JPS63137746A - Microcapsule and its preparation - Google Patents

Abstract

PURPOSE:To easily control the particle size of a microcapsule, by encapsulating a core substance, which is obtained by compounding a water-soluble or water absorbable polymer and at least one kind of a substance selected from among salts, polyhydric alcohol and a surfactant with an effective component, with a semipermeable wall film. CONSTITUTION:After a solution containing a semipermeable wall film forming high-molecular compound is prepared, an aqueous core substance composition containing at least one kind of a polymer (A) selected from among a water-soluble polymer and a water absorbable polymer and at least one kind of a component (B) selected from among salts, polyhydric alcohol and a surfactant is dispersed in said solution along with an effective component. Subsequently, a non-solvent or a phase separation inducing agent is added to said composition to prepare a microcapsule wherein a semipermeable wall film is formed to the periphery of the core substance. As the aforementioned water-soluble polymer, cellulose ether is designated and, as the water absorbable polymer, a polyacrylic acid resin is designated.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to microcapsules having excellent properties and a method for producing the same. More specifically, the present invention provides a microcapsule that is stable during storage, but whose wall membrane easily disintegrates to release all of the active ingredient when it comes into contact with water during use, and the entire manufacturing process thereof. It concerns a novel method for doing so.

Conventional technology Microcapsules are widely used as coating materials for pressure-sensitive copying paper, pharmaceuticals, agricultural chemicals, fragrances, adhesives, activated carbon, enzymes, dyes, solvents, etc.

The main functions of these microcapsules are to protect the core substance and to control the release conditions of the core substance.In particular, the core substance can be used to control the time, timing, location, and amount of release of the entire core substance as desired. Controlling the release conditions of substances is an extremely important function in making full use of microcapsules.

By the way, microcapsules are extremely useful and widely used in many industrial fields because they are stable during storage and have the property of collapsing their wall membranes and releasing active ingredients when they come into contact with water. .

Such microcapsules are known, for example, those whose wall membrane is made of ethyl cellulose, and those whose core material contains carbonate, organic acid, or water-swellable polymer (
JP-A-57-150612, JP-A No. 58-58145
No. 58-58146).

These microcapsules quickly release the core substance when they come into contact with water, but during their production, it is difficult to use the core substance as an all-aqueous solution or dispersion, so it is difficult to control the particle size of the capsules. Difficult, especially 100μ
It is difficult to obtain particles with a particle size of less than 55 to 75 m.
Since it is operated at a relatively high temperature of .degree. C., there are problems such as not being able to use all heat-labile core materials, which inevitably limits its applications.

Problems to be Solved by the Invention Under these circumstances, the present invention is stable during storage, but the wall membrane easily disintegrates when it comes into contact with water during use, resulting in By using microcapsules that can release all of the core material containing the ingredients and using them as an aqueous solution or dispersion of the core material, it is easy to control the particle size of the capsules, and high temperatures are not required to form a wall film. The purpose of this study was to provide a manufacturing method.

Means for Solving the Problems The inventors have obtained microcapsules that maintain good stability during storage, easily release the core substance during use, and whose release conditions can all be easily controlled. As a result of intensive research, we discovered that all of the objectives can be achieved by using a specific compound as the wall membrane of the microcapsule, and by using a specific ingredient as the core material along with the active ingredient. Based on this, the present invention has been completely completed.

That is, the present invention has a semipermeable wall membrane, and the core material contains, together with the active ingredient, (A) at least one selected from water-soluble polymers and water-absorbing polymers; and (B) salts;
The present invention provides microcapsules containing at least one selected from polyhydric alcohols and surfactants.

According to the invention, such microcapsules are prepared by dipping into a solution containing a semipermeable wall-forming polymeric compound, and then injecting into this solution together with the active ingredient (A) a water-soluble polymer and a water-absorbing polymer; After dispersing an aqueous core material composition containing at least one type selected from polyhydric polymers and (B) at least one type selected from salts, polyhydric alcohols, and surfactants, a non-solvent or by adding a phase separation-inducing agent to form a semipermeable wall membrane around the core material; An aqueous core material composition containing at least one kind, (B) at least one kind selected from salts, polyhydric alcohols, and surfactants, and (C) a water-soluble semipermeable wall-forming monomer. After dispersing the composition in an organic solvent, an oil-soluble semipermeable wall-forming monomer that is soluble in the organic solvent and capable of reacting with the monomer is added. It can be manufactured by carrying out a polymerization reaction to completely form a semipermeable wall film around the core material.

The present invention will be explained in detail below.

It is necessary for the microcapsules of the present invention to have a semipermeable wall membrane around the core substance. This semi-permeable wall membrane allows low molecular weight substances such as water and metal ions to pass through, but high molecular weight substances such as polymers and enzymes (molecular weight approximately 5.00
0 or more) are impermeable wall membranes, such as cellulose acetate, cellulose acetate butyrate, cellulose acetate propinate, ethylcellulose, polyvinyl acetate, polystyrene, epoxy resin, polyvinylpyrrolidone. -vinyl acetate copolymer, vinyl chloride-vinyl acetate copolymer, polyamide, polyester, polyurea, polyurethane, etc., and these may be used alone or in combination of two or more.

The core substance in the microcapsules of the present invention includes, together with the active ingredient, (A) at least one selected from water-soluble polymers and water-absorbing polymers; and (B) salts, polyhydric alcohols, and surfactants. It contains at least one type of

When the water-soluble polymer and water-absorbing polymer of component (A) come into contact with water, the microcapsules completely penetrate through the semi-permeable wall membrane, absorb invading water and gold, and swell, preventing the wall membrane from rupturing. Contains a causative effect.

Examples of water-soluble polymers include polysaccharides, polysaccharide ethers, cellulose ethers, acrylic polymers, vinyl
Examples include fluorine-based polymers and proteins.

On the other hand, water-absorbing polymers are essentially water-insoluble, but have the property of absorbing a large amount of water and swelling, and are crosslinked polymers. Examples of such materials include polyacrylic acid resins, polyacrylonitrile hydrolysates, vinyl acetate-acrylic acid copolymers, polyvinyl alcohol-maleic anhydride copolymers, inbutylene-maleic anhydride copolymers, and ethylene oxide resin,
Examples include starch/acrylonitrile graft polymers, starch/acrylic acid graft polymers, crosslinked polyvinyl alcohol, crosslinked polysaccharides, polysaccharide ethers, gelatin, etc., and many of them are commercially available and easily available. Commercially available products include, for example, Aqua Keep (manufactured by Steel Chemical Co., Ltd., trade name) and Wonder Shell (manufactured by Kao Soap Co., Ltd., trade name).
, Magic Water Gel (Super Absorbent company name, product name), Sunwet (Sanyo Kasei company name, product name), etc. These water-absorbing polymers preferably have a particle size of 1 to 500 μm, preferably 1 to 100 μm.

In the present invention, one type of water-soluble polymer or water-absorbing polymer may be used, or two or more types may be used as a mixture, or one or more water-soluble polymer and one or more water-absorbing polymer may be used. A polymer can also be used in combination.

The salts, polyhydric alcohols, and surfactants used as component (B) of the core substance are thinners for aqueous bath liquids or aqueous dispersions containing all of the above-mentioned water-soluble polymers and water-absorbing polymers;
It functions as a water absorption inhibitor for the polymer and a capsule rupture regulator.

Salts include water-soluble inorganic salts such as chlorides such as sodium chloride, calcium chloride, and magnesium chloride, sulfates, phosphates, and organic acid salts such as citrate, malate, tartrate, succinate, acetate,
Maleate, etc.

Examples include amino acids such as glycine, alanine, theanine, glutamic acid, aspartic acid, and inosine, and their salts. These may be used alone or in combination of two or more.

Examples of polyhydric alcohols include glycerin, ethylene glycol, propylene gelicol, butanediol, etc., and these may be used alone or in combination of two or more. Anionic surfactants, cationic surfactants, amphoteric surfactants, and nonionic surfactants can be used. Examples of anionic surfactants include soaps, N-acyl amino acid salts, alkyl ether carboxylates, carboxylates such as acylated peptides, alkyl sulfonates, alkylbenzene or alkylnaphthalene sulfonates, and sulfoconolate salts. , α-olefin sulfonates, N-acylsulfonates, alkylamides sulfonates, sulfonates such as α-sulfo fatty acid esters, sulfated oils, alkyl sulfates, alkyl ether sulfates, alkylaryl ether sulfates Examples of the O cationic surfactant include sulfuric acid ester salts such as alkylamide sulfates, phosphoric acid ester salts such as alkyl phosphates, alkyl ether phosphates, and alkylaryl ether phosphates. Examples of amphoteric surfactants include aliphatic quaternary ammonium salts, aromatic quaternary ammonium salts, and heterocyclic quaternary ammonium salts such as alkylpyridium salts and alkylimidazolium salts. For example, alkyl betaine type amphoteric surfactants such as alkyl carboxybetaine type and alkyl sulfobetaine type, imidacillin derivative type amphoteric surfactants such as alkylimidazolinium betaine type, phosphate ester type amphoteric surfactants, or alkylaminocarboxylic acids. Examples include salt.

Examples of nonionic surfactants include alkyl polyoxyethylene ether, alkylphenol phosphoryoxyethylene ether, fatty acid alkanolamide, fatty acid polyoxyethylene ester, fatty acid rubitan ester, sucrose fatty acid ester, polypropylene glycol/polyethylene glycol condensate, Examples include alkylamine oxides.

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

In the present invention, the above-mentioned salts, polyhydric alcohols and surfactants may be used alone or in combination of two or more, but the water-soluble polymer and water-absorbing polymer of component (A) It is preferable to select it appropriately depending on the type.

For example, as water-soluble polymers and water-absorbing polymers, polyacrylic acid-based polymers (e.g., manufactured by Gudrich Co., Ltd.,
(carbo-pol), polyvinyl alcohol, sulfated cellulose, casein alkali metal salts, gelatin, methyl cellulose, hydroxypropyl methyl cellulose, polyacrylic acid, cross-linked polyacrylate, cross-linked gelatin, etc. When kumquats are used, salts, polyhydric alcohols, Surfactants are not effective even if they are present all around; on the other hand, cellulosic polymers such as CMC, hydroxyethyl cellulose, and hydroxypropyl cellulose, and natural substances such as gum arabic, guar gum, locust bean gum, gum tragacanth, pectin, alginate, and carrageenan, When using polysaccharides, microbial polysaccharides such as pullulan and xanthan gum, polysaccharide carboxymethyl, hydroxypropyl, derivatives of phosphate esters, various water-absorbing polymers, etc., it is preferable to use polyhydric alcohols or surfactants. .

Furthermore, the active ingredient used in the core substance is not particularly limited and is appropriately selected depending on the intended use of the microcapsule. Specific examples of active ingredients include enzymes, pesticides, pharmaceuticals, health foods, colorants, bleaching agents, and the like.

The preferred ratio of each component in the core substance varies depending on the type of the component, but cannot be generally limited, but generally the active ingredient is 1 to 60% by weight and the component (A) is 0.5 to 2% by weight.
It is preferable to contain all the components in such proportions that 0% by weight, component (B) 5 to 80% by weight, and water remaining.

The weight ratio of the semipermeable wall membrane to the core substance in the microcapsules of the present invention is '/200 before capsule drying.
- It is preferable to select within the range of 'i6. If this weight ratio is less than 1/200, the strength of the wall film will be low and it will be easily broken, and if it exceeds 1/200, the wall film will not rupture when it comes into contact with water, which is not preferable.

In addition, the particle size of the microcapsules is usually 1 to 3000 μm.
, preferably in the range of 10 to 1000μ.

Next, a method for manufacturing the microcapsules will be explained.

Materials for the semipermeable wall membrane include, for example, cellulose acetate, cellulose acetate butyrate, cellulose acetate butyrate, ethercellulose, polyvinyl acetate,
Hozostyrene, epoxy resin, polyvinylpyrrolidone
When using vinyl acetate copolymer, vinyl chloride-vinyl acetate copolymer, etc., first, a semipermeable wall film-forming polymer compound selected from the above wall film materials is dissolved in an appropriate organic solvent. A solution gold preferably having a concentration of 0.3 to 10% by weight is prepared by dissolving. At this time, the polymer compound? A bath liquid may be prepared by pre-wetting with a non-solvent and then adding the solvent thereto. On the other hand, an active ingredient, (A) at least one selected from water-soluble polymers and water-absorbing polymers, (B) at least one selected from salts, polyhydric alcohols, and surfactants, and gold, as specified. prepare an aqueous core material composition by dissolving or dispersing it in an aqueous medium in a proportion of
This product is added to a solution containing all of the above-mentioned semipermeable wall film-forming polymer compounds, dispersed to a desired particle size, and then added with a non-solvent or phase separation inducer at usually room temperature. Then, a semipermeable wall membrane is completely formed around the core material. At this time, when using a phase separation inducing agent, it is desirable to change the temperature after addition, and in order to harden the formed wall film,
It may be cooled as desired (C).

The combination of the organic solvent and the non-solvent or phase separation inducing agent is appropriately selected depending on the type of semipermeable wall film-forming polymer compound used. Examples of preferred combinations are shown in Table 1.

The microcapsules thus obtained are separated by known means, such as filtration, and then dried. As the drying means, drying with dry air or vacuum drying is usually used.

Next, when using, for example, polyamide, polyester, polyurea, epoxy resin, polyurethane, etc. as a semipermeable wall material, the active ingredient and (A) are selected from water-soluble polymers and water-absorbing polymers. (B) at least one selected from salts, polyhydric alcohols and surfactants, and (C) a water-soluble semi-permeable wall film-forming monomer in a predetermined ratio. An aqueous core material composition is prepared by dissolving or dispersing it in an aqueous medium. At this time, the neutralizing agent may be added in its entirety if necessary. Next, this aqueous core material composition is dispersed in a suitable organic solvent to obtain a desired particle size, and then an oil bath property that can be dissolved in the organic solvent and reacted with the monomers is added. The entire semipermeable wall film-forming monomer is polymerized to form a semipermeable wall film around the core material. This polymerization reaction is usually carried out at 0 to 30°C, but at a temperature of 40 to 60°C.
It can also be heated to ℃. At this time, the entire polymerization catalyst may be added if necessary.

The combination of the water-soluble semipermeable wall film-forming monomer, the oil-soluble semipermeable wall film-forming monomer, and the organic solvent is appropriately selected depending on the Wi6 of the desired wall film material.

Table 2 shows preferred examples of this combination. The microcapsules thus obtained are separated and dried in the same manner as described above.

In addition, the microcapsules produced by the method of the present invention include:
Although salts, polyhydric alcohols, and surfactants are included, these can be removed by washing the microcapsules with a low-boiling point water-soluble organic aqueous solution.

Examples of the low-boiling water-soluble organic solvent include methyl alcohol, ethyl alcohol, propyl alcohol, inglobil alcohol, and acetone.

Dioxane, tetrahydrofuran, etc. can be used, and the concentration of the aqueous solution thereof is preferably in the range of 20 to 80% by weight.

Effects of the Invention The uninvented microcapsules have a semipermeable wall membrane 1 to 1 and contain a water-soluble polymer or a water-absorbing polymer f in the core substance,
When it comes into contact with water, the water completely penetrates the core wall membrane and enters the interior, and the water swells the polymer, causing the wall membrane to collapse and release all of the active ingredients contained in the core material. It is stable during storage and can smoothly release the active ingredient during use.

Therefore, they are suitable as microcapsules for use in fields such as cosmetics, pharmaceuticals, agricultural chemicals, health foods, and detergents.

Furthermore, unlike the conventional method, according to the uninvented method, it is easy to control the particle size of microcapsules, and it is possible to create particles with a particle size of 100 μm or less, and the entire wall film can be formed at room temperature. This has the advantage that thermally unstable active ingredients can also be used as the core material, further expanding the range of uses of the resulting microcapsules.

EXAMPLES Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples in any way.

Example 1 Sodium chloride 162 and ethylene glycol 62 were completely dissolved in 50 f of water, and then acrylic acid-based water-absorbing polymer 22 with a particle size of 10 to 20 μm and alkaline glothiase (manufactured by Sigma Chemical Co., Ltd., type 4) were added to 30 f. '
The whole core material composition was prepared by dispersing it in

When this composition was observed under optical IM imaging, it was found that the water-absorbing polymer hardly absorbed any water.

On the other hand, put 80d of hexane in a 1t tall beaker,
To this, cellulose acetate butyrate powder 1.79
After dispersing with a stirrer, 23 odk of chloroform was added and cellulose acetate glylate was added. Next, the core material composition 207 with a particle size of 100 ml was added to this solution.
After dispersing to a thickness of ~300 μm, hexane was added dropwise at 190 d'i for 30 minutes at room temperature, and then cooled to ~2° C. At this point, when observing the dispersion using a full optical microscope,
Formation of capsules in which the core material particles were enveloped by the adult film was observed. After hardening the capsule wall membrane by adding 400 td of hexane, the capsules were separated by filtration, and then all the moisture inside the capsules was removed using a vacuum dryer.The capsules thus obtained were semipermeable. The cellulose acetate butyrate wall membrane contained 47% of total enzyme by weight. Compared to enzyme powder, this capsule does not generate fine powder and is highly safe for the human body.

Core substance release test: 1 microcapsule was added to 1 ton of tap water at 20°C while stirring, and the release properties of the core were investigated using optical microscopy and measurement of enzyme activity in the water.

As a result, it was found that in most capsules, the capsule wall membrane ruptured and the core substance was released after 30 days, and the secretion was about 60%, 95% after 5 minutes, and 100% after 10 minutes.

The capsules can be used in laundry detergents.

The enzyme activity was measured by these tests in accordance with the Ca5in-275 mμ absorption method A described in "Enzyme Research Method 2" (edited by Akahori Yobe) published by Shokusen Shoten, page 283 et seq.

Example 2 Acrylic water-absorbing polymers 22 and 1.3 with an average particle size of 5 μm were added to 100 r of a 20% by weight sodium sulfate water bath solution.
A core material composition was prepared by completely mixing bis(carbamoylthio)-2-(N,N-dimethylamine)propane hydrochloride-152.

On the other hand, hexane 807 in a tall beaker! money purse,
After dispersing 1.72 of cellulose acetate gropionate in a stirrer, 230 rnt' of chloroform was added and dissolved.Next, the core material composition 2 was added to this solution.
02 After dispersing to a total particle size of 30 to 50 μm,
At room temperature, after adding 190mZi of hexane for 30 minutes,
Cooled to 2°C □Furthermore, 400 - of hexane was added to harden the capsule wall film.

The capsules were separated by filtration and dried with dry air.

The capsules thus obtained have a semipermeable cellulose acetate gropionate wall and contain the insecticide 1,3-bis(carbamoylthio)-2-(N,N-dimethylamino)propane. It was confirmed using an optical microscope that when water was sprinkled on the microcapsules containing 36% of gold hydrochloride, part of the capsule membrane was ruptured and the core material was released.

This capsule can be used as an insecticide. Example 3 A total core material composition was prepared by mixing 152 parts of vitamin, 32 parts of gelatin, 12 parts of starch-acrylic acid graft polymer type water-absorbing polymer, 152 parts of sodium sulfate, and 662 parts of water.

Separately, cellulose acetate (degree of acetylation: 55, average degree of polymerization: 140) was dissolved in 600 grams of dichloromethane-ethanol (volume ratio 93:7), and then 100 tons of the core material composition was dispersed therein. Particle size total 5O
- After adjusting to 100 μm, petroleum ether 7 at room temperature
After dropping for 30 minutes, the solution was cooled to 1 to 3°C. Further, 100'i of petroleum ether was added to harden the capsule wall film, and then the capsules were separated by filtration and dried in a vacuum drier.

The capsules thus obtained had a semipermeable cellulose acetate wall and contained a total of 4-35% by weight of vitamins.

Capsule evaluation: 12 capsules and 0 vitamin C (ascorbic acid) powder
．． The samples were placed in 35 and 50 glass bottles and stored uncovered in the air at 40°C (humidity 80%), and the residual amount of vitamin C was measured.The results are shown in Figure 3. As for the analysis of vitamin C.

It was performed according to the Japanese Pharmacopoeia (9th revision).

Table 3 The capsules were also mixed with artificial gastric fluid (sodium chloride 2.0
When added to f, a 10% hydrochloric acid aqueous solution adjusted to 1000-1000 (pH approximately 1.2), the capsule wall ruptured in 3 to 5 minutes and the core substance was released using an optical microscope. Observed and confirmed.

This capsule can be used as a medicine.

Example 1 Ethylene glycol 802.1offiH% sodium bicarbonate water bath solution 20F, hexamethylene diamine 22 are mixed and dissolved, and acrylic water-absorbing polymer 22 with an average particle size of 5 μm and papain (proteolytic enzyme) 10
A core material composition was prepared by mixing r'i.

Next, chloroform-cyclohexane (volume ratio 1:
3) After completely dispersing 100 f of the core material composition in 200-g, and adjusting the particle size to 20 to 50 μm by stirring, toluylene diisocyanate 4- was added to 1
Stir for 30 minutes at 0°C.

Next, after all of the produced capsules were separated by filtration, the capsules were washed with 1 liter of ethanol water bath solution of 50 volume in order to remove ethylene glycol and unreacted hexamethylene diamine inside the capsules, and then air-dried. After drying, microcapsules having a semipermeable voluric wall membrane and containing about 70% papain and about 14% gold by weight of a water-absorbing polymer are obtained.

The microcapsules obtained in this way were added in an amount of 0.5% by weight to a 50 volume aqueous ethanol solution to prepare a capsule dispersion. The microcapsules were placed in a 50 ml glass bottle, sealed, and stored at 35°C for 30 days, but the microcapsules remained stable without being destroyed. The membrane ruptured and all of the core material was released. In addition, when capsules are dispersed and left in air, the water concentration increases due to the evaporation of ethanol, which causes the water-absorbing polymer inside the capsule to absorb water and swell, causing the wall membrane to rupture and the core material to be released. observed under a microscope.

Papain, a proteolytic enzyme, does not have any adverse effects on healthy tissues and specifically acts on necrotic tissues, so these capsules can be used in facial cleansers, bags, exfoliants, lotions, etc.

Example 5 Carbo Ball 941 (manufactured by Gutdrich, polyacrylic acid-based water-soluble polymer) 22, sodium carbonate z4y
, IE chain alkylbenzene sulfone sodium l? ,
Hexamethylene diamine 32 capsules can be applied to water leak detectors, etc.

A core material composition was prepared by mixing 152 parts of red iron oxide (triferric oxide) and 842 parts of water. Next, this core material'ft composition 100? 2. In a bath medium of taloloform-cyclohexane (volume ratio 1:3), the particle size is 100-5.
00 μm.

Next, this dispersion was kept at 2 to 3°C and terephthaloylcyclo+)do49'fKchloroform-7chlorohexane(
The FC solution was dissolved in a volume ratio i23RJ medium 500+d, and the mixture was stirred for 30 minutes to completely form a polyamide wall film on the surface of the core material.The capsules were then separated by filtration and dried with dry air.

The microcapsules thus obtained had a semipermeable polyamide wall and contained 40% by weight of the red pigment Bengara.

When this capsule was placed in water, it was confirmed using an optical microscope that part of the capsule membrane ruptured and the core material was released.

Claims (1)

[Scope of Claims] 1. It has a semi-permeable wall membrane, and together with an active ingredient as a core substance, (A) at least one selected from water-soluble polymers and water-absorbing polymers, and (B) salts and polyesters. A microcapsule containing at least one selected from a hydrolic alcohol and a surfactant. 2. Prepare a solution containing a semipermeable wall-forming polymer compound, and then add (A) into this solution together with the active ingredient.
Dispersing an aqueous core material composition containing at least one selected from water-soluble polymers and water-absorbing polymers and (B) at least one selected from salts, polyhydric alcohols, and surfactants. A method for producing microcapsules, which comprises subsequently adding a non-solvent or a phase separation inducing agent to form a semipermeable wall film around the core substance. 3. Along with the active ingredients, (A) at least one selected from water-soluble polymers and water-absorbing polymers, (B) at least one selected from salts, polyhydric alcohols, and surfactants, and (C) An aqueous core material composition containing a water-soluble semipermeable wall-forming monomer is prepared, and then this composition is dispersed in an organic solvent, and then dissolved in the organic solvent and the monomer is dissolved in the organic solvent. 1. A method for producing microcapsules, which comprises adding an oil-soluble semipermeable wall film-forming monomer capable of reacting with a polymer and causing a polymerization reaction to form a semipermeable wall film around a core substance.