Eco-biological cosmetic composition suitable for reducing the signs of cutaneous ageing

Abstract

The present invention relates to a cosmetic composition, advantageously eco-biological, comprising: at least one bacterioruberin; and at least one active form of proline selected from the group consisting of dipalmitoyl hydroxyproline, hydroxyproline, acetyl proline, amidinoproline, cocoyl proline, dihydroxypropyl proline, proline, N-acetyl-hydroxyproline, and salts thereof.

Description

[0001] DESCRIPTION

[0002] TITLE: ECOBIOLOGICAL COSMETIC COMPOSITION CAPABLE OF LONG-TERM REDUCING THE SIGNS OF SKIN AGING

[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 preventing and / or combating the appearance of signs of skin aging or ensuring or promoting skin regeneration, in particular skin healing.

[0005] STATE OF THE ART

[0006] The skin is the heaviest and largest organ in the human body, composed of three main layers, from the deepest to the most superficial: the hypodermis, the dermis, and the epidermis. This organ constitutes the main barrier that prevents the loss of water by the body and separates the body from the external environment to combat various physical, chemical, and microbial attacks from the surrounding environment.

[0007] The epidermis, in contact with the external environment, is a multi-stratified, keratinized, non-vascularized squamous epithelium; it is mainly composed of layers of keratinocytes which represent 90 to 95% of the epidermal cells; it also contains melanocytes, Langerhans cells and Merkel cells. In this tissue, the extracellular compartment is reduced to the intercellular cement.

[0008] In contrast, the dermis is composed of a small number of cells and a well-developed matrix. Fibroblasts constitute the majority of resident cells in the dermis. They are dispersed throughout the extracellular matrix, a network of polymers predominantly composed of proteins, including collagen and elastin, as well as glycoproteins, proteoglycans (PGs), and glycosaminoglycans (GAGs). The dermis is traversed by a branching network of blood vessels, lymphatic vessels, and nerves that connects the skin to the rest of the body.

[0009] The hypodermis is the deepest and thickest part of the skin (up to 3 cm thick on the abdomen); it is a major area of ​​fatty deposits. The hypodermis separates the skin from the underlying tissues.

[0010] It is known that the signs of skin aging are reflected in changes in the condition of the skin which are essentially due to a slowdown and an imbalance in skin functioning. We thus observe a decrease in the quality of the dermis with a drop in the levels of matrix structural proteins, eg, PG and GAG, accompanied by a loss of consistency of the extracellular matrix; a decrease in the thickness of the epidermis (slowdown of cell renewal or hypoplasia), a decrease in the production of lipids and epidermal structural proteins, an imbalance in desquamation as well as a reduction in the water content of the skin.

[0011] The most obvious manifestations of skin aging, especially on the face, are the formation of wrinkles and fine lines, the appearance of pigment spots, and the loss of radiance and density of the skin.

[0012] A solution currently proposed to mask superficial skin defects is the use of fillers or so-called "blurring" agents such as talc, starch, mica, silica, poly-beta-alanine, sericite, brown iron oxide or titanium dioxide. However, these compounds, which are generally in powder form, will only provide a visual correction of surface defects (e.g., wrinkles, fine lines or even dilated pores), via an optical / visual smoothing effect of the skin surface with light diffusing agents whose sole role is to fill in relief defects. Thus, the skin is visually unified, mattified and the appearance of wrinkles / fine lines and dilated pores is reduced by a process corresponding to "camouflage". This solution is not sustainable, particularly because these compounds tend to migrate into wrinkles during the day, but also because of makeup removal at the end of the day.

[0013] Another approach is to apply cosmetic compositions capable of biologically combating skin aging, promoting the regeneration of skin cells, and therefore likely to also help the healing of damaged skin, particularly in the elderly. These different applications are generally grouped under the "anti-aging" indication. Examples include the products "Repaskin Suncare Gel" from Sesderma®, "Night Line Smoothing Cream for Combination Oily to Oily Skin" marketed by Clinique, "High Performance Anti-Aging Cream" from the company NY Derm, or "DNA Repair C Serum" marketed by Osmosis.In parallel, document US 8,529,925 describes a cosmetic composition comprising a combination of topical anti-aging ingredients that are microencapsulated, document US 2016 / 256375 describes a cosmetic product having DNA repair properties that have suffered damage caused by exposure to UV radiation, document EP 1 640041 describes a cosmetic or dermatological topical composition comprising at least one agent stimulating collagen synthesis, and at least one active substance that increases and / or improves the interaction between the extracellular matrix and fibroblasts. In these products, active ingredients are integrated to directly or indirectly stimulate the growth of fibroblasts, strengthen the dermo-epidermal junction, combat oxidative stress or promote the production of structural proteins and glycans and thereby promote the regeneration and repair of the skin.

[0014] Among the prior art solutions, many compounds are not free from deleterious side effects. For example, retinoids are described for their ability to stimulate fibroblast growth. However, their use is not recommended in cosmetics due to their phototoxic and potentially mutagenic action (Mei et al., 2005).

[0015] Furthermore, in the majority of cases, so-called anti-aging cosmetic compositions have a rapid positive effect on the signs of skin aging, often linked to the improvement of skin hydration. However, the long-term benefits of applying these anti-aging compositions are negligible. It is clear from the above that there remains a need to offer an effective anti-aging solution that offers long-term beneficial effects.

[0016] Prior art solutions that offer long-term effects are invasive solutions such as dermabrasion, filler or botulinum toxin injections, laser treatment or other forms of cosmetic surgery. These solutions allow for a more lasting reduction in the signs of skin aging but present significant risks to human health.

[0017] There is therefore a clear need to develop, in particular according to the principles of ecobiology, non-pharmaceutical cosmetic compositions, in particular ecobiological ones, which make it possible to fight effectively and sustainably ( / .e., in the long term) against skin aging and the appearance of its signs, and which make it possible to promote skin regeneration, in particular healing, especially of aged skin.

[0018] DETAILED DESCRIPTION OF THE INVENTION

[0019] Surprisingly, the Applicant, continuing its ecobiological approach to action on the cause of skin disorders, has found that a combination of compounds, safe and suitable for human cosmetic use, act in synergy to meet these needs.

[0020] More specifically, the Applicant has found that the combination of particular compounds (also called active ingredients) makes it possible to synergistically increase the expression of the “Heparin-Binding Epidermal Growth factor” (HBEGF) receptor, a constituent of the hyalurosome (Barnes et al. 2010) known to stimulate the proliferation of keratinocytes (Kaya et al., 2006) and necessary for proper wound healing (Thônes et al., 2019). Thus, a first subject of the present invention relates to a cosmetic composition, advantageously ecobiological, comprising:

[0021] -at least one bacterioruberin;

[0022] -at least one active form of proline selected from the group consisting of dipalmitoyl hydroxyproline, hydroxyproline, acetyl proline, amidinoproline, cocoyl proline, dihydroxypropyl proline, proline, N-acetylhydroxyproline, and their salts.

[0023] The present invention offers various advantages, including effectively preventing and / or combating the signs of skin aging, in particular stimulating the growth and proliferation of fibroblasts, strengthening the dermo-epidermal junction, combating oxidative stress or promoting the production of structural proteins and glycans. In addition, the present invention promotes skin regeneration and repair, particularly in the context of dermatoporosis. The various effects of the composition of the invention are visible quickly and are prolonged over time. In other words, the invention is effective in the short, medium and long term. In addition, regular application of the composition of the invention, e.g., 1 or 2 times a day, improves its beneficial effects.

[0024] In the context of the invention, the term "bacterioruberin" designates a molecule of the bacterioruberin family which are C50 carotenoids characteristic of extremophile bacteria, in particular halophilic archaea and certain psychrophilic actinobacteria; as well as derivatives of said carotenoids, in particular glycosylated derivatives; bacterioruberins are present in various forms, the best known of which is α-bacterioruberin, which has the following structure (CAS No. 32719-43-0):

[0025] [Chem 1]

[0026] In the context of the invention, the expressions "glycosylated bacterioruberin" or "glycosylated form of bacterioruberin" and "bacterioruberin in a glycosylated form" are used interchangeably and designate a bacterioruberin in which at least one hydroxyl group is substituted with one or more, for example 2 or 3, or even 4 sugar residues by means of an ether bond between the backbone of the bacterioruberin and the sugar. The bacterioruberins comprise 4 terminal hydroxyl groups, each of which is capable of being substituted by an ether bond with a sugar group, or even one or more covalently linked sugars. For example, a "glycosylated bacterioruberin" within the meaning of the invention corresponds to the following structure:

[0027] [Chem 2]

[0028] Wherein R is independently selected from a hydrogen atom and a sugar residue and where R at least one occurrence represents a sugar residue.

[0029] In practice, glycosylated or non-glycosylated bacterioruberins can be obtained by extraction and purification, for example by chromatography, of total extracts of carotenoids of actinobacteria of the genera Micrococcus or Arthrobacter, advantageously the species A. agilis and / or M. roseus. The species A. agilis is also known under the name Micrococcus agilis. Thus the extracts and strains described in the documents Strand et al., 1997, Fong et al., 2001 and in the document WO 2014 / 167247 can be used as sources of glycosylated bacterioruberins. Preferably, the strains of A. agilis used as sources of glycosylated bacterioruberins within the meaning of the invention are strain MB813 (described in Fong et al., 2001), NP20 (described in Noby et al. 2023) and / or SB5 (described in document WO2014 / 167247).The methods for obtaining total carotenoid extracts from these bacterial species are known to those skilled in the art and are, for example, described in the documents Strand et al., 1997, Fong et al., 2001 and WO2014 / 167247.

[0030] In the context of the invention, the expressions "active form of proline" and "proline in active form" are used interchangeably and designate proline (L-proline or D-proline, advantageously L-proline), which is an essential amino acid found in all organisms and in animals and which is a constituent of collagen, this particular amino acid is in an active form, that is to say a form capable of exerting a biological action when this proline is administered to a subject, in particular a human.

[0031] In the context of the invention, "ecobiological" means respectful of the person, their interactions with the world and the planet. The expression "ecobiological approach" designates the particular approach initiated and developed by the inventor which combines skin biology and ecology in particular to help the skin live according to its natural biology, over the long term.

[0032] In the context of the invention, the expression "signs of skin aging" designates the appearance of wrinkles and fine lines, loss of firmness, density and / or volume of the skin, the appearance of pigment spots, loss of radiance of the skin, a change in the texture of the skin (it becomes rougher), sagging of the oval of the face, an uneven complexion, very visible pores and / or dry skin.

[0033] For the purposes of the invention, the terms "healing" and "heal" are used interchangeably and refer to the different phases of the process by which tissue damage is repaired, or the integrity of damaged tissue is restored, following injury. The different stages of this process are:

[0034] - an inflammatory phase: phagocytosis and elimination of bacteria and other dirt and the factors that produce the migration and division of cells that participate in the proliferative phase are released;

[0035] - a proliferative phase: angiogenesis, increase in collagen content, formation of granular tissue, epithelialization and contraction of the wound; and

[0036] - a maturation and remodeling phase: collagen is remodeled and realigned along the lines of tension and cells that are no longer needed are eliminated by apoptosis.

[0037] In the context of the invention, the expression "active ingredient" designates a compound which has biological and / or therapeutic properties which underlie a physiological effect. The active ingredient is to be distinguished from an excipient, present in the composition according to the invention.

[0038] In the context of the invention, the term “excipient” designates a compound other than an active ingredient which gives the composition properties, in particular, of consistency, galenic and / or vectorization of the active ingredient.

[0039] In the context of the invention, the expressions "composition for cutaneous application" and "for topical use" are used interchangeably and designate a composition compatible with application to the skin, mucous membranes, hair and / or scalp, preferably human skin.

[0040] In the context of the invention, the expressions “so-called “blurring agent”, “soft-focus particle” and “blurring particle” are used interchangeably and designate a particle, advantageously colored, intended to give more transparency to the complexion and a blurring effect. In particular, the blurring particle allows the composition containing it to attenuate, by optical effect, the skin microrelief, and in particular skin defects such as spots, wrinkles, fine lines.

[0041] In the context of the invention, the expressions “moisturizing compound”, “moisturizing active”, “moisturizing agent” and “moisturizer” are used interchangeably and designate an active ingredient / compound capable of improving the hydration state of the skin. This hydration state can be measured by means known to those skilled in the art, for example, by corneometric analysis.

[0042] Preferably, the subject of the present invention is a cosmetic composition, preferably ecobiological, as defined above and having the following technical characteristics, taken alone or in combinations:

[0043] - the at least one active form of proline is selected from the group consisting of dipalmitoyl hydroxyproline, hydroxyproline and their salts;

[0044] - the at least one active form of proline represents between 0.001% and 10% by total weight of the composition, advantageously between 0.01% and 5%, preferably between 0.1% and 2%;

[0045] - the at least one bacterioruberin represents between 0.00001% and 5% by total weight of the composition, advantageously between 0.0001% and 1%;

[0046] - at least one bacterioruberin is derived from a bacterial extract;

[0047] - at least one bacterioruberin is in glycosylated form;

[0048] - at least one bacterioruberin is chemically synthesized;

[0049] - the composition further comprises at least two bacterioruberins, advantageously different;

[0050] - one of the at least two bacterioruberins is in a glycosylated form;

[0051] - the at least two bacterioruberins represent between 0.00001% and 5% by total weight of the composition, advantageously between 0.0001% and 1%;

[0052] - the at least two bacterioruberins are derived from a bacterial extract;

[0053] - the at least two bacterioruberins come from the same bacterial extract;

[0054] - the at least two bacterioruberins are chemically synthesized;

[0055] - the bacterial extract is an extract of Micrococcus agilis;

[0056] - the ratio between at least one bacterioruberin and at least one active form of proline is between 1 / 10000 and 1 / 1;

[0057] - the ratio between the at least two bacterioruberins and the at least one active form of proline is between 1 / 10000 and 1 / 1;

[0058] - at least one bacterioruberin corresponds to the INCI designation Micrococcus lysate;

[0059] - the at least two bacterioruberins correspond to the INCI designation Micrococcus lysate;

[0060] - the at least one bacterioruberin is an a-bacterioruberin; - the at least one bacterioruberin corresponds to the INCI designation Halobacterium salinarum carotenoids;

[0061] - at least one bacterioruberin corresponds to the raw material HALORUBINE marketed by the company HALOTEK GMBH;

[0062] - the at least two bacterioruberins, glycosylated or not, correspond to the INCI designation Micrococcus lysate;

[0063] - the at least two bacterioruberins, glycosylated or not, correspond to the INCI designation CAPRYLIC / CAPRIC TRIGLYCERIDE & MICROCOCCUS LYSATE & TOCOPHEROL;

[0064] - at least one bacterioruberin corresponds to the raw material MIRORUBERINE marketed by the company GREENTECH;

[0065] - the at least two bacterioruberins, glycosylated or not, correspond to the raw material MIRORUBERINE marketed by the company GREENTECH;

[0066] - at least one active form of proline corresponds to the materials ORISTAR HPRO and ORISTAR PRO marketed by the company ORIENT STARS LLC and corresponds respectively to the INCI designations hydroxyproline and proline;

[0067] - at least one active form of proline corresponds to the raw material NATISOL marketed by the company SINERGA SPA and corresponds to the INCI designation cocoyl proline;

[0068] - at least one active form of proline corresponds to the raw material N-ACETYL-L-PROLINE marketed by the company NARIS COSMETICS CO., LTD and corresponding to the INCI designation acetyl proline;

[0069] - the at least one active form of proline is dipalmitoyl hydroxyproline (CAS No. 41672-81-5) which is a lipophilic N-acylated derivative of the amino acid hydroxyproline whose purity is advantageously greater than 90%, even more advantageously greater than 95%, or even 98%, corresponding to the crystalline raw material DIPALMITOYL HYDROXYPROLINE marketed by the company SEPPIC under the name SEPILIFT DPHP™;

[0070] - the composition is in a form suitable for topical application, in particular to the skin, mucous membranes, hair and / or scalp, preferably of a human subject;

[0071] - the composition is ecobiological;

[0072] - the composition is in the form of an aqueous, hydroalcoholic, organic or oily solution; a suspension or dispersion in solvents or fatty substances, of a lotion or serum type; 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 according to the invention may also be in the form of an ointment, gel, solid stick, pasty or solid anhydrous products, a foam, in particular an aerosol, a two-phase composition or a sprayable composition - the composition further comprises at least one particle, advantageously colored, more advantageously with a blurring effect;

[0073] - the at least one particle represents between 0.5% and 20% by total weight of the composition, advantageously between 1% and 10%, preferably between 1% and 5%;

[0074] - at least one particle is chosen from the raw materials of the Ronasphere range (MERCK) based on silica substrate, in particular RONASPHERE FLAWLESS, as well as several raw materials marketed by the companies JGC-C&C (COVERLEAF range based on sericite or sericite / talc substrate), NIHON KOKEN (RELIEF COLOR range, SILSEEM based on mica / silica substrate), or MIYOSHI KASEI (PC-BAIL range based on silica substrate);

[0075] - the at least one particle is a composite particle comprising sericite, brown iron oxide, titanium dioxide and silica. Such particles are marketed for example under the references COVERLEAF NS or JS or MF by the company CHEMICALS AND CATALYSTS;

[0076] - the at least one particle has a structure which is of the silica microsphere type containing iron oxide, such as that marketed by the company MIYOSHI under the reference PC BALL PC-LL-100 P, this pigment being made up of silica microspheres containing yellow iron oxide;

[0077] - the at least one particle corresponds to a composite particle having a sericite / brown iron oxide / titanium dioxide / silica type structure such as that marketed under the reference COVERLEAF MF by the company CHEMICALS AND CATALYSTS. Alternatively, it may be cellulose derivatives, such as CELLULOBEADS D-5 marketed by the company DAITO KASEI;

[0078] - at least one particle corresponds to the raw material COVAMED PMMA 2 MUSI marketed by the company SENSIENT COSMETICS TECHNOLOGY and corresponding to the INCI designations Methyl methacrylate crosspolymer and Silica; and / or

[0079] - at least one particle corresponds to the raw material KSP-100 marketed by the company SHINETSU corresponding to the INCI designation Vinyl dimethicone / methicone silsesquioxane crosspolymer;

[0080] - at least one particle corresponds to the raw material D-400 marketed by the company TOCHI corresponding to the INCI designations HDI / trimethylol hexyllactone crosspolymer and Silica.

[0081] According to a particular aspect, the composition of the invention further comprises an aqueous base having a defined composition and containing in particular: calcium chloride; potassium chloride; potassium phosphate; magnesium sulfate; sodium chloride; sodium hydrogen carbonate; sodium hydrogen phosphate; sodium citrate; citric acid; carnosine and hypotaurine (2-aminoethanesulfinic acid). Preferably, said aqueous base comprises:

[0082] - From 0.000001% to 0.1% by total weight of the aqueous calcium chloride base, advantageously from 0.0001% to 0.1%; - From 0.0001% to 0.1% by total weight of the aqueous potassium chloride base, advantageously from 0.001% to 0.1%;

[0083] - From 0.00001% to 0.1% by total weight of the aqueous potassium phosphate base, advantageously from 0.0001% to 0.1%;

[0084] - From 0.0001% to 0.1% by total weight of the aqueous base of magnesium sulfate, advantageously from 0.001% to 0.1%;

[0085] - From 0.001 to 4% by total weight of the aqueous sodium chloride base, advantageously from 0.1 to 4%;

[0086] - From 0.0001 to 0.1% by total weight of the aqueous sodium hydrogen carbonate base;

[0087] - From 0.0001% to 0.1% by total weight of the aqueous base of sodium hydrogen phosphate;

[0088] - From 0.0001% to 1% by total weight of the aqueous citric acid base, advantageously from 0.001% to 1%;

[0089] - From 0.001% to 1% by total weight of the aqueous sodium citrate base;

[0090] - From 0.0001% to 1% by total weight of the aqueous carnosine base, advantageously from 0.001% to 1%;

[0091] - From 0.0001 to 1% by total weight of the aqueous base of 2-aminoethanesulfinic acid, advantageously from 0.001 to 1%.

[0092] According to another particular aspect, the composition of 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. In practice, the combination of these active ingredients makes it possible to catalyze the metabolic activity of skin cells while obtaining a dermocosmetic or therapeutic effect thanks to the use of the biomimetic peptides. In practice, in the bioactive system according to the invention, the nucleotide represents at most 10% by weight of the composition, preferably between 0.001% and 5%; and the biomimetic peptide represents between 0.001% to 1% by weight of the composition.

[0093] According to another particular aspect, the composition of the invention further comprises peptide extracts of soybean and / or wheat. In practice, the peptide extracts originating from soybean and wheat seeds are derived from an enzymatic hydrolysis of said seeds via peptidases which makes it possible to recover peptides with an average size of 700 Daltons. Preferably, the soybean peptide extract is the extract identified under CAS number 68607-88-5, just as the wheat peptide extract is the extract identified under CAS number 70084-87-6. The wheat and soybean extracts may correspond to the INCI designations Hydrolyzed wheat protein and Hydrolyzed soy protein, respectively. In a particular embodiment, the soy and wheat peptide extracts are used together, for example in a weight ratio respectively between 80 / 20 and 20 / 80, advantageously between 70 / 30 and 30 / 70, preferably equal to 60 / 40.In an advantageous embodiment, the soy and / or wheat peptide extracts are free of synthetic GHK tripeptides (glycyl-histidyl-lysine; INCI: Tripeptide-1). In practice, the soy and / or wheat peptide extracts represent between 0.01% and 20% by weight of the composition, advantageously between 0.1% and 10%, preferably between 0.2% and 0.7%.

[0094] The galenic form of the composition and its method of preparation, and consequently the excipients suitable for the composition of the invention, may 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 may comprise any fatty substance usually used in the cosmetic field. Mention may in particular be made of silicone fatty substances such as silicone oils, gums and waxes, as well as non-silicone fatty substances such as oils and waxes of vegetable, mineral, animal and / or synthetic origin. The oils may be volatile or non-volatile. Mention may also be made of hydrocarbons, synthetic esters and ethers, fatty alcohols and fatty acids.The composition may 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 Cl-6 alcohols, in particular ethanol and isopropanol, glycols such as propylene glycol, ketones.

[0095] The composition may comprise at least one conventional emulsifier, chosen from amphoteric, anionic, cationic or non-ionic emulsifiers, used alone or as a mixture.

[0096] It may also include the usual adjuvants in the field in question, such as hydrophilic or lipophilic thickeners or gelling agents, hydrophilic or lipophilic additives, active ingredients, particularly cosmetic ones, preservatives, antioxidants, perfumes, fillers, pigments, UV filters, odor absorbers, colorants, moisturizers (glycerin), vitamins, essential fatty acids, liposoluble polymers, particularly hydrocarbon polymers, opacifiers, stabilizers, sequestrants, conditioners and propellants.

[0097] 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.

[0098] 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. Another subject of the present invention also relates to the cosmetic use of the composition as described above, for preventing and / or treating the appearance of signs of skin aging, advantageously for preventing and / or combating skin aging and / or the appearance of wrinkles and fine lines and / or for inducing the synthesis of compounds constituting the extracellular matrix, advantageously proteoglycans (PG), glycosaminoglycans (GAG) or collagen.

[0099] Another object of the present invention also relates to the cosmetic use of the composition as described above, to stimulate the growth and proliferation ( / .e., hyperplasia) of fibroblasts, strengthen the dermo-epidermal junction, and / or combat oxidative stress.

[0100] Another object of the present invention also relates to the cosmetic use of the composition as described above, for preventing and / or treating dermatoporosis.

[0101] Another subject of the present invention also relates to the cosmetic use of the composition as described above, for regenerating the skin, advantageously for promoting the healing of the skin, 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.

[0102] Another subject of the present invention also relates to the composition as described above for use in preventing and / or treating the appearance of signs of skin aging, advantageously in preventing and / or combating skin aging and / or the appearance of wrinkles and fine lines and / or in inducing the synthesis of compounds constituting the extracellular matrix, advantageously proteoglycans (PG), glycosaminoglycans (GAG) or collagen.

[0103] Another object of the present invention also relates to the composition as described above for use in stimulating the growth and proliferation ( / .e., hyperplasia) of fibroblasts, strengthening the dermo-epidermal junction, and / or combating oxidative stress.

[0104] Another object of the present invention also relates to the composition as described above for use in preventing and / or treating dermatoporosis.

[0105] Another subject of the present invention also relates to the composition as described above for its use in a method for regenerating the skin, advantageously for promoting the healing of the skin, 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.

[0106] Another subject of the present invention relates to a method for the cosmetic, non-therapeutic treatment of the skin, in particular of a human subject, intended to prevent and / or treat the appearance of signs of skin aging, advantageously to prevent and / or combat skin aging and / or the appearance of wrinkles and fine lines and / or to induce the synthesis of compounds constituting the extracellular matrix, advantageously proteoglycans (PG), glycosaminoglycans (GAG) or collagen, to stimulate the growth and proliferation ( / .e., hyperplasia) of fibroblasts, strengthen the dermo-epidermal junction, and / or combat oxidative stress.

[0107] Another subject of the present invention relates to a method for the cosmetic, non-therapeutic treatment of the skin, in particular of a human subject, intended to prevent and / or treat dermatoporosis.

[0108] Another subject of the present invention relates to a method for the cosmetic, non-therapeutic treatment of the skin, in particular of a human subject, intended to regenerate the skin, advantageously promoting the healing of the skin, 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.

[0109] Any of the cosmetic, non-therapeutic skin treatment methods, as described above, comprises a step of applying the composition of the invention to the skin at least once, advantageously twice, per day for a period of at least one month, advantageously 2 months, or even 3 months, even more advantageously 6 months.

[0110] Another subject of the present invention relates to a kit comprising a moisturizing active compound and a composition according to the invention.

[0111] In particular, the moisturizing compound and the composition of the invention are in the form of a combined preparation intended for simultaneous, separate or sequential use for:

[0112] Prevent and / or treat the appearance of signs of skin aging, advantageously to prevent and / or combat skin aging and / or the appearance of wrinkles and fine lines and / or to induce the synthesis of compounds constituting the extracellular matrix, advantageously proteoglycans (PG), glycosaminoglycans (GAG) or collagen, to stimulate the growth and proliferation ( / .e., hyperplasia) of fibroblasts, strengthen the dermo-epidermal junction, and / or combat oxidative stress;

[0113] Prevent and / or treat dermatoporosis; and / or

[0114] Regenerate the skin, advantageously 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.

[0115] The manner in which the invention can be implemented and the advantages which result therefrom will become more apparent from the following examples of implementation, given for informational and non-limiting purposes, in support of the appended figure.

[0116] Figures

[0117] [Fig. 1]: Evaluation of the synergistic effect of the composition according to the invention on the expression of the HBEGF gene in human dermal fibroblasts. The results are from an experiment with 3 replicates per condition. Statistics: t-test, unpaired, bilateral; *: 0.05 < p-value (or p-value or p) < 0.01.

[0118] EXAMPLES OF ACHIEVEMENT

[0119] The percentages indicated are given by weight of product relative to the total weight of the composition in the tables below.

[0120] Example 1: Cosmetic composition within the meaning of the invention - Day face serum

[0121] A composition according to the invention is described in Table 1.

[0122] [Table 1]

[0123] Example 2: Cosmetic composition within the meaning of the invention - Body cream

[0124] A composition according to the invention is described in Table 2.

[0125] [Table 2] Example 3: Study of the effect of the active ingredients according to the invention on the expression of the HBEGF gene

[0126] 1. Objective of the study

[0127] The objective of the study was to evaluate the effect of the active ingredients according to the invention on the expression of the HBEGF gene.

[0128] 2. Materials and methods

[0129] 2.1. Biological models Normal human dermal fibroblasts (NHDF).

[0130] - Cell type: NHDF, Bioalternatives PF2 reference used in the 8th passage.

[0131] - Cultivation conditions: 37°C, 5% CO2.

[0132] - Culture medium: DMEM optimized for the test, supplemented with 10% fetal calf serum (FCS).

[0133] - Test medium: DMEM optimized for the test, supplemented with 1% FCS. 2.2. Active ingredients tested

[0134] The compounds / active agents according to the invention tested are described in Table 3. [Table 3]

[0135] The active ingredients were solubilized in a mixture of DMSO and ethanol whose concentration in the samples was: 0.06% DMSO and 0.012% ethanol (% by total weight). The concentrations of the active ingredients to be tested were chosen on the basis of results of cell viability tests (MTT tests) and were non-cytotoxic under the analysis conditions.

[0136] 2.3. Gene expression profile in NHDF a) Culture and treatment

[0137] Fibroblasts were seeded in 24-well plates and cultured for 24 hours in culture medium and in test medium for another 24 hours. The medium was then replaced with test medium containing or not (control) the compounds, combinations, solvent control (DMSO + 0.06% Ethanol + 0.012%, by total weight) or reference (TGF-P at 10 ng / ml) and the cells were incubated for 24 hours. All experimental conditions were performed in n=3. At the end of the incubation, the cells were washed in phosphate-buffered saline (PBS) and immediately frozen at 80°C. b) Differential gene expression analysis

[0138] Marker expression was analyzed by RT-qPCR method on total RNA extracted from cell monolayers of each experimental condition. Transcript analysis was performed in n=2 using a PCR matrix (“MV220909 - mQPA 16 customized”) dedicated to research and adapted to the 'screening' format (Marker qPCR array or “mQPA”) and also targeting the HBEGF gene. c). RNA extraction and reverse transcription

[0139] Total RNA was extracted from each sample using TriPure Isolation Reagent™ according to the supplier's instructions. RNA quality was assessed by capillary electrophoresis (Bioanalyzer 2100, Agilent Technologies). RNA quantity was assessed using a spectrophotometer (Synergy HI, BioTek Instruments).

[0140] Complementary DNA (cDNA) was synthesized by reverse transcription of total RNA in the presence of oligo(dT) and Transcriptor Reverse Transcriptase (Roche). The cDNA quantities were then adjusted before the PCR step. d) Quantitative PCR

[0141] Fluorescence incorporation into the amplified DNA was continuously measured during PCR cycles. This resulted in a plot of fluorescence intensity versus PCR cycle allowing the assessment of a relative expression (RE) value for each marker. The “control” condition corresponds to the DMSO solvent control used to solubilize the actives (i.e., a solution of 0.06% DMSO and 0.012% ethanol, % by total weight).

[0142] The value selected for calculating ER is the "output point" (Ct) of the fluorescence curve. For a given marker, the highest value is the number of cycles; the lowest is the amount of mRNA.

[0143] The RE value was calculated with the formula: (l / 2number of cycles) x 106.

[0144] The PCR template used in the present study included a reference gene (GAPDH). This reference gene was used for data normalization because its expression is constitutive and theoretically stable. Therefore, the expression level of the target markers was compared to the expression level of this marker for all test conditions. PCRs (Polymerase Chain Reaction) were performed using the "LightCycler™" system (Roche Molecular System Inc.) according to the supplier's instructions.

[0145] The reaction mixture (10 µl final) was prepared as follows:

[0146] - 2.5 μl of cDNA,

[0147] - primers (sense and antisense);

[0148] - reagent mix (Ozyme) containing taq DNA polymerase, SYBR Green I and MgCL. e) Data analysis and processing

[0149] Data were analyzed and processed using Microsoft Excel. Significance was determined using a two-tailed, unpaired t-test. Differences are considered statistically significant at p<0.05. (NS: p>0.05; *: p<0.05; **: p<0.01; ***: p<0.001).

[0150] 3 Results and conclusions

[0151] The data are represented in Figure 1.

[0152] The synergy between two active substances [in this case: bacterioruberins (INCI - Micrococcus lysate) and an active form of proline (DPHP)] is calculated by comparing the results of tests in which the effectiveness of the two substances and that of their mixture is measured. The Colby formula (Tammes, 1964; Schuldt, P. H and Lammont 1962) is then used.

[0153] If the measured effectiveness of the mixture is higher than that expected according to Colby's formula, there is synergy. If it is lower, there is antagonism. And if it is equal, the two substances act without interaction between them.

[0154] Colby formula: E = X+Y - (XxY) / 100

[0155] With X = effect of the active ingredient bacterioruberins on the expression of the gene coding for HBEGF at the dose tested (0.823 pg / L), / .e., 120% relative expression of the HBEGF gene

[0156] With Y = effect of the active ingredient DPHP on the expression of the gene encoding HBEGF at the dose tested (1.37 mg / L), / .e., 130% relative expression of the HBEGF gene

[0157] With E = expected efficacy of the active ingredients bacterioruberins and DPHP at the respective doses of 0.823 pg / L and 1.37 mg / L, without synergy = (120+130) - [(120*130) / 100] = 94%.

[0158] The observed efficacy of the composition is 180%, / .e. well above 94% which was the expected efficacy of the composition.

[0159] These data demonstrate the synergistic effect between the bacterioruberin and DPHP ingredients in a composition according to the invention.

[0160] At the tested concentration, the bacterioruberin active ingredient, which is a bacterial extract containing bacterioruberins in glycosylated or non-glycosylated form, has no significant positive effect on the expression of the HBEGF gene. The DPHP (dipalmitoyl hydroxyproline) active ingredient significantly induces the expression of the HBEGF gene compared to the control. The combination of the bacterioruberin active ingredient and the DPHP active ingredient has a significant synergistic effect on the expression of the HBEGF gene. BIBLIOGRAPHY

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Claims

CLAIMS 1. Cosmetic composition, advantageously ecobiological, comprising: -at least one bacterioruberin; -at least one active form of proline selected from the group consisting of dipalmitoyl hydroxyproline, hydroxyproline, acetyl proline, amidinoproline, cocoyl proline, dihydroxypropyl proline, proline, N-acetylhydroxyproline and their salts.

2. Composition according to claim 1, characterized in that the at least one active form of proline, advantageously dipalmitoyl hydroxyproline, hydroxyproline or one of their 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%.

3. Composition according to one of the preceding claims, characterized in that it comprises at least two bacterioruberins, advantageously different, more advantageously one of the at least two bacterioruberins being in a glycosylated form.

4. Composition according to any one of the preceding claims, characterized in that the at least one bacterioruberin or the at least two bacterioruberins represent between 0.00001% and 5% by total weight of the composition, advantageously between 0.0001% and 1%.

5. Composition according to any one of the preceding claims, characterized in that the at least one bacterioruberin or the at least two bacterioruberins are derived from a bacterial extract, advantageously from the same bacterial extract.

6. Composition according to claim 5, characterized in that the bacterial extract is an extract of Micrococcus agilis.

7. Composition according to any one of the preceding claims, characterized in that the at least one bacterioruberin or the at least two bacterioruberins correspond to the INCI designation Micrococcus lysate.

8. Composition according to any one of the preceding claims, characterized in that the at least one bacterioruberin or the at least two bacterioruberins correspond to the INCI designation Micrococcus lysate; and in that the at least one active form of proline corresponds to the INCI designation Dipalmitoyl hydroxyproline.

9. Composition according to any one of the preceding claims for its use in a method for regenerating the skin, advantageously for promoting the healing of the skin.

10. Method for cosmetic and non-therapeutic treatment of the skin, in particular human skin, intended to prevent and / or treat the cutaneous signs of aging, in particular wrinkles, comprising at least the application to the skin of a cosmetic composition according to claim 1 to 8.

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