JPS588292B2 - Preparation method of microcapsules - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for preparing microcapsules in which a core substance is encapsulated in a polymer shell.

Conventionally, known methods for microencapsulating physiologically active substances such as enzymes, pharmaceuticals, and other chemical agents include phase separation from organic solvents, interfacial precipitation, and interfacial polymerization, but these methods are still unsatisfactory. It wasn't.

For example, in the phase separation method, it is extremely difficult to set the conditions to cause phase separation to an appropriate thickness at the interface in the coacervation region. The disadvantage is that there are many

Further, in the interfacial precipitation method, there is a problem that it is difficult to set the generation conditions to stabilize the secondary emulsion, and the microencapsulation rate tends to be low.

Furthermore, in these two methods, the microcapsule shells obtained are in the form of a liquid film containing an organic solvent, so they have poor strength and strength. In many cases, treatment with a crosslinking agent or the like is required to increase the retention force of the cell core material.

In this case, if the core material is sensitive to the crosslinking agent, a problem arises in that the core material is inhibited by treatment with the crosslinking agent.

Interfacial polymerization cannot avoid the interaction between reactive monomers and core substances, making it unsuitable for microencapsulation of chemically sensitive physiologically active substances. Since the permeation of the monomer to the interface is restricted, there is a drawback that in principle only capsules with a thin film thickness can be obtained.

The present inventors overcame the drawbacks of the conventional microencapsulation techniques as described above, and industrially advantageously prepared microcapsules with good mechanical strength without impairing the physiological and chemical activities of the core substance. As a result of intensive research to develop a method that can be used as a shell material, we have developed a method that uses a hydrophilic polymer as a base material and has a hydrophobic photosensitive group attached to it. By impregnating the microcapsule substrate with a core substance in a solution form, and then irradiating it with light to photocrosslink the polymer via the photosensitive group,
The inventors have discovered that the above object can be achieved and have completed the present invention.

In the present invention, the polymer used as the shell material of the microcapsule is an organic solvent-soluble polymer having a structure in which a hydrophilic polymer is used as a base and a hydrophobic photosensitive group is bonded to the base.

In this case, the hydrophilic polymer substrates include polyvinyl alcohol, polyacrylic acid, polyacrylamide, polyhydroxyalkylmethacrylate, polyamino acids, polysaccharides, mucopolysaccharides, proteins, etc., which have hydroxyl groups, amine groups, etc. Examples include those having hydrophilic groups such as carboxyl groups and amide groups.

In addition, examples of the hydrophobic photosensitive group bonded to this include a 2-furyl acryloyl group, a methacryloyl group, a cinnamoyl group,
Examples include unsaturated carboxyloyl groups such as α-cyanocinnamylidene acetate group, p-azidobetzoyl group, α-cyano p-azidocinnamoyl group, and p-phenylene diacryloyl group.

These hydrophobic photosensitive groups can be bonded to the hydrophilic/aqueous base polymer via the hydrophilic groups of the polymer.

In addition, in order to adjust the hydrophilicity and hydrophobicity of the photocrosslinkable polymer used in the present invention, ionically dissociable groups such as long-chain saturating lupoxyloyl groups, phosphoryl groups, sulfonyl groups, and quaternary ammonium sium groups are added as appropriate. It can also be introduced.

The photocrosslinkable polymer preferably used in the present invention is
Due to easy availability, polyvinyl alcohol, amylose,
Examples include partial cinnamoyl ester, cinnamylidene acetate, α-cyanocinnamylidene acetate, etc. of starch, alginic acid, etc.

To carry out the method of the present invention, first, a microcapsule substrate that does not encapsulate a core substance is prepared.

In this case, the preparation method is not particularly limited, and conventionally known methods can be used, but in the case of the present invention, water-in-oil or oil-in-water type In order to obtain a type of emulsion, it is preferable to carry out emulsification treatment by vigorously stirring a solution in which the polymeric substance is dissolved and a solvent that is immiscible or immiscible with this solution.

In this case, the solvent for forming the polymer solution and the solvent added thereto are mutually immiscible.

Examples of this organic solvent include aromatic, aliphatic, and alicyclic hydrocarbon solvents and their halides.

The polymer concentration in the polymer solution is O. '0 1 to 10 weight ratio, preferably 0.05 to 5 weight ratio.

The emulsification treatment temperature is OO-room temperature, and in some cases, heating is employed.

In emulsification treatment, to form a water-in-oil emulsion, water or an aqueous solvent is added to a solution of a polymer in an organic solvent and stirred vigorously; Add a solution of a polymer in an organic solvent to water or an aqueous medium and stir vigorously.

Further, in this emulsification process, a commonly used emulsifier can be used.

The amount of droplets dispersed in the dispersion medium is usually determined by the o
．． i~10 weight section.

Through such emulsification treatment, the dissolved polymer is precipitated at the interface between the dispersion medium and the droplet due to its hydrophilic-hydrophobic balance, and microcapsules containing the solvent are obtained.

In the present invention, the microcapsules thus obtained are separated from the dispersion medium, and then immersed in a solution that dissolves the core material, and the core material is impregnated into the interior of the microcapsules through the shell.

In this case, since the shell of the microcapsule is uncrosslinked, the core substance in the solution can easily pass through the microcapsule.

Enzymes, hormones, medicines, agricultural chemicals, chemicals, and other various substances are used as the core substance.

The concentration of the core substance in the core substance solution is not particularly limited, and the higher the concentration, the more quickly the core substance can penetrate into the inside of the microcapsule, but it is generally about 1 to 50% by weight.

According to the present invention, when a core substance is impregnated into a microcapsule substrate that does not contain a core substance, the solvent of the core substance solution is one that is miscible or compatible with the solvent encapsulated in the microcapsule substrate. Ru.

In addition, in order to advantageously impregnate the core substance, the microcapsule substrate separated from the emulsification process is placed in a vacuum container, the solvent contained therein is removed, and then the core substance solution is placed in the container. It is better to inject.

In this case, the solvent for the core material solution is not restricted and can be any water-soluble or non-water-soluble solvent.
It also takes less time.

Furthermore, if the solvent contained in the microcapsule substrate is volatile, the internal solvent is evaporated by leaving it in the air for an appropriate period of time or by applying appropriate heating, and then the core It is also possible to impregnate the core material by immersing it in a solution of the material.

The microcapsules encapsulating the core substance in this manner are irradiated with light to crosslink the polymeric substance constituting the shell through the photocrosslinking group.

This crosslinking makes it possible to obtain microcapsules in which the encapsulated core substance is immobilized.

In the present invention, when performing emulsification treatment, appropriate surfactants and other emulsification aids may be added as necessary to obtain a stable emulsion.

In addition, when performing light irradiation treatment, the irradiation light is 250 nm.
It is possible to use both ultraviolet light and visible light, and for this light irradiation treatment, various sensitizers commonly used in photocrosslinking reactions, such as water-soluble sensitizers such as riboflavin, and 2-nitrofluorene, can be used. , 5-nitroacenaphthene, and other organic solvent-soluble sensitizers may optionally be used in combination.

Since the microcapsules obtained by the present invention have shells made of photo-crosslinked polymers, they have high mechanical strength and can achieve good immobilization of the encapsulated core substance.

Furthermore, the preparation of microcapsules according to the present invention is easy to carry out, and since the crosslinking is carried out by light irradiation, there is no possibility of damage such as a decrease in the activity of the core substance, which is seen when using conventional crosslinking agents. There isn't.

In addition, by appropriately adjusting the polymer concentration in the emulsion, it is possible to adjust the thickness of the shell of the microcapsules to an appropriate thickness, and by changing the amount of light irradiation, it is possible to prevent leakage of the core substance to the outside or increase the permeability. Town Noh is about changing the world.

According to the present invention, microcapsules having a particle size in the range of 10 to several hundred μm can be easily obtained, and its industrial significance is great.

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

Example 1 Cinnamate ester (ester {tJ approx. o. 3 4 ) obtained by reacting polyvinyl alcohol with an average degree of polymerization of about 1500 with genamic acid chloride in pyridine 250
mI? and 10 m9 of 2-nitrofluorene to dichloroform-benzene-hequinane (volume ratio: 3:4:3
) in 2001nl of mixed solvent, add 25TL of water.
1 and emulsify under cooling with water.

This emulsion (water-in-oil type) was centrifuged at 4° C. to remove the supernatant, then added to 200 rrLl of a 10% Tween 20 aqueous solution, stirred, and the organic solvent was further removed.

After stirring for 2 hours under water cooling, L-ascorby/
The acid was dissolved at a concentration of 5%, stirred for 2 hours under water cooling, and then irradiated with a 400W high-pressure mercury lamp for 10 minutes.

The capsules were separated by mouth-passing to obtain ascorbic acid-containing microcapsules.

Example 2 50 ml of the cinnamate ester shown in Example 1 was dissolved in 25 ml of chloroform.

After adding 10 μm of sensitizer 2-nitrofluorene to this polymer solution, this was mixed with 250 m of a 20% Tween 20 aqueous solution.
30°C at 35°C as an emulsion (oil-in-water type) in addition to
Stir for a minute to evaporate some of the chloroform.

After centrifuging this emulsion and removing the supernatant, the capsule layer was separated into chloroform-benzene-hexane (containing 10 g of isoprobyl-N-(3-chlorophenyl) carbamate).
Volume ratio: 1:4:5) was suspended in 100 d of mixed solvent, stirred for 30 minutes under water cooling, irradiated with light for 5 minutes using a 400W high-pressure mercury lamp, centrifuged, and inpropyru N-(
3-chlorophenyl). Carbamate-containing microcapsules were obtained.

Claims (1)

[Claims] 1 After impregnating a core material solvent into a microcapsule substrate that does not contain a core material and is made of a hydrophilic polymer as a base material and a shell of a photocrosslinkable polymer with a hydrophobic photosensitive group bonded to the shell. . A method for preparing microcapsules, which comprises irradiating light to photo-crosslink the polymer via a photosensitive group to immobilize the impregnated core material.