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    • 专利摘要:
    Tripeptide X-KGH-Z or X-KHG-Z; at the N-terminus X is selected from H, -CO-R1 and -SO2-R1; at the C-terminal end Z is selected from OH, OR1, NH2, NHR1 or NR1R2; and R1 and R2 being, independently of one another, selected from an alkyl, aryl, aralkyl, alkylaryl, alkoxy and aryloxy group, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and / or or sulfur, said group having 1 to 24 carbon atoms and may have in its backbone heteroatom O, S and / or N; with the exception of tripeptides in which (X = H and Z = OH) or (X = H and Z = NH2). These tripeptides stimulate the synthesis of the molecules constituting the dermal extracellular matrix, in particular collagen 1 and 4 and elastin, and can be used for a cosmetic treatment including anti-aging, anti-wrinkles and fine lines, to improve the mechanical properties of the skin. firmness / tone / elasticity / suppleness, to increase the density and the volume of the skin, for a restructuring effect and / or to fight against stretch marks.
    公开号:FR3029915A1
    申请号:FR1462511
    申请日:2014-12-16
    公开日:2016-06-17
    发明作者:Olivier Peschard；Anne Doucet；Roux Richard Le；Philippe Mondon
    申请人:Sederma SA；
    IPC主号:
    专利说明:

    [0001] The present invention relates to novel tripeptides, compositions comprising them and cosmetic uses of said peptides. It is more particularly tripeptides for the treatment of the skin and its integuments, mammals, humans or animals. It concerns the cosmetics industry (topically or orally), hygiene and personal care products and dermo-pharmacy. Peptides have an important signal function and coordinate many biochemical processes. As a result, they have become unavoidable and promising active ingredients, particularly in the cosmetics industry, where new compounds are constantly being researched that can beautify the skin and the integuments, that is to say, from improve the general condition.
    [0002] The present inventors have been more particularly interested in finding new peptides having an activity on the main constitutive molecules of the extracellular matrix (ECM) dermal which decreases with age, and more particularly active on the synthesis of collagen I and elastin and also active on the synthesis of glycoproteins such as fibronectin. The loss of density and thickness of the dermis are related to a reduction of synthesis of macromolecules during aging by dermal fibroblasts cells in charge of their manufacture. Collagen I is the most abundant protein in the dermis and is essential for firm skin. Elastin is synthesized and secreted in the extracellular dermal space. It constitutes the major component up to 90% of the elastic fibers. Fibronectin is a glycoprotein found in the extracellular matrix, which plays a key role in cell adhesion to the extracellular matrix. It can simultaneously bind to the cell and other extracellular matrix molecules, such as collagen or another fibronectin molecule. For this, the fibronectin molecules assemble to form adhesive elastic fibers on the surface of many cells. This determines the mechanical properties (elasticity, suppleness and firmness) of the skin.
    [0003] The increase of collagen IV and laminin is also sought. It helps to restore / strengthen the dermis / epidermis junction (JDE). Collagen IV forms a two-dimensional network and is one of the major components of the dermis / epidermis junction. Laminins are also contained in the basal layer and participate in the anchoring of cell surfaces to the basal lamina.
    [0004] Together, these two essential components of the JDE ensure the keratinocyte of the basal lamina better anchoring and help maintain the suppleness of the epidermis. The reduction of protein synthesis with age is felt at the level of the JDE. Thus collagen IV is more fragmented and at the same time less produced, as are laminins, which in some areas leads to an alteration of the JDE and a poorer communication between melanocytes, keratinocytes and JDE and less flexibility of the system. The interest in stimulating the synthesis of these two proteins therefore appears clearly.
    [0005] 3029915 2 Stimulated synthesis of these molecules will result from the results on the embellishment and the general state of the skin, in terms of mechanical properties: a denser skin, re-inflated, firmer, more toned, more supple and elastic, the peptide having a volumizing effect, plumping, and therefore anti-wrinkle, and at the level of imperfections of the complexion (more homogeneous color and more brightness).
    [0006] Numerous peptides or peptide mixtures having properties on the ECM and anti-aging applications have already been proposed, in particular by the Applicant, such as the Pal-KTTKS (SEQ ID No. 1) sold under the trademark MATRIXYLTM, the mixture Pal-GHK and Pal-GQPR (SEQ ID No. 2) under the trademark MATRIXYLTM 3000 or more recently Pal-KM02K under the trademark MATRIXYL Synth-6TM (M02 corresponding to a dioxygenated methionine). Other known peptides are mentioned later in the description. The object of the present invention is to propose other peptides capable of improving the general state of the skin and superficial body growths, and more particularly peptides which are active on the synthesis of ECM proteins. In addition, it aims to provide peptides sufficiently effective to be used alone or in combination, in proportions of a few ppm, and 15 can be used in the form of topical composition, including cosmetic. The present invention provides a tripeptide of formula X-KGH-Z or X-KHG-Z; with: at the N-terminus X is selected from H, -CO-R1 and -502-R1 - at the C-terminus Z is selected from OH, OR ', NH2, NHR1 or NR1R2; and R1 and R2 being, independently of one another, selected from an alkyl, aryl, aralkyl, alkylaryl, alkoxy and aryloxy group, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and / or sulfur, said group having from 1 to 24 carbon atoms and which may possess in its backbone an O, S and / or N heteroatom, with the exception of the tripeptides in which (X = H and Z = OH) or (X = H and Z = NH2). Thus, the peptides according to the invention are modified at their N-terminal end, ie at their C-terminal end. The detailed description of in vitro tests given below shows that these peptides show an activity on the MEC marker molecules, active from a few ppm, and that can be used alone or as a mixture to improve the appearance and the general condition. skin and its integuments, and in particular for the treatment and / or prevention of signs of aging, and / or imperfections of the skin and its integuments. The inventors have shown that the peptides according to the invention have in particular a pro-collagen activity, especially with regard to collagen 1 and collagen 4 and pro-elastin activity.
    [0007] According to other preferred features of the invention: R 1 and / or R 2 is an alkyl chain of 1 to 24 carbon atoms, preferably a lipophilic alkyl chain of 3 to 24 carbon atoms; and / or - X is an acyl group CO-R 1 and Z is chosen from OH, OMe, OEt and NH 2, preferably 5 OH; X is preferably selected from octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18), biotinoyl, elaidoyl, oleoyl and lipoyl; more preferably selected from lauroyl (C12), myristoyl (C14) and palmitoyl (C16); and / or - Z is OH and X is selected from palmitoyl (C16), myristoyl (C14) and lauroyl (C12); more preferably palmitoyl (C16).
    [0008] The preferred peptides according to the invention are Pal-KGH-OH and Pal-KHG-OH. The peptides according to the invention may be optically pure, or consist of L or D isomers or a mixture thereof. The naturally occurring L-isomers may be preferred. The peptides may be in the form of salts, especially hydrochloric salt.
    [0009] The present invention also covers derivatives (with modification and / or addition of a chemical function but without change in the carbon skeleton) and the like (with modification and / or addition of a chemical function but with a further change in the carbon skeleton), complexes with other species such as a metal ion (eg copper, zinc, manganese, magnesium, and others).
    [0010] The present invention also provides a composition, in particular a topical composition, comprising at least one peptide according to the invention in a physiologically acceptable medium. Depending on the excipient and the peptide assay, this composition will constitute, for example, a concentrated active ingredient or a less concentrated final composition directly intended for the client or patient. By "physiologically acceptable medium" is meant according to the present invention, without being limiting, an aqueous or hydroalcoholic solution, a water-in-oil emulsion, an oil-in-water emulsion, a microemulsion, an aqueous gel, a gel anhydrous, a serum, a dispersion of vesicles, a powder. "Physiologically acceptable" means that the compositions are suitable for topical or transdermal use, in contact with mucous membranes, nails, scalp, hair, hair and mammalian skin and more particularly human, ingestible compositions. or injected into the skin, without risk of toxicity, incompatibility, instability, allergic response, and others. This "physiologically acceptable medium" forms what is conventionally called the excipient of the composition. The peptides according to the invention may be solubilized in a lipophilic or hydrophilic matrix with, if appropriate, a solubilizer, depending on the future application.
    [0011] The peptide may be combined with other active ingredients at effective concentrations that can act synergistically or in a reinforcing manner to achieve the desired effects described for the invention, such as the following agents: anti-aging, anti-wrinkle and fine lines, lightening, pro-pigmenting, moisturizing, moisturizing, slimming, anti-acne, anti-inflammatory, anti-oxidants, acting on the radiance of complexion, anti-glycation, volumizers, restructuring, anti-carbonylation, dermo-relaxants , anti-hair regrowth, acting on the stratum corneum, on the dermis-epidermis junction, on the production of protein HSPs, on the firmness, the elasticity, the tonicity of the skin, the regrowth of the hairs (eyelashes, eyebrows eg ), etc. These active ingredients can be obtained from plant materials, such as plant extracts or vegetable or fermentation products.
    [0012] More specifically, the peptides may be combined with at least one of the compounds selected from vitamin B3 compounds, compounds such as niacinamide or tocopherol, retinoid compounds such as retinol, hexamidine, and the like. -lipoic, resveratrol or DHEA, peptides, especially N-acetyl-Tyr-Arg-O-hexadecyl, Pal-VGVAPG (SEQ ID No. 3), Pal-KTTKS (SEQ ID No. 1), Pal-GHK, Pal-KMO2K and Pal-GQPR (SEQ ID NO: 2), which are conventional active ingredients used in topical cosmetic or dermopharmaceutical compositions. The composition according to the invention can be applied to the face, the body, the décolleté, the scalp, the hair, the eyelashes, the hairs, in any form or vehicle known to those skilled in the art, in particular in the form of a solution, dispersion, emulsion, paste or powder, individually or in premix or be conveyed individually or premixed with vectors such as macrocapsules, microcapsules or nanocapsules, macrospheres , microspheres, or nanospheres, liposomes, oleosomes or chylomicrons, macroparticles, microparticles or nanoparticles, macro-sponges, micro-sponges or nanoepongs, microemulsions or nanoemulsions, or adsorbed onto powdery organic polymers, talcs, bentonites, spores or exines and other mineral or organic carriers. In cosmetics in particular, applications can be proposed especially in the skincare ranges of the face, body, hair and body hair and makeup-care ranges, including eyelashes and eyebrows.
    [0013] In general, the peptides according to the present invention can be used in any form, in a bound form, incorporated or adsorbed on macro-, micro-, and nanoparticles, or on macro-, micro- and nanocapsules, for the treatment of textiles, natural or synthetic fibers, wool, and any material intended to come into contact with the skin and which may be used in clothing, underwear, day or night, handkerchiefs , Or tissues, in order to exert its cosmetic or therapeutic effect through this skin / textile contact and allow continuous topical delivery.
    [0014] The CTFA ("International cosmetic ingredient dictionary & handbook" (13th Ed. 2010) published by "The Cosmetic, Toiletry, and Fragrance Association, Inc.", Washington, DC) describes a wide variety, without limitation, of cosmetic ingredients. and pharmaceuticals commonly used in the skincare industry, which are suitable for use as additional ingredients in the compositions of the present invention. Other additional skin care actives which are particularly useful can be found in the art. Sederma's commercial documentation and on the website www.sederma.fr Other examples include the following commercial assets: betaine, glycerol, Actimoist Bio 2TM (Active Organics), AquaCacteenTM (Mibelle AG Cosmetics) , AquaphylineTM (Silab), AquaregulKTM (Solabia), CarcilinTM (Greentech), CodiavelaneTM (Biotech Marine), DermafluxTM (Arch Chemicals, Inc.), Hydra'FlowTM (Sochibo), Hydromoist L TM (Symrise), RenovHyalTM (Soliance), SeamossTM (Biotech Marine), ArgirelineTM (commercial name of Lipotec acetyl hexapeptide-3), spilanthol or an extract of Acmella oleracea known as Gatuline ExpressionTM, an extract from Boswellia serrata known as BoswellinTM, Deepaline PVBTM (Seppic), Syn-AKETM (Pentapharm), AmelioxTM, BioxiliftTM (Silab), PhytoCellTecTMArgan (Mibelle), Papilactyl DTM (Silab), PreventheliaTM (Lipotec), SubliskinTM (Sederma), VenuceaneTM (Sederma), Moist 24TM (Sederma), Vegesome Moist 24TM (Sederma), EssenskinTM (Sederma), JuvinityTM (Sederma), RevidratTM (Sederma), ResistemTM (Sederma), ChronodynTM (Sederma), KombuchkaTM (Sederma), ChromocareTM ( Sederma), CalmosensineTM (Sederma), Glycokin factor 20 STM (Sederma), BiobustylTM (Sederma), IdealiftTM (Sederma), Ceramide 2TM, Ceramide A2TM and Ceramide HO3TM (Sederma), LeganceTM (Sederma), IntenslimTM (Sederma), ProdiziaTM ( Sederma), SenestemTM (Sederma), BeautifeyeTM (Sederma), PacifeelTM (Sede rma), SebulessTM (Sederma), NG Unsaponifiables of Shea ButterTM (Sederma) or mixtures thereof. Among the plant extracts which can be combined with a peptide according to the invention, ivy extracts, for example climbing ivy (Hedera Helix), Bupleurum chinensis, Bupleurum Falcatum, arnica, may be mentioned in particular in particular. (Arnica Montana L), rosemary (Rosmarinus officinalis / V), marigold (Calendula officinalis), sage (Salvia officinalis L), ginseng (Panax ginseng), ginko biloba, St. John's wort (Hyperycum Perforatum), birch (Ruscus aculeatus L), Ulmaria (Filipendula ulmaria L), Orthosiphon (Orthosiphon Stamincus 30 Benth), Algae (Fucus Vesiculosus), Birch (Betula alba), Green Tea, Cola Nuts (Cola Nipida), horse chestnut, bamboo, Centella asiatica, heather, fucus, willow, pilosella, escin extracts, cangzhu extracts, chrysanthellum indicum extracts, plants of the genus Armeniacea, Atractylodis Platicodon, Sinnomenum, Pharbitidis, Flemingia, Coleus as C. Forskohlii, C. blume C. esquirolii, C. scutellaroides, C. xanthantus and C. Barbatus, as a raciness extract of Coleus barbatus, extracts of Ballot, Guioa, Davallia, Terminalia, Barringtonia, Trema, antirobia, cecropia, argania, dioscoreae. as Dioscorea 3029915 6 opposita or Mexican, extracts of Ammi visnaga, Siegesbeckia, in particular Siegesbeckia orientalis, plant extracts of the Ericaceae family, in particular extracts of blueberries (Vaccinium angustifollium) from Arctostaphylos uva ursi, aloe vexa, plants containing sterols (in particular phytosterols), Manjistha (extract of plants of the genus Rubia, in particular Rubia 5 Cordifolia), Guggal (extract of plants of the genus Commiphora, in particular Commiphora Mukul), an extract of kola, chamomile, violet clover, Piper methysticum (Kava Kava from Sederma), Bacopa monieri (BacocalmineTM, Sederma) and sea whip, Glycyrrhiza glatira, mulberry, tea tree, Larrea div aricata, Rabdosia rubescens, Euglena gracilis, Fibraurea recisa Hirudinea, Chaparral Sorghum, sunflower, Enantia chlorantha, Mitracarpe of the genus Spermacocea, Buchu barosma, Lawsonia inermis L., Adiantium Capillus -Veneris L., Chelidonium malus, Luffa cylindrical, "Japanese Mandarin" (Citrus reticulata Blanco var. unshiu), Camelia sinensis, Imperata cylindrical, Glaucium Flavum, Cupressus Sempervirens, Polygonatum multiflorum, loveyly hemsleya, Sambucus Nigra, Phaseolus lunatus, Centaurium, Macrocystis Pyrifera, Turnera Diffusa, Anemarrhena asphodeloides , Portulaca pilosa, Humulus lupulus, Arabica coffee, Ilex Paraguariensis, Globularia Cordifolia, Oxydendron arboreum, Albizzia julibrissin and Zingiber zerumbet smith. The compositions of the present invention may include other peptides, including, but not limited to, di-, tri-, tetra-, penta- and hexapeptides and derivatives thereof. According to a particular embodiment, the concentration of the additional peptide in the composition varies between 1 × 10 -7% and 20%, preferably between 1 × 10 -6% and 10%, preferably between 1 × 10 -5% and 5%, weight. The term "peptide" herein refers to peptides containing 10 amino acids or less, their derivatives, isomers and complexes with other species such as a metal ion (e.g. copper, zinc, manganese, magnesium, and others). The term "peptides" refers to both natural peptides and synthetic peptides. It also refers to compositions which contain peptides and which are found in nature, and / or which are commercially available. Nonlimiting examples of dipeptides that may be used in the context of the present invention include Carnosine (beta-AH), YR, VW, NF, DF, KT, KC, CK, KP, KK or TT. Non-limiting examples of tripeptides include RKR, HGG, GKH, GGH, GHG, KFK, KPK, KMOK, KM02K or KAvaK. Non-limiting examples of tetrapeptides are RSRK (SEQ ID NO: 4), GQPR (SEQ ID NO: 5), or KTFK (SEQ ID NO: 6). A non-limiting example of pentapeptide is KTTKS (SEQ ID NO: 7) and hexapeptides GKTTKS (SEQ ID NO: 8) and VGVAPG (SEQ ID NO: 9). Other peptides which may be used in the context of the present invention may be chosen from, without this list being limiting: the lipophilic derivatives of peptides, preferably the myristoyl and palmitoyl derivatives, and the complexes with the metal ions mentioned above ( eg copper complex of 3029915 7 tripeptide HGG). Preferred dipeptides include, for example, N-Palmitoyl-beta-Ala-His, N-Acetyl-Tyr-Arg-hexadecyl ester (Calmosensine ™, Idealift ™, Sederma), Pal-KT, Pal-RT (Sederma). The preferred tripeptides include N-Pal-Gly-Lys-His, (Pal-GKH, Sederma), the copper derivative of HGG (LaminTM, Sigma), lipospondin (N-Elaidoyl-KFK) and its substitution analogues conservative, N-Acetyl-RKR-NH2 (Peptide CK +), N-Biot-GHK (Sederma), Pal-KMO2K (Sederma) and their derivatives. Tetrapeptide derivatives which may be used in the context of the present invention include, but are not limited to, N-Pal-GQPR (Sederma, SEQ ID No. 2) and Ela-KTFK (SEQ ID No. 10). Useful pentapeptide derivatives include, but are not limited to, N-Pal-KTTKS (MATRIXYL ™, Sederma, SEQ ID NO: 1), N-Pal-Tyr-Gly-Gly-Phe-X (SEQ ID NO: 11). ) with X being Met or Leu or their mixture. Useful hexapeptide derivatives include, but are not limited to: N-Pal-VGVAPG (SEQ ID NO: 3), Pal-GKTTKS (SEQ ID NO: 12), and derivatives. We can also mention the mixture Pal-GHK and Pal-GQPR (SEQ ID NO: 2) (MatrixylTM 3000, Sederma). Preferred commercially available compositions containing a tripeptide or derivative include Biopeptide-CLTM, MaxilipTM or Sederma BiobustylTM. Preferred commercially available compositions of tetrapeptide sources include: RIGINTM Eyeliss ™, Matrixyl ™ Reloaded and Matrixyl 3000 ™, which contain between 50 and 500 ppm of palGQPR (SEQ ID NO: 2) and an excipient, provided by Sederma. The following commercial peptides may also be mentioned as additional active ingredients: - Vialox ™ (INCI name = Pentapeptide-3 (synthetic peptide including alanine, arginine, isoleucine, glycine and proline)), Syn-ake ™ ((3-Ala); Pro-Dab-NH-Bz1) or Syn-Coll ™ (PalLys-Val-Lys-OH) sold by Pentapharm, Argireline ™ (Ac-Glu-Glu-Met-Gln-Arg-Arg-NH 2 (Nom INCI = Acetyl hexapeptide-3) (SEQ ID NO: 13), Leuphasyl ™ (Tyr-D-Ala-Gly-Phe-Leu) (SEQ ID No. 14), Aldenine ™ (Gly-His-Lys), TrylagenTM (INCI name = Pseudoalteromonas Ferment Extract, Hydro lyzed Wheat Protein, Hydro Lyzed Soy Protein, Tripeptide-10 Citrulline (product of the reaction of Citrulline and Tripeptide-10 (synthetic peptide consisting of aspartic acid, isoleucine and lysine)), Tripeptide-1), Eyeseryl ™ (Ac- (3-Ala-His-Ser-His) (SEQ ID No. 15), Serilesine ™ 30 (Ser-Ile-Lys-Val-Ala-Val) (SEQ ID No. 16) or DecorinylTM (INCI name: Tripeptide-10 Citrulline = product of the reaction of Citrulline and Tripeptide-10 (synthetic peptide consisting of aspartic acid, isoleucine and lysine) sold by Lipotec, - CollaxylTM (Gly-Pro-Gln-Gly-Pro-Gln (SEQ ID No. 17)) or QuintescineTM (Cys-Gly) sold by Vincience, 35 - CytokinolTMLS (casein hydrolyzate) sold by Laboratoires Serobiologiques / Cognis, 3029915 8 - KollarenTM (Gly-His-Lys), IP2000TM (Pal-Val-Tyr-Val) or MelipreneTM (INCI name = Monofluoroheptapeptide-1: product of the reaction of acetic acid and a synthetic peptide containing arginine, glycine, glutamic acid, histidine, norleucine, p -Fluorophenylalanine and tryptophan) sold by the European Institute of Cell Biology, NeutrazenTM (Pal-His-D-Phe-Arg-NH2) sold by the company Innovations, or - BONT-L-PeptideTM (INCI name = Palmitoyl Hexapeptide-19: product of the reaction of palmitic acid and Hexapeptide-19 (synthetic peptide consisting of asparagine , aspartic acid, lysine and methionine), Timp-PeptideTM (INCI name = Acetyl Hexapeptide20: product obtained by acetylation of Hexapeptide-20 (synthetic peptide consisting of alanine, glycine, lysine, valine and proline) or ECM ModulinTM (INCI name = Palmitoyl Tripeptide-28: product of the reaction of palmitic acid and Tripeptide-28 (synthetic peptide consisting of arginine, lysine and phenylalanine) sold by the company Infinite Activos. The present invention thus proposes the use of at least one peptide according to the invention or a composition comprising it, as defined above, for a non-therapeutic cosmetic treatment to improve the general condition of the skin and / or its integuments and treat imperfections. Preferably according to the invention, the treatment is topical. The peptide according to the invention is more particularly recommended according to the invention for an anti-aging treatment, in particular a treatment: anti-wrinkles and fine lines; and / or improving the mechanical properties of the skin: firmness, tone, elasticity and / or suppleness; and / or increasing the density and volume of the skin (volumizing effect, plumping and / or restructuring); and / or 25 - to fight against stretch marks; and / or to improve the homogeneity and / or radiance of the complexion. Other applications are of course conceivable for the tripeptides according to the invention (alone or in combination), for example moisturizing, slimming, detoxification, anti-glycation, anti-free radicals, tensors, anti-fatigue, anti-bags and / or dark circles. calming, action on the growth of hair and hair, action on the radiance of the complexion, pigmentation, on the scalp, etc. as a preventive or curative. The present invention covers a cosmetic, non-therapeutic topical treatment method for improving the appearance and the general condition of the skin and its integuments, including the topical application to the skin of a subject who has require an effective amount of a peptide or a mixture of peptides according to the invention or a composition according to the invention comprising said peptide or the mixture of peptides, the peptides being as defined above.
    [0015] By "topical treatment" or "topical use" is meant an application which is intended to act at the place where it is applied: skin, mucous membrane, superficial body growths. The peptide or the composition according to the invention may be applied locally to the targeted zones. The "effective" amount depends on a variety of factors, such as the age, the condition of the patient, the severity of the disorder or condition and the mode of administration. An effective amount means a non-toxic amount sufficient to achieve the desired effect. In a cosmetic composition according to the invention, the peptides to be present in an effective amount may be in proportions of between 0.000001% and 15% relative to the total weight of the composition, preferably between 0.00001% and 5%, more preferably between 0.0001% and 0.01% (between 1 and 100 ppm) for topical cosmetic application, depending on the destination of the composition and the desired effect more or less pronounced. The peptides may be present in the compositions according to the invention in variable relative proportions, in equivalent amounts, or on the contrary in different proportions. All percentages and ratios used in this application are by weight of the total composition and all measurements are made at 25 ° C unless otherwise specified. For example, for a cosmetic facial treatment, the European Cosmetics Directive has set a standard application amount of a cream of 2.72 mg / cm2 / day / person and for a lotion for the body of 0.5 mg / cm2 / day / person. According to other particularities, the cosmetic treatment method according to the invention may be associated with one or more other treatment methods for the skin, such as, for example, light therapy, heat or aromatherapy treatments. According to the invention, it is possible to propose devices with several compartments or kits intended for the implementation of the method described above, and which could include, by way of example, and without being limiting, in a first compartment a composition containing a peptide of the invention and in a second compartment an additional excipient and / or active, the compositions contained in said first and second compartments being here considered as a combination composition for simultaneous use, separate or spread in the time especially in one of the treatments defined above. The treatment method according to the invention is more particularly adapted to slow down the degradations of the molecules of the dermal extracellular matrix and / or to act on the JDE via the stimulation of collagen IV and / or laminins. Other applications are of course conceivable for the peptides according to the invention (alone or in combination), for example moisturizing, slimming, detoxification, anti-glycation, anti-free radicals, tensors, anti-fatigue, anti-bags and / or dark circles. , calming, action on the growth of hair and hair, action on the radiance of the complexion, on the pigmentation, on the scalp, etc. The following examples describe and illustrate certain aspects of the invention. They should not be perceived as limiting the disclosure, as they mainly provide useful information for its understanding and implementation. A) Synthesis Example of a Peptide According to the Invention: Pal-KGH-OH The Pal-PPL-OH peptide is prepared by peptide synthesis. Histidine is coupled with a resin via its terminal acid function (with a coupling agent, for example DCC (diclyclohexylcarbodiimide) / NHS (N-hydroxysuccinimide) or HBTU (2- (1H-benzotriazol-1-yl) - 1, 1 , 3,3-tetramethyluronium hexafluorophosphate) / HOBT (1-hydroxy-benzotriazole)). The thus protected histidine is then reacted with a glycine derivative in the presence of a coupling agent, followed by the same operation to add lysine. This is then acylated on its amine function with an activated palmitic acid derivative (palmitoyl chloride for example) in the presence of a base. After precipitation, washing and drying, the palmitoyl-lysylglycyl-histidine product is obtained in solid form. This same synthetic process can be applied to the peptides of formula I according to the invention, for example to the peptide Pal-KHG-OH. B) Preparation of a Composition According to the Invention Comprising the Pal-KGH-OH Peptide of Example A) Starting materials: - the pure peptide, synthesized according to the synthesis method explained above; Excipient: a mixture of fatty esters chosen to form an oily matrix, for example intended to form a composition without water for the subsequent formulation of cosmetic compositions without water. Procedure: The peptide is mixed with the excipient and gently stirred and heated until solubilization and total limpidity.
    [0016] C) In vitro evaluations The peptides according to the invention have a number of remarkable effects presented below. Peptides prepared according to A) above and dissolved in an excipient were tested in vitro and showed activities which are presented hereinafter. 1) ELISA Assays Protocol Normal human fibroblasts (FHN) in culture are brought into contact with the test products or their excipient (negative control) for 72 hours. At the end of the contact, the culture supernatants are taken and the syntheses of the dermal macromolecules are estimated by ELISA assays. An estimate of cell viability is made by Hoechst assay and allows the data obtained to be weighted.
    [0017] 3029915 11 Results Table 1: Collagen I Product Concentration% of variation / control Significance (Student test) Pal-KGH-OH 3 ppm +69 p <0.05 7 ppm +123 p <0.01 Pal-KHG-OH 3 ppm +66 p <0.05 7 ppm +116 p <0.01 12.5 ppm + 132 p <0.01 Table 2: Collagen IV 5 Product Concentration% of variation / control Significance (Student test) Pal-KGH-OH 7 ppm + 35 p <0.01 10 ppm + 74 p <0.01 12.5 ppm + 199 p <0.01 Pal-KHG-OH 7 ppm + 62 p <0.01 10 ppm + 109 p <0 , 01 12.5 ppm + 183 P <0.01 Table 3: Fibronectin Product Concentration% of variation / control Significance (Student test) Pal-KGH-OH 7 ppm + 40 p <0.05 10 ppm + 45 p <0 12.5 ppm + 79 p <0.01 Pal-KHG-OH 7 ppm + 46 p <0.01 10 ppm + 50 p <0.01 12.5 ppm + 91 p <0.01 Table 4: Elastin Product Concentration% of variation / control Significance (Student test) Pal-KHG-OH 3 ppm +139 p <0.05 7 ppm +113 p <0.01 The results show that the peptides according to the invention stimulate synthesis of collagens I and IV, F ibronectin, laminin and elastin for Pal-KHG on normal human fibroblasts at concentrations of a few ppm and in significant proportions. 2) Immunofluorescent Assays Protocol Normal human fibroblasts (FHN) are cultured for 24 hours. The cells are placed in contact or not with the test products or their excipient at different concentrations for 6 days for collagen I or 14 days for elastin (DMEMc 5% FCS). The synthesis of collagen I and elastin produced by the cells in extracellular matrix form is then quantified by immunoblotting on the fixed mats. A count of Hoechst-labeled nuclei is performed in parallel in order to have an estimate of the viability and to weight the data. Results Table 5: Collagen I Product Concentration% of variation / control Significance (Student test) Pal-KGH-OH 3 ppm + 408.8 p <0.01 7 ppm + 724.4 p <0.01 + 399.4 p <0.01 Pal-KHG-OH 3 ppm + 133.8 p <0.01 10 ppm + 644.8 p <0.01 15 ppm + 394.9 p <0.01 Table 6: Elastin Product Concentration% Variability / control Significance (Student test) Pal-KHG-OH 3 ppm + 59.1 p <0.01 7 ppm + 41.2 p <0.01 15 ppm + 51.5 p <0.01 Pal-KGH -OH 3 ppm + 82.8 p <0.01 7 ppm + 76.3 p <0.01 + 126.8 p <0.01 Table 7: Collagen IV Product Concentration% of variation / control Significance (Student test ) Pal-KHG-OH 3 ppm + 215.2 p <0.01 7 ppm + 504.9 p <0.01 15 ppm + 436.8 p <0.01 Pal-KGH-OH 3 ppm +323.7 p <0.01 7 ppm +274.4 p <0.01 +259.5 p <0.01 3029915 13 Table 7: Hyaluronic Acid Product Concentration% of variation / control Significance (Student test) Pal-KGH-OH 3 ppm +37.6 p <0.01 7 ppm +42.2 p <0.05 D) GALENIC 5 Various formulations are described below. Additional active cosmetic ingredients, possibly resulting in support and / or in addition to the activity of the active ingredient according to the invention, may be added in the appropriate phase according to their hydrophobic or hydrophilic nature. These ingredients can be of any category depending on their function (s), the place of application (body, face, neck, bust, hands, hair, eyelashes, eyebrows, hair, etc.), the final effect 10 sought after and targeted consumer, eg antioxidant, moisturizing, nourishing, protective, smoothing, remodeling, volumizing (lipofiling), acting on radiance, anti-dark spots, anti-dark circles, anti-glycation, slimming, soothing, myo -Relaxant, anti-redness, anti-vergetures, etc. They are mentioned above in the description. 1) Cream form, for example an anti-aging day cream for the face Ingredient (INCI name)% by weight Phase A Sorbitan Stearate 3.00 Cyclopentasiloxane (and) Cyclohexasiloxane 2.00 Ethylhexyl Palmitate 3.00 Glyceryl Stearate (and) PEG-100 Stearate 3.00 Ethylhexyl Methoxycinnamate 1.00 Ethylhexyl Dimethyl PABA 1.00 Phase B Demineralized Water Qs 100 Ultrez 10 (Carbomer) 0.40 Phase C Glycerin 5.00 Preservative qs Phase D Peptide according to the invention in a carrier Fat 3.00 Phase E Potassium Sorbate 0.10 Phase F 3029915 14 Sodium Hydroxide 30% (Sodium Hydroxide) 0.60 Demineralized Water 6.00 Phase G Perfume 0.10 Protocol: Weigh phase A and heat to 75 ° C in a water bath. Weigh phase B and let it swell for 20 minutes. Melt phase C until dissolved and add to phase B. Heat phase (B + C) at 75 ° C in a water bath. Pour phase A into phase (B + C) with Staro stirring. Extemporally, add phase D to phase (A + B + C). At about 45 ° C. add phase E and neutralize with phase F. Thoroughly homogenize. At 35 ° C, add phase G. Thoroughly homogenize. pH: 6.20. Examples of ingredients that can be added to this formulation: CALMOSENSINETM: sedative active ingredient marketed by Sederma (W01998 / 07744) containing the lipo-dipeptide Tyr-Arg. It reduces feelings of discomfort. - SEBULESSTM: active ingredient marketed by Sederma including an extract of Syringa vulgaris obtained by cell culture in vitro, sebum regulating purifying, mattifies and refreshes the complexion, blurs the imperfections. PRODIZIATM: active ingredient marketed by Sederma comprising an extract of Albizia julibrissin, which promotes the visible reduction of signs of fatigue: dark circles, pockets, dull complexion and drawn features in repairing and protecting the skin from damage caused by glycation. - PACIFEELTM: active ingredient marketed by Sederma, including an extract of natural origin from the plant Mirabilis Jalapa (Belle de nuit) which relieves feelings of discomfort (itching, tingling), reduces the redness of sensitive and reactive skin. 2) Gel form, e.g. body firming gel Ingredient (INCI name)% by weight Phase A Qs 100 Demineralized water Ultrez 10 (Carbomer) 0.20 Phase B PEG 400 5.00 Preservatives qs Phase C Thicone Dime 4 , 00 Pemulen TR2 (Acrylates / C10-30 Alkyl Acrylate Cross Polymer) 0.20 Phase D 3029915 Tween 20 (Polysorbate 20) 1.00 Peptide in a fatty excipient 2.00 Phase E Potassium Sorbate (Potassium Sorbate) 0, 10 Phase F Sodium Hydroxide 30% (Sodium Hydroxide) 0.60 Demineralized Water 5.00 Phase G Fragrance 0.10 Protocol: Disperse Ultrez 10 in water and allow to swell for 15 minutes. Heat phase B until dissolved and add to phase A. Weigh and mix phase C. Mix phase D and add it to phase C; well homogenize. Add the phase (C + D) to the phase (A + B). Then add phase E. Allow to swell for 1 hour. Well homogenize. Neutralize with phase 5 F. Finally, add phase G. pH: 6.10. Examples of ingredients that can be added to this formulation: AQUALANCETM: osmoprotective moisturizing active ingredient marketed by Sederma (WO2009 / 104118) composed of homarine and erythritol. LEGANCETM: anti-aging active ingredient marketed by Sederma, corresponding to an extract of Zingiber zerumbet Smith obtained by supercritical CO2 in a water-soluble excipient and titrated with zerumbone. It is an overall anti-aging ingredient for the legs. It improves their appearance and comfort by reducing water retention, improving microcirculation and refining fat tissue. - BODYFITTM: active ingredient marketed by Sederma (WO 2004/024695) slimming / firming. JUVINITYTM: Active ingredient marketed by Sederma (WO 2011/125039) which reduces the signs of aging on the face and décolleté, smoothes wrinkles, restructures and densifies the dermis. Can be used as reinforcement of activity. 3) Compact powder form 20 Ingredient (INCI name)% by weight Phase A Qsp 100 2.00 1.00 4.00 1.00 Talc Kaolin Calcium Stearate Mica Silica 3029915 16 Bismuth Oxychloride Potassium Sorbate Phenoxyethanol 2.00 qs qs Phase B Unipure Black LC 989 HLC [CI 77499 (and) Hydrogenated Lecithin] 0.20 Unipure Red LC 381 HLC [CI 77491 (and) Hydrogenated Lecithin] 0.60 Unipure Yellow LC 182 HLC [CI 77492 (and) Hydrogenated Lecithin] 1, 00 Covapearl Star Gold 2302 AS [CI 77891 (and) CI 77491 (and) Synthetic 0.50 Fluorphlogopite (and) Triethoxycaprylylsilane] Covapearl Brown 838 HLC [CI 77491 (and) Mica (and) Hydrogenated 1.00 Lecithin) Covapearl Dark Blue 637 [CI 77510 (&) CI 77891 (&) Mica] 0.10 Phase C Crodamol PTIS-LQ- (MV) [Pentaelythrityl Tetraisostearate] 4.00 Peptide according to the invention in a fatty matrix 3.00 Phase D Perfume 0 Protocol: Weigh phase A and mix. Weigh phase B and pour it into phase B. Pour A + B into the mixer and mix. Add phase C to A + B in several times and mix each time. Add phase D. Check at each step for homogeneity. Example of an ingredient that can be added to this formulation: 5 - VEGESOME MOIST 24TM, an ingredient marketed by Sederma specifically designed for the formulation of moisturizing makeup powders; it is a powder composed of 25 μm hollow particles (Lycopodium clavatum exines) loaded with Imperata cylindrica extract with moisturizing properties. 4) Other cream form (face or body) Ingredient (INCI name)% by weight Phase A Arlacel 170 (Glyceryl Stearate (and) PEG-100 Stearate) 5.50 Abil Wax 2434 (Stearoxy Dimethicone) 3.00 Acetulan (Cetyl Acetate) (and) Acetylated Lanolin Alcohol 1.50 Crodacol C 90 (Cetyl Alcohol) 1.50 Mineral Oil 3.00 Shea Butter 5.00 Unsaponifiable Shea 1.00 3029915 17 Parsol MCX (Ethylhexyl Methoxicinnamate) 3.50 Phase B Qs 100 Demineralized water Phase C 0.20 Carbopol 940 (Carbomer) Phase D 2.00 Demineralized water 0.20 Triethanolamine 99% (Triethanolamine) Phase E 0.10 Propylene Glycol Mixed Parabens Phase F 5.00 Sodium Hydroxide 30% (Sodium Hydroxide Deionized water qs Phase G 2.00 Peptide according to the invention in a hydrophilic matrix Protocol: Weigh phase A and heat it to 75 ° C. in a water bath. Weigh phase B and let it swell for 20 minutes. Melt phase C until dissolved and add to phase B. Heat phase (B + C) at 75 ° C in a water bath. Pour phase A into phase (B + C) with Staro stirring. Extemporally, add phase D to phase (A + B + C). At about 45 ° C. add phase E and neutralize with phase F. Thoroughly homogenize. At 35 ° C, add phase G. Thoroughly homogenize. pH: 6.20. Examples of ingredients that can be added to this formulation: - SUBLISKINTM: active ingredient marketed by Sederma (WO2009 / 055663) that moisturizes and smooths the skin while allowing it to withstand external aggressions. 10 - VENUCEANETM: active ingredient marketed by Sederma (WO2002 / 066668) which prevents visible signs of photoaging (spots, wrinkles, dryness, etc.), protects cellular structures from damage caused by UV and reinforces the integrity of the skin . - KOMBUCHKATm: active ingredient acting on the radiance of the complexion, marketed by Sederma (W02004 / 012650). 15 - INTENSLIMim: slimming active ingredient marketed by Sederma. It is a synergistic combination of extracts of Globularia cordifolia obtained by plant cell culture, Zingiber zerumbet Smith titrated in zerumbone and vegetable caffeine obtained by supercritical CO2 extraction.
    权利要求:
    Claims (14)
    [0001]
    REVENDICATIONS1. Tripeptide of formula X-KGH-Z or X-KHG-Z; with: at the N-terminus X is selected from H, -CO-R1 and -SO2-R1 - at the C-terminus Z is selected from OH, OR ', NH2, NHR1 or NR1R2; and - R1 and R2 being, independently of one another, chosen from an alkyl, aryl, aralkyl, alkylaryl, alkoxy and aryloxy group, which may be linear, branched, cyclic, polycyclic, unsaturated, hydroxylated, carbonylated, phosphorylated and or sulfur, said group having 1 to 24 carbon atoms and may have in its backbone O, S and / or N heteroatom, with the exception of tripeptides in which (X = H and Z = OH) or (X = H and Z = NH2).
    [0002]
    2. Tripeptide according to claim 1, characterized in that said group comprises from 3 to 24 carbon atoms.
    [0003]
    Tripeptide according to claim 1 or 2, characterized in that X is an acyl group -CO-R1 and at the C-terminal end Z is a group chosen from OH, OMe, OEt and NH2.
    [0004]
    4. Tripeptide according to one of the preceding claims, characterized in that the acyl group CO-R1 is chosen from octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14), palmitoyl (C16), stearoyl (C18), biotinoyl, elaidoyl, oleoyl and lipoyl.
    [0005]
    Tripeptide according to claim 4, characterized in that Z is OH.
    [0006]
    6. Tripeptide according to claim 5, corresponding to Pal-KGH-OH or Pal-KHG-OH.
    [0007]
    A cosmetic composition comprising as an active ingredient an effective amount of at least one tripeptide according to any one of the preceding claims in a physiologically acceptable medium.
    [0008]
    8. Composition according to claim 7, characterized in that the effective amount is between 0.000001% and 15% relative to the total weight of the composition.
    [0009]
    9. Composition according to claim 7, characterized in that the effective amount is between 0.0001% and 5% relative to the total weight of the composition.
    [0010]
    10. Composition according to one of claims 7 to 9, characterized in that it comprises at least one additional active ingredient selected from the compounds of vitamin B3, niacinamide, tocopherol, retinoid compounds, hexamidine α-lipoic acid, resveratrol, DHEA and peptides.
    [0011]
    11. Use of at least one peptide according to any one of claims 1 to 6 or a composition according to one of claims 7 to 10 for a non-therapeutic cosmetic treatment to improve the general condition of the skin and / or its integuments and treat imperfections. 3029915 19
    [0012]
    12. Use according to claim 10 for topical treatment. Use according to claim 9 or 10 for anti-aging treatment. Use according to claim 9 to 12 for treatment.
    [0013]
    13. anti-wrinkles and fine lines; and or
    [0014]
    14. improving the mechanical properties of the skin: firmness, tone, suppleness; and / or increasing the density and volume of the skin (volumizing effect, restructuring); and / or to fight against stretch marks, and / or to improve the homogeneity and radiance of the complexion. 5 elasticity, and / or plumping and / or
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    同族专利:
    公开号 | 公开日
    WO2016097966A1|2016-06-23|
    EP3233210A1|2017-10-25|
    FR3029915B1|2016-12-09|
    EP3233210B1|2020-02-05|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    FR3097750A1|2019-06-28|2021-01-01|Laboratoire Promicea|New anti-aging cosmetic composition|US5118665A|1990-02-09|1992-06-02|Procyte Corporation|Anti-oxidative and anti-inflammatory metal:peptide complexes and uses thereof|
    WO1998007744A1|1996-08-23|1998-02-26|Sederma S.A.|Synthetic peptides and their use in cosmetic or dermopharmaceutical compositions|
    FR2821086B1|2001-02-21|2003-12-12|Sederma Sa|PROCESS FOR THE MANUFACTURE OF PROTEINS BY FERMENTATION OF MICROORGANISMS OF THE THERMUS FAMILY, MIXTURE OF PROTEINS THUS OBTAINED AND COSMETIC COMPOSITION CONTAINING THEM|
    FR2843023B1|2002-07-30|2004-09-24|Sederma Sa|COSMETIC OR DERMOPHARMACEUTICAL COMPOSITIONS CONTAINING KOMBUCHA.|
    FR2843963B1|2002-08-30|2004-10-22|Sederma Sa|NEW NORAPORPHIN-DERIVED MOLECULES|
    FR2927801B1|2008-02-22|2010-03-05|Sederma Sa|MOISTURIZING COSMETIC COMPOSITION COMPRISING A COMBINATION OF HOMARIN AND ERYTHRITOL|
    FR2939799B1|2008-12-11|2011-03-11|Sederma Sa|COSMETIC COMPOSITION COMPRISING ACETYL OLIGOGLUCURONANS.|
    FR2980362B1|2011-09-27|2013-10-04|Sederma Sa|NOVEL COSMETIC USE OF ALBIZIA JULIBRISSIN EXTRACT AND CORRESPONDING TOPICAL COMPOSITION|
    FR2985425A1|2012-01-10|2013-07-12|Sederma Sa|NEW USE OF ZERUMBON|
    FR2985424B1|2012-01-10|2019-03-29|Sederma|NEW TOPICAL USE OF ZERUMBON|JP6966455B2|2016-02-04|2021-11-17|アラスティン スキンケア，インク．|Compositions and Methods for Invasive and Non-Invasive Treatment Skin Care|
    CA3071645A1|2017-08-03|2019-02-07|ALASTIN Skincare, Inc.|Compositions and methods for ameliorating skin laxity and body contour|
    WO2020028694A1|2018-08-02|2020-02-06|ALASTIN Skincare, Inc.|Liposomal compositions and methods of use|
    FR3107708A1|2020-02-28|2021-09-03|Alganelle|Recombinant microalgae capable of producing KTTKS peptides, polypeptides and proteins and their derivatives, and their associated method and uses|
    法律状态:
    2015-12-11| PLFP| Fee payment|Year of fee payment: 2 |
    2016-06-17| PLSC| Search report ready|Effective date: 20160617 |
    2016-12-19| PLFP| Fee payment|Year of fee payment: 3 |
    2017-12-18| PLFP| Fee payment|Year of fee payment: 4 |
    2019-12-20| PLFP| Fee payment|Year of fee payment: 6 |
    2020-12-10| PLFP| Fee payment|Year of fee payment: 7 |
    2021-09-22| PLFP| Fee payment|Year of fee payment: 8 |
    优先权:
    申请号 | 申请日 | 专利标题
    FR1462511A|FR3029915B1|2014-12-16|2014-12-16|TRIPEPTIDES, COMPOSITIONS COMPRISING THE SAME, AND USES IN PARTICULAR COSMETICS|FR1462511A| FR3029915B1|2014-12-16|2014-12-16|TRIPEPTIDES, COMPOSITIONS COMPRISING THE SAME, AND USES IN PARTICULAR COSMETICS|
    PCT/IB2015/059581| WO2016097966A1|2014-12-16|2015-12-14|Tripeptides, compositions thereof and their cosmetic uses|
    EP15817569.5A| EP3233210B1|2014-12-16|2015-12-14|Tripeptides, compositions thereof and their cosmetic uses|
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