WO2004105933A2

WO2004105933A2 - Calcium phosphate capsules, method for the production thereof, and uses of the same

Info

Publication number: WO2004105933A2
Application number: PCT/FR2004/001222
Authority: WO
Inventors: Dominique Dupuis; Franck Aurissergues
Original assignee: Rhodia Chimie
Priority date: 2003-05-22
Filing date: 2004-05-18
Publication date: 2004-12-09
Also published as: WO2004105933A3; FR2855074A1

Abstract

The invention relates to capsules having an organic core and a mineral hull, and is characterised in that said core partially or entirely consists of at least one active ingredient, said mineral hull partially or entirely consists of calcium phosphate, and the capsule itself contains at least one surfactant and/or at least one amphiphilic polymer. The invention also relates to a method for producing said capsules, and to the uses of the same.

Description

CALCIUM PHOSPHATE CAPSULES, PROCESS FOR PREPARING ETSES

USES

The present invention relates to calcium phosphate capsules, as well as its production process and their uses. Encapsulation systems are widely used by manufacturers for the formulation of chemical compounds.

Various encapsulation techniques are already available for packaging various active ingredients also called active ingredients. This type of packaging is particularly preferred when seeking to mask the taste of an active ingredient, to control its release over time and / or to protect it from its surrounding medium. Overall, we can distinguish two types of encapsulation techniques. The first type leads to a so-called reservoir system. The active ingredient is immobilized in the center of a capsule by a polymeric membrane. This type of capsule is generally obtained by the technique known as interfacial polycondensation. It consists in causing the synthesis of a polymer at the interface of two immiscible liquids. Microspheres 10 to 30 μm in average diameter are thus obtained consisting of a liquid core surrounded by a polymer envelope representing only 5 to 15% of the total weight of the capsule. The polymer membrane provides protection vis-à-vis the external environment of the liquid core which generally contains an active material and its porosity makes it possible to control its diffusion outside the capsule. This type of encapsulation is in particular proposed for the packaging of active substances of pesticide type whose release it is desired to control over time. Also leading to this so-called reservoir system, the techniques known as atomization coating, coating by phase separation and coating by solidification.

The second type of encapsulation technique leads to a so-called matrix system. The active material to be encapsulated is dispersed within an organic or polymeric or mineral network, for example silica. As a representative of this type of encapsulation, one can more particularly mention the technique of mineral encapsulation by the sol-gel route. The conventional sol-gel technique consists in initiating the hydrolysis and polycondensation of a metal alkoxide, in an aqueous or hydroalcoholic medium and comprising the active material. to condition. This results in the formation of a gel, in which is dispersed said active material, which leads after drying to a porous glass. According to a variant of the sol-gel technique, known as an emulsion, a network of mineral oxide, generally silica, is formed from a molecular precursor of the alkoxide type, in the presence of a water-in-oil emulsion in which is dispersed active ingredient. The active material present during the hydrolysis and condensation step of the mineral material is then trapped in the powder. However, depending on the fields of application envisaged or according to the active principle to be encapsulated, the implementation of these techniques is not always feasible.

Indeed in the case of the encapsulation of food ingredients, it is necessary to use materials compatible with the food field. In order to meet the requirements of manufacturers, it has become necessary to find capsules and encapsulation methods usable in the food industry.

The problem which the invention aims to solve is therefore to propose new capsules using materials compatible with the food sector and to propose a process for the preparation of these capsules which is easy to implement.

For this purpose, the invention provides capsules comprising an organic heart and a mineral shell characterized in that the heart is made up in whole or in part of at least one active principle and in that the mineral rind is made up in whole or in part of calcium phosphate and in that said capsule comprises at least one surfactant and / or at least one amphiphilic polymer.

The invention also provides a process for preparing the capsules mentioned above, characterized in that it comprises: the precipitation in aqueous media of calcium phosphate in the presence of the active principle and in the presence of at least one surfactant and / or at less an amphiphilic polymer; separating the capsules formed from the dispersion obtained previously; and optionally the formulation in dry form. The invention also relates to the use of these capsules in the food, cosmetic, phytosanitary, therapeutic, aromatic, polymers, for example textile polymers.

The capsules according to the invention have the advantage of having a mineral shell made up in whole or in part of calcium phosphate, said calcium phosphate being compatible with the food sector. The capsules also have the advantage of allowing controlled release of the encapsulated active ingredient. In particular, the active principles which they contain can be released generally by fractionation of the capsule or by induced degradation thereof, in particular by a change in pH _;

The mineral nature of the bark of the capsules according to the invention constitutes an effective protection barrier for the active principle vis-à-vis the surrounding medium while allowing, where appropriate, its exchanges with it.

Advantageously, the capsules according to the invention have a thermal stability of up to 350 ° C. Indeed it is possible to thermally protect a principle active. For example, an active principle which usually degrades at 100 ° C. can be protected by the capsule and remained sufficiently stable when the capsule containing the active principle is brought to a temperature up to 200 ° C.

Finally, this capsule is prepared in the context of the present invention under operating conditions which are sufficiently gentle to not affect the integrity of said active ingredients. By the expression "sufficiently mild operating conditions" is meant within the meaning of the present invention temperatures not exceeding 100 ° C., and pHs greater than 5 and less than 9, without the use of organic precursors. Thanks to these mild conditions, the active principle to be immobilized is in fact not exposed during its conditioning to temperature and, where appropriate, pH values liable to harm it.

Other advantages and characteristics of the present invention will become clear on reading the description and examples given by way of purely illustrative and nonlimiting description, which will follow. The invention relates first of all to capsules comprising an organic heart and a mineral bark characterized in that the heart consists in whole or in part of at least one active principle and in that the mineral bark is constituted in all or part of calcium phosphate and that said capsule comprises at least one surfactant and / or at least one amphiphilic polymer. The capsules according to the invention can advantageously have a spherical morphology.

The size of the capsules according to the invention is representative of the size of the emulsion, determined in particular by scanning electron microscopy, when an emulsion occurs during the manufacturing process. The capsules according to the invention can also be in the form of a powder, more or less agglomerated, lyophilized or not.

The first essential constituent of the capsules according to the invention consists of an organic core.

By organic core is meant any organic substance capable of being encapsulated and consisting in whole or in part of at least one active principle.

The organic substance capable of being encapsulated can in particular consist of an organic compound insoluble in water. As organic compound insoluble in suitable water, there may be mentioned in particular organic solvents, organic oils, of animal or vegetable origin, or mineral, as well as waxes originating from the same origins, or their mixtures.

As organic solvents, there may be mentioned, inter alia, petroleum fractions, naphthenic, paraffinic oils (petroleum jelly or ISOPAR M parafinic fraction from Exxon), petroleum ether, liner or branched alkanes such as pentane, hexane and their mixtures, aromatic hydrocarbons such as benzene, toluene, xylenes and anisole, ethers such as tetrahydrofuran, diethyl ether, methyl and tert-butyl oxide, chlorinated solvents such as dichloromethane, chlorobenzene, dichlorobenzene, chloroform or trifluoromethylbenzene, and mixtures thereof. As organic oils of animal origin, mention may be made, among others, of sperm whale oil, whale oil, seal oil, sardine oil, herring oil, shark oil, Cod liver oil ; pork and mutton fats (tallow). As waxes of animal origin, mention may be made of beeswax. As examples of organic oils of vegetable origin, there may be mentioned, among others, rapeseed oil, sunflower oil, peanut oil, olive oil, oil nuts, corn oil, soybean oil, linseed oil, hemp oil, grape seed oil, copra oil, palm oil, oil cottonseed, babassu oil, jojoba oil, sesame oil, castor oil, cocoa butter, shea butter. As waxes of vegetable origin, mention may be made of carnauba wax.

With regard to mineral oils, mention may be made, inter alia, of petroleum fractions, naphthenic and paraffinic oils (petroleum jelly or ISOPAR M parafinic fraction from Exxon).

Paraffinic waxes can likewise be suitable for the preparation of the emulsion. The products derived from the alcoholysis of the abovementioned oils can also be used as well as essential oils and silicone oils.

Fatty acids, saturated or not, fatty alcohols, saturated or not, fatty acid esters, or mixtures thereof can also be used. More particularly, said acids comprise 8 to 40 carbon atoms, more particularly 10 to 40 carbon atoms, preferably 18 to 40 carbon atoms, and can comprise one or more ethylenic unsaturations, conjugated or not, and optionally one or more groups hydroxyls. As for the alcohols, they can comprise one or more hydroxyl groups. As examples of saturated fatty acids, mention may be made of palmitic, stearic and behenic acids. As examples of unsaturated fatty acids, there may be mentioned myristoleic, palmitoleic, oleic, erucic, linoleic, linolenic, arachidonic, ricinoleic acids, as well as their surfactant and non-solvent mixtures. As for the alcohols, these more particularly comprise 8 to 40 carbon atoms, preferably 10 to 40 carbon atoms, optionally one or more ethylenic unsaturations, conjugated or not, and optionally several hydroxyl groups. Polymers comprising several hydroxyl groups may likewise be suitable, such as, for example, polypropylene glycols. As an example of alcohols, mention may be made, for example, of those corresponding to the abovementioned acids. Regarding fatty acid esters, these can advantageously be obtained at starting from fatty acids, chosen from the compounds named above. The alcohols from which these esters are prepared more particularly comprise 1 to 6 carbon atoms. Preferably, these are methyl, ethyl, propyl and isopropyl esters. Furthermore, it is not excluded to use as organic substance mono-, di- and tri-glycerides.

The preferred preferred encapsulated organic substance according to the invention is soybean oil.

As active principle, one can use according to the invention a compound or a mixture of compounds of food, cosmetic, phytosanitary, therapeutic, aromatic interest, or usable in the field of polymers, for example textile polymers. In particular, mention may be made of vitamins, food additives such as polysaccharides, flavors such as vanillin, colorants, leavening powders, anti-UV agents, perfumes such as menthol, anti-mite agents such as benzyl benzoate, insecticides, or fungicides.

The second essential constituent of the capsules according to the invention consists of the mineral shell of calcium phosphate.

By calcium phosphate is also meant calcium pyrophosphate according to the invention. The mineral shell of the capsules according to the invention is preferably constituted by a compound having an apatitic structure of calcium phosphate shown by an X-ray analysis. In particular among these apatitic compounds, the compounds of type hydroxyapatite of calcium phosphate, monetite of calcium phosphate or brushite of calcium phosphate or octocalcium phosphate. This apatitic calcium phosphate compound may optionally be partially substituted by magnesium, or fluorine

The third essential constituent of the capsules according to the invention consists of at least one surfactant and / or at least one amphiphilic polymer.

By surfactants is meant any substance which lowers the surface tension of the water or the medium in which it is dissolved.

The surfactant can be found in the capsule at the level of the mineral bark or of the organic heart or at the interface of the heart and the bark.

The surfactants used according to the invention can be ionic or nonionic, and can be used alone or in mixtures. Mention may be made, as ionic surfactants, without limitation, of the alkyl ester sulfonates, the alkyl sulfonates, the alkyl sulfates and their alkoxylated derivatives (in particular ethoxylated (OE) and / or propoxylated (OP)), the alkylamide sulfates and their alkoxylated derivatives (in particular (OE) and / or (OP)), the salts of saturated fatty acids or unsaturated and / or their alkoxylated derivatives (in particular (OE) and / or (OP)), alkylbenzenesulfonates, primary or secondary alkylsulfonates, alkylglycerol sulfonates, sulfonated polycarboxylic acids, paraffin sulfonates, N-acyl N-alkyltaurates , alkylphosphates, isethionates, alkylsuccinamates, alkylsulfosuccinates, monoesters or diesters of sulfosuccinates, N-acyl sarcosinates, sulfates of alkyl glycosides, sophorolipids, such as those in particular in acid or lactone form and acid derivatives 17-hydroxyoctadécénique.

As examples of ionic surfactants, non-limiting mention may be made of anionic surfactants such as: "the alkyl esters sulfonates of formula of the type R-CH (Sθ3M) -COOR ', where R represents a Cs-20 alkyl radical> preferably at C-JQ-C-16 'R' ^a C- - alkyl radical

CQ, preferably in C1-C3 and M, an alkali cation (sodium, potassium, lithium), substituted or unsubstituted ammonium (methyl-, dimethyl-, trimethyl-, tetramethylammonium, dimethylpiperidinium ...) or derived from an alkanolamine ( monoethanolamine, diethanolamine, triethanolamine ...). Mention may very particularly be made of methyl ester sulfonates, the radical R of which is C14-C-16;

• the alkyl sulphates of formula of the ROSO3M type, where R represents a C5-C-24, preferably C-IQ- I S. alkyl or hydroxyalkyl radical representing a hydrogen atom or a cation of the same definition as above above, as well as their alkoxylated derivatives (in particular (OE) and or (OP)), having on average from 0.5 to 30 units, preferably from 0.5 to 10 OE and / or OP units; mention may, for example, be made of sodium dodecyl sulfate.

• sulfated alkylamides in particular of formula of the RCONHROSO3 type where R represents a C2-C22 alkyl radical. preferably in Cβ-C2o, R 'an alkyl radical in C2-C3, M representing a hydrogen atom or a cation of the same definition as above, as well as their alkoxylated derivatives (in particular (OE) and / or (OP )), with an average of 0.5 to 60 OE and / or OP motifs;

• the salts of saturated or unsaturated fatty acids in particular and / or their alkoxylated derivatives (in particular (EO) and / or (OP)), in C8-C24, preferably in C-j4-C2o _> Cb-C20 alkylbenzenesulfonates . primary or secondary alkyl sulfonates in

^C ~ 8 _22> ^the alkylgrycérol sulfonates, paraffin sulfonates, N-acyl N-alkyl taurates, alkyl phosphates, isethionates, alkylsuccinamates, sulfosuccinates, monoesters or diesters of sulphosuccinates, N-acyl sarcosinates, sulfates alkylglycosides; the cation being an alkali metal (sodium, potassium, lithium), a substituted or unsubstituted ammonium residue (methyl-, dimethyl-, trimethyl-, tetramethylammonium, dimethylpiperidinium ...) or derived from an alkanolamine (monoethanolamine, diethanolamine, triethanolamine ...); As nonionic surfactants, non-limiting mention may be made of alkoxylated alkylphenols (in particular (EO) and or (OP)), aliphatic alcohols more particularly of C ₈ -C ₂₂ , the products resulting from the condensation of ethylene oxide or propylene oxide with propylene glycol or ethylene glycol, products resulting from the condensation of ethylene oxide or propylene oxide with ethylene diamine, fatty acids alkoxylated (in particular (OE) and / or (OP)), the amides of alkoxylated fatty acids (in particular (OE) and or (OP)), the alkoxylated amines (in particular (OE) and / or (OP)), alkoxylated amidoamines (in particular (OE) and / or (OP)), amine oxides, alkoxylated terpene hydrocarbons (in particular (OE) and / or (OP)), alkylpolyglycosides, amphiphilic polymers or oligomers, ethoxylated alcohols , sorbitan esters, oxyethylenated sorbitan esters or pyrrolidone derivatives.

As examples of non-ionic surfactants, non-limiting mention may be made of surfactants such as: “alkoxylated alkylphenols (in particular (OE) and / or (OP)), the alkyl substituent of which is in particular Cβ-C- ^ and containing from 5 to 25 oxyalkylene units; by way of example, mention may be made TRITON ^® X-45, X-114, X-100 or X-102 sold by Rohm and Haas Cy. ;

• glucosamide, glucamide, glycerolamide; • aliphatic alcohols, in particular C8-C22 and their alkoxylated derivatives (in particular (OE) and or (OP)), containing from 1 to 25 units (OE) and / or (OP); by way of example, mention may be made of TERGITOL ^® 15-S-9, TERGITOL ^® 24-L-6 NMW sold by Union Carbide Corp., NEODOL ^® 45-9, NEODOL ^® 23-65, NEODOL ^® 45-7 , NEODOL ^® 45-4 marketed by Shell Chemical Cy., KYRO EOB ^® marketed by The Procter & Gamble Cy. ;

• products resulting from the condensation of ethylene oxide, the compound resulting from the condensation of propylene oxide with propylene glycol, such as PLURONIC ^® marketed by BASF;

• the products resulting from the condensation of ethylene oxide, the compound resulting from the condensation of propylene oxide with ethylenediamine, such as

TETRONIC ^® marketed by BASF;

• amine oxides such as oxides including alkyl especially ^C ιo ^_ i8 dimethylamines, oxides of C8-C22 alkoxy ethyl dihydroxy ethylamines;

• the alkylpolyglycosides in particular described in US-A-4,565,647; • fatty acid amides, more particularly C8-C20:

• sorbitan esters such as Span, oxyethylenated sorbitan esters such as polyoxyethylenesorbitan (Tween);

• pyrrolidone derivatives such as polyvinyl pyrrolidone (PVP). According to a particular embodiment of the invention, the nonionic surfactant can be combined with at least one anionic surfactant.

As for the nonionic amphiphilic polymers or oligomers entering into the composition according to the invention, they are more particularly chosen, alone or in mixtures, among the polymers, oligomers or copolymers at least partially miscible in the aqueous composition.

By amphiphilic polymers or oligomers is meant polymers or oligomers having a surface tension in an aqueous medium.

The amphiphilic polymers or oligomers can have a statistical distribution or a multiblock distribution.

The amphiphilic polymers or oligomers used according to the invention are chosen from block polymers comprising at least one hydrophilic block and at least one hydrophobic block, the hydrophilic block being obtained from at least one nonionic and / or anionic monomer. By way of example of such amphiphilic polymers or oligomers, mention may in particular be made of polysaccharides having hydrophobic groups, in particular alkyl groups. Examples include guars.

Examples of amphiphilic polymers or oligomers can also be made of triblock polymers polyhydroxystearate - polyethylene glycol - polyhydroxystearate (products of Arlacel ^® range of ICI are an example), the hydrophobic polyacrylamides.

As regards non-ionic amphiphilic polymers more particularly alkoxylated (in particular (OE) and / or (OP)), the latter are more particularly chosen from polymers of which at least a part (at least 50% by weight) is miscible in water.

Examples of polymers of this type that may be mentioned, inter alia, are polyethylene glycol / polypropylene glycol / polyethylene glycol triblock polymers.

The preferred surfactants according to the invention are nonionic surfactants and anionic surfactants. Mention may be made, as preferred nonionic surfactants, of alkoxylated fatty alcohols

(OE and / or OP), sorbitan esters and oxyethylenated sorbitan esters.

The invention also relates to a process for preparing the capsules described above, characterized in that it comprises: the precipitation in aqueous media of calcium phosphate in the presence of the active principle and in the presence of at least one surfactant and / or at less an amphiphilic polymer; separating the capsules formed from the dispersion obtained previously; and optionally the formulation in dry form. The precipitation step in aqueous media of calcium phosphate is preferably carried out by contacting an aqueous solution comprising a soluble calcium salt and an aqueous solution comprising a soluble phosphate salt. As the soluble calcium salt, preferably calcium chloride or calcium nitrate will be used.

As the soluble phosphate salt, an alkali metal or ammonium salt will preferably be used.

The operating conditions for implementing the method according to the invention are generally mild conditions, that is to say preferably at room temperature.

The precipitation of calcium phosphate according to the process of the invention is preferably carried out at a pH of at least 5, preferably at least 6.

The method according to the invention makes it possible to precipitate an apatic compound, in particular calcium hydroxyapatite, or calcium phosphate monetite or calcium phosphate brushite.

In a particular case of the process according to the invention, it is possible to partially substitute the apatitic calcium phosphate compound with magnesium or fluorine. In this case, for example, magnesium sulfate is added to the solution of soluble calcium salt. It is also possible to consider adding a fluorine salt, for example of ammonium fluoride, to the solution of soluble phosphate salt (di-ammonium phosphate for example).

The method according to the invention makes it possible to use the active principle in the form of a direct emulsion or in the form of a dispersion. By direct emulsion is meant an emulsion where the continuous phase is an aqueous phase and the discontinuous phase is an immiscible or extremely immiscible phase in the aqueous phase.

In the particular case where the active principle is in the form of a direct emulsion, an emulsion comprising the active principle is preferably used in the form of an oil or in the form of a compound dissolved in an organic phase.

In the case where the active principle to be encapsulated is in the form of a solid, it is possible to produce a dispersion in an aqueous medium of said solid, optionally stabilized by the surfactants and / or amphiphilic polymers mentioned above. The surfactant and / or the amphiphilic polymer used in the process according to the invention is preferably as defined above, to stabilize the direct emulsion or the dispersion. Preferably, a concentration of surfactant and / or amphiphilic polymer of at most 5% by weight relative to the direct emulsion or to the dispersion is used.

The capsules obtained according to the process of the invention can be washed in a conventional manner and according to techniques well known to those skilled in the art. These capsules can preferably be dried at room temperature.

It is also possible before or after the drying step to add a polymer or an organic compound to the capsules previously obtained. By way of example of a polymer or of organic compounds, mention may be made of cellulose derivatives, guar gums, xanthan, carrageenans, or even any type of polysaccharides. This polymer or organic compound is preferably used in the form of an aqueous solution which is preferably added to the aqueous dispersion of capsules.

After obtaining the capsules according to the invention, the active principle can be released inter alia by dissolution of the mineral bark, in particular by a change in pH, or by mechanical destruction of the bark, in particular by crushing or by diffusion. Finally, the invention relates to the use of capsules according to the invention or capsules obtained according to the process described above in the food, cosmetic, phytosanitary, therapeutic, aromatic, polymers, for example textile polymers.

The following examples illustrate the invention without, however, limiting its scope.

EXAMPLES

EXAMPLE 1 Encapsulation of Soybean Oil in a Calcium Hydroxyapatite Capsule

1) Preparation of the mother emulsion:

27 g of soybean oil are introduced into a 200 ml beaker

2.25 g Span 80 (sorbitan esters)

0.75 g Tween 80 (polyoxyethylenesorbitan)

20 g of deionized water

This mixture is introduced into an ultraturax homogenizer at power 3 (16000 rpm) for 5 minutes. An emulsion is obtained. The particle size of this emulsion is determined using a HORIBA. The median diameter of the emulsion droplets is approximately 2 microns. 2) Encapsulation with rhvdroxyapatite (clacium PAH

In a glass reactor fitted with a double-jacket stirring thermostatically controlled at 45 ° C., the following are introduced:

400 g of deionized water

0.4 g sodium dodecyl sulfate (SDS)

33.32 g of mother emulsion prepared in 1)

Then we prepare the following solutions:

- A solution containing 26.46 g of CaCI2.2H2O with 1.8 g of polyvinylpirrolidone (PVP K30) added to it and made up to 200 g with deionized water.

- a solution B of 15.3 g of Na2HPO4 supplemented to 200 g with permuted water

These two solutions A and B are added simultaneously to the reactor, and at the same flow rate (0.8 g / min) and their concentrations are such that the Ca / P molar ratio used is 1.67 in the reactor . The reaction medium is regulated at pH = 7 at 45 ° C. with a 0.5 mol / l NaOH solution introduced continuously.

After the additions, a maturing period of two hours is carried out at 45 ° C., then the reaction medium is centrifuged and two washes are carried out. It is dried at room temperature for 12 hours. After drying, a powder containing 48% oil is recovered (determination by extraction with acetone).

The weight yield is 100%. The median diameter of the capsules is 20 microns (COULTER granulometer type LS measurement with dry process module, according to Fraunhoffer optical model).

The analysis of the capsules obtained by X-ray diffraction clearly highlights the apatitic structure.

The characterization of the capsules by scanning electron microscopy highlights the production of spherical particles which have a size between 1 and 5 microns. This characterization also shows that the capsules are agglomerated.

The molar chemical assay Ca / P = 1.66. (ICP method)

The stability of the encapsulation was determined as follows: 2 g of the powder are suspended in 50 ml of water and left to stir for 2 hours. The powder is left to settle and there is no trace of oil on the surface of the liquid. EXAMPLE 2 Encapsulation of a Menthol / Soybean Oil Mixture with Calcium Hydroxyapatite

1) Preparation of the mother emulsion:

The following are introduced into a 200 ml beaker:

8.1 g of menthol previously dissolved in 18.9 g of soybean oil (at 50 ° C) 2.25 g of Span 80 (sorbitan esters) 0.75 g of Tween 80 (polyoxyethylenesorbitan) 20 g of permuted water

This mixture is introduced into an ultraturax homogenizer at power 3 (16000 rpm) for 5 minutes. An emulsion is obtained. The emulsion is maintained at 50 ° C. The particle size of this emulsion is determined using a HORIBA. The median diameter of the emulsion droplets is approximately 2 microns.

2) Encapsulation by H.A.P

In a glass reactor fitted with a double jacket stirring thermostate at 50 ° C are introduced:

400 g of deionized water 0.4 g of sodium dodecyi sulfate 33.32 g of mother emulsion prepared in 1. This should give a theoretical menthol level of 15% / capsules

Then we prepare the following solutions:

- a solution B of 15.3 g of Na2HPO4 supplemented to 200 g with permuted water

These two solutions A and B are added simultaneously to the reactor, and at the same flow rate (0.8 g / min) and their concentrations are such that the Ca / P molar ratio used is 1.67 in the reactor . The reaction medium is regulated at pH = 7 at 50 ° C. with a 0.5 mol / l NaOH solution introduced continuously. After the additions, a maturing period of two hours is carried out at 50 ° C., then the reaction medium is centrifuged and two washes are carried out. It is dried at room temperature for 12 hours. After drying, a powder containing 48% oil is recovered (determination by extraction with acetone).

The weight yield is 85%).

The product obtained is referenced 02FAS 091 is dosed in menthol by gas chromatography. Menthol level in the capsules is 4.8% (assay by gas chromatography)

EXAMPLE 3 Encapsulation of a Vitamin A / Soybean Oil Mixture with Calcium Hydroxyapatite

1) Preparation of the mother emulsion:

1.031 g of vitamin A acetate dissolved in 27 g of soybean oil 2.25 g of Span 80 (sorbitan esters) 0.75 g of Tween 80 (polyoxyethylenesorbitan) are introduced into a 200 ml beaker 20 g of deionized water

This mixture is introduced into an ultraturax homogenizer at power 3 (16000 rpm) for 5 minutes. An emulsion is obtained. The emulsion is maintained at 45 ° C. The particle size of this emulsion is determined using a HORIBA. The median diameter of the emulsion droplets is approximately 2 microns.

2) Encapsulation by H.AP

In a glass reactor fitted with a double jacket stirring thermostate at 45 ° C are introduced:

400 g of deionized water

0.4 g of sodium dodecyl sulfate 33.32 g of mother emulsion prepared in 1. This gives capsules dosed at 50,000 IU of vitamin A.

Then we prepare the following solutions: - A solution containing 26.46 g of CaCl2.2H2O with 1.8 g of polyvinylpirrolidone (PVP K30) added to it and made up to 200 g with deionized water.

- a solution B of 15.3 g of Na2HPO4 supplemented to 200 g with permuted water

After the additions, a ripening period is carried out, then the reaction medium is centrifuged and two washes are carried out. It is dried at room temperature for 12 hours. After drying, a powder containing 48% oil is recovered (determination by extraction with acetone).

The weight yield is 100%.

The median diameter of the capsules is 20 microns (COULTER granulometer type LS measurement with dry process module, according to Fraunhoffer optical model).

The characterization of the capsules by scanning electron microscopy highlights the production of spherical particles which have a size between 1 and 5 microns. This characterization also shows that the capsules are agglomerated. The molar chemical assay Ca / P = 1.66. (ICP method)

EXAMPLE 4 Encapsulation of Vitamin D3 / Soybean Oil by Calcium Hydroxyapatite

Preparation of the emulsion:

1.59 g of vitamin D3 at 42% in soybean oil 0.1 g of Tween 80 (polyoxyethylenesorbitan) 8.31 g of soybean oil 290 g of water

This mixture is introduced into an ultraturax homogenizer at power 3 (16000 rpm) for 2 minutes. An emulsion is obtained. The particle size of this emulsion is determined using a HORIBA. The median diameter of the emulsion droplets is approximately 2 microns.

The emulsion is introduced into a thermostate reactor at 30 ° C. into which are simultaneously introduced:

- a solution A containing 13.23 g of CaCl2.2H2O supplemented to 100 g with deionized water

- a solution B containing 7.12 g of (NH4) 2HPO4 supplemented to 100 g with water and adjusted to pH = 7 with HNO3

The reaction medium is regulated at pH = 7 with a solution. 20% de-NH4OH introduced continuously.

After the additions, a ripening period is carried out, then the reaction medium is centrifuged at 3000 rpm and 3 washes are carried out. It is dried at room temperature for 12 hours. After drying, a powder containing 48% oil is recovered (determination by extraction with acetone).

Weight yield is 77%. The capsule is characterized by NMR and there is the spectrum of vitamin D3 not degraded and a vitamin D3 molar ratio on soybean oil = 0.1, which means that the vitamin is well encapsulated without having undergone degradation.

Claims

1. Capsule comprising an organic heart and a mineral bark characterized in that the heart consists in whole or in part of at least one active principle and in that the mineral bark is made up in whole or in part of calcium phosphate and in that said capsule comprises at least one surfactant and / or at least one amphiphilic polymer.

2. Capsule according to claim 1 characterized in that the mineral shell consists of an apatite compound of calcium phosphate in particular of the hydroxyapatite type of calcium phosphate, calcium phosphate monetite or brushite of calcium phosphate or octocalcium phosphate .

3. Capsule according to one of the preceding claims, characterized in that the mineral shell consists of an apatitic calcium phosphate compound partially substituted by magnesium, or fluorine.

4. Capsule according to one of the preceding claims, characterized in that the surfactant is chosen from ionic, nonionic surfactants, alone or as a mixture.

Capsule according to claim 4 characterized in that the surfactant is ionic.

6. Capsule according to any one of claims 4 or 5 characterized in that the ionic surfactant is chosen from alkylestersulfonates, alkylsulfonates, alkylsulfates as well as their alkoxylated derivatives (in particular ethoxylated (OE) and or propoxylated (OP)) , the sulphate alkylamides and their alkoxylated derivatives (in particular (OE) and / or (OP)), the salts of saturated or unsaturated fatty acids and / or their alkoxylated derivatives (in particular (OE) and / or (OP)), alkylbenzenesulfonates, primary or secondary alkylsulfonates, alkylglycerol sulfonates, sulfonated polycarboxylic acids, paraffin sulfonates, N-acyl N-alkyltaurates, alkylphosphates, isethionates, alkylsuccinamates, alkylsulfosuccinates, monoesters or diesters or diestersucciates N-acyl sarcosinates, alkyl glycoside sulfates, sophorolipids, such as those in particular in acid or lactone form and derivatives of 17-hydroxyoctadecenic acid.

7. Capsule according to any one of claims 1 to 4 characterized in that the surfactant is non-ionic.

8. Capsule according to any one of claims 1 to 4 and 7 characterized in that the nonionic surfactant is chosen from alkoxylated alkylphenols

(in particular (OE) and / or (OP)), aliphatic alcohols more particularly of C ₈ - C ₂₂ , the products resulting from the condensation of ethylene oxide or of propylene oxide with propylene glycol or ethylene glycol, products resulting from the condensation of ethylene oxide or propylene oxide with ethylene diamine, alkoxylated fatty acids (especially (OE) and / or (OP)), amides alkoxylated fatty acids (especially (OE) and / or (OP)), alkoxylated amines (especially (OE) and / or (OP)), alkoxylated amidoamines (especially (OE) and / or (OP)), amine oxides, alkoxylated terpene hydrocarbons (in particular (OE) and / or (OP)), alkylpolyglycosides, amphiphilic polymers or oligomers, ethoxylated alcohols, sorbitan esters, oxyethylenated sorbitan esters or derivatives of pyrrolidones.

9. Capsule according to any one of the preceding claims, characterized in that the nonionic surfactant is combined with at least one anionic surfactant.

10. Capsule according to claim 1 characterized in that the amphiphilic polymer is chosen from block polymers comprising at least one hydrophilic block and at least one hydrophobic block, the hydrophilic block being obtained from at least one nonionic monomer and / or anionic.

11. Capsule according to any one of claims 1 to 10 characterized in that the active principle is a compound or a mixture of compounds of food, cosmetic, phytosanitary, therapeutic, aromatic interest, or usable in the field of polyemes for example textile polymers.

12. Method for preparing the capsules according to one of claims 1 to 11 characterized in that it comprises: the precipitation in aqueous media of calcium phosphate in the presence of the active principle and in the presence of at least one surfactant and / or at least one amphiphilic polymer; separating the capsules formed from the dispersion obtained previously; and optionally the formulation in dry form.

13. The method of claim 12 characterized in that the precipitation is carried out in aqueous media of calcium phosphate by contacting an aqueous solution comprising a soluble salt of calcium and an aqueous solution comprising a soluble salt of phosphate.

14. The method of claim 13 characterized in that as the soluble calcium salt of calcium chloride, calcium nitrate.

15. The method of claim 13 characterized in that one uses as a soluble phosphate salt, an alkali metal or ammonium salt.

16. Method according to any one of claims 12 to 15 characterized in that the active principle is used in the form of a direct emulsion or in the form of a dispersion.

17. The method of claim 16 characterized in that an emulsion is used comprising the active principle in the form of an oil or in the form of a compound dissolved in an organic phase.

18. The method of claim 16 characterized in that a dispersion is used comprising the active principle in the form of a mineral.

19. Method according to any one of claims 16 to 18 characterized in that the surfactant and / or the amphiphilic polymer as defined in claims 2 to 8 are used to stabilize the direct emulsion or the dispersion.

20. The method of claim 19 characterized in that a concentration of surfactant and / or amphiphilic polymer of at most 5% by weight relative to the direct emulsion or to the dispersion is used.

21. Process according to any one of claims 12 to 20, characterized in that the calcium phosphate is precipitated at a pH of at least 7, preferably at least 9.

22. Process according to any one of claims 12 to 21, characterized in that calcium hydroxyapatite is precipitated.

3. Use of the capsules according to any one of claims 1 to 11 or capsules obtained according to the process of any one of claims 12 to 22 in the food, cosmetic, phytosanitary, aromatic therapeutic fields, polyemes, for example polymers textiles.