Ecobiological composition comprising a combination of active principles capable of protecting components of the basement membrane of human epithelia

Abstract

The invention relates to a topical composition, advantageously an ecobiological topical composition, comprising: (i) at least one compound of general formula (I), (ii) at least one monosaccharide, which is a deoxy sugar; and to the use thereof for combating skin aging and / or for regenerating the skin.

Description

[0001] ECOBIOLOGICAL COMPOSITION COMPRISING A COMBINATION OF ACTIVE INGREDIENTS CAPABLE OF PROTECTING COMPONENTS OF THE BASAL MEMBRANE OF HUMAN EPITHELIA - SCOPE OF THE INVENTION

[0002] The present invention relates to the field of cosmetics, in particular to topical compositions, advantageously ecobiological, and their uses to reduce, or even stop, the proteolysis of structural proteins of the basement membrane of human epithelia, to fight against skin aging or to ensure or promote skin regeneration.

[0003] STATE OF THE ART

[0004] The skin consists of three superimposed layers: the epidermis, the dermis, and the hypodermis. The epidermis is a stratified epithelium composed primarily of keratinocytes, which make up 90 to 95% of the epidermal cells. The dermis is mainly composed of fibroblasts dispersed in the extracellular matrix (ECM), which is primarily made up of proteins and proteoglycans. The hypodermis, also called subcutaneous tissue, is the deepest layer of human skin. It is mainly composed of cells called adipocytes, which store fat and act as an energy reserve.

[0005] The epidermis and dermis are separated by a thin layer of extracellular matrix (ECM) with a distinct and unique composition called the basement membrane, basal lamina, or dermo-epidermal junction (DEJ). The DEJ is composed primarily of glycoproteins, notably laminins; proteoglycans, particularly perlecan; and proteins such as several types of collagen. Its main structural function is to provide mechanical support for epithelial cells, allowing them to anchor firmly and maintain the integrity of the epithelium, as well as ensuring cohesion between the epidermis and dermis. The DEJ also plays a crucial role in regulating cell proliferation, differentiation, and migration. In addition, the basement membrane acts as a selective barrier, controlling the passage of certain molecules between the epithelial and connective tissues.

[0006] Among the structural components of the DEJ, a particular role is played by a 180 kDa transmembrane protein, type XVII collagen (also known as COL17, Coll7Al, BP 180, or BPAG2 for bullous pemphigoid antigen 2). COL17 is a component of hemidesmosomes that anchors keratinocytes to the DEJ (Nishizawa et al., 1993). A reduction in physiological COL17 levels has negative effects on the structure of the epidermis, particularly a loss of hemidesmosomes and consequently a thinning of this skin layer, which compromises the adhesion between the epidermis and the dermis (Mondon et al., 2015; Langton et al., 2016). Furthermore, it has been shown that in vivo overexpression of the human COL17 protein in aged mice prevented age-related epidermal thinning (Liu et al., 2019). COL17 also ensures the self-renewal and differentiation of hair follicle stem cells.

[0007] The COL17 protein is also involved in cutaneous pigment homeostasis, as well as in the maintenance of hair follicle stem cells and melanocyte stem cells located within the hair follicle (Shirai et al., 2019). The importance of the COL17 protein in maintaining cutaneous homeostasis has also been demonstrated through gene inactivation (i.e., knockout) of the COL17A1 gene in a mouse model, which then exhibits pigmentation abnormalities similar to those observed during aging in humans. Furthermore, in vivo, COL17 knockout mice show a decrease in hair follicle stem cells (HFSCs) (Tanimura et al., 2011). In addition, repeated exposure to UVB also induces hypopigmentation similar to that observed in COL17 deficiency in normal mice. These pigmentary abnormalities do not appear when overexpression of human COL 17 is performed in a mouse model.Furthermore, it has also been shown that the healing of deep wounds in aged mice is comparable to that of young mice in which COL17A1 gene expression is inhibited. These results demonstrate that hemidesmosomes' instability, due in particular to the loss of COL17, leads to delayed wound healing during aging (Liu et al., 2019).

[0008] In humans, several studies have shown that cutaneous COL17 levels decrease with age (Langton et al., 2016; Mondon et al., 2015; Watanabe et al., 2017). Generally, however, this decrease does not appear to be linked to a reduction in gene expression (Watanabe et al., 2017; Langton et al., 2016). The progressive reduction in COL17 levels in the skin therefore seems to be due to a loss of the protein, or at least of the functional protein, with age, particularly through its cleavage by proteases.

[0009] These findings indicate that COL17 is an important component of skin homeostasis and that the reduction in its concentration in the skin, which occurs during aging, leads to epidermal disturbances, including hemidesmosomes, pigmentary and hair abnormalities, and delayed wound healing. Several compounds are known for their cosmetic effects in treating skin aging. Documents FR 3 000742 and EP 3 466419, for example, describe derivatives of sinapic acid, in particular the molecule with CAS number 1469299-98-6, which corresponds to the INCI names trimethoxybenzyl acetyl sinapate or ethylhexyl ferulate, and their function as antioxidants and sunscreens.

[0010] Document XP2668697 describes F ethylhexyl ferulate as having a different chemical structure than the molecule associated with the INCI name ethylhexyl ferulate mentioned above. The molecule described in this document actually corresponds to CAS number 391900-25-7, marketed, for example, by Tsuno Rice Chemicals Company under the name 2-Ethy 1-1-Hexyl Ferulate.

[0011] Document EP3466419A1 relates to compositions for topical application, comprising trimethoxybenzyl acetyl sinapate (CAS number 1469299-98-6) and a UV filter. Document XP093305761 refers to the formulation 'Chando Sun Protective Total-Effect Lotion SPF 35 PA++' comprising an undefined compound with the INCI designation ethylhexyl ferulate and glucose.

[0012] There therefore remains an obvious need to develop a topical composition, preferably ecobiological, comprising active compounds capable of reducing or even inhibiting the fall in COL17 protein levels in the skin in order to ultimately combat skin aging and / or promote skin regeneration, which are safe for human topical use, while ensuring good tolerance and without inducing harmful side effects.

[0013] DESCRIPTION OF THE INVENTION

[0014] After much research, it is to the Applicant's credit that she was able to identify, unexpectedly and surprisingly, a combination of compounds / active ingredients that act synergistically to meet the aforementioned needs.

[0015] In accordance with the ecobiological approach to addressing the biological causes of skin disorders, one objective of the present invention is to combat the decrease in the amount of COL 17 protein in the skin, which ultimately helps to combat skin aging, the loss of hemidesmosomes' stability, epidermal thinning, the appearance of wrinkles and fine lines, the appearance of pigmentary and / or hair abnormalities, to maintain skin homeostasis, and to promote skin regeneration and even healing. Thus, a first object of the present invention relates to a topical composition, advantageously ecobiological, comprising

[0016] (i) at least one compound of general formula (I) or one of its salts, said general formula (I) being the following:

[0017] [Chem. 1]

[0018]

[0019] In which:

[0020] - Ri is chosen from the group consisting of: alkyl in C2-C6 or acyl -C(0)(R3);

[0021] - R2 is chosen from the group consisting of: alkoxyl radicals -OR4 or amine radicals -NfRsjfRô); - R3 represents an alkyl radical in CI-CO;

[0022] - R4 represents a C12-C16 alkyl radical, C12-C16 alkenyl, C12-C16 alkynyl, phenyl, 4-pyranone, C1-C16 alkylphenyl, C2-C16 alkenylphenyl, C2-C16 alkynylphenyl, C3-C6 cycloalkyl, possibly substituted by a C1-C16 alkyl, C2-Ci-alkenyl-C3-Co-cycloalkyl and C2-Ci6-alkynyl-C3-C6-cycloalkyl; said radicals being possibly substituted by one or more substituents chosen independently of each other in the hydroxy, amine, alkyl in CI-CÔ, hydroxyalkyl in CI-CÔ, alkoxyl in CI-CÔ, thioalkyl in CI-CÔ, alkylcarbonyloxy in CI-CÔ, phenyl, alkoxyphenyl in CI-CÔ, or alkenylphenyl in C2-C6 possibly substituted by one or more substituents chosen independently of each other as being an alkyl in CI-CÔ, hydroxyalkyl in CI-CÔ, alkoxyl in CI-CÔ, thioalkyl in CI-CÔ or alkylcarbonyloxy in CI-CÔ group;

[0023] - R5 and RÔ represent, independently of each other, a hydrogen atom or an alkyl radical in CI-CIÔ, alkenyl in C2-C16, alkynyl in C2-C16, phenyl, alkylphenyl in CI-CIÔ, alkenylphenyl in C2-C16, alkynylphenyl in C2-C16, N-alkoxyindole in CI-CIÔ, cycloalkyl in C3-C6, possibly substituted by an alkyl in CI-CIÔ, C2-Ci6-alkenyl-C3-Cô-cycloalkyl and C2-Ci6-alkynyl-C3-Cô-cycloalkyl;said radicals being optionally substituted by one or more substituents chosen independently of each other from the hydroxy, amine, alkyl in C-C0, hydroxyalkyl in C-C0, alkoxyl in C-C0, thioalkyl in C-C0, alkylcarbonyloxy in C-C0, phenyl, alkoxyphenyl in C-C0, or alkenylphenyl in C2-C6, optionally substituted by one or more substituents chosen independently of each other as being an alkyl in C-C0, hydroxyalkyl in C-C0, alkoxyl in C-C0, thioalkyl in C-C0 or alkylcarbonyloxy in C-C0, or R5 and R0, form, with the nitrogen atom to which they are bonded, a heterocycle chosen from piperidine, morpholine, hexamethyleneimine or the pyrrolidine, possibly substituted by one or more alkyl groups in CI-CO;

[0024] (ii) at least one monosaccharide.

[0025] The present invention offers various advantages, including the ability to use simply and routinely an effective composition whose compounds act synergistically on the aforementioned causes of skin dysfunctions, which is respectful of the communities of living cells that constitute the skin and that constantly interact with each other and with their environment to maintain the balance of this skin ecosystem, and which is inexpensive.

[0026] In particular, the present invention makes it possible to combat the loss of functionality of the COL 17 protein.

[0027] In the general formula (I), the hydrogen atoms are not shown. Within the scope of the invention, when a tautomeric form exists for the chemical functions of the invention, these functions can be represented in either tautomeric form. In other words, within the scope of the invention, the representation of a chemical structure of a compound encompasses its tautomeric forms.

[0028] Within the context of this invention, the term "ecobiological composition" refers to a composition that respects the individual, their interactions with the world, and the planet. Preferably, it designates a composition that respects the communities of living cells that constitute the skin (i.e., skin microbiota, keratinocytes, fibroblasts, etc.) and that constantly interact with each other and with their environment to maintain the balance of this skin ecosystem. The term "ecobiological approach" refers to the specific approach initiated by the inventor, Jean-Noël Thorel, which combines skin biology and ecology to help the skin function according to its natural biology over the long term.

[0029] Within the framework of the invention, the expressions "loss of protein functionality" and "inactive protein" are used interchangeably and refer to a loss of biological activity of a protein originating, for example, from a spatial disorganization / loss of folding induced by denaturing agents of a physical nature (i.e. modification of temperature, pH or irradiation) or chemical nature (i.e. oxidizing agents, thiol reducers, detergents or heavy metal ions) or biological nature (i.e. enzymatic degradation for example).

[0030] In the context of the invention, "healing" or "to heal" refers to the different phases of the process by which tissue damage is repaired / the integrity of damaged tissue is restored following an injury. The different stages of this process are: - an inflammatory phase: phagocytosis and elimination of bacteria and other debris, recruitment of inflammatory cells, secretion of various factors that promote the migration and division of cells participating in the proliferative phase;

[0031] - a proliferative phase: angiogenesis, increased dermal protein content, granulation, epithelialization, and wound contraction; and

[0032] - a maturation and remodeling phase: dermal proteins are remodeled and realigned along the lines of tension and cells that are no longer needed are eliminated by apoptosis.

[0033] Within the framework of the invention, the expressions "promote regeneration and / or healing", "improve regeneration and / or healing", "increase regeneration and / or healing" and "facilitate regeneration and / or healing" are used interchangeably and designate the mechanism by which the phases of healing are more efficient (i.e., better cell survival, increased frequency and / or quantity of cell cloning...) and / or follow one another more rapidly than the foreseeable time frame, i.e., faster and more stable healing, that is to say, little or no risk of scar reopening.

[0034] In the context of this invention, the terms "active ingredient" and "active compound" are used interchangeably and refer to a substance or compound possessing biological and / or therapeutic properties that underlie a physiological effect. The active ingredient is distinct from at least one excipient present in the composition according to the invention.

[0035] In the context of the invention, "molecular weight (Mw)" refers to the average molecular weight (Mw) of a protein or other polymer, such as, for example, a polysaccharide or a proteoglycan, said molecular weight being expressed in Daltons (Da). In the context of the invention, "composition for cutaneous application" or "for topical use" refers to a composition compatible with application to the skin, mucous membranes, hair and / or scalp, preferably human skin.

[0036] According to a particular embodiment, in the composition according to the invention, at least one compound of general formula (I) or one of its salts is characterized in that:

[0037] - Ri is chosen from the group consisting of: alkyl in C2-C6 or acyl -C(O)(R3);

[0038] - R2 is chosen from the group consisting of: alkoxyl radicals -OR4 or amine -(N)RsR6; - R4 represents 4-pyranone, 3,4,5-trimethoxybenzyl or a Ci6 alkyl.

[0039] According to another particular embodiment, in the composition according to the invention, at least one compound of general formula (I) or one of its salts is characterized in that:

[0040] - Ri is an acyl -C(O)(R3) in which R3 is an alkyl in Ci;

[0041] - R2 is an alkoxyl radical -OR4;

[0042] - R4 is 3,4,5-trimethoxybenzyl.

[0043] According to a particular embodiment, in the composition according to the invention, at least one compound of general formula (I) or one of its salts corresponds to 3-[4-(acetyloxy)-3,5-dimethoxyphenyl]-(3,4,5-trimethoxyphenyl)methyl ester- (2E)-Propenoic acid and to CAS number 1469299-98-6, characterized by the following general formula (II):

[0044] [Chem. 2]

[0045]

[0046] Advantageously, in the composition according to the invention, at least one compound of general formula (II) or one of its salts corresponds to the INCI designation trimethoxybenzyl acetyl sinapate or ethylhexyl ferulate and to CAS number 1469299-98-6.

[0047] According to a particular embodiment, in the composition according to the invention, at least one compound of general formula (I) or one of its salts, advantageously corresponding to the INCI designation trimethoxybenzyl acetylsinapate or ethylhexyl ferulate, is obtained from plant or microorganism extracts, or alternatively by chemical synthesis, more advantageously by chemical synthesis.

[0048] According to a particular embodiment, at least one compound of general formula (I) or one of its salts, advantageously the compound corresponding to the INCI designation trimethoxybenzyl acetylsinapate or ethylhexyl ferulate, is present in the composition according to the invention in purified or isolated form, preferably of purity at least equal to 60% by weight or 70%, 80%, 90% by weight or even at least equal to 95% by weight.

[0049] The CAS number for molecule II (1469299-98-6) can be found in the Personal Care Product Council (PCPC; https: / / incipedia.personalcarecouncil.org / ) cosmetic ingredients database, which also indicates that the product marketed under this CAS number corresponds to the INACLEAR product offered by INABATA and PHARMASYNTHESE. These companies market this product under the two INCI names mentioned above (trimethoxybenzyl acetylsinapate or ethylhexyl ferulate), depending on the country of sale.

[0050] According to a particular embodiment, in the composition according to the invention, at least one compound of general formula (I) or one of its salts, advantageously the compound corresponding to the INCI designation trimethoxybenzyl acetylsinapate or ethylhexyl ferulate, is vectorized in a clay support.

[0051] According to a particular embodiment, in the composition according to the invention, at least one compound of general formula (I) or one of its salts, advantageously the compound corresponding to the INCI designation trimethoxybenzyl acetylsinapate or ethylhexyl ferulate, preferably vectorized in a clay support, corresponds to the raw material INACLEAR VECTORISE marketed by the companies INABATA and PHARMASYNTHESE and corresponding to the INCI designations bentonite (and) trimethoxybenzyl acetylsinapate or bentonite (and) ethylhexyl ferulate.

[0052] According to a particular embodiment, in the composition according to the invention, at least one compound of general formula (I) or one of its salts, advantageously the compound corresponding to the INCI designation trimethoxybenzyl acetylsinapate or ethylhexyl ferulate, represents between 0.0001% and 10% by total weight of the composition according to the invention, advantageously between 0.001% and 1%, preferably between 0.003% and 0.3%. According to a particular embodiment, in the composition according to the invention, at least one monosaccharide is selected from fucose, ribulose, allose, lyxose, xylulose, altrose, gulose, idose, talose, mannose, glucose, galactose, fructose, psicose, tagatose, arabinose, sorbose, ribose, colitose, deoxyribose and abequose.

[0053] According to a particular embodiment, in the composition according to the invention, at least one monosaccharide is not rhamnose.

[0054] According to a particular embodiment, in the composition according to the invention, at least one monosaccharide is a deoxyose.

[0055] According to a particular embodiment, in the composition according to the invention, at least one deoxyose is chosen from fucose, colitose, deoxyribose, abequose, advantageously fucose.

[0056] According to a particular embodiment, in the composition according to the invention, at least one monosaccharide is fucose, preferably L-fucose.

[0057] According to a particular embodiment, in the composition according to the invention, at least one monosaccharide, advantageously a deoxyose, preferably fucose, represents between 0.00001% and 10% by total weight of the composition, advantageously between 0.0001% and 1%. By way of example, the fucose used in the composition according to the invention may correspond to the cosmetic raw material L-FUCOSE F2252 marketed by MMP EUROPE and corresponding to the INCI designation fucose, or to the cosmetic raw material L-Fucose marketed by Jennewein Biotechnologie GMBH, or to the raw material L-Fucose marketed by Hangzhou Rebtech Novel Material Co., Ltd.

[0058] Preferably, the fucose used in the composition according to the invention is derived from plant extracts.

[0059] According to a particular embodiment, in the composition according to the invention, the mass ratio between the compound of general formula (I) or one of its salts, advantageously the compound corresponding to the INCI designation trimethoxybenzyl acetyl sinapate or Ethylhexyl ferulate, and at least one monosaccharide, advantageously a deoxyose, preferably fucose, is between 20:1 and 1:20, advantageously between 10:1 and 1:10, preferably between 1:5. According to a particular embodiment, the composition according to the invention further comprises vitamin PP, corresponding to the INCI designation NIACINAMIDE, or one of its derivatives, representing advantageously between 0.0001% and 10% by total weight of the composition, even more advantageously between 0.001% and 5%, preferably between 0.1% and 2%.The niacinamide present in the composition according to the invention may correspond, for example, to the cosmetic raw material NIACINAMIDE marketed by QLŒMICA, and niacinamide or to the cosmetic raw material Niacinamide PC marketed by DSM Nutritional Products, Inc., to the raw material OriStar NA marketed by Orient Stars LLC or to the cosmetic raw material RonaCare Nicotinamide marketed by Merck KGaA.

[0060] According to a particular embodiment, the composition according to the invention further comprises at least one compound selected from the group consisting of: fructooligosaccharides, boldo extracts, hyaluronic acid or its salts, hyaluronic acid derivatives, carnosine, adenosine, palmitoyl tripeptide-1 (INCI), palmitoyl tetrapeptide-7 (INCI), glycyrrhetinic acid, acetyl dipeptide-1 cetyl ester, squalane, jojoba oil, mannitol, xylitol, ectoine, dipalmitoyl hydroxyproline, glabridin, the raw material corresponding to the INCI designation Himanthalia elongata extract, cross-linked sulfated galactomannans and galactans corresponding to the INCI designations Caesalpinia spinosa extract and Kappaphycus alvarezii extract, caprooyl tetrapeptide-3 (INCI) and their mixtures.

[0061] According to a particular embodiment, the cross-linked sulfated galactomannans and / or galactans, corresponding to the INCI designations Caesalpinia spinosa extract and Kappaphycus alvarezii extract, to be used in the composition according to the invention, individually represent, advantageously, between 0.000001% and 5% by total weight of the composition, preferably between 0.0001% and 1%.

[0062] According to a particular embodiment, the composition according to the invention further comprises a compound corresponding to the INCI designation caprooyl Tetrapeptide-3, advantageously representing between 0.000001% and 5% by total weight of the composition, preferably between 0.0001% and 1%.

[0063] According to a particular embodiment, the palmitoyl peptides corresponding to the INCI designations Palmitoyl Tripeptide-1 and Palmitoyl Tetrapeptide-7, to be used in the composition according to the invention, each represent between 0.000001% and 1% by total weight of the composition according to the invention, advantageously from 0.00001% to 0.1%. According to a particular embodiment, the seaweed extract corresponding to the INCI designation Himanthalia elongata extract, to be used in the composition according to the invention, represents between 0.000001% and 1% by total weight of the composition, advantageously between 0.00001% and 0.1%. According to a particular embodiment, the glabridin to be used in the composition according to the invention represents between 0.0001% and 5% by total weight of the composition, advantageously between 0.001% and 1%. For example, the raw material GLABRILIANCE (GIVAUDAN), corresponding to the INCI designation Glabridin, or the raw material OLI-2186 Glabridin 90 (Shanghai Oli Enterprises Co., Ltd.) corresponding to the INCI designation Glabridin, or the raw material Polyol Soluble Licorice Extract PT(40) (Maruzen Pharmaceuticals Co., Ltd.), corresponding to the INCI designation Glycyrrhiza glabra (licorice) root extract may be used in the composition according to the invention.

[0064] According to a particular embodiment, the dipalmitoyl hydroxyproline (CAS No. 41672-81-5) to be used in the composition according to the invention represents between 0.0001% and 5% by total weight of the composition, advantageously between 0.01% and 2%, and has a degree of purity advantageously greater than or equal to 90% by weight, even more advantageously greater than or equal to 95% by weight, or even 98% by weight. By way of example, the crystalline raw material DIPALMITOYL HYDROXYPROLINE, marketed under the name SEPILIFT DPHP™ (SEPPIC), can be used in the composition of the invention.

[0065] According to a particular embodiment, the glycyrrhetinic acid to be used in the composition according to the invention represents between 0.01% and 2% by total weight of the composition according to the invention, advantageously between 0.1% and 1%, and is advantageously in a pure form or characterized by a purity greater than 90% by weight. By way of example, products marketed by MARUZEN, INDENA, or MAFCO under the INCI name glycyrrhetinic acid can be used in the composition of the invention.

[0066] According to a particular embodiment, the xylitol to be used in the composition according to the invention represents between 0.0001% and 2% by total weight of the composition, advantageously between 0.001% and 0.1%, and is advantageously in pure form or characterized by a purity greater than 90% by weight. For example, the raw materials XYLITOL GENENCARE® XL (International Flavors & Fragrances Inc.) and Beauté by Roquette® PO 370 (Roquette Frères) can be used in the composition of the invention.

[0067] According to a particular embodiment, the mannitol to be used in the composition according to the invention represents between 0.0001% and 2% by total weight of the composition, advantageously between 0.001% and 0.1%, and is advantageously in pure form or characterized by a purity greater than 90% by weight. For example, the raw material OriStar MNT (Orient Stars LLC), with the INCI designation mannitol, or the raw materials Beauté by Roquette® PO 260 (Roquette Frères) or MANNITOL (VWR International) can be used in the composition according to the invention.

[0068] According to a particular embodiment, the jojoba oil to be used in the composition according to the invention represents between 0.1% and 20% by total weight of the composition, advantageously between 1% and 10%. The jojoba oil (INCI: Simmondsia chinensis (jojoba) seed oil) used according to the invention is available from several suppliers of cosmetic raw materials (e.g., CAUVIN and VANTAGE SPECIALTY CHEMICALS).

[0069] According to a particular embodiment, the squalane to be used in the composition according to the invention represents between 0.01% and 25% by total weight of the composition, advantageously between 1% and 15%, and is advantageously of vegetable origin and characterized by a degree of purity greater than 90% by weight. By way of example, the raw material PHYTOSQUALAN (SOPHIM), PLANTASENS OLIVE SQUALANE, or PLANTASENS OLIVE SQUALANE (CLARIANT) can be used in the composition of the invention.

[0070] According to a particular embodiment, the adenosine to be used in the composition according to the invention represents between 0.0001% and 5% by total weight of the composition, advantageously between 0.001% and 1%, preferably between 0.01% and 0.05%, and is advantageously in a non-phosphated form, preferably in powder form, and corresponds to the INCI designation ADENOSINE marketed by PHARMA WALDHOF or ACTYLIS GMBH. According to a particular embodiment, the carnosine to be used in the composition according to the invention represents between 0.001% and 5% by total weight of the composition, advantageously between 0.01% and 1%, and is advantageously in purified or highly purified form, preferably obtained by chemical synthesis.For example, the raw material Kopsine corresponding to the INCI name CARNOSINE marketed by the company KUMAR ORGANIC PRODUCTS LTD or DRAGOSINE / L-CARNOSINE marketed by the company SYMRISE can be used in the composition of the invention.

[0071] According to a particular embodiment, the fructooligosaccharides to be used in the composition according to the invention, also called oligofructoses or FOS, represent between 0.001% and 10% by weight of the composition, advantageously between 0.01% and 5%, and are advantageously in purified or highly purified form. For example, the fructooligosaccharides raw material corresponding to the INCI name fructooligosaccharides marketed by SHAANXI BOLIN BIOTECHNOLOGY CO, or AZELIS, or TEREOS, can be used in the composition of the invention.

[0072] According to a particular embodiment, the hyaluronic acid to be used in the composition according to the invention has a molecular weight (Mw) greater than 300 kDa, advantageously greater than 1 MDa, and is present in acidic or salt form, in particular sodium, potassium, or magnesium salts, preferably sodium salts, and advantageously represents between 0.0001% and 10% by total weight of the composition, more advantageously between 0.001% and 2%, preferably between 0.01% and 1%. By way of example, the raw material BIOSODIUM HYALURONATE MMW (DKSH) or PHYLCARE™ SODIUM HYALURONATE MW (SAFIC ALCAN SCIENCES DE LA VIE) or PURE SODIUM HYALURONATE (HTL), corresponding to the INCI name SODIUM HYALURONATE, can be used in the composition of the invention.

[0073] According to a particular embodiment, boldo (Peumus boldus) or boldo extract to be used in the composition according to the invention represents between 0.0001% and 10% by total weight of the composition, advantageously between 0.001% and 2%, preferably between 0.01% and 1%.

[0074] According to another particular embodiment, the composition of the invention further comprises peptide extracts of soy and / or wheat representing, advantageously, between 0.01% and 20% by total weight of the composition, advantageously between 0.1% and 10%, preferably between 0.2% and 0.7%.

[0075] Advantageously, the composition according to the invention further comprises peptide extracts of soy and wheat in a weight ratio respectively between 80 / 20 and 20 / 80, advantageously between 70 / 30 and 30 / 70, preferably equal to 60 / 40.

[0076] According to a particular embodiment of the invention, the peptide extracts of soy and / or wheat are free of synthetic tripeptides GHK (glycyl-histidyl-lysine; INCI: Tripeptide-1).

[0077] Advantageously, the soy peptide extract is the extract identified under CAS number 68607-88-5 and the wheat peptide extract is the extract identified under CAS number 70084-87-6; preferably, the wheat and soy extracts correspond to the INCI designations HYDROLYZED WHEAT PROTEIN and HYDROLYZED SOY PROTEIN, respectively. According to a particular embodiment, the composition according to the invention is incorporated into a delivery support, advantageously a liposome.

[0078] Advantageously, the liposome incorporating the composition according to the invention comprises at least one lecithin or at least one lysolecithin, and more particularly at least one lecithin, for example soy lecithin comprising at least 50% by weight of phosphatidylcholine, optionally mixed with a second soy lecithin of different composition. Preferably, the liposome comprises at least two soy lecithins of different phospholipid compositions, one being a phospholipid mixture comprising more than 90% by weight of phosphatidylcholine, for example soy lecithin marketed under the name Emulmetik™ 930 by Lucas Meyer, the second being a phospholipid mixture comprising between 15 and 30% phosphatidylcholine, for example soy lecithin marketed under the name Emulmetik™ 300 IP by Lucas Meyer.The liposomes used as delivery carriers in the composition according to the invention can correspond to the raw material NATIPIDE™ ECO marketed by LIPOID AG and having the INCI designations aqua, lecithin, glycerin, pentylene glycol, tocopherol, and sodium hydroxide. Thus, according to a particular embodiment, the composition according to the invention is incorporated into a liposome bearing the INCI designations aqua, lecithin, glycerin, pentylene glycol, tocopherol, and sodium hydroxide.

[0079] According to a particular embodiment, the composition according to the invention is characterized in that:

[0080] - the compound of general formula (I) or one of its salts, advantageously the compound of general formula (II), corresponds to the INCI designation trimethoxybenzyl acetyl sinapate or ethylhexyl ferulate and

[0081] - at least one monosaccharide, advantageously fucose, corresponds to the INCI designation fucose.

[0082] According to a particular embodiment, the composition of the invention further comprises at least one emulsifier selected from the following group of compounds identified by their INCI designation: sodium stearoyl glutamate, potassium cetyl phosphate, glyceryl stearate, C20-22 alkyl phosphate / C20-C22 alkyl alcohols, tribehenin PEG-20 esters, C14-C22 alcohols / Cl 2-20 alkyl glucoside, cetearyl alcohol, coco-glucoside, polyglyceryl-6 stearate, polyglyceryl-6 behenate, PEG-30 dipolyhydroxystearate, polyglyceryl-4 diisostearate / polyhydroxystearate / sebacate and mixtures thereof, each advantageously representing between 0.1% and 5% by total weight of the composition, preferably between 0.5% and 3%.

[0083] The composition according to the invention is presented in any galenic form normally used or usable in the cosmetic and dermatological fields, preferably compatible with the formulation of an oil phase.

[0084] The composition according to the invention is presented in a galenic form suitable for topical application on the skin, mucous membranes, hair and / or scalp.

[0085] According to a particular embodiment, the composition according to the invention is in the form of an O / W or W / O emulsion, more or less fluid; a multiple emulsion such as a triple emulsion (W / O / W or W / O / O); a vesicular dispersion of ionic (liposomes) and / or non-ionic type; a biphasic composition devoid of emulsifiers and gelling agents whose immiscible phases separate during storage; a foam; a stick; an anhydrous oil; an aqueous solution without a fat phase, gelled or not; a spray or mist.

[0086] Another object of the present invention also relates to the topical use, preferably cosmetic, advantageously non-therapeutic, of the composition as described above, to reduce or even prevent the loss of functionality of the COL 17 protein, advantageously the loss of functionality induced by proteolysis, glycation, acetylation and / or acylation of the COL17 protein.

[0087] In particular, this cosmetic use of the composition of the invention makes it possible to combat, reduce, or even partially or totally inhibit the proteolysis of the COL17 protein.

[0088] Another object of the present invention also relates to the topical use, preferably cosmetic, advantageously non-therapeutic, of the composition as described above, to combat skin aging, advantageously to combat the appearance of wrinkles.

[0089] Another object of the present invention relates to the topical use, preferably cosmetic, advantageously non-therapeutic, of the composition as described above, to regenerate the skin, advantageously to promote skin healing, preferably by accelerating at least one of the phases of the healing process, advantageously the inflammatory phase and / or the proliferative phase and / or the maturation and remodeling phase. Another object of the present invention also relates to a method, preferably cosmetic, advantageously non-therapeutic, for the topical application of the composition as described above to the skin, mucous membranes, hair and / or scalp.Another object of the present invention also relates to the composition as described above for its use in reducing, or even preventing, the loss of functionality of the COL 17 protein, advantageously the loss of functionality induced by proteolysis, glycation, acetylation and / or acylation.

[0090] In particular, the composition of the invention for its use described above makes it possible to combat the proteolysis of the COL 17 protein.

[0091] Another object of the present invention also relates to the composition as described above for its use in a method to combat skin aging, advantageously to combat the appearance of wrinkles.

[0092] Another object of the present invention also relates to the composition as described above for its use in regenerating the skin, advantageously to promote skin healing, preferably via an acceleration of at least one of the phases of the healing process, advantageously the inflammatory phase and / or the proliferative phase and / or the maturation and remodeling phase.

[0093] The manner in which the invention can be implemented and the resulting advantages will be more clearly shown in the following examples of implementation, given by way of illustration and not limitation, in support of the attached figures.

[0094] FIGURE

[0095] [Fig. 1]: Evaluation of the protection conferred by the active compounds of the invention used alone or in combination against the proteolysis of the COL17 protein in a culture of normal human keratinocytes. The results are from an experiment with 3 wells per condition.

[0096] EXAMPLES OF ACHIEVEMENTS

[0097] The percentages indicated are given as product weight relative to the total weight of the composition in the tables below.

[0098] Example 1: Cosmetic composition according to the invention - light moisturizing cream [Table 1]

[0099]

[0100]

[0101] Example 2: Cosmetic composition according to the invention - rich repairing cream [Table 2]

[0102]

[0103]

[0104] Example 3: Cosmetic composition according to the invention - SPF50+ sun mist

[0105] [Table 3]

[0106]

[0107]

[0108] Example 4: Protection of COL17 from proteolysis by the composition according to the invention 4-1 Purpose of the study

[0109] The purpose of this study is to determine the protective capacity of the composition according to the invention and corresponding to the mixture of active compounds corresponding to the INCI designations TRIMETHOXYBENZYL ACETYL S IN AP ATE and FUCOSE against the proteolysis of the COL 17 protein.

[0110] 4-2 Materials and methods

[0111] 4-2.1 - Cell culture

[0112] Normal human keratinocytes were used in this study. The cells were seeded in 96-well plates at a density of 15,000 cells / well in a complete culture medium (KGM, Keratinocyte Growth Medium). After 24 hours of incubation, the cells were incubated with the compounds of the invention or the positive control (EGF 10 ng / ml) in KBM (Keratinocyte Basal Medium). After 48 hours of incubation at 37°C, 5% CO2, the culture supernatants were collected and stored at -80°C before being used for the quantification of cleaved COL 17 protein released into the medium by ELISA. An assessment of cell viability is performed using the MTT (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay in order to normalize the results relating to the amount of cleaved COL17 released to cell viability.

[0113] 4-2.2 - Tested Products

[0114] The compounds referenced in Table 4 were tested alone or in combination.

[0115] [Table 4]

[0116]

[0117] Since TRIMETHOXYBENZYL ACETYLSINAPATE is soluble in DMSO, the tested concentrations were adjusted to 0.1% final DMSO for all tested conditions to normalize the effect of the solvent to the results.

[0118] 4-2.3 Quantification of COL 17 proteolysis in KHN supernatants

[0119] COL17 proteolysis was quantified in supernatants by ELISA (Ref.: E-EL-H0785, Elabsciences, USA) by measuring the amount of cleaved COL17 protein released by cells into the supernatant, according to the manufacturer's instructions. Optical density (OD) was read using a spectrophotometer at 450 nm. COL17 protein quantification was obtained from a standard curve (0 to 200 ng / ml) established with recombinant COL17 protein. Results are expressed as the percentage of COL17 protein proteolysis normalized to the percentage of viability per well. COL17 assays were performed only when cell viability was greater than 80%.

[0120] 4-2.4 Cell viability using an MTT assay

[0121] MTT ((3-4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) is a soluble yellow dye that is metabolized by mitochondrial enzymes (succinate dehydrogenase) into a dark blue compound: formazan. Formazan crystals are then solubilized in DMSO, and the optical density is measured spectrophotometrically at 540 nm. Cells are treated with 1 mg / ml of MTT for 3 hours, and formazan crystals are solubilized in 100 µL of DMSO.

[0122] 4-2.5 Statistical Analysis Data were collected from independent experiments conducted in triplicate. Quantitative analyses are expressed as mean with standard deviation. Statistical significance is determined by a Student's t-test. Differences are considered statistically significant from p<0.05. (NS: p>0.05; *: p<0.05; **: p<0.01; ***: p<0.001).

[0123] 4.3 Results and conclusions

[0124] The protective effect of the active ingredients in the composition, i.e., TRIMETHOXYBENZYL ACETYLSINAPATE and FUCOSE, against the proteolysis of the COL 17 protein was evaluated by measuring this protein in vitro. The results are shown graphically in Figure 1.

[0125] The untreated condition corresponds to the control which arbitrarily represents 100% proteolysis of the COL-17 protein under basal conditions.

[0126] The positive control (EGF-10 ng / ml) corresponds to the control of inhibition of proteolysis of the COL17 protein. It induces a significant decrease in proteolysis of approximately 38%.

[0127] The solvent control (DMSO 0.1%) corresponds to the solvent of the combination of TRIMETHOXYBENZYL ACETYLSINAPATE and FUCOSE. It does not have a significant effect on the degradation of COL17.

[0128] The active ingredient FUCOSE induces a non-significant decrease in COL 17 proteolysis at the tested doses (i.e., 0.01% and 0.005%).

[0129] The active ingredient TRIMETHOXYBENZYL ACETYLSINAPATE (TMBAS) induces a significant 58% decrease in COL 17 degradation at the higher tested dose (i.e., 0.0025%), and has no effect at the other dose (i.e., 0.00125%).

[0130] The composition according to the invention, comprising the active ingredients TRIMETHOXYBENZYL ACETYLSINAPATE (T) and FUCOSE (F), provides significant, synergistic, and dose-dependent protection against COL17 proteolysis of approximately 43% and 73%, at concentrations of [0.01% (F) + 0.0025% (T)] and [0.005% (F) + 0.00125% (T)], respectively. BIBLIOGRAPHY

[0131] Langton, AK, Halai, P., Griffiths, CEM, Sherratt, MJ, and Watson, REB (2016). The impact of intrinsic aging on the protein composition of the dermal-epidermal junction. Meeh. Aging Dev. 156, 14-16.

[0132] Liu, N., Matsumura, H., Kato, T., Ichinose, S., Takada, A., Namiki, T., Asakawa, K., Morinaga, H., Mohri, Y., De Arcangelis, A., et al. (2019). Stem cell competition orchestrates skin homeostasis and ageing. Nature 568, 344-350.

[0133] Mondon, P., Hillion, M., Peschard, O., Andre, N., Marchand, T., Doridot, E., Feuilloley, M.G., Pionneau, C., and Chardonnet, S. (2015). Evaluation of dermal extracellular matrix and epidermal-dermal junction modifications using matrix-assisted laser desorption / ionization mass spectrometric imaging, in vivo reflectance confocal microscopy, echography, and histology: effect of age and pepti. J. Cosmet. Dermatol. 14, 152-160.

[0134] Nishizawa, Y., Uematsu, J., and Owaribe, K. (1993). HD4, a 180 kDa Bullous Pemphigoid Antigen, Is a Major Transmembrane Glycoprotein of the Hemidesmosomel. J. Biochem. (Tokyo) 113, 493-501.

[0135] Shirai , K. , Obara , K. , Tohgi , N. , Yamazaki , A. , Aki , R. , Hamada , Y. , Arakawa , N. , Singh , SR , Hoffman , RM , and Am oh , Y. (2019). Expression of anti-aging type-XVII collagen (COL17A1 / BP180) in hair follicle-associated pluripotent (HAP) stem cells during differentiation. Tissue Cell 59, 33–38.

[0136] Tanimura , S. , Tadokoro , Y. , Inomata , K. , Binh , NT , Nishie , W. , Yamazaki , S. , Nakauchi , H. , Tanaka , Y. , McMillan , JR , Sawamura , D. , et al. (2011). Hair Follicle Stem Cells Provide a Functional Niche for Melanocyte Stem Cells. Cell Stem Cell 8, 177–187.

[0137] Watanabe , M. , Natsuga , K. , Nishie , W. , Kobayashi , Y. , Donati , G. , Suzuki , S. , Fujimura , Y. , Tsukiyama , T. , Ujiie , H. , Shinkuma , S. , et al. (2017). Type XVII collagen coordinates proliferation in the interfollicular epidermis. ELife 6 , e26635.

Claims

DEMANDS

1. Topical composition, advantageously ecobiological, comprising (i) at least one compound of general formula (I) or one of its salts, said general formula (I) being the following: [Chem. 3] in which: - Ri is chosen from the group consisting of: alkyl in C2-C6 or acyl -C(0)(R3); - R2 is chosen from the group consisting of: alkoxyl radicals -OR4 or amine radicals -N(RS)(RÔ); - R3 represents an alkyl radical in CI-CO; - R4 represents a C12-C16 alkyl radical, C12-C16 alkenyl, C12-C16 alkynyl, phenyl, 4-pyranone, C1-C16 alkylphenyl, C2-C16 alkenylphenyl, C2-C16 alkynylphenyl, C3-C6 cycloalkyl, possibly substituted by a C1-C16 alkyl, C2-Ci-alkenyl-C3-Co-cycloalkyl and C2-Ci6-alkynyl-C3-C6-cycloalkyl; said radicals being possibly substituted by one or more substituents chosen independently of each other in the hydroxy, amine, alkyl in CI-CÔ, hydroxyalkyl in CI-CÔ, alkoxyl in CI-CÔ, thioalkyl in CI-CÔ, alkylcarbonyloxy in CI-CÔ, phenyl, alkoxyphenyl in CI-CÔ, or alkenylphenyl in C2-C6 possibly substituted by one or more substituents chosen independently of each other as being an alkyl in CI-CÔ, hydroxyalkyl in CI-CÔ, alkoxyl in CI-CÔ, thioalkyl in CI-CÔ or alkylcarbonyloxy in CI-CÔ group; - R5 and RÔ represent, independently of each other, a hydrogen atom or an alkyl radical in CI-CIÔ, alkenyl in C2-C16, alkynyl in C2-C16, phenyl, alkylphenyl in CI-CIÔ, alkenylphenyl in C2-C16, alkynylphenyl in C2-C16, N-alkoxyindole in CI-CIÔ, cycloalkyl in C3-C6, possibly substituted by an alkyl in CI-CIÔ, C2-Ci6-alkenyl-C3-Cô-cycloalkyl and C2-Ci6-alkynyl-C3-Cô-cycloalkyl;said radicals being optionally substituted by one or more substituents chosen independently of each other from the hydroxy, amine, alkyl in C-C0, hydroxyalkyl in C-C0, alkoxyl in C-C0, thioalkyl in C-C0, alkylcarbonyloxy in C-C0, phenyl, alkoxyphenyl in C-C0, or alkenylphenyl in C2-C6 optionally substituted by one or more substituents chosen independently of each other as being an alkyl in C-C0, hydroxyalkyl in C-C0, alkoxyl in C-C0, thioalkyl in C-C0 or alkylcarbonyloxy in C-C0 or R5 and R0 form, with the nitrogen atom to which they are bonded, a heterocycle chosen from piperidine, morpholine, hexamethyleneimine or the pyrrolidine, possibly substituted by one or more alkyl groups in CI-CO; (ii) at least one monosaccharide that is a deoxyose.

2. Topical composition according to claim 1 characterized in that: - Ri is chosen from the group consisting of: alkyl in C2-C6 and acyl -C(0)(R3); - R2 is chosen from the group consisting of: the alkoxyl radicals -OR4 and amine -(N)RSRÔ; - R4 is chosen from the group consisting of: 4-pyranone, 3,4,5-trimethoxybenzyl and an alkyl in C1O.

3. Composition according to any one of the preceding claims, characterized in that: - Ri is an acyl -C(0)(R3) in which R3 is an alkyl in Ci; - R2 is an alkoxyl radical -OR4; - R4 is 3,4,5-trimethoxybenzyl.

4. Composition according to any one of the preceding claims, characterized in that the compound of general formula (I) or one of its salts corresponds to 3-[4-(acetyloxy)-3,5-dimethoxyphenyl]-(3,4,5-trimethoxyphenyl)methyl ester-(2E)-Propenoic acid (CAS number 1469299-98-6), characterized by the following general formula (II): [Chem. 4]

5. Composition according to claim 4, characterized in that the compound of general formula (II) or one of its salts corresponds to the INCI designation trimethoxybenzyl acetyl sinapate or ethylhexyl ferulate.

6. Composition according to any one of the preceding claims, characterized in that the compound of general formula (I) or one of its salts represents between 0.0001% and 10% by total weight of the composition according to the invention, advantageously between 0.001% and 1%, preferably between 0.003% and 0.3%.

7. Composition according to any one of the preceding claims, characterized in that at least one deoxyose is selected from fucose, colitose, deoxyribose and abequose, advantageously fucose.

8. Composition according to claim 7, characterized in that the deoxyose is fucose.

9. Composition according to any one of the preceding claims, characterized in that at least one monosaccharide represents between 0.00001% and 10% by total weight of the composition, advantageously between 0.0001% and 1%.

10. Composition according to any one of the preceding claims, characterized in that the mass ratio between the compound of general formula (I) or one of its salts, advantageously the compound corresponding to the INCI designation trimethoxybenzyl acetyl sinapate or ethylhexyl ferulate, and the at least deoxyose, preferably fucose, is between 20:1 and 1:20, advantageously between 10:1 and 1:10, preferably between 1:

5.

11. Composition according to any one of the preceding claims, characterized in that: - the compound of general formula (I) or one of its salts, advantageously the compound of general formula (II), corresponds to the INCI designation trimethoxybenzyl acetyl sinapate or ethylhexyl ferulate and - at least one deoxyose, advantageously fucose, corresponds to the INCI designation fucose.

12. A composition according to any one of the preceding claims, characterized in that it further comprises at least one compound selected from the group consisting of: fructooligosaccharides, boldo extracts, hyaluronic acid or its salts, hyaluronic acid derivatives, carnosine, adenosine, palmitoyl tripeptide-1, palmitoyl tetrapeptide-7, glycyrrhetinic acid, acetyl dipeptide-1 cetyl ester, squalane, jojoba oil, mannitol, xylitol, ectoine, dipalmitoyl hydroxyproline, glabridin, the raw material corresponding to the INCI designation Himanthalia elongata extract, galactomannans and cross-linked sulfated galactans corresponding to the INCI designations Caesalpinia spinosa extract and Kappaphycus alvarezii extract, of caprooyl tetrapeptide-3 and their mixtures.

13. Composition according to any one of the preceding claims, characterized in that it is incorporated in a vectorization support, advantageously a liposome, preferably corresponding to the INCI designations aqua & lecithin & glycerin & pentylene glycol & tocopherol & sodium hydroxide.

14. Composition according to any one of claims 1 to 13 for its use in combating skin aging, advantageously in combating the appearance of wrinkles.

15. Composition according to any one of claims 1 to 13 for its use in regenerating the skin, advantageously in promoting skin healing.

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