JPS5810131B2 - Microcapsule Seizouhou - 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 (corltpl), 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 interactions occur and phase separation occurs.
ex coacervation); the other one is
Adding to an aqueous solution of a water-soluble polymer a non-solvent that is a water-miscible non-electrolyte for the polymer, e.g.
The so-called simple coacervation method utilizes the phenomenon that when ethanol is added to an aqueous gelatin solution, the concentrated polymer phase first separates into droplets; A method of precipitating and insolubilizing the polymer in the aqueous solution system by changing the pH of the aqueous solution system, taking advantage of the fact that some polymers precipitate with reduced solubility on either the alkaline side or the acidic side depending on their structure. , i.e., polymer insolubilization coacervation method by pH; and the other method is a salting-out method that occurs when electrolyte salts are added to an aqueous solution of a water-soluble polymer, such as the phase separation of an aqueous gelatin solution by sodium sulfate. The so-called salt coacervation method (5alt coaseryation) uses the effect to cause coacervation.
It is.

The above-mentioned complex coacervation method has the drawback that the microcapsules cannot be separated from the system unless the formed capsule wall membrane is made water-insolubilized with formalin, and it 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, (a) a hydrophilic sol having wall-forming ability that does not form metal bonds with alkaline earth metal ions and trivalent metal ions; (b) a hydrophilic sol that does not form metal bonds with alkaline earth metal ions; (c) a hydrophilic sol that does not gel even when formed, has the action of gelling by forming metal bonds with trivalent metal ions, and has the ability to form a wall film, and (c) an aqueous solution capable of producing alkaline earth metal ions. in an aqueous medium in which a chemical compound is dissolved,
(d) react with the water-soluble compound of (c) above to form a water-insoluble salt; When the resulting trivalent metal ion-producing water-soluble compound is added, the hydrophilic sol of (b) and the trivalent metal ion-producing water-soluble compound of (d) form a water-insoluble metal salt. As a result, co-aggregation of the hydrophilic sol (a) occurs, and during this co-aggregation, the trivalent metal ion-producing water-soluble compound of (d) above has the ability to generate alkaline earth metal ions of (c). We speculate that this may be related to the fact that it can react with water-soluble compounds to form water-insoluble salts, and this water-insoluble salt-forming reaction advantageously prevents the agglomeration caused by co-aggregation. It has been discovered that superior microcapsules can be produced which exhibit useful effects and achieve the above-mentioned improvements.

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, moderately controlled coacervation occurs, resulting in easy operation, advantageously overcoming the disadvantages or deficiencies of the various types of microencapsulation methods described above, and producing excellent microencapsulation. Capsules can be provided with good quality reproducibility and at low cost.

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

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 present 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 hydrophilic sol (a) having a wall film-forming ability that does not form metal bonds with alkaline earth metal ions and trivalent metal ions dissolved in the aqueous medium includes gelatin; gelatin derivatives such as gelatin; Dicarboxylic acid adduct rings such as succinic acid and maleic acid; gum arabic;
Methyl cellulose: polyvinyl alcohol; starch; starch derivatives having no carboxyl group; examples include alkyl or arylalkyl derivatives of starch such as methyl, ethyl, isopropyl, pendel, etc.; dextrin, hydroxyethyl cellulose; albumin.

These can be used alone or in combination.

In addition, a hydrophilic sol that does not form a metal bond with an alkaline earth metal ion or does not gel even if it does form, 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 (b) include hydrophilic starch derivatives having a carboxyl group such as carboxymethyl cellulose Na salt or salt; carboxyethyl cellulose; carboxymethyl hydroxyethyl cellulose; carboxymethyl starch; carboxyethyl starch, and polyvinyl alkyl ether-maleic anhydride. Copolymer ammonium, Na
, K salt, etc.

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

The degree of water solubility can be appropriately selected, and it can be used as long as it is water soluble to the extent that it can form a water-insoluble salt with the trivalent metal ion-forming water-soluble compound (d).

For example, those having a water solubility of about 0.1.9 (0°C) or higher relative to 101 water can be used.

Specific examples of these water-soluble compounds (c) include ca+ calcium hydroxide, calcium halides (e.g. calcium chloride), calcium nitrate, calcium citrate,
Calcium acetate, calcium lactate, calcium cyclamate, calcium adipate, Ba + barium decahydroxide, barium halide (e.g. barium chloride), barium nitrate, barium acetate, sr++ strontium hydroxide, strontium halide (e.g. strontium chloride), nitric acid Strontium, etc. can be mentioned.

In the method of the present invention, the hydrophilic sol (
An oil-in-water emulsion in which hydrophobic core material particles are dispersed is formed in an aqueous medium in which a) and (b) and the alkaline earth metal ion-producing water-soluble compound (c) as described above are dissolved.

The formation of the emulsion described above can be carried out in various addition orders, in which the hydrophilic sols (a), (b) and the alkaline earth metal ion-generating water-soluble compound (C>) and the hydrophobic core substance are added in any order and Can be added in combination.

Preferably, the hydrophilic sols (a) and (b) and the alkaline earth metal ion-generating water-soluble compound (c) are dissolved in an aqueous medium in any order or together, and the hydrophobic core substance is added to this system. Added.

It is preferable to add the stiff flour under stirring conditions.

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

In addition, the amount ratio of the hydrophilic sols (a) and (b) 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. For 100 parts by weight of sol (a),
The hydrophilic sol (b) is used in an amount of about 5 to about 40 parts by weight.

Also, an alkaline earth metal ion-generating water-soluble compound (c)
The amount used can be appropriately changed depending mainly on the amount of the trivalent metal ion-producing water-soluble compound (d) used.

Usually, the amount of metal ions is about 0.5 to about 2 mol ions, preferably about 0.5 to about 1 mol ions, per 1 mol of the trivalent metal ion-producing water-soluble compound (d).

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.

Usually about 80 to about 500%, preferably about 100 to about 400% based on the total weight of hydrophilic sols (a) and (b)
That's about it.

The formation of the above oil-in-water emulsion consists of a hydrophilic sol (a)
can be carried out at any temperature that does not cause thermal gelation of
Although it is customary to carry out at room temperature, suitable heating temperatures may be employed if desired, or cooling conditions may be employed if the core material is a highly volatile material.

As the hydrophobic core substance, any substance that is immiscible with water and forms a liquid phase under oil-in-water emulsion forming conditions can be used;
Various medicinal substances, fragrances, food additives, dyes, agricultural chemicals, etc. can be mentioned.

In the method of the present invention, the trivalent metal ion-producing water-soluble compound (d) is added to the oil-in-water emulsion formed as described above.

The addition is usually carried out under stirring conditions.

The addition is preferably carried out in portions or continuously and gradually, but if desired, it can be added all at once under conditions of sufficient stirring.

The above compound (d) 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 (d) added is:
It can be changed appropriately depending mainly on the amount of the hydrophilic sol (b) used, and usually about 1 to 1 real mole ions, preferably about 100 to 100 mol ions, per 1 mole of the hydrophilic sol (b) as metal ions.
It is about 1 mole ion.

Trivalent metal ion-forming water-soluble compounds that can react with the above-mentioned water-soluble compound Cl to form water-insoluble salts include aluminum sulfate, aluminum alum, ferric sulfate,
Mention may be made of compounds selected from sulfates containing iron and/or aluminum metals, such as iron alum, etc.

The microcapsules formed can be easily separated by any liquid-individual separation means and no special means are required, although spray drying means can be utilized if desired.

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

Example 1 10.9 g of gelatin as hydrophilic sol (a) and 2 g of carboxymethyl cellulose Na salt as hydrophilic sol (b)
was dissolved in 200 ml of water to make a mixed polymer sol, and to this was added 2 g of calcium chloride dissolved in a small amount of water as an alkaline earth metal ion-forming water-soluble compound (C). An oil-in-water emulsion is prepared by emulsifying and dispersing 70 g of lemon oil as a core substance.

Next, a trivalent metal ion-forming water-soluble compound (d) that can react with the water-soluble compound of (c) above to form a water-insoluble salt.
When aluminum sulfate 41 is dissolved in a small amount of water and the same amount is gradually added under stirring, the whole undergoes phase separation and becomes a suspension in which fine gels are dispersed.

Stirring is continued for an additional 30 minutes to obtain flavored lemon microcapsules (mainly comprised of approximately spherical particles in the range of about 20 to 300 microns).

This product can be used as is or after dehydration using an appropriate method.

Example 2 A mixed polymer sol was prepared by dissolving 10 g of gum arabic and 3 g of gelatin as the hydrophilic sol (a) and 2 g of carboxymethyl starch Na salt as the hydrophilic sol (b) in 200 ml of water. Add 2 g of calcium chloride dissolved in a small amount of water as an alkaline earth metal ion-generating water-soluble compound (C), and then emulsify and disperse 30 g of fragrant orange oil as a hydrophobic core substance to make an oil-in-water emulsion. .

Next, a polyvalent metal ion-forming water-soluble compound (d) that can react with the water-soluble compound of (c) above to form a water-insoluble salt.
When 4 g of aluminum sulfate is dissolved in a small amount of water and gradually added under stirring, phase separation occurs in the same manner as in Example 1, resulting in a fine gel-dispersed suspension. (occupied by approximately spherical particles in the range of 20-300μ).

Claims (1)

[Scope of Claims] 1(a) A hydrophilic sol having wall-forming ability that does not form metal bonds with alkaline earth metal ions and trivalent metal ions; (b) Forms metal bonds with alkaline earth metal ions. (c) alkaline earth metal ions; and (c) alkaline earth metal ions. (d) iron capable of reacting with the water-soluble compound of (c) above to form a water-insoluble salt; and/or a method for producing microcapsules, which comprises adding a trivalent metal ion-generating water-soluble compound selected from aluminum metal-containing sulfates.