JPH0780921B2 - Microcrystalline chitosan and method for producing the same - Google Patents

Description

TECHNICAL FIELD The present invention relates to microcrystalline chitosan and a method for producing the same. More particularly, it relates to microcrystalline chitosan obtained by removing an amorphous portion of chitosan obtained by separating 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, collagen and the like, and crystalline synthetic polymers such as polyamide, polyester, polyolefin and the like, which are acid-hydrolyzed from substances having a crystalline portion and an amorphous portion. OABattista's "Microcry" describes the properties and manufacturing method of various microcrystalline polymers obtained by removing the amorphous part by removing the crystalline part by
stal Polymer Science "Mc Graw Hill (1975).

Among these microcrystalline polymers, what is common to the properties of hydrophilic polymers is that they can be molded by compression, and that an aqueous dispersion of a microcrystalline polymer can easily become a gel when stirred at high speed under shear.

On the other hand, chitin, which is widely distributed in nature as a tissue support for crustaceans and insects, and chitosan obtained by deacetylating chitin have been attracting attention in recent years as functional materials in many fields including medical materials. Active research is being done. Since chitosan has a free amine group, 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 dissolves in water. Is not applicable, and no prior art for obtaining chitosan as fine crystals has been published.

<Problems to be solved by the invention> According to the conventional technique, even if an attempt is made to acid-hydrolyze chitosan in a heterogeneous system, chitosan is dissolved and becomes a homogeneous system, and the decomposition proceeds, regardless of whether it is a crystalline part or an amorphous part. However, 2-amino-2-deoxy-D-glycose, which is a monomer unit, is decomposed and microcrystalline chitosan cannot be obtained.

The present invention is intended to solve the above-mentioned problems of the conventional techniques and provide a microcrystalline chitosan and a method for producing the same, which have excellent uses.

<Means for Solving Problems> The present inventor can treat acid in a heterogeneous system of chitosan by treating chitosan with a system of a suitable organic solvent, water and a mineral acid. The present inventors have reached the present invention by discovering the fact that it is possible to recover a portion as microcrystalline chitosan.

Chitosan is a fine powder obtained by treating chitosan with a system of organic solvent-water-mineral acid, and removing the amorphous part, and it is a fine powder when compared with the raw material chitosan It can be seen that the degree is high.

<Structure of the Invention> The present invention has an intrinsic viscosity in the range of 1.5% to 2.0 dl / g measured using a 1% acetic acid aqueous solution as a solvent, and an X-ray crystallinity of 80.
It relates to microcrystalline chitosan, which is characterized by being in the range of up to 90%.

The present invention also relates to a method for producing microcrystalline chitosan, which comprises partially hydrolyzing chitosan with 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 purifying crustacean shells of shrimp and crab by alkali treatment, but flaky chitosan produced by this method is commercially available. ing.

In the production method of the present invention, the organic solvent used during the acid hydrolysis of the raw material chitosan is preferably one that is compatible with water, and alcohols, ketones and the like are preferable. Especially n-
Propanol, iso-propanol, n-butanol, sec-
Butanol, iso-butanol, tert-butanol and the like are particularly preferable. Since these solvents have good compatibility with water and also have a relatively high boiling point, the reaction temperature is set high to enable a short reaction time.

Examples of the mineral acid used in the production method of the present invention include hydrochloric acid, sulfuric acid,
Examples include nitric acid and phosphoric acid.

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

The amounts of chitosan and the substances listed below (both chitosan 10
Organic solvent: 300-1,000 parts by weight Water: 300-1,000 parts by weight Mineral acid: 100-200 parts by weight Mix in a hydrolysis vessel at the reflux temperature (85
Stir at ~ 90 ° C) for 0.5-2 hours. The above-mentioned treatment completes the acid hydrolysis of chitosan. Then
The system was cooled to room temperature, and the obtained crude fine crystalline chitosan was added to 1,000 parts by weight of the same type of organic solvent used for the hydrolysis, and the mixture was stirred at room temperature for 15 to 30 minutes and then separated.
A finely divided product is obtained in the wet state. This is a microcrystalline chitosan from which most of the deposited mineral acid has been removed. This is 30 parts by weight caustic soda, 1,500 parts by weight of water, organic solvent (preferably the same type used for hydrolysis).
It is added to a solution consisting of 1,500 parts by weight and stirred at room temperature for 15 to 30 minutes to neutralize the attached acid and the acid added to the amino group. After that, the microcrystalline chitosan is washed with water until the washing liquid becomes neutral. After washing with water, the microcrystalline chitosan is dried. The function of microcrystalline chitosan is affected by this drying method.

Preferred embodiments of drying include (1) freeze-drying,
(2) After substituting water with an organic solvent, it is dried at a temperature of 50 to 60 ° C., and (3) spray drying is mentioned. (1) or (2)
When dried by the above method, the fine powder is secondarily aggregated to form a lump. The desired microcrystalline chitosan is obtained by crushing the lumpy dried product. Usually, 90% or more is obtained as a fine powder having a particle size of 60 μm or less.

<Effects of the Invention> The microcrystalline chitosan obtainable by the method of the present invention has compression moldability and can be formed into tablets, and therefore can be used as an excipient / disintegrant for tablets. The disintegration property when used for tableting a medicine is superior to that of microcrystalline cellulose. Further, when microcrystalline chitosan is suspended in water and stirred under high shear, the suspension system becomes a viscous gel, and therefore it can be added to foods and used as an excipient. Further, the above gel-like material is spread on a glass plate with an applicator and dried to be used as a carrier for thin film chromatography.

<Example> Hereinafter, the present invention will be described in more detail with reference to Examples.

Example 1 Commercially available chitosan flakes (manufactured by Kyowa Yushi Co., Ltd., [η] _1%
100 g of _{acetic acid} = 141, crystallinity of 60%) was added to a mixed solution of 524 g of isopropanol (IPA), 60 g of water, and 478 g of 36% hydrochloric acid, and the mixture was heated to a reflux temperature (87 ° C) and stirred to 30 Hold for minutes. Then, the mixture was cooled, and the crude fine crystal chitosan obtained was put into 1,000 g of IPA and stirred at room temperature for 30 minutes. After passing this, the solid content is 30 g of caustic soda, 1,500 of water.
It was put in a mixed solution of 1,500 g of IPA and treated for 30 minutes at room temperature. After the treatment, it was washed with water, replaced with acetone, dried, and pulverized to obtain fine crystalline chitosan powder ([η] _{1% acetic acid} = 1.9, crystallinity).
70% (85%, particle size 95% or more 60 μm or less) was obtained.

Example 2 The same chitosan flakes as 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 the other conditions were exactly the same. Post-treatment, drying, and pulverization were carried out in the same manner as in Example 1, and microcrystalline chitosan powder ([η]
60% of _{1% acetic acid} = 1.9, crystallinity 87%, particle size: 95% or more and 60 μm or less) were obtained.

Example 3 100 g of the same chitosan flakes as used in Example 1 was put into a mixed solution of 524 g of isopropanol, 219 g of water and 319 g of 36% hydrochloric acid, heated to a reflux temperature (88 ° C.) and kept for 1 hour while stirring. did. Subsequent post-treatment was carried out in the same manner as in Example 1 to obtain 73 g of microcrystalline chitosan powder ([η] _{1% acetic acid} = 2.0, crystallinity 80%, particle size 90% or more 60 μm or less).

Examples 4 and 5 The microcrystalline chitosan obtained in Example 1 was used to prepare an aqueous suspension, which was stirred with a homomixer at 10,000 rpm to obtain a viscous gel. The viscosity of the obtained gel-like material was measured with a B-type viscometer (rotor No. 4, 60 rpm, 25 ° C). The results are shown in the table below.

Claims (6)

[Claims] 1. The intrinsic viscosity number measured with a 1% acetic acid aqueous solution as a solvent is in the range of 1.5 to 2.0 dl / g, and the X-ray crystallinity is
Microcrystalline chitosan characterized by being in the range of 80-90%. 2. A method for producing microcrystalline chitosan, which comprises partially hydrolyzing chitosan with 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. The organic solvent 300 to 1,00 per 100 parts by weight of chitosan used in the production by the partial hydrolysis.
Claims 2 and 3 in which the amount of use is 0 parts by weight, 300 to 1,000 parts by weight of water, and 100 to 200 parts by weight of mineral acid.
Item 6. A method for producing microcrystalline chitosan according to any one of Items 4, 4 and 5.