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    • 专利摘要:
    The peptide compound comprises at least one amino acid which is lysine, ornithine, diaminopropionic acid or diaminobutyric acid or a derivative of these amino acids, to which is grafted by peptide bond on the nitrogen of the side chain an acid carboxylic acid comprising a (poly) ring or (poly) heterocycle. Preferably, the grafted carboxylic acid is an amino acid or a derivative, especially chosen from a proline, a hydroxyproline or a pyroglutamic acid. The peptide compound is adapted to stimulate the synthesis of the main molecules constituting the extracellular matrix of the skin, in particular collagen 1 and 4 and elastin. It can be used for a topical cosmetic treatment as global anti-aging, or for specific activities, including anti-wrinkles and fine lines, moisturizing, to improve the mechanical properties of the skin, firmness / tone / elasticity / suppleness, to increase the density and volume of the skin, to improve the radiance of the complexion, for a restructuring effect and / or to fight against stretch marks.
    公开号:FR3029782A1
    申请号:FR1462510
    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 peptide compounds, compositions comprising them and cosmetic or dermatological uses of said compounds. It is thus more particularly compounds and compositions for the treatment of the skin and its integuments, mammals, humans or animals.
    [0002] A peptide compound according to the invention is defined as comprising at least one amino acid and more commonly from 2 to 10 amino acids, derivatives and analogs linked by peptide bonds. It concerns the cosmetics industry (topically or orally), hygiene and personal care products and dermo-pharmacy. Small peptides or peptide compounds are formed by enzymatic degradation in the extracellular matrix of the skin and it has been shown that these peptides or compounds, which have been called "matrikines", are able to regulate cell activity because they had an important signal function. Many peptides or mixtures of peptides, obtained by extraction or by synthesis, have thus been proposed as active ingredients in cosmetics to mimic these processes. By way of examples, mention may be made of the well-known lipopeptides Pal-KTTKS (SEQ ID No. 1) sold under the trademark MATRIXYLTM and the Pal-GHK / Pal-GQPR mixture (SEQ ID No. 2) under the trademark MATRIXYLTM 3000, corresponding to fragments of collagen, for which thanks to in vitro tests it was possible to measure effectively a stimulation of collagen synthesis and thanks to in vivo tests a significant improvement of various factors such as firmness, elasticity, density , the thickness, the microrelief of the skin (wrinkles and fine lines), etc.
    [0003] Peptides have thus become unavoidable and promising active ingredients, particularly in the cosmetics industry, where new compounds are constantly being researched, capable of beautifying the skin and the integuments, that is to say of improve the overall condition by correcting imperfections. The present inventors have thus been more particularly interested in searching for novel peptide compounds having an activity on the main molecules that constitute the extracellular matrix (ECM) of the skin and which decrease with age, and more particularly new peptide compounds capable of to intervene in the synthesis of collagen, the main protein of the skin. 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, the most abundant protein in the dermis, is essential for firm skin. Elastin is synthesized and secreted in the extracellular dermal space. It is the major component, up to 90%, of elastic fibers.
    [0004] Fibronectin is a glycoprotein present in the extracellular matrix, which plays a key role in the adhesion of cells 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, 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. The increase in collagen IV and laminin syntheses 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 anchoring cell surfaces to the basal lamina. 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 JDE and 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. The stimulated synthesis of these molecules by the peptide compound will result from the results on the embellishment and the general state of the skin, in terms of its mechanical properties: a denser, thicker, denser, firmer, more toned skin , more flexible and elastic, a volumizing effect, plumping, and therefore anti-wrinkles, and also at the level of the perception of the complexion, its homogeneity and its brightness. Numerous peptides, peptide compounds or mixtures thereof having properties on the MEC and anti-aging applications have already been proposed, in particular by the Applicant, such as the MATRIXYLTM, the MATRIXYLTM 3000 cited above, or more recently the Pal-KMO2K under the trademark MATRIXYL Synth-6TM (M02 corresponding to a dioxygenated methionine). Other known peptides having a cosmetic activity, in particular on the synthesis of the ECM compounds, are mentioned later in the description.
    [0005] The object of the present invention is to propose other peptide compounds which may improve the general state of the skin and superficial body growths, and more particularly peptide compounds which are active on the synthesis of dermal ECM proteins. In addition, it aims to provide peptide compounds sufficiently effective to be used alone or in combination, in proportions of a few ppm, and can be used in the form of a topical composition, including cosmetic. Preferably, the present invention also aims to propose active peptide compounds on the most possible targets (the various types of collagen, elastin, fibronectin, laminin and hyaluronic acid in particular) to offer the best and most complete cosmetic benefit possible .
    [0006] The present invention provides a peptide compound which can be used in cosmetics and dermatology comprising at least one amino acid selected from lysine, a lysine analogue and a hydroxyl derivative of these amino acids, to which is grafted by peptide bond to the nitrogen of the side chain a carboxylic acid comprising at least one ring or a heterocycle. As shown in Table 1 below, ornithine, diaminobutyric acid and diaminopropionic acid are lysine analogs according to the present invention, each comprising a side chain of 3, 2 and 1 atom ( s) of carbon instead of 4 for lysine and ending with an amine NH2 function The number of carbon playing the role of spacer more or less long. According to the invention, it is on this lateral amine function that a carboxylic acid comprising at least one ring or heterocycle is grafted. Lysine Ornithine Diaminobutyric acid Diaminopropionic acid, E . The hydroxylated derivatives include, for example, hydroxylysine: According to the invention, at least one ring or heterocycle is understood to mean a unicycle or a polycycle with 2 or 3 contiguous rings, each ring being a carbon cycle at 5, 6 or 7 atoms, aromatic or otherwise, which may contain a N, O or S heteroatom, said ring or heterocycle may thus contain a function -OH, -O-, -CO-, -S-, -N =, -NH- , -N = C-NH-, as well as a charged nitrogen function.
    [0007] According to the invention, the charged nitrogen function corresponds to -N ± (r1) = or -N ± (ri, r2) -; ri and r2, independently of one another, being alkyl radicals, preferentially Me, Et, Pr and Bu. Preferably according to the invention, the ring or heterocycle comprises 5 or 6 atoms. The present invention is based on the fact that lysine is very predominantly involved in the "cross-linking" (crosslinking) of collagen fibrils, and that cross-linking is very important for good cohesion of the various constituents of the skin. . The lysine of a peptide chain of collagen, under the action of lysyl hydrolase, is converted into hydroxylysine (Hyl). Lysyl oxidase (LOX) then converts the amine (-NH 2) function of lysine (or hydroxylysine) to aldehyde (-CHO) which reacts spontaneously with another lysine (or hydroxylysine) to give an immature cross-link. between the two peptide chains (Hyl + Hyl ketoamine, Lys + Hyl aldimine). This cross-link of two chains is said to be immature because the functions aldimine (-N = CH-) or ketoamine (-C = O-CH2-NH-) can still react with a third lysine (or Hyl) to form a trivalent crosslink. mature having a nitrogen cycle with 5 or 6 bonds which will not react any more and will maintain between them 3 chains of collagen. There is also another possibility of reacting the aldehyde form of lysine (= Allysine) (and / or hydroxylysine = hydroxyallysine) on itself (aldol reaction) which also produces a divalent cross-link. Telopeptide Telopeptide Ketoamine Pyridinolines-CH-Hyl or Lys Aldehyde CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 (CHOH) H) CH 2 CHO NH 2 NH 9 H 2 CH 2 CH 2 CHOH (H) CHOH (H) CHOH (H) CH 2 CH 2 CH 2 CH 2 CH 2, 9112 H // - CH Helix / CH 2 CH 2 CH 2 CH 2 9 H 2 9H 2 CH2 CH2 CH2 CH2 CH2 CH2 (CH2) CH2 (CH2) CH2 (CH2) CHH (H) 9H2 9H2 9H2CH CH2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H2H thus small peptides or peptide compounds in the matrix are formed which have one or more lysines carrying a ring on the side chain of lysine.
    [0008] The present inventors have found that such peptides having lysine on which is grafted a (poly) (hetero) ring could also serve as a signal, such as matrikines, for the renewal of collagen and / or extracellular matrix. The description of in vitro tests given below shows that such peptide compounds effectively exhibit an activity of stimulating the synthesis of the MEC marker molecules. They are active from a few ppm, and can be used alone or in combination to improve the appearance and general condition of the skin and its integuments, and in particular for the treatment and / or prevention of the signs of aging, and / or or imperfections of the skin and its integuments. The inventors have shown that the peptide compounds according to the invention have, in particular, a stimulating activity for the synthesis of collagen I and IV, elastin, fibronectin, laminins and hyaluronic acid. Comparative tests also show the superiority of the peptide compounds according to the invention over these syntheses compared to ungrafted peptides. It has also been demonstrated that these peptides show an improvement in their physicochemical properties, especially their stability. More particularly, the peptide compound according to the invention has the following general formula I: X- (AA) .- (AA) * - (AA) .- Z (I) in which: - (AA) * is lysine (K *), ornithine (Orn *), diaminopropionic acid (Dap *) or diaminobutyric acid (Dab *) or a derivative of these amino acids, on which is grafted by peptide bond on the a side-chain nitrogen containing a carboxylic acid comprising at least one aromatic or non-aromatic ring or heterocyclic ring containing 5, 6 or 7 atoms, said ring or heterocycle possibly containing a function -OH, -O-, -CO-, -S- , -N =, -NH-, -N = C-NH-, as well as a charged nitrogen function. n = 0, 1, 2, 3 or 4; - m = 0, 1, 2, 3 or 4; - AA = (AA) * or an amino acid selected from alanine (A, Ala), cysteine (C, Cys), aspartic acid (D, Asp), glutamic acid (E, Glu), phenylalanine (F, Phe), glycine (G, Gly), histidine (H, His), isoleucine (I, Ile), lysine (K, Lys), leucine (L, Leu), methionine (M, Met), asparagine (N, Asn), proline (P, Pro), glutamine (Q, Gln), arginine (R, Arg), serine (S, Ser), threonine (T, Thr), valine (V, Val), tryptophan (W, Trp) and tyrosine (Y, Tyr), their derivatives or the like; AA being independently selected from each other when n + m> 1; At the N-terminus, X is chosen from H, -CO-R 1 and -SO 2 -R 1 - at the C-terminal end, Z is chosen from OH, OR ', NH 2, NHR 1 or N 1211 22; 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 or phosphorylated; and / or sulfur, said group may possess in its backbone a heteroatom particularly O, S and / or N. In the formula (I), preferably the amino acid AA is (AA) * or an amino acid selected from: - glycine (G, Gly), proline (P, Pro) or lysine (K, Lys), which are the most common amino acids in collagens; Their hydroxylated derivatives, such as hydroxyproline (Hyp) and hydroxylysine (Hyl); amino acids having an alcohol function such as serine (S, Ser), threonine (T, Thr) and tyrosine (Y, Tyr); and the other natural amino acids having a ring, that is to say histidine (H, His) and phenylalanine (F, Phe).
    [0009] More preferably, in formula (I), the amino acid AA is (AA) * or glycine (G, Gly), histidine (H, His) or lysine (K, Lys), or derivatives thereof hydroxylated; more preferably the amino acid AA is selected from glycine (G, Gly), histidine (H, His) and lysine (K, Lys). According to the invention, the carboxylic acid grafted with (AA) * may be an encoded amino acid comprising a (poly) ring or (poly) heterocycle as defined above according to the invention, that is to say -deside selected from: (AA) * Peptide compound: p = 1, 2, 3 or 4 proline (P, Pro) (A) hydroxyproline (Hyp) ,, (B) 3029782 7 pyroglutamic acid (Pyr ), (C) histidine (H, His), (D) phenylalanine (F, Phe), (E) tyrosine (Y, Tyr); and (F) tryptophan (W, Trp), or (G) 3029782 8 According to the invention, the (AA) * grafted carboxylic acid may also be a derivative or analogues of these amino acids, such as: (AA) * Peptide compound p = 1, 2, 3 or 4 carboxylic acid tetrahydroisoquinoline-3 (Tic) which is a derivative of phenylalanine. (H) the carboxylic acid tetrahydronorharman-3 (Tpi) which is a derivative of tryptophan (I). As preferred examples of carboxylic acid according to the invention which are not amino acids or derivatives, mention may also be made of the following acids: (AA) * Peptide compound p = 1,2,3 or 4 Pipecolic acid (Hpr) (proline analogue) (J) Nipecotic acid (Nip) (proline analogue) (K) ) Nicotinic acid (Nic) (L) Picolinic acid (Pic) (M) 4- (1) - (N) imidazole carboxylic acid (Im4COOH) Stachydrine (Sta) ti (0) The invention thus preferably covers the compounds of the following formula (II): X; Z; n, m and p are as previously defined; and 0 = a ring or a polycycle, each ring having 5 or 6 carbon atoms, aromatic or not, which may contain one or more nitrogen heteroatoms N charged or not; 5 or the following formula (III): wherein: (AA); X; Z; n, m and p are as previously defined; and 0 = a ring or polycycle, each ring having 5 or 6 carbon atoms, aromatic or non-aromatic, containing one or more nitrogen heteroatoms N charged or unloaded. As before, the nitrogen-filled form corresponds to -N + (r1) = or -N + (r1, r2) -; R 1 and R 2, independently of one another, being alkyl radicals, preferentially Me, Et, Pr and Bu. Preferably in the formula III, the nitrogen of ring 0 is in (3 or y with respect to the carbonyl function to which said ring O is linked.
    [0010] Preferably according to the invention, (AA) * is a grafted lysine (K *), the compound then having the general formula IV: X- (AA) nK * - (AA) mZ (IV). Peptide compound K * is chosen from: o K * = K (P): a proline (P, Pro) grafted onto a lysine (K, Lys); K * = K (Hyp): a hydroxyproline (Hyp) grafted on a lysine (K, Lys); and K = K (Pyr): a pyroglutamic acid (Pyr) grafted on a lysine (K, Lys). According to the invention, preference will be given to "small" peptide compounds corresponding to n + m of between 1 to 5 (hexapeptide dipeptides) and preferably n + m = 1 or 2 (dipeptides or tripeptides). Preferably n = 0.
    [0011] According to other preferred features of the invention, in formula (I) above: - 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-R1 and Z is selected from OH, OMe, OEt and NH2, preferably Z is 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 a myristoyl (C14) or a palmitoyl (C16). The preferred compounds according to the invention are the tripeptide compounds: XK (P) -HG-Z, XK (Pyr) -HG-Z, XK (Hyp) -HG-Z, or XK (P) -GH-Z , XK (Pyr) -GH-Z and XK (Hyp) -GH-Z and more particularly peptide compounds: Pal-K (P) -HG-OH, Pal-K (Pyr) -HG-OH, Pal- K (Hyp) -HG-OH, or Pal-K (P) -GH-OH, Pal-K (Pyr) -GH-OH, Pal-K (Hyp) -GH-OH.
    [0012] The present invention also provides a method for increasing the activity on the synthesis of ECM macromolecules of the skin of a peptide compound comprising at least one lysine (K, Lys), an ornithine (Orn), a diaminopropionic acid ( Dap) or a diaminobutyric acid (Dab) or a derivative of these amino acids, characterized in that peptide bonding is carried out on the nitrogen of the side chain of the at least one lysine (K, Lys), ornithine ( Orn), diaminopropionic acid (Dap) or diaminobutyric acid (Dab) or derivative of these amino acids, a carboxylic acid comprising at least one ring or heterocyclic carbon with 5, 6 or 7 atoms, aromatic or not, said ring or heterocycle may contain a function -OH, -O-, -CO-, -S-, N =, -NH-, -N = C-NH-, as well as a charged nitrogen function. This process is preferably applied to peptide compounds of 1 to 9 amino acids.
    [0013] This process can be applied to peptides known in cosmetics having, for example, a lysine as in the following peptide sequences (X zr Z being as defined above): X-KT-Z, X-GHK-Z-X -KPK-Z, -X-KFK-Z, -X-KAvaK-Z (Ava = 5-aminovaleric acid), -X-KMO2K-Z (Matrixyl Synth6) (M02 = dioxygenated methionine), -X-KTFK -Z (SEQ ID NO: 3) -X-KGHK-Z, (Kollaren 6TM or Folixyl ™ or Chronoline ™) (SEQ ID NO: 4) 30-X-KTTKS-Z (Matrixyl®) (SEQ ID NO: 1), or - X-GKTTKS-Z (SEQ ID NO: 5) In these peptides, one, several or all lysine (K, Lys), ornithine (Orn), diaminopropionic acid (Dap) or diaminobutyric acid (Dab) can be grafted, and preferably all.
    [0014] Also preferably according to the invention, the carboxylic acids that will be chosen to be grafted will be proline (P, Pro) or pyroglutamic acid (Pyr). The peptide compounds 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 peptide compounds may be in the form of salts, especially hydrochloric salt. 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). The present invention also provides a cosmetic composition (topical or oral) or dermatological comprising as active ingredient at least one peptide compound according to the invention and as defined above in a physiologically acceptable medium.
    [0015] It also proposes the use of at least one peptide compound according to the invention for the preparation of a composition for a dermatological treatment as well as the use of at least one peptide compound according to the invention or a composition according to the invention comprising said compound for a cosmetic treatment, in particular a topical treatment, for improving the general condition of the skin and / or its integuments, said treatment being intended to stimulate the synthesis of at least one of the molecules of the dermal extracellular matrix. According to the invention, the proposed cosmetic treatment makes it possible to combat aging and / or imperfections of the skin and / or its integuments, in particular as a treatment: global anti-aging; and / or - anti-wrinkles and fine lines (flattened skin surface, filled wrinkles), and / or - improving the mechanical properties of the skin: firmness / tone / elasticity / suppleness, and / or - increasing the density of the skin ( restructuring effect); and / or - increasing the volume of the skin (plumping effect); and / or - to combat the appearance of stretch marks, and / or - moisturizer, and / or - anti-stains, and / or - to improve the homogeneity and / or radiance of the complexion, and / or - acting on the pigmentation of the skin.
    [0016] According to the excipient and the assay for peptide compound (s), the composition according to the invention 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 oral, topical or transdermal use, in contact with the mucous membranes, nails, scalp, hair, hair and mammalian skin and more particularly human, compositions be ingested 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 peptide compounds according to the invention may be solubilized in a lipophilic or hydrophilic matrix with, if appropriate, a solubilizer, depending on the future application. The peptide compound (s) 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-oxidant, acting on the radiance of the complexion, anti-glycation, volumizing, restructuring, anti-carbonylation, dermal, relaxing, 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 by ex), etc. The composition according to the invention can be applied to the face, body, décolleté, scalp, hair, eyelashes, hairs, in any form or vehicles known to those skilled in the art , especially in the form of a solution, a dispersion, an emulsion, a paste or a powder, individually or premixed or can 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 on powdery organic polymers, talcs, bentonites, spores or exines and other mineral or organic carriers.
    [0017] In particular, in cosmetics, applications may be proposed in particular in the skincare ranges of the face, the body, the hair and the hairs and the make-up care ranges, in particular eyelashes and eyebrows. In general, the peptide compounds 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, wools, and any materials intended to come into contact with the skin and which may be used in clothing, underwear, daytime or nightwear, handkerchiefs, or tissues, in order to exert its cosmetic or therapeutic effect through this skin / textile contact and to allow continuous topical delivery. 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 and pharmaceutical ingredients commonly used in the skin care 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 commercial literature Sederma and on the website www.sederma.fr The following commercial ingredients can also be mentioned: 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 LTM (Symri se), RenovHyalTM (Soliance), SeamossTM (Biotech Marine), ArgirelineTM (trade name for acetyl hexapeptide-3 from Lipotec), spilanthol or an extract of Acmella oleracea known as Gatuline ExpressionTM, an extract of 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 30 STM (Sederma), BiobustylTM (Sederma), IdealiftTM (Sederma), Ceramide 2TM, Ceramide A2TM and Ceramide HO3TM (Sederma), LeganceTM (Sederma), IntenslimTM (Sederma), ProdiziaTM (Sedenna) , SenestemTM (Sederma), BeautifeyeTM (Sederma), PacifeelTM (Sederma), Seb ulessTM (Sederma), NG Unsaponifiables of Shea ButterTM (Sederma) or mixtures thereof.
    [0018] 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, can also be mentioned in particular. arnica (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), bergamot (Ruscus aculeatus L), water lilies (Filipendula ulmaria L), orthosiphon (Orthosiphon Stamincus Benth), algae (Fucus Vesiculosus), birch (Betula alba), green tea, kola nut ( 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. blumei, C. esquirolii, C. scutellaroides, C. xanthantus and C. barbatus, as an extract of raciness of Coleus barbatus, extracts of Ballot, Guioa, Davallia, Terminalia, Barringtonia, Trema, antirobia, cecropia, argania dioscoreae such as Dioscorea opposita or mexico, extracts of Ammi visnaga, Siegesbeckia, in particular Siegesbeckia orientalis, plant extracts of the family Ericaceae, in particular extracts of blueberries (Vaccinium angustifollium) from Arctostaphylos uva ursi, alpe vexa, plants containing sterols (in particular phytosterols), Manjistha (extract of plants of the genus Rubia, in particular Rubia Cordifolia), Guggal (extract of plants of the genus Commiphora, in particular Commiphora Mukul), an extract of kola, chamomile, violet clover, Piper methysticum (Kava Kava Sederma), Bacopa monieri (BacocalmineTM, Sederma) and sea whip, Glycyrrhiza glatira, mulberry, tea tree, Larrea di varicata, 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, of Portulaca pilosa, Humulus lupulus, Arabica coffee, Ilex Paraguariensis, Globularia Cordifolia, Oxydendron 30 arboreum, Albizzia julibrissin and Zingiber zerumbet smith. The compositions according to the present invention may comprise other peptide compounds or 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%, by weight. . The term "peptide" herein refers to peptides containing 10 or less amino acids, their derivatives, isomers and complexes with other species such as a metal ion (e.g. copper, zinc, manganese, magnesium, and the like). 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.
    [0019] Non-limiting examples of dipeptides useful in the context of the present invention include Carnosine (beta-AH), YR, VW, NF, DF, KT, RT, KC, CK, KP, KK or TT. Non-limiting examples of tripeptides include RKR, HGG, GHK, GKH, GGH, GHG, KFK, KPK, KMOK, KMO2K or KAvaK. Non-limiting examples of tetrapeptide are RSRK (SEQ ID NO: 6), GQPR (SEQ ID NO: 7), or KTFK (SEQ ID NO: 3). A non-limiting example of pentapeptide 10 is KTTKS (SEQ ID NO: 8) and hexapeptides GKTTKS (SEQ ID NO: 5) and VGVAPG (SEQ ID NO: 9). Other peptides that can be used in the context of the present invention may be chosen from, without this list being limiting: lipophilic derivatives of peptides, preferably the myristoyl and palmitoyl derivatives, and the complexes with the metal ions mentioned above (eg copper tripeptide complex HGG). Preferred dipeptides include, for example, N-Palmitoyl-beta-Ala-His, N-Acetyl-Tyr-Arg-hexadecyl ester (Calmosensine ™, Idealift ™, Sederma), Pal-KT (Sederma) and Pal-RT. 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 conservative substitution analogues 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: 12), Pal-GKTTKS (SEQ ID NO: 13), 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 Sederma Biopeptide-CLTM, MaxilipTM or BiobustylTM which include Pal-GHK. Preferred commercially available sources of tetrapeptide sources include: RIGINTM, Eyeliss ™, Matrixyl ™ Reloaded and Matrixyl 3000 ™, which contain between 50 and 500 ppm of Pal-GQPR (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: 14), Leuphasyl ™ (Tyr-D-Ala-Gly-Phe-Leu) (SEQ ID NO: 15), 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. 16), Serilesine ™ 10 (Ser-Ile-Lys-Val-Ala-Val) (SEQ ID NO: 17) or DecorinylTM (INCI name: Tripeptide-10 Citrul line = 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. 18)) or QuintescineTM (Cys-Gly) sold by Vincience, CytokinolTMLS (casein hydrolyzate) sold by Serobiological / Cognis Laboratories, Ko11arenTM (Gly-His-Lys), IP2O00TM (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 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, spartic, 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 Modulin TM (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. More specifically, the peptide compound (s) according to the invention may be combined with at least one of the compounds selected from vitamin B 3 compounds, compounds such as niacinamide or tocopherol, retinoid compounds such as retinol, hexamidine, α-lipoic acid, resveratrol or DHEA, peptides including N-acetyl-Tyr-Arg-O-hexadecyl, Pal-VGVAPG, Pal-KTTKS, Pal-GHK, Pal -KMO2K and Pal-GQPR, which are conventional active ingredients used in topical cosmetic or dermo-pharmaceutical compositions.
    [0020] The present invention also proposes a cosmetic, cosmeceutical or therapeutic topical treatment method for improving the appearance and the general condition of the skin and its integuments, including topical application to the skin of the skin. a subject in need of an effective amount of a peptide compound or a mixture of peptide compounds according to the invention or a composition according to the invention comprising said compound or said mixture of compounds, the peptide compounds being as defined above. By "topical treatment" or "topical use" is meant an application that is intended to act at the place where it is applied: skin, mucous membrane, appendages. The peptide compound or the composition according to the invention may be applied locally to the targeted zones. The "effective" amount depends on various factors, such as age, condition of the patient, severity of the disorder or pathology, 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 peptide compounds 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 % 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 peptide compounds 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. As an example, for a cosmetic facial treatment, the European Cosmetics Directive has set a standard application amount of a cream of 2.72 mg / cm 2 / day / person and for a body lotion 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 aimed at the skin, such as, for example, treatments by light therapy, by heat or by aromatherapy. According to the invention, it is possible to propose devices with several compartments or kits 30 intended to implement the method described above, and which could include, by way of example, and without being limiting, in a first compartment containing a composition containing a peptide compound of the invention or a mixture thereof and in a second compartment an additional excipient and / or active, the compositions contained in said first and second compartments being here considered as composition of combination for simultaneous use, separate or spread over time in particular in one of the treatments defined above. The cosmetic treatment method according to the invention is more particularly adapted to slow the degradation of the molecules of the dermal extracellular matrix and / or to act on the JDE via the stimulation of collagen IV and / or laminin, more particularly adapted to the treatment. - global anti-aging; and / or - anti-wrinkles and fine lines (flattened skin surface, filled wrinkles), and / or - improving the mechanical properties of the skin: firmness / tone / elasticity / suppleness, and / or - increasing the density of the skin (effect restructuring); and / or increasing the volume of the skin (plumping effect); and / or - to fight against the appearance of stretch marks, and / or - moisturizer, and / or - anti-stains, and / or - to improve the homogeneity and / or radiance of the complexion, and / or 15 - acting on pigmentation of the skin. Other applications are of course conceivable for the peptide compounds 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. as a preventive or curative. A composition according to the invention comprising at least one of the peptide compounds defined by formula I is suitable for a therapeutic treatment of skin deficient in molecules constituting the dermal extracellular matrix. The following examples describe and illustrate certain aspects of the invention. They should not be perceived as limiting the disclosure since they provide mainly information useful for its understanding and implementation. A) General Protocol for Synthesis of the Peptide Compounds of the Invention with Modified Lysine The peptide compounds are synthesized in the solid phase using the Fmoc coupling chemistry (amine protecting group (fluorenylmethoxycarboyle) to protect the next amino acid in the sense of the N-terminus of the peptide). The carrier comprising the first Fmocamino acid (250 μM) is suspended in DMSO and is deprotected with a solution of pyrrolidine (20% in DMSO) for 30 min. It is then rinsed several times with DMSO. The coupling of the following Fmoc-amino acid (200 mM / DMSO) is carried out with HATU (0.5M / DMSO) (agent used to transform the carboxylic acid into an active ester) in the presence of N-methylmorpholine (2M / DMSO) for 2 hours. . When the coupling is complete, the resin is rinsed several times with DMSO. This duty cycle is performed to couple each amino acid of the peptide compound sequence as well as to couple an N-terminal group (eg palmitoyl (Pal)). A linear peptide compound is then completely protected on a support. To carry out the modification of the lysine, care should be taken to incorporate in the sequence a protected lysine derivative on its side amine with the methyltrityl (Fmoc-Lys (Mtt) -OH) group. This Mtt group is released with a solution of TFA-TIS-DCM (5-10-85) and the liberated amine is neutralized with the preceding pyrrolidine solution. After rinsing with DMSO, the desired acid is coupled, with the same protocol as above, and rinses, ending with DCM. Final deprotection and cleavage of the support is performed with a solution of TFA-TIS-H20 (952.5-2.5) for 30 min. The solid support is filtered and the solution is evaporated under reduced pressure to remove TFA. The deprotected peptide is then precipitated with ether. The suspension is centrifuged and rinsed with ether. The centrifugation operation is repeated 3 times by changing the ether and then the crude peptide compound is allowed to dry. It is then taken up in 0.1N HCl, frozen and freeze-dried. B) Preparation of a Composition According to the Invention Comprising a Peptide Compound Prepared According to Example A)
    [0021] Starting materials: - the pure peptide compound, synthesized according to the synthesis method explained above; Excipient: a mixture of fatty esters, chosen so as to form an oily matrix, for example intended to form a composition without water for the subsequent formulation of cosmetic compositions without water.
    [0022] Procedure: The peptide compound is mixed with the excipient and gently stirred and heated until solubilization and total clarity. C) In vitro evaluations The peptide compounds according to the invention have a number of remarkable effects presented below. Compounds prepared according to A) above and dissolved in an excipient have been tested in vitro and have shown activities which are presented hereinafter. 1) ELISA assays Protocol Normal human fibroblasts (FHN) in culture are placed in contact with the test products or their excipient (negative control) for 72 hours. At the end of the contact, the culture supernatants are removed and the syntheses of the dermal macromolecules are estimated by ELISA assays. An estimate of cell viability is made by Hoechst assay and allows to weight the data obtained. Results Table 1: Collagen I Product Concentration% of variation / control Significance (Student test) Pal-K (P) -HG-OH 3 ppm + 104 p <0.05 7 ppm + 71 p <0.01 10 ppm + 107 p <0.01 Pal-K (Pyr) -HG-OH 7 ppm + 71 p <0.01 10 ppm + 93 p <0.01 Table 2: Collagen IV Product Concentration% of variation / control Significance (Student test ) Pal-K (P) -HG-OH 3 ppm + 36 p <0.01 7 ppm + 79 p <0.01 10 ppm + 182 p <0.01 Pal-K (Pyr) -HG-OH 12, 5 ppm + 234 p <0.01 Table 3: Fibronectin Product Concentration% of variation / control Significance (Student test) Pal-K (P) -HG-OH 3 ppm + 32 p <0.01 7 ppm + 53 p < 0.01 10 ppm + 59 p <0.01 Pal-K (Pyr) -HG-OH 7 ppm + 50 p <0.01 10 ppm + 71 p <0.01 12.5 ppm + 249 p <0, 01 Pal-K (P) -GH-OH 7 ppm + 46 p <0.01 Pal-K (Pyr) -GH-OH 3 ppm + 22 p <0.01 7 ppm + 37 p <0.01 10 ppm + 54 p <0.01 3029782 22 Table 4: Laminins Product Concentration% of variation / control Significance (Student test) Pal-K (Pyr) -HG-OH 7 ppm + 23 p <0.05 10 ppm + 30 p < 0.05 Pal-K (Pyr) -GH -OH 10 ppm + 33 p <0.01 Table 5: Elastin Product Concentration% of variation / control Significance (Student test) Pal-K (P) -HG-OH 10 ppm + 224 p <0.05 Pal-K ( Pyr) -HG-OH 7 ppm + 156 p <0.01 Table 6: Hyaluronic acid Product Concentration% of variation / control Significance (Student test) Pal-K (P) -HG-OH 3 ppm + 53 p <0 , 01 5 ppm + 44 p <0.01 Pal-K (Pyr) -HG-OH 12.5 ppm + 310 p <0.01 Pal-K (Pyr) -GH-OH 7 ppm + 67 p <0, 01 10 ppm + 168 p <0.01 Comparative ELISA Assays Pal-K (P) -HG-OH and / or Pal-K (Pyr) -HG-OH are compared with Pal-KHG-OH on the same ELISA tests .
    [0023] Table 7: Collagen I Product Concentration% of variation / control Significance (Student test) Pal-KHG-OH 3 ppm + 27 p <0.05 10 ppm + 78 p <0.01 Pal-K (P) -HG- OH 3 ppm + 104 p <0.05 10 ppm + 107 p <0.01 Pal-K (Pyr) -HG-OH 10 ppm + 93 p <0.01 3029782 Table 8: Collagen IV Product Concentration% of variation / control Significance (Student test) Pal-KHG-OH 10 ppm + 116 p <0.01 Pal-K (P) -HG-OH 10 ppm + 182 p <0.01 Pal-K (Pyr) -HG-OH 12.5 ppm + 234 p <0.01 Table 9: Fibronectin Product Concentration% of variation / control Significance (Student test) Pal-KHG-OH 12.5 ppm + 64 p <0.05 Pal-K (Pyr) - HG-OH 12.5 ppm + 249 p <0.01 Table 10: Laminin Product Concentration% of variation / control Significance (Student test) Pal-KHG-OH 10 ppm - 38 p <0.01 Pal-K (P) -HG-OH 10 ppm + 32 p <0.05 Pal-K (Pyr) -HG-OH 10 ppm + 30 p <0.05 Table 11: Elastin Product Concentration% of variation / control Significance (Student test) KHG-OH 7 ppm + 113 p <0.01 12.5 ppm + 93 p <0.01 Pal-K (P) -HG-OH 10 ppm + 224 p <0.05 Pal-K (Pyr) -HG-OH 7 ppm + 156 p <0.01 Table 12: Hyaluronic Acid Product Concentration % of variation / control Significance (Student test) Pal-KHG-OH 12.5 ppm + 225 p <0.05 Pal-K (Pyr) -HG-OH 125 ppm + 310 p <0.01 3029782 24 D) GALENIC Different formulations are described below. Additional cosmetic active ingredients, optionally supporting and / or complementing the activity of the active ingredient according to the invention may be added in the appropriate phase depending on 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 desired end effect and the targeted consumer, for example antioxidant, moisturizing, nourishing, protective, smoothing, remodeling, volumizing (lipofiling), acting on the radiance of the complexion, anti-stain, concealer, anti-glycation, slimming, soothing, myogenic relaxing, 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 compound according to the invention in a Fat Excipient 3.00 Phase E Potassium Sorbate 0.10 Phase F Sodium Hydroxide 30% (Sodium Hydroxide) 0.60 Demineralized Water 6.00 G Phase Perfume 0.10 3029782 25 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: CALMOSENSINETm: sedative active ingredient marketed by Sederma (W01998 / 07744) containing lipo-dipeptide Tyr-Arg. It reduces feelings of discomfort. 10 - SEBULESSTM: active ingredient marketed by Sederma comprising an extract of Syringa vulgaris obtained by in vitro cell culture, sebum regulator 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, puffiness, dullness and pulled 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, for example firming gel for the body Ingredient (INCI name)% by weight Phase A Demineralized water Qs 100 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 Tween 20 (Polysorbate 20) 1.00 Peptide compound according to the invention 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 Perfume 0.10 3029782 26 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 Talc Qsp 100 Kaolin 2.00 Calcium Stearate 1.00 Mica 4.00 Silica 1.00 Bismuth Oxychloride 2.00 Potassium Sorbate qs Phenoxyethanol 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 3029782 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 Compound According to the Invention in a Fatty Matrix 3.00 Phase D Perfume 0.30 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 Parsol MCX (Ethylhexyl Methoxicinnamate) 3.50 Phase B Demineralized Water Qs 100 Phase C 0.20 Carbopol 940 (Carbomer) Phase D Demineralized Water 2.00 3029782 28 Triethanolamine 99% (Triethanolamine) 0.20 Phase E Propylene Glycol 0.10 Mixed Parabens Phase F Sodium Hydroxide 30% (Sodium Hydroxide) 5, Deionized water qs Phase G Peptide compound according to the invention in a hydrophilic matrix 2.00 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 (30)
    [0001]
    REVENDICATIONS1. A peptide compound that can be used in cosmetics and dermatology comprising at least one amino acid selected from lysine, a lysine analogue and a hydroxylated derivative of these amino acids, to which a carboxylic acid is grafted by peptide bonding to the nitrogen of the side chain. comprising at least one ring or heterocycle.
    [0002]
    2. Compound according to claim 1, characterized in that the lysine analogue is chosen from ornithine (Orn), diaminopropionic acid (Dap) or diaminobutyric acid (Dab).
    [0003]
    Peptide compound according to claim 1 or 2 of the following general formula I: X- (AA) .- (AA) * - (AA) .- Z (I) wherein: - (AA) * is lysine (K) *), ornithine (Orn *), diaminopropionic acid (Dap *) or diaminobutyric acid (Dab *) or a hydroxylated derivative of these amino acids, on which is grafted by peptide bond on the nitrogen of the chain a carboxylic acid comprising at least one aromatic or non-aromatic ring or heterocyclic ring having 5, 6 or 7 atoms, said ring or heterocycle possibly containing a function -OH, -O-, -CO-, -S-, -N = , -NH-, -N = C-NH-, as well as a charged nitrogen function; - AA = (AA) * or an amino acid selected from alanine (A, Ala), cysteine (C, Cys), aspartic acid (D, Asp), glutamic acid (E, Glu), phenylalanine (F, Phe), glycine (G, Gly), histidine (H, His), isoleucine (I, Ile), lysine (K, Lys), leucine (L, Leu), methionine (M, Met), asparagine (N, Asn), proline (P, Pro), glutamine (Q, Gln), arginine (R, Arg), serine (S, Ser), threonine (T, Thr), valine (V, Val), tryptophan (W, Trp) and tyrosine (Y, Tyr), their derivatives or the like; the AA being chosen independently of each other when n + m> 1; at the N-terminus, X is chosen from H, -CO-R1 and -502-R1-at the C-terminal end, Z is chosen 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 may have in its backbone a heteroatom particularly 0, S and / or N. - n = 0, 1, 2, 3 or 4; - m = 0, 1, 2, 3 or 4; 3029782 30
    [0004]
    4. Compound according to claim 3, characterized in that AA = (AA) * or an amino acid chosen from glycine (G, Gly), histidine (H, His), lysine (K, Lys), hydroxylysine (Hyl), serine (S, Ser), threonine (T, Thr), proline (P, Pro), hydroxyproline (Hyp), phenylalanine (F, Phe) and tyrosine (Y, Tyr ), their derivatives or the like. 5
    [0005]
    5. Compound according to claim 3 or 4, characterized in that AA = (AA) * or an amino acid selected from glycine (G, Gly), histidine (H, His), lysine (K, Lys), serine (S, Ser) and threonine (T, Thr).
    [0006]
    6. Compound according to one of claims 3 to 5, characterized in that the carboxylic acid grafted with (AA) * is an amino acid selected from proline (P, Pro), hydroxyproline (Hyp), pyroglutamic acid (Pyr), histidine (H, His), phenylalanine (F, Phe), tyrosine (Y, Tyr) and tryptophan (W, Trp) or a derivative of these amino acids.
    [0007]
    7. Compound according to claim 6, characterized in that said derivative is the carboxylic acid tetrahydroisoquinoline-3 (Tic) or the carboxylic acid tetrahydronorharman3 (Tpi). 15
    [0008]
    8. Compound according to one of claims 3 to 5, characterized in that the carboxylic acid grafted with (AA) * is chosen from: pipecolic acid (Hpr) nipecotic acid (Nip) nicotinic acid ( Nic) picolinic acid (Pic); carboxylic acid 4-imidazole (Im4COOH) stachydrine (Sta) betonicin (Btn); and the homarine (Hom). 25
    [0009]
    9. Compound according to one of claims 3 to 8, characterized in that (AA) * = K *, the compound having the general formula IV: X- (AA) n-K * - (AA) m -Z (IV)
    [0010]
    10. Compound according to claim 9, characterized in that K * is chosen from: K * = K (P): a proline (P, Pro) grafted onto a lysine (K, Lys); K * = K (Hyp): a hydroxyproline (Hyp) grafted on a lysine (K, Lys); and K * = K (Pyr): a pyroglutamic acid (Pyr) grafted on a lysine (K, Lys).
    [0011]
    11. Compound according to one of claims 3 to 10, characterized in that R1 and / or R2 is an alkyl chain of 1 to 24 carbon atoms.
    [0012]
    12. A compound according to claim 11, characterized in that R1 and / or R2 is an alkyl chain of 3 to 24 carbon atoms. 3029782 31
    [0013]
    13. Compound according to one of claims 3 to 12, characterized in that X is an acyl group CO-R1 and Z is selected from OH, OMe, OEt and NH2.
    [0014]
    14. Compound according to claim 13, characterized in that Z is OH.
    [0015]
    15. Compound according to one of claims 3 to 14, characterized in that X is an acyl group CO-R1 chosen from octanoyl (C8), decanoyl (C10), lauroyl (C12), myristoyl (C14) and palmitoyl. (C16), stearoyl (C18), biotinoyl, elaidoyl, oleoyl and lipoyl.
    [0016]
    16. A compound according to claim 15, characterized in that X is selected from a myristoyl (C14) or a palmitoyl (C16).
    [0017]
    17. Compound according to one of claims 3 to 16, characterized in that n = 0. 10
    [0018]
    18. A compound according to claim 17, characterized in that it is selected from XK (P) -HG-Z, XK (Pyr) -HG-Z, XK (Hyp) -HG-Z, XK (P) -GH. -Z, XK (Pyr) -GH-Z and XK (Hyp) -GH-Z.
    [0019]
    19. Compound according to claim 18, characterized in that it is chosen from: Pal-K (P) -HG-OH, Pal-K (Pyr) -HG-OH, Pal-K (Hyp) -HG-OH , Pal-K (P) -GH-OH, Pal-K (Pyr) -GH-OH and Pal-K (Hyp) -GH-OH.
    [0020]
    20. Cosmetic or dermatological composition comprising as active ingredient at least one peptide compound according to any one of the preceding claims in a physiologically acceptable medium.
    [0021]
    21. Use of at least one peptide compound according to any one of the preceding claims for the preparation of a composition for a dermatological treatment.
    [0022]
    22. Use of at least one peptide compound according to any one of the preceding claims or a composition according to claim 20, for a cosmetic treatment for improving the general condition of the skin and / or its integuments.
    [0023]
    23. Use according to claim 22 for a treatment to combat aging and / or imperfections of the skin and / or its integuments.
    [0024]
    24. Use according to claim 22 or 23 for topical treatment.
    [0025]
    25. Use according to one of claims 22 to 24 for a treatment: - global anti-aging; and / or - anti-wrinkles and fine lines (flattened skin surface, filled wrinkles), and / or - improving the mechanical properties of the skin: firmness / tone / elasticity / suppleness, and / or - increasing the density of the skin ( restructuring effect); and / or - increasing the volume of the skin (plumping effect); and / or - to combat the appearance of stretch marks, and / or - moisturizer, and / or - anti-stains, and / or 3029782 32 - to improve the homogeneity and / or radiance of the complexion, and / or - acting on the pigmentation of the skin.
    [0026]
    26. A method for increasing the activity on the synthesis of ECM macromolecules of the skin of a peptide compound comprising at least one lysine (K, Lys), a lysine analogue, or a derivative of these amino acids, characterized in that a carboxylic acid comprising at least one ring or at least one lysine (K, Lys), a lysine-like analogue or a derivative of these amino acids, is peptide-bonded to the side chain nitrogen; 5- or 6- or 7-membered carbon heterocyclic ring, aromatic or otherwise, said (poly) ring or (poly) heterocycle may contain a function -OH, -O-, -CO-, -S-, -N =, -NH- , -N = C- 10 NH-, as well as a charged nitrogen function.
    [0027]
    27. Process according to claim 26, characterized in that the lysine analogue is an ornithine (Orn), a diaminopropionic acid (Dap) or a diaminobutyric acid (Dab).
    [0028]
    28. Process according to claim 26 or 27, characterized in that the grafted carboxylic acid is an amino acid selected from proline (P, Pro), hydroxyproline (Hyp), pyroglutamic acid (Pyr), histidine (H, His), phenylalanine (F, Phe), tyrosine (Y, Tyr) and tryptophan (W, Trp) or a derivative of these amino acids.
    [0029]
    29. The method of claim 28, characterized in that said derivative is the carboxylic acid tetrahydroisoquinoline-3 (Tic) or the carboxylic acid tetrahydronorharman3 (Tpi). 20
    [0030]
    30. Process according to claim 27, characterized in that the grafted carboxylic acid is chosen from: o pipecolic acid (Hpr); o Nipecotic acid (Nip); Nicotinic acid (Nic); Picolinic acid (Pic); o the carboxylic acid 4-imidazole (Im4COOH); o stachydrine (Sta); o Betonicin (Btn); and o homarine (Hom). 30
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    BR112017012474A2|2018-02-27|
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    US20180000717A1|2018-01-04|
    KR20170086680A|2017-07-26|
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    法律状态:
    2015-12-11| PLFP| Fee payment|Year of fee payment: 2 |
    2016-06-17| PLSC| Publication of the preliminary search report|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
    FR1462510|2014-12-16|
    FR1462510A|FR3029782B1|2014-12-16|2014-12-16|PEPTIDE COMPOUNDS, COMPOSITIONS COMPRISING THEM AND USES IN PARTICULAR COSMETICS|FR1462510A| FR3029782B1|2014-12-16|2014-12-16|PEPTIDE COMPOUNDS, COMPOSITIONS COMPRISING THEM AND USES IN PARTICULAR COSMETICS|
    PCT/IB2015/059580| WO2016097965A1|2014-12-16|2015-12-14|Peptidic compounds, compositions comprising them and uses of said compounds, in particular cosmetic uses|
    KR1020177019778A| KR20170086680A|2014-12-16|2015-12-14|Peptidic compounds, compositions comprising them and uses of said compounds, in particular cosmetic uses|
    BR112017012474-2A| BR112017012474B1|2014-12-16|2015-12-14|peptide compound, cosmetic or dermopharmaceutical composition, and, use of at least one peptide compound|
    JP2017532130A| JP2018500330A|2014-12-16|2015-12-14|Peptide compounds, compositions containing them and uses of said compounds, in particular cosmetic applications|
    US15/535,651| US20180000717A1|2014-12-16|2015-12-14|Peptidic compounds, compositions comprising them and uses of said compounds, in particular cosmetic uses|
    CN202110544333.0A| CN113264984A|2014-12-16|2015-12-14|Peptide compounds, compositions containing them and use of said compounds, in particular in cosmetics|
    MX2017007819A| MX2017007819A|2014-12-16|2015-12-14|Peptidic compounds, compositions comprising them and uses of said compounds, in particular cosmetic uses.|
    EP15817568.7A| EP3256102A1|2014-12-16|2015-12-14|Peptidic compounds, compositions comprising them and uses of said compounds, in particular cosmetic uses|
    CN201580068679.0A| CN106999401B|2014-12-16|2015-12-14|Peptide compounds, compositions containing them and use of said compounds, in particular in cosmetics|
    JP2021180956A| JP2022019764A|2014-12-16|2021-11-05|Peptide compounds, compositions containing them and the use of said compounds, especially cosmetic applications.|
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