JPH04130101A - Production of carboxymethylalkylcellulose - Google Patents

Abstract

PURPOSE:To obtain the title compound prevented from blocking during the reaction and having a uniform degree of etherification by using a mixture of a plurality of specified metal salts as a metal salt of carboxymethylcellulose in producing the title compound by reacting carboxymethylcellulose with an alkali and an alkyl halide. CONSTITUTION:A process for producing the title compound by reacting carboxymethylcellulose with an alkali and an alkyl halide, wherein a mixture of a sodium salt with a polyvalent metal salt, desirably an alkaline earth metal salt (e.g. magnesium salt) is used as a metal salt of carboxymethylcellulose.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing carboxymethylalkyl cellulose which can be applied to pharmaceutical coating agents and the like.

[Prior art] Conventionally, methods for producing carboxymethylalkyl cellulose include: ■ alkylating sodium carboxymethyl cellulose using an alkyl halide, ■ carboxymethylating alkyl cellulose using sodium monochloroacetate, and ■ simultaneously adding alkyl cellulose to cellulose. There are methods such as reacting two types of etherification agents.

[Problems to be Solved by the Invention] Among the above methods, ■ is the most practical, but in the conventional method, sodium carboxyalkyl cellulose swells in the presence of water necessary for alkyl etherification.
This will cause blocking. For this reason, there were problems in that the penetration of the alkylating agent was poor, uniform etherification was difficult, and the quality of the obtained polymer was also insufficient.

[Means for Solving the Problems] In order to solve the above problems, as a result of intensive studies, the present invention was arrived at. That is, when carboxymethylalkylcellulose is produced by adding an alkali and an alkyl halide to carboxymethylcellulose and causing a reaction, a mixture of a sodium salt and a polyvalent metal salt is used as the carboxylic acid metal salt in carboxymethylcellulose. This is a method for producing carboxymethylalkylcellulose.

In the present invention, the alkali is sodium hydroxide,
Examples include potassium hydroxide, lithium hydroxide, and industrially inexpensive sodium hydroxide.

Examples of the alkyl halide include methyl chloride, ethyl chloride, propyl bromide, benzyl chloride, etc., and methyl chloride and ethyl chloride are preferred from the viewpoint of solvent solubility and cost expected from applications such as coating agents.

As carboxymethylcellulose, a mixture of a sodium carboxylic acid salt and a polyvalent metal salt is used. Polyvalent metals that form salts include magnesium,
Examples include alkaline earth metals such as calcium, and heavy metals such as zinc, copper, and manganese. Alkaline earth metals are preferred from the viewpoint of safety, and magnesium is particularly preferred.

The content of polyvalent metal salt is 0°03 to carboxylic acid.
Preferably, it is 15 equivalent %. If it is less than 0.03 equivalent %, the effect of preventing blocking will be reduced, and if it exceeds 15 equivalent %, the degree of water swelling will be too low and the permeability of the alkyl halide, which is an etherification agent, will be inhibited.

In the method for producing carboxymethylalkylcellulose of the present invention, conventional methods can be used except for using carboxymethylcellulose in which a portion of the carboxylic acid is substituted with a polyvalent metal. For example, (1) Using commercially available sodium carboxymethyl cellulose as a starting material, using a polyvalent metal salt and an alkali, prepare carboxymethyl alkali cellulose partially substituted with a polyvalent metal, and converting it into an alkyl ether using an alkyl halide. ■Using pulp and linter as starting materials,
After reacting with an alkali using sodium monochloroacetate to synthesize carboxymethyl cellulose, adding a polyvalent metal salt to this to prepare carboxymethyl alkali cellulose partially substituted with a polyvalent metal, similarly alkyl Etherification method: Using pulp and linter as starting materials, synthesize carboxymethyl alkali cellulose partially substituted with polyvalent metals using alkali, sodium monochloroacetate, and polyvalent metal salts, and then similarly Examples include a method of alkyl etherification.

Commercially available sodium carboxymethylcellulose is not particularly limited and may be conveniently selected depending on the intended use, but considering the intended use as enteric coating agents, etc., the degree of carboxylic acid substitution (hereinafter abbreviated as S) is 0.4. ~0.7 is preferred.

Examples of the polyvalent metal salt include magnesium acetate, calcium acetate, calcium hydroxide, magnesium hydroxide, etc. Magnesium acetate is preferred because it can be easily removed by washing with water after the reaction.

The amount of polyvalent metal salt added is 0.0 of carboxylic acid polyvalent metal salt.
It may be added to produce 3 to 15 equivalent %.

This amount is set based on the basicity when the metal is a hydroxide and the basicity of the alkali such as sodium hydroxide, potassium hydroxide, etc. used together with the metal.
．． 03 to 30 equivalent%.

Further, a solvent may be used if necessary. Solvents used include aromatic solvents such as toluene and xylene, heptane,
Examples include hydrocarbon solvents such as kerosene, ketone solvents such as methyl ethyl ketone, alcohol solvents such as Impropatol, ethanol, and mixtures thereof. Preferred are methyl ethyl ketone, toluene, and combinations of toluene and Impropatol. Particularly preferred mixtures are methyl ethyl ketone.

[Example] The present invention will be described below with reference to Examples, but the present invention is not limited thereto. In addition, parts represent parts by weight, and unless otherwise specified, % means weight %. Moreover, CPS means centipoise.

Solvent solubility was determined by dispersing 1 part of the product in 9 parts of a methanol/methylene chloride mixture (weight ratio 1/1) and visually evaluating the appearance after 3 hours.

Transparent dissolution: 01 Haze: △, Gel content: x For pH responsiveness, 1 part of the product was dispersed in 10 parts of pinequilpine buffer, and the appearance after 30 minutes was visually evaluated.

Example 1 Using an autoclave, D, S, = o, eo, 1
Partial viscosity: 750CP 30 parts of sodium carboxymethylcellulose (including 0.9 parts of water) of 5180 mesh is dispersed in 150 parts of methyl ethyl ketone, 12 parts of water and an aqueous solution of 1 part of magnesium acetate are added with stirring, and then flakes are added. 22 parts of sodium hydroxide were added. The atmosphere was replaced with nitrogen, and heat treatment was performed at 100° C. for 2 hours to mercerize and simultaneously replace 3 mol% or more of the sodium carboxylate in carboxymethyl cellulose with magnesium salt. After cooling and adding 50 parts of ethyl chloride,
The reaction was carried out at 100°C for 7 hours. After cooling, 13 parts of flaky sodium hydroxide was added and reacted at 100° C. for 7 hours.

The reactant is a slurry without blocking. It is treated with an aqueous sulfuric acid solution in an amount sufficient to convert the reactant into an acid form. Water and methyl ethyl ketone are added to dissolve the product, and at the same time the product is adjusted to a predetermined molecular weight with sulfuric acid. The solvent was recovered under stirring to obtain an aqueous slurry in which carboxymethylethyl cellulose was precipitated. This material was filtered, washed with water, and dried.

Table 1 shows the solvent solubility and pH responsiveness of the obtained carboxymethylethyl cellulose.

Example 2 Instead of sodium carboxymethyl cellulose in Example 1, D, S, = 0.50.1 part Viscosity 400 CPS1
Carboxymethylethylcellulose was obtained in the same manner except that 30 parts of sodium carboxymethylcellulose (containing 0.9 parts of water) of 80 meshes was used. No blocking was observed during the reaction. Table 1 shows the solvent solubility and pH responsiveness of the obtained carboxymethylethylcellulose.

Example 3 Instead of methyl ethyl ketone in Example 1, a mixed solvent of methyl ethyl ketone and Improper Tool (weight ratio 1/1) was used.
0) Carboxymethylethylcellulose was obtained in the same manner except that 30 parts were used. No blocking was observed during the reaction.

The solvent solubility and pH responsiveness of the obtained carboxymethylethylcellulose are shown in Table 1.

Comparative Example 1 Carboxymethylethyl cellulose was obtained in the same manner as in Example 1 except that magnesium acetate was not used.

Blocking was observed during the reaction.

Table 1 shows the solvent solubility and pH responsiveness of the obtained carboxymethylethyl cellulose.

[Table 1] [Effects of the Invention] The method for producing carboxymethylalkyl cellulose of the present invention is a method in which blocking does not occur during the reaction, and it is possible to synthesize a product with a uniform degree of etherification.

Therefore, it is suitable for use in pharmaceutical coating agents and the like.

Claims (1)

[Claims] 1. In producing carboxymethylalkylcellulose by adding and reacting an alkali and alkyl halide to carboxymethylcellulose, a mixture of a sodium salt and a polyvalent metal salt is used as the carboxymethylcellulose metal salt. A method for producing carboxymethylalkylcellulose, characterized by: 2. Polyvalent metal salt has a ratio of 0.03 to carboxyl group
The manufacturing method according to claim 1, wherein the amount is 15 equivalent %. 3. Claim 1, wherein the polyvalent metal salt is an alkaline earth metal salt.
Or the manufacturing method described in 2.