Ecobiological composition capable of preventing and treating redness, signs of skin ageing, and vascular anomalies

Abstract

The invention relates to a cosmetic composition, advantageously an ecobiological cosmetic composition, comprising: - polyglutamic acid or a salt thereof; and - at least one peptide derivative represented by general formula (I), in which: - R1 represents a hydrogen atom, an acyl radical or an acyloxy radical; and - R2 represents the side chain of an α-amino acid selected from the group consisting of: tryptophan, glutamic acid, arginine, cysteine, methionine, histidine and tyrosine. The invention also relates to the use of the cosmetic composition for combatting skin redness and / or skin ageing; to the use thereof for preventing and / or combatting cutaneous hypervascularisation and / or skin inflammation and / or rosacea; and to a method for selecting compounds suitable for preventing and / or combatting these conditions.

Description

[0001] DESCRIPTION

[0002] ECOBIOLOGICAL COMPOSITION SUITABLE FOR PREVENTING AND TREATING REDNESS AND SIGNS OF SKIN AGING, AS WELL AS VASCULAR ABNORMALITIES

[0003] FIELD OF THE INVENTION

[0004] The present invention relates to the field of cosmetics, in particular cosmetic compositions, advantageously ecobiological, and their uses for effectively combating skin aging, in particular photoaging, aging of skin prone to redness, vascular abnormalities associated with skin aging, as well as skin inflammation associated with skin redness, in particular redness linked to skin hypervascularization, skin inflammation and rosacea.

[0005] STATE OF THE PRIOR ART

[0006] The skin constitutes the main barrier that separates the organism from the external environment and is composed of the superposition of three main layers and a surface layer, respectively from the deepest to the most superficial: the hypodermis, the dermis and the epidermis, colonized by the microbiota which is often considered as the last "cutaneous layer". Due to its constant interaction with the environment, the skin undergoes multiple aggressions that alter its balance. The different exogenous and endogenous factors generate sometimes significant differences between individuals in the levels of irritability of the skin. Thus, a growing part of the population perceives their skin as prone to redness, often chronic.

[0007] Skin redness, also known as erythema, is a common condition characterized by an abnormal red or pink discoloration of the skin. It can be caused by various factors such as sun exposure, vascular abnormalities, allergic reactions, irritation, or hormonal changes. In its chronic form, redness is generally referred to as rosacea. It is a skin condition that manifests itself by persistent redness, dilated blood vessels, significant skin hypervascularization, pimples, and inflammatory plaques on the face, particularly on the cheeks, chin, nose, and forehead. Whether skin redness is transient or chronic, it is nonetheless a source of aesthetic complexes, discomfort, and even social embarrassment, sometimes leading to withdrawal.

[0008] Cutaneous hypervascularity refers to a condition in which there is an abnormal increase in the number and size of blood vessels in the skin. Hypervascularized skin is generally more sensitive and reactive, resulting in itching, irritation, or even pain. In addition to sensory symptoms, cutaneous hypervascularity usually has cosmetic implications. Areas of hypervascularized skin remain red, even when the skin is not inflamed, and may have visible blood vessels as red lines. In some cases, this can affect the self-confidence and quality of life of affected individuals.Furthermore, as the skin ages, vascular abnormalities tend to become increasingly prominent, particularly due to the progressive thinning of the epidermis thickness, the dermal extracellular matrix that protects and surrounds the vessels, as well as the reduction of its natural biological resources for maintaining, functioning and defending the skin.

[0009] Skin redness and / or rosacea, in particular, are caused by a complex set of factors including the individual's age and general health. It is therefore difficult to propose skin treatments that can act in a concerted manner on the causes of these heterogeneous dermatological conditions.

[0010] According to its ecobiological approach, the Applicant seeks to identify and act on the causes of skin disorders, in particular by modulating the function of key epidermal and dermal regulators to intervene on multiple fronts simultaneously. In recent years, the PEDF protein has been identified, particularly at the cutaneous level, as one of these factors playing a major role in the control of inflammation, skin redness, and in particular cutaneous hypervascularization.

[0011] PEDF protein, also known as pigment epithelium-derived factor, belongs to the group of non-inhibitory serpins. This 50 kDa, 398 amino acid protein is a secreted glycoprotein (Filleur et al., 2009), mainly produced by retinoblastoma epithelial cells (Tombran-Tink et al., 2004), but it is also present in other tissues, including skin (Yan et al., 2018). The dermal functions of PEDF protein are diverse and extensive. First, it is involved in the regulation of cell differentiation and promotes keratinocyte maturation, while maintaining the balance between cell proliferation and differentiation in the epidermis (Belkacemi and Zhang, 2016). Additionally, PEDF protein is known for its anti-inflammatory and immune response modulation activity in the skin.It can suppress the expression of proinflammatory cytokines and reduce the infiltration of immune cells into the skin, which contributes to the attenuation of cutaneous inflammatory responses (Zamiri et al., 2006). In addition, PEDF protein has significant anti-angiogenic properties; specifically, PEDF regulates the homeostatic balance of angiogenesis by inhibiting VEGF synthesis (Filleur et al., 2009; Yan et al., 2018). Other useful properties of PEDF include its ability to inhibit the expression of metalloproteinases MMP-2 and 9 in vitro in human pancreatic cancer cell lines (Grippo et al., 2012), and of MMP MT1-MMP (also called MMP-14) in vitro in a human chondrosarcoma cell line (Tan et al., 2010), as well as its ability to inhibit the production of ROS (reactive oxygen species; Yamagishi et al., 2004; Li and Karin, 1999).

[0012] However, PEDF expression decreases with age, particularly from the age of 30, which is, for example, an age positively correlated with the onset of rosacea (Francis et al. 2004).

[0013] Overall, the PEDF protein plays a key role in maintaining the integrity and functions of the skin, by regulating various cellular processes, by helping to modulate the immune and inflammatory response of the skin and by intervening in particular on the main causes of skin redness (eg, inflammation and hypervascularization).

[0014] Therefore, the topical use of PEDF-derived polypeptides has been proposed in EP 2 897 976 to combat inflammation and skin aging. However, the formulation of PEDF or one of its fragments in cosmetic compositions, particularly for topical use, is difficult due to issues of stability, bioavailability, lack of skin penetration and maintenance of biological activity on the skin surface, due to rapid inactivation of these polypeptides by the skin microbiota and skin proteases.

[0015] There therefore remains a clear need to develop, in particular according to the principles of ecobiology, (i) compositions which protect and / or restore the skin balance in order, ultimately, to improve the aesthetic appearance and social life of subjects suffering from skin redness and / or rosacea and / or skin hypervascularization and / or skin inflammation and / or aging, in particular photoaging and / or vascular anomalies associated with skin aging and (ii) a process for identifying and selecting compounds or active ingredients capable of preventing and / or treating said skin redness and / or said rosacea and / or said aging in order to protect and / or restore the skin balance.

[0016] DESCRIPTION OF THE INVENTION

[0017] After extensive research, it is to the Applicant's credit that, in an unexpected and surprising manner, it has identified a composition comprising a combination of compounds (or active ingredients) which act in synergy to meet the aforementioned needs. Furthermore, it is also to the Applicant's credit that it has identified a method for selecting said compounds via an innovative process implementing a surprising step of inhibition of the PEDF content.

[0018] In accordance with the ecobiological approach of action on the biological causes of skin disorders, an objective of the present invention is to protect and / or restore skin balance via the prevention and / or treatment of skin redness, skin hypervascularization, skin inflammation and / or rosacea and / or skin aging, in particular vascular anomalies associated with skin aging (or vascular aging), in particular photoaging, while exploiting endogenous mechanisms, in particular by acting on the increase or restoration of the endogenous PEDF content.

[0019] Thus, a first object of the present invention relates to a topical composition, advantageously ecobiological, comprising:

[0020] - polyglutamic acid or one of its salts; and

[0021] - at least one peptide derivative represented by the following general formula (I): in which:

[0022] - RI represents a hydrogen atom, an acyl or acyloxy radical; and

[0023] -R2 represents the side chain of an α-amino acid selected from the group consisting of: tryptophan, glutamic acid, arginine, cysteine, methionine, histidine and tyrosine.

[0024] According to a particular embodiment, it is a cosmetic composition, advantageously ecobiological, presented in a form suitable for topical application.

[0025] According to a particular embodiment, R2 represents the side chain of an α-amino acid selected from the group consisting of: L-tryptophan, L-glutamic acid, L-arginine, L-cysteine, L-methionine, L-histidine, and L-tyrosine.

[0026] The present invention provides various advantages, including:

[0027] (i) it allows the simple and routinely integrable use of an effective composition whose compounds act in synergy, to prevent and / or treat the aforementioned skin dysfunctions;

[0028] (ii) it respects the communities of living cells that make up the skin and which constantly interact with each other and with their environment to maintain the balance of this cutaneous ecosystem;

[0029] (iii) it helps to protect and / or restore the skin's balance; and

[0030] (iv) it is inexpensive. In particular, the present invention allows in particular:

[0031] - to prevent and / or combat skin redness and / or;

[0032] - to prevent and / or combat skin aging, in particular photoaging; and / or

[0033] - to prevent and / or combat cutaneous hypervascularization; and / or

[0034] - to prevent and / or combat skin inflammation; and / or

[0035] - to prevent and / or fight against rosacea; and / or

[0036] - to protect and / or restore skin balance; and / or

[0037] - to protect against skin effects associated with UV irradiation; and / or

[0038] - to prevent and / or combat vascular anomalies associated with skin aging; and / or

[0039] - to protect against skin effects associated with the environment, particularly pollution.

[0040] In the context of the invention, the expressions "ecobiological composition", "ecobiological active ingredient" or "ecobiological excipient" mean a composition, an ingredient or an excipient that is respectful of the person, of their interactions with the world, and of the planet. In other words, this designates a composition, an active ingredient or an excipient that is respectful of the homeostasis of an individual, of their interactions with the world, and of the environment. In particular, it designates a composition, an active ingredient or an excipient that is respectful of the communities of living cells that make up the skin (i.e., skin microbiota, keratinocytes, fibroblasts, etc.) and that constantly interact with each other and with their environment to maintain the homeostasis / balance of this skin ecosystem.

[0041] In the context of the invention, the expression "ecobiological approach" refers to the particular approach initiated by the inventor and developed by the Applicant which combines biology and skin ecosystem to help the skin live according to its natural biology, over the long term.

[0042] In the context of the invention, the expression "polyglutamic acid and its salts" denotes polymers composed of monomers of glutamic acid, which is an amino acid found in all organisms on earth as a constituent of proteins.

[0043] For the purposes of the invention, the term "inducer" and the expression "PEDF synthesis inducer" are used interchangeably and designate an agent, treatment or culture condition capable of triggering a determined reaction or a programmed sequence of reactions in the biological system, namely the production or synthesis (i.e., transcription and / or translation) of PEDF.

[0044] In the context of the invention, the expressions "active compound", "active ingredient" and "active principle" are used interchangeably and designate a substance or a compound which has biological and / or therapeutic properties which underlie a physiological effect. The active compound, active ingredient or active principle is to be distinguished from at least one excipient, present in the composition according to the invention.

[0045] In the context of the invention, the term "excipient" refers to a substance or compound that does not possess any biological and / or therapeutic properties. The excipient guarantees the creation of a particular texture, fragrance and / or color for a cosmetic formulation, but also its preservation, stability, safety and longevity, in compliance with regulations. The excipient is to be distinguished from the at least one active compound, the active ingredient or the active principle present in the composition according to the invention.

[0046] In the context of the invention, “molecular weight (Mw)” means the weight-average molecular weight (Mw or “Molecular Weight”) of a compound, a protein, or another advantageously natural polymer, such as polyglutamic acid and its salts.

[0047] In the context of the invention, the expression “composition for cutaneous application” or “for topical use” denotes a composition compatible with application to the skin, mucous membranes, hair and / or scalp, preferably human skin.

[0048] In the context of the invention, the term “care” designates a cosmetic and non-therapeutic care.

[0049] In the context of the invention, the expression "bringing into contact with at least one skin cell" designates any direct exposure (e.g., cells in culture) or indirect exposure (e.g., by topical application) to said at least one candidate compound according to the invention. In particular, indirect exposure by topical application can be carried out on the skin of a whole living organism, advantageously of a human being, on a skin explant, on a reconstructed epidermis, on reconstructed skin. Preferably, indirect exposure is carried out on a skin explant, on a reconstructed epidermis or on reconstructed skin.

[0050] In the context of the present invention, the expression “skin explant” designates a biopsy of human skin from surgical waste and which comprises the entire epidermis and a dermal and / or hypodermal compartment.

[0051] In the context of the present invention, the expression "skin substitute" designates a reconstructed skin or a reconstructed epidermis, preferably human, which contains differentiated cells distributed in several layers. In particular, within the meaning of the invention, the reconstructed skin contains at least two compartments, namely: a dermal compartment and an epidermal compartment. These models can be generated by 3D printing or by cell differentiation and can include several cell types in order to come as close as possible to the complete functionalities of the human or animal epidermis (innervation, immunization, pigmentation, vascularization, etc.). Examples of suitable models of this type are marketed by the companies LabSkin Creations or Straticell, SkinEthic, Episkin or Phenion.

[0052] In the context of the present invention, the expression "reconstructed epidermis" designates an epidermis generated in vitro by conventional techniques well known to those skilled in the art (eg, Limât and Hunziker, 2002; Poumay et al., 2004). The keratinocytes used in this epidermis are advantageously derived from sensitive / rosacea human skin.

[0053] In the context of the present invention, the expression "reconstructed skin" refers to an epidermal component, containing keratinocytes, generated in vitro and a dermal component, containing fibroblasts, generated in vitro integrated into a dermal matrix tissue. The reconstructed skin is commercially available. The keratinocytes and fibroblasts used in this skin may advantageously be derived from sensitive / rosacea human skin, more advantageously from sensitive skin.

[0054] In the context of the present invention, the expression "skin cells" designates any cell type likely to be found, at least partially, in one of the three layers of the skin, i.e. epidermal cells (for example keratinocytes, melanocytes, Merkel cells, immune cells such as Langerhans cells, nerve endings of type C fibers), dermal cells (for example mast cells, vascular smooth muscle cells, specialized muscle cells, fibroblasts and immune cells, dermal dendritic cells, fibrocytes, endothelial cells), hypodermal cells (for example adipocytes), nerve cells and macrophages. It is clear that according to the invention, the expression "skin cell" includes any neuronal cell whose endings or fibers are found in the skin.In particular, skin cells are fibroblasts or keratinocytes, advantageously of human origin.

[0055] In the context of the invention, the expressions “reference value”, “normal value”, “normal”, “standard”, “usual value” or “reference biological sample” are used interchangeably and designate a value or an average of the values ​​of a parameter (e.g., gene expression, in particular at the mRNA level, etc.), derived from one or more subjects and representing the basal state of the measurement envisaged; as opposed to a “tested value”, “test value”, “candidate compound” value, or “test biological sample”. The reference value and the test value are obtained by implementing the same method of detection, quantification, identification, etc.

[0056] For the purposes of the invention, the terms "content", "amount" and "level" are used interchangeably. For the purposes of the invention, the terms "PEDF protein" and "PEDF" are used interchangeably.

[0057] In the context of the invention, the expression "endogenous cutaneous content of PEDF and / or of the nucleic acids encoding it" or "content of PEDF and / or of nucleic acid encoding PEDF" designates the levels present in the skin cells and / or in the extracellular medium after secretion by said skin cells under normal conditions, in particular under normal culture conditions, and without induction or depletion of the expression of PEDF.

[0058] As used herein, the term "extracellular space" or "extracellular matrix" or "extracellular medium" or "supernatant" refers to the space outside the cell. This space is considered to be outside a plasma membrane. The term is used in contrast to intracellular, which refers to the interior of the cell.

[0059] In the context of the invention, the expression "variation of expression" designates an overexpression or an underexpression of the gene. In particular, the term "overexpression" means that the expression of a gene is increased compared to a reference value; the term "underexpression" means that the expression of a gene is decreased compared to a reference value.

[0060] The terms "coding" or "coding for," "code" or "codes for" are used interchangeably and refer to the inherent property of specific nucleotide sequences in a polynucleotide, such as a gene, cDNA, or mRNA, to serve as a template for the synthesis of polypeptides having a defined sequence of amino acids, and the biological properties that result therefrom. Thus, a gene codes for a protein if transcription and translation of the mRNA corresponding to that gene produces the protein in a cell or other biological system. Both the coding strand, whose nucleotide sequence is identical to the mRNA sequence and which is generally described in sequence listings and databases, and the non-coding strand, used as a template for transcription of a gene or cDNA, may be designated as coding for the protein or other product of that gene or cDNA.

[0061] In the context of the invention, the expression "biologically active derivatives" designates isoforms, fragments or modified versions of isoforms or fragments, in particular covalently modified with grafts of organic groups, such as capryloyl, stearoyl, palmitoyl fatty chains or even by acetylation, methylation, etc. Said derivatives may have a biological activity similar to or even superior to the protein from which they are derived.

[0062] Within the scope of the present invention, all the embodiments described below may be combined. According to a particular embodiment, the at least one polyglutamic acid or one of its salts according to the invention has a molecular weight (Mw) of between 0.1 MDa and 20 MDa, advantageously between 1 MDa and 5 MDa.

[0063] According to another particular embodiment, the at least one polyglutamic acid or one of its salts according to the invention has a molecular weight (Mw) of between 0.01 kDa and 10 kDa, advantageously between 0.1 kDa and 5 kDa.

[0064] According to another particular embodiment, the at least one polyglutamic acid or one of its salts according to the invention is poly-y-glutamic acid, advantageously the potassium salt of poly-y-glutamic acid.

[0065] In particular, polyglutamic acid or one of its salts corresponds to the following INCI name: polyglutamic acid, sodium polyglutamate, natto gum, or potassium hydrolyzed polygamma glutamate.

[0066] According to the invention, the at least one polyglutamic acid or one of its salts is of synthetic, plant or microbiological origin, such as poly-y-glutamic acid synthesized by Bacillus subtilis subsp. Chungkookjang or other analogous bacterial strains.

[0067] In particular, the at least one polyglutamic acid or one of its salts according to the invention corresponds to the raw materials AminoPGALE®-301 marketed by the company Toyobo Co. LTD; AquaMax™ HM marketed by the company CP Kelco; Sodium Polyglutamate marketed by the company Vedan Biotechnology Corporation; TEGO® Cosmo PGA marketed by the company Evonik Nutrition & Care GmbH; or Gamma-Max or Gamma-Oligo marketed by the company Rahn corporation. Preferably, it is the raw material Gamma-Oligo marketed by the company Rahn corporation.

[0068] According to a particular embodiment, the at least one peptide derivative is selected from the group consisting of α-L-glutamyltryptamine, L-tryptophantryptamine, and L-methionyltryptamine.

[0069] Advantageously, the at least one peptide derivative is α-L-glutamyltryptamine, preferably α-L-glutamyltryptamine corresponding to the CAS number 478273-36-8 ((4S)-4-Amino-5-[[2-(1H-indol-3-yl)ethyl]amino]-5-oxopentanoic acid) and / or the INCI name glutamylamidoethyl indole.

[0070] In particular, the at least one peptide derivative corresponds to the cosmetic raw material GLISTIN marketed by the company EXSYMOL under the INCI name glutamylamidoethyl indole (and) propanediol (and) aqua. According to a particular embodiment, the composition of the invention comprises a mass ratio between the at least one peptide derivative and polyglutamic acid or one of its salts of between 1:200 and 1:10, advantageously between 1:100 and 1:30.

[0071] According to a particular embodiment, the composition of the invention comprises:

[0072] - polyglutamic acid or one of its salts representing between 0.001% and 10% by total weight of the composition, advantageously between 0.01% and 5%, preferably between 0.1% and 2%; and / or

[0073] - at least one peptide derivative representing between 0.00001% and 10% by total weight of the composition, advantageously between 0.0001% and 1%.

[0074] Advantageously, the composition according to the invention has the following additional technical characteristics, taken alone or in combination:

[0075] - The composition according to the invention further comprises at least one additional compound selected from the group consisting of glycyrrhetinic acid, a derivative or a salt of this acid; hyaluronic acid or one of its salts or one of its derivatives; bakuchiol; dipotassium glycyrrhizinate, acetyl dipeptide-1 cetyl ester; squalane; jojoba oil; fructooligosaccharides; rhamnose; mannitol; xylitol; ectoin, and mixtures thereof;

[0076] - The composition according to the invention comprises glycyrrhetinic acid, a derivative or a salt of this acid, preferably representing between 0.01% and 2% by total weight of the composition, advantageously between 0.1% and 1% by total weight of the composition;

[0077] - The composition according to the invention comprises hyaluronic acid or one of its salts or one of its derivatives, advantageously:

[0078] Hyaluronic acid is in acid or salt form, including sodium, potassium or magnesium salts, preferably sodium salts;

[0079] Hyaluronic acid or one of its salts has a molecular weight (Mw) between 0.1 kDa and 2 MDa, preferably between 400 and 600 kDa or between 0.1 and 5 KDa;

[0080] Hyaluronic acid or one of its salts represents between 0.0001% and 10% by total weight of the composition, advantageously between 0.001 and 2% by total weight of the composition, even more advantageously between 0.01% and 1% by total weight of the composition;

[0081] Hyaluronic acid or one of its salts corresponds to the raw material BIOSODIUM HYALURONATE MMW corresponding to the INCI name SODIUM HYALURONATE marketed by the company DKSH; - The composition according to the invention further comprises a bioactive system combining, on the one hand, a stable form in aqueous solution of a nucleotide chosen from ATP (adenosine triphosphate), Gp4G (diguanosine tetraphosphate) and Ap4A (diadenosine tetraphosphate); and, on the other hand, at least one biomimetic peptide comprising at most six amino acids, mimicking a cutaneous polypeptide or a cutaneous protein, or an agonist or antagonist biomolecule of said peptide or said protein. This bioactive system makes it possible to catalyze the metabolic activity of skin cells while obtaining a dermocosmetic or therapeutic effect thanks to the use of biomimetic peptides.These can be selected to achieve the desired effect, for example, an effect of inhibiting irritations of neurogenic origin, a depigmenting activity, an effect inhibiting any intolerance or sensitization, etc.

[0082] In the bioactive system according to the invention and advantageously, the nucleotide represents at most 10% by total weight of the composition, preferably between 0.001% and 5% by total weight of the composition; and the biomimetic peptide represents between 0.001% to 1% by total weight of the composition;

[0083] - The composition according to the invention comprises compounds which can contribute to internal protection by an action which can consist of protection of DNA, a reduction in immunosuppression induced by UV radiation, an anti-radical action or a combined effect of these actions;

[0084] - The composition according to the invention comprises an anti-radical agent preserving cellular structures, such as for example vitamin E and / or its liposoluble or hydrosoluble derivatives, in particular tocotrienol and / or tocopherol, advantageously representing between 0.001% and 10% by total weight of the composition, even more advantageously between 0.02% and 2%, preferably 0.04% by total weight of the composition;

[0085] - the composition according to the invention further comprises at least one compound selected from the group consisting of: fructooligosaccharides, boldo extracts, carnosine, adenosine, creatinine and creatine;

[0086] - The composition according to the invention comprises boldo (Peumus boldus) or a boldo extract. Boldo is a species of tree of the Monimiaceae family and whose leaf extracts induce the synthesis of defensins and cathelicidins. Advantageously, the boldo extract represents between 0.0001% and 10% by total weight of the composition, even more advantageously between 0.001% and 2% by total weight of the composition, preferably between 0.01% and 1% by total weight of the composition;

[0087] The boldo extract in the composition according to the invention advantageously corresponds to the raw material MP BETAPUR PGF corresponding to the INCI name WATER (AND) BUTYLENE GLYCOL (AND) PEUMUS BOLDUS LEAF EXTRACT (AND) PENTYLENE GLYCOL (AND) XANTHAN GUM marketed by the company BASF;

[0088] - The composition according to the invention comprises adenosine, advantageously representing between 0.0001% and 5% by total weight of the composition, even more advantageously between 0.001 and 1%, preferably between 0.01% and 0.05% by total weight of the composition;

[0089] The adenosine in the composition according to the invention is advantageously in a non-phosphated form, even more advantageously in powder form, and may correspond to the INCI designation ADENOSINE marketed by the company PHARMA WALDHOF;

[0090] - The composition according to the invention comprises carnosine, advantageously representing between 0.001% and 5% by total weight of the composition, even more advantageously between 0.01% and 1%;

[0091] The carnosine in the composition according to the invention is preferably in purified or highly purified form, advantageously obtained by chemical synthesis, and may be the raw material Kopsine corresponding to the INCI name CARNOSINE marketed by the company KUMAR ORGANIC PRODUCTS LTD;

[0092] - The composition according to the invention comprises creatinine, advantageously representing between 0.001% and 5% by total weight of the composition, even more advantageously between 0.01% and 1% by total weight of the composition;

[0093] The creatinine in the composition according to the invention is advantageously in purified or highly purified form, even more advantageously obtained by chemical synthesis, and may be the raw material TEGO COSMO C 250 corresponding to the INCI name METHYLHYDANTOIN-2-IMIDE marketed by the company EVONIK;

[0094] - The composition according to the invention comprises fructo-oligosaccharides, also called oligofructoses or FOS, advantageously representing between 0.001% and 10% by total weight of the composition, preferably between 0.01% and 5% by total weight of the composition;

[0095] The FOS in the composition according to the invention are advantageously in purified or highly purified form, and may correspond to the raw material fructooligosaccharides corresponding to the INCI name FRUCTOOLIGOSACCHARIDES marketed by the company SHAANXI BOLIN BIOTECHNOLOGY CO;

[0096] - The composition according to the invention further comprises soy and / or wheat peptide extracts, advantageously representing between 0.01% and 20% by total weight of the composition, even more advantageously between 0.1% and 10%; The soy and wheat peptide extracts in the composition according to the invention advantageously have a weight ratio respectively between 80 / 20 and 20 / 80, even more advantageously between 70 / 30 and 30 / 70, preferably equal to 60 / 40;

[0097] The soy and / or wheat peptide extracts in the composition according to the invention are preferably free of synthetic tripeptides GHK (glycyl-histidyl-lysine; INCI: Tripeptide-1);

[0098] The soy peptide extract in the composition according to the invention may be the extract identified under the CAS number 68607-88-5, advantageously it corresponds to the INCI designation HYDROLYZED SOY PROTEIN;

[0099] The wheat peptide extract in the composition according to the invention may be the extract identified under the CAS number 70084-87-6, advantageously it corresponds to the INCI designation HYDROLYZED WHEAT PROTEIN;

[0100] - The composition according to the invention comprises at least one hydrogenated homopolymer of branched glucose comprising α (1-4) and α (1-6) bonds, advantageously representing between 0.001% and 2% by weight of the composition, even more advantageously between 0.01% and 0.5%;

[0101] The hydrogenated homopolymer of branched glucose comprising α (1-4) and α (1-6) bonds in the composition according to the invention advantageously corresponds to the INCI designation hydrogenated starch hydrolysate, even more advantageously to the raw material MG-60 marketed by the company HAYASHIBARA and corresponding to the INCI designation Maltooligosyl Glucoside & Hydrogenated Starch Hydrolysate;

[0102] - The composition according to the invention comprises at least one heteropolymer of glucose and trehalose, advantageously maltooligosyl glucoside, more advantageously representing between 0.001% and 2% by weight of the composition, even more advantageously between 0.01% and 0.5%.

[0103] According to a particular embodiment, the composition according to the invention is in a galenic form suitable for acceptable cosmetic use, that is to say compatible with the skin, mucous membranes, hair and scalp.

[0104] In particular, the composition is in a galenic form suitable for cutaneous application and / or topical use.

[0105] Thus, the composition according to the invention may be in the form of an aqueous, hydroalcoholic, organic or oily solution; suspension or dispersion in solvents or fatty substances, such as lotion or serum; in the form of a vesicular dispersion; in the form of a water-in-oil (W / O), oil-in-water (O / W) or multiple emulsion such as a water-in-oil-in-water (W / O / W) emulsion. The emulsion may be more or less thick and is in the form of a cream or milk; the composition of the invention may also be in the form of an ointment, gel, solid stick, pasty or solid anhydrous products, foam, in particular aerosol, two-phase composition or even a sprayable composition.

[0106] The galenic form of the composition as well as its method of preparation, and consequently the excipients suitable for the composition of the invention, can be chosen by a person skilled in the art on the basis of his general knowledge depending on the type of composition sought. In particular, the composition can comprise any fatty substance usually used in the cosmetic field. Mention may in particular be made of fatty substances such as oils and waxes of vegetable, mineral, animal and / or synthetic origin. The oils can be volatile or non-volatile. Mention may also be made of synthetic esters and ethers, fatty alcohols and fatty acids. The composition can also comprise an aqueous medium, a hydroalcoholic medium containing an alcohol such as ethanol or isopropanol, or an organic medium comprising usual organic solvents such as C1-6 alcohols, in particular ethanol and isopropanol, glycols such as propylene glycol, ketones.Of course, the person skilled in the art will take care to choose this or these possible additional adjuvants or excipients, and / or their quantity, in such a way that the advantageous properties of the composition according to the invention are not, or not substantially, altered by the envisaged addition. The composition may comprise at least one conventional emulsifier, chosen from amphoteric, anionic, cationic or non-ionic emulsifiers, used alone or as a mixture. It may be particularly advantageous to formulate the composition of the invention so that it is sprayable. This may be achieved, for example, by formulating specific emulsions comprising particular combinations of excipients.

[0107] Another subject of the invention relates to the use, advantageously ecobiological and / or cosmetic, of the composition according to the invention to stimulate, improve, restore or even increase the expression of the gene coding the PEDF protein and / or the production or synthesis of the PEDF protein.

[0108] In other words, the invention also aims at:

[0109] - the composition according to the invention, advantageously ecobiological, as described previously for its use to stimulate the expression of the gene coding the PEDF protein and / or the synthesis of the PEDF protein; and / or

[0110] - the use of the composition according to the invention, advantageously ecobiological, for preparing a medicament for stimulating the expression of the gene coding the PEDF protein and / or the synthesis of the PEDF protein; and / or

[0111] - a method for stimulating the expression of the gene coding for the PEDF protein and / or the synthesis of the PEDF protein comprising the administration, advantageously the topical administration, of the composition according to the invention, advantageously ecobiological.

[0112] Another subject of the invention relates to the use, advantageously ecobiological, of the composition according to the invention to prevent and / or treat a condition or pathology associated with a PEDF deficiency and / or a reduction in the PEDF content compared to a reference value.

[0113] In other words, the invention also aims at:

[0114] - the composition according to the invention, advantageously ecobiological, for its use in preventing and / or treating a condition or pathology associated with a PEDF deficiency and / or a reduction in the PEDF content compared to a reference value; and / or

[0115] - the use of the composition according to the invention, advantageously ecobiological, for preparing a medicament for preventing and / or treating a condition or pathology associated with a PEDF deficiency and / or a reduction in the PEDF content compared to a reference value; and / or

[0116] - a method for preventing and / or treating a condition or pathology associated with a PEDF deficiency and / or a decrease in PEDF content compared to a reference value, comprising the administration, advantageously the topical administration, of the composition according to the invention, advantageously ecobiological.

[0117] Another subject of the invention relates to the use, advantageously ecobiological, of the composition according to the invention to prevent and / or combat skin aging, advantageously photoaging and / or vascular aging, namely vascular anomalies associated with skin aging.

[0118] In the context of the present invention, the expressions "vascular abnormalities associated with skin aging" and "vascular aging" are used interchangeably and designate in particular a loss of elasticity of the blood vessels of an individual.

[0119] In other words, the invention also aims at:

[0120] - the composition according to the invention, advantageously ecobiological, to prevent and / or combat skin aging, advantageously photoaging and / or vascular aging; and / or

[0121] - the use of the composition according to the invention, advantageously ecobiological, to prepare a medicament to prevent and / or combat skin aging, advantageously photoaging and / or vascular aging; and / or

[0122] - a method for preventing and / or combating skin aging, advantageously photoaging and / or vascular aging, comprising the administration, advantageously topical administration, of the composition according to the invention, advantageously ecobiological.

[0123] Another subject of the invention relates to the cosmetic, non-therapeutic, advantageously ecobiological use of the composition according to the invention to prevent and / or combat skin redness.

[0124] In other words, the invention also aims at:

[0125] - the composition according to the invention, advantageously ecobiological, to prevent and / or combat skin redness; and / or

[0126] - the use of the composition according to the invention, advantageously ecobiological, to prepare a medicament to prevent and / or combat skin redness; and / or

[0127] - a method for preventing and / or combating skin redness comprising the administration, advantageously the topical administration, of the composition according to the invention, advantageously ecobiological.

[0128] Another subject of the invention relates to the use, advantageously ecobiological, of the composition according to the invention to prevent and / or treat cutaneous hypervascularization.

[0129] In other words, the invention also aims at:

[0130] - the composition according to the invention, advantageously ecobiological, for preventing and / or treating cutaneous hypervascularization; and / or

[0131] - the use of the composition according to the invention, advantageously ecobiological, to prepare a medicament for preventing and / or treating cutaneous hypervascularization; and / or

[0132] - a method for preventing and / or treating cutaneous hypervascularization comprising the administration, advantageously the topical administration, of the composition according to the invention, advantageously ecobiological.

[0133] Another subject of the invention relates to the use, advantageously ecobiological, of the composition according to the invention to prevent and / or treat skin inflammation.

[0134] In other words, the invention also aims at:

[0135] - the composition according to the invention, advantageously ecobiological, for preventing and / or treating skin inflammation;

[0136] - the use of the composition according to the invention, advantageously ecobiological, to prepare a medicament to prevent and / or combat skin inflammation; and / or

[0137] - a method for preventing and / or treating skin inflammation comprising the administration, advantageously the topical administration, of the composition according to the invention, advantageously ecobiological.

[0138] Another subject of the invention relates to the use, advantageously ecobiological and / or cosmetic, of the composition according to the invention to prevent and / or treat rosacea.

[0139] In other words, the invention also aims at:

[0140] - the composition, advantageously ecobiological according to the invention for preventing and / or treating rosacea;

[0141] - the composition, advantageously ecobiological according to the invention for preparing a medicament for preventing and / or treating rosacea; and / or

[0142] - a method for preventing and / or treating rosacea comprising the administration, advantageously the topical administration, of the composition, advantageously ecobiological according to the invention.

[0143] Furthermore, in an innovative and surprising manner, the Applicant identified PEDF as a target whose synthesis (i) is reduced or inhibited by exposure to UV, in particular UVA; and then (ii) is increased or restored by the active ingredients included in the composition of the invention, leading to the development by the Applicant of the innovative, simple and robust process according to the invention.

[0144] Thus and according to another aspect, the invention relates to a method, advantageously ex vivo or in vitro, for selecting a compound or a mixture of compounds comprising the following steps: a) measuring the value, called the reference value, of the content of PEDF protein (Pigment Epithelium derived Factor) and / or of nucleic acid encoding PEDF in at least one skin cell and / or in the extracellular space; b) inhibiting the synthesis of PEDF by exposure to ultraviolet (UV); c) bringing said compound or mixture of compounds into contact with said skin cell; d) measuring the value, called the “candidate compound” value, of the content of PEDF protein and / or of nucleic acid encoding PEDF in said skin cell and / or in the extracellular space; e) comparing the “candidate compound” value obtained in step d) with the reference value obtained in step a);f) selecting the compound or mixture of compounds when an increase in the content of PEDF and / or nucleic acid encoding PEDF is observed in step e).;

[0145] Step a) of the invention consists in measuring the content of PEDF protein and / or nucleic acid encoding PEDF in at least one skin cell and / or in the extracellular space, representing the basal state of the envisaged measurement; as opposed to a “tested value”, “test value” or “test biological sample” or “candidate compound value”. The reference value and the test value are obtained by implementing the same method of detection, quantification, identification, etc. Advantageously, the measurement of this content is carried out at a protein level by an ELISA test, immunohistochemistry, colorimetric method, or westernblot and / or at the nucleic level by in situ hybridization, northern blot, sequencing or RT-PCR, more advantageously RT-qPCR.

[0146] According to a particular embodiment, step b) consists of inhibiting the expression of the gene coding PEDF and / or the production of PEDF mRNA and / or the synthesis of PEDF protein.

[0147] According to the invention, step c) of bringing said compound or mixture of compounds into contact with said skin cell is carried out for at least 1 minute, or even at least 30 minutes and at most 120 hours.

[0148] According to a particular embodiment, the exposure to UV, including via the full solar spectrum, of step b) is an exposure to UVA and / or UVB and / or the total spectrum. Advantageously, this involves:

[0149] - exposure to UVA, preferably at a surface energy of between 7.5 J / cm 2 and 80 J / cm 2 at 750 W / m 2 ; Or

[0150] - exposure to the full solar spectrum, preferably at a surface energy of between 7.5 J / cm 2 and 80 J / cm 2at 750 W / m 2 .

[0151] UV exposure can be carried out using any method known to those skilled in the art, for example using a Suntest XLS+ instrument (Atlas France).

[0152] According to an embodiment which can be combined with the previous embodiment, step b) is carried out for at least 30 minutes and at most 72 hours, preferably under the following culture conditions: 37°C, 5% CO2 and / or humidity-saturated atmosphere.

[0153] According to one embodiment, when the method of the invention is an ex vivo method, the contacting of step c) can be carried out by topical application of said compound or mixture of compounds on a skin explant, a reconstructed epidermis or a reconstructed skin.

[0154] According to an alternative embodiment, when the method of the invention is an in vitro method, the contacting of step c) can be carried out by adding cells, advantageously keratinocytes, fibroblasts or melanocytes, to the culture medium.

[0155] According to a particular embodiment, the method of the invention further comprises, between steps a) and b), a step of bringing said compound or mixture of compounds into contact with said skin cell, advantageously for at least 1 minute, or even at least 30 minutes and at most 120 hours. Advantageously, following this step of bringing said compound or mixture of compounds into contact with said skin cell and before implementing the inhibition of PEDF synthesis by exposure to UV, the culture medium is replaced so that it does not contain the compound or mixture of compounds at the time of exposure to UV.

[0156] The measurement of the content of PEDF protein and / or nucleic acid, advantageously mRNA, encoding it can be carried out with any method known to those skilled in the art.

[0157] Advantageously, the quantification of the expressed PEDF protein can be carried out by immunohistochemistry on cell sections; by western blotting; alternatively, it can be carried out by an ELISA test, for example, on the supernatants of cell cultures or cell extracts, by interpolating the optical density of the sample on a calibration curve obtained with serial dilutions of the recombinant human PEDF protein (for example from 0.1 ng / ml to 10 ng / ml). In practice, on the cell lawn, an MTT viability test, known to those skilled in the art, can be carried out. The PEDF assays are used only if the cell viability is greater than 80%, and are reported to this cell viability value.

[0158] Measurement of the content of messenger ribonucleic acid (mRNA) encoding PEDF can be carried out by in situ hybridization on cell sections; by northern blot; or by RT-qPCR. Advantageously, total RNA is extracted from tissues, for example using commercially available kits (such as the Rneasy Plus Mini QIAGEN). The extraction can be followed by a total RNA assay which makes it possible to know the quantity and quality of RNA in the cell extract; this step can be carried out for example using the Bioanalyzer and the RNA 6000 Nano kit. cDNA is generated using the QuantiTect Reverse Transcription Kit (QIAGEN), followed by real-time quantitative PCR at each processing time, using for example the QuantiFast SYBR Green PCR Kit (QIAGEN), and monitoring the expression of a housekeeping gene (e.g., GAPDH) as a control and PEDF with specific primers.

[0159] Thus, and according to a particular embodiment, the measurement of the PEDF content is carried out by an ELISA test, by immunohistochemistry on cell sections; by western blot; the measurement of the content of messenger ribonucleic acids (mRNA) coding PEDF is carried out by immunohistochemistry, in situ hybridization on cell sections, by northern blot, sequencing or RT-PCR, advantageously RT-qPCR.

[0160] According to a particular embodiment, the candidate compound is not the PEDF protein or one of its biologically active derivatives. According to another aspect, the invention relates to a topical composition, advantageously ecobiological, comprising at least one compound or a mixture of compounds selected using the method of the invention described above.

[0161] According to a particular embodiment, the composition is in a galenic form suitable for topical use, advantageously cosmetically acceptable, that is to say compatible with the skin, mucous membranes, hair and scalp.

[0162] In particular, the composition is in a galenic form suitable for cutaneous application.

[0163] Thus, the composition of the invention is presented in one of the galenic forms as described previously.

[0164] Another subject of the invention relates to the use, advantageously ecobiological, of the composition comprising at least one compound or a mixture of compounds selected by the method according to the invention for:

[0165] - stimulate, improve or otherwise increase the expression of the gene coding for the PEDF protein and / or the synthesis of the PEDF protein; and / or

[0166] - prevent and / or treat a condition or pathology associated with a PEDF deficiency and / or a decrease in PEDF content compared to a reference value; and / or

[0167] - to prevent and / or combat skin aging, advantageously photoaging and / or vascular aging; and / or

[0168] - prevent and / or treat cutaneous hypervascularization; and / or

[0169] - prevent and / or treat skin inflammation; and / or

[0170] - prevent and / or treat rosacea.

[0171] The following examples, without being limiting, form an integral part of the invention and any characteristic which appears to be new compared to the state of the prior art is claimed as such and as a general means.

[0172] FIGURES

[0173] [Fig. 1]: Evaluation of the effect of PGA and L-GAEI, alone or in combination, on the synthesis of PEDF by normal human fibroblasts (NHF) or normal human keratinocytes (NHK) following exposure to UVA at an energy density of 30j / cm 2 . The results are from an experiment with 3 wells per condition. Statistical tests are performed versus the “untreated, unirradiated” condition (significance: *: p<0.05; **: p<0.01; ***: p<0.001).

[0174] EXAMPLES OF IMPLEMENTATION The percentages indicated are given by weight of product in relation to the total weight of the composition in the tables below.

[0175] Example 1: Cosmetic composition within the meaning of the invention - O / W emulsion

[0176] A composition according to the invention is described in Table 1. [Table 1]

[0177] Example 2: Cosmetic composition within the meaning of the invention - Gel

[0178] A composition according to the invention is described in Table 2. [Table 2]

[0179] Example 3: In vitro evaluation of the effect of the composition according to the invention on the synthesis of PEDF

[0180] 1. Objective of the study

[0181] The aim of this study is (i) to demonstrate that exposure to UV, particularly UVA, reduces PEDF synthesis; and (ii) to determine the induction capacity of two cosmetic active ingredients, alone or in combination, on PEDF synthesis following its inhibition induced by UVA exposure.

[0182] It should be noted that an inhibitor of the expression of the gene encoding PEDF and / or of the synthesis of PEDF can be used to identify a candidate compound (or active ingredient) capable of inducing a production and / or an increase in the content of PEDF and / or of nucleic acid encoding PEDF. In other words, a candidate compound which induces an increase in the content of PEDF and / or of nucleic acid encoding PEDF, following the step of inhibiting this production, makes it possible to classify the candidate compound (or active ingredient) in the category of compounds, preferably ecobiological, of interest according to the invention, that is to say capable of preventing and / or treating aging and / or cutaneous hypervascularization and / or cutaneous inflammation and / or rosacea, as described above.

[0183] 2. Materials and methods

[0184] 2.1. Cell culture

[0185] Normal Human Fibroblasts (NHF) from Lonza (France) were used in this study. The cells were seeded in 96-well plates at 15,000 cells / well in complete culture medium (DMEM + 10% FCS + 1% penicillin-streptomycin or P / S). After 24 hours of incubation, the cells were pre-incubated with the active ingredients diluted in DMEM + 1% P / S, for 24 hours at 37°C, 5% CO2. Then, the medium was replaced with irradiation medium (HBSS without Ca) and the cultured cells were irradiated with UVA at a surface energy of 30j / cm 2 (750 w / m 2Suntest XLS+, Atlas FRANCE). After irradiation, the cells were incubated for an additional 24 hours with the active ingredients of the invention. The culture supernatants were collected and stored at -80 C before being used for the quantification of PEDF content in the medium by ELISA. An assessment of cell viability was carried out on the cell lawn using the MTT test and with the aim of normalizing the PEDF results to MTT.

[0186] 2.2. Tested assets

[0187] The tested assets are listed in Table 3 below.

[0188] [Table 3]

[0189] 2.3. PEDF synthesis inhibitor tested

[0190] Surprisingly, the Applicant has shown that exposure to UVA makes it possible to inhibit the synthesis of PEDF and / or nucleic acid encoding PEDF (see point 1. above). Consequently, exposure to UVA at a surface energy of 30 J / cm 2at 750 W / m 2 has been applied.

[0191] 2.4. PEDF determination in culture supernatants by ELISA

[0192] The quantification of PEDF in the supernatants is carried out using an ELISA test, Enzyme Linked Immunosorbent Assay (Human Serpin Fl / PEDF DuoSet ELISA, Ref: DY1177-05, R&D systems, France) with the reagents recommended by the manufacturer. The Optical Density (OD) is read with a spectrophotometer at 450 nm. The PEDF concentration is calculated from the standard range (39 pg / ml to 2500 pg / ml) established with the recombinant human PEDF protein. The results are expressed in pg / ml of PEDF per well. On the cell lawn, an MTT viability test is carried out. PEDF assays are used only if cell viability is greater than 80%, and are reported to this cell viability value. 2.5. MTT Cell Viability Test

[0193] The principle of the test is based on the use of a tetrazolium salt, MTT ((3-4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) which is reduced to formazan by a mitochondrial enzyme, succinate dehydrogenase in living cells. The amount of formazan produced is proportional to the metabolic activity of the cells. This insoluble, purple-colored compound must be solubilized with DMSO to allow its spectrophotometric determination at 540 nm.

[0194] 2.6.

[0195] Quantitative analyses are expressed as mean ± standard deviation. Statistical significance is determined by Student's t-test. Differences are considered statistically significant at p<0.05. (NS: p>0.05; *: p<0.05; **: p<0.01; ***: p<0.001).

[0196] 3. Results and conclusions

[0197] The results are shown in Figure 1.

[0198] It appears that:

[0199] - the “untreated, unirradiated” condition represents the percentage of PEDF synthesis in the absence of stress;

[0200] - the “untreated, irradiated” condition arbitrarily represents 100% PEDF synthesis in the presence of stress;

[0201] - PGA, tested at 0.005% and 0.0025%, does not provide any significant protection against UVA stress-induced inhibition of PEDF synthesis, Le., -0.9% and +2% PEDF synthesis for PGA 0.005% and PGA 0.0025%, respectively (% included based on raw data);

[0202] - L-GAEI, tested at 0.0001% and 0.00005%, does not provide any significant protection against UVA stress-induced PEDF synthesis inhibition, Le., -6.5% and +2.5% PEDF synthesis for L-GAEI 0.0001% and L-GAEI 0.00005%, respectively (% included based on raw data);

[0203] - both doses of the PGA + L-GAEI combination resulted in significant protection on PEDF synthesis after UVA stress, Le., +27% and +36% PEDF synthesis for PGA 0.005% + L-GAEI 0.0001% and PGA 0.0025% + L-GAEI 0.00005%, respectively.

[0204] The synergy between 2 active substances (in this case: a polyglutamic acid or one of its salts (Le., PGA) and a peptide derivative represented by the general formula (I) as defined by claim 1 (Le., L-GAEI)) is calculated by comparing the results of tests in which the effectiveness of the 2 substances and that of their mixture are measured. The Colby formula (Tammes, 1964; Schuldt, P. H and Lammont 1962) is then used. If the measured effectiveness of the mixture is higher than that expected according to the Colby formula, there is a synergy. If it is lower, there is an antagonism. And if it is equal, the 2 substances act without interaction between them.

[0205] Colby formula: E = X+Y - (XxY) / 100

[0206] Regarding the condition “PGA (0.005%) and L-GAEI (0.0001%), taken alone or in combination”:

[0207] With X = effect of the compound (or active ingredient) PGA on the synthesis of PEDF at the dose tested (0.005%), i.e., 99.1% synthesis of PEDF

[0208] With Y = effect of the compound (or active ingredient) L-GAEI on the synthesis of PEDF at the dose tested (0.0001%), i.e., 93.5% synthesis of PEDF

[0209] With E = expected efficacy of the active ingredients PGA and L-GAEI at the respective doses of 0.005% and 0.0001%, without synergy = (99.1+93.5) - [(99.1*93.5) / 100] = 99.94%.

[0210] The observed efficiency of the composition is 127%, i.e. well above 99.94% which was the expected efficiency of the composition.

[0211] Regarding the condition “PGA (0.0025%) and L-GAEI (0.00005%), taken alone or in combination”:

[0212] With X = effect of the compound (or active ingredient) PGA on the synthesis of PEDF at the dose tested (0.0025%), i.e., 102% synthesis of PEDF

[0213] With Y = effect of the compound (or active ingredient) L-GAEI on PEDF synthesis at the dose tested (0.00005%), i.e., 102.5% PEDF synthesis

[0214] With E = expected efficacy of the active ingredients PGA and L-GAEI at the respective doses of 0.0025% and 0.00005%, without synergy = (102+102.5) - [(102*102.5) / 100] = 99.95%.

[0215] The observed efficiency of the composition is 136%, i.e. well above 99.95% which was the expected efficiency of the composition.

[0216] These data demonstrate the synergistic effect between the PGA and L-GAEI ingredients in a composition according to the invention.

[0217] At the concentrations tested, the active ingredients PGA and L-GAEI taken alone do not have a significant positive effect on the quantity of PEDF. The combination of these active ingredients PGA and L-GAEI has a significant synergistic effect on the quantity of PEDF and therefore on the expression and / or synthesis of PEDF. BIBLIOGRAPHY

[0218] Belkacemi, L., and Zhang, S.X. (2016). Anti-tumor effects of pigment epithelium-derived factor (PEDF): implication for cancer therapy. A mini-review. J.Exp. Clin. Cancer Res. CR 35, 4.

[0219] Filleur, S., Nelius, T., de Riese, W., and Kennedy, RC (2009). Characterization of PEDF: A multifunctional serpin family protein. J. Cell. Biochem. 106, 769-775.

[0220] Francis, MK, Appel, S., Meyer, C., Balin, SJ, Balin, AK, and Cristofalo, VJ. (2004). Loss of EPC-1 / PEDF expression during skin aging in vivo. J. Invest. Dermatol. 122, 1096-1105.

[0221] Grippo, J.O., Simring, M., Coleman, T.A. (2012). Abfraction, abrasion, biocorrosion, and the enigma of noncarious cervical lesions: a 20-year perspective. J Esthet Restor Dent. 24(1), 10-23.

[0222] Li and Karin (1999). Is NF-kappaB the sensor of oxidative stress? FASEB J. 13(10), 1137-43.

[0223] Limat and Hunziker (2002). Use of epidermal equivalents generated from follicular outer root sheath cells in vitro and for autologous grafting of chronic wounds. Cells Tissues Organs 172(2), 79-85.

[0224] Poumay, Y., Dupont, F., S Marcoux, S., Leclercq-Smekens, M., Hérin, M., Coquette, A. (2004). A simple reconstructed human epidermis: preparation of the culture model and utilization in in vitro studies. Arch Dermatol Res. 296(5), 203-11.

[0225] Tan, K.T., Zheng, G., Hsu, T.T., Wang, Y., Lee, V.W.S., Tian, X., Wang, Y., Cao, Q., Wang, Y., Harris, D.C.H. (2010). Macrophage matrix metalloproteinase-9 mediates epithelial-mesenchymal transition in vitro in murine renal tubular cells. Am. J. Pathol. 176(3), 1256-70.

[0226] Tombran-Tink, J., Lara, N., Apricio, S.E., Potluri, P., Gee, S., Ma, J.-X., Chader, G., and Barnstable, CJ. (2004). Retinoic acid and dexamethasone regulate the expression of PEDF in retinal and endothelial cells. Exp. Eye Res. 78, 945-955.

[0227] Yamagishi, S.I., Inagaki, Y., Nakamura, K., Abe, R., Shimizu, T., Yoshimura, A. Imaizum, T. (2004). Pigment epithelium-derived factor inhibits TNF-a-induced interleukin-6 expression in endothelial cells by suppressing NADPH oxidase-mediated reactive oxygen species generation. J. Mol. Cell. Cardio. 37, 497-506. Yan, B.-X., Zheng, Y.-X., Li, W., Chen, J.-Q., Zhou, J., Cai, S.-Q., Zheng, M., and Man, X.-Y. (2018). Comparative expression of PEDF and VEGF in human epidermal. Discov Med. 25(136):47-56.

[0228] Zamiri, P., Masli, S., Streilein, J.W., and Taylor, A.W. (2006). Pigment epithelial growth factor suppresses inflammation by modulating macrophage activation. Invest. Ophthalmol. Vis. Sci. 47, 3912-3918.

Claims

CLAIMS 1. Topical composition, advantageously ecobiological, comprising: - polyglutamic acid or one of its salts; and - at least one peptide derivative represented by the following general formula (I): in which: - RI represents a hydrogen atom, an acyl or acyloxy radical; and -R2 represents the side chain of an α-amino acid selected from the group consisting of: tryptophan, glutamic acid, arginine, cysteine, methionine, histidine and tyrosine.

2. Composition according to claim 1, characterized in that the polyglutamic acid or one of its salts has a molecular weight (Mw) of between 0.01 kDa and 10 kDa, advantageously between 0.1 kDa and 5 kDa.

3. Composition according to claim 1 or 2, characterized in that the polyglutamic acid or one of its salts is poly-y-glutamic acid, advantageously the potassium salt of poly-y-glutamic acid.

4. Composition according to any one of the preceding claims, characterized in that the at least one peptide derivative is selected from the group consisting of: α-L-glutamyltryptamine, L-tryptophantryptamine and L-methionyltryptamine, advantageously α-L-glutamyltryptamine.

5. Composition according to any one of the preceding claims, characterized in that: - polyglutamic acid or one of its salts corresponds to the following INCI name: polyglutamic acid, sodium polyglutamate, natto gum, or potassium hydrolyzed polygamma glutamate; and / or - the at least one peptide derivative is a-L-glutamyltryptamine corresponding to the CAS number 478273-36-8 ((4S)-4-Amino-5-[[2-(lH-indol-3-yl)ethyl]amino]-5-oxopentanoic acid) and / or the INCI name glutamylamidoethyl indole.

6. Composition according to any one of the preceding claims, characterized in that the mass ratio between the at least one peptide derivative and the polyglutamic acid or one of its salts is between 1:200 and 1:10, advantageously between 1:100 and 1:

30.

7. Composition according to any one of the preceding claims, characterized in that: - polyglutamic acid or one of its salts represents between 0.001% and 10% by total weight of the composition, advantageously between 0.01% and 5%, preferably between 0.1% and 2%; and / or - the at least one peptide derivative represents between 0.00001% and 10% by total weight of the composition, advantageously between 0.0001% and 1%.

8. Non-therapeutic use of the composition according to any one of claims 1 to 7 for combating skin redness and / or skin aging.

9. Composition according to any one of claims 1 to 7 for use in preventing and / or treating: - cutaneous hypervascularization; and / or - skin inflammation; and / or - rosacea.

10. Ex vivo or in vitro method for selecting a compound or a mixture of compounds comprising the following steps: a) measuring the value, called the reference value, of the content of PEDF protein (Pigment Epithelium derived Factor) and / or of nucleic acid encoding PEDF in at least one skin cell and / or in the extracellular space; b) inhibiting the synthesis of PEDF by exposure to ultraviolet (UV) light; c) bringing said compound or mixture of compounds into contact with said skin cell; d) measuring the value, called the “candidate compound” value, of the content of PEDF protein and / or of nucleic acid encoding PEDF in said skin cell and / or in the extracellular space; e) comparing the “candidate compound” value obtained in step d) with the reference value obtained in step a); f) selecting the compound or mixture of compounds when an increase in the content of PEDF and / or nucleic acid encoding PEDF is observed in step e).

11. Method according to claim 10, characterized in that the UV exposure is carried out by: - exposure to UVA, preferably at a surface energy of between 7.5 J / cm 2 and 80 J / cm 2 at 750 W / m 2 ; Or - exposure to the full solar spectrum, preferably at a surface energy of between 7.5 J / cm 2 and 80 J / cm 2 at 750 W / m 2 .

Images