JPS63170437A - Production of microsponge - Google Patents

Abstract

PURPOSE:To readily regulate particle diameter, etc., and simply obtain a microsponge suitable as sustained release carriers, etc., by suspension polymerizing a polymerizable monomer in the presence of a crosslinking agent and hydrophobic liquid and extracting the hydrophobic liquid with a specific solvent. CONSTITUTION:A polymerizable monomer selected from styrene, (meth)acrylic acid esters, vinyl acetate, etc., is subjected to in-situ polymerization in water in the presence of a crosslinking agent, e.g. divinylbenzene, ethylene dimethacrylate, etc., and a hydrophobic liquid, having a higher boiling point than the softening temperature of the formed polymer and selected from hydrocarbons, ketones, etc., in an amount of 10-90wt.% based on the total polymerization system in water under condition of 50-95 deg.C temperature and 50-500rpm stirring speed and the hydrophobic liquid is then extracted with a low-boiling organic solvent, e.g. hydrocarbon, alcohols having <=150 deg.C boiling point, etc., to afford the aimed microsponge having 5-500mum particle diameter.

Description

[Detailed description of the invention] Sakiwagami Zenshafu Trust Entrustment The present invention relates to a method for manufacturing microsponge.

Prior Art and Problems Microsponges have countless fine pores in their resin microbeads, and are used to adsorb fragrances, medicines, agricultural chemicals, cosmetic agents, etc., and to gradually release the adsorbed components during use. sustained-release carriers, colorants that have absorbed dyes and pigments, oils and skin medicines, etc., and when rubbed on the skin, the sponge collapses and the oils and medicines adhere to the skin. Recently, it has been attracting a lot of attention as a cosmetic or pharmaceutical compounding agent.

However, no technical literature describing such a method for manufacturing microsponge is known.

Means for Solving the Problems The present invention is characterized in that a polymerizable monomer is polymerized in suspension in water in the presence of a crosslinking agent and a hydrophobic liquid, and the hydrophobic liquid is extracted with a low boiling point organic solvent. The present invention provides a method for producing microsponge.

In the present invention, the polymerizable monomers include styrene, methylstyrene, vinyltoluene, methacrylic esters, acrylic esters, vinyl acetate and acrylonitrile, vinyl chloride, vinylidene chloride, isoprene, chlorobrene, butadiene, acrolein, acrylamide, Examples include allyl alcohol, vinylpyridine, vinyl benzoate, and allyl benzoate. The ester residue of acrylic acid, methacrylic acid, etc. has 1 to 18 carbon atoms, preferably 1 to 4 carbon atoms, and is particularly preferably methyl or ethyl. Part of free acrylic acid or methacrylic acid may be copolymerized, or after polymerization, a polyvalent metal compound such as calcium, magnesium, or zinc, such as hydroxide, may be added to the polymerization system to form an ionomer. good.

The above monomers may be used alone or in combination to form a copolymer. Particularly preferred are styrene, methacrylic ester, acrylic ester, vinyl acetate, acrylonitrile, etc., and copolymers are preferred.

Examples of crosslinking agents include divinylbenzene, ethylene dimethacrylate, triethylene glycol dimethacrylate, 1,3-butylene dimethacrylate, allyl methacrylate, and trimethylolpropane trimethacrylate. good.

These crosslinking agents are important for improving the solvent resistance and shape retention of the copolymer and for obtaining a good microsponge.

The amount of crosslinking agent relative to the polymer monomer may be such that 0.1 to 20%, preferably 0.5 to 10%, of the functional groups of the polymerizable monomer are crosslinked. This amount varies depending on the use of the microsponge, and may be relatively large when used as a normal sustained release composition, and may be relatively small when it is necessary to grind it before use.

If the amount is less than 0.5%, the strength will decrease and a good microsponge will not be obtained; if the amount of crosslinking agent is too large, it will be compatible with polymerizable monomers as a hydrophobic liquid and Those that also have affinity for coalescence are preferred. In the present invention, since the hydrophobic liquid is extracted with a low boiling point organic solvent after treatment, the hydrophobic liquid itself does not need to have a low boiling point. Organic solvents with a boiling point higher than the softening temperature of the polymerization product can be used.

Therefore, this method can be applied to high-boiling hydrophobic liquids with favorable properties for forming microsponges.

Hydrophobic liquids that can be used in the present invention include hydrocarbons such as paraffin, liquid paraffin, isoparaffin, diisopropylnaphthalene; ketones such as cyclohexanone, acetophenone; esters such as vegetable oil,
Animal oil, diglyceride; Sorbitan higher fatty acid esters, dibutyl phthalate, dioctyl phthalate, methyl myristate, isopropyl myristate, dibutyl sebacate, lauryl isostearate; ethers,
For example, high molecular weight (approximately 2000 or more) polypropylene glycol 1, dibutyl ether, butyl cellosolve, anthor, phenetol, ethyl glyco-ludiacetate; amides, such as N,N-dimethylformamide, formamide; halides, such as chlorobenzene, α-Chlornaphthalene; silicones, e.g.
Examples include octamethyltrisiloxane, octamethylcyclotetrasiloxane, and various silicone oils.

These hydrophobic liquids may be used alone or in combination of two or more.

In particular, the viscosity may be any value, but preferably 1 to 500c.
It is ps. Solubility in water is 59/100J112 (
25°C) or lower.

Particularly preferred are animal and vegetable oils, long-chain aliphatic esters, silicone oils, and isoparaffins.

The hydrophobic liquid is encapsulated in the polymer microparticles formed during polymerization, and is extracted with a low boiling point organic solvent to form fine air holes in the microparticles to form a sponge. A thin skin layer is formed on the surface of the resulting microsponge, which has extremely small pores on a molecular level and covers the inner sponge layer.

This film affects the strength of the sponge, sustained release rate, etc.

When a large amount of hydrophobic liquid is added, the skin layer becomes thinner and at the same time, the sponge becomes more prone to collapse. Therefore, in general, 30 to 70% by weight of the polymer is appropriate when used as a sustained release composition, and 50 to 90% by weight when used for crushing purposes. If it exceeds 90% by weight, a sponge layer will not be formed during extraction and the particles will be crushed.
If the amount is less than 30% by weight, the formation of a sponge will be insufficient.

The above components are subjected to suspension polymerization while stirring in water.

This polymerization is a type of in-situ polymerization carried out in the presence of a hydrophobic volatile solvent.

Examples of polymerization catalysts include radical catalysts such as benzoyl peroxide, methyl ethyl ketone peroxide, ditert-butyl peroxide, and 2.2°-azobis(
isobutyronitrile), 2.2°-azobis(2,4dimethyl)valeronitrile, etc. are suitable.

The polymerization temperature is preferably below the boiling point of the volatile solvent.

Generally, a temperature of 50 to 95°C is suitable.

Polymerization is carried out under stirring. The stirring conditions govern the size of the polymer particles produced. Suitable stirring speed is 50-500r
pm, especially 100-300 rpm.

Under the above conditions, fine particles of about 1 to 100 μm are obtained.

A polymerization time of 3 hours to 24 hours, usually 5 hours to 10 hours is sufficient.

Suspension stabilizers such as polyvinyl alcohol, gelatin, methylcellulose, alginic acid, calcium phosphate, colloidal silica, bentonite, aluminum oxide, etc. may be included in the suspension polymerization. Further, a suitable anti-caking agent such as titanium oxide, calcium carbonate, barium sulfate, mica, talc, magnesium carbonate, etc. may be added to prevent the produced particles from coagulating during drying. Coloring agents and the like may be added, but substances that inhibit radical polymerization such as azulene should not be used.

After the produced polymer particles are filtered, the non-volatile liquid contained in the particles is extracted with a suitable solvent without drying or after drying. Preferably, it is extracted after drying.

The organic solvent used for extraction is a water-insoluble solvent with a boiling point of 150°C or lower, preferably 60 to 120°C, such as a hydrocarbon solvent, such as an aliphatic carbonaceous solvent having a linear or side chain, to facilitate subsequent drying. Hydrogen, aromatic hydrocarbons such as toluene and xylene, ring hydrocarbons such as cyclohexane, alcohols such as methyl alcohol, ethyl alcohol and isopropyl alcohol; ketone solvents such as acetone and methyl ethyl ketone; esters such as methyl acetate and acetic acid Ethyl, halides such as carbon tetrachloride, chloroform, trichlene; ethers such as diethyl ether dipropyl ether, isopropyl ether, tetrahydrofuran; silicones such as hexamethyldisiloxane, octamethyltrisiloxane,
Examples include hexamethylcyclotrisiloxane. These solvents may be used alone or in combination of two or more.

It goes without saying that the solvent has excellent compatibility with the hydrophobic liquid, but it is also preferable that it has excellent compatibility with the polymer to be produced.

Soxhlet extraction is preferred for extraction, but other methods such as diffusion extraction, washing extraction, and leaching may also be used.

The extracted polymer particles are dried. Drying is carried out at a temperature above the boiling point of the solvent and below the softening temperature of the polymer particles, usually 30 to 8
0°C is preferred. When the softening temperature of the polymer particles and the boiling point of the solvent are close to each other, drying may be performed under reduced pressure.

During drying, the solvent used for extraction evaporates from the polymerized particles, forming a sponge inside the particles. A dense skin layer is formed on the surface of the resulting microsponge.

The microsponge obtained as described above has 5 to 50
They are spherical particles with a particle size of about 0 μm, and usually have a dense skin layer of 0.1 μl or less, although it depends on the conditions.

The present invention will be explained below with reference to Examples.

Example 1 An oil phase consisting of 40 parts of methyl methacrylate, 5 parts of methyl acrylate, 2 parts of ethylene glycol dimethacrylate, 150 parts of isopropyl myristate, and 1 part of benzoyl peroxide was prepared. Then 50 ml of deionized water
An aqueous phase was prepared by adjusting the pH to 3.2 with hydrochloric acid from a mixture consisting of 10 WJ of colloidal silica having a solid content of 0 parts, 20% solid content, and 2 parts of a 50% aqueous solution of a condensate of adipic acid and jetanolamine.

Next, the above oil phase and aqueous phase were stirred at high speed for 2 minutes using a homo mixer (manufactured by Tokushu Kika Kogyo) to disperse the oil phase in the aqueous phase, and then charged into a 2I separable flask that was purged with nitrogen. Polymerization was carried out at 75° C. for 6 hours with stirring at 150 rpm.

The product thus obtained was repeatedly subjected to absorption filtration and washing with water to obtain a cake-like product with a water content of 32%. The obtained cake was dried at 40° C. for 12 hours, and then subjected to Soxhlet extraction using hexane to obtain white resin spherical powder with an average particle size of 30 to 60 μm. A cross-sectional SEM photograph is shown in FIG.

When squalane was added to the resulting powder under a microscope, it was observed that the squalane penetrated into the resin spheres. The same result was obtained when water was used instead of squalane.

Example 2 60 parts of styrene, 5 parts of vinyl acetate, 5 parts of divinylbenzene
The procedure was repeated in the same manner as in Example 1 except that 100 parts of liquid paraffin and 50 parts of glycerin octanoate were used.
A white powder of 50 μm size was obtained.

Effects of the Invention The present invention provides a novel method for producing microsponges useful as sustained-release carriers and the like. According to the method of the present invention, microsponges can be obtained in an extremely simple manner. It is easy to adjust the particle size of the microsponge, the thickness of the skin layer (which is related to the sustained release rate), the sponge density (which is related to the amount of liquid absorbed), etc.

[Brief explanation of the drawing]

FIG. 1 is a photograph showing a cross-sectional SEM of a resin spherical powder. Patent Applicant Matsumoto Yushi Pharmaceutical Co., Ltd. Representative Patent Attorney Aoyama Baka 2 Figure 1 Procedures Amendment Book Mr. Tsutomu, Commissioner of the Patent Office April 1988 681, Display of Case Patent Application No. 2095 No. 3 of 1988, Amendment Relationship with the case of a person who does the following: Patent applicant 4, agent address: 2-1-61 Mihigashi-ku, Osaka City, Osaka Prefecture 540
No. [Attachment] 4. Brief explanation of the drawings Figure 1 is a cross-sectional SEM photograph showing the structure of resin spherical particles.

Claims (1)

[Claims] 1. A microsponge characterized by polymerizing a polymerizable monomer in suspension in water in the presence of a crosslinking agent and a hydrophobic liquid, and extracting the hydrophobic liquid with a low-boiling organic solvent. manufacturing method. 2. Polymerizable monomer is styrene, methacrylic ester,
2. The method according to item 1, wherein the monomer contains at least one monomer selected from acrylic acid ester, vinyl acetate, and acrylonitrile. 3. The crosslinking agent is one or a mixture of two or more selected from divinylbenzene, ethylene dimethacrylate, triethylene glycol dimethacrylate, 1,3-butylene dimethacrylate, allyl methacrylate, and trimethylolpropane trimethacrylate. A manufacturing method according to item 1. 4. The production method according to item 1, wherein the hydrophobic liquid has a boiling point higher than the softening temperature of the polymer produced. 5. The production method according to item 1, wherein the hydrophobic liquid is highly compatible with the produced polymer. 6. The production method according to item 4, wherein the hydrophobic liquid contains one or more selected from hydrocarbons, ketones, esters, halides, ethers, and silicones. 7. The production method according to item 1, wherein the low-boiling organic solvent is one or a mixture of two or more selected from hydrocarbons, alcohols, ketones, esters, halides, ethers, and silicones with a boiling point of 150°C or less. . 8. The production method according to item 1, wherein the polymerization is carried out by in-situ polymerization. 9. The production method according to item 1, wherein the amount of the hydrophobic liquid is 10 to 90% by weight of the total polymerization system. 10. The production method according to item 1, wherein the polymerization is carried out under stirring conditions of 50 to 500 rpm. 11. The manufacturing method according to item 1, wherein the polymerization temperature is 50 to 95°C. 12. The manufacturing method according to item 1, wherein the microsponge has a particle size of 5 to 500 μm.