JP3489033B2 - Microcapsule and method for producing the same - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention is applied to pharmaceuticals, agricultural chemicals, cosmetics,
The present invention relates to a microcapsule that can be used in the field of liquid crystal and the like and a method for producing the same.

[0002]

2. Description of the Related Art In recent years, microcapsules have been used in a wide variety of fields including pharmaceuticals and foods. As a method for forming a target layer of the microcapsules thus many techniques have been put into practical use. For example, a method utilizing an interfacial polymerization reaction and a method utilizing an ion exchange reaction have been well known in the past, but each has a serious drawback.
Interfacial polymerization method is generally to be film of the polymer is reacted with an oil-water interface aqueous phase containing hydrophilic monomer were added hydrophobic monomer emulsion after the oil phase in the oil phase is precipitated around the water droplets in This is a method for obtaining microcapsules (Tamotsu Kondo, Masumi Koishi:
"Microcapsule", Sankyo Publishing (1987)). The method aqueous solution can be efficiently encapsulated in fine microcapsules, yet the target membrane has a unique barrier properties of semi-permeable. As described above, the microcapsules of the interfacial polymerization method are practically used in spite of having many excellent characteristics. This thin the film to be formed, the strength is weak, because the microcapsules having a strength enough handled as a general powder can not be obtained. The insolubilized by the microcapsules of the water-soluble dissolved in the aqueous phase droplets as preparation compound ion exchange under W / O emulsion using an ion exchange reaction, there is a method of forming a microcapsule target film ( Journal of the Chemical Society of Japan,
No. 5, p. 727-731, 1976). Easily soluble contents are leaked to form a target <br/> film at relatively strength of certain things make those aqueous phase in this method, a dense object <br/> film had hardly drawbacks can .

[0003]

The film having semipermeable in microcapsules [0008] The order to transmit only a small molecule, a very useful property is also possible to make a unique feature in the design becomes available. For example if encapsulated enzyme in microcapsules such the film, it is possible to emit a useful metabolite to the film outside crowded preparative substrate to remain membrane isolated from the membrane outside environment . The film of the microcapsules by interfacial polymerization reaction, although with the film properties excellent that this semipermeable, strength is weak, it is difficult to the intact handled as a general powder, interfacial polymerization for this shortcoming At present, the applications of microcapsules using reactions are greatly limited. Also, fineness is a great advantage. For example, when it is embedded in a living body, mechanical irritation is less than that of a large one, which is very advantageous in that carcinogenicity, toxicity, etc. can be suppressed. Further, since the surface area per unit weight becomes large, it is advantageous that the reaction rate can be increased. However, in general, the finer the particles, the thinner the capsule wall, so that it is difficult to obtain only weak ones.

[0004]

In view of the above circumstances SUMMARY OF THE INVENTION The present inventors have results of extensive studies, the aqueous phase droplets containing the contents in the water-insoluble salt of the membrane and interfacial polymerization extracorporeal target film The present invention was completed as a result of further research based on the finding that microcapsules encapsulated in a double layer have fine properties and high strength and semi-permeable physical properties. The present invention is, (1) microcapsules aqueous phase droplets containing the contents enclosing at bilayer of the membrane and interfacial polymerization extracorporeal the film in the water-insoluble salt, (2) both the water-insoluble by ion-exchange with a water-soluble Single layer with W / O emulsion containing one of two components capable of forming a salt in a water phase and the other component added in a solid powder state for reaction
The microcapsules are manufactured and then in the oil phase
Characterized by being subjected to a reaction to form an interfacial polymer film
And (3) the oil phase of the W / O emulsion is a high-viscosity oil phase,
The other component is reacted in the presence of a low viscosity solvent.
(2) The method for producing a microcapsule as described above . As the content contained in the aqueous phase droplet, the feature of the present invention is that it has a double film structure as described above, and the target is not particularly limited, but for example, pharmaceuticals, cosmetics, agricultural chemicals , Chemicals, pigments, fragrances, liquid crystals, enzymes, microorganisms, etc. The drug is preferably, for example, a drug for topical administration, and examples thereof include an antitumor agent and a drug for dermis. Examples of the cosmetics include makeup cosmetics, and examples thereof include makeup colorants and pigments.
As the pesticide, for example, a pesticide which is sprayed on a field to remove poisonous insects can be preferably applied. Examples of the chemicals include adhesives. Examples of the coloring matter include pigments, dyes, lipsticks and the like. Examples of the fragrance include deodorants and fragrances.
Examples of the liquid crystal include materials for display. Examples of the enzyme include a drug for local administration and an enzyme that produces a biometabolite. Examples of the microorganism include peptides and antibiotic-producing microorganisms.

The double-layer microcapsules of the present invention can be manufactured, for example, by the following method. First,
A single layer microcapsule is produced. This production is carried out by adding the other component in the form of a solid powder to the W / O emulsion containing one of the two components, both of which are water-soluble and capable of forming a water-insoluble salt by ion exchange, in the aqueous phase and reacted. The aqueous phase droplets referred to in the present invention may contain gas or solid fine particles. As the gas, for example,
Those that are isotopes (those that can be used for detection) are mentioned, and specific examples thereof include hydrogen and carbon dioxide gas. As the solid fine particles, for example,
A magnetic substance (after administration, it is locally concentrated with a magnet) is used. As one of the two components forming a water-insoluble salt by the ion exchange, for example, a salt that is water-soluble and solidifies by contact with a cation can be mentioned. More specifically, for example, sodium silicate, sodium carbonate, sodium pyrophosphate, sodium alginate, potassium silicate, potassium carbonate, potassium pyrophosphate, potassium alginate and the like can be mentioned. Among these, sodium silicate is particularly preferable. Examples of the other component include salts that release cations, and more specific examples include calcium chloride and magnesium chloride. Particularly, calcium chloride is preferably used. The other component is added in a solid powder state, and it is desirable that the solid powder state is as fine as possible, but the size of primary particles (minimum unit of crystal particles) is approximately 1 μm to 500 μm, Preferably about 1 μm
It may be 50 μm. When producing the single-layered microcapsules, it is preferable that the oil phase of the W / O emulsion is a highly viscous oil phase and the other component is reacted in the presence of a low viscous solvent. The highly viscous oil phase preferably has a viscosity of 20 centipoise or more at 20 ° C., and more specifically, liquid paraffin, polyethylene glycol, vegetable oils (coconut oil, palm oil) and the like can be mentioned. To be Among them, liquid paraffin is preferably used. As the low-viscosity solvent, for example, one having a viscosity of 5 centipoise or less at 20 ° C. is preferable, and one having a viscosity of 1 centipoise or less at 20 ° C. is particularly preferable. Specific examples thereof include heptane,
Hexane, pentane, toluene, xylene, ethyl acetate, methyl acetate, methyl chloride, ethyl chloride, acetone,
Examples include methanol and ethanol. Particularly, heptane, hexane and pentane are preferably used.

Under the reaction conditions of the above steps, the water-insoluble salt-forming component present in the aqueous phase is, for example, about 2-6.
It is used at a molar concentration, more preferably about 3-5 molar. The amount of the content contained in the aqueous phase in advance is preferably, for example, about 50% (w / v) or less, more preferably about 1 to 20% (w / v). The highly viscous oil phase is about 2 to 20 times the amount of the aqueous phase (v /
v) is preferably used, and about 3 to 10 times the amount (v /
v) is preferred. The amount of the other component is, for example, about 0.2 to 10 times equivalent to the equivalent of sodium such as sodium silicate and the like, and further about 0.5 to 5 times equivalent. preferable. During this reaction, a surfactant such as a nonionic surfactant (eg, sorbitan monooleate), a cationic surfactant, an anionic surfactant, an amphoteric surfactant, etc. may be added. The amount of the low-viscosity solvent is preferably about 0.2 to 10 times (v / v), more preferably about 0.5 to 5 times (v / v) the amount of the W / O emulsion liquid. ) Is preferably used. The W / O emulsification and single layer microencapsulation reactions described above may be performed, for example, in the range of about 10
It is good to carry out at 40 ° C., preferably about 15 to 30 ° C.

The W / O emulsification and the production of the monolayer microcapsules are carried out by stirring. The machine used for the stirring is not particularly limited,
Examples include propeller type stirrer, ultrasonic type stirrer, magnetic stirrer, jet stirrer stirrer and homogenizer. The stirring conditions are, for example, about 200 to 10 using a magnetic stirrer.
00 rpm, more preferably about 500-1000 r
The purpose of emulsion preparation can be achieved in pm. In the W / O emulsification, the stirring time may be, for example, about 2 to 20 minutes, more preferably 3 to 10 minutes.
The stirring time after adding the other component in the solid powder state is, for example, about 2 to 20 minutes, preferably about 3 to 10 minutes.

[0008] Next subjected to a reaction to form an interface polymer to be film on the outside of one layer of microcapsules, for producing a double-layer microcapsules. The monolayer microcapsules of the raw material to be subjected to the reaction are those produced by the method described above, Miyata et al., Journal of the Chemical Society of Japan, No. 5, 727-7.
Page 31, silicate microcapsules obtained by the method described in 1976, or carbonate microcapsules obtained by the same method, pyrophosphate microcapsules,
Examples include alginate microcapsules. The reaction is interfacial polymer on the outside of the microcapsules in oil phase containing the aqueous phase droplets containing the contents with a water-insoluble salt to be film
It carried out by subjecting the reaction to form the film. The reaction to form the target membrane in the oil phase, for example, (a) the aqueous phase droplets containing the contents as the raw material the microcapsules suspension containing water-insoluble salt to be film, hydrophilic to the liquid The hydrophilic monomer dissolved in a solvent that is highly soluble in the oil phase is added, and the monomer is distributed along with the solvent to the microcapsule surface by stirring, and then the other interfacially polymerized hydrophobic monomer that pairs with the former monomer carried out by advancing the interfacial polymerization reaction, or a microcapsule suspension enclosing water-insoluble salt to be film aqueous phase droplets containing (b) content as a starting material by the addition of the oil phase, the The ability to dissolve the hydrophilic monomer in the interfacial polymerization reaction is inferior to that of water, but the hydrophilic monomer dissolved in a solvent that is compatible with the oil phase is added, and the monomer is added to the surface of the microcapsule. After dispensing by utilizing the difference in solubility to a separatory layer, the other hydrophobic monomers comprising the former monomer pair is performed by adding to the oil phase.

As the above-mentioned interfacially polymerized hydrophilic monomer, for example, diamine and polyhydric alcohol are preferable, and examples thereof include linear alkyldiamine, branched alkyldiamine, aromatic diamine and polyhydric alcohol. More specifically, for example, ethylenediamine, propylenediamine, trimethylenediamine, tetramethylenediamine, pentamethylenediamine, hexamethylenediamine, heptamethylenediamine, octamethylenediamine, nonamethylenediamine, decamethylenediamine, O
-Phenylenediamine, m-phenylenediamine, p-
Examples thereof include phenylenediamine, ε-caprolactam, xylylenediamine, ethylene glycol, 1,2-propylene glycol and diethylene glycol. Among them, hexamethylenediamine is preferable. Examples of the other hydrophobic monomer include acid halides when reacting with diamines and diisocyanates when reacting with polyhydric alcohols. Specific examples of the hydrophobic monomer include oxalic acid chloride, malonic acid chloride, succinic acid chloride, glutaric acid chloride, 1-methylbutanedicarboxylic acid chloride, adipic acid chloride (adipoyl chloride), pimelic acid chloride, and isopimelic acid. Chloride, succinic acid chloride, azelaic acid chloride, sebacic acid chloride (sebacyl chloride), nonanedicarboxylic acid chloride, phthalic acid chloride, terephthalic acid chloride, maleic acid chloride, fumaric acid chloride, terephthalic acid, ethylene diisocyanate, merimethylene diisocyanate, Tetramethylene diisocyanate, pentamethylene diisocyanate,
Examples include hexamethylene diisocyanate, pentamethylene diisocyanate, octamethylene diisocyanate, phenylene diisocyanate, toluidine isocyanate. Of these, adipic acid chloride and sebacic acid chloride are preferable. Examples of the solvent which is used in the reaction (a) and has a high hydrophilicity and which is insoluble in the oil phase include methanol, ethanol, ethylene glycol, diethylene glycol, triethylene glycol and glycerin. Especially ethylene glycol is preferable. Examples of the "solvent which has a lower ability to dissolve the hydrophilic monomer in the interfacial polymerization reaction but is soluble in the oil phase" used in the above reaction (b) include, for example, heptane, dichloromethane, liquid paraffin and the like. Heptane is particularly preferable.

The following are examples of the above reaction conditions. The concentration of the hydrophilic monomer liquid is preferably about 1 to 30% (w / v) with respect to the hydrophilic solvent when a hydrophilic solvent is used (reaction (a)), Especially, about 3 to 15% (w / v) is preferable. When a hydrophobic solvent is used (reaction (b)), the amount thereof is preferably about 1 to 100% (w / v) with respect to the hydrophobic solvent, and particularly about 3 to 15% (w / v). ) Is preferable. The amount of the hydrophilic monomer liquid is about 0.01 to 0.5 times (v / v) the microcapsule suspension amount, and more preferably about 0.05 to 0.2 times the amount (v / v). The range of v) is good. The reaction after addition of the hydrophilic monomer is preferably carried out by stirring, but as the stirrer used,
The same as mentioned above can be mentioned. The stirring conditions include
For example, using a magnetic stirrer, about 200
~ 1000 rpm, more preferably about 500-100
It may be set to be 0 rpm. The reaction temperature is
The temperature is in the range of about 10 to 40 ° C, more preferably about 15 to 30 ° C. The reaction time is in the range of about 2 to 20 minutes, more preferably about 3 to 10 minutes. Then, the microcapsules formed to be film of hydrophilic monomers on the outside of the resulting water-insoluble salt in the film, it is reacted by adding a hydrophobic monomer. At this time, the hydrophobic monomer liquid is, for example, about 1 to 100% (w / v) with respect to the solvent, more preferably about 3 to
Used at a concentration of 15% (w / v). The amount of the hydrophobic monomer liquid is about 0.5 to 5 times (v
/ V), more preferably about 1-2 times the amount (v / v). This reaction is also preferably carried out by stirring, but the conditions thereof, that is, the stirrer, the rotation speed, the reaction time, and the reaction temperature are the same as those when the hydrophilic monomer is reacted.

A single-layer microstructure obtained by a method in which a W / O emulsion containing one of two components, both of which are water-soluble and forms a water-insoluble salt by ion exchange, in a water phase is added to the other component in a solid powder state and reacted. The capsule is formed in a state where fine microcapsules having a dense surface and good monodispersity are dispersed in the oil phase, and the surface of the microcapsule is in a wet state having a thin water layer. Ukoto have a monodispersity is good is a very important characteristic in order to continue subsequently further surface treatment (to modify the surface.) With respect to the microcapsules. For example, in the field of pharmaceuticals, microcapsules need to be designed very delicately, and the secondary surface treatment of microcapsules requires complete treatment for each single particle. It Therefore, if there is agglomeration at the stage before treatment, it cannot be used.

The above method is characterized in that the ion exchange agent is supplied in the solid state instead of being supplied as an aqueous solution. By this method, the ion exchange reaction can be sufficiently promoted as it is with the W / O emulsion, so that the water-soluble capsule contents can be prevented from leaking to the outside. Also the target film having different characteristics from the microcapsules obtained by the conventional methods for also prevented elution of ions generated by the exchange reaction similar to the contents in this way.
That is, in the conventional method dense and smooth microcapsules the film under the influence of the interface formation in the effects and an aqueous solution between the dissolution of ions is difficult to obtain. On the other hand if it is supplied with an ion exchange agent in the solid state microcapsule target membrane surface dense and smooth intended since there is no elution of ions exchanged after formed along the distinct interface of aqueous phase droplets and the oil phase Can be done. Moreover the solubility or more ions can contribute as the membrane reinforcing agent deposited in the capsule as a salt. That can be obtained microcapsules having a target film properties excellent not obtainable when supplying an aqueous solution by feeding ion exchanger in the solid state.

Furthermore, double-layer microcapsules of the present invention, i.e., microcapsules encapsulating an aqueous phase droplets containing the contents in bilayers in the water-insoluble salt to be film and interfacial polymerization extracorporeal target film strength fine Strong, yet interfacial polymer
It has the advantage that impaired nor the film characteristics of the film specific semipermeable. Microcapsules of the present invention, there is handled that strength as well powder, a fine close to that sub-micron order, as the object to be film properties by making microcapsules having semipermeable microcapsules by interfacial polymerization It is possible to increase the value of the microcapsules while expanding the uses of the microcapsules while taking advantage of the fineness. The microcapsules of the invention can be confined within the microcapsules without leaking water soluble content so formed to be film in the oil phase. Especially when trying to obtain fine capsules, this effect is large, and there is a large difference in the encapsulation rate of the contents compared with encapsulation in an aqueous solution.
Together with salts resulting from the ion-exchange reaction to enhance the film deposited in microcapsules, it was also different from the microcapsules salt in aqueous solution was Desa dissolved so increase the osmotic pressure in the microcapsule excellent effect It can be applied to the microcapsules of the present invention.

[0014] Microcapsules of the present invention, there is handled that strength as well powder, a fine close to that sub-micron order has a semipermeable as the film properties. Microcapsules of the composite target film obtained by this method are fine size, high strength, by utilizing the excellent characteristics such as semi-permeable membrane physical properties can be deployed in applications on various industries. For example, in the field of electronic engineering, encapsulation of nematic liquid crystal in the present microcapsule is expected to dramatically enhance the function of a liquid crystal display device as an ideal encapsulated liquid crystal in terms of size, shape, strength and the like. In the field of pharmaceuticals, sustained release microcapsules can be used, and if the agent for periodontitis is enclosed in this microcapsule and added to the toothpaste paste, the size is so small that the periodontal teeth can be easily brushed during brushing. Since the drug is distributed in the pocket and the drug is continuously released, a far superior effect can be expected as compared with the case where the drug is simply added to the paste. Moreover, toxicity to living body is low Te fit poles. In the field of fermentation, if the enzyme is encapsulated in the present microcapsule, it can be used without deactivation even in the organic solvent phase, and since the microcapsule is small, the microcapsule surface area per enzyme unit is large and the reaction rate is fast. Since it is easily dispersed in the reaction substrate and does not easily settle, the reaction can be uniformly progressed throughout the fermentation tank, which is expected to have great advantages. In the field of fibers, if the dye dissolved in water is confined in this microcapsule as it is, it can be made into a pigment with a vivid color tone that cannot be produced with conventional pigments, and since it is small in size and strong, it can be kneaded into fibers as it is. It can be used in a complicated manner.

By encapsulating a water-soluble pesticide in the present microcapsules, it is possible to provide a continuous rainfall-release pesticide that releases the pesticide little by little when it rains. It is especially effective against insects that become more active after rain. By encapsulating pigments in the microcapsules to make up makeup products, it is possible to produce vivid pigment-free colors. In addition, because it is extremely fine and has a high sphericity, it is possible to form smooth powders and creams that spread far better than before, and make highly valuable cosmetics. The microcapsules can be used in various ways as described above. The usage amount is appropriately determined in each case.

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto. Reference Example 1 Formulation Example 1 Tartrazine 50 mg Water glass liquid (1) 1 ml Liquid paraffin liquid (2) 3 ml Calcium chloride liquid (3) 1 ml Heptane liquid (4) 12 ml (1) Composition of water glass liquid Water glass No. 1 21.7 g Water 20 ml (2) Liquid paraffin liquid composition Liquid paraffin 100 ml Span 80 2 g (3) Calcium chloride liquid composition Calcium chloride (ground product) 10 g Liquid paraffin liquid 100 ml (4) Heptane liquid composition Heptane 100 ml Span 80 2 g Prescription example 1 Prepared the ingredients. Tartrazine was dissolved in a water glass solution, added to a liquid paraffin solution, and stirred and emulsified for 5 minutes with a magnetic stirrer at a rotation speed of 500 rpm. Next, a calcium chloride solution was added and stirring was continued for 5 minutes in the same manner. Next, a heptane solution was added and stirring was continued for another 5 minutes to complete the reaction. This was dissolved Tartrazine in water glass solution containing sodium silicate as the film forming agent was an aqueous phase. Tartrazine (Edible dye yellow No. 4)
Was used as water soluble model contents. The liquid paraffin liquid was used as an oil phase having a high viscosity and a high emulsion stabilizing effect. Span 80 is a nonionic surfactant that promotes emulsification.
Stabilized. A fine and stable W / O type emulsion was obtained by stirring. The calcium chloride solution to be added next is an ion exchange agent, and is a suspension of ground calcium chloride in a liquid paraffin solution. Sodium silicate as an object to be film-forming agent in the aqueous phase to form a target layer of deposited calcium silicate calcium to the oil-water interface sodium is replaced by the action of ionic calcium chloride microcapsules. The particle size of calcium chloride is preferably as small as possible, but may be such that it can be suspended and dispersed in a liquid paraffin solution without easily settling. When calcium chloride solution was added and stirring was continued, fine particles of calcium chloride were suspended and distributed in the vicinity of the aqueous phase droplets. Since the viscosity of the oil phase is high, ion exchange due to this operation is suppressed and it is effective in preventing aggregation. It is also a consideration to add the powder in a pre-suspended state as it is, rather than adding the powder as it is, in order to distribute calcium chloride as evenly as possible and prevent unnecessary aggregation. Next, when heptane was added with stirring, the viscosity drastically decreased, the calcium chloride in the vicinity of the water phase water droplets became easy to move, the chance of being taken into the water phase increased greatly, and the ion exchange reaction proceeded at once and was completed in a short time. Strong periods of adhesion in the film formation process is the aggregation of the microcapsules was suppressed since the very short time. Calcium temporarily accumulated in the calcium silicate to be film formed is the sodium ions and chloride ions generated with the ion exchange reaction it means that dissolved in the aqueous phase droplets reactions chloride also increases the osmotic pressure within the capsule . Which further sodium chloride Progress in strengthening of the film deposited on the microcapsule is timed. The target film formation process W / O 100% in theory the added tartrazine as a model contents of the internal aqueous phase to proceed never leaks in the oil phase in the emulsion systems microcapsules in It can be enclosed.

Example 1 Formulation Example 2 Microcapsule suspension (5) 17 ml Hexamethylenediamine solution (6) 1 ml Sebacoyl chloride solution (7) 1 ml (5) Microcapsule suspension The microcapsules obtained in Reference Example 1 Capsule suspension (all liquids) (6) Composition of hexamethylenediamine solution Hexamethylenediamine 5 g Ethylene glycol 100 ml (7) Composition of sebacoyl chloride solution Sebacyl chloride 10 g Chloroform 100 ml Microcapsule suspension obtained in Reference Example 1 Prescription example 2 for liquid
The hexamethylenediamine solution of 1 is added and stirred with a magnetic stirrer at a rotation speed of 500 rpm for 5 minutes, and then the sebacoyl chloride solution is added, followed by stirring for 30 minutes to complete the operation. It may further have to be able to form the secondary of the film used as such in the W / O emulsion under One major feature microcapsule suspension obtained by using ion-exchange reaction of the present invention. When particles having a wet surface in the oil phase is suspended becomes possible to produce a microcapsule having the film structure in complex capable of various target film formed by utilizing the surface properties. It is an example of forming a nylon-film by further interfacial polymerization reaction calcium silicate obtained in Reference Example 1 on the surface of the microcapsules and the film in this example. As an object to be film formed of polyamide nylon 610 by interfacial polymerization reaction of hexamethylene diamine and sebacoyl chloride. Microcapsules their preparation are currently already commercialized to the film of nylon is basically as follows. Which first diamine to obtain an aqueous solution emulsified in the oil phase of W / O emulsion containing, then allowed to interfacial polymerization by adding the oil-water interface of the acid dichloride in the oil phase to form a nylon-membrane around the water phase droplets Is. This method is simple, easy and excellent for producing microcapsules. However, it is difficult to obtain microcapsules taken out from the interfacial polymerization reaction the reaction solution for thick hard the film is formed thick as disadvantages of a strength enough to be handled as a general powder. In addition, since the diamine is uniformly dissolved in the aqueous phase, it may have a bad effect on the contents of the microcapsules. Micro utility value capsules nylon-membrane if overcome these deficiencies are believed to greatly expands. The nuclei or the surface after forming a shell for keep the order first intensity thought be covered by the film of nylon. So that is completed excellent high strength while utilizing the characteristics ideal microcapsules so them if contents diamine effect without addition nylon-membranes for product.

In this example, the manufacturing method was invented based on this idea. In order to realize this, there were the following two major issues. That is, it was possible to obtain microcapsules having high strength as a core efficiently and in a non-aggregated form, and to continuously and forcibly distribute the nylon-polymerized monomer to the surface thereof. The first core microcapsules could be obtained in Reference Example 1 . Regarding the distribution of the second nylon synthesis reagent to the surface of the microcapsules, the following phenomenon leading to a clue of solution was found and applied to this Example 1 . That is, it was found that if a solvent having a high hydrophilicity and incompatible with the oil phase is added and stirred, the microcapsules suspended in the oil phase are easily placed on the wetted and highly hydrophilic surface of the microcapsules. Therefore, if the nylon-polymerized monomer is dissolved in such a solvent, the monomer can be easily and efficiently distributed on the surface of the microcapsules. In the case of this example, ethylene glycol was selected as a solvent satisfying the conditions as a solvent for distributing hexamethylenediamine on the surface of the microcapsules. That is, ethylene glycol in which hexamethylenediamine was dissolved was added to the microcapsule suspension obtained in Reference Example 1 and stirred to cover the surface of the microcapsules with the hexamethylenediamine solution.
As a result, the required concentration of hexamethylenediamine was efficiently distributed to the required sites. Next, sebacoyl chloride dissolved in chloroform was added to the oil phase to cause an interfacial polymerization reaction with hexamethylenediamine on the surface of the microcapsules. The chloroform was used as a solvent for sebacoyl chloride is because been found that a high effect of preventing the microcapsule aggregation tendency at nylon-film formation. Hexamethylenediamine and sebacoyl chloride were selected as typical nylon polymerization monomers. As a result of Example 1 , microcapsules having very excellent characteristics were obtained as follows. It has sufficient strength to handle as a general powder. Very fine about 2
The average particle size is μ. The particle size distribution range is 0.1μ
To 10μ, which is very narrow. Little aggregation. The particle shape has few irregular particles and has a very high degree of spherical shape. The film does not impair the color tone of the transparent content. The film has a semi-permeable membrane physical properties.
The osmotic pressure is high due to the high concentration of sodium chloride or its constituent ions in the microcapsules. Therefore, water is absorbed in water and the microcapsules gradually release the dye contained in the model contents. The manufacturing characteristics of Reference Example 1 and Example 1 are as follows. No expensive equipment is required, and it can be manufactured with a magnetic stirrer. The process and operation are very simple, and it is possible to manufacture by simply adding the reagent with stirring and in a short time. The water-soluble content can theoretically be 100% encapsulated. It is economically advantageous because an expensive nylon-polymerized monomer can be efficiently distributed to a required site.

Example 2 Formulation Example 3 Microcapsule suspension (5) 17 ml Hexamethylenediamine solution (8) 1 ml Sebacyl chloride solution (7) 1 ml (5) Microcapsule suspension The microcapsules obtained in Reference Example 1 Capsule suspension (all liquids) (8) Composition of hexamethylenediamine solution Hexamethylenediamine 5 g Heptane 100 ml (7) Composition of sebacoyl chloride solution Sebacoyl chloride 10 g Chloroform 100 ml Microcapsule suspension obtained in Reference Example 1 Prescription Example 3
Hexamethylenediamine solution (having hexamethylenediamine dissolved at 40 ° C.) was added and stirred with a magnetic stirrer at a rotation speed of 500 rpm for 5 minutes, and then sebacoyl chloride solution was added, followed by stirring for 30 minutes, and the operation was completed. The only difference from Example 1 is the solvent of the hexamethylenediamine solution. However, the way of thinking is completely different. That is, heptane constituting the hexamethylenediamine solution of this example is one of the oil phase components of the microcapsule suspension and completely dissolves in the oil phase. Therefore solubility against the oil phase component of what is distributed throughout hexamethylenediamine also once the oil phase dissolved therein preferentially redistributed in a wet aqueous phase naturally microcapsule surface lower than solubility against water To be done. Therefore, it is desirable to keep the difference in solubility between hexamethylenediamine in the oil phase and water as large as possible. By the way, the hexamethylenediamine solution is 40
Hexamethylenediamine is completely dissolved at 0 ° C, but gradually deposits at 20 ° C. Therefore, when the hexamethylenediamine solution was added, it was warmed to 40 ° C. and added in a completely dissolved state. Hexamethylenediamine spontaneously spontaneously preferentially distributed to the wet aqueous phase on the surface of the microcapsules when left for a while with stirring in this state. Then sebacoyl chloride interfacial polymerization reaction to nylon-membranes on the surface of the microcapsules become hexamethylenediamine and nuclei dissolved in a wet aqueous phase when added to an oil phase is formed. Microcapsules having a composite target membrane structure also has substantially the same characteristics as the microcapsules obtained in Example 1 by this method is obtained.

Example 3 Formulation Example 4 Microcapsule suspension (5) 17 ml Cyanoacrylate solution (9) 1 ml (5) Microcapsule suspension Microcapsule suspension (all solutions) obtained in Reference Example 1 ( 9) Composition of cyanoacrylate liquid Cyanoacrylate 2 g Chloroform 100 ml Formulation Example 4 in the microcapsule suspension obtained in Reference Example 1
The cyanoacrylate solution of was added and stirred with a magnetic stirrer at a rotation speed of 500 rpm for 10 minutes to complete the operation. Reacting the water directly available to cyanoacrylate and microcapsules surface that is the surface of the microcapsules obtained in Reference Example 1 is a wet form to be film. The operation is simpler than the case of forming a nylon-membrane only agitation is continued with the addition of the cyanoacrylate liquid in the oil phase.

Reference Example 2 Formulation Example 5 Tartrazine 50 mg Sodium alginate solution (10) 1 ml Liquid paraffin solution (2) 3 ml Calcium chloride solution (3) 1 ml Heptane solution (4) 12 ml (10) Composition of sodium alginate solution Sodium alginate 1. 5g Water 100ml (2) Liquid paraffin liquid composition Liquid paraffin 100ml Span 80 2g (3) Calcium chloride liquid composition Calcium chloride (ground product) 10g Liquid paraffin liquid 100g (4) Heptane liquid composition Heptane 100ml Span 80 2g Prescription example Prepare the ingredients of 5. Dissolve tartrazine in sodium alginate solution, add this to liquid paraffin solution and use a magnetic stirrer at a rotation speed of 500 rpm for 5
The stirring emulsification was performed for a minute. Next, a calcium chloride solution was added and stirring was continued for 5 minutes in the same manner. Next, a heptane solution was added and stirring was continued for another 5 minutes to complete the reaction. The reference example 1 only changed the water glass liquid to a sodium alginate liquid. The film forming agent is sodium alginate, Reference Example 1
This is the only difference. Other only be <br/> film is calcium alginate also formed for subsequent is exactly the same as in Reference Example 1. The completed microcapsule is for reference
Compared to calcium silicate microcapsules of Example 1 when slight hardness can be used as raw material for to and form also come increasingly those variants in more secondary target film shortage.

[0022]

INDUSTRIAL APPLICABILITY The double-layered microcapsules of the present invention are fine, have high strength and semi-permeable physical properties, and therefore can be advantageously used for liquid crystals, pharmaceuticals and the like.

─────────────────────────────────────────────────── ─── Continuation of the front page (56) References Kenichi Miyata, Yoshiko Nakahara, Surface characteristics of alkaline earth metal silicate spherical particles, Journal of the Chemical Society of Japan, Japan, The Chemical Society of Japan, May 10, 1976. Sun, No. 5, p. 727-731 (58) Fields investigated (Int.Cl. ⁷ , DB name) B01J 13/02-13/22

Claims (3)

(57) [Claims] 1. A water phase droplet containing a content in a water insoluble salt
Microcapsules encapsulating at bilayer of the membrane and interfacial polymerization extracorporeal target membrane. 2. A W / O emulsion which is water-soluble and contains one of two components capable of forming a water-insoluble salt by ion exchange in an aqueous phase, and the other component is added in a solid powder state and reacted.
Produce single-layer microcapsules and then
It is characterized by subjecting it to a reaction that forms an interfacial polymer coating on the outside.
The method for producing a microcapsule according to claim 1, wherein 3. The method for producing microcapsules according to claim 2, wherein the oil phase of the W / O emulsion is a high viscosity oil phase, and the other component is reacted in the presence of a low viscosity solvent.