JPH0721062B2 - Chitosan molded article having good water resistance and method for producing the same - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a chitosan-based molded article having good water resistance and a method for producing the same.

[0002]

2. Description of the Related Art Chitosan is 2-amino-2-deoxy-D-
It is a linear basic polysaccharide in which glucose is β-1,4-glucoside linked. To make this industrially, crab,
Natural chitin, which is contained in large amounts in the shells of crustaceans such as shrimp, is completely or partially deacetylated by a concentrated alkali treatment. Chitin is difficult to mold because it is insoluble except for a small amount of solvent such as formic acid, whereas chitosan is soluble in various dilute aqueous acid solutions and can be relatively easily formed into a film, sheet or fiber. Since it can be molded into various materials, such as chemical and biological characteristics of chitosan, in recent years, applied research to functional materials such as biomaterials, drug delivery substrates, separation membranes, and edible films Is actively carried out. As a method of molding a molded product from a chitosan solution,
A so-called drying method in which a dilute aqueous solution of chitosan is dried and solidified to obtain a molded article, a method in which a dilute aqueous solution of chitosan is coagulated in a basic aqueous solution having a pH of 7 or more, and then washed with water and dried (JP-A-56-106901). (See Japanese Patent Publication No. 62-61603), or a method in which a dilute aqueous solution of chitosan is coagulated in an aqueous solution of a divalent metal salt and then treated with a chelating reagent to remove the metal salt in the molded body (see Japanese Patent Publication No. 62-61603). Etc. are known. Of these, a drying method, which is relatively simple in processing operation, is often used.

[0003]

However, since the molded product obtained by the drying method forms a salt with the acid used to dissolve chitosan, it easily dissolves or swells in water as it is, even if it does not dissolve. The strength when absorbing water is extremely low, and cannot be put to practical use. Therefore, in order to remove the acid in the molded product and impart water resistance, the molded product is neutralized with an alkali after drying, and then the salt formed by washing with water and excess alkali are removed (for example, JP-A-55). -81705, JP-A-55-141171, and JP-B-52-41797). However, when attempting to carry out this method industrially, not only the process is complicated, but an extremely large amount of water is required for washing with water, and the wastewater treatment requires a great deal of cost, resulting in High cost of molded products is unavoidable. In addition, this method has a problem that the molded body is largely shrunk and deformed in the washing and subsequent drying steps. The present invention has been made in view of such circumstances, and an object of the present invention is to provide a chitosan molded product which has good water resistance, a simple process, and a low cost, and a method for producing the same.

[0004]

Means for Solving the Problems As a result of intensive studies aimed at achieving the above object, the present inventors have found that a stock solution of chitosan dissolved in an aqueous solution of an organic acid is dried, solidified and molded, and then a water-miscible organic compound. It was found that the organic acid in the molded product can be removed extremely efficiently by washing with a solvent, and a chitosan-based molded product having good water resistance can be obtained, and the present invention has been completed.

The organic acid used for dissolving chitosan in the present invention is not particularly limited and, for example, acetic acid, formic acid, lactic acid, sulfamic acid, toluenesulfonic acid and the like can be used, but they are economical and easy to handle. Acetic acid is preferred. Chitosan is soluble in a dilute aqueous solution of an inorganic acid such as hydrochloric acid and nitric acid, but it is difficult to remove the acid in the molded body by the method of the present invention, and a molded body having water resistance cannot be obtained. It is not possible. Regarding the concentration of this organic acid aqueous solution, the amount of organic acid in the solution is 0.2 to 2 per amino group of chitosan.
A concentration of about the gram equivalent is suitable. If the amount is less than 0.3 gram equivalent, the solubility of chitosan is poor, and if it is more than 1.5 gram equivalent, the acidity of the solution may be high and the hydrolysis of chitosan may be promoted. . Such stock for molding, chitosan was added to an aqueous solution of an organic acid, it can be manufactured by adjusting by stirring dissolved. A suitable concentration of chitosan is 3% by weight or more, more preferably 10% by weight or more. If the concentration is lower than this, the drying time in the molding step becomes extremely long and the productivity is lowered, which is not preferable. It preferred that the <br/> definitive stirred steel stock adjustment performed at a relatively low speed, when multiplied by excessive shear molecular weight of the chitosan is lowered, which may lower the physical properties of the molded article. From this point of view, the stirring is performed at 20 to 200 rpm.

If necessary, additives such as organic and inorganic pigments and dyes, antiseptics such as sodium benzoate, potassium sorbate and calcium propionate, and antifoaming agents such as higher alcohols and silicones are added to the stock solution. be able to. Further, various inorganic or organic fillers and natural or synthetic water-soluble polymers other than chitosan may be added depending on the purpose. As the inorganic filler, calcium carbonate, talc, kaolin, silica, alumina, etc., and as the organic filler, various starch granules such as corn starch, tapioca starch, potato starch, rice starch, powdered or micronized cellulose, etc. The addition of these fillers can be expected to improve the rigidity and dimensional stability of the molded product or reduce the raw material cost. Examples of the water-soluble natural polymer that can be added to the chitosan solution include heat-gelatinized starch, gelatin, agar, carrageenan, and the like, and examples of the water-soluble synthetic polymer include polyvinyl alcohol, polyethylene glycol, methylcellulose, and the like. By adding these, it is expected that the mechanical properties such as strength and flexibility of the molded product, the control of the permeability of various substances, the impartation of thermal adhesiveness, and the like can be expected.

In order to obtain a molded product from this undiluted solution, various methods are adopted depending on the shape of the molded product. For example, in the case of a film, the stock solution is cast onto a stainless steel belt or a chrome-plated rotating drum surface, hot air is blown onto the casting surface to remove water, and then the formed film is peeled from the stainless steel belt surface, etc. Just do it. Also,
By applying the undiluted solution to the surface of a metal mold having a three-dimensional surface by the same method, a molded product such as a medicinal capsule can be obtained. Further, the fiber can be molded by a method of spinning the stock solution through a fine nozzle into hot air. The molded product thus obtained may volatilize a part of the acid used for dissolving chitosan in the drying step, but most of it remains in the molded product, and therefore, in the presence of water, a dilute acid solution is used. Therefore, the water resistance is extremely low. In addition, a large amount of acid remaining may accelerate the hydrolysis of chitosan after molding over time, which may lead to deterioration of the quality of the molded product. In the present invention, the removal of the acid in the molded product obtained by these drying methods can be efficiently achieved by washing the molded product with a water-miscible organic solvent.

In the present invention, examples of the water-miscible organic solvent used for washing include methyl alcohol, ethyl alcohol, propyl alcohol, butyl alcohol, acetone, methyl ethyl ketone, methyl acetate, pyridine and the like. Methyl alcohol, which has a relatively low boiling point, due to the ease of dry removal and recovery of
Acetone is especially preferred. The acid in the molded body can be removed with these water-miscible organic solvents alone, but the acid removal rate can be further increased by adding a small amount of water.
In this case, the amount of water added is 2 to the water-soluble organic solvent.
20% by weight is preferable, and even if the amount of water added is increased more than this, there is no great change in the acid removal rate, and the water resistance strength of the molded product after washing decreases, and the shrinkage also increases. As a method of washing the molded body obtained by the drying method with a water-miscible organic solvent, the method of immersing the molded body in the solvent and stirring is the simplest, but at this time, the solvent is freshly refreshed at regular intervals. If replaced with, the cleaning effect can be further enhanced. It is also effective to apply the Soxhlet extraction method. The organic solvent used for washing can be easily recovered by an ordinary distillation method after neutralizing the acid in the solvent with an alkali and reused, and the economy is also good.

As described above, according to the present invention, a chitosan-based molded article having good water resistance can be economically obtained by a very simple method with a simple operation, and the obtained chitosan-based molded article is obtained. It can be applied to various uses like the conventional chitosan-based molded product.

The present invention will be described in more detail with reference to the following examples.

[0011]

Example 1 12% by weight of chitosan [Flownac C manufactured by Kyowa Technos Co., Ltd.] was dissolved in 4% by weight acetic acid aqueous solution and 6% by weight lactic acid aqueous solution, and then defoamed under reduced pressure to obtain a film forming stock solution. Obtained. This stock solution was cast on a chrome-plated steel sheet heated to 90 ° C. and dried to form a film having a thickness of about 30 μm. Next, the formed film was washed by immersing it in various organic solvents for 2 hours and stirring. At this time, the solvent was replaced with a fresh one every 30 minutes. The washed film was dried to remove the solvent and then immersed in pure water to evaluate the water resistance. For comparison, 12% by weight of chitosan was dissolved in a 2.2% by weight aqueous hydrochloric acid solution and the same treatment as above was carried out to produce a film. Table 1 shows the relationship between water resistance and the types of acid and cleaning solvent used for dissolving chitosan. As is clear from the table, in the film formed by using acetic acid to dissolve chitosan, the film becomes water resistant when washed with a water-miscible solvent, and an unwashed film when washed with a water-immiscible solvent. Similarly dissolved in water.
When hydrochloric acid was used to dissolve chitosan, water resistance could not be obtained by washing with any solvent.

[0012]

[Table 1]

[0013]

[Example 2] A 1.5% by weight aqueous acetic acid solution was added to chitosan [K.
Kyowa Technos: Flownac N low viscosity product] 4.
From the undiluted solution containing 5% by weight, the thickness was about 5 as in Example 1.
A 0 μm film was made. The film was immersed in methyl alcohol, 10% by weight of water-containing methyl alcohol and 10% by weight of water-containing acetone, stirred, and washed for 1 hour or 3 hours while replacing the solvent with a fresh one every 30 minutes. After washing, the film was once dried, immersed in pure water for 24 hours, and then the tensile strength of the film was measured while absorbing water. For comparison, the same film was immersed in a 1% by weight sodium hydroxide aqueous solution for 24 hours to neutralize acetic acid in the film and then washed well with running water, and the tensile strength was similarly measured. Table 2 shows the relationship between the washing conditions and the strength of the film. As shown in the table, the film washed with methyl alcohol alone for 1 hour has a lower tensile strength in a water-absorbed state as compared with the film which is not dissolved in water but is alkali-neutralized. Indicated. In addition, methyl alcohol and acetone containing 10% by weight of water showed the same strength as the alkali-neutralized product even after 1 hour of washing, and it became clear that the washing speed was increased by mixing a small amount of water. It was

[0014]

[Table 2]

[0015]

Example 3 A 4% by weight aqueous acetic acid solution was added to chitosan [K.
12% by weight of Flownac C] manufactured by Kyowa Technos was dissolved, and then the same amount of rice starch powder as that of chitosan was added and dispersed therein to prepare a stock solution for forming a hard capsule for pharmaceuticals.
A capsule mold was dipped in this stock solution, slowly pulled up, and then dried with hot air at 70 ° C. for 30 minutes to prepare a chitosan-based capsule. The film thickness of the capsule was about 80 μm. Next, the capsule was immersed in methyl alcohol containing 5% by weight and 30% by weight of water for 24 hours, stirred and washed, and then air-dried. The capsules washed in this manner had excellent water resistance, whereas those not washed could not retain their shape in water. In addition, when the capsule diameter before and after washing was measured, the shrinkage rate when using 5% by weight of hydrous alcohol was 3.6%, which was slight, but when 30% by weight of water was contained, it showed a large shrinkage of 11.2%. . This is not preferable in the molding of capsules that require high dimensional accuracy, and the water content in the water-containing organic solvent is 2%.
-20% by weight is preferred. In addition, when the same alkali neutralization treatment as in Example 2 was carried out for comparison, the capsules significantly swelled during the alkali treatment, and the deformation was too great to be put to practical use. The chitosan-based capsule is effective as a colon-disintegrating capsule for oral administration of a polypeptide drug or a therapeutic agent for colorectal disease.

[0016]

According to the method of the present invention, it is possible to obtain a chitosan molded product having less shrinkage and good water resistance at a low cost in a short time by a simple operation. Further, the obtained chitosan molded product can be used as a functional material such as a biomaterial, a drug delivery base material, a separation membrane, an edible film, etc., as in the conventional chitosan molded product.

Claims (2)

[Claims] 1. A chitosan-based molding having good water resistance, which is obtained by drying and solidifying a stock solution of chitosan dissolved and dispersed in an aqueous solution of an organic acid, followed by molding and washing with a water-miscible organic solvent. body. 2. A process for producing a chitosan-based molded product having good water resistance, which comprises drying and solidifying an undiluted solution of chitosan dissolved and dispersed in an aqueous solution of an organic acid, followed by washing with a water-miscible organic solvent. Law.