FR2849377A1 - Cosmetic or dermatological skin-treatment composition, useful e.g. for regulating the skin flora, comprises a complex of a specific peptide or protein with a nucleotide or nucleic acid - Google Patents

Abstract

Cosmetic and/or dermo-cosmetic composition (A) contains an active complex (I), between at least one specific peptide and/or protein (Ia) and at least one (poly)nucleotide and/or nucleic acid (Ib). Cosmetic and/or dermo-cosmetic composition (A) contains an active complex (I), between at least one specific polypeptide and/or protein (Ia) and at least one (poly)nucleotide and/or nucleic acid (Ib). (Ia) is nisin, N-acetylglucosamine (sic) or bactinecine (i.e. Arg-Leu-Cys-Arg-Ile-Val-Val-Ile-Arg-Val-Cys-Arg). (Ib) is adenosine (A), guanosine (G), cytosine (C), uridine (U) or thymidine (T) monophosphates; deoxy forms of T, A or C monophosphates; A, G, U or T triphosphates; GP4G; IP3; hydrolyzates of DNA and/or RNA; UDP-glucose-galactose or UDP-N-acetyl glucosamine; G diphosphate-mannose, or C monophosphate-N-acetylneuraminic acid.

Description

i

  The present invention relates to compositions for topical use, intended for the surface or systemic treatment of the surface parts of the human or animal body, for example of the skin.

  The skin constitutes the covering envelope of the body, protecting it from external aggressions. In addition to its physical characteristics, the skin is composed of various chemical compounds, among which: - water which constitutes approximately 70% of the composition of the skin; its distribution varies according to the different skin layers, the hypodermis being the most hydrated; - mineral salts among which a distinction is made between metal salts and metallode salts; - proteins comprising amino acids such as tyrosine, cystine, hydroxyproline, valine, and proteins such as collagens, elastin, keratin, but also enzymes, and hormones; - nucleic acids, namely DNA and / or RNA; - lipids grouping sphingolipids, cholesterol, fatty acids, triglycerides and prostaglandins; - carbohydrates, etc .; Most of these substances or compounds, as well as many more complex ones, form the surface skin film, or hydrolipidic film, defined as a water-in-oil emulsion covering the stratum corneum.

  The role of this film is to maintain the hydration of the stratum corneum, maintain skin acidity, and play a role of barrier against external aggressions and pathogens.

  On the surface, the skin is made up of the epidermis which is a stratified epithelial tissue, that is to say a set of cells which are similar to each other united to perform the same function; in the intermediate layer it consists of the dermis, connective tissue, and in the deep layer of the hypodermis, adipose connective tissue.

  The epidermis is a skin covering epithelium whose main function is to protect; it consists of four types of cells, Langerhans cells, Merckel cells, melanocytes, keratinocytes. The keratinocytes, the most numerous epidermal cells play an essential role in the phenomenon of keratinization of the epidermis, they are distributed over six layers of which the three closest to the surface of the skin are, the stratum lucidum, the stratum cornea and the stratum 5 disjunctum, which form the surface envelope in which the majority of cosmetic and or dermatological products exercise their activity.

  We classically assign three roles to this stratum corneum, including a metabolic role, the other two roles being thermal regulation and the protection of internal organs.

  The epidermis, like all other tissues, has all of the enzymatic systems necessary for maintaining cellular activities, such as, for example, basic metabolism, respiration and cell division.

  These enzymatic systems participate in the development of the main function, that is to say, to establish a barrier to protect the skin from environmental damage, and this function is largely performed by the stratum corneum. The epidermis must also protect the body from ultraviolet radiation, and this function is performed by the pigment system.

  Enzymes are protein macromolecules, acting as biochemical catalysts, their main properties being to accelerate the reactions of the living world. Most of the enzymes contained in the stratum corneum catalyze degradations, they are mainly hydrolases. But if the skin constitutes a very effective barrier, it can however be crossed by small quantities of lipophilic substances, capable of penetrating into the horny layers; depending on their hydrophilicity, these substances may diffuse more deeply and thus have systemic activity.

  The mechanisms of penetration of active ingredients at different levels of the skin are very complex, they however depend on the physicochemical properties of the active ingredients and the excipients used in the formulations, the state of the skin and the mode of application.

  The present invention proceeds from the following inventive concept.

  The answer to different skin dysfunctions is found in the skin itself. The skin has in itself all the answers to fight against external aggressions, to renew itself, to correct small imperfections that appear.

  However, either the aggressions are too numerous, or different at the same time, or too repeated, and the natural defense mechanisms or response existing in the skin can no longer suffice to correct and defend it against said aggressions, or under the effect of aging the mechanisms allowing for example regeneration are no longer active enough to allow sufficient renewal, molecular, cellular, or tissue, to keep the skin looking satisfactory.

  This is when different pathologies of the skin appear.

  The present invention therefore relates to a new class of active agents which confer on the skin or the superficial parts of the human or animal body, the ability to act or react by itself to any aggression or dysfunction, only by activating mechanisms. molecular, and / or cellular, and / or tissue, for example metabolic, preexisting in the skin or said superficial part of the human or animal body.

  In accordance with the present invention, there is proposed, for the abovementioned purposes, a composition for topical use, for example cosmetic or dermocosmetic, comprising in a new way an active complex consisting of at least one peptide or a protein chosen from the group consisting of nisin, and bacterinecin, namely the peptide Arg-Leu-Cys-Arglle-ValVal-lle-Arg-Val-Cys-Arg, and at least one nucleotide, polynucleotide, or nucleic acid, chosen from the group consisting by AMP, GMP, CMP, UMP, dTMP, dAMP, dCMP, GTP, CTP, UTP, TMP, GP4G, IP3,, DNA and or RNA hydrolysates, UDP-Glucose-galactose, GDP-Mannose , UDPN- acetyl glucosamine, CNP-N-acetyl neuraminic acid.

  The active complex according to the invention allows the skin to produce itself the necessary elements which it needs to ensure its balance, and to function ideally by giving or giving back to the skin the capacity to adapt, resist and possibly develop a protection. The action process of an active complex according to the invention is undoubtedly bio-enzymological. It is based on the combined effect of nucleic acids and proteins and / or peptides.

  Nucleic acids and proteins are consubstantial with life.

  The process implemented with an active complex according to the present invention differs radically from the usual processes of cosmetology, because it takes into account all of the interactions of the cutaneous system, acts on the entire cell and its environment, and respects all skin cells.

  By reactivating the mechanisms of the skin cells, any active complex according to the invention teaches the epidermis to use its own resources. By awakening the memory of cells and by stimulating their potentials, any active complex according to the invention allows the skin to regain its original faculties, and / or to use the faculties of defense and of fighting against external aggressions, which were not or were insufficiently stimulated.

  The prior art certainly describes the use of peptides or oligo15 nucleotides in cosmetic applications. Patent FR 98 09193 describes, for example, an application in which peptides are made lipophilic by grafting a fatty acid, of more or less long chain, onto the N-terminal amine, and / or of esterifying the carboxyl group of the peptide. The products according to this invention cannot be used in formulations or lotions consisting solely of aqueous ingredients.

  The use of nucleic acids, in particular oligonucleotides, for treating diseases is known; in particular, an application is described in patent WO 99/25819. The oligonucleotides described are used alone, and they are used as antisense, that is, they block biological mechanisms.

  In an active complex according to the invention, a peptide is used in its natural form, or in combination with an oligonucleotide, for example.

  The synergistic effect obtained is completely unexpected and is the subject of the invention.

  The peptides, forming part of an active complex according to the invention, can be obtained either by conventional chemical synthesis (in solid phase or in homogeneous liquid phase), or by enzymatic synthesis (Kulîman et al., J. Biol Chem. 1980, 255, 8234), from the constituent amino acids or their derivatives.

  The peptides can also be obtained by fermentation of a strain of bacteria, modified or not by genetic engineering, to produce the desired sequences or their different fragments.

  Finally, the peptides can be obtained by extraction of proteins of animal or vegetable origin, preferably vegetable, followed by a controlled hydrolysis which releases the peptide fragments in question. Many proteins found in plants are likely to contain interesting sequences within their structure. The controlled hydrolysis makes it possible to release these peptide fragments.

  To obtain a peptide forming part of an active complex according to the invention, it is possible, but not necessary, to extract either the proteins concerned first and then to hydrolyze them, or to carry out the hydrolysis first on a crude extract and then purifying the peptide fragments. It is also possible to use the hydrolyzate without extracting the peptide fragments in question therefrom, however making sure to have stopped the enzymatic hydrolysis reaction in time and to measure the presence of the peptides in question by appropriate analytical means (tracing by radioactivity, immunofluorescence, or immunoprecipitation with specific antibodies, etc.). Other methods, simpler or more complex, leading to cheaper or purer products can easily be envisaged by those skilled in the art knowing the art of extracting and purifying proteins and peptides.

  The DNA or RNA extracts forming part of an active complex according to the invention are obtained by controlled enzymatic hydrolysis, for example from any readily available natural source.

  They can also be obtained by synthesis using an automatic synthesizer.

  Other methods, simpler or more complex, leading to cheaper or purer products are easily conceivable by those skilled in the art knowing the art of synthesis or hydrolysis of oligonucleotides. The oligonucleotides or nucleotides capable of entering into the constitution of an active complex according to the present invention will be chosen from DNA extracts, RNA extracts, biological extracts such as biolysates of microorganisms, plant extracts, and extracts of plankton rich in oligonucleotides, depending on the peptides and / or proteins and their capacity to stimulate their action.

  The invention therefore relates to a cosmetic and / or dermocosmetic composition, characterized in that it comprises an active complex combining, at least one peptide and / or a protein, with at least one nucleotide, and / or polynucleotide, and / or one nucleic acid.

  Preferably, the components of the active complex act together synergistically.

  In one embodiment, the peptides and / or proteins represent between 1/10 to 8% and 1% by weight of the composition, and the nucleotide, represents between 2/10 to 8% and 0.2% by weight of said composition. composition, 10 or between 0.1% and 20% by weight of the composition when the nucleotides are extracts or hydrolysates of DNA or RNA.

  According to the invention, the peptides and / or proteins will be used, alone or in combination with one another, in a finished cosmetic or dermopharmaceutical product, in the form of a solution, dispersion, emulsion, or encapsulated in vectors such as macro-, micro- or nanocapsules, liposomes or chylomicrons, or included in macro-, micro- or nanoparticles, or in micro-sponges, or adsorbed on powdery organic polymers, talcs, bentonites and other mineral supports.

  The finished cosmetic or dermopharmaceutical products will be formulated in any galenic form such as O / W and W / O emulsions, milks, lotions, gelling and viscosifying polymers, surfactants and emulsifiers, ointments, hair lotions, shampoos, soaps, powders, sticks and pencils, sprays, body oils.

  The ingredients usually used such as extraction and or synthetic lipids, gelling and viscosifying polymers, surfactants and emulsifiers, hydrosoluble or water-soluble active principles, plant extracts, tissue extracts, marine extracts, and other biological agents will be added to the formulations. according to the rules usually used.

  By way of example, an active complex according to the invention can enter into the composition of a regulating gel for the skin flora, comprising moreover all the ingredients and excipients conventionally used in the composition of a gel.

  By way of example, an antiseptic lotion according to the invention has the following composition: Ethanol Propylene glycol Dimnethicone copolyol PPG1-PEG-9 lauryl glycol ether Nisine (peptide) Adenine Cytosine Guanine

DNA

  preservatives, fragrance Water 5.0% (by weight) 2.0% 0.5% 0.6% 0.001% 0.0005% 0.01% 0.002% 0.01% qs qs 100%

Claims (3)

  1. Cosmetic and / or dermocosmetic composition, characterized in that it comprises an active complex consisting of at least one peptide or a protein chosen from the group consisting of nisin, Nacetylglucosamine and bacterinecin, namely the peptide Arg- Leu-Cys-ArgleVal-Val-lle-Arg-Val-Cys-Arg, and at least one polynucleotide nucleotide, or 10 nucleic acid, chosen from the group consisting of AMP, GMP, CMP, UMP, dTMP, dAMP , dCMP, ATP, GTP, CTP, UTP, TMP, GP4G, IP3 ,, DNA and or RNA hydrolysates, UDP-Glucose-galactose, GDP-Mannose, UDPNacetyl glucosamine, CNP-N-acetyl neuraminic acid.   2. Composition according to claim 1, characterized in that the peptides and / or proteins represent between 1/10 to 8% and 1% by weight of the composition. 3. Composition according to claim 1, characterized in that the nucleotide represents between 2/10 to 8% and 0.2% by weight of the composition, or between 0.1% and 20% by weight of the composition when the nucleotides are extracts or hydrosates of DNA or RNA.