JPS63287543A - Production of microcapsule - Google Patents

Abstract

PURPOSE:To detoxify capsule by forming microcapsule by phase separation with addition of aq. liquid, etc., using polyvinylacetal diethylaminoacetate, methyl methacrylate, etc., as wall material. CONSTITUTION:A solution of the wall material contg. one or more kinds of polyvinylacetal diethylaminoacetate, dimethylaminoethyl methacrylate-methyl methacrylate copolymer, methyl methacrylate-methacrylic acid copolymer, hydroxypropylmethylcellulose acetate phthalate, etc., is prepared. The microcapsule is produced by phase separation adding aq. liquid, or acid or base, etc., to the soln. of wall material. Water or aq. soln. of polymer soluble in water or water and ethanol is pref. as the aq. liquid above-mentioned.

Description

[Detailed Description of the Invention] Chestnuts are grown in abundance! The present invention relates to a method for manufacturing microcapsules by phase separation by adding an aqueous liquid or adding an acid/base, and can be used in various fields such as pharmaceuticals, foods, paper manufacturing, and photographic films. . In particular, since a substance with high safety for living organisms is used as a wall material due to phase separation, it is particularly useful in fields such as pharmaceuticals.

Many methods have been conventionally provided for producing Ibaraki microcapsules. Broadly speaking, these methods include chemical methods, physicochemical methods (phase separation methods), physicomechanical methods, and arbitrary combinations of these methods.

However, these conventional methods have difficulties in application to fields such as pharmaceuticals.

For example, the phase separation method has the disadvantage that the operation is complicated and takes a long time.

In addition, 1. Since highly toxic substances such as formaldehyde, dichloroethane, cyclohexane, etc. are used as organic solvents in the phase separation method, there is a drawback that it is difficult to employ in fields such as pharmaceuticals. This is because it is difficult to completely remove these substances.

Phase separation here refers to the phenomenon in which a solution containing a polymeric substance or a hydrophilic colloid solution separates into two liquid phases: a colloid-rich liquid phase and a colloid-poor liquid phase. This is also called cellvation.

. In order to eliminate the above-mentioned drawbacks of ``
We have developed a method for manufacturing microcapsules by using a specific wall material during phase separation by adding an aqueous liquid or adding an acid or base, and have completed the present invention.

In the method for producing microcapsules of the present invention, one type or a mixture of any number of compounds listed below is used as the wall material.

Polyvinyl acetal diethylamino acetate, dimethylaminoethyl methacrylate/methyl methacrylate copolymer, methyl methacrylate/methacrylic acid copolymer, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, and polyvinyl acetate phthalate.

Since these materials are non-toxic, they are particularly useful for applications in fields such as medicine.

In the method for producing microcapsules of the present invention, phase separation is performed using the above-mentioned wall material. In this case, phase separation is performed by adding an aqueous liquid or by adding an acid or a base.

As the aqueous liquid, water alone or an aqueous solution of a polymeric substance soluble in water and ethanol is used.

The fact that water can be used as an aqueous liquid is
It is extremely beneficial from an economic point of view.

Examples of polymeric substances soluble in water and ethanol include the following compounds.

hydroxypropylcellulose, polyvinyl pyrrolidone, or Hydroxypropyl methylcellulose.

Since these substances are non-toxic, they can be advantageously applied in fields such as medicine.

The concentration of these solutions is not particularly limited, but is preferably about 3 to 10%.

Further, the amount added is not particularly limited as long as it is at least the amount that forms microcapsules.

The microcapsules obtained by the method of the invention are spherical or cone-shaped particles with an average diameter of, for example, 100 to 200 microns.

Furthermore, one of the characteristics of the method of the present invention is that the average diameter of the microcapsules can be arbitrarily adjusted over the range of several microns to several millimeters.

That is, when phase separation is performed using an aqueous solution of a polymeric substance soluble in water and ethanol, the microcapsules become more spherical in shape than when phase separation is performed using water alone, and the particles of the microcapsules become more spherical. The diameter can be adjusted arbitrarily.

Another means for carrying out the phase separation in the method of the present invention is to add an acid/base.

Non-toxic acids and bases are used as additives for pharmaceuticals, such as acids such as hydrochloric acid, citric acid, tartaric acid, and acetic acid, and bases such as caustic soda and meglumine.

There is no particular limit to the amount of these acids and bases added, and the amount is such that the pH value can be arbitrarily adjusted depending on the purpose.

The material to be embedded in the wall material of the microcapsules of the present invention, the so-called "core material", can be in solid, semi-solid or liquid form.

For example, solid substances include starches, inorganic salts, and the like.

Semi-solid substances include waxes such as monoglycerides.

Examples of liquid substances include fat-soluble vitamins such as vitamins AXD, E, and garlic, poorly water-soluble vitamins, animal oils, vegetable oils, mineral oils, synthetic oils, and the like.

Furthermore, tJ! such as lactose, mannitol, and sorbitol!
II etc. can also be used.

Light Plate Arrival Since the method for producing microcapsules of the present invention uses a non-toxic compound as the wall material, it is particularly useful in fields such as pharmaceuticals. Moreover, the obtained microcapsules are
It will make a huge contribution to industry, as it can turn oily substances into powder, stabilize unstable substances over time, and mask the taste and odor of substances used.

Next, the present invention will be described in more detail with reference to Examples.

However, the present invention is not limited only to these examples.

Example 1 10 g of polyvinyl acetal diethylaminoacetate and 10 g of dJ-α-tocopherol acetate were dissolved in advance in 100 ml of ethanol at room temperature. (Solution A
) Subsequently, solution A was heated at 11,000 rpm using a homomixer.
While stirring at room temperature, 300 g of water was gradually added using a Verister pump. After adding approximately 150 mj of water, formation of spherical microcapsules of 100 to 300 μm was confirmed by microscopic observation.

After adding 300 ml of water, it was filtered using a 200 mesh sieve, washed with water, and vacuum dried in a desiccator loaded with phosphorus pentoxide to obtain a powder of spherical microcapsules of 100 to 300 μm. Ta.

Example 2 5 g of polyvinyl acetal diethylaminoacetate and 10 g of sesame oil were dissolved in 50-g of ethanol at room temperature. (Solution A) Next, solution A was stirred at about 1,100 Orp using a stirrer and heated to 20°C at room temperature.
0 liters of water was gradually added using a peristaltic pump.

Microscopic observation showed that when water was added to about 70
The production of spherical microcapsules of ~500 μm was confirmed.

After adding 200 rnl of water, it was filtered using a 200 mesh sieve, washed with water, and vacuum dried in a desiccator loaded with phosphorus pentoxide to obtain a powder of spherical microcapsules of 100 to 500 μm. Ta.

Example 3 10 g of polyvinyl acetal diethylamino acetate 10 g of acetic acid-dl-α-tocopherol
, 3 g of silicic anhydride was dissolved and dispersed in 100 ml of ethanol at room temperature. (Solution A) Subsequently, while stirring Solution A at about 1100 rpm using a stirrer, 300 liters of water was gradually added at room temperature using a Verister pump. When water was added at 150°, microscopic observation showed that 5.
The production of spherical microcapsules of 0-150 μm was confirmed.

After adding 300 ynl of water, it was filtered using a 300 mesh sieve, washed with water, and dried in an oven kept at 40°C to obtain a powder of spherical microcapsules of 50 to 150 μm. .

Example 4 Example 1 was repeated except that 10 g of diethylaminoethyl methacrylate methyl methacrylate copolymer was used instead of 10 g of polyvinyl acetal diethylamino acetate. The obtained microcapsule powder was spherical and had a diameter of 100 to 300 μm.

Example 5 The procedure of Example 1 was repeated except that 10 g of hydroxypropyl methylcellulose phthalate was used instead of 10 g of polyvinyl acetal diethylaminoacetate. The obtained microcapsule powder is spherical and has a particle size of 200~
It was 500 μm.

Example 6 The procedure of Example 1 was repeated, except that the microencapsulation was performed in a water bath at 60° C. instead of at room temperature. The obtained microencapsulated powder is spherical and has a diameter of 100 to 300 μm.
Met.

Example 7 10 g of polyvinyl acetal diethylaminoacetate and 10 g of dβ-α-tocopherol were dissolved in 100 mff1 of ethanol at room temperature. (Solution A
) Furthermore, add 10 g of hydroxypropyl cellulose to 200 m
Dissolved in 1 liter of water. (Solution B) Subsequently, while stirring Solution A at 11,000 rpm using a homomixer, Solution B was gradually added using a peristaltic pump at room temperature. When 120 rr+1 of solution B was added, formation of spherical microcapsules of 100 to 300 μm was confirmed by microscopic observation.

After adding all of the solution B, it was filtered using a 200 mesh square sieve, washed with water, and vacuum dried in a desiccator preloaded with phosphorus pentoxide to obtain a powder of spherical microcapsules of 100 to 300 μm. Ta.

Example 8 150 g of polyvinyl acetal diethylamino acetate, 300 g of dl-α-tocopherol acetate
g was dissolved in 1000 d of ethanol at room temperature. (Solution A) Furthermore, add 150 g of hydroxypropyl methyl cellulose to 2
Dissolved in 850-g of water. (Solution B) Then, using a homomixer, stirring solution A at 200 rpm,
Solution B was gradually added to this at room temperature using a peristaltic pump.

When about 1500 mf of solution B was added, formation of spherical microcapsules of 100 to 500 μm was confirmed by microscopic observation.

After adding all of solution B, 400g was added using a fluidized bed granulator.
The microencapsulated slurry was sprayed into a fluidized bed of silicic anhydride. After the spraying was completed, it was dried using the same machine. As a result of microscopic observation, it was confirmed that they were spherical microcapsules coated with silicic anhydride with a diameter of 200 to 700 μm.

Example 9 The procedure of Example 7 was repeated except that 10 g of methyl methacrylate methacrylic acid copolymer was used instead of 10 g of polyvinyl acetal diethylaminoacetate. The obtained microcapsule powder was spherical and had a size of 200 to 500 μl.

Example 10 The procedure of Example 7 was repeated except that 10 g of hydroxypropyl methyl cellulose acetate phthalate was used instead of 10 g of polyvinyl acetal diethylamino acetate. The obtained microcapsule powder was spherical and had a diameter of 100 to 300 μm.

Example 11 The procedure of Example 7 was repeated except that polyvinyl pyrrolidone was used instead of hydroxypropylcellulose in the composition of solution B. The obtained microcapsule powder was spherical and had a diameter of 100 to 300 μm.

Example 12 The procedure of Example 7 was repeated except that hydroxypropylmethylcellulose was used instead of hydroxypropylcellulose in the composition of solution B.

The obtained microcapsule powder is spherical and has a particle size of 300 to 600
It was μm.

Example 13 10 g of polyvinyl acetal diethylamino acetate and 10 g of citric acid were dissolved in 200 g of water in advance. 10 g of tocopherol acetate was added to this solution and stirred at high speed for 1 minute using a polytron to obtain an emulsion of several μm.

A solution prepared by dissolving 10 g of meglumine in 100% water was gradually added to this emulsion solution using a peristaltic pump while stirring with a stirrer at room temperature.

At pH 6-7, coacervate of polyvinyl acetal diethylamine acetate began to form and emulsion oil droplets began to collect.

After adding the meglumine solution 100-, the pH is approximately 1.
As a result of microscopic observation at 0, it was confirmed that polynuclear microcapsules with a particle size of 100 to 500 μm were formed by collecting oil droplets of tocopherol acetate. Thereafter, the mixture was filtered using a 300-mesh sieve, washed with water, and vacuum-dried in a desiccator charged with phosphorus pentoxide to obtain a powder of spherical microcapsules of 100 to 500 μm.

Example 14 The procedure of Example 13 was repeated except that 10 g of dimethylaminoethyl methacrylate methyl methacrylate copolymer was used instead of 10 g of polyvinyl acetal diethylaminoacetate. The obtained microencapsulated powder was spherical and had a diameter of 100 to 500 μm.

Example 15 The procedure of Example 13 was repeated except that 10 g of polyvinyl acetate phthalate was used instead of 10 g of polyvinyl acetal diethylamino acetate.

The obtained microencapsulated powder is spherical and has a particle size of 100 to 50
0 μm Example 16 200 log of citric acid was dissolved as an acidic substance.
Instead of ml of citric acid solution, add 20.0 IN of hydrochloric acid solution.
0- and 0.0- in place of a 100- meglumine aqueous solution in which 10 g of meglumine was dissolved as an alkaline substance. IN
The procedure of Example 13 was followed except that the sodium hydroxide solution 100- was used.

The obtained microencapsulated powder is spherical and has a particle size of 100 to 40
It was 0 μm.

Example 17 10 g of hydroxypropyl methyl cellulose phthalate and 10 g of meglumine were dissolved in 200 ml of water in advance. 10 g of sesame oil was added to this solution and stirred at high speed for 1 minute using a Polytron to obtain an emulsion of several μm. A solution prepared by dissolving 20 g of citric acid in 1001 n1 of water was gradually added to this emulsion solution at room temperature with a peristaltic pump while stirring using a homomixer.

At pH 4-5, coacervate of hydroxypropyl methylcellulose phthalate began to form and emulsion oil droplets began to collect. After adding 100 d of citric acid solution, the pH was about 3, and microscopic observation confirmed the formation of multinuclear microcapsules with a particle size of 100 to 400 μm that collected sesame oil droplets. Thereafter, it was filtered using a 200-mesh sieve, washed with water, and vacuum-dried in a desiccator charged with phosphorus pentoxide to obtain spherical microcapsules of 100 to 400 μm.

Example 18 The procedure of Example 17 was repeated except that 10 g of methyl methacrylate methacrylic acid copolymer was used instead of 10 g of hydroxypropyl methyl phthalate.

The obtained microencapsulated powder is spherical and has a particle size of 100 to 40
It was 0 μm.

Example 19 The procedure of Example 17 was repeated except that 10 g of hydroxypropyl methylcellulose acetate phthalate was used instead of 10 g of hydroxypropyl methylcellulose phthalate.

The obtained microencapsulated powder is spherical and has a particle size of 100 to 30
It was 0IIm.

Claims (1)

[Claims] 1. In producing microcapsules by phase separation by adding an aqueous liquid or adding an acid/base, polyvinyl acetal diethylamino acetate, dimethylaminoethyl methacrylate/methyl methacrylate copolymer, methyl A method for producing microcapsules, characterized in that one or more of methacrylate/methacrylic acid copolymer, hydroxypropyl methyl cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, and polyvinyl acetate phthalate are used. 2. The method according to claim 1, wherein the aqueous liquid is water or an aqueous solution of a polymeric substance soluble in water and ethanol. 3. The method according to claim 2, wherein the polymeric substance soluble in water and ethanol is hydroxypropylcellulose, polyvinylpyrrolidone, or hydroxypropylmethylcellulose.