JPS6328453A - Production of chitosan having anion exchange capacity - Google Patents

Abstract

PURPOSE:To produce a chitosan molding having excellent anion exchange capacity by bringing a compd. having plural nitrogens of a quaternary ammonium salt type and plural reactive groups in the molecule into reaction with the chitosan molding. CONSTITUTION:The compd. I is brought into reaction with the chitosan molding for which low mol.wt. chitosan is used to produce the chitosan molding such as packing material for chromatography and medium for culturing cells. The compd. I has >=2 nitrogens of the quaternary ammonium salt type and >=2 reactive groups in the molecule (where R = ethyl group or methyl group, X = halogen atom, n=2-10). The chitosan molding obtd. in such a manner is insoluble in water, solvents, etc., forms a stable anion exchanger and has a wide range of application.

Description

[Detailed description of the invention]

INDUSTRIAL APPLICATION FIELD The present invention relates to a method for producing a chitosan molded article having anion exchange ability, and the chitosan molded article having an anion exchange ability according to the present invention can be used as a filler for chromatography, a physiologically active substance immobilization material, etc. It is suitable for many uses such as a carrier for medical purposes, a carrier for cell culture, and a carrier for adsorbing heavy metals.

[Prior art 1] In recent years, continuous automation of reaction processes using catalytic action has been progressing in the enzyme/cell utilization industry. In such a process, it is important that the carrier with anion exchange capacity used works completely efficiently.
We still haven't gotten enough. As a method for producing an anion exchanger using chitin/chitosan as a carrier, for example, a method described in Japanese Patent Publication No. 35180/1983 has been proposed. The method disclosed in this publication involves using chitin or chitosan itself as a raw material, contacting it with an alkaline solution, and then bonding it with a condyl halide having a substituted or unsubstituted amino group or @-substituted quaternary ammonium group to perform anion exchange. This is a method for producing a body, which has the disadvantage that it swells or dissolves due to acid or alkali and water during processing, and also has a disadvantage of low ion exchange ability. In addition, the method disclosed in JP-A-61-35180 uses chitosan itself as a raw material, although it is not an anion exchanger, and reacts it with a cationizing agent having quaternary ammonium salt type nitrogen in the molecule. This is a method for producing a cationic chitosan derivative. Furthermore, the present inventors have previously
As the invention of No. 1, a method for producing a chitosan-based anion exchanger is proposed. This method involves dissolving low-molecular-weight chitosan in an acidic aqueous solution, dropping the solution into a basic solution, and crosslinking the obtained porous granular chitosan with a diincyanate compound in a polar solvent. This is a method for producing a chitosan-based anion exchanger obtained by contacting with a solution and reacting with a halide. This invention solves the problem that the ion exchanger swells or dissolves in acid, alkali or water during treatment. In the method described in the above-mentioned publication, since the reaction between chitosan and a reagent into which a quaternary nitrogen-containing group is introduced, which contains only one reactive group in the molecule of any anion exchanger, there is no reaction product. The product does not have a crosslinked structure and has the disadvantage that it dissolves in water or dilute acids due to the strong basicity of the quaternary nitrogen. On the other hand, according to the method described in Japanese Patent Application No. 60-175265, the disadvantage of swelling or dissolving in dilute acids, alkalis, or water could be solved, but the method described in Japanese Patent Application No. 60-175265 solved the problem of swelling or dissolving in dilute acids, alkalis, or water. Because they are bonded together, there is a drawback that the manufacturing process is complicated. Problems to be Solved by the Invention X The object of the present invention is to provide a method for producing a chitosan molded article having excellent anion exchange ability, which solves the drawbacks of the above-mentioned conventional methods. The present invention significantly improves ion exchange ability compared to anion exchangers obtained by conventional methods by bonding quaternary ammonium bases within the chitosan molecules constituting the chitosan molded product. This method solves the above-mentioned drawbacks of the conventional method by producing a molded chitosan product that is insoluble in acids and alkalis and has an anion exchange ability that can be used in a wide range of ion exchange ability ranges. [Means for Solving the Problems] The present invention provides a chitosan molded article using low molecular weight chitosan, which contains at least 2@quaternary, ammonium salt type nitrogen in the molecule, which is represented by the following general formula. This is similar to a method for producing a chitosan molded article having anion exchange ability, which is characterized by reacting a compound (I) having at least two reactive groups. (I) (In the formula (1), R is an ethyl group or a methyl group, X is a halogen atom, and n is an integer of 2 to 10) In the present invention, a low molecular weight with an average molecular weight of 10,000 to 230,000 is used. Chitosan is used. High-quality chitosan having a desired molecular weight can be obtained by heating flaky high-molecular-weight chitosan in an aqueous solution of sodium chloride. Low molecular weight chitosan is acetic acid. Chitosan is dissolved in an aqueous solution of dichloroacetic acid or formic acid alone or as a mixture to form an acidic chitosan solution, and its concentration can be freely selected within a range that is easy to handle, that is, from 2 to 20%. In order to regenerate chitosan from the chitosan acidic solution and obtain a molded article, the acidic solution is dropped into a basic coagulation bath under pressure in a fixed amount through a nozzle with a pore diameter of, for example, 0.1 to 0.25 mm. Kudzu produces fine granular chitosan. In addition, chitosan fibers are obtained by extruding and regenerating a chitosan acidic solution into a basic coagulation bath using a metering pump through a nozzle with a pore diameter of 0.1 to 0.25, and distributing the chitosan acidic solution on a glass plate. A chitosan film can be obtained by regeneration with a basic coagulation solution. All of these molded products are thoroughly washed with water. Basic substances in the coagulation bath include sodium hydroxide, potassium hydroxide, and sodium carbonate. An alkaline substance such as IBM potassium, ammonia, or ethylene diamine is used, and the basic substance is added to water, a polar alcohol such as methanol or ethanol, or a mixture of water and alcohol for the basic solution. The chitosan molded product prepared as described above is reacted with a compound having in its molecule at least two quaternary ammonium salt type nitrogens and at least 2@ reactive groups. As the alkyl bis-(2,3-epoxyprobyl dialkyl ammonium halide) represented by general formula (I), chloride is particularly preferable, such as hexamethylene bis-(2,3 epoxyprobyl dimethyl ammonium chloride), hexamethylene Bis-(2,3 epoxypropyl diethylammonium chloride), propylene bis-(2,3 epoxypropyl dimethyl ammonium chloride), propylene bis-(2,3 epoxypropyl diethylammonium chloride), and the like. As the No. 41 ammonium base introduction reagent, there is alkylene bis-(3-chloro-2-hydroxypropyldialkylammonium halide), which is also preferably a chloride, such as hexamethylene bis-(3-chloro-2-hydroxy propyldimethylammonium chloride), hexamethylenebis-(3-chloro-2-hydroxypropyldiethylammonium chloride),
Examples include propylene bis-(3-chloro-2-hydroxypropyldiethylammonium chloride). However, it is difficult to directly react these with a molded chitosan product, and it is preferable to react the compound represented by the general formula (I) with an equivalent amount of sodium hydroxide or potassium hydroxide in advance. The chitosan molded product obtained as described above and the general formula (I
) in an aqueous solution with a reaction time of 20 to 10
This is carried out by gentle stirring at 0°C, preferably 25-90°C, for 1-24 hours. Further, when the compound represented by the general formula (I) has low solubility in water, it is also possible to add alcohol. Methanol is alcohol. Ethanol, propatool, isopropyl alcohol, etc. are used. The amount of the compound represented by general formula (I) to be used can be appropriately selected depending on the anion exchange ability to be introduced. By thoroughly washing with water after repulsion, a molded chitosan product having excellent anion exchange ability can be obtained.

[Example 1] The present invention will be explained in detail by examples below, but the present invention is not limited to the scope described in the examples. The anion exchange capacity, specific surface area, and degree of swelling of the chitosan molded product having interstitial ion exchange capacity were determined as follows. ◇Anion exchange capacity sample 50rRI! was treated in 500ml of 1N-NaOH for 1 hour with gentle stirring, washed thoroughly with deionized water until neutral, and dehydrated taking care not to absorb carbon dioxide gas in the air. Quickly measure the amount, add it to N1511c 500d, and leave it for 5 hours while stirring gently. This supernatant liquid is used as the test liquid. Ten precepts of this were collected and neutralized and titrated with N/10 to Na leaves using a phenolphthalene solution as an indicator, and the value was determined from the following formula. (b-a) x f x 10x 10CTV (-M
l, Ni/Kai) = Va; N required to neutralize 10 d of test liquid, /10 NaOH amount b: Blank test Same as above f: N/10 Mail titer ■, wet sample hanging (30 resistance) , to convert this to neq/g, 16m1q
Therefore, calculate by multiplying by 16. ◇Specific surface area Measured using a specific surface area measuring device using the 8-day method. ◇rf/Moisture degree Y Swelling degree = 70 Cl of chitosan having a degree of acetylation of 95% and an average molecular size of Φ4f3,000 was dissolved in 3.5% acetic acid aqueous solution 9309. This solution was placed in a mixed solution of 10% Na0Il, 30% ethanol, and 60% water at a diameter of 0.25 m/mφ.
After solidification and regeneration by dropping it through a nozzle with a hole diameter of
It was washed with water until it became neutral, and one piece of porous granular chitosan having an average particle size of about ITIL/m was obtained. To 100 m (1 m wet) of the obtained porous granular chitosan were added 50 ml of water and 209 ml of hexamethylene bis-(2,3-epoxyprobyl dimethylammonium chloride), and the mixture was reacted at 60°C for 4 hours. After the reaction was completed, the mixture was thoroughly washed with water to obtain a porous granular chitosan derivative. The specific surface area of this product was 80.6 nt/9, and the anion exchange capacity was 7.52 ieq/a. After storing this porous granular chitosan derivative at room temperature for 72 hours, the degree of swelling in water, acid, alkali, and solvent was examined. IN-)1cI 0.97. 1 N-NaOH 1.00, methyl alcohol 1.0
0. Acetonitrile 1,06 and 1,4-dioxane 1
．． It was confirmed that they were insoluble in water, vi, alkali, and solvents. Example 2 To 100 parts of porous granular chitosan (wet state) obtained in the same manner as in Example 1, 50 parts of water and hexamethylene bis(3-
3.7 g to 50 g of chloro-2-hydroxypropyldimethylammonium chloride aqueous solution (purity 40%)
of NaOH, add the aqueous solution thoroughly stirred, and add 6
The reaction was carried out at 0°C for 4 hours. After the reaction was completed, the mixture was thoroughly washed with water to obtain a porous particulate chitosan derivative insoluble in water, acid, and alkali. The specific surface area of this product was 78.3 TIt/g, and the anion exchange capacity was 7.2 IIeQ/9. Example 3 7.0 g of chitosan with a degree of deacetylation of 95% and an average molecular weight of 142,000 was dissolved in 93.0 g of a 3.5% acetic acid aqueous solution. After casting this solution on a glass plate, 10% Mail,
It was immersed in a mixed solution of 30% ethanol and 60% water, solidified and regenerated, and thoroughly washed with water until it became neutral, to obtain a regenerated chitosan film with a thickness of 24 μm. This regenerated chitosan membrane is about 500ci! was added to 400 d of a 4% aqueous solution of hexamethylenebis-(3-chloro-2-hydroxypropyldimethylammonium chloride) with 2.979 NaO
The mixture was reacted at 60° C. for 4 hours in an aqueous solution that had been thoroughly stirred with H added thereto. After the reaction was completed, it was thoroughly washed with water to obtain a chitosan derivative film that is insoluble in water, acid, and alkali. The anion exchange capacity of this membrane was 0.01811 eq/d. Example 4 Degree of deacetylation 95%, average molecular fi 170,000
50g of chitosan and 950g of an aqueous solution containing 259 acetic acid
dissolved in This solution was mixed with 10% Na0tl and 30% ethanol. 0.14 m/mφ× in a mixed solution consisting of 60% water
Extrude using a 18011 nozzle, solidify and regenerate,
Regenerated chitosan fibers were obtained by thoroughly washing with water until neutral. This regenerated chitosan fiber 1209 (wet state) was added to 200 d of a 4% aqueous solution of hexamethylene bis(3-chloro-2-hydroxypropyldimethylammonium chloride) and 1.49 d of NaOH (j) added thereto and mixed with sufficient stirring. The reaction was carried out at 60°C for 4 hours. After the reaction was completed, it was thoroughly washed with water to obtain a chitosan derivative S fiber of 3.8 denier (after drying) that was insoluble in water, acid, and alkali. The anion exchange capacity of this fiber was 0. .50℃geq/g (wet fiber)
Met.

【Effect of the invention】

As mentioned above, the chitosan molded article of the present invention having an anion exchange ability obtained by reacting an alkylene bis-(2,3-epoxypropyl dialkylammonium halide) with a chitosan molded article has an anion exchange ability. In particular, the porous particulate chitosan derivative obtained using porous particulate chitosan has an anion exchange capacity of 7.52 neq/g. , 2 neq/g, which is very excellent. Moreover, the chitosan molded product according to the present invention is insoluble in water, acidic solutions, basic solutions, solvents, etc., has a low degree of swelling, and is a stable anion exchanger, so it can be used in a wide range of ion exchange capacity. is possible. Furthermore, the chitosan molded article having anion exchange ability of the present invention has the advantage that the manufacturing process is simple and that it can be easily washed since no solvent is used.

Claims (1)

[Scope of Claims] 1. A compound having at least two quaternary ammonium salt type nitrogens and at least two reactive groups in the molecule represented by the following general formula [I] 1. A method for producing a chitosan molded article having anion exchange ability, which comprises reacting. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [I] (R in the formula [I] is an ethyl group or a methyl group, X is a halogen atom, and n is an integer from 2 to 10.) 2. A method for producing a chitosan molded article having anion exchange ability according to claim 1, which is any one of a spherical body, a membrane-like body, and a fibrous body.