JPS62125852A - Production of slowly releasable microcapsule - Google Patents

Abstract

PURPOSE:To control the degree of releasability of the titled microcapsule by further heating a microcapsule capsuling an aq. soln. of a substance to be slowly released and formed by interfacial polymerization, etc., in the aq. soln. of a substance to be slowly released. CONSTITUTION:An aq. soln. of the substance to be slowly released and polyethyleneimine is added to a diisocyanate soln. and subjected to interfacial polymerization, etc., and the aq. soln. of the substance to be slowly released is capsuled in a microcapsule. The microcapsule thus obtained is further heated in the aq. soln. of the substance to be slowly released. Consequently, the thickness of the microcapsule is increased, the pore diameter is reduced, and hence the releasing speed is decreased. A microcapsule with controlled releasing speed is thus obtained.

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to a method for producing sustained release microcapsules.

More specifically, the present invention relates to a method for producing sustained release microcapsules that can control the degree of sustained release.

[Conventional technology]

Conventionally, microcapsules have been produced by an interfacial polymerization method, an in-situ duplex method, an in-liquid curing coating method, a coacervation method, a spray drying method, an inorganic wall method, and the like.

The manufactured microcapsules can dynamically utilize the protective ability of the membrane and the release suitability of the substances encapsulated within the membrane, and are particularly useful for maintaining the efficacy of pharmaceuticals and agricultural chemicals, controlling the medicinal efficacy, and fragrances. It is also widely used in applications that effectively utilize the release suitability of substances within membranes, which are sustained release substances, such as sustaining aromas such as flavors, and controlling the reactivity of immobilized enzymes and prepolymers.

When used in such applications, it is practically important to adjust the degree of sustained release, and for this purpose, the thickness and permeability of the membrane are adjusted. It is generally difficult to control the degree of sustained release.

[Problem that the invention seeks to solve]

As a result of various studies in search of a method that can replace such difficult sustained release control means, the present inventors have discovered that microcapsules containing an aqueous solution of a sustained release substance formed by an interfacial polymerization method, etc. It has been found that the degree of sustained release can be adjusted by simply selecting the heating temperature.

[Means for Solving the Problems] and [Operation] Therefore, the present invention relates to a method for producing sustained-release microcapsules, and the production of sustained-release microcapsules involves microcapsules encapsulating an aqueous solution of a sustained-release substance. This is carried out by further heating the capsule in an aqueous solution of the substance to be sustained-released.

Microcapsules encapsulating an aqueous solution of a sustained release substance can be produced by various microencapsulation methods as described above, but preferably, an aqueous solution in which a sustained release substance and polyethyleneimine are dissolved is dissolved in a diisocyanate solution. This is done by interfacial polymerization method.

The aqueous solution components that form the interfacially polymerized capsule membrane include, for example, agricultural chemicals such as methyl parathion, pharmaceuticals such as aspirin, acetaminophenone, papaverine, and tetracycline;
It is prepared by dissolving sustained release substances such as aromatic esters, higher alcohols, synthetic fragrances, etc., and flavors, and polyethyleneimine (concentration of about 0.1 to 1%) in water.

The diisocyanate solution component that reacts with these aqueous solution components includes diisocyanates such as toluene diisocyanate, isophorone diisocyanate, and hexamethylene diisocyanate in an inert organic solvent that is immiscible with water, such as n-hexane, at a concentration of about 0.1 to A solution dissolved to a concentration of 10% is used.

Microencapsulation by interfacial polymerization reaction is approximately 10 to 3
At a temperature of 0°C, an aqueous solution at the same temperature is added to the diisocyanate solution under stirring conditions, preferably at a stirring speed of 10 revolutions/second or less, using a dropping jig such as a microsyringe, at a rate of about 0.0°C per drop. 001~0.02m Q
This is carried out by means of addition such as dropping at a dropwise amount of .

By operating in this manner, the incyanate group forms a urea bond with the terminal amino group and/or intermediate imino group of polyethyleneimine, is bonded two-dimensionally or three-dimensionally, and polymerized. The microcapsules formed as a result of this polymerization reaction contain an aqueous solution of the target substance (sustained release substance) to be sustainedly released.

The formed microcapsules are further heat-treated in an aqueous solution of the sustained release substance in order to adjust the sustained release rate of the sustained release substance encapsulated therein. This aqueous solution has the same concentration as the encapsulated aqueous solution, and is about 30 to 9
Heat treatment is performed at a temperature of 0° C. for about 5 to 20 minutes. The reason why aqueous solutions of the same concentration are used is to prevent the sustained release substance encapsulated in the microcapsules from diffusing into the aqueous solution used for heat treatment.

As a result of such heat treatment, the thickness of the microcapsules increases and the pore size decreases, that is, the sustained release rate decreases.

〔Effect of the invention〕

According to the method of the present invention, microcapsules containing an aqueous solution of a sustained release substance formed by an interfacial polymerization method or the like are further heat-treated in an aqueous solution of a sustained release substance, and the sustained release rate is adjusted by selecting the heating temperature at that time. Microcapsules can be obtained.

〔Example〕

Next, the present invention will be explained with reference to examples.

Reference Example: 0.8% polyethyleneimine and polyethylene glycol (molecular weight 200%) were added to water purified by reverse osmosis.
) 0.05% was dissolved to prepare a polyethyleneimine solution.

Separately, 0.5% n of toluene diisocyanate
-Pour 100 mfl of hexane solution into a beaker and
Stir with a stirrer at 5°C and a stirring speed of 2 revolutions/second.

The above polyethyleneimine aqueous solution is sucked up using a microsyringe with a horizontally cut tip, and the polyethyleneimine aqueous solution is pumped at a rate of 0.0 per second.
When dropped at a rate of 1 m Q perpendicularly to the surface of the above-mentioned toluene diisocyanate solution under stirring, microcapsules with a diameter of about 21 were formed therein.

Five polyethylene glycol-containing microcapsules thus formed were transferred to 5 mQ of water, and while stirring with a stirrer at a stirring speed of 2 revolutions/second, a total organic carbon meter (TO
C-10B) was used to measure the sustained release properties of polyethylene glycol. As a result, 2.65μg/min・rnQ-
A sustained release rate of 1 was obtained.

Furthermore, when the film thickness of this microcapsule was observed using an electron microscope, it was approximately 25 μm.

Example In the above reference example, the formed microcapsules were placed in a 0.05% aqueous solution of polyethylene glycol in a beaker and heated at 50°C or 70°C for 10 minutes, respectively.

Regarding these microcapsules, the sustained release properties of polyethylene glycol were similarly measured, and the film thickness was determined by [9], and the values shown in the following table were obtained.

table

Claims (1)

[Scope of Claims] 1. A method for producing sustained-release microcapsules, which comprises further heat-treating microcapsules encapsulating an aqueous solution of a sustained-release substance in an aqueous solution of a sustained-release substance. 2. The sustained-release microcapsule according to claim 1, which uses microcapsules containing an aqueous solution of a sustained-release substance formed by adding an aqueous solution in which a sustained-release substance and polyethyleneimine are dissolved into a diisocyanate solution. Capsule manufacturing method. 3. The method for producing sustained-release microcapsules according to claim 2, wherein the aqueous solution is added dropwise to the diisocyanate solution under stirring conditions. 4. The method for producing sustained-release microcapsules according to claim 1 or 2, wherein heat treatment is performed in an aqueous solution of a sustained-release substance having the same concentration as the aqueous solution encapsulated in the formed microcapsules. . 5. The method for producing sustained-release microcapsules according to claim 1 or 4, wherein the heat treatment is performed at a temperature of about 30 to 90°C.