FR2826548A1 - PARTICLE COMPRISING A MATRIX AND AT LEAST ONE BIOACTIVE AGENT, ITS PREPARATION METHOD AND ITS APPLICATIONS - Google Patents

Abstract

The invention relates to a novel particle comprising a matrix and at least one bioactive agent mixed with said matrix, whereby the concentration of the at least one bioactive agent in the particle is not constant between the core and the periphery of said particle. The invention also relates to a method for the production of said particle and the use thereof in polymer compositions.

Description

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PARTICLE COMPRISING A MATRIX AND AT LEAST ONE BIOACTIVE AGENT,
ITS PREPARATION METHOD AND APPLICATIONS
The present invention relates to a new particle comprising a matrix and at least one bioactive agent mixed with the matrix, its preparation process and its applications. The invention also relates to polymeric compositions comprising such particles.

 For many applications, it is sought to limit the development of microorganisms in the vicinity of thermoplastic articles. In the textile fields for example, it is sought to avoid smelly effects by limiting the development of a bacterial flora on the tissues. In the medical sectors it is of great importance to limit the development of bacteria or fungi on work tools, on construction materials, on clothing. Another field of application of bioactive compounds is the prevention of dust mite allergies.

 Agents having bioactive properties have been known for a very long time and are used for example for cosmetic applications or for fungicidal applications. Among these agents, metal compounds such as silver, copper or zinc are the most well known.

 Other agents are described in the literature. Patent EP 085 877 describes, for example, the use of dendrimers bearing primary amine functions, these functions being neutralized. These agents are formulated in aqueous or emulsion compositions to be applied in the form of lotions, creams, gels, sprays. These agents are however not incorporable into thermoplastic polymers and do not withstand the shaping temperatures of the latter.

 In order to give textile surfaces bioactive properties, many primers containing bioactive compounds, applied on the surface of fit / fiber / fitament in the dye bath for example, have been developed. Capsules of organic nature (for example polyamide capsules) containing bioactive agents may also be introduced onto the yarn / fiber / filament by size. These capsules are hung on the yarn / fiber / filament by gluing or superficial fusion of the capsules.

However, these primers or sizing still have a limited performance and their effects disappear after one or more washes. It is therefore in many cases more interesting to introduce the active ingredient directly into the fiber to have a bioactive property.

 For this purpose it is known to introduce a bioactive compound into yarns spun in solution or spun by coagulation. The bioactive compound is then introduced into the solvent of the polymer.

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 For polymers shaped in the melt phase, it is known to introduce inorganic fillers supporting a bioactivity agent such as a metal compound. These fillers can be introduced during the polymerization process or during the shaping process. Many solutions are proposed for the realization of mineral fillers. These fillers must have sufficient dispersibility in the polymer, an acceptable color, a controlled and durable bioactivity in the polymer, and they must not unduly impair the properties of the polymers.

 The bioactive agent responsible for the bioactivity of the feed often causes degradation of the properties of the polymers (such as yellowing) in which the feed is dispersed.

 In order to control the bioactivity of the charges while limiting the degradation of the properties of the polymers induced by these charges, it is necessary to control the kinetics of release of the bioactive agent (most often in cationic form) contained in these charges.

 Encapsulations of mineral type capable of releasing in a controlled manner the (or) cation (s) active (s) are known.

 For example, US Pat. No. 4,775,855 describes the use of silver-bearing zeolites.

US Pat. No. 5,180,585 describes mineral fillers with onion structure comprising three layers: a support core (for example silica, titanium dioxide), a layer of bioactive agent in metallic form or not (for example a silver layer), a protective layer (eg silica). The protective layer is described as protecting the polymer from degradations induced by the presence of the bioactive agent, such as yellowing of the polymer for example. An example of this type of charge is the charge Microfree &commat; marketed by DU PONT
Particles having a glass structure in which the active cation is trapped are also known. The cation is released by dissolving the mineral material in basic medium (phosphate, lonpure &commat; ISHIZUKA GLASS).

The article "Role of Ion Exchange in Solid State Chemistry" (A. Clearfield, Chemical
Review, 1988, 88, n, p. 125-148) describes three-dimensional networks referred to
NASICON (Na super ion conductor), consisting of anionic structures (for example tetravalent phosphates) forming cavities in which the active cation is inserted very probably by substitution of protons or cations (sodium, ammonium, etc.). Such products are in particular based on zirconium phosphate, this is particularly the case of NOVARON TOA GOSEI.

 With particles as described above, the kinetics of release of the bioactive agent is not perfectly controlled, since it is located and

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 accumulated at a particular location of the load, and is therefore not released in a controlled manner out of it.

l'agent, sont assurés par le maintien au cours du temps, à la surface de la charge : - d'une quantité suffisante d'agent bioactif pour conférer au polymère la bioactivité désirée - d'une quantité limitée d'agent bioactif afin de ne pas dégrader les propriétés du polymère. The control of the release of the bioactive agent out of the charge, and consequently the best compromise between the bioactivity and the degradation of the polymer caused by

the agent, are ensured by the maintenance over time, on the surface of the load: - a sufficient quantity of bioactive agent to give the polymer the desired bioactivity - a limited amount of bioactive agent in order to do not degrade the properties of the polymer.

 For this purpose, the object of the present invention is the development of a particle in which a bioactive agent is distributed in a non-uniform and particular manner, in particular according to an agent concentration gradient in the particle.

 Thus the first subject of the invention is a particle comprising a matrix and at least one bioactive agent mixed with the matrix, characterized in that the concentration of at least one bioactive agent in the particle is not constant between the core and the periphery of said particle.

 The invention also relates, and this is the second object of the invention, to a process for the preparation of the particle described above, characterized in that a precursor of the matrix and a precursor of the bioactive agent; the particle is formed and grown by precipitation of the reaction mixture thus obtained; during the precipitation, the concentration of the precursor of the introduced bioactive agent is varied as a function of the desired concentration distribution of the agent in the particle, and the concentration of the precursor of the introduced matrix is kept substantially constant.

 The invention finally relates to the use of the particle in a composition, in particular a polymer. The corresponding compositions are also part of the invention.

 The matrix of the invention is generally of a mineral nature. It is most often an amorphous matrix. Generally the matrix is a metal compound, advantageously an oxygenated metal compound.

 Preferably, the matrix is chosen from metal oxides and their mixed oxides. It may be chosen from oxides of titanium, aluminum, zinc, copper, zirconium, and cerium, calcium sulphate, strontium and barium compounds, zinc sulphide, copper sulphide, zeolites, mica, talc, kaolin, mullite and silica.

 Preferably, the matrix is chosen from oxides of titanium, zirconium, silicon cerium or aluminum, and more advantageously the matrix is silica.

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 By "bioactive" agent is meant an agent that can prevent the proliferation of certain living species, either by killing them or by limiting their reproduction.In the latter case, we also often talk about biostatic agents. be anti-bacterial, bacteriostatic, antimicrobial, antifungal, anti-mite.The particle comprising it will then be used for these purposes.

 The bioactive agent of the invention is generally formed by a metal compound.

que l'ion métallique ou toute composition chimique contenant l'élément métal, comme les complexes ou les sels. By metal compound for the bioactive agent is meant both the metal element

as the metal ion or any chemical composition containing the metal element, such as complexes or salts.

Advantageously, the bioactive agent is chosen from the following list.

metallic silver, its Ag + cation, its oxides, for example Ag2O, its halides, copper metal, its Cu + and Cu2 + cations, its CuO and CU20 oxides, its CuS sulphide, its hydroxides, hydroxycarbonates, oxycations, halides, carbonates, metallic zinc, its Zn2 + cation, its ZnO oxide, its ZnS sulphide, ZnSiO3 -the other compounds and ions of groups 3 to 12 of the international classification, such as Ru, Rh, Pd, Os, Ir, Pt, Au, Hg , Cd, Cr, Ni, Pb
They can be used alone or in combination.

 According to a preferred embodiment of the invention, the bioactive agent is chosen from the compounds of Ag, Cu, Zn and their combinations. Even more preferably, the bioactive agent is a compound of Ag.

 In general, the concentration of bioactive agent in the particle is between 0.05 and 20% by weight relative to the total weight of the particle. It is preferably between 0.1 and 5%.

 The particle, when it comprises silver compounds used as a bioactive agent, preferably contains at most 1% by weight of Ag element relative to the total weight of the particle.

 Similarly, the particle, when it comprises zinc compounds used as a bioactive agent, preferably contains at most 15% by weight of Zn element relative to the total weight of the particle.

 According to a particular variant of the invention, the particle is substantially spherical. The average diameter of the particle is then advantageously at most equal to 5 ju. m, preferably at most equal to 1 μm.

 According to another variant of the invention, the average diameter of the particle is advantageously at most equal to 300 nm. Particle diameters as small as 30 nm can be obtained.

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 According to one characteristic of the invention, the concentration of at least one bioactive agent in the particle is not constant between the core and the periphery of the particle.

In general, the concentration of the bioactive agent is greater at the heart of the particle than at the periphery. More particularly, the concentration of bioactive agent decreases from the core to the periphery of the particle. Indeed the goal is to constitute a "reserve" of bioactive agent within the particle, and maintain a small amount of bioactive agent on the surface of the particle.

 According to a particular embodiment of the invention, the concentration of bioactive agent on the surface of the particle is zero, or close to zero.

 According to a preferred embodiment of the invention, the particle comprises two bioactive agents: a silver compound and a zinc compound. More particularly, the concentration of the silver compound decreases from the core to the periphery of the particle, and the concentration of the zinc compound is constant or increases from the center to the periphery of the particle.

 The matrix may be functionalized for the purpose of acquiring properties such as hydrophilicity and hydrophobicity.

 In particular, the matrix may be associated with products such as stearic acid, calcium stearate, in order to obtain a better dispersion of the particle in reaction media in which it could be used.

 The invention also relates, and this is the second object of the invention, to a process for the preparation of the particle described above, characterized in that a precursor of the matrix and a precursor of the bioactive agent; the particle is formed and grown by precipitation of the reaction mixture thus obtained; the concentration of the precursor of the introduced bioactive agent is varied during the precipitation depending on the desired concentration distribution of the agent in the particle, and the precursor concentration of the introduced matrix is maintained.

 The precursor of the matrix is generally a metal compound, advantageously an oxygenated metal compound, preferably a metal oxide, such as an alkali metal oxide or a metal alkoxide. In the case of a method for preparing a silica-based particle for example, the precursor of the matrix may be an alkali silicate or an alkyl silicate.

 The precursor of the matrix is advantageously a metal alkoxide.

The alkoxide is generally selected from the alkoxides of Si, Ti, Zr, Ce, Mg, Al,
Hf, Nb and Ta. Advantageously, this alkoxide is an alkoxide of Si, Ti, Zr or Ce. More preferably, it is an alkoxide of Si.

 The alkyl group is preferably the methyl or ethyl group.

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 An example of an alkoxide that can be used for the present invention is methyl silicate SiO (Me) 4.

 The precursor of the matrix may be a complex.

invention est Ago3. Le sel est introduit au cours de la synthèse de la particule sous forme par exemple d'une solution aqueuse. La préparation de la matrice est généralement réalisée selon une méthode classique connue de l'homme du métier : la "voie Stöber", qui permet de limiter le phénomène d'agglomération des particules. Dans ce cas, la solution du procédé de l'invention comprend de l'ammoniaque et un solvant alcoolique adéquat, plus particulièrement un solvant hydroalcoolique. The precursor of the bioactive agent is usually a metal salt. It may be more particularly chosen from nitrates, acetates or metal halides. An example of a metal salt that can be used for the present

invention is Ago3. The salt is introduced during the synthesis of the particle in the form of, for example, an aqueous solution. The preparation of the matrix is generally carried out according to a conventional method known to those skilled in the art: the "Stöber route", which makes it possible to limit the agglomeration phenomenon of the particles. In this case, the solution of the process of the invention comprises ammonia and a suitable alcoholic solvent, more particularly a hydroalcoholic solvent.

The precursor of the bioactive agent can be a complex
According to a first variant of the method, the precursor of the matrix and the precursor of the bioactive agent are introduced into a solution containing seeds.

 These seeds, which are smaller than the desired particle size, may be of the same nature or of a different nature from that of the matrix of the particle to be prepared.

These seeds make it possible to initiate the process for preparing the particles according to the invention. The choice of operating conditions, in particular the rate of germs, is made according to the desired particle size. The use of these seeds makes it possible to prepare particles having a size of between about 300 nm and a few microns.

 According to another process variant, the particle is prepared directly from a solution without seeds, choosing during the preparation the appropriate operating conditions, in particular the temperature, depending on the desired particle size. The temperature during the preparation is generally between 20 and 65 C. This variant makes it possible to prepare particles of size less than or equal to about 300 nm. Particles as small as 30 nm can thus be obtained.

 This particle preparation route makes it possible to obtain structured particles and a precisely targeted particle size.

 According to the process of the invention, the precursor of the matrix is introduced into the solution with or without seeds, the reaction mixture then obtained precipitates and the particle generally grows by aggregation.

 The concentration of the precursor of the matrix is maintained in the solution, in order to allow regular aggregation, and thus particle growth as desired. According to a particular embodiment of the invention, the precursor of the matrix is introduced continuously into the reaction mixture.

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 According to the process of the invention, the precursor of the bioactive agent is introduced into the solution with or without germs. The concentration of the precursor of the bioactive agent introduced during the precipitation is varied according to the desired concentration distribution of the bioactive agent in the particle. According to a particular variant of the invention, the precursor of the bioactive agent is introduced simultaneously to the precursor of the matrix in the reaction mixture. This is to introduce the bioactive agent during the precipitation of the reaction mixture, thus during the growth of the particle.

 The more it is desired to have a large amount of bioactive agent present at a given point of the particle, the higher the concentration of the precursor of the bioactive agent introduced into the reaction mixture must be raised at the corresponding instant of the precipitation. And conversely if we want a small amount of bioactive agent present at a given point of the particle. By this method, this concentration can be varied at any time and at will, and so consider all possible distributions of bioactive agent in the particle. In practice, it is generally carried out by "stages", that is to say by modifying the concentration of the precursor of the bioactive agent introduced at regular or irregular time intervals. At the end of the precipitation, if it is desired to have a particle whose concentration of bioactive agent is zero at the periphery, it is possible, for example, to stop the supply of the bioactive agent precursor while continuing to supply the precursor reaction mixture. of the matrix for a few moments.

 The particles obtained by the process according to the invention can be dried according to any drying method known to those skilled in the art. They can then be calcined according to a method also known to those skilled in the art. The calcination temperature may be between 100 and 800 ° C., it is preferably between 450 and 650 ° C.

 The invention also relates to polymeric matrix-based compositions comprising particles as described above.

 The proportion by weight of the particle in the polymer compositions depends on the bioactivity of the particle and the level of bioactivity desired for the use that will be made. It is generally between 0.01 and 10% by weight. The proportion by weight of the bioactive agent in the composition is generally between 5 ppm and 10000 ppm.

 The matrix consists of a polymer or copolymer or a material containing a polymer or copolymer. It may consist of a mixture of polymers or copolymers, optionally compatibilized by grafting or by the use of compatibilizing agents.

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 Any type of polymer is suitable as a matrix. In particular, thermoplastic materials are mentioned.

cite : les polylactones telles que la poly (pivalolactone), la poly (caprolactone) et les polymères de la même famille ; les polyuréthanes obtenus par réaction entre des diisocyanates comme le 1, 5-naphtalène diisocyanate ; le p-phénylène diisocyanate, le m-phénylène diisocyanate, le 2, 4-toluène diisocyanate, le 4, 4'-diphénylméthane diisocyanate, le 3, 3'-diméthyl-4, 4'-diphényl-méthane diisocyanate, le 3, 3-'diméthyl-4, 4'biphényl diisocyanate, le 4, 4'-diphénylisopropylidène diisocyanate, le 3, 3'-diméthyl-4, 4'diphényl diisocyanate, le 3, 3'-diméthyl-4, 4'-diphénylméthane diisocyanate, le 3,3'diméthoxy-4, 4'-biphényl diisocyanate, le dianisidine diisocyanate, le toluidine diisocyanate, le hexaméthylène diisocyanate, le 4, 4'-diisocyanatodiphénylméthane et composés de la même famille et les diols à longues chaines linéaires comme le poly (tétraméthylène adipate), le poly (éthylène adipate), le poly (1, 4-butylène adipate), le poly (éthylène succinate), le poly (2, 3-butylène succinate), les polyéther diols et composés de la même famille ; les polycarbonates comme le poly [méthane bis (4-phényl)

carbonate], le poly[1, 1-éther bis (4-phényl) carbonate], le poly [diphénylméthane bis (4- phényl) carbonate], le poly[1, 1-cyclohexane bis (4-phényl) carbonate] et polymères de la même famille ; les polysulfones ; les polyéthers ; les polycétones ; les polyamides comme le poly (4-amino butyrique acide), le poly (hexaméthylène adipamide), le poly (acide 6aminohexanoïque), le poly (m-xylylène adipamide), le poly (p-xylylène sebacamide), le poly (2,2, 2-triméthyl hexaméthylène téréphthalamide), le poly (métaphénylène isophtalamide), le poly (p-phénylène téréphtalamide), et polymères de la même famille ; les polyesters comme le poly (éthylène azélate), le poly (éthylène-1, 5-naphtalate, le poly (1, 4-cyclohexane diméthylène téréphtalate), le poly (éthylène oxybenzoate), le poly (para-hydroxy benzoate), le poly (1, 4-cyclohexylidène diméthylène téréphtalate), le poly (1, 4-cyclohexylidène diméthylène téréphtalate), le polyéthylène téréphtalate, le polybutylène téréphtalate et les polymères de la même famille ; les poly (arylène oxydes)

comme le poly (2, 6-diméthyl-1, 4-phénylène oxyde), le poly (2, 6-diphényl-1, 4-phénylène oxyde) et les polymères de la même famille ; les poly (arylène sulfures) comme le poly (phénylène sulfure) et les polymères de la même famille ; les polyétherimides ; les polymères vinyliques et leurs copolymères comme l'acétate de polyvinyle, l'alcool polyvinylique, le chlorure de polyvinyle ; le polyvinyle butyral, le chlorure de polyvinylidène, les copolymères éthylène-acétate de vinyle, et les polymères de la même famille ; les polymères acryliques, les polyacrylates et leurs copolymères comme

l'acrylate de polyéthyle, le poly (n-butyl acrylate), le polyméthylméthacrylate, le polyéthyl méthacrylate, le poly (n-butyl méthacrylate), le poly (n-propyl méthacrylate), le By way of example of thermoplastic materials that are suitable as a matrix,

mention: polylactones such as poly (pivalolactone), poly (caprolactone) and polymers of the same family; polyurethanes obtained by reaction between diisocyanates such as 1,5-naphthalene diisocyanate; p-phenylene diisocyanate, m-phenylene diisocyanate, 2,4-toluene diisocyanate, 4,4'-diphenylmethane diisocyanate, 3,3'-dimethyl-4,4'-diphenylmethane diisocyanate, 3, 3-dimethyl-4,4'-biphenyl diisocyanate, 4,4'-diphenylisopropylidene diisocyanate, 3,3'-dimethyl-4,4'-diphenyl diisocyanate, 3,3'-dimethyl-4,4'-diphenylmethane diisocyanate, 3,3'-dimethoxy-4,4'-biphenyl diisocyanate, dianisidine diisocyanate, toluidine diisocyanate, hexamethylene diisocyanate, 4,4'-diisocyanatodiphenylmethane and compounds of the same family and linear long-chain diols such as poly (tetramethylene adipate), poly (ethylene adipate), poly (1,4-butylene adipate), poly (ethylene succinate), poly (2,3-butylene succinate), polyether diols and compounds of same family ; polycarbonates such as poly [methane bis (4-phenyl)

carbonate], poly [1,1-ether bis (4-phenyl) carbonate], poly [diphenylmethane bis (4-phenyl) carbonate], poly [1,1-cyclohexane bis (4-phenyl) carbonate] and polymers of the same family; polysulfones; polyethers; polyketones; polyamides such as poly (4-amino-butyric acid), poly (hexamethylene adipamide), poly (6-aminohexanoic acid), poly (m-xylylene adipamide), poly (p-xylylene sebacamide), poly (2, 2,2-trimethyl hexamethylene terephthalamide), poly (metaphenylene isophthalamide), poly (p-phenylene terephthalamide), and polymers of the same family; polyesters such as poly (ethylene azelate), poly (ethylene-1,5-naphthalate, poly (1,4-cyclohexane dimethylene terephthalate), poly (ethylene oxybenzoate), poly (para-hydroxy benzoate), poly (1,4-cyclohexylidene dimethylene terephthalate), poly (1,4-cyclohexylidene dimethylene terephthalate), polyethylene terephthalate, polybutylene terephthalate and polymers of the same family; poly (arylene oxides)

such as poly (2,6-dimethyl-1,4-phenylene oxide), poly (2,6-diphenyl-1,4-phenylene oxide) and polymers of the same family; poly (arylene sulfides) such as poly (phenylene sulfide) and polymers of the same family; polyetherimides; vinyl polymers and their copolymers such as polyvinyl acetate, polyvinyl alcohol, polyvinyl chloride; polyvinyl butyral, polyvinylidene chloride, ethylene-vinyl acetate copolymers, and polymers of the same family; acrylic polymers, polyacrylates and their copolymers as

polyethyl acrylate, poly (n-butyl acrylate), polymethyl methacrylate, polyethyl methacrylate, poly (n-butyl methacrylate), poly (n-propyl methacrylate),

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tolylène diisocyanate, le 4, 4'-diphénylméthane diisocyanate, le 1, 6-hexaméthylène diisocyanate, le 4, 4'-dicycohexylméthane diisocyanate et les composés de la même famille ; et les polysulfones telles que les produits de réaction entre un sel de sodium du 2,2-bis (4-hydroxyphényl) propane et de la 4, 4'-dichlorodiphényl sulfone ; les résines furane comme le poly (furane) ; les plastiques cellulose-ester comme l'acétate de cellulose, l'acétate-butyrate de cellulose, propionate de cellulose et les polymères de la même famille ; les silicones comme le poly (diméthyl siloxane), le poly (diméthyl siloxane co-phénylméthyl siloxane), et les polymères de la même famille ; les mélanges d'au moins deux des polymères précédents. polyacrylamide, polyacrylonitrile, poly (acrylic acid), ethylene-acrylic acid copolymers, ethylene-vinyl alcohol copolymers, acrylonitrile copolymers, methyl methacrylate-styrene copolymers, ethylene-ethyl acrylate copolymers, methacrylate-butadiene-styrene copolymers, ABS, and polymers of the same family; polyolefins such as low density poly (ethylene), polypropylene, low density chlorinated poly (ethylene), poly (4-methyl-1-pentene), poly (ethylene), poly (styrene), and polymers of the same family; ionomers; poly (epichlorohydrins); poly (urethane) such as diol polymerization products such as glycerine, trimethylolpropane, 1,2,6-hexantriol, sorbitol, pentaerythritol, polyether polyols, polyester polyols and compounds of the same family with polyisocyanates such as 2,4-tolylene diisocyanate, 2,6-diisocyanate

tolylene diisocyanate, 4,4'-diphenylmethane diisocyanate, 1,6-hexamethylene diisocyanate, 4,4'-dicycohexylmethane diisocyanate and compounds of the same family; and polysulfones such as the reaction products between a sodium salt of 2,2-bis (4-hydroxyphenyl) propane and 4,4'-dichlorodiphenyl sulfone; furan resins such as poly (furan); cellulose-ester plastics such as cellulose acetate, cellulose acetate butyrate, cellulose propionate and polymers of the same family; silicones such as poly (dimethyl siloxane), poly (dimethyl siloxane co-phenylmethyl siloxane), and polymers of the same family; mixtures of at least two of the above polymers.

 The thermoplastic polymer is advantageously chosen from polyesters, such as PET, PPT, PBT, their coplymers and mixtures, polyamides such as nylon 6, nylon 6.6, nylon 4, polyamides 6-10,4. 6, 6-36, their copolymers and blends, PVC, polyolefins.

 The particles according to the invention may have been subjected to compatibilization treatments with the polymeric matrix. These treatments are, for example, surface treatments or a surface deposition of a compound different from that constituting the core of the particles. Treatments and deposits can likewise be implemented in order to promote the dispersion of the particles, either in the polymerization medium of the polymer matrix or in the molten polymer.

 Any method for obtaining a dispersion of particles in a resin can be used to implement the invention. A first method consists in mixing the particles in molten resin and possibly subjecting the mixture to a large shear, for example in a twin-screw extrusion device, in order to achieve a good dispersion. Such a device is generally located upstream of the spinning. The yarns, fibers and filaments, as well as the textile articles obtained therefrom, are bioactive. This is the preferred method of the invention.

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 Another method consists of mixing the particles with the monomers in the polymerization medium and then polymerizing the resin. Another method consists in mixing with the molten resin a concentrated mixture of a resin and particles, prepared for example according to one of the processes described above.

 In a process where the particles are mixed with the molten resin, the particles may be in the form of powder, dispersion in a liquid, granules, masterbatch in a polymer of the same nature as the polymer matrix.

 According to another embodiment of the invention, the particle is used in the composition of fiber and filament sizing formulations, in formulations of primers or dyes applied to textile surfaces, or in laundry formulations or cosmetics, or in formulations in the field of paper.

 The compositions may contain any other additives or adjuvants which may be used, for example, flame retardants, UV stabilizers, heat, mattifying agents, lubricants, plasticizers, compounds useful for the catalysis of matrix synthesis. polymeric, antioxidants, antistats. This list has no limiting character. The particles may also be associated with other reinforcing additives such as resilience modifiers such as optionally grafted elastomers, mineral reinforcements such as clays, kaolin, fibrous reinforcements such as glass fibers, polyester fibers, and other fibers. aramids, carbon fibers, ceramic fibers.

 The compositions according to the invention may be shaped into threads, fibers or filaments by melt-spinning. They can also be used in the field of engineering plastics, for example for the production of molded articles.

 Other details and advantages of the invention will become apparent in view of the examples below given for information only.

The antibacterial or bacteriostatic activity of the particles and compositions containing them is measured according to the test called "Shake Flask Test" and described in US Pat. No. 4,708,870. The operating protocol for the test is as follows:
1 g of product to be tested is brought into contact with 70 ml of phosphate buffer at pH 7.2 and 5 ml of a bacterial suspension at 1-310 5 CFU / ml in a 250 ml Erlenmeyer flask. A powderless Erlenmeyer flask is used as a control test. The bacterial strain used is Klebsiella pneumoniae. The Erlenmeyer flasks are stirred at 300 movements per minute at room temperature. A count of bacteria is made after 0.1 and 24 hours of incubation. A reduction rate is defined by the

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ratio between the number of bacteria before and after incubation and the number of bacteria before incubation (measured at 0 hours).

- Bioactive agent relaraaae test
Apparatus: ICP / EOS
External calibration according to the quality procedure: 249 ET 035
Solution in HF / HN03
Relative uncertainty: 10%
In a beaker, 0.5 g of charged particles are dispersed in 50 ml of deionized water.

 The suspension is stirred for the duration of the test, then samples are taken at different times and the bioactive agent (in ppm) present in the supernatant is measured.

EXAMPLES Example 1 Preparation of Silica Spreads In a 1 L reactor equipped with a double jacket thermostatically controlled at 250 ° C. and a stirring anchor rotating at 250 rpm, the reactants are introduced as follows: Foot of tank 262 g water 312.1% 950 ethanol 52.07 g NH 4 OH (28%) 156 g of ethyl silicate are added at 350 ° C. and 1.4 ml / min. The dispersion is used as such for inoculation (Example 2). ) Dry extract: 5.6% Average particle size: 130 nm Example 2: Preparation of silica / Ag particles (uniform distribution of silver in the silica matrix) In a 1 L reactor equipped with a double jacket thermostated at 25 ° C. C. and a stirring anchor rotating at 250 rpm, the reactants are introduced as follows: Feet of the tank 147.4 g of water 308.7% of methanol
135.1 gNH40H20% 29.75 g of 130 nm seeds

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The solutions below are then added via two pumps so that the two solutions are diametrically opposed.

<Tb>
<Tb>

Solution <SEP> 1 <SEP> Solution <SEP> 2
<tb> 36.8 <SEP> g <SEP> of water <SEP> 114 <SEP> g <SEP> of <SEP> tetramethylortho <SEP> silicate
<tb> 3.68 <SEP> g <SEP> of <SEP> CH3COOH
<tb> 0, <SEP> 85g <SEP> from <SEP> AgN03
<Tb>
Flow rate: 0.37 g / min Flow rate: 0.93 g / min Centrifugation is carried out at 4500 rpm for 15 min and then washed with water by centrifugation at 4500 rpm for 15 min.

Then we dry overnight at 60 C.

Characteristics of the final product The particles have an average size of 380 nm determined by quasi-elastic light scattering. The effective weight ratio of silver contained in the particles is 0.98%. After redispersion of the final particles at pH 10, the amount of silver released is 3.1% by weight relative to the total weight of silver introduced (after 2 hours).

EXAMPLE 3 Preparation of Silica / Ag Precursor Particles Ethyl Silicate (Silver Concentration Gradient in the Silica Matrix) In a 1 L reactor equipped with a double jacket thermostated at 250 ° C. and an anchor stirring at 250 rpm the reactants are introduced as follows: Feet of the tank 147.4 g of water 308.7 g of ethanol 135.1 g of NH40H 20% 29.75 g of 130 nm seeds The solutions below are then added for 2 hours by means of two pumps so that the two solutions are diametrically opposed.

<Tb>
<Tb>

Solution <SEP> 1 <SEP> Solution <SEP> 2
<tb> 100 <SEP> g <SEP> of water <SEP> 152 <SEP> g <SEP> of <SEP> tetraethylortho <SEP> silicate
<tb> 0, <SEP> 85g <SEP> from <SEP> AgN03
<Tb>
Flow rate: Flow rate: 1.26 g / min + 0 to 30 min: 1, 33 g / min (40% of the money introduced) + 30 to 60 min: 1 g / min (30% of the money

<Desc / Clms Page number 13>

l'argent introduit) + 115 à 120 min : 0 g/min On réalise une centrifugation à 4500 tours/min pendant 15 min, puis on lave à l'eau par centrifugation à 4500 tours/min pendant 15 min. introduced) + 60 to 90 min: 0.66 g / min (20% of the money introduced). 90 to 115 min: 0.33 g / min (10% of

the introduced silver) + 115 to 120 min: 0 g / min Centrifugation is carried out at 4500 rpm for 15 min and then washed with water by centrifugation at 4500 rpm for 15 min.

Then we dry overnight at 60 C.

Characteristics of the final product The particles have an average size of 370 nm determined by quasi-elastic light scattering. The EDS analysis confirms the absence of grain-free money. The effective weight ratio of silver contained in the particles is close to 1%. After redispersion of the final particles at pH 10, the amount of silver released is 0.7% by weight relative to the total weight of silver introduced (after 2 hours).

Example 4 The product from Example 3 is calcined in air at 5500C for 2 hours.

EXAMPLE 5 Preparation of Silica / Ag Precursor Methyl Silicate Particles (with a Silver Concentration Gradient in the Silica) In a 1 L reactor equipped with a double jacket thermostated at 250 ° C. and a rotating stirring anchor at 250 rpm the reactants are introduced as follows: Feet 147, 4 g of water 308.7 g of methanol 135.1 g of NH40H 20% 29.75 g of 130 nm seeds 2 hours the solutions below through two pumps so that the two solutions arrived are diametrically opposed.

<Tb>
<Tb>

Solution <SEP> 1 <SEP> Solution <SEP> 2
<tb> 36.8 <SEP> g <SEP> of water <SEP> 114 <SEP> g <SEP> of <SEP> tetramethylortho <SEP> silicate
<tb> 3, <SEP> 68 <SEP> g <SEP> of <SEP> CH3COOH <SEP> 1 <SEP> M
<tb> 0, <SEP> 85gdeAgN03
<Tb>
Flow rate: Flow rate: 0, 93 g / min + 0 to 30 min: 0.66 g / min (40% of the money introduced)

<Desc / Clms Page number 14>

l'argent introduit) + 115 à 120 min : 0 g/min On réalise une centrifugation à 4500 tours/min pendant 15 min, puis on lave à l'eau par centrifugation à 4500 tours/min pendant 15 min. + 30 to 60 min: 0.33 g / min (30% of the money introduced). 60 to 90 min: 0.26 g / min (20% of the silver introduced) + 90 to 115 min: 0, 11 g / min (10% of

the introduced silver) + 115 to 120 min: 0 g / min Centrifugation is carried out at 4500 rpm for 15 min and then washed with water by centrifugation at 4500 rpm for 15 min.

Then we dry overnight at 60 C.

Characteristics of the final product The particles have an average size of 375 nm determined by quasi-elastic light scattering. The EDS analysis confirms the absence of grain-free money. The effective weight ratio of silver contained in the particles is close to 1%. After redispersion of the final particles at pH 10, the amount of silver released is 0.75% by weight relative to the total weight of silver introduced. (after 2 hours).

EXAMPLE 6 Preparation of Silica Particles Containing Silver and Zinc In a 1 L reactor equipped with a thermostatically controlled double jacket at 25 ° C. and a stirring anchor rotating at 250 rpm, the reagents are introduced. 147.4 g of water 308.7 g of methanol 135, 1 g of NH40H 20% 29.75 g of seeds of 130 nm are then added. The solutions below are then added over a period of 2 hours. two pumps so that the two solutions are diametrically opposed.

<Tb>
<Tb>

Solution <SEP> 1 <SEP> Solution <SEP> 2 <SEP> Solution <SEP> 3
<tb> 36.8 <SEP> g <SEP> water <SEP> 8, <SEP> 16 <SEP> g <SEP> from <SEP> Zn <SEP> (N03) <SEP> 2. <SEP > 6H20 <SEP> 114 <SEP> g <SEP> of <SEP> tetramethylortho
<tb> 3.68 <SEP> g <SEP> of <SEP> CH3COOH <SEP> 1 <SEP> M <SEP> 110g <SEP> of water <SEP> silicate
<tb> 0, <SEP> 32g <SEP> from <SEP> AgNOs
<tb> Flow rate <SEP>: <SEP> Flow rate <SEP>: <SEP> Flow rate <SEP>: <SEP> 0.93 <SEP> g / min
<tb> + <SEP> 0 <SEP> to <SEP> 60 <SEP> min <SEP>: <SEP> 0, <SEP> 66 <SEP> g / min <SEP> + <SEP> 0 <SEP> at <SEP> 60 <SEP> min <SEP>: <SEP> 0 <SEP> g / min
<tb> + <SEP> 60 <SEP> to <SEP> 120 <SEP> min <SEP>: <SEP> 0 <SEP> g / min <SEP> + <SEP> 60 <SEP> to <SEP> 120 <SEP> min <SEP>: <SEP> 1, <SEP> 8 <SEP> g / min
<Tb>

<Desc / Clms Page number 15>

 Centrifugation is carried out at 4500 rpm for 15 minutes and then washed with water by centrifugation at 4500 rpm for 15 minutes.

Then we dry overnight at 60 C.

Characteristics of the final product The particles have an average size of 400 nm determined by quasi-elastic light scattering. MET / EDS analysis confirms the absence of grain-free money. The effective weight ratio of silver and zinc contained in the particles is respectively close to 0.4% and close to 4%.

Example 7 The product from Example 2 is calcined in air at 550 ° C. for 4 hours. After redispersion of the final particles at pH 10, the amount of silver released is 0.7% by weight relative to the total weight of silver introduced (after 2 hours).

EXAMPLE 8 Polyamide 66 granules with a viscosity index of 140.6 ml / g (measured at 25 ° C. in a Hubbelhode viscometer of a solution containing 5 g / l of polymer dissolved in a mixture composed of 90% by weight of formic acid and 10% by weight of water). are dried at 80 ° C. under vacuum for 16 hours. Bioactive agents according to Examples 4 and 5 are incorporated into the polyamide using a Leistriz 30.34 twin-screw extruder. The compositions obtained are crushed by cryogenic grinding into a powder of which 90% of the grains have a diameter of less than 850 μm.

The characteristics of the compositions are specified in Table 1.

conditions que l'exemple 8 (composition DO).

Comparative Example 1 A control sample containing no bioactive agent is made in the same

conditions as Example 8 (composition DO).

<Tb>
<Tb>

Table <SEP> 1
<tb> Composition <SEP> Agent <SEP> bioactive <SEP>% <SEP> in <SEP> weight <SEP> of <SEP> agent
<tb> bioactive <SEP> in <SEP> the <SEP> composition
<tb> DO <SEP> 1 <SEP> a
<tb> 01 <SEP> Example <SEP> 4 <SEP> 0, <SEP> 8
<tb> 02 <SEP> Example <SEP> 5 <SEP> 0, <SEP> 8
<Tb>

<Desc / Clms Page number 16>

 The bioactivity of the compositions is tested according to the protocol described above. A test control without powder is carried out. The results are specified in Table 2.

Table 2

<Tb>
<tb> Concentration <SEP> of <SEP> bacteria <SEP> (CFU / ml) <SEP><SEP> rate of <SEP> reduction <SEP> (%)
<tb> Composition <SEP> Initial <SEP> 1 <SEP> hour <SEP> 24 <SEP> hours <SEP> 1 <SEP> hour <SEP> 24 <SEP> hours
<tb> Control <SEP> of assay <SEP> 9, <SEP> 80 * 103 <SEP> 1 <SEP> 00 * 104 <SEP> 1 <SEP> 05 * 104 <SEP> - <SEP> DO9, <SEP> 55 * 103 <SEP> 1, <SEP> 03 * 104 <SEP> 1, <SEP> 12 * 104-D1 <SEP> 1.03 * 104 <SEP> 9.45 * 103 <SEP> 0 <SEP> 7, <SEP> 80 <SEP> 100
<tb> D21, <SEP> 06 * 104 <SEP> 6, <SEP> 85 * 103 <SEP> 1, <SEP> 00 * 10 <SEP> 35.38 <SEP> 99.99
<Tb>

Claims (30)

CLAIMS 1. Particle comprising a matrix and at least one bioactive agent mixed with the matrix, characterized in that the concentration of the agent in the particle is not constant between the core and the periphery of said particle. 2. Particle according to claim 1, characterized in that the concentration of at least one bioactive agent is greater in the core of the particle than in the periphery. 3. Particle according to one of the preceding claims, characterized in that the concentration of the bioactive agent is zero or close to zero at the periphery of the particle. 4. Particle according to one of the preceding claims, characterized in that said matrix is a mineral matrix. 5. Particle according to claim 4, characterized in that the mineral matrix is chosen from metal oxides and their mixed oxides. 6. Particle according to claim 5, characterized in that the mineral matrix is selected from oxides of titanium, zirconium, cerium, silicon, aluminum or their mixed oxides, and mixtures thereof. 7. Particle according to claim 6, characterized in that the mineral matrix is silica. 8. Particle according to any one of claims 1 to 7, characterized in that said bioactive agent is formed by a metal compound. 9. Particle according to claim 8, characterized in that the bioactive agent is selected from the compounds of silver, copper, zinc and mixtures thereof. 10. Particle according to claim 9, characterized in that the bioactive agent is a silver compound. 11. Particle according to claim 10, characterized in that it comprises at most 1% by weight of silver element relative to the total weight of the particle. <Desc / Clms Page number 18> 12. Particle according to claim 9, characterized in that it comprises a bioactive agent consisting of a silver compound and a bioactive agent consisting of a zinc compound, the concentration of the silver compound decreasing from the core to the periphery of the particle, and the concentration of the zinc compound remaining constant or increasing from the core to the periphery of the particle. 13. Particle according to any one of the preceding claims, characterized in that

 it is substantially spherical, the average diameter of the particle being at most equal to 1 lim. 14. Particle according to claim 12, characterized in that the mean diameter of the particle is at most equal to 300 nm. 15. Process for the preparation of a particle according to claim 1, characterized in that a precursor of the matrix and a precursor of the bioactive agent are introduced into a solution; the particle is formed and grown by precipitation of the reaction mixture thus obtained; during the precipitation, the concentration of the precursor of the introduced bioactive agent is varied as a function of the desired concentration distribution of the agent in the particle, and the concentration of the precursor of the introduced matrix is kept substantially constant. 16. The method of claim 14, characterized in that the solution contains seeds. 17. The method of claim 14 or 15, characterized in that the precursor of the matrix is continuously introduced into the reaction mixture. 18. Method according to one of claims 14 to 16, characterized in that the precursor of said agent is introduced simultaneously to the precursor of the matrix in the reaction mixture. 19. Method according to one of claims 14 to 17, characterized in that the particles obtained are dried and / or calcined. 20. Method according to one of claims 14 to 18, characterized in that the precursor of the matrix is a metal oxide compound. <Desc / Clms Page number 19> 21. The method of claim 19, characterized in that said precursor of the matrix is a metal alkoxide. 22. Process according to claim 20, characterized in that the metal alkoxide is an alkyl silicate, in particular a methyl or ethyl silicate. 23. Method according to one of claims 14 to 21, characterized in that the precursor of said bioactive agent is a metal salt, in particular a nitrate or an acetate. 24. Use of particles according to one of the preceding claims as an additive in compositions based on polymeric matrix, in particular polyamide, polyester or polyvinyl chloride. 25. Composition based on polymeric matrix, containing a joint additive according to one of claims 1 to 22. 26. Composition according to claim 24, characterized in that the polymeric matrix is a polyamide or polyester matrix. 27. The composition of claim 24 or 25, characterized in that the proportion by weight of the joint additive in the composition is between 0.01 and 10%. 28. Yarns, fibers and filaments obtained by shaping a composition according to claim 24 or 25. 29. Textile articles made from yarns, fibers or filaments according to claim 27. 30. Cosmetic or detergent composition comprising particles according to one of claims 1 to 22.