COSMETIC OR DERMATOLOGICAL ACTIVE INGREDIENT COMPRISING A MIXTURE OF UNSATURATED FATTY DICARBOXYLIC

专利摘要:
The ingredient comprises a mixture of unsaturated dicarboxylic acids comprising the Z and E isomers of at least one C12-C24 monounsaturated dicarboxylic acid, the E-isomer concentration being at least 25% by weight based on the weight total isomers Z and E. It can be used to form cosmetic or dermatological compositions, in particular intended to lighten the skin, to improve the clarity and unification of the complexion.
公开号:FR3024037A1
申请号:FR1457213
申请日:2014-07-25
公开日:2016-01-29
发明作者:Bas Wels；Arnaud Fournial
申请人:Sederma SA；Croda International PLC；
IPC主号:

专利说明:

[0001] The present invention relates to a cosmetic or dermatological active ingredient comprising a mixture of unsaturated fatty dicarboxylic acids, also called dioecious acids, a cosmetic or dermatological composition comprising said active ingredient and cosmetic and dermatological uses of said ingredient or said composition.
[0002] The invention relates more particularly to the treatment of the skin and its integuments, of human or animal mammals, and more particularly the topical treatment. An active ingredient based on a mixture of unsaturated dioic acids, predominantly comprising octadec-9-ene-1,18-dicarboxylic acid (HO (O) C (CH2) 7CH = CH (CH2) 7C (0 ) 0H)), hereinafter octadecene dioic acid, is already used in cosmetics, mainly as a skin lightening agent. It has also been described as anti-wrinkle or antioxidant. Medical treatments have also been described, including treatments for acne, rosacea, lentigo, dermatosis especially hyperpigmentaire, eczema, impetigo, anti-microbial or deodorant. All documents refer to the same biotechnological process for producing a mixture of dioic acids, including octadecene dioic acid, which is described in WO94 / 07837.
[0003] This process involves the biotransformation of a mixture of fatty acids mainly comprising oleic acid), by a yeast strain, for example of the genus Candida, in particular Candida cloacae, which converts the co-methyl group of the acid. fat in carboxyl group, then creating a dioecious acid with the same chain length and unsaturations as the starting acid. A parasitic desaturase activity present in yeast is also observed in this manufacturing process. As a result, the amount of C18 dioic acid with two or more unsaturations (i.e., eg octadecadiene dioic acid or octadecatrienedioic acid) is increased as compared to the initial mixture. The manufacturing method provides a mixture containing about 60% octadecene dioic acid, about 35% other di-C18 dio acids containing two or more unsaturations and about 5% non-transfected monocarboxylic acids. This mixture is marketed under the trademark Arlatone DIOIC DCATM by the company CRODA. The cosmetics and dermopharmacy industry is always in demand of new ingredients, in particular, more efficient, less expensive in term of manufacture and / or acting on a wider panel of activity. The present invention aims to respond to this request.
[0004] Accordingly, the present invention provides a cosmetic or dermatological active ingredient comprising a mixture of unsaturated dicarboxylic acids comprising the Z and E isomers of at least one C12-C24 monounsaturated dicarboxylic acid, the E-isomer concentration being at least 25% by weight based on the total weight of Z and E isomers.
[0005] The invention proposes the use of an ingredient according to the invention as defined above for the manufacture of a cosmetic or dermatological composition. The invention also provides a cosmetic or dermatological composition comprising an effective amount of a cosmetic or dermatological active ingredient according to the invention and a physiologically acceptable excipient. The invention furthermore proposes an ingredient according to the invention, or a composition according to the invention, for a dermatological treatment. The invention furthermore proposes the use of an ingredient according to the invention or a composition according to the invention for a non-therapeutic cosmetic treatment of the skin and its integuments. The invention also proposes a method for the cosmetic or dermatological treatment of the skin and its integuments comprising the application, particularly topically, to a subject in need of such treatment, of an effective amount of a composition according to the invention. The invention also further provides a mixture of unsaturated dicarboxylic acids comprising the Z and E isomers of at least one C12 to C24 monounsaturated dicarboxylic acid, characterized in that the concentration of (i) E isomer is from at least 40% by weight and Z isomer is at most 60% by weight both based on the total weight of Z and E isomers, (ii) saturated dicarboxylic acid is 0.1% to 4% by weight based on the total weight of the composition, and (iii) monocarboxylic acid is 0.1% to 3% by weight based on the total weight of the mixture.
[0006] The unsaturated dicarboxylic acid mixture of the present invention preferably comprises, consists essentially of, or consists of, at least one C 12 to C 24, preferably C 14 to C 22, even more preferentially C 16 to C 20 dicarboxylic acid. and more particularly C18. The unsaturated dicarboxylic acid mixture comprises both the E (or trans isomer) isomer and the Z isomer (or cis isomer) of at least one C12 to C24, preferably C14, monounsaturated dicarboxylic acid. C22, even more preferably C16 to C20 and more particularly C18. The number associated with C (carbon chain) takes into account the carbons of the carboxylic groups. Thus, the C18 monounsaturated di-carboxylic acid refers to a compound having a hydrocarbon chain with 16 carbon atoms, preferably linear, containing a double bond between 2 carbons, with a carboxylic group at both ends of the hydrocarbon chain, for example (HO (O) C (CH2) 11CH = CH (CH2) .C (O) OH) with n + m = 14. As used herein, the term "unsaturated dicarboxylic acid" includes derivatives thereof, which in the present context include esters, salts, and organo-sulfur compounds in which one or both carboxylic groups have been derived. In particular, the esters and the smaller alkyls, ie C1 to C4, are preferred. Salts, for example of alkali metal, are particularly preferred derivatives, because these can form spontaneously depending on the pH of the medium in which the dicarboxylic acids are present. The position of the double bond between the two carbons can vary along the hydrocarbon chain.
[0007] It is preferably in the central part of the chain and more specifically, exactly in the center of this chain. The preferred C18 mono-unsaturated dicarboxylic acid is octadec-9-ene-1,18-dicarboxylic acid (or octadec). -9-ene-1,18-dioic acid) (HO (O) C (CH2) 7CH = CH (CH2) 7C (O) OH). In one embodiment of the invention, the E-isomer of the at least one monounsaturated dicarboxylic acid is present in the mixture of unsaturated dicarboxylic acids at a concentration of at least 40%, preferably at least minus 55%, especially at least 65%, and more particularly at least 75% by weight based on the total weight of Z and E isomers in the mixture. A preferred isomer E is the E-isomer of octadec-9-ene-1,18-dicarboxylic acid. In one embodiment of the invention, the Z-isomer of the at least one monounsaturated dicarboxylic acid is present in the unsaturated dicarboxylic acid mixture at a concentration of at most 60%, preferably at most 45%. %, especially at most 35%, and more particularly at most 25% by weight based on the total weight of Z and E isomers in the mixture. A preferred Z isomer is the Z-isomer of octadec-9-ene-1,18-dicarboxylic acid (or octadec-9-ene-1,18-dioic acid). In one embodiment of the invention, the mixture according to the invention has at least one of the following indices: (i) iodine number of 50 to 120 g / 100 g, (ii) acid number of 310 to 380 mg of KOH / g, and (iii) saponification number of 315 to 380 mg KOH / g. In one embodiment of the invention, the weight ratio of the E / Z isomers present in the mixture of unsaturated dicarboxylic acids is suitably from 0.5 to 19: 1, preferably from 2 to 10: 1, more preferably from 3 to 6: 1, particularly from 4 to 5: 1, and still more particularly from 4.5 to 4.6: 1 based on the total weight of the mixture of Z and E isomers. -unsaturated carboxylic acid, the composition of unsaturated dicarboxylic acids of the invention may also contain at least one di-unsaturated dicarboxylic acid and / or at least one tri-unsaturated dicarboxylic acid. The unsaturated dicarboxylic acid mixture of the invention suitably comprises (i) at least 65%, preferably at least 80%, particularly at least 90%, more preferably 95% to 99.5%, and especially between 96% and 98% by weight of at least one monounsaturated C12 to C24, preferably C14 to C22, especially C16 to C20, and more particularly C18 (ii) less than 25% dicarboxylic acid, of preferably less than 15%, even more preferably less than 8%, especially between 0.4% and 4% and more particularly between 1.7% and 3.4% by weight of at least one di-unsaturated dicarboxylic acid C12 to C24, preferably C14 to C22, especially C16 to C20, and more particularly C18; and / or (iii) less than 10%, preferably less than 5%, even more preferably less than 2%, particularly between 0.1% and 1% and more particularly between 0.3% and 0.6% by weight of at least one C12 to C24, preferably C14 to C22, especially C16 to C20, tri-unsaturated dicarboxylic acid, and more particularly C18, all based on the total weight of unsaturated dicarboxylic acids in the mixture. In one embodiment of the invention, the combined concentration of the at least one di-unsaturated dicarboxylic acid, and the at least one tri-unsaturated dicarboxylic acid in the unsaturated dicarboxylic acid mixture of the invention is less than 35%, preferably less than 10%, more preferably less than 10%, particularly preferably between 0.5% and 5% and more preferably between 2% and 4% by weight, based on total weight of unsaturated dicarboxylic acids in the mixture. In another embodiment of the invention, the mixture is substantially free of di-unsaturated and / or tri-unsaturated C12-C24 dicarboxylic acid.
[0008] The unsaturated dicarboxylic acid mixture of the invention suitably comprises less than 10%, preferably less than 6%, even more preferably 0.1% to 4%, particularly preferably 1% to 3%, and more particularly between 1.5% and 2.5% by weight of at least one saturated C12 to C24, preferably C14 to C22, especially C16 to C20, and more particularly C18, dicarboxylic acid based on the total weight of the mixture.
[0009] The unsaturated dicarboxylic acid mixture of the invention suitably comprises less than 5%, preferably less than 3%, even more preferably 0.01% to 1%, particularly preferably 0.15% to 0%. , 5%, and more particularly between 0.25% and 0.35% by weight of at least one C12 to C24, preferably C14 to C22, especially C16 to C20, monocarboxylic acid, and more particularly in C18, based on the total weight of the mixture.
[0010] The unsaturated dicarboxylic acid mixture of the invention suitably has an iodine number (measured and described below) of less than 200, preferably from 30 to 150, more preferably from 50 to 120, in particular from 60 to 100, and more particularly from 70 to 90 g of iodine / 100 g. The iodine index dose unsaturations. The unsaturated dicarboxylic acid mixture of the invention suitably has an acid number (measured and described below) of less than 450, preferably from 290 to 400, more preferably from 310 to 380, particularly from 330 to 360, and more particularly between 340 and 350 mg of KOH / g. The acid number dose the free acid functions. The unsaturated dicarboxylic acid mixture of the invention suitably has a saponification number (measured and described below) of less than 450, preferably from 295 to 400, more preferably from 315 to 380. particularly from 335 to 360, and more particularly from 345 to 350 mg KOH / g. The saponification index measures the free and esterified acid functions. In one embodiment of the invention, the active ingredient of the invention further comprises at least one antioxidant or free radical scavenger to protect the mixture against oxidation and to allow long-term storage thereof without significant degradation. . The active ingredient of the invention preferably comprises from about 0.001% to 5%, and more preferably from 0.01% to 1% by weight of at least one antioxidant or radical scavenger, relative to to the total weight of the ingredient. The at least one anti-oxidant / radical scavenger may be added to the active ingredient of the invention during its manufacture, and / or added to the cosmetic or dermatological composition during its manufacture. Suitable antioxidants / radical scavengers may be selected from the group consisting of ascorbic acid (vitamin C) and its salts, ascorbyl fatty esters such as ascorbyl palmitate, ascorbic acid derivatives (ie, magnesium). ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl sorbate), tocopherol (vitamin E), tocopherol sorbate, tocopheryl acetate, other tocopherol esters, tocotrienols, with or without tocopherols, bisabolol, linoleic acid, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (commercially available as TroloxTM), gallic acid and its alkyl esters, especially propyl gallate, uric acid its salts and its alkyl esters, sorbic acid and its salts; lipoic acid, amines (ie N, N-diethylhydroxylamine, amino-guanidine), sulfhydryl compounds (ie glutathione), dihydroxy fumaric acid and its salts, lysine pidolate, amino acids, silymarin lysine, 1-methionine, proline, olive extracts, tea extracts, polyphenols such as proanthocyanidin of pine bark, carotenoids, curcumin compounds such as tetrahydrocurcumin, OCTA (L-2-oxo-4-thiazolidine carboxylic acid), melanin, rosemary extract, skin / grape extract, pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate, butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA), orizanol, ethyl hexyl ferulate can be used. Preferably, the antioxidants / radical scavengers that can be used according to the invention are chosen from tocopherol (such as CovioxTM T70), bisabolol, tocopherol acetate, ascorbyl palmitate and butylated hydroxytoluene (BHT). and pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate and mixtures thereof. The inventors have shown that, very surprisingly, such an active ingredient had improved efficacy on cosmetic and dermatological treatments compared with an active ingredient of the state of the art which does not have at least 25% of the E-isomer, in particular relative to a mixture of unsaturated dioic acids obtained by biotransformation. Comparative results are given further in the detailed description. The biotechnological process of the state of the art described above applied to oleic acid leads to the obtaining of the Z isomer of octadecene dioic acid. , the oleic acid of natural origin used being more than 99% of the isomer Z (cis)). The isomer E can be obtained in particular by means of another so-called metathesis process, more particularly of auto-metathesis, which implements the rearrangement of double bonds according to the scheme below in the presence of a specific catalyst based on ruthenium catalyst: Catalyst R1 R3 R4 For the synthesis of octadecene dioic acid, two molecules of methyl oleate can be recombined by metathesis to obtain the corresponding diester (1,18-octadecen-9-dioate dimethyl and 9-octadecene), as shown in the diagram below: 0 -CH3 2x methyl oleate 9-octadecene dimethyl dioic ester 2x C19H3602 C181-136 C20113604 The two products formed as well as the unreacted substrate are then separated by distillation and to finish a hydrolysis step of the dimethyl dioic ester leads to octadecene dioic acid. It is also possible to use oleic acid as starting material. The metathesis reaction is described in international applications WO 2013/140144 and WO 2013/140145. A choice of catalyst / catalyst activator pair is described in patent applications WO 2013/140144 and WO 2013/140145. This reaction produces predominantly E isomers (in an E / Z ratio of about 80/20). The particular ratio of isomers E to Z isomers required in the composition of at least one unsaturated dicarboxylic acid according to the present invention can be obtained by combining a mixture resulting from the metathesis (majority of E isomers of dicarboxylic acid (s)) ( s) mono-unsaturated (s)) with a mixture of fermentation biotransformation (Z-isomers of monounsaturated dicarboxylic acid (s)). The ingredient according to the invention can be advantageously used for a non-therapeutic cosmetic treatment of the skin and its integuments, in particular a topical treatment. Such a cosmetic treatment is intended to improve the general condition of the skin and superficial body growths. In a cosmetic composition, the ingredient will generally be used at a concentration of between 0.01% and 20%, preferably from 0.05% to 10%, particularly from 0.1% to 5%, and especially around 1%, 2% and 4% by weight relative to the total weight of the composition. More particularly, the cosmetic treatments according to the invention may be chosen in particular from the following treatments: to reduce the production of melanin in the skin, to lighten the skin and its integuments, to reduce skin spots, to homogenize the coloration of the skin, 15 - to moisturize, - to combat cutaneous dryness, - to protect the cutaneous barrier, - to stimulate the synthesis of at least one of the extracellular dermal matrix molecules, - anti-oxidant, - anti-wrinkles and fine lines, - slimming, - to improve the mechanical properties of the skin: firmness, and / or elasticity, and / or flexibility, 25 - lipofiling by promoting expansion and / or training subcutaneous adipose tissue to improve and / or embellish any body part deficient in lipids, - anti-aging, - oily skin, - skin acne-prone, 30 - anti-dandruff, - acting on the skin. growth hair, hair and nails, - desquamant, - anti-solar radiation, - deodorant, 35 - anti-seborrhoeic, - anti-glycation, 3024037 8 - promoting re-epithelialization and / or regeneration of the skin or lips and contour of the hair root or nails, and / or - to improve the comfort of the skin altered by either cold, UV or mechanical friction.
[0011] A particularly advantageous use according to the invention, as shown by the in vivo tests given later in the description, is the lightening treatment of skins of phenotypes V and / or VI, and more particularly of phenotypes VI (black skins). According to the invention, the active ingredient can also be used for dermatological treatment, in particular topical anti-bacterial, anti-microbial, anti-inflammatory, anti-acne, against pimples, rosacea, lentigo, dermatosis especially hyperpigmentaire, eczema or impetigo. It goes without saying that other cosmetic and therapeutic applications are possible. According to other advantageous features, the active ingredient according to the invention may be used in combination with one or more additional or complementary active ingredients, advantageously making it possible to offer a wider range of cosmetic properties. The combined effects may advantageously be additive and advantageously have a synergistic effect. The additional active ingredients may be, for example, chosen from lightening, pro-pigmenting, anti-redness, anti-blot, soothing agents, sunscreens, moisturizing, moisturizing, exfoliating, smoothing, toning, anti-aging, anti-aging and anti-aging agents. fine lines and wrinkles, improving the mechanical and elastic properties, the brightness of the complexion, the detoxifying active agents, anti-hair regrowth, anti-acne, acting on the secretion of sebum, mattifying, unifying, anti-inflammatory, anti-oxidants / radical scavengers (especially those described above for their use in the ingredient according to the invention), anti-free radicals, anti-glycation agents, anti-dandruff, eye contours (anti-dark circles and anti-puffiness), promoting blood circulation , peptides and vitamins, etc. These active ingredients can be obtained from plant materials, such as plant extracts or vegetable or fermentation products. More specifically, the composition according to the invention may be combined with at least one of the compounds chosen from vitamin B3 compounds, compounds such as niacinamide or tocopherol, retinoid compounds such as retinol, hexamidine, α-lipoic acid, resveratrol or DHEA, peptides, especially 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 dermopharmaceutical compositions. CTFA ("International Cosmetic Ingredient Dictionary & Handbook" (15th Ed. 2014) published by "The Personal Care Products Council", formerly "The Cosmetic, Toiletry, and Fragrance Association, Inc.", Washington, DC) describes a large 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 that are particularly useful can be found in Sederma's commercial literature and at www.sederma.com.
[0012] The following commercial active agents may also be mentioned as examples: betaine, glycerol, Actimoist Bio 2TM (Active Organics), AquaCacteenTM (Mibelle AG Cosmetics), AquaphylineTM (Silab), AquaregulKTM (Solabia), CarcilineTM ( Greentech), CodiavelaneTM (Biotech Marine), DermafluxTM (Arch Chemicals, Inc.), Hydra'FlowTM (Sochibo), Hydromoist LTM (Symrise), RenovHyalTM (Soliance), SeamossTM (Biotech Marine), ArgirelineTM (trade name acetyl 10 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 15 (Sederma), RevidratTM (Sederma), ResistemTM (Sederma), ChronodynTM (Sederma), KombuchkaTM (Sederma), ChromocareTM (Sederma), CalmosensineTM (Sederma), Glycokin factor STM (Sederma), Biobustyl TM (Sederma), IdealiftTM (Sederma), Ceramide 2TM, Ceramide A2TM and Ceramide HO3TM (Sederma), LeganceTM (Sederma), IntenslimTM (Sederma), ProdiziaTM (Sederma), BeautifeyeTM (Sederma), Unsaponifiable Shea Butter (Natural Grade) (Sederma) or mixtures thereof.
[0013] Among the plant extracts which may be combined with the composition according to the invention, ivy extracts, for example climbing ivy (Hedera Helix), Bupleurum chinensis, Bupleurum Falcatum, arnica, may be mentioned in particular. (Arnica Montana L), Rosemary (Rosmarinus officinalis N), Calendula officinalis, Salvia officinalis L, Ginseng (Panax ginseng), Ginko biloba, St. Ruscus 25 aculeatus L), of Ulmaria (Filipendula ulmaria L), Orthosiphon (Orthosiphon Stamincus Benth), Algae (Fucus Vesiculosus), Birch (Betula alba), Green Tea, Kola Nut (Cola Nipida) ), horse chestnuts, bamboo, Centella asiatica, heather, fucus, willow, piloselle, escin extracts, cangzhu extracts, chrysanthellum indicum extracts of chrysanthellum indicum, plants of the genus Armeniacea, Atractylodis Platicodon , Sinnomenum, Pharbitidis, Flemingia, 30 C oleus such as C. Forskohlii, C. blumei, C. esquirolii, C. scutellaroides, C. xanthantus and C. Barbatus, as a raciness extract of Coleus barbatus, extracts of Ballote, Guioa, Davallia, Terminalia, Barringtonia, Trema, antirobia, cecropia, argania, dioscoreae like 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 vera, 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), 3024037 cola extract, chamomile, violet treffle, Piper methysticum (Kava Kava from Sederma), Bacopa monieri (BacocalmineTM, Sederma) and sea whip, Glycyrrhiza glabra, mulberry, melaleu ca (tea tree), Larrea divaricata, Rabdosia rubescens, Euglena gracilis, Fibraurea recisa Hirudinea, Chaparral Sorghum, sunflower flower, Enantia chlorantha, 5 Mitracarpe of the genus Spermacocea, Buchu barosma, Lawsonia inermis L., Adiantium Capillus-Veneris L., Chelidonium majus, 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 10 asphodeloides , Portulaca pilosa, Humulus lupulus, Arabica coffee or Ilex Paraguariensis, Albizzia julibrissin, Oxydendron arboreum, Plantago lanceolata. The compositions of the present invention may include 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. In the context of the present invention, the term "peptide" refers to peptides containing 10 amino acids or less, their derivatives, isomers and complexes with other species such as a metal ion (eg 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, GHK, GKH, GGH, GHG, KFK, GKH, KPK, KMOK, KMO2K or KAvaK. Nonlimiting examples of tetrapeptides are RSRK, GQPR or KTFK. A non-limiting example of pentapeptide is KTTKS and hexapeptides GKTTKS and VGVAPG. 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 palmitoyl derivatives, and the complexes with the metal ions mentioned above (eg complex tripeptide copper HGG). Preferred dipeptides include, for example, N-Palmitoyl-beta-Ala-His, N-Acetyl-Tyr-Arghexadecylester (Calmosensine ™, Idealift ™, 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 conservative substitution analogues N-Acetyl-RKR-NH2 (CK + peptide), N-Biot-GHK (Sederma), Pal-KMO2K (Sederma) and their derivatives. Tetrapeptide derivatives useful in the context of the present invention include, but are not limited to, NPal-GQPR (Sederma), useful pentapeptide derivatives are, but are not limited to, N-Pal-KTTKS 3024037 (MATRIXYL ™, Sederma). , N-Pal-Tyr-Gly-Gly-Phe-X with X being Met or Leu or their mixture. Useful hexapeptide derivatives include, but are not limited to: N-Pal-VGVAPG and derivatives. We can also mention the mixture Pal-GHK and Pal-GQPR (MatrixylTM 3000, Sederma). The preferred commercially available compositions containing a tripeptide or derivative include Biopeptide-CLTM, MaxilipTM or Sederma BiobustylTM. The preferred commercially available compositions of tetrapeptides include: RIGINTM, Eyeliss ™ Matrixyl ™ Reloaded and Matrixyl 3000 ™, which contain between 50 and 500 ppm of palmitoyl-GQPR and an excipient, provided by Sederma. The following commercial peptides may also be mentioned as additional active ingredients: VialoxTM, Syn-akeTM or Syn-Co11TM (Pentapharm), Hydroxyprolisilane CNTM (Exsymol), Argireline TM, LeuphasylTM, AldenineTM, TrylgenTM, EyeserylTM, SerilesineTM or DecorinylTM (Lipotec ), CollaxylTM or QuintescineTM (Vincience), BONT-L-PeptideTM (Infinitec Activos), CytokinolTMLS (Serobiological Laboratories / Cognis), KollarenTM, IP2000TM or MelipreneTM (European Institute of Cell Biology), NeutrazenTM (Innovations), ECM-ProtectTM 15 ( Atrium Innovations), Timp-PeptideTM or ECM ModulinTM (lnfinitec Activos). According to other characteristics of the invention, in a cosmetic or dermatological composition, the ingredient according to the invention can be combined with a sunscreen, preferably having the widest possible spectrum of protection, filtering the UVA and UVB, but also able to filter more specifically IR, UV-close and / or HEV (visible at high energy).
[0014] Useful sunscreens may be organic or inorganic. A wide variety of conventional organic and inorganic sunscreens is usable in the context of the present invention. The exact amount of filter varies depending on the sunscreen chosen and the desired sun protection factor (SPF). Examples of organic filters that may be mentioned include: para-aminobenzoic acid (PABA) derivatives: ethyl dihydroxypropyl PABA, ethylhexyl dimethyl PABA sold in particular under the trade name Escalol 507w by ISP, glyceryl PABA, PEG-25 PABA sold under the trade name Uvinul P25Tm by BASF - salicylic derivatives: homosalate sold under the trade name Eusolex HMSTm by Rona / EM Industries, ethylhexyl salicylate sold under the trade name Neo Heliopan OSTm by Haarmann and Reimer, dipropylene glycol salicylate sold under the trade name Dipsal by Scher, TEA salicylate sold under the trade name Neo Heliopan TSTm by Haarmann and Reimer - derivatives of dibenzoylmethane - butyl methoxydibenzoylmethane sold in particular under the trade name Parsol 1789 by Hoffmann La Roche and isopropyl dibenzoylmethane - cinnamic derivatives: ethylhexyl methoxycinnamate sold under the trade name Parsol MCXTm by Hoffmann La Roche, isopropyl methoxy cinnamate, isoamyl methoxy cinnamate sold under the trade name Neo Heliopan E 1000 by Haarmann and Reimer, cinoxate, DEA 3024037 12 methoxycinnamate, diisopropyl methylcinnamate and glyceryl ethylhexanoate dimethoxycinnamate; - derivatives of (3 (3'-diphenylacrylate: octocrylene sold in particular under the trade name Uvinul N539 by BASF and etocrylene, sold in particular under the trade name Uvinul N35Tm by BASF; - derivatives of benzophenone: the benzophenone-1 sold under the trade name Uvinul 400Tm by BASF, benzophenone-2 sold under the trade name Uvinul D50Tm by BASF, benzophenone-3 or oxybenzone, sold under the trade name Uvinul M40Tm by BASF, benzophenone-4 sold under the Uvinul MS40Tm trade name by BASF, benzophenone-5, benzophenone-6 sold under the trade name Helisorb 11 by Norquay, benzophenone-8 sold under the trade name Spectra-Sorb UV-24 by American Cyanamid, benzophenone- 9 sold under the trade name Uvinul DS-49Tm by BASF and benzophenone-12; - benzylidene camphor derivatives: 3-benzylidene camphor, 4-methylbenzylidene camphor sold under the trade name Eusolex 6300 by Merck, sulfonic acidcamphor benzylidene, benzalkonium methosulfate camphor, terephthalylidene dicamphor sulfonic acid, camphor polyacrylamidomethyl benzylidene; phenyl benzimidazole derivatives: phenylbenzimidazole sulfonic acid sold in particular under the trade name Eusolex 232Tm by Merck, the benzimidazilate sold under the trade name Neo Heliopan APTm by Haarmann and Reimer; Triazine derivatives: anisotriazine sold under the trade name Tinosorb STm by Ciba Geigy, ethylhexytriazone sold in particular under the trade name Uvinul T150Tm by BASF, diethylhexylbutamido triazone sold under the trade name Uvasorb HEBTm by Sigma 3V ; derivatives of phenyl benzotriazole: drometrizole trisiloxane sold under the trade name SilatrizoleTm by Rhodia Chimie; Anthranilic derivatives: menthyl anthranilate sold under the trade name Neo Heliopan by Haarmann and Reimer; imidazoline derivatives: ethylhexyl dimethoxybenzylidene dioxoimidazoline propionate; benzalmalonate derivatives: the benzalmalonate functional polyorganosiloxane sold under the trade name Parsol SLXT ™ by Hoffmann La Roche; Derivatives of dihydroxycinnamic acid (umbelliferone, methylumbelliferone, methylacetobmbelliferone); derivatives of trihydroxy-cinnamic acid (esculetin, methylesculetin, daphnetin, and glucosides, esculin and daphnin); hydrocarbons (diphenylbutadiene, stilbene); dibenzalacetone and benzalacetophenone; naphtholsulfonates (sodium salts of 2-naphthol-3,6-disulfonic acid and 2-naphthol-6,8-disulfonic acid); dihydroxynaphthoic acid and its salts; o- and p-hydroxybiphenyldisulfonates; coumarin derivatives (7-hydroxy, 7-methyl, 3-phenyl); diazoles (2-acetyl-3-bromoindazole, phenyl benzoxazole, methyl naphthoxazole, various aryl benzothiazoles); Quinoline derivatives (2-phenylquinoline salts); uric and violuric acids; tannic acid and its derivatives (e.g., hexaethylether); (butyl carbotol) (6-propyl piperonyl) ether; hydroquinone. The more particularly preferred organic UV filters are chosen from the following compounds: ethylhexyl salicylate, butyl methoxydibenzoylmethane, ethylhexyl methoxycinnamate, octocrylene, phenylbenzimidazole sulfonic acid, terephthalylidene dicamphor sulfonic acid, benzophenone-3 benzophenone-4, benzophenone-5,4-methylbenzylidene camphor, benzimidazilate, anisotriazine, ethylhexyl triazone, diethylhexylbutamido triazone, methylene bis-benzotriazolyl tetramethylbutylphenol, drometrizole trisiloxane, and mixtures thereof. Also preferred are the compositions described in US Pat. No. 6,190,645 and in particular the sunscreen active ingredients sold under the trademark Incroquat-UV-283 by Croda. The inorganic filters that can be used in the composition according to the invention are, in particular, the nanopigments (average size of the primary particles generally between 5 nm and 100 nm, preferably between 10 nm and 50 nm) of coated or uncoated metal oxides, such as, for example, nanopigments of titanium oxide (amorphous or crystallized in rutile and / or anatase form), iron, zinc, zirconium, cerium or maganese. Coating agents are, moreover, alumina and / or aluminum stearate. Such nanopigments metal dioxides, coated or uncoated, are in particular described in patent applications EP0518772 and EP0518773. As a preferred example, it is advantageous to mention the inorganic filter sold by Croda under the name Solaveill® commercial range having a broad spectrum of protection, particularly remarkable vis-à-vis the UVA and / or UVB. Another preferred inorganic sunscreen is Optisol marketed by Oxonica or a TiO2 filter modified with Manganese (TiO2Mn). TiO2Mn provides the skin advantageously, in addition to its filtering action vis-à-vis the UV, a unifying, mattifying and bright effect, without white residue. According to still further features of the invention, in a cosmetic or dermatological composition, the ingredient according to the invention may be combined with an active known to protect and / or treat damage to the skin or its integuments caused by different radiations, including the following commercial assets: Cosmedia DCA from Cognis-Care Chemicals, Helioguard 365Tm, NanoVitTm and PhytoCellTecTm Solar Vitis from Mibelle AG Cosmetics, Melanezei'm from Dragoco, VanireaTm from Solabia, Solarine IIITm, NucleolysTm and Sun Protection complexTm from Greentech , 30 Pronalen Sunlife from S. Black Ltd., C1C21m and Antikeuline 6 from Biotech Marine (Secma Marine Biotechnology), Parsol SLX and Alpaflor Edelweissi'm from DSM Nutritional Products, DNAGE2Tm, DN-AGE LS 9547 and Sunactyl LS 9610 from Serobiological Laboratories , Uniprotect PT 3 from Induchem, Maricol S CLR from Chemisches Laboratorium Dr. Richter, IllumiscinTm from Indena, Caspaline 14 and Natriance Antioxidizeirm from Vincience / ISP, Lip oshield HEV MelaninTm 3024037 14 from Lipo Chemicals, Fruit Vinegar from Provital SA, IBR-TCLC 0701 from IBR, VenuceaneTm from Sederma and Muciliance Fruit from Soliance. In a particularly advantageous manner, the compositions according to the present invention may additionally contain at least one lightening and / or whitening agent for the skin. The compositions then advantageously comprise from 0.01% to 20%, preferably from 0.02% to 10%, and in particular from 0.05% to 5% by weight of the at least one lightening and / or whitening agent. the skin relative to the total weight of the composition. The skin lightening and / or whitening agents may act according to different mechanisms: they may be tyrosinase activity inhibitors, tyrosinase suppressors, tyrosinase competitors, melanin formation reducers, antioxidants. It can be observed that these agents have with the active ingredient of the invention a complementary, additive or even synergistic effect. These agents include those known to those skilled in the art, for example vitamin C and ascorbic acid derivatives (ethyl ascorbic acid, ascorbyl glucoside, magnesium ascorbyl phosphate, sodium ascorbyl phosphate, disodium ascorbyl sulfate, ascorbyl tetraisopalmitate). , niacinamide, licorice root extract (Glycyrrhiza glabra (licorice) root extract), arbutin, kojic acid, alpha-bisabolol, elagic acid, linoleic acid, acid m-tranexamic acid, hydroquinone, corticosteroids, mercury, aminophenol derivatives, N-cholesteryloxycarbonyl-para-aminophenol and N-methyloxycarbonyl-para-aminophenol; iminophenol derivatives, L-2-oxothiazolidine-4-carboxylic acid or procysteine, and its salts and esters, and extracts (ie blackberry extract (Broussonetia extract), licorice (Lycoris aurea extract), placenta extract , skullcap, soluble licorice oil (ie proposed by Maruzen), camomile extracts (ie proposed by Kao), t-AMCHA 4MSK (proposed by Shiseido), adenosine monophosphate disodium (APM proposed by Otsuka), rucinol (Pola). Skin lightening and / or whitening agents useful in the present invention include combinations with the lightening agents of MelermaTM, EtiolineTM, MelaslowTM WonderlightTM, InexwhiteTM, and LumiskinTM / LumisphereTM provided by Sederma. Other skin lightening and / or whitening agents that can be used in the context of the present invention include the products marketed under the names: NAB Asefetida extract TM (Arch Chemicals, Inc.), Actiwhite TM (BASF), Tego Pep 4 EvenTM (Evonik), Synerlight 2TM 30 (Gatefossed), ClerilysTM (Greentech), AA2GTM (Hayashibara), Uninontan U 34TM (Induchem), B-WhiteTM, TyrostatTM, and Melanostatin 5TM (Lucas Meyer - Unipex), NanoWhiteTM (Mibelle AG Cosmetics) , MelavoidTM (Provital SA), Cellactive WhiteTM (Rahn GmbH), EmblicaTM (Rona), InexwhiteTM (Sederma), AzeloglicinaTM (Sinerga), Sepicalm VGTM and Sepiwhite MSHTM (Seppic), WhitonylTM (Silab), AxolightTM (Soliance), and Symwhite 377TM (Symrise).
[0015] The preferred skin lightening and / or whitening agents are vitamin C and ascorbic acid derivatives (ethyl ascorbic acid, ascorbyl glucoside, magnesium ascorbyl phosphate, sodium ascorbyl phosphate, disodium ascorbyl sulfate, ascorbyl tetraisopalmitate), niacinamide, licorice root extract (Glycyrrhiza glabra (licorice) root extract), and arbutin.
[0016] Preparation of Cosmetic or Dermatological Compositions By "physiologically acceptable excipient" 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, an anhydrous gel, a serum, a dispersion of vesicles, a powder. "Physiologically acceptable" means that the compositions are suitable for topical or transdermal use, in contact with the mucous membranes, superficial body growths (nails, hair, hair), scalp and mammalian and especially human skin, preparations which may be ingested or injected into the skin, without risk of toxicity, incompatibility, instability, allergic response, and others. This "physiologically acceptable excipient" forms what is conventionally called the excipient or medium of the composition.
[0017] For the use according to the invention, the effective amount of the active ingredient in the composition according to the invention, i.e. its dosage, depends on various factors, such as age, the patient's skin, etc. An effective amount means a non-toxic amount sufficient to achieve the desired effect. For the use according to the invention, the ingredient according to the invention, to be present in an effective amount, is generally in proportions of between 0.01% and 20%, preferably 0.05% to 10%. %, Especially from 0.1% to 5%, and especially around 1%, 2% and 4% by weight relative to the total weight of the composition. The skilled person is able to adjust the amount of active ingredient according to the desired effect. All percentages and ratios used in the present invention are by weight of the total composition and all measurements are made at 25 ° C unless otherwise specified.
[0018] The choice of the excipient of the composition is made according to the constraints related to the ingredient itself (stability, solubilization, etc.) and, if appropriate, to the pharmaceutical form envisaged thereafter. The active ingredient of the invention may be incorporated into a preparation by means of physiologically acceptable standard solubilizers, for example and without being limited to this list: alkaline water, ethanol, propanol, isopropanol propylene glycol, butylene glycol, 1,3-propane diol, or polyethylene glycol or any combination thereof. According to one embodiment, the composition according to the invention is in an emulsion (or dispersion) form, such as an oil-in-water or water-in-oil emulsion. The oily phase of the emulsion will preferably be an emollient oil of the type used in cosmetics. This type of material is preferably liquid at room temperature.
[0019] However, it is also possible to use a solid material at room temperature (wax type), which will be incorporated hot in the final composition.
[0020] Suitable liquid oils in which the active ingredient according to the invention can be solubilized hot include nonpolar oils for example, mineral or paraffin, or oils of medium polarity, such as esterified vegetable oils (jojoba oil by for example), vegetable or animal oils based on glycerides (caprylic / capric triglycerides, for example), synthetic ester oils such as, for example, isopropyl palmitate, etherified oils such as dicaprylether, octyl dodecanol or vegetable oils. silicones such as dimethicione oil, cyclomethicone, or silicone oils having polyoxyalkylene side chains to increase their hydrophilicity, or finally highly polar oils such as propoxylated fatty alcohols.
[0021] It is also possible to use a powder support. Compositions suitable for the present invention are generally prepared by usual methods well known to those skilled in the art of making topical and oral preparations and preparations for injection. Such methods may involve mixing ingredients in one or more steps to achieve a uniform state, with or without heating, cooling, etc.
[0022] The various galenic forms which may contain the composition according to the invention are in any form namely creams, lotions, ointments milks or creams, gels, emulsions, dispersions, solutions, suspensions, cleaners, foundations, anhydrous preparations (sticks in lip balm, body and bath oils), shower and bath gels, shampoos and hair care lotions, milks or creams for skin or hair care, lotions or make-up removers, 20 lotions , sunscreen or sun creams, lotions, artificial tanning milks or creams, creams, mousses, gels or lotions of pre-shave, shaving, or aftershave, make-up, lipsticks, mascaras or nail polish, "essences Skin, serums, adhesive or absorbent materials, transdermal patches, or powders, lotions, emollient milks or creams, sprays, body and bath oils, foundation bases, ointments, emulsions, colloids, compact or solid suspensions, pencils, 25 sprayable, brushable, blush, red, eyeliners, lipliners, lip gloss, face or body powders, mousse or styling gels, nail conditioners, lip balms, conditioners for skin, moisturizers, lacquers, soaps, exfoliants, astringents, hair removal products permanent waving solutions, anti-dandruff formulations, antiperspirant or antiperspirant compositions, especially sticks, roll-on deodorants, deodorants, sprays for nose and so on . These compositions may also be in the form of sticks for the lips intended either to color or avoid chapped skin, or eye makeup products or makeup and makeup for the face. The compositions according to the invention include beauty products, personal care products and pharmaceutical preparations. It is also possible to envisage a composition in the form of a foam or in the form of an aerosol composition also comprising a propellant under pressure. The compositions according to the invention can also be for oral use, for example a toothpaste. In this case, the compositions may contain adjuvants and additives customary for oral compositions and especially surfactants, thickeners, humectants, polishing agents such as silica, various active ingredients such as fluorides. , especially sodium fluoride, and optionally sweetening agents sum sodium saccharinate.
[0023] The active ingredient in the context of the present invention may be used in solution, dispersion, emulsion, paste or powder form, individually or premixed or conveyed individually or premixed with vectors. such as macrocapsules, microcapsules or nanocapsules, macrospheres, microspheres, or nanospheres, liposomes, oléosomes or chylomicrons, macroparticles, microparticles or nanoparticles, macroeponges, microeponges or nanoepongs, microemulsions or nanoemulsions, or adsorbed on powdery organic polymers, talcs, bentonites, spores or exines and other inorganic or organic substrates. In particular, it will be possible to encapsulate the acid mixture or the ingredient according to the invention in microcapsules of polymethylmethacrylate and of manganese-modified titanium dioxide (TiO2Mn).
[0024] The composition in the context of the present invention may be used in any form, in a bound form, incorporated or adsorbed on macro-, micro-, and nanoparticles, or on macro-, micro- and nanocapsules, for 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, day or night underwear, tissues, or tissues in order to exert its cosmetic effect through this skin / textile contact and to allow continuous topical delivery. Method of treatment The invention also proposes a method for the cosmetic or dermatological treatment of the skin and its integuments, comprising the application, especially topically, to a subject in need of such treatment, of an effective amount of a composition according to the invention. 'invention. By "topical treatment" is meant an application that is intended to act at the place where it is applied: skin, mucosa, dander. Improvements in the appearance and general condition of the skin can be achieved by topical application on a regular basis such as daily.
[0025] The practitioner will appreciate the dermatological treatment which will comprise a preparation containing the ingredient according to the invention, this treatment being able to be carried out for example by topically applying the preparation described in the present invention, according to a technique usually used to apply such a composition. The topical preparation is preferably applied once daily for a period of at least one week, but may be applied for periods of 2, 4, 8 or 12 weeks. The topical composition is preferentially applied to the face and the neck, but may be applied to any part of the skin requiring treatment, where the preparation remains on the skin area to be treated, and preferably is not removed or rinsed off. the skin. For example, for a cosmetic facial treatment, the European Cosmetics Directive has set a standard application level of a cream of 2.72 mg / cm2 / day / person and 5 for a body lotion 0.5 mg / cm2 / day / person. It should also be understood that, as used herein, the terms treat and treat include and include, in particular, the improvement, prevention, protection of skin, appendages, and mucous membranes in need. The compositions of the present invention as well as the methods are suitable for use in treating dermatological conditions of the skin in many areas of the skin, including but not limited to, the face, forehead, lips, neck, cleavage, arms, hands, body, legs, knees, feet, chest, back, buttocks, and others. One of the great advantages of the present invention lies in the possibility of being able to proceed, whenever necessary or desirable, to localized and selective "soft" treatments thanks to the topical, non-invasive mode of application. An application can be performed in a very localized manner using a syringe or microcannula. However, it is also possible to envisage a preparation according to the invention intended to be injected subcutaneously. According to other particularities, the dermatological or cosmetic treatment method according to the invention may be associated with one or more other treatment methods for the skin, such as, for example, treatments by light therapy, heat or aromatherapy. 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 the ingredient according to the invention and in a second compartment a composition containing at least one other active ingredient and / or excipient, the compositions contained in said first and second compartments being here considered as a combination preparation for use simultaneous, separated or spread over time, in particular in one of the treatments defined above. More particularly, the method according to the invention can be applied to the following non-therapeutic cosmetic treatments: treatments for reducing the production of melanin in the skin, for lightening the skin and its integuments, for attenuating cutaneous spots, to homogenize the coloration of the skin, to moisturize, to combat cutaneous dryness, to protect the cutaneous barrier, to stimulate the synthesis of at least one of the molecules of the matrix extracellular dermal, anti-oxidant, anti-wrinkle and fine lines, 5 slimming, to improve the mechanical properties of the skin: firmness, and / or elasticity, and / or flexibility, lipofiling by promoting the expansion and / or formation of the tissue subcutaneous adipose for improving and / or beautifying any body part deficient in lipids, - anti-aging, 10 - oily skin, - acne-prone skin, - anti-dandruff, - acting on the growth of hair, hair and nails, - desquamant, 15 - anti-solar radiation, - deodorant, - anti-seborrhoeic, - anti-glycation, - promoting re-epithelialization and / or regeneration of the skin or lips and the contour of the hair root or nails, and / or - to improve the comfort of the skin altered by either cold, UV or mechanical friction. Or for therapeutic treatments, including dermatological, following: anti-bacterial, anti-microbial, anti-inflammatory, anti-acne, against pimples, rosacea, lentigo, 25 dermatitis including hyperpigmentaire, eczema or impetigo. The treatments, lightening, whitening, moisturizing, anti-dandruff and anti-acne are more particularly targeted according to the invention. A) Example of preparation of a mixture of unsaturated dicarboxylic acids according to the invention obtained by metathesis Metathesis reaction For the metathesis reaction, 50 grams of methyl oleate purified to more than 90%, preferably stabilized by 100 ppm tert-butylhydroquinone are heated to a temperature of 100 ° C under nitrogen. 200 ppm (final) of titanium isopropoxide (catalyst activator) are added with stirring. Umicore M73SIMES, ruthenium catalytic complex (final 5 ppm in 100 μl of tetrahydrofuran) is then added. After about 5 minutes of reaction, the theoretical equilibrium (previously determined by gas chromatography) is reached. 2 grams of activated bentonite are added to the reaction mixture to trap catalyst and catalyst activator. The mixture is then filtered on a cellulose filter. The filtrate freed from the catalyst and the catalytic activator is recovered. Purification Fractional distillation is then carried out to separate the 2 products of the reaction (9-octadecene and dimethyl octadecenedioate) and the unconverted substrate (methyl oleate). This distillation is carried out under a vacuum of 1 to 10mbar. Dimethyl octadecenedioate is collected / purified at a temperature between 210 ° C and 220 ° C. This fraction has a purity greater than 85% (determined by gas chromatography).
[0026] Hydrolysis The dimethyl octadecenedioate fraction obtained from the distillation is hydrolysed by saponification (KOH in an ethanol / water mixture under reflux at 70 ° C.) and then cooled to 55 ° C. During a gradual acidification with phosphoric acid with stirring, the product of the hydrolysis, octadec-9-ene1,18-carboxylic acid, precipitates. It is then filtered and washed with water until the washings have a neutral pH. It is then dried under vacuum (under about 10mbar at 60 ° C) and finally purified by molecular distillation at 180 ° C and 0.00 lmbar. An antioxidant can be added during this last step. The mixture according to the invention thus obtained is a white solid, which can be used as an active ingredient in any cosmetic or dermatological composition. It is this mixture that is used in the in vitro and in vivo evaluations as well as in the galenic formula below.
[0027] Analysis / Characterization of the mixture according to the invention obtained Parameter Value Acid number (mg KOH / g) 345 Saponification number (mg KOH / g) 347 Iodine number (g 1/100 g) 80 Peroxide number ( mmol 02 / kg) Melting point 90-95 ° C% octadec-9-ene-1,18-dicarboxylic acid 94.4%% monocarboxylic acids 0.3% dicarboxylic acid di or tri unsaturated 2.9% by weight of saturated dicarboxylic acids 2% of isomer E in the total mass of 82% octadec-9-ene-1,18-dicarboxylic acid% of Z isomer in the total mass of acid 18% octadec-9-ene-1,18-dicarboxylic acid A mixture of highly purified unsaturated dicarboxylic acids is thus obtained.
[0028] 3024037 21 Methods used: (i) Iodine number The iodine number of the unsaturated dicarboxylic acid composition is determined by the method of Wijs (AOCS) Official Method Tg 1-64 (1993) and expressed in number of grams of iodine absorbed per 100 grams of sample, under the defined test conditions. Acid Number The acid number of the unsaturated dicarboxylic acid composition is measured using the official method of A.O.C.S. No. 64 (Reapproved in 1997) and expressed as the number of milligrams of potassium hydroxide required to neutralize the free fatty acids in 1 gram of sample. (iii) Saponification Index The saponification number of the unsaturated dicarboxylic acid composition is measured using the official method of A.O.C.S. : Official Method Tl la-64 (1997) and expressed in number of milligrams of potassium hydroxide which reacts with 1 gram of sample under the defined conditions. (iv) Fatty Acid Composition The fatty acid composition of the unsaturated dicarboxylic acid composition according to the invention is determined by gas chromatography (GC). Prior to this analysis, the sample was methylated using the Combipal system. 8 mg of fatty acid sample are dissolved in 100 ml of methanol. 0.5 ml of the catalyst BF3 (boron trifluoride) at 20% in methanol are added. The mixture is stirred and heated at 80 ° C for 4 minutes. After cooling to room temperature, 600 μl of heptane and 600 μl of water are added. The biphasic system is stirred for 2 minutes, and the upper phase (heptane) is transferred to a clean tube, ready for analysis. Instrumentation and conditions of Gas Chromatography (GC): Column: CP-FFAP CB, length: 25m, internal diameter: 0.32mm, film thickness: 0.30mm. Temperature: 120 ° C and rise of 8 ° C per minute at 250 ° C (6.25 minutes). Vector gas: Hydrogen. Flow rate: 120 ml / min. Injection: 30 Detection: F.I.D. Pressure: 9 psi. Duration of the analysis: 22.5 minutes. (V) Isomeric Composition Z and E The methylated samples produced in (iv) above are also used for the determination of the EIZ ratio using GC. The standard method for the determination of E and Z isomers on monomethyl esters is not suitable for dimethyl esters. Thus, the temperature of the isothermal oven was raised from 160 ° C to 210 ° C and the analysis time was 15 minutes. The results are based on a comparison with a Z standard. Instrumentation and GC conditions: Column: CP Sil 88, length: 25m, internal diameter: 0.32mm, film thickness: 0.20 lm. Temperature: 210 ° C (15 minutes).
[0029] 10 Vector gas: Hydrogen. Flow rate: 1.39 ml / min. Injection: 1: 100 split ratio. Detection: F.I.D. Pressure: 5.6 psi.
[0030] Duration of analysis: 15 minutes. B) In vitro evaluations The interest of the dermatological or cosmetic treatment of the active ingredient according to the invention compared to the ingredient of the state of the art obtained by biotransformation as described above is illustrated by the tests in vitro. vitro given below. The comparative mixtures of dicarboxylic acid (s) tested are defined in the following table: Mixture according to the invention Mixture according to the state of the art Percentage of octadec-9-ene-1,18-dicarboxylic acid 94.4% 60.8% by weight of monocarboxylic acids 0.3% 5.6% by weight of di or tri-unsaturated dicarboxylic acids 2.9% 26.4% by weight of saturated dicarboxylic acids 2% 6.8% % E isomer in the total mass of octadec-9-ene-1,18-dicarboxylic acid 82% 1%% isomer Z in the total mass of octadec-9-ene-1,18-dicarboxylic acid 18% 99% Melting point 90-95 ° C z57 ° C 3024037 23 1. Effect on pigmentation Inhibition of melanin synthesis on human melanocytes The cosmetics industry is looking for compounds with depigmenting properties ( bleaching, depigmentation and lightening of the skin, elimination or reduction of freckles, age spots, etc.). In vitro, it is possible to demonstrate such an effect by assaying the synthesized melanin, on melanocyte cultures that have or have not been in contact with the compounds to be evaluated.
[0031] Protocol Normal human melanocytes are inoculated into their maintenance medium and then contacted with the test products in the test medium for 10 days. At the end of the contact, the melanins are extracted from the cells and assayed by spectrophotometry (490 nm). An estimate of the viability of the cells is made at the end of culture using a protein assay by the BCA method. Melanin concentrations are normalized by the protein content of the sample. Results Table 1: Inhibition of melanogenesis compared to control. Concentration Mixture of the state of the art Mixture according to the invention -16% -26% 3Oppm p <0.01 p <0.01 -20 -29 5Oppm p <0.01 _ p <0.01 ... 100 ppm p <0.01 p <0.01 The positive 0.01% arbutin control gives a -33% inhibition compared to the control. Both ingredients significantly and dose-dependently inhibit melanin synthesis in normal human melanocytes. It is surprisingly observed that the ingredient according to the invention gives better results than the ingredient of the state of the art, at all the doses tested. 2. Effect on prevention of skin aging a) Action against reactive oxygen species (ROS) at the cellular level Excess ROS in the cell leads to increased immediate oxidative damage to biological material, lipids, proteins, sugars and nucleic acids and leads to long-term cellular aging. Hence the permanent search by the cosmetic industry of antioxidants capable of acting at the cellular level.
[0032] The evaluation of the ROS was performed on dermal human fibroblasts (FHD) using the DCFH-DA probe which, once in the cell, becomes fluorescent on contact with the ROS (fluorescence level directly proportional to the amount of ERO). Protocol 5 The fibroblasts are inoculated. After 24 hours of attachment, the cells are put in contact with the products to be tested for 24 hours. The products are eliminated, rinsed carpets and cells are "loaded" with the DCFH-DA probe. After rinsing, the cells are again brought into contact with the test products and an oxidant (H 2 O 2 600 μM). A fluorescence reading makes it possible to estimate the amount of ERO present in the cells. The fluorescence results are reduced to the number of cells. Results Table 2: Variation in the amount of intracellular ERO post-oxidative stress relative to the control Concentration Ingredient of the state of the art Ingredient according to the invention -31% -54% lOppm p <0.01 p <0, 01 The 500mM trolox positive control gives -77% inhibition over control. The two ingredients have a protective effect of normal human fibroblasts in the face of oxidative stress. However, it is observed that the ingredient according to the invention gives better results than the ingredient of the state of the art. b) Action on the Extra Cellular Dermal Matrix Collagen I is the most abundant protein of the dermis, it is essential for having a firm skin. The loss of density and thickness of the dermis is linked to a reduction of the syntheses of these macromolecules (in particular collagens I and IV) by dermal fibroblasts, cells in charge of their manufacture, during aging. 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. It is therefore important to stimulate the synthesis of these two macromolecules. Immuno-labeling of the carpets Protocol Normal human fibroblasts (FHN) in culture are brought into contact with the test product (or its excipient for control) for 6 days. The synthesis of collagen I is quantified in photos after immuno-marking of the fixed mats. A count of the nuclei of the cells is carried out using the DNA dye (Hoescht 33258), so as to reduce the collagen result to the number of cells. Results Table 3: Variation of collagen I synthesis (FHN carpet) versus control. Concentration Ingredient of the state of the art Ingredient according to the invention + 45.5% + 101.9% 2Oppm p <0.01 p <0.01 The two ingredients stimulate the synthesis of collagen on normal human fibroblasts. It is observed that the ingredient according to the invention gives better results than the ingredient of the state of the art. ELISA tests on culture supernatants. Protocol Normal human fibroblasts (FHN) in culture are brought into contact with the test product (or its excipient for control) for 3 days in the test medium. The culture supernatants are removed and an assay of the amount of dermal macromolecules (Collagen I, Fibronectin) is carried out by ELISA. Quantification of the cells present on the carpet is performed with the DNA dye (Hoescht 33258), so as to reduce the assays to the number of cells. Results Table 4: Variation of the synthesis of collagen I and fibronectin (FHN supernatants) compared to the control. Ingredient according to the invention Concentration Collagen I Fibronectin lOppm + 67% + 43% p <0.01 p <0.01 Thus, with the ingredient according to the invention, the syntheses of collagens I and fibronectin are increased, 20 which improves the density and elasticity of the dermis. No stimulation was observed with the ingredient of the state of the technic. c) Action on the dermo-epidermal junction (JDE) The basal keratinocytes are attached to each other forming a thin layer connected to the dermis via the JDE and its complex network of proteins and fibers. Among them are laminins, boat-anchored proteins whose branches bind together collagen IV, dermal proteoglycans and keratinocytes.
[0033] 3024037 26 Collagen IV is an essential element of the skin by its role in the JDE. It is organized in a fine felting where other elements essential to cutaneous homeostasis like laminines cling. Together, these two essential components of JDE provide the basal lamina keratinocyte with 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.
[0034] The interest in stimulating the synthesis of these 2 proteins therefore clearly appears. Protocol Normal human fibroblasts (FHN) in culture are brought into contact with the test product (or its excipient for control) for 3 days in the test medium. The culture supernatants are removed and an assay of the amount of dermal macromolecules (collagen IV, laminin) is carried out by ELISA. Quantification of the cells present on the carpet is carried out with the dye of the DNA (Hoescht 33258), so as to reduce the assays to the number of cells. Results Table 5: Variation of collagen IV and laminin synthesis (FHN supernatants) compared to control. Ingredient according to the invention Concentration Collagen IV Laminin lOppm + 63% + 33% p <0.01 p <0.05 With the ingredient according to the invention, the collagen IV and laminin syntheses are increased, which reinforces the JDE, the relations of these components with the basal layer of keratinocytes, its anchorage between the dermis and the epidermis. No stimulation was observed with the ingredient of the state of the art. 3) Effect on dry skin. Improvement of the barrier function of the epidermis and the stratum corneum a) Synthesis of hyaluronic acid by human keratinocytes. The main interest of hyaluronic acid is its role as a moisturizer of the epidermis. Hyaluronic acid is present in the intercellular spaces of the basal and spinous layers, but absent in the upper layers (granular and horny). Its moisturizing role of the skin will therefore be positioned at the level of the lower layers of the epidermis.
[0035] 3024037 27 Protocol Human keratinocytes are cultured for 24 hours. The cells are put in contact with the products to be tested or their excipient for 3 days. The culture supernatants are removed and an assay of the amount of Hyaluronic Acid is performed. Retinoic acid is used as a positive control. Quantification of the cells present on the carpet is carried out with the dye of the DNA (Hoescht 33258), so as to reduce the assays to the number of cells. Table 6: Variation of Hyaluronic Acid Synthesis (Human Keratinocyte Supernatants) Compared to Control. Concentration Ingredient of the state of the art Ingredient according to the invention + 40% + 37% lOppm p <0.01 p <0.01 The positive control, retinoic acid at 14uM gives a stimulation of + 106%; p <0.01 compared to the control. Both ingredients stimulate the synthesis of hyaluronic acid on human keratinocytes. They therefore participate in improving the hydration of the epidermis. b) Differentiation of keratinocytes An active agent capable of stimulating the differentiation of keratinocytes is particularly useful for reinforcing the skin barrier effect. Protocol Human keratinocytes in culture at confluence are brought into contact with the test product in a medium slightly enriched in calcium to promote the establishment of intercellular junctions and thus improve the anchoring of the differentiated cells to the underlying cells and to the culture support .
[0036] A negative control is carried out in the same medium. At 3, 5 and 7 days, the appearance of differentiation is assessed visually. Results Visually, it is observed that both the ingredient according to the invention and the ingredient in the state of the art cause an acceleration of the differentiation at 10 and 20 ppm compared to the control. At all times of observation, with the two ingredients, stimulation of the formation of structures typical of the upper layers of the epidermis is observed (presence of branched structures characteristic of the rigid proteolipidic matrix and multilayer of the epidermis). horny envelope). The cells are associated in large cohesive clusters, sometimes interconnected as by a network. This is not observed at the same times on the control mats. 4) Test related to a plumping action Some cosmetic compounds are intended to promote the installation of subcutaneous fat for better aesthetics and a greater volume.
[0037] In this perspective, in vitro tests aimed at showing an increase in adipocyte differentiation (with glycerol-3-phosphate dehydrogenase or G3PDH as the key enzyme of this differentiation) on pre-adipocyte cultures have been implemented. . Other in vitro tests seek to show a slowing down of lipolysis on adipocyte cultures to validate the efficacy of these compounds. a) G3PDH activity on human adipocytes Protocol Human preadipocytes are inoculated and induced to differentiate using a specific cocktail of inducers (without indomethacin *) in the presence or absence (negative control) of the test products. After 10 days, cultures are stopped and residual G3PDH activity is measured spectrophotometrically on a cell lysate. In parallel, an estimation of the quantity of cells is carried out by Hoechst assay and makes it possible to weight the obtained data. Indomethacin, an agonist PPAR, is deleted from the differentiation inducers to release these receptors and to highlight the effect of products acting on this pathway (such as Pioglytazone = positive control). Results Table 7: Variation of G3PDH Activity Relative to Control (Human Adipocytes Mat) Concentration Ingredient of the State of the Art Ingredient according to the invention 30 ppm + 262% + 299% p <0.01 p <0.01 The positive control, pioglitazone at 104uM gives a stimulation of + 712%; p <0.01 compared to control.
[0038] Both ingredients stimulate G3PDH activity on human adipocytes. b) Measurement of Lipolysis on Human Adipocytes Protocol Human preadipocytes are seeded and induced to differentiate using a specific cocktail of inducers. To obtain mature adipocytes well loaded with triglycerides, the cells are placed in contact with the test products (or their excipient). After incubation for 3 hours, the supernatants are recovered and the quantity of glycerol released from the hydrolysis of the intracellular triglycerides is measured. Table 8: Concentration Ingredient of the state of the art Ingredient according to the invention -36% -37% 100 ppm p <0.05 p <0.05 The two ingredients slow down lipolysis on human adipocytes.
[0039] C) Examples of galenic formulations As mentioned above in the description, it goes without saying that different cosmetic formulations can be implemented that can integrate the active ingredient of the invention. A cream formula is given below as an example.
[0040] Additional active ingredients, optionally in support of and / or in addition to the activity of the active ingredient according to the invention, may be added in the appropriate phase of the formulations, 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 anti-aging, anti-wrinkle, moisturizing, lightening, anti-acne, concealer, firming, anti-glycation, slimming, soothing, myo-relaxing, anti-redness, anti-vergetures, etc. Example of Day Cream Product% INCI Name Phase A H2O Qsp100 Water Potassium Sorbate qs Potassium Sorbate Phase B Butylene Glycol 3.00 Butylene Glycol Octanediol 0.50 Caprylyl Glycol Phase C Phenoxyethanol qs Phenoxyethanol Keltrol CG-SFT 0.60 Xanthan Gum Supercol GF 0,20 Cyamopsis Tetragonoloba (Guar) Gum Phase D Brij S2-SS- (RB) 1.00 Steareth-2 Crodafos MCA-SO- (RB) 2.00 Cetyl Phosphate Stearic Acid 2.50 Stearic Acid Laurocapram 2.00 Laurocapram BRB CM-56 3.00 Cyclopentasiloxane & Cyclohexasiloxane Arlacel 170-PA- (RB) 3.00 Glyceryl Stearate & PEG-100 Stearate Crodamol GTCC-LQ- (MV) 3.00 Caprylic / Capric Triglyceride Ingredient according to the invention 4 , 00 Phase E H2O 4.50 Water NaOH 30% 0.90 Sodium Hydroxide Phase G Fragrance 0.10 Fragrance Protocol: Weigh phase A. Weigh phase B and melt at 45 ° C, then allow to cool to 25 ° C. Add one by one the compounds of phase C in phase B. Thoroughly homogenize. Add phase B + C to phase A with propeller stirring v = 500 rpm for a minimum of 30 minutes. Phase A + B + C to be heated to 85 ° C in a water bath. Put phase D to heat to 85 ° C in a water bath. Add phase D to phase A + B + C with Staro stirring v = 3000 rpm. Add phase E with stirring Staro, homogenize well. Add phase F, below 35 ° C, mix well. Examples of ingredients that can be added to this cream-like formula in one of the phases or extemporaneously according to their hydrophobic or hydrophilic physical property, to a certain% depending on their concentration and the desired effect: - LUMISPHERETm: active ingredient marketed by Sederma (WO2004 / 024695). It is the combination of diacetylboldine (DAB) encapsulated in microcapsules of polymethylmethacrylate and manganese-modified titanium dioxide (TiO2Mn). TiO2Mn 10 gives the skin a unifying, mattifying and luminous effect and DAB provides a brightening physiological effect. 4% of this ingredient can for example be added to the formulation. - CENTECELLTm: anti-redness active ingredient based on an extract of Centella asiatica, marketed by Sederma which protects the blood capillary and the extracellular matrix of oxidative attacks and collagenase; 2% of this ingredient can be added at the end of the formulation before the E.-NG Birch ThimbleTM phase: toning and moisturizing active ingredient marketed by Sederma, based on raw Sap of the birch sapwood. - MATRIXYL 3000TM: anti-wrinkle active ingredient based on peptides marketed by Sederma (WO2005 / 048968) which helps repair skin damage caused by aging. 20 - MATRIXYL synthe'6TM: peptide-based anti-wrinkle active ingredient marketed by Sederma (W02010 / 082175) which helps repair the skin damage caused by aging. - Tocopherol (vitamin E) or a-lipoic acid (ALA): active with anti-oxidant and anti-radical properties. 0.5% by weight can be for example added to the formulation. PRODIZIATM: active ingredient marketed by Sederma that fights the cutaneous signs of fatigue caused by glycation and glycoxidation. - Niacinamide (vitamin B3), Retinol, Resveratrol, DHEA: active anti-aging, especially anti-wrinkle. 0.5% by weight of Retinol, Resveratrol or DHEA may for example be added extemporaneously to the formulation. For example, 10% by weight of 10% Niacinamide in water can be added to the formulation. Hexamidine: anti-bacterial active agent that can be added to the 0.5% by weight formulation. As other galenic forms which are particularly advantageous for the implementation of the cosmetic treatment according to the invention, mention may be made of: Mask form, with as examples of ingredients that may be added: SEBULESSTM: purifying sebo-regulating ingredient based on Syringa extract vulgaris, which matifies and refreshes the complexion, blurs the imperfections. 3024037 31 - YEAST WALLSTM: active ingredient based on cell membranes having a high enzymatic activity, marketed by Sederma, having an anti-seborrhea activity, an effect on the texture and the complexion of the skin and on its suppleness. AQUALANCETM: osmoprotective moisturizing active ingredient marketed by Sederma 5 (WO2009 / 104118) composed of homarine and erythritol. 4% can be added at the end of the formula. - Ac.netTM: active marketed by SEDERMA (W02003 / 02828692) offering a complete treatment of oily and acne-prone skin. Serum form (fluid emulsion), with as examples of ingredients that can be added: RESISTEMTm: anti-aging ingredient marketed by Sederma (WO2012 / 104774), helping the skin to build its own anti-aging defense system, based on of an extract obtained by cell culture of the plant Globularia cordifolia. - MARUCELLTM: anti-pollution active ingredient, anti-oxidant, marketed by Sederma, based on an extract of Marrubium vulgare. 15 - Unsaponifiables of shea butter: possessing nourishing and protective properties for the treatment of skin attacked by the environment. - VENUCEANETM: active ingredient marketed by Sederma (WO2002 / 066668) which prevents visible signs of photoaging (spots, wrinkles, dryness ...), protects cell structures from damage caused by UV and reinforces the integrity of the skin. - EVERMATTm: active marketed by Sederma (WO2007 / 029187), which decreases the secretion of sebum and thus participates in the treatment of oily skin. 4% of this ingredient can for example be added to the formulation. WONDERLIGHT TM: active marketed by Sederma (Caprylic / Capric Triglyceride and Humulus Lupulus (Hops) Strobile), which helps to reduce hyperpigmentation accentuated by age and stress. 3% of this ingredient solubilized in Optasense G82 (Croda) can for example be added to the formulation. The addition of OSMOCIDE 4TM, active marketed by Sederma (WO 97/05856 - Glycerin, Water (Aqua) (and) Caprylyl Glycol, Carbomer, Acrylates / C10-30 Alkyl Acrylate Crosspolymer), makes it possible to reduce the concentration of preservatives. traditional.
[0041] Washing lotion form, with as examples of ingredients that can be added: ECODERMINETm: active ingredient marketed by Sederma for combating skin problems due to microbial imbalance (acne, dryness, itching tendency) while preserving the natural defense mechanism of the skin, includes a combination of lactitol and xylitol. 35 - HAIRSPATM: Soothing and moisturizing active ingredient of the scalp marketed by Sederma, also based on lactitol, xylitol and glycerin.
[0042] 3024037 32 Milk form, with as examples of ingredients that can be added: - LEONTOCELL ™: anti-wrinkle active ingredient marketed by Sederma based on extract of Leontopodium alpinum (Edelweiss). 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. - INTENSLIMTm: 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. Form Gel (for example for the eye area, particularly sensitive area), with as examples of ingredients that can be added: 15 - EYELISSTM: Active ingredient contours of the eyes (acts especially on dark circles and puffiness) marketed by Sederma, combination of 3 active molecules in solution: hesperidin methyl chalcone, dipeptide VW and lipopeptide Pal-GQPR. BEAUTIFEYETm: active ingredient marketed by Sederma which is a combination of an extract of Albizia julibrissin and darutoside extracted from Siegesbeckia orientalis, lifts the upper eyelid, reduces crow's feet wrinkles, reduces dark circles and reduces bags under the eyes. Dandruff Shampoo Product%% INCI Name Phase A H2O Qsp100 Qsp100 Water Citric Acid 0.24 0.24 Citric Acid Trisodium Citrate 1.20 1.20 Sodium Citrate NaCL 0.50 0.50 Sodium Chloride Phase B Butylene Glycol 5.00 5 , 00 Butylene Glycol Preservative qs qs - Activsoft S 0.30 0.30 Cyamopsis Tetragonoloba (Guar) Gum Keltrol CG-SFT 0.50 0.50 Xanthan Gum Phase C Empicol ESB 3 / 6M 30.00 30.00 Sodium Laureth Sulfate Plantacare 818 UP 5.00 5.00 Coco Glucoside 3024037 33 Crodateric CAB-30-LQ- (MH) 8.00 8.00 Cocamidopropyl Betaine Crodasinic LS-30 10.00 10.00 Sodium Lauroyl Sarcosinate Phase D Ingredient according to invention 1.00 4.00 Cithrol EGMS-PA- (SG) 3.00 6.00 Glycol Stearate Phase E H2O 10.00 10.00 Water Zinc Pyrion 48% 2.00 2.00 Zinc Pyrithione Phase F Datura Hypo 0 , 0.10 Fragrance Protocol: Step 1: Weigh phase A and stir 4 branches v = 200 rpm. Step 2: Weigh and homogenize phase B. Step 3: Add phase B to phase A with 4-branched helix stirring; Allow the gel to swell for 1 hour. Step 4: Weigh phase C and mix well. Step 5: Add phase C to phase A + B with propeller stirring v = 300 rpm.
[0043] Step 6: Put phase A + B + C to heat to 85 ° C in a water bath. Step 7: Place phase D to heat to 85 ° C in a water bath. Step 8: Add the phase D in the phase A + B + C with slow stirring staro v = 1000temin, well homogenize. Step 9: Below 35 ° C, add phase E, with slow stirring Staro v = 600 rpm. Step 10: Add phase F, homogenize well. Anti-Acne Stick & Repairer Product INCI Name Supplier% Crodacol Phase C90-PA- (RB) Cetyl Alcohol Croda 24.00 Syncrowax HRC-PA- (RB) Tribehenin Croda 5.00 3.00 Span 60-PW - (MV) Sorbitan Stearate Croda 2.00 2.00 NG Unsaponifiables Shea Butyrospermum Parkii (Shea) Butter Unsaponifiables (and) Butyrospermum Parkii (Shea) Butter Sederma 1.50 1.50 Ingredient according to the invention 1.00 4, 00 Phase B Butylene Glycol Qsp 100 Qsp 100 Phenoxyethanol Qs Qs Crodesta F160-PW- (RB) Sucrose Stearate Croda 2.00 Phase C Fragrance (Pure Wave) 0.20 0.20 3024037 34 Protocol: Weigh phase A and heat it to 85 ° C. Weigh and mix phase B. Heat phase B to 85 ° C until the powder is completely solubilized. Mix phase B with phase A and mix well. Weigh and homogenize phase C. Add phase C to phase A + B at about 50 ° C. Homogenize and pour into molds extemporaneously.
[0044] D) In Vivo Assessments The lightening / whitening activity of the active ingredient according to the invention has been shown in the in vivo test described below. A day cream prepared according to the example described above, part C), with 4% of the active ingredient according to the invention, was used for these tests, in comparison with a placebo cream prepared by replacing the ingredient. active according to the invention by water. Principle The test was conducted on a panel of 23 people with African-style skin and a Fitzpatrick VI phototype (30% tolerated V), male or female, in good health, especially without skin problems, aged between 22 and 43 years old. (average: 32 years). It lasted 56 days (measurements and evaluations made at TO, T28 15 days and T56 days). The evaluation was carried out by the method known as digital facial photography for colorimetric analysis (VISIA CR, Canfield) associated with a self-evaluation questionnaire by volunteers. Specific non-inclusion criteria A number of "good health" criteria were checked in volunteers before the start of the test: not being treated for diabetes, not having thyroid problems, skin hypersensitivity, of allergy to certain cosmetic ingredients, not to follow a medical treatment due to a chronic illness or to be under medical treatment during the study with aspirin-based products, anti-inflammatories, antihistamines, corticosteroids . Volunteers were also asked not to have undergone general anesthesia for more than one hour in the 6 months preceding the test. For female volunteers, they were asked: - not to have started, modified or stopped hormone treatment in the 3 months before the test, 30 - not to be pregnant, not to breastfeed, to have stopped breastfeeding more than 3 months before the start of the test). All volunteers were asked - not to have taken medical treatment that could lead to hyperpigmentation of the skin during the 6 months preceding the test, 35 - to have had no cosmetic treatment during the week preceding the test, - not to have applied depigmenting product during the 4 weeks before the test, - to put no other cosmetic product than those of the test on the study area (face) during the test.
[0045] 5 Type of study and duration The study was conducted in single blind: volunteers are not informed of the type of product tested. This is a contralateral comparative study in which the results obtained after application of the cream according to the invention to a test zone (right part of the face, for example) are compared with the results obtained after application of the placebo cream to another test zone. (left part of the 10 face). Each volunteer is thus his own reference and the results obtained at the two evaluation times are compared with those obtained at TO. The creams were applied to the face in a bi-daily massage for 56 days. The synopsis of the study can be summarized according to the diagram below: 15 TO T 28 days T 56 days Photos for analysis Photos for analysis Photos for colorimetric analysis colorimetric colorimetric 20 Self-evaluation Self-evaluation Statistical analysis: For analysis colorimetric, whether it is the evolution over time for each cream or the comparison between the two products, the normality of the distributions has previously been verified by a Shapiro-Wilk test (level of significance fixed at 1%).
[0046] Statistical studies were then performed using Student's t-test (normal distributions) or with a non-parametric Wilcoxon test (if normality is rejected). In both cases the tests were performed bilaterally on matched series. The level of significance of the results is set at 5%. For the treatment of the questionnaires, each product (placebo cream or cream containing the active ingredient according to the invention) gave rise to 2 percentages, one evaluating the percentage of favorable opinions, the other the percentage of unfavorable opinions. (taking into account the frequency of each answer). The statistical treatment of the differences (between favorable and unfavorable opinions) was evaluated by the Chi-2 test with a level of significance set at 5%. Protocol 1. Digital facial photographs for colorimetric analysis (Visia-CR) 35 Acquisitions are made with a VISIA-CR. The VISIA-CR is a device for acquiring up to 7 standardized high resolution digital images of the entire face in one shot. These 7 images allow to visualize the 3024037 36 particularities of the facial skin such as the texture, the color, the shine, the "photo-damage", the vascular characteristics, the wrinkles and fine lines and finally the porphyrins (P. Acnes) . The photos are taken on the left and right sides (45 degrees angle) and face, face, under lighting conditions, temperature, hygrometry, reproducible and standardized. The display 5 of the initial photograph (TO), at later times, ensures a good repositioning of the subject. Black skin color analysis: The parameters L * (relative brightness between 0 total darkness and 100 absolute white), a * (on a red-green spectral axis) and b * (on a yellow-blue spectral axis) are determined from the RGB (Red-Green-Blue) values of digital photos.
[0047] ITA ° (Individual Typological Angle) = Arctg [(L * -50) / b *] x (180/70 These parameters are determined on an area of interest defined on each half-face of the face at TO, T28 days and T56 days For a whitening effect on black skin, the analysis is based on the variations observed on the parameter L * which reflects the brightness (clarity) of the skin (quantity of white) and on the parameter ITA ° 15 which reflects the A significant increase in these two parameters on the half-face receiving the day cream containing the active ingredient according to the invention, in comparison with the half-face treated with the placebo cream, reflects an effect 2. Self-assessment questionnaires 20 The volunteers have to complete a questionnaire at T28 and T56 days (2 questionnaires at each examination time, one per half-face) to evaluate their opinion on the effectiveness of the tests. products tested Results Table 9: Comparison of differences e TO, T28 and T56 for the day cream containing the active ingredient according to the invention versus the placebo cream for the parameter L * (Clarity). L * (Clarity) Placebo Cream according to the invention TO T28 T56 TO T28 T56 Average 44.13 44.74 44.26 43.48 45.21 45.48 E-type 5.82 5.98 5.91 5, 68 6,12 5,65 Variation vs TO 0.61 0.13 1.73 1.99% variation vs.TO 1.4 0.3 4 4.6 Significance p <0.05 dns p <0.01 p <0.01 Significance vs placebo p <0.05 p <0.01 25 Statistical analysis of the values compared to TO show significant differences, at the 2 evaluation times, between the 2 half-faces treated, for the parameter L *. For the cream according to the invention, the evolution is + 4% and + 4.6% respectively after 28 days and 56 days; against + 1.4% and + 0.3% for the placebo cream. Table 10: Comparison of the differences between TO, T28 and T56 for the day cream containing the active ingredient according to the invention versus the placebo for the ITA ° (Pigmentation) parameter. ITA ° (Pigmentation) Placebo Cream according to the invention TO T28 T56 TO T28 T56 Medium -21.34 -19.06 -20.60 -23.35 -17.24 -16.28 E-type 20.30 20, 82 20.68 19.74 21.47 19.77 Variation vs TO 2.28 0.74 6.11 7.07% variation vs.TO 10.7 3.5 26.2 30.3 Significance p <0, 05 dns p <0.01 p <0.01 Significance vs placebo p <0.05 p <0.01 5 Statistical analysis of the values compared to TO show significant differences, at the 2 assessment times, between the 2 processed half-faces, for parameter ITA °. For the cream according to the invention, the evolution is + 26.2% and + 30.3% respectively after 28 days and 56 days; against + 10.7% and + 3.5% for the placebo cream. In conclusion, the active ingredient according to the invention provides the day cream with a significant whitening effect measured here by a parameter measuring the clarity of the complexion and another related to the color of the skin. Evaluation questionnaires, it appears: In terms of cosmetic efficacy, after 56 days of testing, the day cream containing the active ingredient according to the invention is recognized as leaving the skin lighter by 87% of the panel (result 15 significant with p <0.05), while the placebo cream received only 65% positive (not significant) opinion. At the end of the study, the overall judgment was favorable to the cream according to the invention (significant satisfaction index of 74%) while the placebo cream only collected 65% satisfaction index (not significant).

权利要求:
Claims (27)
[0001]
REVENDICATIONS1. A cosmetic or dermatological active ingredient comprising a mixture of unsaturated dicarboxylic acids comprising the Z and E isomers of at least one C12 to C24 monounsaturated dicarboxylic acid, the concentration of the E isomer being at least 25% by weight based on the total weight of Z and E isomers
[0002]
2. Ingredient according to claim 1, characterized in that the weight ratio of E / Z isomers is from 3 to 6: 1 based on the total weight of Z and E isomers.
[0003]
3. Ingredient according to claim 1 or 2, characterized in that the mixture comprises at least 80% by weight of said at least one monounsaturated C12 to C24 dicarboxylic acid and / or less than 20% by weight of at least one di-unsaturated and / or tri-unsaturated C12-C24 dicarboxylic acid based on the total weight of unsaturated dicarboxylic acid.
[0004]
4. Ingredient according to one of the preceding claims, characterized in that the mixture is substantially free of di-unsaturated dicarboxylic acid and / or tri-unsaturated C12 to C24.
[0005]
5. Ingredient according to one of the preceding claims, characterized in that the mixture of at least one unsaturated dicarboxylic acid has an iodine number of 50 to 120 g / 100g, and / or an acid number of 310 to 380 mg KOH / g, and / or a saponification number of 315 to 380 mg KOH / g.
[0006]
6. Ingredient according to one of the preceding claims, characterized in that the mixture of at least one unsaturated dicarboxylic acid is formed by mixing E isomers of mono-unsaturated C12 to C24 dicarboxylic acid obtained by metathesis with Z isomers. of mono-unsaturated C12 to C24 dicarboxylic acid obtained by fermentation.
[0007]
7. Ingredient according to one of the preceding claims, characterized in that the carbon chain of the monounsaturated dicarboxylic acid comprises 16 to 20 carbon atoms.
[0008]
8. Ingredient according to one of the preceding claims, characterized in that the concentration of isomer E is at least 40% by weight and / or the Z-isomer concentration is at most 60% by weight, based on the total weight of Z and E isomers
[0009]
9. Ingredient according to one of the preceding claims, characterized in that the position of the double bond of the at least one monounsaturated C12 to C24 dicarboxylic acid is at the center of the hydrocarbon chain.
[0010]
10. Ingredient according to one of the preceding claims, characterized in that the at least one monounsaturated dicarboxylic acid is octadec-9-ene-1,18-dicarboxylic acid (HO (0) C (CH2) 7CH = CH (CH2) 7C (0) OH).
[0011]
11. Ingredient according to one of the preceding claims, characterized in that it further comprises between 0.001% and 5% by weight of at least one antioxidant or radical scavenger, relative to the total weight of the ingredient . 3024037 39
[0012]
12. Ingredient according to claim 11 characterized in that the antioxidant or radical scavenger is selected from tocopherol, bisabolol, tocopherol acetate, ascorbyl palmitate, butylated hydroxytoluene and pentaerythrityl tetra. -di-t-butyl hydroxyhydrocinnamate and mixtures thereof. 5
[0013]
13. Use of an ingredient according to one of claims 1 to 12 for the manufacture of a cosmetic or dermatological composition.
[0014]
14. Cosmetic or dermatological composition comprising an effective amount of an ingredient according to any one of claims 1 to 12 and a physiologically acceptable excipient. 10
[0015]
15. Composition according to claim 14, characterized in that it comprises at least one complementary active ingredient.
[0016]
16. Composition according to claim 15, characterized in that the complementary active agent is chosen from lightening, pro-pigmenting, anti-redness, anti-stain, soothing active agents, sunscreens, moisturizing, moisturizing, exfoliating and smoothing active ingredients. , toners, anti-aging, anti-wrinkles and fine lines, improving the mechanical and elastic properties, the radiance of the complexion, the detoxifying active agents, anti-hair regrowth, anti-acne, acting on the secretion of sebum, mattifying, unifying agents Anti-inflammatory, anti-oxidant, anti-radical, anti-glycemic, anti-dandruff, eye contour (anti-dark circles and anti-puffiness), promoting blood circulation, peptides and vitamins. 20
[0017]
17. A composition according to claim 15 or 16, characterized in that it comprises at least one lightening complementary active agent chosen from vitamin C and ascorbic acid derivatives (ethyl ascorbic acid, ascorbyl glucoside, magnesium ascorbyl phosphate, sodium ascorbyl phosphate, disodium ascorbyl sulfate, ascorbyl tetraisopalmitate), niacinamide, licorice root extract (Glycyrrhiza glabra (licorice) root extract), and arbutin.
[0018]
18. Composition according to one of claims 14 to 17, in a form bound, 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 materials intended to come into contact with the skin and which may be used in clothing, day or night underwear, tissues, or tissues, for the purpose of exercising a cosmetic or dermatological effect through this skin / textile contact and allow continuous topical delivery.
[0019]
19. Ingredient according to any one of claims 1 to 12, or composition according to one of claims 14 to 18, for a dermatological treatment. 35
[0020]
20. Ingredient or composition according to claim 19, characterized in that the treatment is a topical anti-bacterial, anti-microbial, anti-inflammatory, anti-acne, against 3024037 buttons, rosacea, lentigo, dermatosis especially hyperpigmentaire, eczema, or impetigo.
[0021]
21. Use of an ingredient according to one of claims 1 to 12 or a composition according to one of claims 14 to 18 for a non-therapeutic cosmetic treatment of the skin 5 and its integuments.
[0022]
22. Use according to claim 21, characterized in that the ingredient is used at a concentration of 0.01% to 20% by weight relative to the total weight of the composition.
[0023]
23. Use according to claim 21 or 22 for topical treatment.
[0024]
24. Use according to one of claims 21 to 23, for a treatment chosen from among the 10 treatments: - to reduce the production of melanin in the skin, - to lighten the skin and its integuments, - to reduce cutaneous spots, - to homogenize the coloration of the skin, 15 - to moisturize, - to fight against cutaneous dryness, - to protect the cutaneous barrier, - to stimulate the synthesis of at least one of the molecules of the dermal extracellular matrix, 20 - anti-oxidant, - anti-wrinkles and fine lines, - slimming, - to improve the mechanical properties of the skin: firmness, and / or elasticity, and / or flexibility,
[0025]
Lipofiling by promoting the expansion and / or the formation of the subcutaneous adipose tissue with a view to improving and / or embellishing any body part deficient in lipids, anti-aging, oily skin, skins acne prone, 30 - anti-dandruff, - acting on the growth of hair, hair and nails, - desquamant, - anti-solar radiation, - deodorant, 35 - anti-seborrhoeic, - anti-glycation, 3024037 41 5 25.
[0026]
26. 10
[0027]
- promoting the re-epithelialization and / or regeneration of the skin or lips and the contour of the hair root or nails, and / or - to improve the comfort of the skin altered by either the cold or UV, mechanical friction. Use according to one of Claims 21 to 24 for a treatment of skins of phenotypes V and / or VI. Mixture of unsaturated dicarboxylic acids comprising the Z and E isomers of at least one C12 to C24 monounsaturated dicarboxylic acid, characterized in that the concentration of (i) isomer E is at least 40% by weight and Z isomer is at most 60% by weight both based on the total weight of Z and E isomers, (ii) saturated di-carboxylic acid is 0.1% to 4% by weight based on the total weight of the composition, and (iii) monocarboxylic acid is 0.15 to 0.5% by weight based on the total weight of the mixture. Mixture according to Claim 26, characterized in that it has at least one of the following indices: (i) iodine number of 50 to 120 g / 100 g, (ii) acid number of 310 to 380 mg of KOH / g and (iii) saponification number of 315 to 380 mg KOH / g.

类似技术:

---

公开号 | 公开日 | 专利标题

---

US9918916B2|2018-03-20|Active ingredient comprising a mixture of unsaturated dicarboxylic fatty acids, compositions comprising said ingredient and cosmetic or dermatological uses

---

FR2998570A1|2014-05-30|PEPTIDES, COMPOSITIONS COMPRISING THE SAME, AND PARTICULARLY COSMETIC USES THEREOF

---

US11166897B2|2021-11-09|Topical cosmetic treatment of scalp and corresponding active ingredient based on an extract of Apium graveolens

---

FR2880802A1|2006-07-21|COSMETIC OR DERMOPHARMACEUTICAL COMPOSITION CONTAINING EUGLENE EXTRACT

---

FR2980362A1|2013-03-29|NOVEL COSMETIC USE OF ALBIZIA JULIBRISSIN EXTRACT AND CORRESPONDING TOPICAL COMPOSITION

---

JP2017039749A|2017-02-23|Novel use of extract of plant origin of globularia and method for obtaining extract by in vitro plant culture

---

FR3021319A1|2015-11-27|PEPTIDES, COMPOSITIONS COMPRISING THE SAME, AND PARTICULARLY COSMETIC USES

---

FR3029782A1|2016-06-17|PEPTIDE COMPOUNDS, COMPOSITIONS COMPRISING THEM AND USES IN PARTICULAR COSMETICS

---

US9126060B2|2015-09-08|Cosmetic use of geranylgeranyl-2-propanol

---

FR2974297A1|2012-10-26|NOVEL COSMETIC OR THERAPEUTIC USE OF GHK TRIPEPTIDE

---

FR2985424A1|2013-07-12|NEW TOPICAL USE OF ZERUMBON

---

FR2975904A1|2012-12-07|NOVEL TOP USE, COSMETIC OR DERMOPHARMACEUTICAL, OF A MIXTURE COMPRISING A GHK TYPE TRIPEPTIDE AND A GQPR TYPE TETRAPEPTIDE

---

FR3029915A1|2016-06-17|TRIPEPTIDES, COMPOSITIONS COMPRISING THE SAME, AND USES IN PARTICULAR COSMETICS

---

EP2914349B1|2018-12-19|Combination of plant extracts, cosmetic ingredient and composition containing it and topical cosmetic use thereof

---

BR112012017716B1|2018-02-06|COMPOUND, AND, COMPOSITION

---

US20210052480A1|2021-02-25|Use of cyclic peptides in cosmetic

---

FR2978351A1|2013-02-01|PLANT ORIGINAL MATERIAL, COMPOSITION CONTAINING SAME, AND TOPICAL COSMETIC USE

---

FR3011742A1|2015-04-17|NOVEL ACTIVE TO HOMOGENIZE LIP VERMILLON AND COSMETIC COMPOSITIONS COMPRISING SAME

---

WO2015140679A1|2015-09-24|Cosmetic use of an extract of mirabilis jalapa

---

FR3004351A1|2014-10-17|PREVENTION AND TREATMENT OF SKIN DAMAGE ASSOCIATED WITH INFRA-RED

---

WO2015067525A1|2015-05-14|Oligopeptides and uses of same

同族专利:

---

公开号 | 公开日

---

EP3171869A1|2017-05-31|

---

US9918916B2|2018-03-20|

---

CN106794124B|2020-07-14|

---

CN106794124B9|2020-08-21|

---

WO2016012973A1|2016-01-28|

---

EP3171869B1|2021-10-20|

---

FR3024037B1|2018-03-02|

---

CN106794124A|2017-05-31|

---

US20170209350A1|2017-07-27|

引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

WO1994007837A1|1992-09-30|1994-04-14|Unichema Chemie B.V.|Unsaturated aliphatic dicarboxylic acids|

---

DE10150731A1|2001-10-13|2003-04-17|Beiersdorf Ag|Cosmetic or dermatological compositions useful for e.g. reducing skin and hair pigmentation comprise one or more antioxidants and 8-hexadecene-1,16-dicarboxylic acid|

---

DE10150732A1|2001-10-13|2003-04-17|Beiersdorf Ag|Cosmetic or dermatological compositions useful for e.g. reducing skin and hair pigmentation comprise one or more antioxidants and 8-hexadecene-1,16-dicarboxylic acid|

---

EP1754513A2|2005-08-17|2007-02-21|L'oreal|Use of 8-hexadecene-1,16-dicarboxylic acid as a care agent for promoting the horny layer cohesion|

---

WO2012061093A1|2010-10-25|2012-05-10|Stepan Company|Esteramines and derivatives from natural oil metathesis|

---

FR2992642A1|2012-06-29|2014-01-03|Novance|PROCESS FOR THE SYNTHESIS OF BIOSOURCES UNSATURATED ACIDS|

---

FR2677543B1|1991-06-13|1993-09-24|Oreal|COSMETIC FILTERING COMPOSITION BASED ON BENZENE 1,4-DI ACID AND NANOPIGMENTS OF METAL OXIDES.|

---

FR2677544B1|1991-06-14|1993-09-24|Oreal|COSMETIC COMPOSITION CONTAINING A MIXTURE OF NANOPIGMENTS OF METAL OXIDES AND MELANIC PIGMENTS.|

---

FR2737406B1|1995-08-04|1997-10-24|Sederma Sa|PHYSICAL ACTIVITY GEL FOR COSMETIC PRODUCTS|

---

US6190645B1|1999-07-15|2001-02-20|Playtex Products, Inc.|Sunscreen for the scalp hair and hair|

---

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|

---

FR2830195B1|2001-10-03|2004-10-22|Sederma Sa|COSMETIC AND DERMOPHARMACEUTICAL COMPOSITIONS FOR SKINS WITH ACNE TREND|

---

WO2003032941A2|2001-10-13|2003-04-24|Beiersdorf Ag|Cosmetic and/or dermatological active ingredient combination|

---

EP1448157A1|2001-11-09|2004-08-25|Beiersdorf AG|Cosmetic and/or dermatological preparation containing octadecene dicarboxylic acid and uv filtering substances|

---

FR2836042B1|2002-02-15|2004-04-02|Sederma Sa|COSMETIC OR DERMOPHARMACEUTICAL COMPOSITIONS FOR REDUCING POCKETS AND DARK CIRCLES UNDER EYES|

---

DE10233599A1|2002-07-24|2004-02-12|Beiersdorf Ag|Cosmetic or dermatological composition, especially for skin depigmentation, comprises hexadecene-1,16-dicarboxylic acid and a cyclodextrin derivative|

---

DE10238449A1|2002-08-22|2004-03-04|Beiersdorf Ag|Cosmetic and / or dermatological preparation|

---

FR2843963B1|2002-08-30|2004-10-22|Sederma Sa|NEW NORAPORPHIN-DERIVED MOLECULES|

---

TW200407172A|2002-10-17|2004-05-16|Unilever Nv|Scalp treatment|

---

DE10305965A1|2003-02-12|2004-08-26|Beiersdorf Ag|Cosmetic or dermatological composition used e.g. for rejuvenating and revitalizing skin, promoting skin metabolism and combating wrinkles contains 8-hexadecene-1,16-dicarboxylic acid|

---

FR2857266B1|2003-07-07|2007-09-21|Jean Noel Thorel|COMPOSITION FOR DERMATOLOGICAL AND / OR COSMETIC USE, COMPRISING AS ACTIVE INGREDIENT AT LEAST ONE LIPOPHILIC ANTIOXIDANT|

---

DE10346954A1|2003-10-09|2005-06-09|Beiersdorf Ag|Temperature-stable cosmetic cleaning preparation with dicarboxylic acids|

---

DE10348631A1|2003-10-15|2005-05-12|Beiersdorf Ag|Cosmetic or dermatological formulation containing 8-hexadecen-1,16-dicarboxylic acid, used against undesired pigmentation and lightening, e.g. of Mediterranean or Asiatic skin and hair types, has low lipophilic phase and emulsifier contents|

---

BRPI0415977A|2003-10-29|2007-01-23|Johnson & Johnson Consumer Fr|compositions comprising soy products and dioic acids|

---

AU2003296248A1|2003-11-17|2005-06-08|Sederma|Compositions containing mixtures of tetrapeptides and tripeptides|

---

FR2866563B1|2004-02-19|2008-01-11|Oreal|PEELING COMPOSITION COMPRISING 8-HEXADECENE-1,16-DICARBOXYLIC ACID|

---

FR2890310B1|2005-09-06|2009-04-03|Sederma Soc Par Actions Simpli|USE OF PROTOBERBERINS AS AGENTS REGULATING THE ACTIVITY OF THE PILOSEBACEE UNIT|

---

WO2007041548A2|2005-09-30|2007-04-12|The Procter & Gamble Company|Composition for regulation of mammalian keratinous tissue|

---

FR2902998B1|2006-07-03|2012-09-21|Oreal|USE OF AT LEAST ONE C-GLYCOSIDE DERIVATIVE AS A SOOTHING AGENT|

---

DE102006055043A1|2006-11-17|2008-05-21|Beiersdorf Ag|Cosmetic formulation with glucosylglycerides and skin brighteners|

---

FR2927801B1|2008-02-22|2010-03-05|Sederma Sa|MOISTURIZING COSMETIC COMPOSITION COMPRISING A COMBINATION OF HOMARIN AND ERYTHRITOL|

---

FR2941231B1|2009-01-16|2016-04-01|Sederma Sa|NOVEL PEPTIDES, COMPOSITIONS COMPRISING THEM AND COSMETIC AND DERMO-PHARMACEUTICAL USES|

---

US9000246B2|2009-10-12|2015-04-07|Elevance Renewable Sciences, Inc.|Methods of refining and producing dibasic esters and acids from natural oil feedstocks|

---

DE102010008321A1|2010-02-17|2011-08-18|Beiersdorf AG, 20253|Cosmetic preparations with improved sun protection performance|

---

FR2970868A1|2011-01-31|2012-08-03|Sederma Sa|PLANT ORIGIN EXTRACT, COMPOSITION CONTAINING THE SAME, PROCESS FOR OBTAINING BY VEGETABLE CULTURE AND USES IN THE COSMETIC, PHARMACEUTICAL AND COSMECEUTICAL FIELDS|

---

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|

---

GB201204715D0|2012-03-18|2012-05-02|Croda Int Plc|Metathesis of olefins using ruthenium-based catalytic complexes|

---

JP5599433B2|2012-06-21|2014-10-01|花王株式会社|Hair cosmetics|CN107118098B|2016-02-25|2020-07-14|中国科学院上海药物研究所|Fatty acid compounds, preparation method and application thereof|

---

WO2017197221A1|2016-05-13|2017-11-16|Englewood Lab, Llc|Compositions for skin application|

---

MX2019001827A|2016-08-19|2019-06-06|Unilever Nv|An antimicrobial composition.|

---

MX2019001788A|2016-08-19|2019-06-13|Unilever Nv|An antimicrobial composition.|

---

KR20210015854A|2018-05-24|2021-02-10|디에스엠 아이피 어셋츠 비.브이.|New uses of proline derivatives|

---

FR3110408A1|2020-05-20|2021-11-26|Laboratoire Dermatologique Inderma|ACTIVE COMPLEX AGAINST SKIN COLORING AND PIGMENTATION AND COSMETIC APPLICATIONS|

法律状态:
2015-05-18| PLFP| Fee payment|Year of fee payment: 2 |

---

2016-01-29| PLSC| Publication of the preliminary search report|Effective date: 20160129 |

---

2016-05-11| PLFP| Fee payment|Year of fee payment: 3 |

---

2017-05-05| PLFP| Fee payment|Year of fee payment: 4 |

---

2018-05-16| PLFP| Fee payment|Year of fee payment: 5 |

---

2020-05-04| PLFP| Fee payment|Year of fee payment: 7 |

---

2021-05-20| PLFP| Fee payment|Year of fee payment: 8 |

优先权:

---

申请号 | 申请日 | 专利标题

---

FR1457213A|FR3024037B1|2014-07-25|2014-07-25|COSMETIC OR DERMATOLOGICAL ACTIVE INGREDIENT COMPRISING A MIXTURE OF UNSATURATED FATTY DICARBOXYLIC ACIDS, COMPOSITIONS COMPRISING THE SAME, AND COSMETIC OR DERMATOLOGICAL USES|

---

FR1457213|2014-07-25|FR1457213A| FR3024037B1|2014-07-25|2014-07-25|COSMETIC OR DERMATOLOGICAL ACTIVE INGREDIENT COMPRISING A MIXTURE OF UNSATURATED FATTY DICARBOXYLIC ACIDS, COMPOSITIONS COMPRISING THE SAME, AND COSMETIC OR DERMATOLOGICAL USES|

---

EP15760262.4A| EP3171869B1|2014-07-25|2015-07-23|Active ingredient comprising a mixture of unsaturated dicarboxylic fatty acids, compositions comprising said ingredient and cosmetic or dermatological uses|

---

PCT/IB2015/055590| WO2016012973A1|2014-07-25|2015-07-23|Active ingredient comprising a mixture of unsaturated dicarboxylic fatty acids, compositions comprising said ingredient and cosmetic or dermatological uses|

---

US15/328,705| US9918916B2|2014-07-25|2015-07-23|Active ingredient comprising a mixture of unsaturated dicarboxylic fatty acids, compositions comprising said ingredient and cosmetic or dermatological uses|

---

CN201580039944.2A| CN106794124B9|2014-07-25|2015-07-23|Active ingredient containing a mixture of unsaturated dicarboxylic fatty acids, composition containing said ingredient and cosmetic or dermatological use|