FR2702929A1 - Matrix type microparticles containing at least one biocidal agent, process for their preparation and manufactured products containing them - Google Patents

Abstract

The subject of the present invention is matrix-type microparticles which contain at least one biocidal agent, a process for their preparation and manufactured products containing them. The said biocidal agent(s) is (are) (a) compound(s) which has (have) a water-solubility at room temperature of less than 500 mg/l and which is (are) active at low concentrations, and the matrix in which the said biocidal agent(s) is (are) dispersed is based on one or more meltable hydrophobic constituents selected to confer on the said microparticles little sensitivity to pH values and to organic solvents as well as a stability up to temperatures of the order of 95-120 DEG C and to permit the controlled release of the said biocidal agent(s) in the presence of water or moisture. Such microparticles are especially intended to be incorporated into manufactured products such as the soles of shoes, sponges, mastic for sealing and the like, so as to discharge therein, in a controlled manner, the biocidal agent or agents which they contain.

Description

Matrix type microparticles containing at least one biocidal agent process for their preparation and manufactured products containing them.

 The present invention firstly relates to matrix-type microparticles which contain at least one biocidal agent. It also relates to a process for the preparation of said microparticles and manufactured products containing them.

 The Applicant has developed, according to the invention, programmed release systems of biocidal agents, alone or as a mixture, in particular intended to be incorporated in manufactured products, during their manufacture, and to avoid, within said products in the presence of moisture or water, bacterial and / or fungal developments for the duration of use of said products, without external intervention.

The applicant is therefore proposing a solution to the technical problem according to which we wish:
- Incorporate at least one biocidal agent into a manufactured product, during its manufacture while protecting said biocide from various aggression due to the product manufacturing process and avoiding pollution by said biocide of the reaction media involved during said process. manufacturing process; and
- Release said biocide, in a programmed manner, to preserve said manufactured product throughout its life of use.

 Such a programmed release of biocidal agent into a product is of great interest, especially when said product is placed, definitively or temporarily, under conditions where fungal and / or bacterial proliferation is possible in it is likely to alter its mechanical properties and / or its physical appearance ... it is the same when the product in question is intended to come into contact with materials, to be preserved from contamination, food or containers of food, for example.

 The programmed biocide release systems according to the invention are particularly advantageous for incorporation during their manufacture, in products for packaging, coating or surface treatment products, building materials, products of the invention. maintenance and cleaning; these examples of application of the invention being given without limitation. Of particular interest is the introduction of such systems into sponges or cellulosic sponge webs.

 Compositions intended to ensure the programmed release of biocidal agents have already been described but without ever taking into account the advantage of incorporating them into a manufactured product, during its manufacture, so that said biocide acts within said manufactured product.

 Thus, EP-A-106 563 has described compositions containing a biocide, in particular of the isothiazolone family, having a solubility in water of greater than 500 mg / l, dispersed on a support. in a hydrophobic compound having a melting point of 40 to 200 ° C; said compositions for controlling, by slow dissolution of the biocide, the proliferation of microorganisms in aqueous systems such as industrial baths, swimming pools, tanks. Also disclosed in US-A-3,753,676 is the use of a soluble chlorinating agent embedded in a hydrophobic matrix.

 In these two publications, as well as in many others, the compositions, intended to slowly release the disinfecting agent, are in the form of massive objects that are soaked in the volume of liquid to be protected.

 According to the prior art, medicinal active principles have also been encapsulated in various variants in order to schedule their release into the body.

 According to the invention, a double selection was made at the level of the active principle and the constituents of the matrix to solve the technical problem set out above: that of the anti-bacterial and / or anti-fungal protection of products manufactured by release within them of biocide (s); the said protected biocide (s) being introduced during the manufacturing process of the said manufactured products.

 Said double selection has led, in a non-obvious way, to the preparation of microparticles which, on the one hand, are resistant to severe chemical and physical conditions for their incorporation into the product during its manufacturing process and which on the other hand, allow in the presence of water or moisture the controlled release of the biocide during the period of use of said product (under generally mild conditions).

 Said microparticles of the invention are of the matrix type and therefore contain at least one biocidal agent.

They are characterized in that:
the said biocidal agent (s) is (are) a compound (s) having a solubility in water at room temperature of less than 500 mg / l and that is (are) active at low concentrations, and that:
the matrix in which is dispersed the said biocide agent (s) is based on one or more hydrophobic constituent (s) fusible (s) ), selected to impart to said microparticles little sensitivity to pH and organic solvents and stability up to temperatures of the order of 95-120iC and to allow the controlled release of the said (s) ) biocidal agent (s) in the presence of water or moisture.

The intervening biocidal agent (s) must have the characteristics set out above, namely: - be slightly soluble in water: the low solubility of the active principle makes it possible to introduce into the particulate system proportions of active ingredient greater than the percolation rate and to reduce the amount of particulate system to be introduced,
- Being active (s) at low concentrations: it is understood that one is, in practice, limited as to the amount of active ingredient to be introduced into the product to be protected, that is to say as to the amount of microparticles to introduce. Active biocides are advantageously used at concentrations of the order of 0.1% by weight relative to the weight of product to be protected.

 Advantageously, the intervening biocidal agent (s) is (are) solid compound (s) at room temperature. However, it is in no way excluded to use according to the invention a (or) agent (s) biocide (s) liquid (s) at room temperature.

 It will be indicated, moreover, that the said intervening biocidal agent (s) present (s) advantageously a heat resistance compatible with the conditions of incorporation of the microparticles in the product under development. In any case, the microparticles (biocide (s) fortified in one or more hydrophobic constituent (s) fuse (s) must be stable at temperatures of the order of 95-120iC.

 From the precisions given above, the skilled person is able to select active ingredients - biocides - suitable for the purposes of the present invention.

Suitable for these purposes include:
2- (1,3-thiazol-4-yl) benzimidazole (or thiabendazole),
methylbenzimidazol-2-yl carbamate (or cari, endazim),
2,2'-dihydroxy-5,5'-dichlorodiphenylmethane (or dichlorophene),
2,4,4'-trichloro-2'-hydroxybiphenyl ether (or triclosan),
1- [[2- (2,4-dichlorophenyl) -1,3-dioxalan-2-yl] methyl] -1H-1,2,4-triazole (or azaconazole), and
- their mixtures.

 This list is by no means exhaustive.

 The matrix in which the said biocide agent (s) is (are) dispersed is based on one or more fusible hydrophobic constituent (s). .

The hydrophobicity required for said materials is easily conceived. Their fusible character is required to allow the manufacture of microparticles at reasonable temperatures. It is advantageous to choose materials whose melting temperature is less than or equal to 150. Said melting temperature must, however, be greater than the temperatures at which said microparticles must resist. It is advantageously between 120 and 150in.

As indicated further in the present text, said matrix must, as far as possible, isolate and protect the active ingredient from the medium in which it is introduced for its incorporation into the manufactured product (and likewise isolate and protect said active principle said medium) while allowing controlled release in a moist environment or in the presence of water. The constituents of said matrix must be chosen to confer on the microparticles:
a relative inertia to the pH of the manufacturing media and to the organic solvents they may contain; said pH being able, according to the methods, to have values as different as 0-1 or 12-14;
a thermal stability, up to temperatures of the order of 95-120 Ci; rarely exceeded temperatures in common processes.

 The matrix must be characterized by an ability to withstand extreme physicochemical conditions and, as a result, it is able to withstand a large number of industrial manufacturing processes.

 Said matrix advantageously has a melting temperature greater than 95in; resistance at pH 14 at 60 ° C for at least 15 minutes; resistance at pH 1 at 700C for at least 15 min; resistance to the action of carbon disulfide for at least 15 minutes; the resistance being defined as limiting the release in the test medium of the biocide (s), in an amount not exceeding 50% by weight, preferably 15% by weight of the amount of biocide (s), initially present.

 From the precisions given above, the skilled person is able to select the base component (s) of said matrix.

Advantageously, said basic constituents have a melting point greater than 100 μl and are chosen from:
microcrystalline waxes;
linear saturated hydrocarbons with a molecular weight of between 500 and 3,000;
polyethylene waxes, of molecular weight between 500 and 3000;
linear-chain fatty acid amides, especially stearamide;
ethylene bistearamide; and
- their mixtures.

 In addition to said basic constituents and the biocidal agent (s) it contains, the matrix may also contain one or more additives of the compatibilizing agent, plasticization, surfactant type ...

 It is advantageously used therein, to increase its hydrophilicity, at least one optionally polyoxyethylenated lipophilic nonionic surfactant having from 0 to 40 ethylene oxide units per molecule. Such surfactants may be used up to 30% by weight of the microparticles of the invention. According to a preferred variant, they intervene up to 15% by weight. They advantageously consist of polyoxyethylenated fatty alcohols which have a linear carbon chain containing from 10 to 100 carbon atoms and from 2 to 40 ethylene oxide units per molecule.

 By involving several of said surfactants, one can observe a synergistic effect on the expected result.

 By thus modifying the composition of the matrix, the kinetics of release of the biocide (s) contained in said matrix are notably influenced.

 A surfactant of the type specified above or a mixture of such agents is advantageously used in combination with at least one linear chain saturated hydrocarbon for the production of microparticles according to the invention.

 Said microparticles generally contain from 5 to 70% by weight, advantageously from 15 to 50% by weight, of active principle - biocide (s) - within them.

 They are generally in the form of spheres, whose diameter is between 0.05 and 2 mm, preferably between 0.1 and 1 mm. The particle size of said microparticles is an important parameter that influences the kinetics of release of the active ingredient.

 They can be in other forms, which result from their manufacturing process, and in particular in the form of scales.

Said method for producing the microparticles of the invention constitutes another subject of the present invention. n consists in implementing known techniques in themselves with the active principles and constituents of the matrix selected according to the invention. It includes:
dispersing or dissolving the biocidal agent (s) in the hydrophobic constituent (s) of the molten matrix (s);
fractionation of the mixture obtained in the form of liquid or semi-liquid microparticles of desired shape and size; and
- Curing said microparticles by cooling.

The techniques used, which are well known in their own right to the person skilled in the art, may especially consist of:
the dispersion methods in a liquid medium known under the name of "meltable dispersions" or "hot melt", according to which the melt or dispersion of the active ingredient in the molten matrix is dispersed in a non-solvent liquid medium at a temperature greater than the solidification temperature of the system.The suspension is then cooled until solidification of the product;
- Hot extrusion followed by granulation, according to the traditional technique of manufacturing plastic compounds;
- The spray or prilling methods, according to which the melt or dispersion of the active ingredient in the molten matrix is formed into droplets of desired particle size, by casting through a possibly vibrated nozzle. The drops are then subjected to a spontaneous or forced cooling, so that they solidify during their fall;
the flaking method, according to which a cooled cylinder is partially immersed in a bath containing the mixture or molten dispersion. The rotation of the cylinder makes it possible to recover in the cold zone a solidified mixture film, which is granulated by coarse grinding and sieving.

 Said techniques allow the preparation of matrix-type microparticles (to be considered in opposition to the microparticles of the reservoir type).

 According to its last object, the invention relates to manufactured products which contain the microparticles, as defined above.

 Advantageously, said microparticles intervene within said products in an amount effective to ensure their preservation throughout their duration of use.

 Advantageously, they intervene in the heart of said products, insofar as they were incorporated during the manufacture thereof.

Such incorporation is carried out without damage, for the microparticles and the reaction media in which they are involved, insofar as the composition of the matrix of said microparticles has been optimized to withstand extreme physicochemical conditions.

 In a non-obvious manner, the microparticles of the invention are capable of withstanding the said extreme physicochemical conditions and of delivering, in a controlled manner, in the presence of water or moisture, the agent or the biocidal agents which are they enclose.

 Said microparticles can advantageously intervene, as indicated in the introduction of the present application, in products for packaging, coating or surface treatment products, building materials, cleaning and cleaning products. for example in shoe soles, sponges, sealants ...

 All of these products, which contain microparticles of the invention, are within the scope of the present invention.

 This is illustrated by the examples below.

The applicant has worked with the following products:
Biocides Azaconazole = 1- [2- (2,4-dichlorophenyl) -1,3-dioxalan-2-yl] methyl] -1H-1,2,4-triazole; marketed by Janssen Pharmaceutica under the trademark RODEWOD ~.

 Dichlorophen = 2,2'-dihydroxy-5,5'-dichlorodiphenylmethane, marketed by Bayer under the brand name Preventol GD8.

 Carbendazim = methylbenzimidazol-2-yl carbamate (MBC), sold by the company Intace under the trademark Carbendazim B300 #.

 Triclosan = 2,4,4'-trichloro-2'-hydroxybiphenyl ether; marketed by CIBA GEIGY under the trademark Irgasan Du300 ~.

 Thiabendazole = 2- (1,3-thiazol-4-yl) benzimidazole CBZ); marketed by CIBA GEIGY.

Constituents of the matrix
Stearamide (C17H35-CONH2), such as, for example, UNIWAX # 1750 marketed by UNICHEMA CHEMIE GmbH.

 ~ PHROLFIE ~ PE 1040: oxidized polyethylene wax, marketed by PETROLL1E Co.

. PolywaxX 2000: linear chain saturated hydrocarbon, marketed by
PETROLITE Co.

 . EPOLENE) C10: polyethylene wax, marketed by EASTMAN CHEMICAL PRODUCIS.

 . UNITHOXss 550: polyoxyethylenated alcohol, marketed by PETROLITE Co.

EXAMPLE 1
a) 50 g of azaconazole are introduced into 50 g of molten stearamide with stirring at a temperature between 1350C and 180-C until the azaconazole is melted and dissolved in the stearamide.

 The mixture is formed into spherical particles by the prilling technique. For this purpose, the molten mixture is cast using a nozzle having a calibrated orifice, and the resulting droplets are cooled during their fall to the solidification temperature. The product is then calibrated, and the off-board particles can be recycled directly into the melter.

 Particles with a diameter of between 500 and 1000 μg are thus collected, grading 50% by weight of azaconazole.

 b) By the method described in Example 1a, particles of a mixture of azaconazole and oxidized polyethylene wax (PETROL1IEs PE 1040), containing 50% by weight of azaconazole, are produced.

c) In order to simulate the release of the active ingredient (azaconazole) in a given volume of frequently renewed water, the particles prepared in a) and b) are subjected to the following test:
500 mg of coated azaconazole equivalent are introduced into a perforated bag of mesh 95 x 95 m. The sachet is introduced into a bottle containing 100 ml of distilled water. Every 24 hours, the azaconazole dissolved in water is determined by UV spectrophotometry, and the water in the flask is replaced with 100 ml of pure distilled water.

The table below shows the amount of azaconazole released based on the number of water renewals.

<tb><SEP> Number <SEP> of <SEP><SEP> Indicator azaco- <SEP> Example <SEP><SEP> Example <SEP> lb
<tb> renewal <SEP> nazole <SEP> (quantity <SEP> (quantity <SEP> dissolved <SEP> (quantity <SEP> dissolved
<tb><SEP> dissolved <SEP> cumulative, <SEP> cumulative, <SEP> mg) <SEP> cumulative, <SEP> mg)
<tb><SEP> mg)
<tb><SEP> 1 <SEP> 35 <SEP> 17.7 <SEP> 12.5
<tb><SEP> 3 <SEP> 105 <SEP> 36.2
<tb><SEP> 5 <SEP> 175 <SEP> 55.3
<tb><SEP> 10 <SEP> 350 <SEP> 109.3 <SEP> 79
<tb><SEP> 20 <SEP> exhausted <SEP> 174 <SEP> 129.4
<tb><SEP> 30 <SEP> 215.9 <SEP> 174.3
<tb><SEP> 40 <SEP> 263.1 <SEP> 202.2
<tb><SEP> 50 <SEP> 300 <SEQ> 232.9
<tb><SEP> 60 <SEP> 332 <SEP> 262.3
<Tb>

EXAMPLE 2
a) By the method described in Example la, is prepared, by stamping azaconazole in a mixture polywax ~ 2000 / EPOLLNEg) C10 (90/10 by weight), particles of the invention, titrating different percentages by weight of principle active.

<Tb>

Examples <SEP> Content <SEP> in <SEP> azaconazole <SEP> Content <SEP> en <SEP>"enameling"
<tb><SEP> in <SEP><SEP> in weight) <SEP> (% <SEP> in <SEP> weight)
<tb><SEP> 2A <SEP> 20 <SEP> 80
<tb><SEP> 2B <SEP> 30 <SEP> 70
<tb><SEP> 2C <SEP> 40 <SEP> 60
<tb><SEP> 2D <SEP> 50 <SEP> 50
<Tb>
b) The dissolution of azaconazole is studied by introducing 50 mg of azaconazole equivalent in one liter of distilled water at 40 ° C.

The table below shows the percentage of azaconazole released over time.

<tb><SEP> Time <SEP> of <SEP> Example <SEP> 2A <SEP> Example <SEP> 2B <SEP> Example <SEP> 2D
<tb><SEP> dissolve <SEP> (dissolved <SEP>) <SEP> (dissolved <SEP>) <dissolved SEP> (% <SEP>)
<tb><SEP> (min)
<tb><SEP> 60 <SEP> 4 <SEP> 1,9 <SEP> 4,6
<tb><SEP> 120 <SEP> 5.3 <SEP> 2.3 <SEP> 9.2
<tb><SEP> 300 <SEP> 5.6 <SEP> 3.3 <SEP> 18.2
<tb> 1440 <SEP> 10.7 <SEP> 20.3 <SEP> 50
<tb> 2400 <SEP> 12 <SEP> 26.3
<tb> 2800 <SEP> 12.6 <SEP> 28.2
<Tb>

 c) The particles prepared in a are subjected to a hot resistance test in basic and acidic media under the conditions specified below.

50 mg protected azaconazole equivalent are introduced into a sachet
Nylon mesh 95 Crm dipped successively in 50 ml of molar soda at 60iC for 10 min, then in 50 ml of sulfuric acid molar at 75-C for 15 min.

The dissolved azaconazole is measured in each of the baths and expresses the overall resistance level which is the non-extracted fraction of the active ingredient.

<Tb>

<SEP> Azaconazole <SEP> Example <SEP> Example <SEP><SEP> Example <SEP> 2C <SEP> Example
<tb><SEP> No <SEP> Protected <SEP> 2A <SEP> 2B <SEP> 2D
<tb><SEP><SEP><SEP> Soluble <SEP> Ratio <SEP> 96 <SEP> 94.5 <SEP> 94.3 <SEP> 20
<tb> resistance <SEP> medium <SEP> acid
<tb> base / acid
<tb> global <SEP> (%) <SEP>
<Tb>
EXAMPLE 3
a) By the method described in Example 1a, microparticles containing 30% by weight of Carbendazim B300 dispersed in a matrix of Polywax 2000 are prepared.

 b) By the method described in Example 1a, microparticles containing 30% by weight of Carbendazim are prepared; > B300 dispersed in a composition (constituting the matrix) of Polywax 2000 IUNflROX ~ 550 (70/30 by weight).

c) The dissolution of carbendazim is studied by introducing 10 mg of carbendazim equivalent into one liter of distilled water at 40 μl. The values below show that the dissolution rate is considerably limited when the carbendazim is introduced in die form.

<Tb>

<SEP> Time <SEP> of <SEP> Carbendazim <SEP> no <SEP> Example <SEP> 3a <SEP> Example <SEP> 3b
<tb> dissolved <SEP> (min) <SEP> protected <SEP> (dissolved <% SEP>) <SEP> (% <SEP> dissolved)
<tb><SEP> (% <SEP> dissolved)
<tb><SEP> 10 <SEP> 10.3 <SEP> 0 <SEP> 0.5
<tb><SEP> 20 <SEP> 20.8 <SEP> 0 <SEP> 0.8
<tb><SEP> 30 <SEP> 28.9 <SEP> 0 <SEP> 1.1
<tb><SEP> 60 <SEP> 46.3 <SEP> 0 <SEP> 1.7
<tb><SEP> 120 <SEP> 64.3 <SEP> 0 <SEP> 2.5
<tb><SEP> 300 <SEP> 83.2 <SEP> 0.3 <SEP> 4.2
<tb><SEP> 1440 <SEP> 96.4 <SEP> 3.7 <SEP> 10.5
<tb><SEP> 2400 <SEP> 100 <SEP> 5.7 <SEP> 14.2
<tb><SEP> 2800 <SEP> 6.7 <SEP> 15.8
<Tb>
d) Resistance to basic and acidic media is measured by the method described in Example 2c.

<Tb>

<SEP> Carbendazim <SEP> no <SEP> Example <SEP> 3a <SEP> Example <SEP> 3b
<tb><SEP> protected
<tb> Rate <SEP> of <SEP> resistance <SEP> soluble <SEP> in <SEP> medium <SEP> 85 <SEP> 50
<tb><SEP> base / acid <SEP> global <SEP> acid
<tb><SEP> (E) <SEP>
<Tb>
EXAMPLE 4
a) By the method described in Example 1a, microparticles containing 30% by weight of thiabendazole are prepared in a stearamide matrix.

 b) By the method described in Example 1a, microparticles containing 30% by weight of thiabendazole are prepared in a Polywax ~ 2000 matrix.

c) The tests of dissolution in batten and resistance to the acid and basic media give the following results:

<tb><SEP> Time <SEP> of <SEP> Thiabendazole <SEP> no <SEP> Example <SEP> 4a <SEP> Example <SEP> 4b
<tb><SEP> dissolving <SEP> (min) <SEP> protected <SEP> embedding <SEP> embedding
<tb><SEP> (% <SEP> dissolved) <SEP> stearamide <SEP> PolywaxX <SEP><SEP> 2000
<tb><SEP> (dissolved% <SEP>) <SEP> (% <SEP> dissolved)
<tb><SEP> 10 <SEP> 18 <SEP> 0.1 <SEP> o
<tb><SEP> 20 <SEP> 49 <SEP> 0.3 <SEP> 0
<tb><SEP> 30 <SEP> 72 <SEP> 0.4 <SEP> 0.1
<tb><SEP> 60 <SEP> 79 <SEP> 0.7 <SEP> 0.2
<tb><SEP> 120 <SEP> 88 <SEP> 1,1 <SEP> 0,2
<tb><SEP> 300 <SEP> 91 <SEP> 2 <SEP> 0.4
<tb><SEP> 1440 <SEP> 94 <SEP> 5.2 <SEP> 1.7
<tb><SEP> 2400 <SEP> 100 <SEP> 6.6 <SEP> 2,3
<tb> Rate <SEP> of <SEP> resistance <SEP> soluble <SEP> in <SEP> medium <SEP> 98 <SEP> 97
<tb> basicJacid <SEP><SEP> global <SEP> acid
<tb><SEP> (%)
<Tb>
The present invention has been described with reference to the technical problem of incorporating biocide (s) into manufactured products, for the programmed release of said biocide (s) within said products. It will be readily understood that the incorporation for similar purposes of another active ingredient, having the same characteristics (soluble in water at room temperature at less than 500 mg / l, active at low concentration) is part of the scope of the invention. just like the microparticles containing said active ingredient.

Claims (10)

1. Matrix-type microparticles containing at least one biocidal agent, in particular intended to be incorporated into a manufactured product during its manufacture in order to avoid, by controlled release of said biocide (s), the proliferation bacterial and / or fungal, characterized in that:  the said biocidal agent (s) is (are) a compound (s) having a solubility in water at room temperature of less than 500 mg / l and which is (are) active at low concentrations, and that  the matrix in which is dispersed the said biocide agent (s) is based on one or more hydrophobic constituent (s) fusible (s) ), selected to impart to said microparticles little sensitivity to pH and organic solvents as well as stability up to temperatures of the order of 95-120 ° C and to allow the controlled release of the said (s) biocidal agent (s) in the presence of water or moisture. 2. Microparticles according to claim 1, characterized in that said fusible constituents have a melting point greater than 100-C and are chosen from:  microcrystalline waxes;  saturated linear chain hydrocarbons with a molecular weight between 500 and 3000;  polyethylene waxes, of molecular weight between 500 and 3000;  linear-chain fatty acid amides, especially stearamide;  ethylene bistearamide; and  - their mixtures. 3. Microparticles according to one of claims I or 2, characterized in that they contain up to 30% by weight, preferably up to 15% by weight, of at least one lipophilic nonionic surfactant having 0 to 40 ethylene oxide units per molecule. 4. Microparticles according to claim 3, characterized in that said surfactant is a polyoxyethylenated fatty alcohol having a linear carbon chain containing from 10 to 100 carbon atoms and from 2 to 40 ethylene oxide units per molecule. 5. Microparticles according to any one of claims 1 to 4, characterized in that said biocidal agent is chosen from:  2- (1,3-thiazol-4-yl) benzimidazole,  methylbenzimidazol-2-yl-carbamate,  2,2'-dihydroxy-5,5'-dichlorodiphenylmethane,  2,4,4'-trichloro-2'-hydroxybiphenyl ether,  1- [[2- (2,4-dichlorophenyl) -1,3-dioxolan-2-yl] methyl] -1H-1,2,4-triazole, and  - their mixtures. 6. Microparticles according to any one of claims 1 to 5, characterized in that the biocide content in them is between 5 and 70% by weight, preferably between 15 and 50% by weight. 7. Microparticles according to any one of the preceding claims characterized in that they are in the form of spheres whose diameter is between 0.05 and 2 mm, preferably between 0.1 and 1 mm or in the form of scales.  8. Process for the preparation of microparticles according to any one of the preceding claims, characterized in that it comprises:  dispersing or dissolving the biocidal agent (s) in the hydrophobic constituent (s) of the molten matrix (s);  fractionation of the mixture obtained in the form of liquid or semi-liquid microparticles of desired shape and size; and  - Curing said microparticles by cooling. 9. Manufactured products, characterized in that they contain for their preservation during their period of use an effective amount of microcapsules according to any one of claims 1 to 7. 10. Manufactured products according to claim 9, characterized in that said microparticles have been incorporated into them during their manufacture.