FR2902333A1 - Cosmetic use of an amphiphilic block copolymer of alkyl poly(meth)acrylate-polyoxyethylene as a moisturizer for keratinous materials, preferably skin - Google Patents

Abstract

Cosmetic use of an amphiphilic block copolymer (I) of 1-6C alkyl poly(meth)acrylate -polyoxyethylene as a moisturizer for keratinous materials, preferably skin.

Description

USE OF AMPHIPHILIC BLOCK COPOLYMERS OF POLY (METH) ACRYLATE TYPE

  The present application relates to the use of amphiphilic block copolymers of the poly (meth) acrylates type C1-C6-polyoxyethylene as hydrating agents of keratinous materials. and more particularly the skin.

  The Stratum Corneum is the thin stratum corneum that forms the interface between the body and the drying environment. It is formed of the upper epithelial tissue: the epidermis, and connective tissue located below: the dermis. The Stratum Corneum, about 10 to 15 m thick, consists of vertically stacked corneocytes surrounded by a matrix of lipids organized in lamellar liquid crystal phase. Thus, it is a two-compartment system that can be compared to a brick wall, consisting of anucleate cells (bricks) and intercellular lamellar liquid crystal phases (cement).

  One of the functions of the Stratum Corneum is to regulate the flow of water into and out of the skin and thus to delay the excessive loss of water from the deeper layers of the epidermis. The Stratum Corneum also protects against mechanical aggression and the passage of chemicals and foreign microorganisms. It is also the first defense against UV radiation. In general, a moisturizing agent is defined as a substance that decreases the feeling of dry skin by affecting the water content of the skin by addition or retention.

  Generally, corneometry is the method used to measure the hydration provided by humectants such as glycerol, urea and its derivatives. But this method can not be used to highlight the moisturizing properties of polymers, so it was necessary to develop a suitable method to highlight the moisturizing properties of polymers. Different methods based on spectroscopic techniques (infrared, Raman, NMR, etc.) have been developed in recent years with the aim of improving the knowledge of the skin, in particular in the medical field. These techniques have the advantage of not requiring any special preparation of the sample and are non-invasive and non-destructive. These methods are described in particular in: 1. K. Wichrowski, G. Sore, and A. Khaiat, "Use of infrared spectroscopy for in vivo measurement of stratum corneum moisturization after application of cosmetic preparations," Int. J. Cos. Sci. 17, 1-11 (1995). 2. Querleux B, Richard S, Bittoun J, Jolivet O, Idy-peretti I, Bazin R, Lévêque JL: In vivo hydration profile in skin layers by highresolution magnetic resonance imaging. Skin Pharmacol 1994; 7: 210-216. 3. B. Schrader, B. Dippel, S. Fendel, S. Keller, T. Lochte, M. Riedl, R. Schulte, and E. Tatsch, "NIR FT Raman Spectroscopy, New Tool in Medical Diagnosis," Mol. Struct. 408/409, 23-31 (1997). In the context of the present application, the method adopted for measuring the amount of water supplied by polymer solutions at 1% by weight is laser confocal microscopy associated with Raman spectroscopy. Raman spectroscopy provides information on the molecular composition and structure of the test sample. Associated with confocal microscopy, it offers the advantage of providing information on the Stratum Corneum from the surface of the skin to a depth of a few tens of microns. In addition, the method used in this application has the advantage of being non-invasive and non-destructive.

  This method has established that the polymers used in accordance with the present application are such that a 1% solution by weight of these polymers makes it possible to provide a water content at least equal to that provided by a 7% solution. % by weight of glycerol.

  To implement this method, Isolated Stratum Corneum, compacted Stratum Corneum dander pellets, artificial skin (Episkin, Matek, Skinethic ...) from cosmetic surgery skin can be used as an evaluation support. . These examples are not limiting, all the media modeling the skin can be used. In the context of the present application, compacted dander pellets, weighing from 80 to 100mg, with a thickness of more than 100m and a surface area of about 1cm 2 are used as a model of Stratum Corneum; 5 measurements are made on each plantar pellet and 5 pellets are used for each polymer solution, 25 measurements for each polymer solution. The amount of polymer solution applied to each pellet is approximately 500. A Raman laser confocal microscope of LabRam type (Jobin Yvon to Horiba) equipped with a He: Ne laser (k = 633 nm power of approximately 8.4 mW ) and a CCD detector is used to perform the measurements. The laser beam is focused in the skin with an X50 objective and the Raman spectra are recorded using a point-to-point mode, from the sample surface, to the depth. The acquisition parameters of the spectra are: hole (hole) and slot (slit): 2001, tm, acquisition time: 30 s on a frequency of 2800 to 4000 cm -1 The microscope in question was the subject of a technical modification essential to the measurement of water, with the incorporation of an enclosure allowing to control during the acquisitions the temperature and the humidity: the parameters are of 25 C and 50% Relative Humidity The quantification of the Water is determined by the ratio of the water OH bands / CH3 protein bands, in Raman spectrography, as described in: 1 Chrit L, Hadjur C, Morel S, Sockalingum GD, Lebourdon G, Leroy F, Manfait M: In vivo Chemical Investigation of Human Skin Using a Confocal Raman Optic Microbiology J. Biomed Opt 2005. 2 Caspers PJ, Lucassen GW, EA Carter, Bruining HA, GJ Puppels: In vivo Confocal Raman Microspectroscopy of the Skin: Noninvasive Determination of Molecular Concentration profiles Journal of Investigative Dermatology 2 001; 116 (3): 434-442.

  The water / protein ratios in the Stratum Corneum were determined in Raman spectrography, by calculating the ratio between the intensity of the OH bands of the water (area under the curve) integrated between 3350cm "1 and 3550 cm-1 and the intensity of the protein CH3 bands (area under the curve) integrated between 2910cm "1 and 2965 cm" 1.

  Quantification of water is calculated from the following equations

  W / P = (m / mp) R Water content (%): m ,,,, (m ,,, + mp) = 100% (W / P) / (W / (P + R)) 20 m ,,, and mp respectively being the masses of water and protein in the volume of the tested sample W being the intensity of the Raman signal of the integrated water (integrated OH bands of the water (area under the curve) ); Where P is the intensity of the integrated protein Raman signal (embedded protein CH3 (area-under-the-curve) bands); R is a proportionality constant expressing the ratio between the Raman signals of water and proteins in a 50% solution. The water content is expressed in grams of water per 100 grams of wet tissue. These features are integrated into Jobin-Yvon Horiba's LabSpec software.

  To evaluate the moisturizing performance, the measurements are made at T = 0, before the treatment and at T + 1 hour after the treatment, from the surface to 20 m depth. The problem posed by the present application was to propose families of compounds that can be used as moisturizing agents for keratin materials and more particularly for the skin. The inventors of the present application have shown that this problem could be solved by means of amphiphilic block copolymers of poly (meth) acrylates C1-C6 alkyl-polyoxyethylene. The present application relates to the cosmetic use of at least one amphiphilic block copolymer of the poly (meth) acrylate C1-C6-polyoxyethylene as hydrating agent keratin materials and more particularly the skin.

  The amphiphilic block copolymers of poly (meth) acrylates C1-C6-polyoxyethylene have been found to be more moisturizing than glycerol. The amphiphilic block copolymers of poly (meth) acrylates C1-C6-polyoxyethylene used in the context of the present application may be used alone or in mixtures. Advantageously, the amphiphilic block copolymers used in the present application have the property of forming in contact with water micelles. The amphiphilic block copolymers used in the present application are diblocks (A-B), A corresponding to a hydrophobic polymeric block and B to a nonionic hydrophilic polymeric block. The weight average molecular weight of the copolymers may be between 1000 and 100,000; the weight ratio A / B can be between 1/100 and 50/1. The hydrophobic polymeric block (A) is formed from hydrophobic vinyl monomers of the formula: ## STR2 ## in which: R is chosen from H, or -CH 3, X is where R 'is a hydrocarbon radical; , linear or branched, saturated or unsaturated, having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms. Among the hydrophobic vinyl monomers that can be used to form the polymer A, mention may be made of methyl methacrylate, ethyl methacrylate, n-butyl (meth) acrylate, tert-butyl (meth) acrylate, cyclohexyl. The nonionic hydrophilic polymeric block (B) is polyethylene oxide (POE). The amphiphilic block copolymer is preferably chosen from the following block copolymers: polymethyl methacrylate / polyoxyethylene-butyl polymethacrylate / polyoxyethylene. By way of example, mention may be made of Tegomer BE 1010 (butyl polymethacrylate -POE 1000/1000) and BE 1030 (butyl polymethacrylate -POE 1000/3000) and Tegomer ME 1010 (polymethyl methacrylate -POE 1000/1000 ) and ME 1030 (polymethyl methacrylate POE 1000/3000) marketed by DEGUSSA. These amphiphilic block copolymers are obtained by transesterification of two polymeric blocks A and B according to the following reaction: ## STR2 ## ## STR2 ## ## STR1 ## where ## STR2 ## The inventors of the present application have shown that the polymers used in accordance with the present application are such that a solution containing 1% by weight of these polymers makes it possible to bring a quantity of water into the Stratum Corneum at least equal to that provided by a solution containing 7% by weight of glycerol.

  In the context of the present application, the amphiphilic block copolymers of poly (meth) acrylates C1-C6-polyoxyethylene can be used in cosmetic compositions in an amount of between 0.01% and 20% by weight of preferably between 0, 1% and 10% by weight relative to the total weight of said composition. The usable cosmetic compositions then contain a physiologically acceptable medium, that is to say, compatible with cutaneous tissues such as the skin and the scalp. This physiologically acceptable medium may more particularly consist of water and optionally of a physiologically acceptable organic solvent chosen, for example, from lower alcohols having from 1 to 8 carbon atoms and in particular from 1 to 6 RS carbon atoms, such as ethanol, isopropanol, propanol, butanol; polyethylene glycols having from 6 to 80 ethylene oxide units and polyols such as propylene glycol, isoprene glycol, butylene glycol, glycerine and sorbitol.

  The compositions that can be used can be in any of the galenical forms conventionally used for topical application and especially in the form of aqueous, hydroalcoholic solutions, oil-in-water (O / W) or water-in-oil (W / O) emulsions. ) or multiple (triple: W / O / W or H / E / H), aqueous gels, or dispersions of a fatty phase in an aqueous phase using spherules, these spherules may be polymeric nanoparticles such as nanospheres and nanocapsules or lipid vesicles of ionic and / or nonionic type (liposomes, niosomes, oleosomes). These compositions are prepared according to the usual methods. In addition, the compositions that can be used according to the invention can be more or less fluid and have the appearance of a white or colored cream, an ointment, a milk, a lotion, a serum, a paste or foam. They may optionally be applied to the skin in the form of an aerosol. They may also be in solid form, for example in the form of a stick. When the composition that can be used according to the invention comprises an oily phase, the latter preferably contains at least one oil. It may also contain other fatty substances.

  As oils that can be used in the composition of the invention, mention may be made, for example, of: hydrocarbon-based oils of animal origin, such as perhydrosqualene; hydrocarbon-based oils of vegetable origin, such as liquid triglycerides of fatty acids containing from 4 to 10 carbon atoms, for instance triglycerides of heptanoic or octanoic acids or, for example, sunflower, corn or soybean oils, squash, grape seed, sesame, hazelnut, apricot, macadamia, arara, castor oil, avocado, triglycerides of caprylic / capric acids such as those sold by Stearineries Dubois or those sold under the names Miglyol 810, 812 and 818 by Dynamit Nobel, jojoba oil, shea butter oil; esters and synthetic ethers, in particular of fatty acids, such as the oils of formulas R 1 COOR 2 and R 1 OR 2 in which R 1 represents the residue of a fatty acid comprising from 8 to 29 carbon atoms, and R 2 represents a hydrocarbon-based chain, branched or unbranched, containing from 3 to 30 carbon atoms, such as for example purcellin oil, isononyl isononanoate, isopropyl myristate, 2-ethylhexyl palmitate, octyl stearate -2-dodecyl, octyl-2-dodecyl erucate, isostearyl isostearate; hydroxylated esters such as isostearyl lactate, octyl hydroxystearate, octyldodecyl hydroxystearate, diisostearyl malate, triisocetyl citrate; heptanoates, octanoates, decanoates of fatty alcohols; polyol esters, such as propylene glycol dioctanoate, neopentyl glycol diheptanoate and diethylene glycol diisononanoate; and pentaerythritol esters such as pentaerythrityl tetraisostearate; linear or branched hydrocarbons of mineral or synthetic origin, such as paraffin oils, volatile or not, and their derivatives, petroleum jelly, polydecenes, hydrogenated polyisobutene such as parleam oil; fatty alcohols having from 8 to 26 carbon atoms, such as cetyl alcohol, stearyl alcohol and their mixture (cetylstearyl alcohol), octyldodecanol, 2-butyloctanol, 2-hexyldecanol, 2-undecylpentadecanol, oleic alcohol or linoleic alcohol; partially fluorinated hydrocarbon oils and / or silicone oils such as those described in document JP-A-2-295912; silicone oils such as volatile or non-volatile polymethylsiloxanes (PDMS) with a linear or cyclic silicone chain, which are liquid or pasty at room temperature, in particular cyclopolydimethylsiloxanes (cyclomethicones) such as cyclohexasiloxane; polydimethylsiloxanes comprising alkyl, alkoxy or phenyl groups, during or at the end of the silicone chain, groups having from 2 to 24 carbon atoms; phenyl silicones such as phenyltrimethicones, phenyldimethicones, phenyltrimethylsiloxydiphenylsiloxanes, diphenyl-dimethicones, diphenylmethyldiphenyltrisiloxanes, 2-phenylethyltrimethylsiloxysilicates, and polymethylphenylsiloxanes; their mixtures. By hydrocarbon oil is meant in the list of oils mentioned above, any oil predominantly comprising carbon and hydrogen atoms, and optionally ester, ether, fluoro, carboxylic acid and / or alcohol groups. The other fatty substances that may be present in the oily phase are, for example, fatty acids containing from 8 to 30 carbon atoms, such as stearic acid, lauric acid, palmitic acid and oleic acid; waxes such as lanolin, beeswax, carnauba or candelilla wax, paraffin waxes, lignite waxes or microcrystalline waxes, ceresin or ozokerite, synthetic waxes such as polyethylene waxes, waxes Fischer-Tropsch; silicone resins such as trifluoromethyl-C 1-4 alkyl dimethicone and trifluoropropyldimethicone; and silicone elastomers such as the products sold under the names KSG by the company Shin-Etsu, under the names Trefil, BY29 or EPSX by the company Dow Corning or under the names Gransil by the company Grant Industries.

  These fatty substances may be chosen in a varied manner by those skilled in the art in order to prepare a composition having the desired properties, for example of consistency or texture.

  The emulsions generally contain at least one emulsifier chosen from amphoteric, anionic, cationic or nonionic emulsifiers, used alone or as a mixture, and optionally a co-emulsifier. The emulsifiers are suitably selected according to the emulsion to be obtained (W / O or O / W). The emulsifier and the co-emulsifier are generally present in the composition, in a proportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight relative to the total weight of the composition.

  For the W / O emulsions, examples of emulsifiers that may be mentioned include dimethicone copolyols such as the mixture of cyclomethicone and dimethicone copolyol, sold under the name DC 5225 C by Dow Corning, and alkyldimethicone copolyols such as Laurylmethicone copolyol. sold under the name Dow Corning 5200 Formulation Aid by the company Dow Corning and cetyl dimethicone copolyol sold under the name Abil EM 90 by the company Goldschmidt. It is also possible to use, as surfactant of W / O emulsions, a crosslinked solid elastomeric organopolysiloxane comprising at least one oxyalkylene group, such as those obtained according to the procedure of Examples 3, 4 and 8 of US Pat. No. 5,412,004 and examples US-A-5,811,487, especially the product of Example 3 (synthetic example) of US-A-5,412,004. and such as that sold under the reference KSG 21 by Shin Etsu. For the HIE emulsions, mention may be made, for example, as emulsifiers, of nonionic emulsifiers such as oxyalkylenated (more particularly polyoxyethylenated) fatty acid esters of glycerol; oxyalkylenated fatty acid and sorbitan esters; oxyalkylenated fatty acid esters (oxyethylenated and / or oxypropylenated); oxyalkylenated fatty alcohol ethers (oxyethylenated and / or oxypropylenated); sugar esters such as sucrose stearate; and mixtures thereof such as the mixture of glyceryl stearate and PEG-40 stearate. In a known manner, the cosmetic or dermatological composition that may be used according to the invention may also contain adjuvants that are usual in the cosmetic or dermatological field, such as gelling agents, film-forming polymers, preservatives, solvents, perfumes, fillers, and filters. UV, bactericides, odor absorbers, dyestuffs, plant extracts and salts. The amounts of these various adjuvants are those conventionally used in the field under consideration, and for example from 0.01 to 20% of the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase and / or into the aqueous phase. In the context of cosmetic compositions, amphiphilic block copolymers of poly (meth) acrylates C1-C6 alkyl polyoxyethylene can be associated with each other, or other additional skin hydration agents and / or at least one other cosmetic active. As such an additional cosmetic asset, there may be mentioned the active agents acting on the barrier function of the skin, the active agents promoting the hydration of the skin and the desquamating agents. In the context of dermatological compositions, amphiphilic block copolymers of poly (meth) acrylates C1-C6 polyoxyethylene can be combined with each other, or with other additional skin hydrating agents and / or at less another asset, this asset can be cosmetic or dermatological. As such an additional asset, there may be mentioned active agents acting on the barrier function of the skin, the active agents promoting the hydration of the skin and the desquamating agents. By desquamating agent is meant any compound capable of acting: or directly on desquamation by promoting exfoliation, such as (3-hydroxyacids, in particular salicylic acid and its derivatives (including n-octanoyl 5-salicylic acid), α-hydroxyacids, such as glycolic, citric, lactic, tartaric, malic or mandelic acids, urea, gentisic acid, oligofucoses, cinnamic acid, Saphora japonica extract, resveratrol, or enzymes involved in desquamation or the degradation of corneodesmosomes, such as glycosidases, the Stratum Corneum chymotryptic enzyme (SCCE) or even other proteases (trypsin, chymotrypsin-like), mention may be made of the chelating agents of mineral salts: EDTA; acyl-N, N ', N' ethylene diaminetriacetic; aminosulfonic compounds and in particular N- (2-hydroxyethyl) piperazine-N'-2-ethanesulfonic acid (HEPES); 2-oxothiazolidine-4-carboxylic acid derivatives (procysteine); glycine-type alpha amino acid derivatives (as described in EP-0 852 949, as well as the sodium methyl glycine diacetate marketed by BASF under the trade name TRILON M); honey ; sugar derivatives such as O-octanoyl-6-D-maltose and N-acetyl glucosamine. Among the active agents acting on the barrier function of the skin, or promoting the hydration of the skin, mention may be made of: - either the compounds acting on the barrier function, with a view to maintaining the hydration of the stratum corneum, or the occlusive compounds , in particular ceramides, sphingoid-based compounds, lecithins, glycosphingolipids, phospholipids, cholesterol and its derivatives, phytosterols (stigmasterol, 13-sitosterol, campesterol), essential fatty acids, 1-2 diacylglycerol, 4-chromanone, pentacyclic triterpenes such as ursolic acid, petrolatum and lanolin; or compounds directly increasing the water content of Stratum Corneum, such as thralose and its derivatives, hyaluronic acid and its derivatives, glycerol, pentanediol, sodium pidolate, serine, xylitol, lactate sodium, glycerol polyacrylate, ectoin and its derivatives, chitosan, oligo- and polysaccharides, cyclic carbonates, N-lauroyl pyrrolidone carboxylic acid, and Na-benzoyl-L-arginine; or compounds that activate the sebaceous glands, such as steroid derivatives (including DHEA) and vitamin D and its derivatives. The compositions can show their effectiveness as a non-therapeutic skin care treatment, that is, as a preventive measure. They can also be used as a non-therapeutic treatment of the skin after a manifestation of disorders of the hydration of the skin. The composition may be presented as a non-therapeutic care product and / or makeup, and also a lip balm. The amphiphilic block copolymers of poly (meth) acrylates C1-C6 alkylpolyoxyethylene type can also be used in or for the implementation of a cosmetic treatment process for the non-therapeutic care and / or for the makeup of the skin characterized in that it comprises the application to the skin of at least one cosmetic composition according to the present invention comprising at least one amphiphilic block copolymer of poly (meth) acrylate C1-C6-polyoxyethylene as defined herein above or one of their mixtures in all proportions.

  Among the makeup type applications that the cosmetic treatment process makes it possible to envisage, mention may be made of foundations, blushers, eyeshadows, concealer and body make-up. The amphiphilic block copolymers of the poly (meth) acrylates C1-C6 alkylpolyoxyethylene as defined above or a mixture thereof can also be used for the preparation of a dermatological composition for the hydration of skin and more particularly to the treatment of dry skin or the treatment of dry skin.

  The following examples are illustrative of the present invention and can not limit the scope thereof. Examples The moisturizing performance of the following solutions was tested. Solution A Distilled water 93% Glycerol 7% 15 Solution B Distilled water 99% Tegomer ME 1010 (PolyMethyl Methacrylate-POE 1000/1000) 1% Solution C 20 Distilled water 99% Tegomer ME 1030 (PolyMethyl Methacrylate-POE 1000/3000) 1 % Solution D Distilled water 99% 25 Tegomer BE 1030 (PolyButyl Methacrylate-POE 1000/3000) 1% Solution E Distilled water 99% Tegomer BE 1010 (Polybutyl methacrylate POE 1000/1000) 1% 30 Moisture performance solution MCL Raman A 1 B 1.44 C 1.10 D 1.45 E 1.11 Significantly, amphiphilic block copolymers of poly (meth) acrylates C1-C6-polyoxyethylene, in solution in water at 1%, have a performance hydrating, measured in confocal laser Raman microscopy, higher than that of glycerol at 7% in water.

Sample composition

  The following moisturizing cosmetic composition was carried out: Phase Al: Sucrose distearate (marketed by the company 2.0% "STEARINERIE DUBOIS") Sorbitan stearate oxyethylenated with 4 moles of oxide 1.4% ethylene (marketed under the name "TWEEN 61" by the company ICI) stearic acid 0.75% Stearyl heptanoate (marketed by the company 5.50% DRAGOCO under the name PCL solid) Vaseline codex 2, 1% Avocado oil 4.50 % Jojoba oil 4.10% Volatile silicone oil 3.70% Vitamin E acetate 0.50% Perfume Propylparaben Methyl paraben Triethanolamine Demineralized water Phase A2: Phase B: Phase C: Mix of carboxyvinyl polymers 0.30% (marketed under the name "CARBOPOL 980" by the company GOODRICH) Tegomer BE 1030 (PolyButyl methacrylate POE 2% 1000/3000) Demineralized water 9.70% The two phases Al and B are brought to 65 C before being associated ( B in Al) under very vigorous agitation (rotor-stator). After checking for perfect dispersion, it is possible, optionally, to homogenize the dispersion between 20 × 10 6 Pascal and 60 × 10 6 Pascal, silicone rubber (marketed by the company 4.00% Dow Corning under the name "Q2-1403 Fluid"). ) 0.3% 0.1% 0.30% 0.40% qs 100.00% to obtain a dispersion whose size of the oil globules is less than 500 nm. Phase A2 is dispersed at room temperature in the first dispersion, with vigorous stirring. Laphase C, previously prepared, is then dispersed to gel the suspension. A moisturizing emulsion adapted for dry skin is obtained. Tegomer BE 1030 contributes to this moisturizing activity.

Claims (4)

  1. Cosmetic use of at least one amphiphilic block copolymer of the poly (meth) acrylate C1-C6-polyoxyethylene as hydrating agent keratin materials, preferably the skin.   2. Cosmetic use according to claim 1 characterized in that the amphiphilic block copolymer is an AB diblock with A corresponding to a hydrophobic polymeric block of formula: Co x in which: - R is chosen from H or -CH3, X is ûOR ' wherein R 'is a linear or branched, saturated or unsaturated hydrocarbon radical having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms; and B is an ethylene polyoxide.   3. Cosmetic use according to claim 1 or 2 characterized in that the amphiphilic block copolymer is chosen from polymethyl methacrylate / polyoxyethylene and polymethyl methacrylate / polyoxyethylene.   4. Cosmetic use according to one of claims 2 or 3 characterized in that the amphiphilic block copolymer diblock type A-B has a weight average molecular weight of between 1000 and 100 00020. Cosmetic use according to one of Claims 2 to 4, characterized in that the amphiphilic block copolymer of diblock type A-B has a weight ratio A / B of between 1/100 and 50/1.