptide has a molecular weight of 2672.01 g / mol, and a thermal disassembly temperature of 32°C. This 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 article by Ahmad et al., J. Nucl. Med. 2025; Feb 2025.
[0031] 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:
[0032] SEQ ID No. 2: GPO- GPO- GPO- GPO-GFPGER- GPO- GPO- GPO- GPO
[0033] O denoting hydroxyproline, preferentially (2S,4R)-4-hydroxyproline(4-Hyp).
[0034] This same peptide is also written under the general formula 3: (Gly-Pro-Hyp)4- Gly-Phe-Pro-Gly-Glu-Arg-(Gly-Pro-Hyp)4(3)
[0035] 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.
[0036] 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.
[0037] In this particular embodiment, the peptide derivative according to the invention of SEQ ID No. 1 has the general formula 4:
[0038] CH3-C(=O)-(Gly-Pro-Pro)4- Gly- Phe -Pro - Gly- Glu- Arg -(Gly-Pro-Pro)4(4) and that of SEQ ID N°2 has the general formula 5:
[0039] CH3-C(=O)-(Gly-Pro-Hyp)4-Gly-Phe-Pro-Gly-Glu-Arg-(Gly-Pro-Hyp)4(5) where Hyp denotes hydroxyproline, preferably (2S,4R)-4-hydroxyproline (4-Hyp). According to another embodiment of the invention, the term "peptide derivative" denotes the peptide which comprises a modification of the C-terminal amino acid with an amide function, in C1-C24 or an ester in C1-C24, said function being linear or branched, saturated or unsaturated, substituted or unsubstituted, or with a primary amide function, preferably a primary amide (-NH2).
[0040] 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.
[0041] In this particular embodiment, the peptide derivative according to the invention of SEQ ID No. 1 has the general formula 6:
[0042] (Gly-Pro-Pro)4 - Gly- Phe -Pro - Gly- Glu- Arg -(Gly-Pro-Pro)4- NH2 (6) and that of SEQ ID N°2 has the general formula 7:
[0043] (Gly-Pro- Hyp)4- Gly- Phe -Pro - Gly- Glu- Arg -(Gly-Pro- Hyp)4- NH2 (7) in which Hyp denotes hydroxyproline, preferentially (2S,4R)-4-hydroxyproline (4- Hyp).
[0044] 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 SEQ ID No. 1 derivative of formula
[0045] CH3-C(=O)-GPP-GPP-GPP-GPP-GFPGER-GPP-GPP-GPP-GPP-NH2.
[0046] This same peptide can also be written according to the general formula 2:
[0047] CH3-C(=O)- (Gly-Pro-Pro)4- Gly- Phe -Pro - Gly- Glu- Arg -(Gly-Pro-Pro)4 - NH2(2)
[0048] Thus, this peptide comprises 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. This derivative of the peptide according to the invention is described in Example 1b).
[0049] According to one 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 in the N and / or C terminal position by the addition of a functional group as previously described.
[0050] 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:
[0051] CH3-C(=O)- GPO- GPO- GPO- GPO-GFPGER- GPO- GPO- GPO- GPO-NH2.
[0052] O in the GPO motif designates hydroxyproline, preferentially (2S,4R)-4-hydroxyproline (4-Hyp).
[0053] This same peptide can also be written according to the general formula 8: CH3-C(=O)- (Gly-Pro- Hyp)4- Gly- Phe -Pro - Gly- Glu- Arg -(Gly-Pro- Hyp)4- NH2(8).
[0054] The derivatives of the peptide according to the invention are cosmetically and / or dermatologically acceptable, in particular topically acceptable.
[0055] 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.
[0056] The salts of the peptide according to the invention are cosmetically and / or dermatologically acceptable, in particular topically acceptable.
[0057] 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.
[0058] In a preferred embodiment, the peptide according to the invention is exactly that of SEQ ID No. 1.
[0059] In another embodiment, the peptide according to the invention is the derivative of the SEQ ID No. 1 peptide in the N-terminal acetylated and C-terminal amidated form of general formula 2:
[0060] CH3- C(=O)- (Gly-Pro-Pro)4- Gly- Phe -Pro - Gly- Glu- Arg -(Gly-Pro-Pro)4- NH2(2) Or CH3- C(=O)- GPP-GPP-GPP-GPP-GFPGER- GPP-GPP-GPP-GPP- NH2(SEQ ID No. 1).
[0061] 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).
[0062] 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:
[0063] Biotin - GGG-GPP-GPP-GPP-GPP-GFPGER- GPP-GPP-GPP-GPP-NH2
[0064] The peptide according to the invention, its derivatives, and its salts can be obtained by chemical synthesis or by biotechnological synthesis using a microorganism, either naturally occurring or by recombinant technologies, with methods well known to those skilled in the art. In 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 J.M. Stewart and D. Young, *Solid Phase Peptide Synthesis*, 2 ndeditions, 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.
[0065] 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.
[0066] 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%, even more preferably at least 95% (w / w).
[0067] 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.
[0068] The bacterial strain is preferentially Escherichia coii, the yeast strain is preferentially chosen from Pichia and Saccharomyces, in particular Pichia pastoris and Saccharomyces cerevisiae.
[0069] The production of the peptide by a yeast strain classically involves the following steps, which are well known to those skilled in the art:
[0070] - transformation of yeast using a peptide expression system according to the invention coupled to export signal sequences, typically of plasmid type;
[0071] - culture of the transgenic yeast on a culture medium;
[0072] - batch and / or fed-batch fermentation;
[0073] - recovery of fermentation must and removal of yeast biomass, for example by centrifugation and filtration or tangential microfiltration;
[0074] - Concentration and / or purification of the peptide.
[0075] 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.
[0076] 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.
[0077] According to the invention, a "recombinant bacterium" or "recombinant yeast" is understood to mean a bacterium or yeast whose cells have been genetically modified to genetically express the peptide according to the invention.
[0078] According to the invention, a "lysate" of a bacterium or yeast is understood to be a preparation from the cells, either 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 completely 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.
[0079] 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.
[0080] According to an alternative embodiment of the invention, the peptide according to the invention, one of its salts and / 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.
[0081] 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)).
[0082] 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).
[0083] 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 and / or maltodextrin, even more preferably maltodextrin.
[0084] 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.
[0085] 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.
[0086] The peptide according to the invention can be used alone, as a cosmetic or dermatological ingredient and / or in a cosmetic or dermatological composition.
[0087] 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).
[0088] 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.
[0089] 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.
[0090] Preferably, the cosmetic or dermatological ingredient comprises the SEQ ID No. 1 peptide, possibly in the form of one of its salts and / or one of its derivatives, in a content greater than or equal to 0.0001% by weight, preferably between 0.0001% and 10% by weight, more preferably between 0.001% and 2% by weight, even more preferably between 0.01% and 1% by weight, advantageously between 0.05% and 0.5% by weight, and even more preferably about 0.25% by weight, of dry matter in relation to the total weight of the cosmetic ingredient.
[0091] Thus the cosmetic or dermatological ingredient may be used in a cosmetic or dermatological composition, preferably in a content of 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.
[0092] 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 5xl0' 2 % by weight, still advantageously of lxl0' 4 % to 2xl0' 2 %, preferably of lxl0' 3 % to lxl0' 2 % by weight of dry matter relative to the total weight of the composition.
[0093] The cosmetic or dermatological ingredient according to the invention may be in powder or liquid form.
[0094] In a preferred embodiment, the cosmetic or dermatological ingredient is in powder form, obtained in particular after the drying step, preferably by spray drying or freeze-drying, the peptide being mixed with an inert support, conventionally a spray-drying support such as mannitol, maltodextrin, cyclodextrin, preferably mannitol and / or maltodextrin, and again preferably mannitol. Thus, in one embodiment, the cosmetic or dermatological ingredient according to the invention is in powder form further containing maltodextrin and / or mannitol.
[0095] 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, cyclodextrin, preferably a mixture of the peptide according to the invention and maltodextrin and / or mannitol.
[0096] In another particular embodiment, the ingredient according to the invention in powder form consists of a mixture of peptide according to the invention in the fermentation filtrate or lysate of a yeast and the drying support such as mannitol, maltodextrin, cyclodextrin and preferably maltodextrin.
[0097] 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 1% by weight, preferably between 0.05% and 0.5% by weight, and again preferably about 0.1% by weight, of dry matter relative to the total weight of the ingredient. Preferably, the ingredient according to the invention in powder form further comprises a drying agent, preferably mannitol and / or maltodextrin. In a particular embodiment, the cosmetic or dermatological ingredient according to the invention is in powder form and contains 99.75% by weight of mannitol and / or maltodextrin and 0.25% by weight of the peptide according to the invention, of dry matter relative to the total weight of the ingredient, in particular as described in Examples 8a) and 8c).
[0098] 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 l,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 (or l,2-hexanediol).
[0099] The peptide can also be contained in the lysate or production fermentate, particularly in aqueous solution, and can 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 0.01% and 1% by weight, preferably between 0.05% and 0.5% by weight, and more preferably about 0.25% by weight, of dry matter relative to the total weight of the ingredient.
[0100] 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.
[0101] The peptide according to the invention, its salts and derivatives are topically acceptable.
[0102] 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.
[0103] For the purposes of the present 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.
[0104] For the purposes of the present 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.
[0105] The peptide according to the invention, its salts and derivatives are particularly suitable for application on the skin, mucous membranes and hair.
[0106] 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.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.
[0107] For the purposes of the present invention, "phaneres" means nails and "keratin fibers".
[0108] The term “keratin fibers” refers to hair, eyelashes, eyebrows, body hair, particularly beard and / or mustache hair, preferentially hair.
[0109] 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.
[0110] 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.
[0111] The term "maintaining" a parameter means preventing and / or inhibiting the decrease in the value of the parameter measured after treatment with the peptide according to the invention by comparison to the value of the decrease in this parameter obtained without treatment with this peptide, particularly under the effect of aggressive agent(s).
[0112] 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, especially hard water.
[0113] 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 said to be "non-pathological" by a dermatologist, i.e., not presenting with cancer, infection, pathological scar, skin disease or condition such as candidiasis, impetigo, psoriasis, eczema, acne, ichthyosis, gingivitis or dermatitis, in particular atopic dermatitis, or wounds, in particular diabetic lesions or injuries or aphthous ulcers or ulcerations or burns and / or other dermatoses, or aphthous ulcers or inflammation or irritation such as erythema, in particular solar erythema and / or diaper rash, elastosis, in particular solar elastosis,or urticaria or allergies such as contact allergy or alopecia, or pathologies associated with glycation and / or wound healing and / or associated with a decrease in the quantity and / or quality of collagen or the quantity of talin or FabP4 protein. It is therefore not a case of inflamed, atopic, reactive, damaged and / or irritated skin or mucous membranes.
[0114] 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.
[0115] The peptide according to the invention, optionally in the form of its salts and / or derivatives, 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:
[0116] - to prevent and / or reduce the signs of aging of healthy skin and / or healthy mucous membranes, and / or
[0117] - 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
[0118] - 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
[0119] - 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
[0120] - 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, especially to improve and / or maintain the growth of hair, especially keratin fibers, and / or the quality of the keratin material produced at the level of the hair, especially keratin fibers, and / or to prevent and / or reduce the loss of hair, especially keratin fibers, preferentially hair.
[0121] The applicant has indeed discovered that the peptide according to the invention allows:
[0122] - to increase the amount of collagen, in particular the synthesis of collagen, especially type I (example 3), as well as the quantity and / or quality of collagen fibers, notably by decreasing the amount of damaged collagen thanks to its strong affinity for it (example 2) in the skin and / or mucous membranes,
[0123] - to increase the proliferation and / or migration of keratinocytes in the skin and / or mucous membranes, particularly when the epidermis is weakened (example 4),
[0124] - to increase the thickness of the skin and / or mucous membranes, in particular the average relative thickness of the epidermis (example 4),
[0125] - to reduce glycation in the skin and / or mucous membranes (example 5),
[0126] - to maintain the quality of the hypodermis, in particular by increasing the quantity, and especially the expression of the FabP4 protein (example 6),
[0127] - to increase the amount of talin, in particular its protein expression (example 7), and can therefore be used for these properties in the skin and / or mucous membranes.
[0128] The peptide according to the invention allows for a very comprehensive "improvement of collagen fibers," that is, it increases the quality and / or quantity of collagen fibers and / or prevents their degradation. Indeed, it increases the amount of collagen in the skin, particularly by stimulating the synthesis of type I collagen, as demonstrated in Example 3, in the dermis. Furthermore, the peptide according to the invention is capable of binding significantly to damaged collagen, as demonstrated in Example 2, which suggests its ability to reduce the amount of damaged collagen present in the skin. Thus, the peptide allows both the repair of damaged collagen fibers and the stimulation of the production of new collagen fibers.
[0129] 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, as well as rigidity. This property is demonstrated, in particular, by the inhibition of the formation of advanced glycation end products (AGEs) in Example 5.
[0130] The peptide according to the invention increases the quantity and, in particular, the synthesis of the FabP4 protein. This protein plays a crucial role in lipid metabolism under stress, and the restoration of its expression by the peptide in cases of TNFα inflammation indicates a return to normal lipid metabolism. The health of adipose tissue influences that of the dermis (Chuin Ying Ung et al., The International Journal of Biochemistry & Cell Biology, Volume 139, 2021; Nancy Wareing et al., bioRxiv [Preprint]. 2024). As demonstrated in Example 6, the peptide according to the invention stimulates the expression, particularly gene expression, of the FabP4 protein and thus maintains the quality of the hypodermis, protecting it from the effects of aging and / or aggressive agents. Maintaining the structure and function of the hypodermis contributes to the overall health and proper functioning of the skin, mucous membranes, and skin appendages.
[0131] Furthermore, the applicant has shown that the peptide according to the invention increases the amount of talin in the skin and / or mucous membranes, in particular its protein expression (Example 7). 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 integrin activation 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.
[0132] Furthermore, the peptide according to the invention has the advantage of acting very comprehensively on the different compartments of the skin and / or mucous membranes:
[0133] - on the epidermis by stimulating the proliferation and migration of keratinocytes,
[0134] - on the dermis through the improvement of collagen, in particular its quality and / or quantity, anti-glycation activity, and the stimulation of talin expression,
[0135] - on the hypodermis via the maintenance of the synthesis of the FabP4 protein.
[0136] 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 in a comprehensive manner, 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.
[0137] 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:
[0138] - a decrease in the amount of collagen, particularly collagen synthesis, especially type I, and / or a decrease in the quality and / or quantity of collagen fibers and / or an increase in damaged collagen in healthy skin and / or healthy mucous membranes and / or
[0139] - a decrease in the proliferation and / or migration of keratinocytes in healthy skin and / or healthy mucous membranes, and / or
[0140] - a decrease in the thickness of healthy skin and / or healthy mucous membranes, in particular the thickness of the dermis and / or epidermis, more preferentially the epidermis, and / or
[0141] - an increase in glycation in healthy skin and / or healthy mucous membranes, and / or
[0142] - a decrease in the quality of the hypodermis and / or a decrease in the quantity, particularly of FabP4 protein expression, and / or
[0143] - a decrease in quantity, particularly in the expression of talin.
[0144] The peptide according to the invention, possibly in the form of a cosmetic ingredient and / or cosmetic composition, is useful for preventing and / or treating signs of aging of healthy skin and / or healthy mucous membranes.
[0145] The term "preventing and / or reducing the signs of aging" refers to delaying and / or preventing the appearance and / or reducing the quantity and / or extent of signs of aging in healthy skin and / or mucous membranes, whether natural or induced by aggressive agents (particularly photo-induced). "Signs of aging" encompass all unsightly manifestations in healthy skin due to skin aging and include the decline in the biomechanical properties of healthy skin and / or mucous membranes, particularly firmness and / or tone, and / or the structure of healthy skin and / or mucous membranes due to natural aging or aging induced by aggressive agents (particularly photo-induced), especially the reduction in the thickness of healthy skin.
[0146] Preferably, the signs of aging of healthy skin are the appearance of a marked microrelief of the healthy skin, the formation and / or presence of fine lines, fine wrinkles and / or wrinkles in particular the frown line and crow's feet, especially under the eyes and around the lips, sagging of the healthy skin, roughness of the healthy skin and / or withering of the healthy skin and / or lack of firmness and / or tone of the healthy skin.
[0147] The peptide according to the invention has demonstrated its properties to prevent and / or reduce the signs of aging by binding to damaged collagen and reducing its quantity (example 2), stimulating the synthesis of type I collagen (example 3), reducing glycation (example 5), increasing gene expression of the FabP4 protein (example 6) and protein expression of talin (example 7) and increasing the thickness of the epidermis (example 4).
[0148] These signs of aging can be measured by clinical tests, particularly on wrinkles, especially crow's feet and forehead wrinkles, and on skin tone, for example with the cosmetic composition described in example 9.
[0149] The peptide according to the invention, possibly in the form of its salts and / or derivatives, can therefore be used to prevent and / or stop natural aging and / or aging induced by aggressive agents (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.
[0150] 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 of healthy skin and / or healthy mucous membranes.
[0151] The peptide according to the invention, possibly in the form of a cosmetic ingredient and / or cosmetic composition, is also useful for improving the architecture of healthy skin and / or healthy mucous membranes, in particular for regenerating healthy skin and / or healthy mucous membranes, and / or increasing the thickness of healthy skin and / or healthy mucous membranes, and / or preventing the thinning of healthy skin and / or healthy mucous membranes, in particular preventing thin healthy skin and / or thin healthy mucous membranes, and / or strengthening the barrier of healthy skin and / or healthy mucous membranes.
[0152] The peptide according to the invention improves the architecture of healthy skin and mucous membranes through its properties on their different compartments: - at the level of the epidermis, the peptide increases the proliferation and migration of keratinocytes and the average relative thickness of the epidermis (example 5)
[0153] - at the dermal level, the peptide binds to damaged collagen and reduces it (example 2) and increases the amount of collagen, particularly type I (example 3), has an anti-glycation effect (example 5) and increases the expression, particularly the protein expression of talin (example 7)
[0154] - at the level of the hypodermis, the peptide increases the expression, particularly gene expression, of the FabP4 protein (example 6) without overstimulating it
[0155] 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.
[0156] The applicant has indeed shown that the peptide according to the invention improves the amount of collagen, specifically by increasing the synthesis of type I collagen in the skin and decreasing damaged collagen (Examples 2 and 3), increasing the expression of talin, particularly the protein form (Example 7), and increasing the expression, particularly the gene expression, of the FabP4 protein (Example 6), all of which contribute to dermal thickness and function. The thicknesses of the epidermis and / or dermis can, for example, be measured in vivo using ultrasound, and the average relative thickness of the epidermis can also be measured in vitro, as described in Example 4.
[0157] The peptide according to the invention, by its properties on the migration and proliferation of keratinocytes, particularly improves the skin and / or mucosal barrier (example 4).
[0158] The peptide according to the invention is particularly useful for regenerating healthy skin and / or healthy mucous membranes, in pre-treatment and / or post-treatment aesthetics, in particular laser treatment.
[0159] The peptide according to the invention, possibly in the form of a cosmetic ingredient and / or cosmetic composition, 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.
[0160] 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 blemish marks, and in particular making them less visible.The properties of the peptide for improving the dermis (examples 2 and 3) show that the peptide according to the invention is particularly useful for the prevention and / or treatment of unsightly marks on healthy skin and / or healthy mucous membranes in which the dermis has areas of depression or sagging.
[0161] 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 4), anti-glycation (example 5), regeneration via the stimulation of the expression of talin (example 7) and by increasing the thickness of the epidermis (example 4).
[0162] The peptide according to the invention, possibly in the form of a cosmetic ingredient and / or cosmetic composition, is also useful for improving the biomechanical properties of healthy skin and / or healthy mucous membranes.
[0163] For the purposes of the present invention, "biomechanical properties of healthy skin and / or healthy mucous membranes" means suppleness, firmness, elasticity, tone and / or density, and more preferably firmness of healthy skin and / or healthy mucous membranes.
[0164] 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 and 3.
[0165] 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®.
[0166] 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 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.
[0167] The peptide according to the invention, possibly 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 healthy mucous membranes, in particular by maintaining, improving and / or increasing collagen, preferably collagen fibers, preferably type I collagen fibers (example 3).
[0168] The applicant has shown that the peptide according to the invention is useful as an anti-glycation agent (example 5) which contributes to maintaining the biomechanical properties of healthy skin and / or healthy mucous membranes.
[0169] The stimulation of FabP4 protein expression by the peptide according to the invention as demonstrated in Example 6 also contributes to good dermal quality and therefore to the biomechanical properties of healthy skin and / or healthy mucous membranes.
[0170] The peptide according to the invention, possibly in the form of a cosmetic ingredient and / or cosmetic composition, is also useful for soothing healthy skin and / or healthy mucous membranes.
[0171] The term "soothing healthy skin and / or mucous membranes" refers to the ability to prevent and / or limit signs of discomfort in healthy skin and / or mucous membranes, particularly when they have been exposed to harsh agents, and / or to reduce these signs of discomfort. Signs of discomfort include dryness of healthy skin and / or mucous membranes, uneven skin tone of healthy skin and / or mucous membranes (particularly through the appearance of redness), sensations of tightness, burning, heat, tingling, prickling, or tension, a rough texture of healthy skin and / or mucous membranes, and / or a loss of softness to the touch of healthy skin and / or mucous membranes.
[0172] The applicant has indeed shown that the peptide according to the invention reduces glycation (example 6) which contributes to creating an inflammatory environment and is therefore useful for soothing healthy skin and / or healthy mucous membranes.
[0173] The peptide according to the invention has the advantage of respecting the skin and mucosal microbiota. Indeed, the applicant evaluated the effects of using the peptide at different dosages (5pM, 1pM, and 0.1 pM) on different strains of bacteria, in particular staphylococcus such as S. aureus, S. epidermidis, S. hominis, S. acciens, S. acnes, but also lactobacillus such as L. crispatus, Micrococcus such as M. iuteus, Acinobacter such as A. iwoffiii, and demonstrated that the peptide according to the invention does not decrease the viability of the bacteria and therefore allows the balance of the skin microbiome to be maintained.
[0174] The peptide according to the invention, possibly in the form of a cosmetic ingredient and / or cosmetic composition, is also useful for improving and / or maintaining healthy hair and nails.
[0175] 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 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 healthy scalp skin and the reduction of pro-inflammatory stress in healthy 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.
[0176] The SEQ ID No. 1 peptide, possibly in the form of one of its salts and / or one of its derivatives, 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.
[0177] The present invention therefore also relates to cosmetic and / or dermatological compositions which contain the peptide according to the invention.
[0178] 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 acceptable excipient and / or a suitable cosmetic or dermatological 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.
[0179] 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 their mixtures. The cosmetic or dermatological ingredient and the cosmetic or dermatological composition may be presented in all the galenic forms classically used for topical application, such as liquid or solid forms, or even as a pressurized liquid. They may, in particular, be formulated as a solution, aqueous or oily, a cream or aqueous gel or an oily gel, especially in a jar or tube, including a shower gel, shampoo, lotion, emulsion, hydrogel, microemulsion or nanoemulsion, including oil-in-water, water-in-oil, multiple, or silicone-based emulsion, a serum, a lotion, especially in a glass or plastic bottle or dosing bottle or aerosol, an ampoule, liquid soap, paste, dermatological bar, ointment, foam, aerosol, mask, patch, an anhydrous product, preferably liquid, paste, or solid.For example, in stick form or as powders, particularly makeup. Specifically, the composition is presented as 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 as a cream, lotion for the skin and / or hair, or shampoo, conditioner, rinse-off or leave-on.
[0180] The peptide according to the present invention has the advantage of not irritating and / or stripping the skin, mucous membranes and / or hair, allowing the maintenance of the microbiota and is particularly suitable for the care and / or treatment of sensitive and / or irritated skin and / or mucous membranes.
[0181] 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,
[0182] 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:
[0183] - ingredients that help prevent and / or combat the signs of aging of the skin and / or mucous membranes and / or hair;
[0184] - depigmenting agents and / or agents active on pigment spots;
[0185] - ingredients that improve skin firmness and / or elasticity;
[0186] - metalloproteinase (MMP) inhibitor ingredients;
[0187] - ingredients for treating sensitive skin and / or mucous membranes;
[0188] - active ingredients on the scalp, anti-dandruff and / or active ingredients said to be anti-hair loss and / or stimulating hair growth;
[0189] - the active ingredients on the microbial flora;
[0190] - active ingredients on the barrier function; photoprotective ingredients, UVA and / or UVB filters and / or protection against pollution.
[0191] 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 corn 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 anum 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.;
[0192] For depigmenting agents, we can mention niacinamide or vitamin B3 and derivatives.
[0193] Among the active ingredients for improving skin firmness are the synthetic tetrapeptide marketed as Dermican™, an extract of Hibiscus Abe / moscus te™ 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 EPI 119344 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 Argan pulp extract marketed as Argassenal™, and an extract under the name Sqisandryl™ by the applicant, the peptide SEQ ID N°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 the peptides palmitoyl tripeptide-1 and palmitoyl tetrapeptide-7 marketed under the name Matrixyl™ 3000 by Sederma.
[0194] Among the ingredients that inhibit metalloproteinases, we can mention those that inhibit MMPs 1, 2, 3, 9 in particular, such as retinoids and derivatives, oligopeptides and lipopeptides, lipoamino acids, and malt extract marketed by BASF Beauty Care Solutions France under the trade name Collalift®.
[0195] Among the active ingredients for sensitive skin, we will mention the deoiled ungerminated seed protein extract of Moringa oleifera marketed under the trade name Purisoft®, a plant extract of Cestrum latifolium marketed under the name Symbiocell ™, a butter extracted from the fruit of the Irvingia gabonensis tree marketed under the name Irwinol™, an extract of 'Eperua falcata' root marketed under the name Eperuline™, a peptide SEQ ID N°10: N-acetyl-L-Tyrosyl-L-Prolyl-L-Phenylalaninamide (INCI: Acetyl Tetrapeptide 15) marketed under the name Skinasensyl™, an extract of Inonotus obliquas marketed under the name Inolixir™ by the applicant.
[0196] 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 Ram bu vital™ and described in patent application FR3076734; and the extract of Siiybum marianum to improve keratin fibers described in patent application FR3142088A1 and marketed under the name Kerasylium™.
[0197] Among the anti-hair loss ingredients, the following may be cited: 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 Elestab™ 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, in particular combined with salicylic acid.
[0198] 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.
[0199] 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-glucooligosaccharide 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;
[0200] 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.
[0201] Among the protective agents against pollution, we can mention an extract of leaves of Argania 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.
[0202] 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.
[0203] It is particularly suitable for masking the first unsightly signs of aging in healthy skin, especially the first expression lines and / or for healthy skin considered mature, i.e. men or women aged at least 50, especially menopausal women.
[0204] The peptide according to the invention, possibly in the form of its salts and / or derivatives, 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.
[0205] 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.
[0206] 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.
[0207] 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) and the forehead, skin folds, the buttocks in infants, etc. These areas can therefore be sensitive to skin and / or mucous membranes.
[0208] Similarly, "sensitized skin and / or mucous membranes" are healthy skin and / or mucous membranes made sensitive momentarily and therefore not pathological as such.
[0209] "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.
[0210] "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.
[0211] 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.
[0212] The peptide according to the invention is also suitable for the care of normal, oily, dry, blemished skin and in particular acne-prone or acne-prone skin.
[0213] 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 membranes 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 membranes and / or healthy hair, in particular hair.
[0214] 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 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 on which / in which it is desired:
[0215] - to increase the amount of collagen, in particular collagen synthesis, especially type I collagen, and / or the quantity and / or quality of collagen fibers and / or to decrease the amount of damaged collagen, and / or
[0216] - increase the proliferation and / or migration of keratinocytes, and / or
[0217] - to increase the thickness, particularly of the dermis and / or epidermis, and / or
[0218] - reduce wrinkles, and / or
[0219] - reduce glycation, and / or
[0220] - maintain the quality of the hypodermis and / or increase the amount of FabP4 protein, and / or
[0221] - increase the amount of talin.
[0222] 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:
[0223] - identification on the individual of the area of healthy skin and / or healthy mucous membranes and / or healthy hair and nails whose condition and / or appearance and / or comfort should be or is to be improved, in particular an area of healthy skin and / or healthy mucous membranes and / or healthy hair and nails on / in which it is desired to increase the amount of collagen, including synthesis, particularly of type I collagen, 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, particularly of the dermis and / or epidermis, and / or decrease wrinkles, and / or decrease glycation, and / or maintain the quality of the hypodermis and / or increase the quantity, including expression, of the FabP4 protein and / or increase the quantity, including expression, of talin in healthy skin and / or healthy mucous membranes and
[0224] - 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 and / or the cosmetic ingredient and / or 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 between lxl0' 6 % and 0.1% by weight, preferably of lxlO' 5 % at 5X10' 2 % by weight, still advantageously of lxl0' 4 % to 2xl0' 2 % by weight, preferably of lxl0' 3 % to lxl0' 2 % by weight of dry matter relative to the total weight of the composition.
[0225] 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.
[0226] 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 in a dermatological composition according to the invention, for its use by topical application:
[0227] - 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, in particular for the treatment and / or prevention of scars, especially pathological scars, and / or
[0228] - to prevent and / or treat skin inflammations, particularly of the scalp, and / or mucosal inflammations, such as dermatitis and erythema, especially sunburn, diaper rash, and / or gingivitis, and / or
[0229] - to prevent and / or treat alopecia, and / or - to prevent and / or treat elastosis, particularly solar elastosis, and / or
[0230] - to prevent and / or treat acne.
[0231] Indeed, the peptide reduces glycation in the skin and mucous membranes (example 5), which helps to decrease 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, particularly 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.
[0232] Furthermore, the peptide increases the proliferation and migration of keratinocytes as well as the average relative thickness of the neo-epidermis of injured skin (example 4) and activates the regeneration of irradiated skin by stimulating the expression of talin (example 7), which demonstrates its healing properties.
[0233] 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.
[0234] 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.
[0235] The term “atopic skin and / or mucous membrane” refers to skin and / or mucous membrane affected by the pathology of atopic dermatitis.
[0236] 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.
[0237] 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 lxl0' 5 % at 5X10' 2 % by weight, still advantageously of lxl0' 4 % to 2xl0' 2 % by weight, preferably of lxl0' 3 % to lxl0' 2% by weight of dry matter relative to the total weight of the composition.
[0238] 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.
[0239] 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.
[0240] Thus, each example has a general scope.
[0241] 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.
[0242] EXAMPLES
[0243] Example 1: Synthesis of the peptide according to the invention, i) Synthesis of the SEP IP peptide No. 1:
[0244] The peptide according to the invention was obtained by solid-phase chemical synthesis at a purity of 97.7% 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 1336.8 [M+2H]2+.
[0245] The peptide is that of SEQ ID No. 1: GPP-GPP-GPP-GPP-GFPGER- GPP-GPP-GPP-GPP.
[0246] Such a peptide can also be written according to the following general formula 1: (Gly-Pro-Pro)4 - Gly- Phe -Pro - Gly- Glu- Arg -(Gly-Pro-Pro)4 lb) Synthesis of the derivative of the SEO IP peptide No. 1 with an acetyl function at the N-terminus and an amide function at the C-terminus of general formula 2
[0247] The peptide according to the invention was obtained by solid-phase chemical synthesis at a purity of 98.4% 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 1356.2 [M+2H]2+.
[0248] The peptide is the derivative with general formula 2:
[0249] CH3-C(=O)- GPP-GPP-GPP-GPP-GFPGER- GPP-GPP-GPP-GPP- NH2
[0250] Such a peptide can also be written as: CH3-C(=O)- (Gly-Pro-Pro)4 - Gly- Phe -Pro - Gly- Glu- Arg - (Gly-Pro-Pro)4- NH2 Example 2: Evaluation of the ability of the peptide according to the invention to bind to denatured collagen (gelatin)
[0251] 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.
[0252] 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 with 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).
[0253] Protocol:
[0254] 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) 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 products 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 per condition was prepared, 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.
[0255] Results :
[0256] Table 2 - Gelatin binding test (denatured collagen)
[0257] Conclusion: The peptide with sequence (GPP)4-GFPGER-(GPP)4 (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 (SEQ ID No. 5) (p<0.001) and (GPP)3-GFOGER-(GPP)3 (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. Furthermore, the peptide according to the invention has the property of binding significantly more than the peptide of similar sequence SEQ ID No. 11: GPP-GPP-GPP-GPP-GFOGER- GPP-GPP-GPP-GPP-NH2 in which O designates (2S,4R)-4-hydroxyproline (4-Hyp) and which was also tested in the form of the peptide of SEQ ID No. 15: GGG- GPP-GPP-GPP-GPP-GFOGER- GPP-GPP-GPP-GPP-NH2 and whose result was lower (value: 0.059) than that of the peptide according to the invention.This test thus helps to demonstrate 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, preventing and / or treating unsightly marks on healthy skin and / or healthy mucous membranes, improving and / or maintaining the biomechanical properties of healthy skin and / or healthy mucous membranes and / or improving and / or maintaining healthy hair, by improving their anchoring in a good quality dermis.
[0258] Example 3: Evaluation of the activity of the peptide according to the invention on the stimulation of collagen I synthesis on reconstructed dermis
[0259] Objective: The objective of the study was to evaluate the efficacy of the peptide according to the invention on the synthesis of collagen I in a reconstructed dermis model.
[0260] Protocol:
[0261] 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):
[0262] - An untreated control (NT) group consisted of reconstructed dermis cultures maintained in the aforementioned medium without any further treatment.
[0263] - 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 2%, which corresponds to a peptide concentration of 0.4 pM. Treatments with the peptide were performed every 2 days, from day 7 to day 28.
[0264] Collagen I 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 the commercially available anti-collagen I antibody (Invitrogen) for 2 hours at room temperature. A secondary antibody (Thermofisher) was then applied. 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).
[0265] Collagen I 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).
[0266] 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).
[0267] Results :
[0268] Table 3 - Synthesis of collagen I on reconstructed dermis
[0269] Conclusion: The peptide according to the invention significantly stimulated the synthesis of type I collagen. This demonstrates the property of the peptide according to the invention to stimulate the synthesis of type I 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.
[0270] Example 4: Evaluation of the activity of the peptide according to the invention on the proliferation and migration of keratinocytes in the neo-epidermis
[0271] Principle: The objective of this study is to evaluate the activity of a product on the proliferation and migration of keratinocytes in a neo-epidermis, and therefore on wound healing, using human skin excipients maintained in survival. The first step involves reproducing topical application of the products after creating lesions on the excipients. The second, histological phase allows for the evaluation of the overall morphology of the neo-epidermis that forms to close the wound, as well as the measurement of its length.
[0272] Protocol:
[0273] 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.
[0274] 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.
[0275] 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.
[0276] 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.
[0277] 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).
[0278] The parameters evaluated are as follows:
[0279] A. Analysis of the general morphology of the neo-epidermis formed following the lesion according to the following 5 criteria
[0280] - The number of cell layers (correlated with good proliferation) is evaluated based on the average number of cell layers of the synthesized neo-epidermis.
[0281] - The length of the synthesized neo-epidermis (correlated with good migration) is noted on a scale of 0 to 5.
[0282] - For each criterion, the higher the score, the more the analyzed parameter is increased or improved.
[0283] A score higher than the score of the untreated control (NT) at the same observation time shows a healing activity of the tested peptide.
[0284] B. The length of the newly formed neo-epidermis (expressed in pm) was measured by image analysis. Statistical analysis of the data was performed using Student's t-test, n=12 (3 expiants / condition; 4 images / explant).
[0285] C. The average relative thickness of the neo-epidermis is the ratio between the area A of the neo-epidermis formed in pm 2 and its length L at J8 in pm: A (neo-epidermal area pm 2 ) / L(neo-epidermis length pm).
[0286] Results
[0287] - The morphological analysis, the measurement of the length of the formed neo-epidermis, and the relative average thickness of the neo-epidermis are summarized in the tables below. Table 4.1 - Qualitative morphological analysis of neo-epidermis formed on the injured area condition)
[0288] Table 4.3: Average relative thickness of the newly formed neo-epidermis (newly formed epidermis) Conclusion: This test demonstrates that the peptide according to the invention 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.
[0289] Furthermore, the peptide according to the invention exhibits wound healing activity, based on proliferation and migration processes.
[0290] Example 5: Evaluation of the anti-calcification activity of the peptide according to the invention
[0291] Objective: 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.
[0292] 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 or presence of the peptide obtained according to example (a) at different concentrations, 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 peptide being tested. The peptide obtained according to example (a) was solubilized to 100 pM in water and then diluted in the excipient incubation buffer (PBS buffer) to the desired concentration. Three expiators are tested per condition.
[0293] 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)).
[0294] Statistical analysis of the data was performed using a one-way ANOVA (analysis of variance) followed by a Holm-Sidak test. The significance level was set at 5% (p<0.05). Results:
[0295] Table 5 - Inhibition of glycation on devitalized skin expiants
[0296] Conclusion: The peptide according to the invention significantly inhibits the glycation reaction. 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 mucous membranes, for improving the architecture of healthy skin and / or mucous membranes, in particular for regenerating them, for preventing and / or treating unsightly marks on healthy skin and / or mucous membranes, for improving and / or maintaining the biomechanical properties of healthy skin and / or mucous membranes, for soothing healthy skin and / or mucous membranes, and / or for improving and / or maintaining healthy hair, nails, and skin.
[0297] Example 6: Evaluation of the activity of the peptide according to the invention on the expression of the Fatty Acid Binding Protein - 4 (FabP4) protein
[0298] Objective: The objective of the study was to evaluate the effect of the peptide according to the invention on an ex vivo model of vascularized human adipose tissue stressed with TNFα and therefore the effect of the peptide on the FabP4 protein whose level of expression testifies to the good metabolism of the adipocyte by the quantitative reverse transcription PCR (polymerase chain reaction) technique known as RT-qPCR.
[0299] Protocol:
[0300] A 0.8 mL ali solution of the 100 pM aqueous peptide stock solution (example a) was diluted in 99.2 mL of Dulbecco's Phosphate-Buffered Saline (DPBS). This peptide solution was then diluted and tested at 0.8 pM in a basal medium (EGM Endothelial Cell Growth Medium) supplemented with 2% (v / v) fetal bovine serum (FBS), 22.5 pg / mL heparin, and 1 pg / mL ascorbic acid, with or without the addition of TNFα (unstressed control), in an amount sufficient to induce inflammatory stress, resulting in a significant decrease in FabP4 protein. TNFα mimics inflammation-induced aging (Yong Zhuang and John Lyga, Inflammation & Allergy - Drug Targets, 2014, 13, 153-161; Amir Ajoolabady et al., Trends in Endocrinology & Metabolism, June 2023, Vol. 34, No. 6).
[0301] 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 EGM Plus medium (Lonza) for 2 weeks prior to processing.
[0302] At JO, 50 mg of adipocyte preparation were encapsulated in 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.
[0303] On day 10, cell viability was checked using a commercially available XTT test kit (Roche), following the manufacturer's instructions.
[0304] -RNA extraction and RT-qPCR analysis:
[0305] On day 10, total RNA was extracted from 3 or 4 replicas 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). The expression of the following human genes was analyzed by real-time PCR using the StepOne Plus system from Applied Biosystems in all replicas. The primer sequence used for FabP4 protein detection was: SEQ ID 7: hFABP4 Fw 5'-TGGGCCAGGAATTTGACGAA-3', SEQ ID 8: hFABP4Rv 5'-GCGAACTTCAGTCCAGGTCA-3'
[0306] 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. The significance level was set at 5% (p < 0.05). The number of doses per condition is shown in Table 6.
[0307] Results
[0308] 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).
[0309] Table 6 - Average expression of the FabP4 protein
[0310] The addition of TNFα resulted in a significant 268% decrease in basal FabP4 protein expression. The peptide according to the invention restored FabP4 expression to a similar pre-stress level, increasing its expression by 224% versus the TNFα-stressed control condition.
[0311] This test therefore demonstrates that the peptide has the ability to maintain a significant level of FabP4, despite inflammatory skin stress and thus contributes to maintaining a quality hypodermis, thereby contributing to the maintenance of a quality dermis, promoting better production of extracellular matrix molecules, particularly collagen, and anchoring of the hair follicle and contributing to limiting hair loss.
[0312] 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, for improving the architecture of healthy skin and / or healthy mucous membranes, in particular increasing their thickness, and / or for improving and / or maintaining the biomechanical properties of healthy skin and / or healthy mucous membranes, and / or for improving and / or maintaining healthy hair and nails.
[0313] Example 7: Evaluation of the effect of the peptide according to the invention on talin expression
[0314] Protocol:
[0315] 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.
[0316] 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 (Cell Lytic™, 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.
[0317] 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.
[0318] The chemiluminescent signal obtained was detected and quantified using Compass software version 5.0.1 (ProteinSimple), on six to eight replicates (n=6-8).
[0319] 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%.
[0320] Statistical analyses were performed using SigmaPlot software (version 12.5) (Systat Software Inc., San Jose, California, USA).
[0321] 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).
[0322] Result :
[0323] Table 7: Stimulation of talin expression by GFOGER (SEQ ID No. 3) and by the peptide according to the invention on fibroblasts after UVA stress.
[0324] 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 197% (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.
[0325] 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, for 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.
[0326] Example 8: cosmetic ingredient
[0327] 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):
[0328] • Peptide (la) 0.25%
[0329] • Mannitol qsp 100% b.
[0330] • Peptide (la) 0.1%
[0331] • Maltodextrin qsp 100% c.
[0332] • Peptide (la) 0.25%
[0333] • Maltodextrin qsp 100% d.
[0334] • Peptide (la) 0.01%
[0335] • Maltodextrin qsp 100% e.
[0336] Peptide (la) 0.05%
[0337] 1,2-Hexandiol 1%
[0338] Glycerin 50%
[0339] Water qsp 100%
[0340] Example 9: Cosmetic composition
[0341] The cosmetic ingredient in Example 8 is formulated as the following gel-cream type cosmetic composition (Table 9):
[0342] The formulation was carried out in a conventional cold process.
Claims
1. DEMANDS 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 the preceding claim in which 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 0.001% and 2% by weight, even more preferably between 0.01% and 1% by weight, advantageously between 0.05% and 0.5% by weight, of dry matter in relation to the total weight of the cosmetic ingredient.
3. 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.
4. Cosmetic or dermatological composition comprising the peptide as defined in claim 1 and further comprising a suitable cosmetic and / or dermatological vehicle.
5. 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 5xl0' 2 % by weight, still advantageously from 1x10' 4% to 2x0' 2 % by weight, preferably of lxl0' 3 % to lxl0' 2 % by weight of dry matter relative to the total weight of the composition.
6. 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 3 and / or of a cosmetic composition comprising it according to any one of claims 4 or 5, 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.
7. Non-therapeutic cosmetic use according to claim 6 for: - to prevent and / or treat 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, particularly a healthy scalp, and / or healthy mucous membranes, particularly sensitive skin, including 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, in particular keratin fibers, and / or to prevent and / or reduce the loss of hair and skin appendages, in particular hair.
8. Non-therapeutic cosmetic use according to any one of claims 6 or 7 for: - increase the amount of collagen, preferentially the synthesis of type I collagen, 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 - 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 / or epidermis, and / or - to reduce glycation in healthy skin and / or healthy mucous membranes, and / or - maintain the quality of the hypodermis and / or increase the amount of FabP4 protein in healthy skin and / or healthy mucous membranes, and / or - to increase the amount of talin in healthy skin and / or healthy mucous membranes.
9. Non-therapeutic cosmetic use according to any one of claims 6 to 8, characterized in that it is intended for sensitive skin.
10. Non-therapeutic cosmetic use according to any one of claims 6 to 9, characterized in that it is a topical use.
11. Non-therapeutic cosmetic use according to any one of claims 6 to 10 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.
12. 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 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 3 and / or a cosmetic composition comprising it according to any one of claims 4 or 5, 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.
13. Non-therapeutic cosmetic treatment method according to claim 12, characterized in that it comprises the preliminary step of identifying the area of healthy skin and / or healthy mucous membrane and / or healthy hair 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 on which / in which it is desired to increase the amount of collagen, in particular the synthesis of type I collagen, and / or the amount 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 / or epidermis, and / or decrease wrinkles and / or decrease glycation, and / or maintain the quality of the hypodermis and / or increase the amount of FabP4 protein, and / or increase the amount of talin.
14. 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 alopecia, and / or - to prevent and / or treat elastosis, particularly solar elastosis, and / or - to prevent and / or treat acne.
15. 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 3 and / or in the form of a dermatological composition according to any one of claims 4 or 5.
16. Peptide according to any one of claims 14 or 15, 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.
Citation Information
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