JPH052370B2 - - Google Patents

Description

[Detailed description of the invention]

<Industrial Application Field> The present invention relates to a method for producing microcapsules.
More specifically, the present invention relates to a method for producing microcapsules by coating a hydrophobic core material in an aqueous medium by interfacial polymerization. The microcapsules of the present invention can be used in recording materials, pharmaceuticals, fragrances, agricultural chemicals, chemical products, adhesives, foods, detergents,
It is used in many fields such as dyes, solvents, catalysts, enzymes, and rust inhibitors. <Prior art> There have been many reports regarding the manufacturing method of microcapsules, among which physicochemical and chemical manufacturing methods include complex coacervation method, simple coacervation method, and interfacial polymerization method. Situ polymerization methods and the like are known.
These methods do not require the use of special equipment, can produce capsules with any particle size ranging from less than 1 micron to several millimeters, and are dependent on the properties of the capsule membrane and It is used in many fields because it has advantages such as being able to control precision. In the coacelvation method, gelatin-gum arabic, a natural polymer, is most commonly used as the capsule wall material, but it has poor water resistance, is expensive, and is difficult to obtain a highly concentrated capsule liquid. It has disadvantages such as the complicated process. Therefore, in recent years, encapsulation methods using synthetic polymer membranes have been attracting attention. That is, microcapsule particles containing a hydrophobic core substance are obtained by dispersing a hydrophobic liquid in an aqueous medium and generating polymers at the interface or inside of the droplets. This includes interfacial polymerization and in situ polymerization. These methods enable encapsulation at high concentrations and high yields;
The encapsulation cost is low, the encapsulation process is easy to control, the capsule wall is resistant to temperature, humidity and solvents, the capsule wall does not easily deteriorate during storage, and the encapsulation process is easy to control. It has advantages such as short process time. To further explain these methods, the interfacial polymerization method involves mixing hydrophobic monomers and oligomers with chain-extending ability, such as polyvalent isocyanates, polyvalent carboxylic acid chlorides, and polyvalent sulfonic acid chlorides, with a hydrophobic core material. is dispersed in an aqueous medium, and an aqueous solution of polyvalent amine, polyhydric alcohol, etc. is added to the dispersion to form a polymer film of polyurea, polyamide, polyurethane, polysulfonamide, polyester, etc. at the interface of the dispersed droplets. As a result, microcapsules containing a hydrophobic core substance are obtained. The in situ polymerization method is similar to the interfacial polymerization method in that a hydrophobic core material is dispersed in an aqueous medium and a polymer film is formed at the droplet interface. This encapsulation method differs in that it is supplied from only one direction, either only from the inside of the droplet or only from the outside. <Problems to be solved by the invention> Microcapsules are prepared by coating a hydrophobic core substance using an interfacial polymerization method, and the microcapsules are used particularly in the field of agricultural chemicals.
When applying it as a sustained release capsule,
Factors such as the encapsulation rate (the rate at which the core drug is encapsulated in the capsule during capsule production), the strength of the capsule membrane, and the particle size distribution of the capsule are important. In other words, in capsules containing pesticide active ingredients with an encapsulation rate of approximately 99% or less, if the core substance of the pesticide active ingredient is highly toxic to humans and animals, it will not be effective in reducing toxicity during spraying. . If the strength of the capsule membrane is weak, when the capsule is mixed with soil, the capsule may be destroyed and its residual effect may be lost. In addition, if the particle size distribution of capsule particles is too wide,
It becomes difficult to obtain a capsule dispersion with a constant drug release rate. (The drug release rate also depends on the particle size of the capsule particles.) Also, when applying to pressure-sensitive copying paper, the lack of solvent resistance and abrasion resistance of the capsule particles becomes a problem. There is. However, many of the currently reported microencapsulation methods using interfacial polymerization methods and in situ polymerization methods do not fully satisfy these points. <Means to solve the problems> As a result of intensive studies to solve the above problems,
Polyvalent isocyanate and/or polyvalent as an oil-soluble film-forming substance are added to an aqueous solution in which a water-soluble polymer which is a homopolymer and/or copolymer containing a monomer unit represented by the following general formula (1) is dissolved. After dispersing the mixture of carboxylic acid chloride and/or polyvalent sulfonic acid chloride and hydrophobic core substance, an aqueous solution of polyvalent amine and/or polyvalent hydroxy compound as a water-soluble film-forming substance is added to form an interface. The problem was solved by manufacturing microcapsules by carrying out a reaction and encapsulating the hydrophobic core material with the resulting polymer membrane. (In the formula, R ₁ is a hydrogen atom or a methyl group, R ₂ and R ₃ are alkyl groups having 1 to 8 carbon atoms) As a polymer having a monomer unit represented by the above general formula (1) used in the present invention teeth,
It is a homopolymer consisting of the monomer of general formula (1), or a copolymer consisting of the monomer of general formula (1) as one component. Particularly preferred is a water-soluble copolymer obtained by copolymerizing a monomer unit of general formula (1) with a hydrophobic monomer and a hydrophilic monomer. Examples of monomers copolymerizable with the monomer of general formula (1) include the following vinyl compounds. Styrene, vinyl acetate, (meth) as hydrophobic monomers
Methyl acrylate, ethyl (meth)acrylate,
(meth)acrylate n-butyl, (meth)acrylate isobutyl, (meth)acrylate t-butyl,
Hydrophilic monomers include 2-ethylhexyl (meth)acrylate, acrylonitrile, vinyl chloride, etc., and sodium styrene sulfonate, sodium vinyl sulfonate, (meth)acrylic acid, maleic anhydride, N-vinylpyrrolidone, (meth) Examples include, but are not limited to, acrylamide and dimethylaminoethyl (meth)acrylate. The water-soluble polymer of the present invention can be produced by various known methods. The molecular weight of this water-soluble polymer can be adjusted by changing the amount of polymerization initiator, monomer concentration, polymerization temperature, etc., or by using a chain transfer agent. Preferred molecular weights for the purposes of the present invention are from 0.05 to 5.0, most preferably from 0.2 to 3.0, expressed as intrinsic viscosity [η] (25° C., 0.25 N NaNO ₃ aqueous solution). Further, the object of the present invention cannot be achieved unless the copolymer contains 5% by weight or more, preferably 10% by weight or more of the monomer unit represented by general formula (1). On the other hand, when encapsulating, the amount of the water-soluble polymer synthesized according to the present invention used is 0.1 to 20% by weight, preferably 0.2 to 10% by weight, based on the hydrophobic core material to be dispersed.
It is. Strictly speaking, the appropriate amount is determined within this range depending on the desired particle size of the capsule. In addition, this capsule manufacturing system can be used in combination with general protective colloid agents such as polyvinyl alcohol and gelatin, and surfactants such as polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether, and sorbitan fatty acid ester. However, the amount used is preferably within a range that does not impede the effects of the present invention, for example, 50% or less of the amount of water-soluble polymer used. In the present invention, hexamethylene diisocyanate is used as an oil-soluble film-forming substance such as polyvalent isocyanate, polyvalent carboxylic acid chloride, and polyvalent sulfonic acid chloride as a capsule membrane-forming substance used to cover the surface of the hydrophobic core material. ,
2,2,4-trimethylhexamethylene diisocyanate, 2,44-trimethylhexamethylene diisocyanate, isophorone diisocyanate,
Phenyl diisocyanate, toluene diisocyanate, xylylene diisocyanate, naphthalene diisocyanate, diphenylmethane-4,
4'-diisocyanate, bis(4,4'isocyanobenzylphenyl)carbodiimide, trimer of hexamethylene diisocyanate, trimer of isophorone diisocyanate, polymethylene polyphenyl isocyanate, sebacic acid dichloride, adipic acid dichloride, azelaic acid There are dichloride, terephthalic acid dichloride, trimesic acid trichloride, benzenesulfonyl dichloride, etc. On the other hand, polyvalent amines and polyvalent hydroxy compounds as water-soluble film forming substances include ethylenediamine, 1,4-butanediamine, 1,6
-Hexanediamine, phenylenediamine, diethylenetriamine, triethylenetetramine, piperazine, ethylene glycol, 1,4-butanediol, 1,6-hexanediol, polyethylene glycol, polypropylene glycol, and the like. The amount of these capsule membrane-forming substances used varies depending on the intended use of the capsule, but the range in which the effects of the present invention are exhibited is 0.02% of the hydrophobic core material.
~50 times the amount, preferably 0.04 to 30 times the amount. Microencapsulation can be carried out by the following method. That is, a predetermined amount of the water-soluble polymer obtained by the present invention is dissolved in water, and in this,
A mixture of a hydrophobic core material and an oil-soluble film-forming material is dispersed under predetermined stirring conditions to obtain a dispersion having a desired particle size. Next, the aqueous solution of the water-soluble film-forming substance is dropped by reducing the stirring speed to form a polymer film at the droplet interface to cover the hydrophobic core substance. The reaction temperature at this time is determined by the type and combination of film-forming substances, but in most cases it is carried out between 30 and 70°C. Here, the microcapsules are obtained as an aqueous dispersion, and can be used as is for each purpose, but can also be made into powder by spray drying or the like. The microcapsules obtained by the method of the present invention have a high encapsulation rate, strong capsule membrane strength, and a narrow particle size distribution of capsule particles. The homopolymer and/or copolymer containing the monomer unit of formula (1) acts as a dispersant for dispersing the mixture of the hydrophobic core substance and the oil-soluble film-forming substance in water, and at the same time serves as a dispersant for dispersing the mixture of the hydrophobic core substance and the oil-soluble film-forming substance in water, and at the same time as a hydrophobic droplet interface. It is presumed that this is because it has a catalytic effect on the polymer membrane formation reaction that occurs in the process. Although the microcapsules thus obtained according to the present invention can be effectively used in many fields, they are particularly effective in the field of agricultural chemicals because the above-mentioned problems have been solved. In this case, agricultural chemicals such as insecticides, herbicides, and fungicides are selected as the hydrophobic core substance.
As an insecticide, DOVP (0,0-diethyl-2,
2-dichlorovinyl phosphate) phenitrothion (0,0-dimethyl O-(3-methyl-4 nitrophenyl) phosphorothioate), bisito(0,0-dimethyl-O-(3-methyl, -4 methylthio) phenyl phosphorothioate) ), diazinon (0,0-diethyl-O-(2-isopropyl-4methyl-6pyrimidyl) phosphorothioate), chlorpyrifos (0,0-diethyl-
O-3,5,6-trichloro-2-pyridylphosphorothioate) Marathon (dimethyldicarbethoxyethylthiophosphate) Guardside (0,0-dimethyl-O-(2-chlor)-1-
(2,4,5-trichlorophenyl)vinyl phosphate), calphos (0,0-diethyl-O-
5-phenyl-3 isoxazolyl phosphorothioate), vinylate (2-chloro-1-(2,
(4-dichlorophenyl)vinyl diethyl phosphate), ortolan (O,S-dimethyl-N-acetylphosphoramidothioate) kayaphos (0,0-dipropyl-O-4-methylthiophenyl phosphate), dicistone ( MCPB (2-methyl-
ethyl 4-chlorophenoxybutyrate), butachlor (2-chloro-2'-6'diethyl-N(butoxymethyl)acetamylide), pentazone (3-isopropyl-2-1,3-benzo-thiadiazinone-(4)-2, 2-dioxide), butamiphos (O-ethyl-O-(3-methyl-6nitrophenyl)sec-butylphosphoramidothioate)oxadiazone (5-terbutyl-3-(2,4-dichloro-5-isopropoxy) phenyl)-1,3,
The disinfectants include isoprothiolane (diisopropyl-1,3,-dithiolane-2-ylidene-malonate) and eclomesol (5-ethoxy-3-trichloromethyl-1,2,4). -thiadiazole),
Thiuran(bis(dimethylthiocarbamoyl)disulfide)probenazole(3-allyloxy-1,2-benziisothiazole-1,1'-dioxide)phosdaiphen(0-ethyl-0,0-
di(2,4-dichlorophenyl)phosphate)
and so on. Note that if the hydrophobic core substance to be encapsulated is solid at room temperature, the core substance can be dissolved in a solvent and encapsulated. Furthermore, if the core substances do not react with each other, it is also possible to form a mixture and encapsulate it. EXAMPLES The present invention will be explained below with reference to Examples. Note that the present invention is not limited only to these examples. Example 1 Microencapsulation was carried out using the water-soluble polymer prepared in the Reference Example described below, in combination with various capsule membrane materials and various hydrophobic capsule core materials, according to the following procedure. Pour 500 g of an aqueous solution in which a predetermined amount of the water-soluble polymer prepared in the reference example was dissolved into the reaction pot with a baffle plate in step 1.
A hydrophobic liquid, which is a mixture of a hydrophobic core substance and an oil-soluble film forming substance, is dispersed in this by stirring at a rotational speed of 500 rpm for 5 minutes. Next, the rotation speed is set to 200 rpm, and 50 g of an aqueous solution of a water-soluble film-forming substance is dropped to form a polymer film at the interface of the droplets to obtain microcapsules. (The reaction temperature was between 40 and 70°C, and the encapsulation was completed in 3 hours.) Finally, the capsule dispersion was neutralized with HC1. The particle size and particle size distribution of the capsules were measured using a Coulter counter. The particle size is the arithmetic mean value, and
Particle size distribution was expressed as logarithmic standard deviation value. The encapsulation rate was determined by accurately weighing a predetermined amount of the capsule dispersion, then separating the capsule particles, and quantifying the hydrophobic core substance in the dispersion medium (water). Examples 1 to 12 and Comparative Examples 1 to 3 are shown in Table 2.

【table】

【table】

[Table] As shown above, in all Examples 1 to 11, the encapsulation rate was 99% or more, and the particle size distribution was 1.4 or less in logarithmic standard deviation (approximately 80% within ±5μ from the average particle size).
(including the following particles). On the other hand, comparative example 1
~3, the encapsulation rate is poor, and the logarithmic standard deviation value of the particle size distribution is 1.6 or more (± from the average particle size).
(approximately 50% or less of particles were contained between 15 μm). In addition, when the cross section of the obtained capsule particles was observed with a scanning electron microscope, Examples 1 to 3
The film thickness of the capsules of Examples 1 to 12 was about 5 times or more thicker than that of Comparative Examples 1 to 3. Reference Examples 1 to 11 (Synthesis of water-soluble polymer) Put 270 g of methyl alcohol and 30 g of water into a 500 ml reaction pot equipped with a cooling tube and thermometer, and then
Dimethylacrylamide 70, a monomer mixture
g, 25 g of methyl acrylate, and 5 g of sodium styrene sulfonate were dissolved, and the inside of the reaction vessel was purged with nitrogen gas for about 30 minutes. Thereafter, a solution of 0.1 g of azobisbutylnitrile dissolved in 10 g of methyl alcohol as a polymerization initiator is added to the reaction system through a dropping funnel, and the reaction is allowed to proceed at a reaction temperature of 60° C. for 5 hours. After the reaction is completed, the viscous contents are poured into a large excess of ethyl ether to precipitate the polymer. Filter and dry for encapsulation. Intrinsic viscosity of the obtained polymer [η] (0.25N− _NaNO3 aqueous solution, 25℃)
was 1.43. The following water-soluble polymers with various monomer compositions were prepared by the above-mentioned synthesis method. Table 1 shows the composition and intrinsic viscosity of the water-soluble polymer obtained.

【table】

[Table] Next, the capsules obtained in the examples were subjected to a drug residue test and an acute toxicity test to examine their effects. Test Example 1 The capsule dispersions obtained in Examples 1, 2, and 4 and Comparative Examples 1 and 2 were subjected to a field test for soil persistence of an agricultural chemical active ingredient (diazinon). In other words, the capsule dispersion was prepared into a spray solution containing 1000 ppm of diazinon, and the active ingredient was applied to field soil per 10 acres.
900g was sprayed and then mixed to a depth of 10cm. The amount of chemicals in the soil was measured every predetermined number of days after treatment.

[Table] Test Example 2 Acute toxicity tests were conducted on the capsule dispersions of Examples 1, 2, and 4 and Comparative Examples 1 and 2. The test animals were STD-ddy male mice and
The sample was orally administered to STD-Wister male rats at the age of 5 weeks.

【table】

〔Effect of the invention〕

The microcapsules obtained by the present invention have a higher encapsulation rate of various hydrophobic core substances than conventional ones,
In addition, since the capsule membrane is thick, it has the advantage that the core substance can be stably retained within the capsule for a long period of time.

Claims (1)

[Scope of Claims] 1. Polymer as an oil-soluble film-forming substance in an aqueous solution containing a water-soluble polymer which is a homopolymer and/or copolymer containing a monomer unit represented by the following general formula (1). After dispersing the mixture of polyhydric isocyanate and/or polyhydric carboxylic acid chloride and/or polyhydric sulfonic acid chloride and hydrophobic core material, the polyhydric amine and/or polyhydric hydroxy compound as a water-soluble film-forming substance is dispersed. 1. A method for producing microcapsules, which comprises adding an aqueous solution to cause an interfacial reaction, and enveloping the hydrophobic core substance with the generated polymer membrane. (In the formula, R ₁ represents a hydrogen atom or a methyl group, and R ₂
R ₃ represents an alkyl group having 1 to 8 carbon atoms. )