PROCESS FOR PREPARING CAPSULES

Abstract: Capsules are prepared by bringing a fluid containing a polyanion polysaccharide or its salt as a base into contact with a solution of a soluble chitin derivative solution, particularly chitosan to form a gel membrane around the fluid. Since the capsules are formed under biological, i.e. mild conditions, capsules containing an unstable biological substance in the core solution can be provided.

Description: DESCRIPTION Title of the Invention: CAPSULES AND PREPARATION PROCESS THEREOF Technical Field: This invention relates to capsules making use of a soluble chitin derivative such as chitosan as a wallforming material and their preparation process. Background Art: As preparation processes of capsules, there have conventionally been known to bring a mixture, which has been obtained by adding a multi-valent metal salt such as calcium salt to a fluid material (core liquid) adapted to make up the core parts of capsules, into contact with a solution of an alginate or low methoxy pectin or a mixture thereof so as to form gel-like walls (Japanese Patent Publication No. 16183/1973), to drop with stirring an aqueous solution, which contains .carboxymethylchitin or an N-deacetylated product of a carboxymethylchitin salt, into an aqueous solution of an organic acid anhydride such as a mixed solution of acetic anhydride and acetic acid so as to disperse theformeraqueous solution in the latter aqueous solution (Japanese Patent Laid-open No. 90503/1980), etc. In each of these conventionally known processes, the liquid (core liquid) making up the core parts of capsules have high ionic strength and in addition, the liquid undergoes abrupt changes in its hydrogen ion concentration in the course of formation of capsules. Accordingly, it is difficult to conduct the encapsulation under biologically mild conditions. Hence, such conventional processes are considered to be unsuitable as preparation processes of capsules which serve to enclose a biologically subtle substance therein. Disclosure of the Invention: In the course of a research on the formation of gel-like membranes or walls suitable for the preparation of capsules, the present inventors have found that excellent gel-like membranes or walls can be formed under biologically mild conditions when a solution of chitosan, a chitin derivative, is brought into contact with a solution of a polyanionic polysaccharide or its salt, leading to completion of this invention. Namely, an object of this invention is to provide capsules, which can be formed under biologically mild conditions, and their preparation process. The characteristic feature of this invention is as follow. The characteristic feature of capsules according to this invention reside in that a fluid material, which contains as its base material one of polyanionic polysaccharides and salts thereof or a mixture of two or more of the polyanionic polysaccharides and salts, is enclosed as core parts in gel-like walls formed as a result of contact between the fluid material and a solution of a soluble chitin derivative. On the other hand, the characteristic feature of the preparation process according to this invention resides in that gel-like walls are formed by bringing a fluid material, which is formed of a solution containing one of polyanionic polysaccharides and salts thereof or a mixture of two or more of the polyanionic polysaccharides and salts and is adapted to make up the core parts of capsules, into contact under biologically mild conditions with a solution of a soluble chitin derivative. Best Mode for Carrying Out the Invention: The polyanionic polysaccharides or their salts useful for the formation of the gel-like walls of capsules in the present invention are polysaccharides or--their-salts which-are-converted into polyanionic polymers in aqueous solutions. Low methoxyl pectin, carageenan, carboxymethylcellulose, sodium alginate, chondroitin sulfate and the like may be mentioned by way of example. These polysaccharides may be used either singly or as a mixture. On the other hand, the soluble chitin derivative which is also employed for the formation of gel-like walls is obtained by subjecting chitin, which is an inert substance inherently, to a chemical treatment and hence enhancing its reactivity. As a representative example, may be mentioned chitosan which is obtained by subjecting chitin to an deacetylating treatment. Incidentally, chitin is a straight-chain homopolysaccharide formed of B (1 fez +4)-bonded N-acetyl-Dglucosamine which is contained in cell walls of arthropods such as crabs, Euphausiacea and insects, fungi, etc. It occurs naturally and abundantly. However, it is considered to be an unutilized natural resource because it cannot be used as it is-due to its inert nature. However, chitin derivatives such as chitosan which is obtained by subjecting chitin to a deacetylating treatment have been rendered soluble in mild acids and have hence been imparted with reactivity. Namely, chitosan has a structural unit represented by the following general formula (I): EMI4.1 is charged in positive owing to the amino group contained in its formula, contains chitosan molecules as a polycationic polymer, and shows reactivity. Accordingly, when an aqueous solution of the above-described polyanionic polysaccharide or its salt or a mixture thereof is brought into contact with a solution of chitosan as the above-described soluble chitin derivative, an ionic crosslinking reaction, in other words, ionic crosslinking bonding takes place between the polyanionic polysaccharide and chitosan to form a gel-like substance. In order to achieve the contact between both of the above-described solutions in the present invention, it may be preferred to add dropwise and with stirring an aqueous solution containing the above-mentioned polyanionic polysaccharide or its salt into a chitosan solution by means of a depositor or the like. Upon the dropwise addition, the above-described crosslinking reaction takes place. Once gel-like walls have been formed by the crosslinking reaction, the solution enclosed in the walls and making up the core parts does mot undergo any gellation, thereby obtaining desired capsules. Such a phenomenon may be attributed to such an assumption that once gel-like walls have been formed, the polyanionic polymer (i.e., core liquid) enclosed within the walls and chitosan molecules contained in the solution can no longer penetrate through the walls and the reaction is hence not allowed to proceed any longer in the core liquid. Upon preparation of a solution adapted to be used as a fluid material for making up the core parts of capsules, it is suitable to prepare an aqueous solution containing 0.3 - 1.0 wt.% of the polyanionic polysaccharides or salt or the mixture thereof in the present invention. It is particularly preferred to use caboxymethylcellulose as the polyanionic polysaccharide from the standpoint of formation of gel-like walls. On the other hand, the chitosan solution to which the above aqueous solution is brought into contact is suitably a solution obtained by dissolving chitosan to a concentration of 0.5 - 1.0 wt.% in a mild acid such as acetic acid. As mentioned above" the present invention permits the formation of gel-like capsule walls under extremely mild conditions, namely, biologically mild conditions and in a short period of time without using an organic solvent or the like. It is thus possible to add and disperse subtle biological substances or functional substances and various other additives, which may be chosen depending what end use will be made of the resulting capsules, to the above-described fluid material adapted to form the core parts of the capsules. Hence, the present invention can provide capsules which enclose a core liquid containing various useful substances therein. Furthermore, the present invention can achieve encapsulation, which depends on the formation of gel-like walls, in one step. This invention is therefore considered to be more advantageous from the viewpoint of preparation, compared with the known encapsulation process making use of the salt-formingcrosslinking between polyanions and polycations disclosed for example in Japanese Patent Laid-open No. 197031/1982. In addition, the present invention also allows to change the permeability of the gel-like walls of capsules by controlling certain conditions for the formation of the gel-like walls thereby imparting a fractional function to the gel-like walls. As has been described above, the present invention has a merit that it can provide capsules, which can be used for a wide variety of applications, using a readily-available material, with simple preparation means, and in a short period of time. Examples will be given below to describe the present invention more specifically. Example 1: A 0.5 wt.% aqueous solution of chitosan was prepared by adding chitosan to an aqueous solution which contained 0.28 mole/liter of acetic acid and 0.037 mole/liter of sodium acetate. While stirring the aqueous chitosan solution at a temperature of 250C, a 1 wt.% aqueous solution of k-carageenan which solution had been prepared on the side was dropped under pressure to the former solution through a syringe needle having an inner diameter of 0.4 mm. In 2 - 3 minutes after the contact of both solutions subsequent to the dropwise addition, spherical capsules of 2 - 3 mm in diameter were formed. The walls of the thus-obtained capsules were transparent, and their wall thicknesses were measured to be 10 - 20 pm by an optical microscope. Even when those capsules were left over for a long period of time in water, the core liquid enclosed with the capsules exhibited stable fluidity and no changes were observed thereon. Example 2: Following the procedure of Example 1, spherical capsules of about 4 mm in diameter were formed by aropping at a temperature of 350C a 0.8 wt.% aqueous solution of carboxymethylcellulose, which had been prepared on the side, to an aqueous chitosan solution prepared in the same manner as in Example 1. The walls of the thus-obtained capsules were transparent, and their wall thicknesses were measured to be 2 - 3 pm by a scanning electron microscope. In addition, it was also recognized that the strength of the walls per se was considerably high. The core parts enclosed within the capsules maintained stable fluidity even when the capsules were left over for a long period of time in water.

Claims: CLAIMS 1. Capsules comprising gel-like walls formed as a result of contact between a fluid material, which contains as a base material thereof one of polyanionic polysaccharides and salts thereof or a mixture of two or more of the polyanionic polysaccharides and salts, and a solution of a soluble chitin derivative, and the fluid material enclosed as core parts within the gel-like walls. 2. A process for preparing capsules, which comprises bringing a fluid material, which is formed of an aqueous solution containing one of polyanionic polysaccharides and salts thereof or a mixture of two or more of the polyanionic polysaccharides and salts and adapted to form the core parts of the capsules, into contact under biologically mild conditions with a solution of a soluble chitin derivative, whereby to form gel-like walls.

Inventors: HAYASHI, HIROMICHI, KAKO, MASATOSHI, KIMURA, TOSHIAKI, SHIINOKI, YASUHIKO 1-203, TOEI KITASHINAGAWA, SHIOYA, TOSHIAKI
Applicants: SNOW BRAND MILK PRODUCTS & CO., LTD.
Application year: 1985
Main classification: B01J13
IPC codes: B01J13, A61K9