JPH06509503A - Microencapsulated quaternary ammonium compound - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Microencapsulated Quaternary Ammonium Compound The present invention uses water such as a preservative. Microcapsules containing soluble amphiphiles, their preparation methods and their Regarding usage.

Microcapsules are spherical particles ranging in size from 1 to 1250 μm, and support material containing the encapsulated material ). There are two different types of microcapsules depending on the structure of the supporting material. There is: a support material is a solid material of varying thickness containing the material to be encapsulated. Container type (reservoir) that is a solid envelope type) microcapsules.

- The supporting material is a continuous network in which the material to be encapsulated is dispersed. Matrix type, also called icrosphere Microcapsule.

As far as the present invention is concerned, the term microcapsule refers to container-type microcapsules. Contains only cells.

A large number of substances can be encapsulated: these can be encapsulated, such as drugs or pesticides. It may be a compound, or it may be a macromolecule, such as an enzyme, or a living cell ( living cells).

Microcapsules are used in a large number of fields, e.g., pharmacy, biotechnology industry, cosmetics. , agricultural foods [agri-foodstuffs], paper manufacturing industry, etc. It is.

Several methods have been described for the preparation of microcapsules; in particular: The following can be mentioned.

- In particular, coacervating agents , for example, phase separation techniques using mineral or vegetable oils. tion technique]. Phase separation as described in US Pat. No. 4,675,189 and European Patent Application No. 52,510 method (phase separation method).

However, polymers prepared by this method as well as by other similar methods When preparing the microcapsules, agglomerates (aggluates) are added to the microcapsules. The disadvantage is that tinates (adhesions between particles) are formed.

- In particular, US Pat. No. 4,479,911, European Patent Application No. 301-969 and European Patent Application No. Solvent evaporation method described in Application No. 145240 tion method); This method uses 1. immiscible with water and volatile solvent. the organic phase by dissolving a suitable polymer and ・Separately separate aqueous phase containing predetermined active principles to form into; adding an aqueous phase to an organic phase; mixing the two phases with stirring and/or in the presence of an emulsifier; After that, slowly evaporate the solvent with stirring and at room temperature to obtain the desired microcapsules. It consists of getting a pushel.

More specifically, European Patent Application 145240 discloses that water-immiscible solvents, e.g. In chloromethane, hydrophilic substances and so-called drug-retaining substances ining 5 ubstance) (natural or synthetic mucilage or polymer compound) , especially gelatin). ayer), as well as a polymer, preferably polylactic acid or lactic acid/glyco A W10 emulsion containing an oily layer containing an acid copolymer or mixture thereof ( - by preparing a primary emulsion) The aqueous inner layer is then concentrated or solidified to a viscosity of greater than 5000 centipoise. The W10/W secondary emitter is then heated in the presence of a suitable surfactant. By preparing a secondary emulsion, and finally, by evaporating the solvent from the resulting emulsion. It refers to microcapsules that have been According to the method described in the patent application, the diameter Microcapsules having a diameter of 0.5 to 400 μm can be obtained. But long However, these prior art microcapsules are suitable for encapsulating amphiphiles. Preparation method for controlled release of active ingredients present in the aqueous inner layer There is a significant drawback that the stages are more markedly defined. It is up to the applicant to resolve this issue. The problem is that controlled release microcapsules for internal use are d-release microcapsule] Particularly suitable for external use in nature and only when the microcapsules are crushed , microcapsules that allow the release of preservatives present in the aqueous phase of the central core. Regarding ru.

Other methods used to encapsulate liquid substances include interfacial polycondensation (in Microcaps with terfacial polycondensation There is cellization.

In European patent application 407257, the applicant has Method for obtaining microcapsules containing water-soluble and amphipathic substances developed.

However, these microcapsules have a certain degree of hardness and , preferably only when the microcapsules are crushed (this is the A certain pressure is exerted on the object containing the child, e.g. medical gloves. caused by accidental needle pricking of the potash, certain topical applications in which the active ingredient is released. Not suitable for medicine.

The applicant will continue its research to find a solution that is easy to handle and that is not crushed. release of active ingredients, especially quaternary ammonium compounds, only by Developing more flexible microcapsules that can be used in many tolerable topical medications I tried.

The present invention relates to microcapsules containing at least one active ingredient. Locapsules contain at least one amphiphilic, water-soluble and gelatinable active ingredient. and has a hydrophilic inner core with a viscosity of more than 5 centipoise, the hydrophilic The internal core has walls made of ethylene/vinyl acetate copolymer (EVA). , vinylidene chloride/vinyl chloride copolymer-based walls and polycarbonate surrounded by one type of wall selected from the group consisting of walls whose main components are It is characterized by.

In one advantageous embodiment of these microcapsules, they are amphiphilic, water-soluble and One gelable substance is a quaternary ammonium compound.

In one particularly advantageous embodiment of this embodiment, amphiphilic, water-soluble and gelatable The substance has a concentration of 5 to 50% (w/w), preferably 20 to 35% dimethyldi Decylammonium.

In the context of the present invention, dimethyldidecylammonium is used for basic products and salts thereof (e.g. (e.g., halides, cybarides, organic salts) It is.

Quaternary ammonium compounds are actually fungicides, fungicides, and virus killers. It has unique utility as a topical drug. For example, dimethyl didecyl Ammonium has been shown to be active against HIV.

Surprisingly, the microcapsules according to the invention contain water-soluble amphiphiles, especially Contains quaternary ammonium compounds: such materials are usually It also destabilizes water/oil type emulsions, but Microcapsules have the effect that the active ingredient(s) are crushed by the application of pressure. It is flexible enough to be released only downwards.

In other advantageous embodiments of these microcapsules, they are amphiphilic, water-soluble and A gelatable active ingredient is combined with at least one other substance that can coexist with the active ingredient. Used together.

According to one advantageous measure of this embodiment, the substance is selected from bisguanidines. It is a preservative.

According to the invention, when the first active ingredient is dimethyldidecylammonium, The second substance is in particular a chlorhexidine salt and more particularly a chlorhexidine salt. It is digluconate.

Further, according to the present invention, the hydrophilic inner core can absorb pure water or water and a hydrophilic polymer. or a water-alcohol mixture containing a hydrophilic polymer and a polyol. The main component is something.

By way of example, hydrophilic polymers are especially polyvinyl alcohols, polyols is especially glycerol or ethylene glycol.

In another advantageous embodiment of these microcapsules, the walls are made of ethylene/vinyl When containing an acetate copolymer, the percentage of vinyl acetate in the copolymer The percentage is 30-46%.

In one particularly advantageous embodiment of this embodiment, the percentage of vinyl acetate ji is 40%.

The invention further relates to a method for preparing microcapsules by solvent evaporation. child The method of a water or water-alcoholic hydrophilic phase containing one substance to be encapsulated; Preparing a water-in-oil (W/O) emulsion and evaporating the solvent. The method includes a second step of forming microcapsules by It is characterized by the following points: A-(a) At least one amphiphilic, water-soluble and gelling substance to be encapsulated The viscosity of the water or water-alcohol phase exceeds 5 centipoise. , and the substance optionally contains at least one coexistence with the gelable substance. It may coexist with one other substance (a water-alcoholic phase may be mixed with water). Ethylene/vinyl acetate copolymer dissolved in a volatile solvent without chloride Vinylidene/vinyl chloride copolymer (PVDC/PVC) and polycarbonate polymer Emulsification in an oily phase containing a copolymer selected from the group consisting of copolymer [water-in-oil] (W10′)-next emulsion] step; and (b) The primary emulsion obtained in (a) is known as the first external phase. Emulsification (secondary emulsion) in a pure water phase, i.e. a phase lacking an emulsifier (secondary emulsion) Preparation of a W10 emulsion comprising; and B - (c) By any suitable means, the secondary emulsion obtained in (b) with Oshi A After evaporating the solvent contained in the lubricant, a second By introducing an external phase, microorganisms separated as particles with a diameter of 1 to 1000 μm can be produced. Obtaining Crocapsules: Formation of microcapsules containing.

In particular, by properly stirring the solvent, the solvent can be effectively evaporated. Ru.

In one advantageous embodiment of the method, amphiphilic, water-soluble and gelatinable The substance is dimethyldidecylammonium.

In one preferred embodiment of this embodiment of the method, the dimethyl didecyl ammonium is present in a concentration of 5-50% (w/w), preferably 20-35% .

In another advantageous embodiment of the method, the amphiphilic, water-soluble and gelatinable Other substances that can coexist with the substance are preservatives selected from the bisguanidine family.

According to the invention, when the first active ingredient is dimethyldidecylammonium, the first The second substance is particularly a chlorhexidine salt, such as chlorhexidine dihydrochloride. diacetate or digluconate.

Also according to the invention, when the hydrophilic phase of step (a) is an aqueous phase, it is optional wherein the hydrophilic phase of step (a) contains water containing a hydrophilic polymer; When the microphase is in the macrophase, it may optionally contain a hydrophilic polymer. The capsule walls consist of a polyol that is immiscible with the solvent for the copolymer.

The copolymer preferably includes, for example, but not limited to dichloromethane. and a suitable dichloromethane/acetone mixture. It is dissolved in a solvent.

In another embodiment of the method, the copolymer is an ethylene/vinyl acetate copolymer. When coalesced, it contains 30-46% vinyl acetate, preferably 40% contains.

In another advantageous embodiment of the method, the lubricant preferably has a Talc in water (second aqueous phase) at a concentration on the order of 5%.

Furthermore, in another advantageous embodiment of the method, step (C) is carried out at room temperature or at It is carried out by heating to a temperature of 0 to 70°C.

Surprisingly, according to the method according to the invention it is possible to add emulsifiers and especially surfactants. containing at least one amphiphilic, water-soluble and gelling substance; They are homogeneous in size and are crushed only after appreciable pressure is exerted; is sufficiently elastic to release the active ingredients and not collapse during mere handling. Flexible microcapsules can be obtained.

Such microcapsules are particularly suitable for, but not limited to, external use. burrs, paper, bandages (dressings), compresses [: compr fabrics (woven and non-woven), including surgical sheets), sponges and Devices characterized by polymers, especially elastomer-based devices (medical or surgical) gloves, contraceptive devices, etc.), nail brushes (e.g. surgical brushes), sterilizing powders, etc. You can do it.

In addition to the above-mentioned means, the present invention also provides a method for implementing the method for forming an object of the present invention. Other methods which will become apparent from the following description relating to the examples are also encompassed.

However, these examples merely illustrate the details of the invention without any limitation. provided for illustrative purposes only.

Example 1: Microorganisms of the invention containing a single active ingredient and having an aqueous inner core Preparation of capsules The preservative to be encapsulated is dimethyldidecyl ammonium chloride (trademark “Vada”). BARDAC 22”, LONZA, France) This is a quaternary ammonium salt, which by itself is a chemical of this class. has all the properties of: ・Water-soluble cationic surfactant with high wetting power; soaps, divalent cations, silver Particularly compatible with anionic surfactants such as nucleinates and silver proteinates. I can't get customers.

Adsorbed by elastomers.

- It is a preservative and a bactericidal agent, such as: *Active against Gram-positive bacteria *Gram-negative bacteria, fungi, and viruses (retroviruses, especially Highly active against HIV) and inactive against *mycobacteria and spores It is.

It should be applied to the mucous membranes of the skin (surgical sites, hands, wounds, burns, etc.) and conjunctiva. Can be done. The concentration of the commercially available aqueous solution is 60%. In this example, this solution was Dilute 1:2.

The viscosity of the solution of “Bardack 22” (trademark) was measured using a capillary viscometer (Ubbelohdech). Measurement is performed at 20°C using a tube. 2 The viscosities of 0%, 30% and 40% solutions are 28.36 and 4, respectively, at 20°C. The wall of the 7 centipore microcapsule is made up of 40 vinyl acetate (100%). EVA (ethylene/vinyl acetate copolymer) containing ELVAX” 40. W, Du Pont des Nemoises (W, DU PONT DE NEMOUR8), Paris, France).

The water used in the experiments is purified and deionized.

This property makes it difficult for preservatives to dissolve, as they are incompatible with divalent cations. Required.

b) CH2CI2・ Dichloromethane, or methylene chloride, is a volatile chlorinated solvent that boils at 40°C. Ru.

This is the solvent used to dissolve EVA.

b) Zinc stearate A 40% aqueous suspension of zinc stearate (trademark “ALKON”) do.

C) Sodium benzoate.

a) Preparation of the polymer: Dissolve 4 g of EVAo in 5 ml of dichloromethane.

The polymer is dissolved in the chlorinated solvent for the required amount of time.

b) Prepare the aqueous phase of “Bardac”(TM) in parallel . Each step is done in the following order: 2. Double 60% “Bardak” (trademark) with water. Dilute.

C) The polymer solution in dichloromethane is then added to the "Bardak" prepared above. Dissolve by adding 4 ml of 30% (W/W) solution of (trademark). to this This results in an unstable water/oil primary emulsion: “Bardak” (Trademark) + water in CH2Cl2 ten dissolved EVAo 2. Formation of microcapsules Unstable Water - Primary Emulsion of “Bardak”(TM)/CH2Cl2-EVA Shake the bottle vigorously and pour into 250 g of pure water while stirring (first external phase). secondary emal John is formed instantly.

After 2 minutes, a new preparation of talc and heated water (50-70°C) (second external phase); For example, add 150 ml of water and 5 g of talc.

All dilutions are performed by weight (W/W).

Once the microcapsules are formed, use a Buchner funnel with a vacuum flask, e.g. Then filter it and take it out.

In this way, microcapsules are collected on filter paper and other preparations of Le The procedure is to dilute “Bardak” (trademark) twice with water containing erythrosin. The rest is the same as in Example 1. This gives a pinkish-red solution. , knee microcapsules that enable observation of microcapsules under an optical microscope type, especially the presence of one or more containers, the contour and thickness of the walls, and the color contrast. absorption of water and polymer cross-linking between microcapsules (Figure 1); degree, which is when the microcapsules are crushed between two microscope slides. , proportional to the volume and color intensity of the exudate; and Size and particle size distribution by measuring the scale of an eyepiece with one micrometer . By measuring 30 microcapsules, Gauss symmetric with respect to the average It was possible to plot a histogram, showing the particle size distribution according to the particle size curve. .

Finally, dye is added to differentiate between intact and ruptured microcapsules. By comparing the images, it became possible to photograph the best samples.

Figure 1 shows the appearance of the obtained microcapsules as observed under the microscope; are clearly distinct from each other.

Example 3: Preparation of microcapsules containing a water-alcoholic phase a) Preparation of the polymer: EVA　O.4g5PC0.4g or GiPVDC/PVC0.8g, dichloro Dissolve in 6 ml of methane. Dissolve the polymer in the chlorinated solvent over the required time. let

b) A water-alcohol internal phase is prepared in parallel as follows: “Bardak” (trademark) 40% aqueous solution and polyvinyl alcohol (PVA) A 20% (W/W) solution of Contains 15% (w/w) of polyvinyl 7/1zl-ru (PVA) and 2.5% (w/w) of so that

C) The polymer solution in dichloromethane is then mixed with the water-alcohol prepared in b). Dissolve by adding 2 ml of internal phase solution. This results in instability such as A Wlo-second emulsion is formed: “Bardak” (trademark) +PVA + Water in CH2Cl2 + Dissolved polymer.

2. Composition of microcapsules Shake the unstable Wlo-next emulsion vigorously and pour it into 800 g of pure water while stirring. (First Minister of Foreign Affairs). A secondary emulsion forms instantly.

After 2 minutes, a new preparation of talc and water (second external phase) is added.

All dilutions are performed by weight (W/W).

Once the microcapsules are formed, use a Buchner funnel with a vacuum flask, e.g. Then filter it and take it out.

Microcapsules are collected on filter paper.

Example 4: Another preparation of microcapsules containing a water-alcoholic phase The procedure was as in Example 3, except that the water-alcohol internal phase had the following composition: The same is true.

“Bardak” (trademark’) 2270 20% aqueous solution of 21.5% PVA 12 ．． 5% Glycerol (or ethylene glycol) 66.0% Therefore, in water-alcohol The phase is “Bardak” (trademark) 15% (W/W) and polyvinyl alcohol 2 ．． Contains 5% (W/W).

Example 5: Preparation of microcapsules of the invention (aqueous internal phase) containing two active ingredients a) Preparation of the polymer: The procedure is the same as in Example 1.

b) “Bardak” (trademark) and chlorhexidine digluconate (e.g. , trademark “Hibitane” mixture, was prepared in parallel. Prepare. 60% “Bardak” (trademark) and 20% “Hibitan” (trademark) , dilute 2 times with water, then mix; mixing may precede dilution, if necessary. be able to.

C) The procedure is similar to Example 1.

2. Formation of microcapsules The procedure is similar to Example 1; the mixture of talc in water (second external phase) is 3.5% concentration and heated to 50°C.

Example 6: Microcapsules of the invention containing two active ingredients (in water-alcohol) Other preparations of The procedure is carried out in the same manner as in Example 4 using a water-alcohol internal phase having the following composition: .

“Bardak” (trademark) 2270 18.0% “Hibitan” (trademark) (Kroll 20% aqueous solution of hexidine digluconate) 12.0% PVA (7) 20% aqueous solution 12. 596 glycerol (or ethylene glyco 57.5% Therefore, the water-alcohol internal phase is 2.6% (W/W), “Hibitan” (trademark) 2.4% (W/W) and polyviny alcohol 2.5% (W/W) different surface activities for microcapsule formation Consider the role of agents.

The surfactants tested were: a) PVA (polyvinyl alcohol): In theory, this It is a polymer of 1. However, the latter immediately converts to ethanol and cannot be separated. I can't. It is prepared by deacetylation of polyvinyl acetate. Trademark “Rhodo” RHODOVIOL” 4/125 (PROLABO), Paris, France) utilizes alcoholysis with methanol: Polyvinyl Ru acetate + methanol → PVA + methyl acetate The number 4/125 has the following meaning: 4: Sensitivity of a 2% solution at 20°C. Viscosity in chipoise (cPo), 125: Vinyl acetate in the mixture is 12.5 %.

PVA 4/125 is insoluble in most organic solvents but soluble in water. So solutions are of colloidal type and their viscosity varies with concentration until a gel is formed. increases to

They have a stabilizing effect on polymer dispersions or colloidal metal dispersions. tablet During the production (wet granulation), when they evaporate, the active ingredient particles become solid P Connected by VA crosslinks.

For other hydrophilic polymers such as gelatin, O /W emulsion formation occurs.

However, due to their molecular structure, HLB (hydrophilic-lipophilic balance) is It would be unrealistic to do so.

b) Polyoxyethylated aliphatic alcohol ether (trademark “Simarsols (S) IMULSOLS)”): These are molecules with distinctly hydrophilic and hydrophobic poles. It is a complete surfactant. Therefore, HLB can be defined.

The test product carried out two series of tests with HLB>10: *Table ■ summarizes the results obtained under the following conditions: Inner core: "(trademark) wall: CH2Cl2 + 40% EVA First external phase: water surfactant (PVA or (secondary emulsion) "Simarsol" (trademark)) “Simarsolus” (trademark) is represented by the following symbol in the table below. Yes: “Simalsol” (trademark) 98:S98; “Simalsol” (trademark) 58:S58; “Simalsol” (trademark) P23: P23゜Table ■ (Continued) ) (2) Rotation speed (rpm): 250 Contrary to the accepted opinion, the addition of surfactants to the secondary emulsion may lead to particle agglomeration. It seems to cause a rash.

2. Role of lubricant To prevent microcapsules from adhering to each other, different Lubricants were tested: Talc (2g/148g water and 5g/145g water), “A ＾Ikon” (trademark) (40% in water) or trademark “Fluozinc (F 1 u.

zinc)”, sodium benzoate (2 g in 148 g of water) or trademark “Mary’s (Marlease) W 7689”.

These lubricants are added after the formation of the secondary emulsion (second external phase).

The results are summarized in Table H below and show that talc is the best lubricant in this example. In fact, “Alcon” (trademark) does not inhibit the formation of lumps; Sodium benzoate causes agglomeration of microcapsules. Furthermore, the optimal The results obtained at a talc concentration of the order of 3.5% are shown in Tables ■, ■, and ■. The role of the order of addition of the first and second phases) and the role of temperature are shown.

! −2 Todoroki-y Example 8: Discussion of active ingredient release in the absence and presence of applied pressure The quantitative analysis method involves measuring the surface tension of an aqueous solution containing “Bardac” (trademark). The concentration of the surfactant can be measured by referring to the calibration curve created in advance. It consists of

b) Equipment: The measurements were carried out using an apparatus for measuring dynamic contact angles, namely CAHN DCA 312 (commercial product). This is done using a data acquisition system and data acquisition system adapted to measure surface tension. and data processing software.

A parallelepiped glass slide (with a hood to remove contamination) suspended vertically from a balance pan. (through the frame) into the solution to be analyzed; the surface tension is It can be calculated by the force required to withdraw the slide at the speed applied.

C) Actual protocol: 1. Measurement of “Bardack” (trademark) in solution: “Bardack 22” (trademark) Aqueous solutions were prepared at concentrations ranging from 5 to 1000 mg/1. obtained The results are illustrated in Figure 2. Concentration (C) of “Bardac 22” (trademark) in mg /l on the abscissa and the surface tension in dynes/cm (Ts) on the ordinate. It's a lot.

2. “Bardak” (trademark) when the microcapsules of the present invention are placed in water measurement: "Barduck"(TM) is not found in water at all.

3. Pricking tests: Microcaps of the present invention By puncturing a latex film containing cells (Example 1) with a needle, Determination of the concentration of Duck 22” (trademark).

One way.

Place the latex film on a pill box (PI 11 box) containing demineralized water. Place and pierce with a series of needles to release the solution contained within the microcapsules. Removal results will be guided into the water. As is clear from the foregoing description, the present invention is directed to these aspects more clearly described. There are no restrictions on the implementation, mode and mode of application of the formula. On the contrary, the present invention It encompasses all variations thereof that may occur to those skilled in the art without departing from the framework or scope of Contains.

Claims (34)

[Claims] 1. contains at least one amphiphilic, water-soluble and gelatable active ingredient, and It has a hydrophilic core with a viscosity exceeding 5 centipoise, and the core is made of ethylene. Vinylidene chloride/wall mainly composed of vinyl acetate copolymer (EVA), vinylidene chloride/ Walls mainly composed of vinyl chloride copolymer and walls mainly composed of polycarbonate at least one wall selected from the group consisting of: Microcapsules containing the active ingredients of seeds. 2. The amphipathic, water-soluble and gelatable substance is a quaternary ammonium compound. The microcapsule according to claim 1, characterized in that: 3. Amphipathic, water-soluble and gelatinable substance converted to dimethyldidecylammonium The microcapsule according to claim 2, which is a compound. 4. Dimethyldidecylammonium may be present in a concentration of 5-50% (W/W). The microcapsule according to claim 3, characterized by: 5. Dimethyldidecylammonium is present at a concentration of 20-35% (W/W) The microcapsule according to claim 4, characterized in that: 6. amphiphilic, water-soluble and gelatinable active ingredients; Any one of claims 1 to 5, characterized in that it is used in combination with at least one other substance. Microcapsules described in. 7. A claim characterized in that the substance is a preservative selected from the bisguanidines. The microcapsule according to item 6. 8. The substance is chlorhexidine dihydrochloride, diacetate and digluco chlorhexidine salt selected from the group consisting of The microcapsule according to item 7. 9. Any of claims 1 to 8, wherein the hydrophilic inner core contains pure water as a main component. Microcapsules described in 10. The hydrophilic inner core is characterized by containing water and a hydrophilic polymer as main components. The microcapsule according to any one of claims 1 to 8. 11. A water-alcoholic alcohol whose hydrophilic inner core contains a hydrophilic polymer and a polyol The microorganism according to any one of claims 1 to 8, characterized in that the main component is a mixture of alcoholic acid and alcohol. Crocapsule. 12. The wall is made of ethylene/vinyl acetate copolymer, and the ethylene/vinyl acetate copolymer The percentage of vinyl acetate in the acetate copolymer is 30-46%. The microcapsule according to any one of claims 1 to 11, characterized in that: 13. Claim characterized in that the percentage of vinyl acetate is 40% The microcapsule according to item 12. 14. In an oily phase containing a suitable polymer dissolved in a suitable solvent, at least Water-in-oil (W/O) emul of a hydrophilic phase containing one substance to be encapsulated microcapsules by evaporating the solvent. A-(a) immiscible with water and soluble in volatile solvents; Polymerized ethylene/vinyl acetate copolymer, vinylidene chloride/vinyl chloride copolymer selected from the group consisting of polymers (PVDC/PVC) and polycarbonate polymers. At least one amphiphile to be encapsulated in the oil phase containing the copolymer. The viscosity of the water or water-alcoholic hydrophilic phase is 5. Milk contains water or water-alcohol hydrophilic phase at a concentration exceeding centipoise. (water-in-oil (W/O) primary emulsion) step; and (b) (a) odor The primary emulsion obtained by emulsifying in a phase devoid of agents (secondary emulsion); preparation of an emulsion; and B-(c) by any suitable means; After evaporating the solvent in the secondary emulsion obtained by Microphones were separated into particles with a diameter of 1 to 1000 μm by introducing a second external phase. forming a rocapsule; Formation of microcapsules containing; A method for preparing microcapsules by a solvent evaporation method, comprising: 15. Amphiphilic, water-soluble and gelatinable substance is dimethyldidecylammonium The method for preparing microcapsules according to claim 14. 16. Dimethyldidecylammonium is present at a concentration of 5-50% (W/W) 16. The method for preparing microcapsules according to claim 15. 17. Specifically, dimethyldidecylammonium is present in a concentration of 20-35%. 17. The method for preparing microcapsules according to claim 16. 18. As an amphiphilic, water-soluble and gelatable active ingredient, it coexists with the active ingredient. At least one selected from the group of preservatives and more particularly bisguanidines According to any one of claims 14 to 17, the substance is also used in combination with one kind of other substance. A method for preparing microcapsules as described above. 19. If the substance is chlorhexidine dihydrochloride, diacetate and diglu chlorhexidine salt selected from the group consisting of 19. A method for preparing microcapsules according to claim 18. 20. The hydrophilic phase of step (a) is an aqueous phase, which is optionally combined with a hydrophilic polymer. The microphone according to any one of claims 14 to 19, characterized in that the microphone is water that can be used. Method for preparing rocapsules. 21. The hydrophilic phase of step (a) is a water-alcoholic phase, which Optionally combined with a hydrophilic polymer that is immiscible in the solvent for the copolymer of the wall of the cell according to any one of claims 14 to 19, characterized in that it consists of a polyol obtained from Method for preparing microcapsules. 22. The copolymer is an ethylene/vinyl acetate copolymer, and it has a Any of claims 14 to 21, characterized in that it contains 0% vinyl acetate. A method for preparing microcapsules as described in Crab. 23. Claim characterized in that the percentage of vinyl acetate is 40% 23. The method for preparing microcapsules according to item 22. 24. The lubricant is advantageously talc in water at a concentration of 1.3 to 5% by weight. The method for preparing microcapsules according to any one of claims 14 to 23, characterized in that Law. 25. Any of claims 14 to 24, characterized in that step (c) is carried out at room temperature. A method for preparing microcapsules as described in Crab. 26. A claim characterized in that step (c) is carried out by heating to a temperature of 40 to 70°C. Item 25. The method for preparing microcapsules according to any one of Items 14 to 24. 27. It is characterized by containing a microcapsule according to any one of claims 1 to 13. paper or cloth. 28. It is characterized by containing a microcapsule according to any one of claims 1 to 13. bandage. 29. It is characterized by containing a microcapsule according to any one of claims 1 to 13. Products whose main components are polymers, especially elastomers. 30. It is characterized by containing a microcapsule according to any one of claims 1 to 13. medical or surgical gloves. 31. It is characterized by containing a microcapsule according to any one of claims 1 to 13. contraceptive devices. 32. It is characterized by containing a microcapsule according to any one of claims 1 to 13. Powdered preservative. 33. It is characterized by containing a microcapsule according to any one of claims 1 to 13. A sponge. 34. It is characterized by containing a microcapsule according to any one of claims 1 to 13. Nail brush.