JPS5825497B2 - Microcapsule no seizouhouhou - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an improved method for the preparation of microcapsules, which is based on a significantly different concept from the known microencapsulation methods by phase separation from aqueous systems.

A microencapsulation method is known in which a water-soluble polymer is used as a capsule wall material, and a concentrated phase of the polymer is phase-separated around a core particle by some means to form a capsule wall film. There is.

These can be classified into the following four types.

One of them is the so-called complex coacervation method, which utilizes the fact that when the pH of a mixed system of two types of aqueous solutions, polycation colloid and polyanionic colloid, is adjusted, electrical interaction occurs and phase separation occurs.
coacervation ); :The other one is
When a non-solvent that is not an electrolyte for the polymer and is miscible with water is added to an aqueous solution of a water-soluble polymer, for example, when ethanol is added to an aqueous gelatin solution, the concentrated polymer phase initially separates into droplets. The so-called simple core cell vanecon method (simple c
Another method is to change the pH of the aqueous solution system by taking advantage of the fact that some polymers in the aqueous solution system decrease their solubility and precipitate on either the alkaline side or the acidic side depending on their structure. The other method is to precipitate and insolubilize the polymer in the system by precipitating and insolubilizing the polymer in the system, that is, the polymer insolubilization coacervation method by pH. Utilizing the salting out-like effect that occurs when electrolyte salts are added to an aqueous solution of
This is a so-called salt coacervation method (5altcoacervation) that causes coacervation.

The above-mentioned complex core-cell vane-con method has the drawback that the microcapsules cannot be separated from the system unless the formed capsule wall membrane is made water-insoluble, for example, by formalin, and also requires complicated and difficult-to-control pH adjustment operations. There are disadvantages and the operation takes a long time.

Another drawback is that it can only be operated with dilute solutions, resulting in poor productivity.

In addition, the above-mentioned simple coacervation method has the limitation that the core substance must be insoluble in both water and a non-solvent (non-electrolyte), and furthermore, it is difficult to control the particle size of the capsule. There is a flaw that there is.

Furthermore, in addition to the disadvantage that the polymer insolubilization coacervation method using pH is limited in the structure of the polymer that can be used, the encapsulation rate is too fast, and the pH adjustment operation must be performed very carefully and gradually. There is a cumbersome and disadvantageous operational defect in that it cannot be used.

In addition, in the above-mentioned salt coacervation method, since a considerable amount of electrolyte salts are present in the system, there is a disadvantage that desalination from the formed wall film is required after encapsulation. Another drawback is that it is difficult to control the particle size of the capsules, and the capsules often aggregate to form agglomerates.

The present inventor has overcome the disadvantages and deficiencies of the conventional methods as described above in an operationally advantageous manner, and has achieved a method that allows for easy operation, easy particle size adjustment, no fear of agglomerate formation, and a method that can be used on the rear wall of coacervation. We are conducting research to develop a method that can provide excellent microcapsules with good quality reproducibility and at low cost, without the need for membrane curing means or wall membrane desalting operations after coacervation, and with shortened operation time. I proceeded.

As a result, (b) a hydrophilic sol that has the ability to gel by forming metal bonds with alkaline earth metal ions and trivalent metal ions and has a wall film forming ability; and (d) alkaline earth metal ions. (c) an alkali; Earth metal ions are hydrophilic metals that do not form metal bonds or do not gel even if they do, and have the ability to gel by forming metal bonds with trivalent metal ions and have the ability to form a wall film. The aqueous medium system in which the sol is dissolved forms a stable hydrophilic sol aqueous solution system, and the gelled product particles, which have previously contained a hydrophobic core substance and were gelled by temperature control, are well dispersed. When a stable dispersion mixture system of the above-mentioned gelled product is formed in the above-mentioned hydrophilic sol aqueous solution and the trivalent metal ion-forming water-soluble compound (e) is added to this dispersion mixture system, the above-mentioned various properties are exhibited. It has been discovered that improvements can be achieved and superior microcapsules can be produced.

Therefore, an object of the present invention is to provide a method for producing microcapsules that can achieve the above-mentioned improvements by a method different from those proposed in the past.

Many other objects and advantages of the present invention will become more apparent from the following description.

According to the method of the present invention, in a hydrophilic sol aqueous solution in which the gelling product (a) and the hydrophilic sol (c) coexist in addition to the hydrophilic sol (b) and the water-soluble compound (d), By forming a dispersion of the gelled product, not only a stable dispersion mixture system is obtained, but also rapid insolubility in aqueous medium when a trivalent metal ion-forming water-soluble compound is added to this dispersion mixture system. A combination system of a hydrophilic sol (b) and an alkaline earth metal ion-producing water-soluble compound (a), and a hydrophilic sol (c) and a trivalent metal ion-producing water-soluble compound, in which the formation of metal salts is appropriately controlled. In combination with (e), the inevitable formation of large gelled insoluble metal salts is prevented.

The theoretical details of this inhibition mechanism are not yet clear, but it is speculated that the above-mentioned two groups of insoluble metal salt formation reactions interact with each other in some way in the coexistence of the gelation products. are doing.

As a result of such moderately controlled coacervation, it is possible to advantageously overcome the disadvantages or deficiencies of the various types of microencapsulation methods mentioned above and reproduce the quality of excellent microcapsules with easy operation. It can be provided with good performance and at low cost.

Furthermore, it is virtually impossible to obtain fine microcapsules such as those obtained by the method of the present invention using conventionally known devices and operations such as the orifice method.

Furthermore, if you simply want to adjust phase separation, it should be possible to use stabilizers such as various phosphates and organic acid salts that have been tried in conventional phase separation methods, but these stabilization The agent does not exhibit a usable stabilizing effect in the process of the invention, and its use would lead to disadvantageous prolongation of the operating time and requirement for additional processing to remove the stabilizing side.
It often only comes with disadvantages.

In the method of the present invention, the gelling product of (a) is formed by combining a hydrophilic sol and a hydrophobic core substance that are temperature-gelatable and capable of forming a wall film at a temperature at which the sol does not gel in an aqueous medium. After mixing, the hydrophilic sol is formed by raising or lowering the temperature under stirring conditions to a temperature at which the hydrophilic sol gels, and adjusting the temperature to the gelling temperature.

Specific examples of the above-mentioned hydrophilic sol include compounds that can be mixed at a temperature below the gelling temperature and adjusted to the gelling temperature by raising the temperature to form a gel, such as egg albumin, acrylamide/butyl acrylamide copolymer, etc. and, for example, gelatin; seratin derivatives, such as gelatin adducts with dicarboxylic acids such as succinic acid and maleic acid;
Compounds such as agar that can be gelled by mixing at a temperature higher than the gelling temperature and adjusting the temperature to the gelling temperature by lowering the temperature can be mentioned.

The former and latter groups can be used in combination of multiple types in each group, or other wall film-forming ability that does not form metal bonds with alkaline earth metal ions and trivalent metal ions within the range that can be gelled. It is possible to use a mixture of hydrophilic sols having the following properties.

Such hydrophilic sols include gum arabic; methyl cellulose; polyvinyl alcohol; starch; starch derivatives having no carboxyl group, such as - powdered alkyl or arylalkyl derivatives such as isopropyl, ethyl, benzyl, etc.; textrin; hydroxyethyl cellulose, etc. can be mentioned.

These can be used singly or in combination.

Further, as the hydrophilic sol (b) which has the action of forming a metal bond with an alkaline earth metal ion and a trivalent metal ion to form a gel, and has a wall film forming ability, sodium alginate;
Potassium alginate; polyacrylic acid; sodium polyacrylate
Salts or salts; polyacrylamide partial hydrolyzate salts, such as Na salts; low pectic acid methoxylates: dextran and its sulfuric esters; milk casein; polyethyleneimine and the like.

These can also be used singly or in combination.

Furthermore, it is a hydrophilic compound that does not form a metal bond with an alkaline earth metal ion, or does not gel even if it does, has the ability to form a metal bond with a trivalent metal ion, and has the ability to form a wall film. Specific examples of the sol (c) include carboxymethyl cellulose Na salt or sodium salt; carboxyethyl cellulose:
Carboxymethyl hydroxyethyl cellulose; carboxymethyl starch; hydrophilic starch derivatives having a carboxyl group such as carboxydiethyl starch, and ammonium of polyvinyl alkyl ether-maleic anhydride copolymer;
Salt, etc. can be added to Na.

In the method of the present invention, examples of the alkaline earth metal ion-producing water-soluble compound (d) that is dissolved in the aqueous medium together with the hydrophilic sols (b) and (c) above include Mg, Ca++, Examples include water-soluble compounds that can generate divalent metal ions such as Sra+Ba+10.

The degree of water solubility can be selected as appropriate, and it should be water soluble to the extent that divalent metal ions can be formed in an amount that gives a gelling effect to the hydrophilic sol (b) in cooperation with trivalent metal ions. available.

For example, about 0.1g for 100g of water (0°C)
It is possible to use water-soluble products with a certain degree of water solubility or higher.

Specific examples of these water-soluble compounds (d) include Ca + decahydride calcium hydroxide calcium halide (e.g. calcium chloride), calcium nitrate, carunium citrate, calcium acetate, calcium lactate, calcium cyclamate, carunium adipate, Mg+10 Magnesium chloride (e.g. magnesium chloride), magnesium nitrate, magnesium citrate,
Magnesium acetate, magnesium lactate, magnesium cyclamate, magnesium adipate, barium decahydroxide, barium halide (e.g. barium chloride), barium nitrate, barium acetate, Sr + strontium decahydroxide, strontium halide (e.g. strontium chloride) , strontium nitrate, etc.

In the method of the present invention, the hydrophilic sol (
A dispersion mixture of particles of the gelled product (a) is formed in an aqueous hydrophilic sol solution in which b) and (c) and the divalent metal ion-producing water-soluble compound (a) as described above are dissolved.

The formation of the emulsion described above can be carried out in various addition orders.

For example, hydrophilic alcohols (b), (c) and alkaline earth metal ion-forming water-soluble compound (d) are added in any order and combination to a system in which gelation product (a) is present. be able to.

Conversely, the above (a) can also be added to a system containing (b), (c) and (a) in any order and combination.

Preferably, (b) and (c) are dissolved in any order or together in an aqueous medium and the gelled product (
After adding a) or together with the gelling product (a), the alkaline earth metal ion-forming water-soluble compound (d) is added.

These additions are preferably carried out under stirring conditions.

The amount of water is usually about 5 to about 25 times the total weight of the hydrophilic sols (b) and (c), preferably about 10 to about 2 times the total weight of the hydrophilic sols (b) and (c).
It is about 0 times the amount.

In addition, the amount ratio of the hydrophilic sols (b) and (c) can be appropriately changed depending on the type of these sols used, their combination, the desired concentration of these sols in the oil-in-water emulsion, etc. About 5 to about 20 parts by weight of hydrophilic sol (b) and 100 parts by weight of product (a), about 5 to about 20 parts by weight of hydrophilic sol (
c) Used in an amount of about 5 to about 20 parts by weight.

Also, alkaline earth metal ion-generating water-soluble compound (a)
The amount used can be changed appropriately depending mainly on the amount of hydrophilic sol (b) used.

Usually, per mole of hydrophilic sol (b) as a metal ion,
about 14 to about 1% molar ions, preferably about 1 to about 1
It is on the order of moles and ions.

The amount of the hydrophobic core substance to be used can be appropriately selected depending on the type thereof, the use of the formed microcapsules, the purpose of microencapsulation, etc.

Generally, from about 80 to about 500%, preferably about 100%, based on the weight of the hydrophilic sol used to form the gelled product in (a).
~about 400%.

As the hydrophobic core substance, any substance that is immiscible with water and forms a liquid phase under gelling product formation conditions can be used, including various pharmaceutical substances, fragrances, food additives, dyes, agricultural chemicals, etc. can.

In the method of the present invention, the trivalent metal ion-producing water-soluble compound (e) is added to the dispersion mixture of the gelled product in the aqueous hydrophilic sol solution formed as described above.

The addition is usually carried out under stirring conditions.

It is preferable to add the components gradually and continuously, but if desired, they can be added all at once under sufficient stirring conditions.

The above compound (e) can be added in the form of a finely divided solid, or can be added as an aqueous solution.

The amount of the trivalent metal ion-generating water-soluble compound (e) added is:
The amount can be changed depending mainly on the amount of the hydrophilic sol (c) used, and usually about 1 to 1 h mol ions as metal ions, preferably about 1 mol ion, per 1 mol of the hydrophilic sol (c) as metal ions. It is on the order of moles and ions.

The trivalent metal ion is Fe++ Al-1-+
-1- can be mentioned, and specific examples of these are:
Examples include aluminum chloride, aluminum nitrate, aluminum sulfate, sodium alum AlNa(,SO4)2, potassium alum AIK(SO4)2, aluminum alum, ferric chloride, and the like.

The microcapsules formed can be easily separated by any liquid-solid phase separation means and do not require special means, although spray drying means can be utilized if desired.

Examples now illustrate several aspects of carrying out the method of the invention.

Example 1 10 g of Seratin (200 plumes, freezing point 25.5°C) as a thermogelatable hydrophilic sol (a) was dissolved in 200 TL of warm water at 40°C, and 50p of fragranced lemon oil was emulsified and dispersed as a hydrophobic core substance. do.

This is cooled to 5°C below the freezing point to gel.

On the other hand, 1 g of sodium alginate was used as the hydrophilic sol (b), and carboxymethyl cellulose N was used as the hydrophilic sol (c).
Dissolve 2.9 of salt a in 100 ml of cold water to make a mixed polymer sol, and disperse the lemon oil prepared in advance in (a) to form a gelled product. After dispersion and suspension, 2 g of calunium chloride as the alkaline earth metal ion-forming water-soluble compound (d) is dissolved in a small amount of water and added under stirring conditions.

Next, 4 g of aluminum sulfate as the trivalent metal ion-forming water-soluble compound (e) was dissolved in a small amount of water, and the delivered amount was gradually added under stirring conditions. Phase separation occurred, and the whole became a fine gel. It becomes a dispersed suspension.

Stirring is continued for an additional approximately 30 minutes and upon standing, flavored lemon microcapsules (mainly occupied by approximately spherical particles in the range of approximately 25 to 300 microns) are obtained.

This product can be used as it is in the form of a suspension, after separating the water by an appropriate method such as external filtration, and then drying it.

Example 2 Gelatin (2
Dissolve 65 plume, freezing point 27.5°C) 10,9 and 5 g of gum arabic in 200 Ttl of warm water, emulsify and disperse 50 g of fragrance lavender oil as a hydrophobic core substance, and cool to a suitable temperature below the freezing point to gel. do.

Microcapsules of perfumed lavender (mainly occupied by approximately spherical particles in the range of about 30 to 300 microns) were obtained by dispersing the lavender oil into a gelled product in the same manner as in Example 1 below.

Claims (1)

[Claims] 1 a A hydrophilic sol and a hydrophobic core material that are temperature-gelatable and capable of forming a wall film are mixed in an aqueous medium at a temperature at which the sol does not gel, and then mixed under stirring conditions. The gelled product formed by adjusting the gelling temperature to the following (b) j (C
) and (d), b A hydrophilic salt that has the action of forming a metal bond with an alkaline earth metal ion and a trivalent metal ion to form a gel, and has the ability to form a wall film. What is an alkaline earth metal ion? A hydrophilic sol that does not form metal bonds or does not gel even if it does, has the ability to gel by forming metal bonds with trivalent metal ions, and has the ability to form a wall film, and (d) alkaline earth. Adding a trivalent metal ion-forming water-soluble compound to the dispersion and mixing of the gelled product of (a) above dispersed in a hydrophilic sol aqueous solution containing a similar metal ion-forming water-soluble compound. A method for producing microcapsules.