JPS63182304A - Microcrystalling chitosan and its manufacture - Google Patents

Abstract

PURPOSE:To produce a microcrystalline chitosan having superior uses, by partially hydrolyzing a chitosan in an organic solvent-water-mineral acid system. CONSTITUTION:A chitosan is partially hydrolyzed in an organic solvent-water- mineral acid system to produce a microcrystalline chitosan. The chitosan to be used is one obtained by an deacetylation by alkali treatment of chitin produced by purifying the crusts of a crustacean such as lobsters, crabs, etc., though a flaky chitosan produced by this process is commercially available. Preferably, the organic solvent for use in the acid hydrolysis of the raw material chitosan is one compatible with water, such as alcohole, ketones, etc. Especially, n-propanol, iso-butanol, etc., are preferred. Since these solvents are well compatible with water and have relatively high boiling points, the reaction temperature can be set high, and the reaction time can be shortened.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to microcrystalline chitosan and a method for producing the same. Specifically, the present invention relates to microcrystalline chitosan obtained by removing the amorphous portion of chitosan obtained by separating it from a natural product by acid hydrolysis, and a method for producing the same.

<Prior art> Crystalline natural polymer substances such as cellulose, amylose, chitin, and Clark 9, as well as polyamide, polyester,
Various microcrystalline polymers, such as crystalline synthetic polymers such as lyolefins, obtained by removing the amorphous part by acid hydrolysis and extracting the crystalline part from a substance that has a crystalline part and an amorphous part. The properties and manufacturing method are 0. A. Battist
Author: ``Mi arocrys tal Polymer
5science' McGraw Hill (1
975).

Among these microcrystalline polymers, properties common to hydrophilic polymers are that they can be compression molded and that when an aqueous dispersion of microcrystalline polymers is stirred at high speed under shear, it easily becomes glue-like.

On the other hand, chitin, which is widely distributed in nature as a tissue support for crustaceans and insects, and chitosan, which can be obtained by deacetylating chitin, have recently attracted attention as functional materials in many fields including medical materials. Active research is being carried out.

Since chitosan has free amine groups, it is expected to exhibit various functions as a cationic polymer, but when it comes into contact with an acid, it forms an acid salt and becomes soluble in water.
The above-mentioned microcrystalline polymer production technology cannot be applied, and no prior art has been published to obtain Kitosa 7f microcrystals.

<Problems to be solved by the invention> Even if chitosan is attempted to be acid-hydrolyzed in a heterogeneous system according to the conventional technique, the chitosan will dissolve and become a homogeneous system. Regardless, the monomer unit 2-amino-2-deo-+-/-D-curcose is decomposed, making it impossible to obtain microcrystalline chitosan.

The present invention aims to solve the problems of the conventional techniques as described above, and to provide microcrystalline chitosan with excellent uses and a method for producing the same.

Means for Solving the Problems> The present inventor has discovered that if chitosan is treated with a suitable organic solvent-water-mineral acid system, it is possible to perform acid hydrolysis of chitosan in a heterogeneous system. The present invention was achieved by discovering the fact that this makes it possible to recover the crystalline portion as microcrystalline chitosan.

Microcrystalline chitosan obtained by treating chitosan with a system of organic solvent, water, and mineral acid to remove the amorphous portion is a fine powder.Comparing the physical properties with raw chitosan, the degree of polymerization is low, and it is homogenized and crystallized. It can be seen that the level is increasing.

<Configuration of the Invention> The present invention has an intrinsic viscosity measured using a 1% acetic acid aqueous solution as a solvent in the range of 1.5 to 2.0 dt/g, and an X-ray method crystallinity in the range of 80 to 90%. This invention relates to microcrystalline chitosan characterized by the following.

The present invention also includes: The present invention relates to a method for producing microcrystalline chitosan, which is characterized by partially hydrolyzing chitosan in a system consisting of an organic solvent, water, and a mineral acid.

Chitosan, which is the raw material for the microcrystalline chitosan of the present invention, is obtained by deacetylating chitin obtained by refining the shells of shrimp and crab crustaceans through alkali treatment. It is commercially available.

In the production method of the present invention, the organic solvent used during the acid hydrolysis of raw material chitosan is preferably one that is compatible with water, and alcohols, ketones, etc. are preferable. Especially n-
Gurononol, 1so-prononol, n-butanol + 5ee-butanol.

Particularly preferred are 1so-butanol, tert-butanol, and the like. Since these solvents have good compatibility with water and relatively high boiling points, the reaction temperature can be set high and the reaction can be carried out in a short time.

Examples of mineral acids used in the production method of the present invention include hydrochloric acid.

These include sulfuric acid, nitric acid, and phosphoric acid.

According to a preferred embodiment, the production method of the present invention can be carried out as follows.

Add chitosan and the following substances in the indicated amounts (both chitosan 1
00 parts by weight): Organic solvent 300-1,000 parts by weight water
300-1,000 parts by weight Mineral acid 100-2
00 parts by weight, charged together into a hydrolysis container, and heated to reflux temperature (800 parts by weight).
5-90°C) for 0.5-2 hours. The acid hydrolysis of chitosan is completed by the above treatment. Then, the mixture was cooled to room temperature and separated, and the obtained assembled crystalline chitosan was mixed with the same type of organic solvent 1 used for hydrolysis.
．． 000 parts by weight, stirred at room temperature for 15 to 30 minutes, and then separated.

The finely powdered product is delivered in a wet state. This is microcrystalline chitosan from which most of the attached mineral acids have been removed, and this is mixed with 30 parts by weight of caustic soda, 1.500 parts by weight of water, and an organic solvent (preferably the same type as used for hydrolysis). ) in a solution consisting of 1,500 parts by weight and at room temperature
Stir for ~30 minutes to neutralize the attached acid and the acid added to the amino group. After this, the microcrystalline chitosan is washed with water until the washing solution becomes neutral. After washing with water, the microcrystalline chitosan is dried, and the function of the microcrystalline chitosan depends on the drying method.

Preferred drying embodiments include (1) freeze drying, (
2) drying at a temperature of 50 to 60°C after replacing water with an organic solvent; and (3) spray drying. (1) or (2)
When dried using the method described above, the fine powder is secondary agglomerated and becomes a lump. The desired microcrystalline chitosan can be obtained by crushing the dried block. Usually 90% or more is found as a fine powder with a particle size of 60 μm or less.

<Effects of the Invention> The microcrystalline chitosan obtained by the method of the present invention has compression moldability and can be made into tablets, so it can be used as an excipient and disintegrant for tablets. When used in pharmaceutical tableting, its disintegration properties are superior to microcrystalline cellulose. Also, when microcrystalline chitosan is suspended in water and stirred under high shear, the suspension system becomes viscous and glue-like. It can also be used as an excipient by adding it to foods. Furthermore, when the above-mentioned glue is spread on a glass plate using an applicator and dried, it can be used as a carrier for thin layer chromatography.

<Example> The present invention will be explained in more detail below using examples.

Example 1 Commercially available chitosan flakes (Kyowa Yushi@), [η]
-141, crystallinity 60 coefficient) loOg.

1% acetic acid-isozolopanol (IPA) 524.9, water 60g
, 36 into a mixed solution of 478I of hydrochloric acid, and the reflux temperature (
87° C.) and held for 30 minutes while stirring.

After that, it was cooled and filtered, resulting in assembled crystalline chitosan TL,
000.9 IPA and stirred at room temperature for 30 minutes.

After washing this, total solid content, caustic soda 30.9
, 1,500 g of water, and 1,500.9 g of IPA and treated at room temperature for 30 minutes. After treatment.

After washing with water, replacing with acetone, drying, and pulverizing, microcrystalline chitosan powder ([η], acetic acid ratio = 1.9. Crystallinity: 85 ratio: 1
7011e was obtained.

Example 2 The same chitosan flakes used in Example 1 were treated with the same formulation as in Example 1, except that the hydrolysis time was changed to 1 hour and 30 minutes, and otherwise under the same conditions. Post-treatment, drying, and pulverization were all carried out in the same manner as in Example 1. Microcrystalline chitosan powder ([η
]1% acetic acid" 1.9, crystallinity 87 coefficient 1 particle size: 95
% or more is 60 μm or less) 60 g was obtained.

Example 3 The same chitosan flakes used in Example 1. OO9 was put into a mixed solution of 524.9 g of isozolopanol, 219 g of water, and 319 g of 36% hydrochloric acid, heated to reflux temperature (88° C.), and held for 1 hour while stirring. All subsequent post-treatments were carried out in the same manner as in Example 1, and microcrystalline chitosan powder (
[η) 1% acetic acid = 2-0 = crystallinity 80qb, particle size 90
60 ttm or less) 73I was obtained.

Examples 4 and 5 The microcrystalline chitosan obtained in Example 1 was made into an aqueous suspension, which was stirred with a homomixer at 10.00 Orpm to form a viscous glue. The viscosity of the obtained glue was measured using a B-type viscometer (rotor A: 4.60 rpm, 25° C.). The results are shown in the table below.

Claims (1)

[Claims] The intrinsic viscosity measured using 1.1% acetic acid aqueous solution as a solvent is in the range of 1.5 to 2.0 dl/g, and the crystallinity by X-ray method is in the range of 80 to 90%. Microcrystalline chitosan is characterized by: 2. A method for producing microcrystalline chitosan, which comprises partially hydrolyzing chitosan in a system consisting of an organic solvent, water, and a mineral acid. 3. The method for producing microcrystalline chitosan according to claim 2, wherein the organic solvent is a water-soluble solvent. 4. The method for producing microcrystalline chitosan according to claim 3, wherein the organic solvent is alcohol. 5. The method for producing microcrystalline chitosan according to claim 2, wherein the mineral acid is any one of hydrochloric acid, sulfuric acid, and nitric acid. 6. In the production by partial hydrolysis, the organic solvent is 300 to 1,0 parts per 100 parts by weight of chitosan.
00 parts by weight, 300 to 1,000 parts by weight of water, 100 parts by weight of mineral acid
The method for producing microcrystalline chitosan according to any one of claims 2, 3, 4, and 5, wherein the amount used is 200 parts by weight.