JPS6355525B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for purifying and granulating oxycarboxylic acid type cellulose derivatives. In this application, the oxycarboxylic acid type cellulose derivative is defined as follows. At least a portion of the three hydroxyl groups per glucose skeleton of cellulose or hydroxyalkylcellulose are selected from carboxyalkyl ether groups (-OCnH ₂ nCOOH), half-ester groups based on dibasic carboxylic acids, and ether groups (-OCnH _2o+1 ) Cellulose derivative substituted with one selected from ester groups (-OOCR).
However, alkyl is an alkyl having 1 to 5 carbon atoms, and n is 1.
~5, and R represents an alkyl or higher fatty acid residue having 1 to 5 carbon atoms. Examples of the oxycarboxylic acid type cellulose derivatives include cellulose ethers, cellulose esters, and cellulose ether esters. The term ether group or ester group refers to an atomic group introduced into cellulose through etherification or esterification of cellulose, and examples of the ester group include acetate, propionate, butyrate, and higher fatty acid ester. Therefore, examples of oxycarboxylic acid cellulose derivatives include carboxyalkylalkylcellulose mixed ethers such as carboxymethylethylcellulose, carboxyethylmethylcellulose, and carboxypropylmethylcellulose, hydroxypropylmethylcellulose succinate,
Hydroxypropyl methylcellulose phthalate, acid succinoyl and acid phthaloyl mixed esters of hydroxypropyl methylcellulose,
Included are cellulose mixed ether esters such as acidic succinoyl and propionate esters of hydroxypropyl methylcellulose, cellulose mixed esters such as cellulose acetate phthalate, and cellulose acetate succinate. When such oxycarboxylic acid type cellulose derivatives are used as enteric coating agents, they are naturally required to not dissolve in gastric juices but to dissolve quickly in intestinal fluids, and they also require chemical resistance over time. It is required that no physical changes occur and that a highly flexible and uniform coating film is formed. Previously, cellulose acetate phthalate, a type of cellulose mixed ester, had been frequently used for this purpose, but there were problems such as it hydrolyzed over time and did not perform its original function, so it was used to improve its hydrolysis resistance. Various new enteric coating agents have been proposed. From this point of view, a method in which the substituents bonded to cellulose are chemically stable ether bonds with the main purpose of improving hydrolysis resistance, for example, Japanese Patent No. 649218
The carboxyalkyl cellulose derivatives described in Japanese Patent Publication No. 57-48530 have been proposed;
Hydroxypropyl methylcellulose phthalate is a type of cellulose ester derivative that is generally thought to have problems with hydrolysis, but has improved hydrolysis resistance. Acidic succinoyl and acidic phthaloyl mixed esters of cellulose ethers described in JP-A No. 57-63301 and acidic succinoyl and aliphatic monoacyl mixed esters of cellulose ethers described in JP-B No. 57-25008 have been proposed. It has reached the point where However, although each of these proposed base materials is effective in improving the problems of conventional products, the reality is that they do not necessarily fully satisfy the expected performance. Inconvenient phenomena sometimes occur, such as formation of gel-like insoluble matter, cracking of the coating film due to insufficient film-forming ability, and furthermore, delay in enteric coating. The present inventors have focused on this phenomenon and have conducted extensive studies. As a result, although the chemical structure of the cellulose derivative varies, it is basically an oxycarboxylic acid type cellulose derivative, and because of this, ester bonds such as lactones are bonded during the manufacturing process or during storage. We found that the formation of is one of the main factors of alteration. Such a phenomenon is observed in alginic acid, which is a typical oxycarboxylic acid, and there is also a report that one carboxyl group in four uronic acids forms a lactone (Tomoo Miwa, Nikka, 51 , 738
(1930)). By the way, it goes without saying that when an oxycarboxylic acid type cellulose derivative undergoes deterioration due to esterification of lactone, etc., its enteric properties are reduced due to a decrease in the effective carboxyl group content. Problems such as a decrease in solubility in a coating solvent, an increase in solution viscosity, and a decrease in film-forming ability during coating occur due to bonding. The present inventors have grasped the main deterioration mechanism of the oxycarboxylic acid type cellulose derivative, reviewed the manufacturing process, and conducted intensive studies to prevent inconvenient deterioration, and as a result, have completed the present invention. That is, the production process of the oxycarboxylic acid type cellulose derivative includes at least one step of treatment under acidic conditions, and ester formation is a very serious cause of deterioration. Therefore, it is effective to relax the treatment conditions under acidic conditions in the manufacturing process as much as possible. The method of the present invention was developed after considering these points as the main focus, and the ester-forming part of oxycarboxylic acid is hydrolyzed into an oxycarboxylic acid salt when dissolved in an alkali, and the oxycarboxylic acid form is converted into an oxycarboxylic acid salt under the mildest possible conditions. The main objective is to express the original physical properties that can be expected from the molecular design. It is a well-known fact that it is possible to dehydrate and separate solid-liquid by heating a hydrogel of an oxycarboxylic acid type cellulose derivative, but as mentioned above, the main point of the present invention is to The point is that lower alkanol having 1 to 3 carbon atoms or acetone is allowed to coexist with the product, and this is effective in greatly easing dehydration conditions such as lowering the dehydration temperature, and can also greatly improve quality deterioration. It is in. This is the first gist of the present invention. The basic substance used in the present invention may be any substance as long as it can solubilize the oxycarboxylic cellulose derivative in water, but in order to effectively carry out the present invention, it is necessary to effectively dissolve the ester bond during alkali dissolution. Hydrolysis is also important, and from this point of view, when refining highly denatured products with a high degree of ester formation, it is better to use caustic alkalis such as caustic soda rather than amines such as ammonia as the basic substance. preferable. This is the second gist of the invention. There is no particular restriction on the amount of the basic substance used at this time as long as it is at least an amount sufficient to water-solubilize the oxycarboxylic acid cellulose derivative; Amount or double the amount is sufficient. Needless to say, in order to carry out the present invention more advantageously, it is effective to sufficiently hydrolyze the esterified oxycarboxylic acid, and therefore, the alkaline dissolution conditions are also an important factor. However, since this varies depending on the hydrolysis resistance of the base material used, the degree of esterification modification, etc., it cannot be stated unconditionally, but generally, treatment at room temperature for about 0.5 hours to 24 hours is sufficient. Incidentally, if a water-soluble base salt of an oxycarboxylic acid cellulose derivative is available, it may be dissolved in water to form an aqueous solution. The acid used to dissolve the oxycarboxylic acid type cellulose derivative may be any acid stronger than the cellulose derivative, and may be arbitrarily selected from inorganic acids such as sulfuric acid and hydrochloric acid, and organic acids such as formic acid and acetic acid. can. The system from neutralization to dehydration treatment is weakly acidic,
It goes without saying that in order to prevent deterioration during this time, it is important to carry out the treatment in as short a time as possible. By carrying out the present invention based on the two main points of the present invention described above, it becomes possible to fully exhibit the performance that can be expected from the molecular design of each base material. However, the above two contents alone may not necessarily result in satisfactory commercial value in terms of practical commercial value, that is, in cases where a product with a high degree of whiteness is required, or in cases where powder is disliked as a product form. may not be given. Regarding the first problem, the whiteness of the product, the method of the present invention is basically a purification method that goes through an alkali dissolution step, and depending on the conditions, the whiteness of the product may decrease, so a high whiteness is required. In some cases, it may be necessary to perform some bleaching treatment. The present inventors have conducted intensive studies on bleaching methods in order to meet such demands, and have found that chlorites such as sodium chlorite or hydrogen peroxide are effective as bleaching agents, and that the oxidation It has been found that bleaching can be easily carried out by coexisting with a bleaching agent, and there is almost no deterioration in quality. This is the third gist of the present invention. At this time, the amount of chlorite or hydrogen peroxide added is not particularly limited and varies depending on the required bleaching degree of the product and the whiteness of the raw material base material. Usually less than 20% by weight
10% by weight or less is sufficient. In this case, the addition time of the oxidizing agent is arbitrary as long as it is before the dehydration step and is not particularly limited. Regarding the second problem, regarding the product form, when the present invention is implemented based on the above outline,
The product form that is normally obtained is a fine powder with a particle size of 1 mm or less, but when used, fine powder causes various handling problems, and even in the field of enteric coating agents, it is generally granulated in some form. is always the case.
As mentioned above, the major technical point of the method of the present invention is to coexist with a lower alkanol having 1 to 3 carbon atoms or acetone during neutralization, but this method is more dehydrating than in the case where the alkanol or ketone is not added. This is effective not only for relaxing the sum conditions, but also for increasing the particle size obtained. As a result of further intensive studies from this point of view, the present inventors found that by controlling the solid content concentration of the neutralization treatment system and the amount of lower alkanol or ketone having 1 to 3 carbon atoms added, it is possible to easily produce particles with a diameter of 1 mm or more. I found out that it can be made into grains. This is the fourth gist of the present invention. At this time, the solid content concentration and the amount of lower alkanol or ketone containing 1 to 3 carbon atoms to be added vary depending on the base material used and the required product particle size, but it is generally not possible to make a general statement about the base material with high hydrophilicity. It becomes necessary to set the required solid content concentration and the required addition amount higher as the amount increases. Normal particle size 1mm
In order to obtain the above, it is necessary that the solid content concentration is 5% by weight or more, and the amount of lower alkanol with 1 to 3 carbon atoms or acetone added during neutralization is approximately 1 to 30% by weight of the solution volume. It is said that That is, the present invention relates to a method for purifying and granulating high-grade oxycarboxylic acid type cellulose derivatives, which is based on the following items. 1. After dissolving a water-insoluble oxycarboxylic acid type cellulose derivative in water containing a basic substance, or after dissolving a water-soluble base salt of the oxycarboxylic acid type cellulose derivative in water, neutralize the basic substance. A hydrogel of the oxycarboxylic acid type cellulose derivative is created by adding the obtained acidic substance to the above aqueous solution under stirring and neutralizing it in the presence of a lower alkanol having 1 to 3 carbon atoms or acetone. A method for purifying the oxycarboxylic acid type cellulose derivative, which comprises heating to a temperature higher than the dehydration temperature of the obtained hydrogel. 2. A method for purifying an oxycarboxylic acid type cellulose derivative in 1, characterized in that the basic substance is caustic alkali. 3. A method for purifying the oxycarboxylic acid type cellulose derivative in 1 and 2, which comprises allowing chlorite or hydrogen peroxide to coexist during dissolution or after neutralization of the oxycarboxylic acid type cellulose derivative. 4 After dispersing the oxycarboxylic acid type cellulose derivative in water in the coexistence of chlorite or hydrogen peroxide, adding and dissolving a basic substance sufficient to completely dissolve the oxycarboxylic acid type cellulose derivative. A method for purifying oxycarboxylic acid type cellulose derivatives characterized by 1 or 2. 5 In 1 to 4, the solid content concentration of the oxycarboxylic acid type cellulose derivative in the final homogeneous solution system is 5 wt% or more and the number of coexisting carbon atoms is 1 to 1.
The amount of lower alkanol or acetone added in step 3 is 1 to 30% by weight of the above solution amount, and the particle size is 1 mm.
A method for purifying the oxycarboxylic acid type cellulose derivative, which comprises obtaining the above granular purified product. By carrying out the present invention based on the above-mentioned items, it is possible to reduce the degree of esterification modification of oxycarboxylic acid to 5% or less, depending on the conditions, to 0.5% or less. There is a practical need not only to be able to easily obtain a high-quality product that can fully exhibit physical properties according to the molecular design of the product, but also to have a product form that has high whiteness and is granulated to a particle size of 1 mm or more. It can be provided as a product that meets the following. As explained above, by implementing the present invention, deterioration due to esterification of oxycarboxylic acids can be prevented, but some of the effects obtained by implementing the present invention are as follows. . 1. Solubility in coating solvents is improved. 2. When dissolved in a coating solvent, the solution viscosity is lower than that of a modified substance even at the same concentration, improving coating suitability. 3. Film-forming properties are improved, film properties are improved, one-component resistance is improved, and it is effective in reducing the required minimum amount of coating and preventing cracking of the coating film. 4 Effective in improving enteric properties as the number of available carboxyl groups increases. As described above, by carrying out the present invention, it is extremely effective in improving various drawbacks that have been considered as problems in the past, and has great practical significance. The present invention will be explained in more detail below with reference to Examples, but the present invention is not limited to the following Examples unless the gist thereof is exceeded. In the following examples, parts and % indicate parts by weight and % by weight unless otherwise specified, and various measured values were determined by the following methods. (1) Product viscosity The product was dried at 105°C for 2 hours and mixed with methylene chloride/
A 20% solution was prepared by dissolving it in an isopropyl alcohol mixed solvent (89/11: weight ratio) and was measured at 20°C using a B-type viscometer. (2) Solution Dissolve the product in a methylene chloride/ethanol mixed solvent (50/50: weight ratio) to prepare a 5% solution. Using the methylene chloride/ethanol mixed solvent as a blank, measure the solution at room temperature using a photoelectric colorimeter. Transmittance (T%) is calculated (cell layer thickness 10
mm, without filter). (3) Whiteness: Well-ground product (200 mesh through product)
was measured using a spectrophotometer at a wavelength of 480 mμ using standard clay as 100%. (4) Degree of esterification modification According to the method for measuring the degree of lactone formation of alginic acid (Tomoo Miwa, Nikka, 51 , 738, (1930)), the carboxyl group was determined by the following formula from the difference between the direct titration method and the indirect titration method. I turned and asked. Degree of esterification alteration (%) = Carboxyl group content (indirect titration method, %) - Carboxyl group content (direct titration method, %) / carboxyl group content (indirect titration method, %) x 100 Note that the direct titration method uses a solvent as a solvent. ethanol/
Water mixed solvent (8/2: weight ratio), titration reagent
Use 0.1NNaOH as solvent for indirect titration.
0.1NNaOH and 0.1NH ₂ SO ₄ were used as the titration reagent. Phenol phthalein was used as an indicator in both titration methods, and the carboxyl group content was calculated according to a conventional method. Example 1 Degree of carboxymethyl group substitution (hereinafter abbreviated as DS)
0.42, ethoxyl group DS2.00, product viscosity 5720cps,
After dispersing 1 part of carboxymethylethylcellulose with a solution of 90.2% and a whiteness of 94.5% in 15.2 parts of water,
After adding 6 parts of 0.4N caustic soda and completely dissolving the mixture at room temperature with stirring, the mixture was maintained for an additional 5 hours. Next, add 2 parts of isopropyl alcohol and stir.
A carboxymethylethyl cellulose hydrogel was obtained by neutralizing by adding 6 parts of 0.4N sulfuric acid. When heated in a water bath with stirring, approximately
At 60°C, dehydration began and solid particles began to precipitate. After the temperature of the liquid was further raised to 70°C, it was held at the same temperature for 5 minutes and then suctioned using a hot nuttie to separate solid particles. Further until the liquid becomes neutral
After repeated washing with hot water at 70°C, the product was dried with hot air at 70°C for 4 hours to obtain purified carboxymethylethyl cellulose with a particle size of 1 mm or less. This product has a product viscosity of 3850 cps, a solution of 94.2%, a whiteness of 91.2%,
The degree of esterification alteration was 0.2%, and the solution used for product viscosity and solubility measurements was a completely homogeneous solution, with no gel-like insoluble matter observed at all. On the other hand, the degree of esterification alteration of the raw material carboxymethylethyl cellulose subjected to purification was 10.2%, and the solution used for product viscosity measurement contained some gel-like insoluble matter. The quality was significantly inferior to that of the purified product obtained. Example 2 Purified carboxymethylethylcellulose having a particle size of 1 mm or less was obtained in the same manner as in Example 1 except that the holding time after dissolution with the alkali was 1 hour and methanol was used instead of isopropyl alcohol. This product has a product viscosity of 4220 cps, solubility 93.1%, whiteness 91.4%, and esterification degree 1.2%.
The solution used for product viscosity and solubility measurements was a completely homogeneous solution, and no gel-like insoluble matter was observed. Example 3 Same as Example 1 except that hydroxypropyl methyl cellulose phthalate (trade name, HP-55, manufactured by Shin-Etsu Chemical Co., Ltd.) was used instead of carboxymethyl ethyl cellulose, and 1 part of acetone was used instead of isopropyl alcohol. A hydrogel of hydroxypropyl methylcellulose phthalate was obtained by neutralization treatment. When this material was heated over an aqueous solution with stirring, solid particles began to precipitate at about 55°C. The liquid temperature was further raised to 65°C, held at the same temperature for 5 minutes, and then treated in the same manner as in Example 1 to obtain purified hydroxymethylpropyl cellulose phthalate having a particle size of 1 mm or less. This product had a product viscosity of 1800 cps, a solution state of 98.8%, a whiteness of 92.5%, and a degree of esterification alteration of 4.8%.The solution used for measuring the product viscosity and solution state was a completely homogeneous solution, and no gel-like insoluble matter was observed. On the other hand, the raw material hydroxymethylpropyl cellulose phthalate used for purification has a product viscosity of 2200 cps,
The solubility was 98.2% and the whiteness was 94.5%, but the degree of esterification alteration was extremely high at 13.8%. Example 4 Carboxyethyl group DS0.56, ethoxyl group
Carboxyethylethylcellulose 1 with DS1.81
0.2 parts of a 48% aqueous solution of caustic soda was added thereto, and the mixture was completely dissolved at room temperature with stirring, and then maintained for an additional 5 hours. Next, add 1 part of isopropyl alcohol and then 10% sulfuric acid to adjust the pH of the system.
When the hydrogel of carboxyethyl ethylcellulose obtained with a temperature of 3.2 was heated in a water bath with stirring, dehydration began at about 60°C and solid particles began to precipitate. After further raising the liquid temperature to 75℃,
The mixture was held for a minute and then treated in the same manner as in Example 1 to obtain purified carboxyethyl ethyl cellulose granulated to a particle size of about 2 to 3 mm. This product had a product viscosity of 2300 cps, a solution state of 94.5%, a whiteness of 93.0%, and a degree of esterification alteration of 0.8%. The solution used for measuring the product viscosity and solution state was a completely homogeneous solution, and no gel-like insoluble matter was observed at all. On the other hand, the raw material carboxyethyl ethyl cellulose used for purification has a product viscosity of 2800 cps, a solubility of 92.8%,
The whiteness was 95.2% and the degree of esterification alteration was 8.7%. Comparative Example 1 A hydrogel of carboxymethylethylcellulose was obtained in the same manner as in Example 1 except that the same carboxymethylethylcellulose used in Example 1 was used and no isopropyl alcohol was added. This product was heated in a water bath with stirring, but unlike Example 1, dehydration did not start at 60°C and solid particles began to precipitate at about 65°C. The liquid temperature was further raised to 70°C, but dehydration was insufficient, so the temperature was raised to 80°C and held at the same temperature for 5 minutes.Then, the process was carried out in the same manner as in Example 1 to obtain purified carboxymethylethyl cellulose. At this time, perhaps due to insufficient dehydration, the suction properties after dehydration were extremely poor, and the product viscosity was 4120 cps.
Solubility 92.8%, whiteness 91.0%, esterification degree 5.3
%, and compared to Example 1, the degree of esterification modification was extremely high. Comparative Example 2 A hydrogel of carboxyethyl ethyl cellulose was obtained in the same manner as in Example 4 except that the same carboxyethyl ethyl cellulose used in Example 4 was used and no isopropyl alcohol was added. This material was heated in a water bath with stirring, but unlike Example 4, dehydration did not start at 60°C, and solid particles began to precipitate at about 65°C. The liquid temperature was further raised to 80° C. and maintained at the same temperature for 5 minutes, and then treated in the same manner as in Example 4 to obtain purified carboxyethyl ethyl cellulose. At this time, perhaps due to insufficient dehydration, the suction properties after dehydration were poor, and the product particle size varied widely from 1 mm or more to fine particles of 1 mm or less, and compared to Example 4, the product granulation effect was poor. It was also significantly inferior. Example 5 Carboxymethyl group DS0.50, ethoxyl group
DS2.05, product viscosity 6240cps, solution 92.0%, whiteness
Disperse 1 part of 93.2% carboxymethylethyl cellulose in 11 parts of water, then add 48% caustic soda aqueous solution.
After adding 0.25 parts and completely dissolving at room temperature while stirring, the mixture was further kept at room temperature for 12 hours. Next, 1 part of isopropyl alcohol was added, and then 0.05 part of 10% sodium chlorite was added, and the pH of the system was adjusted with 10% sulfuric acid.
When the carboxymethylethylcellulose hydrogel obtained in 3.2 was heated in a water bath with stirring, dehydration began at about 60°C and solid particles began to precipitate. The liquid temperature was further raised to 70°C, held at the same temperature for 5 minutes, and then suctioned through a hot nuttie to separate solid particles. Further, the solution was repeatedly washed with hot water at 70°C until the liquid became neutral, and then dried with hot air at 70°C for 6 hours to obtain purified carboxyethyl cellulose granulated to a particle size of 2 to 3 mm. This product had a product viscosity of 3200 cps, a solubility of 95.%, a whiteness of 97.0%, and a degree of esterification alteration of 0.0%.The solution used for measuring the product viscosity and solubility was a completely homogeneous solution, and no gel-like insoluble matter was observed. . On the other hand, the degree of esterification alteration of the raw material carboxymethylethyl cellulose subjected to purification was 9.8%, and the solution used for product viscosity measurement contained some gel-like insoluble matter. The quality was significantly inferior to that of the purified product obtained. Example 6 1 part of the same carboxymethylethyl cellulose used in Example 5 was dispersed in 9 parts of water, 0.1 part of 30% hydrogen peroxide solution was added, and the mixture was stirred at room temperature for 1 hour, and then filtered by suction using a Nutsuie filter. . Add 1.8 parts of the obtained wet carboxymethylethylcellulose to water.
After dispersing in 9.2 parts, the same procedure as in Example 5 was carried out except that no sodium chlorite was added, to obtain purified carboxymethylethyl cellulose granulated to a particle size of 2 to 3 mm. This product had a product viscosity of 3360 cps, a solution state of 95.0%, a whiteness of 95.0%, and a degree of esterification alteration of 0.1%. The solution used for measuring the product viscosity and solution state was a completely homogeneous solution, and no gel-like insoluble matter was observed. [Film Coating Test Results] Next, the quality of the purified product obtained by carrying out the present invention as an enteric coating agent was checked by actually coating tablets. (1) Preparation of uncoated tablets for coating test Microcrystalline cellulose (manufactured by Asahi Kasei Corporation,
Approximately one tablet is made by direct compression of a 1:1 mixture of: (trade name: Avicel): Rapidly disintegrating excipient for direct compression (manufactured by Freund Sangyo Co., Ltd., trade name: Perfiller 101)
A tablet of 200 mg and a diameter of 8 mm was obtained. (2) Preparation of coating solution 1 part of enteric base material and 0.1 part of Mybaset 9-40T were dissolved in 11.5 parts of methylene chloride/ethyl alcohol mixed solvent (1/1) to obtain a homogeneous solution and a coating solution. (3) Coating operation and evaluation Place 1 kg of the above uncoated tablets in an automatic film coating pan (FM-type manufactured by Freund Sangyo Co., Ltd.) and add approximately 8 ml of the coating liquid of the above formulation.
The solution was sprayed at a liquid volume of 10 min to cover the uncoated tablets with a coating film of about 5 to 10% of the uncoated tablets. During this time, the coating pan was under rotation (14 rpm) and dried using dry air at 60-70°C. After spraying a predetermined amount, it was dried with the same dry air for 20 minutes. The obtained coated tablets were visually observed to check for cracks in the film, and enteric properties were evaluated according to the disintegration test method described in the Japanese Pharmacopoeia (10th edition). The results are summarized in Table 1. By carrying out the present invention, not only the coating suitability is improved and the one-component resistance is improved, but also the two-component disintegration property is significantly improved, and the molecular design of each base material is improved. It is clear that the functions based on this can be fully expressed.

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Claims (1)

[Scope of Claims] 1. After dissolving a water-insoluble oxycarboxylic acid type cellulose derivative in water containing a basic substance, or after dissolving a water-soluble base salt of the oxycarboxylic acid type cellulose derivative in water, the basic substance A hydrogel of the oxycarboxylic acid type cellulose derivative is obtained by adding an acidic substance capable of neutralizing the hydroxycarboxylic acid type cellulose derivative to the above aqueous solution while stirring, and neutralizing it in the presence of a lower alkanol having 1 to 3 carbon atoms or acetone. A method for purifying the oxycarboxylic acid type cellulose derivative, which comprises heating to a temperature higher than the dehydration temperature of the hydrogel obtained. 2. The method for purifying the oxycarboxylic acid type cellulose derivative according to claim 1, wherein the basic substance is a caustic alkali. 3. The oxycarboxylic acid type cellulose derivative according to claim 1 or 2, characterized in that chlorite or hydrogen peroxide is allowed to coexist with the oxycarboxylic acid type cellulose derivative during dissolution or after neutralization. Purification method. 4 After dispersing the oxycarboxylic acid type cellulose derivative in water in the coexistence of chlorite or hydrogen peroxide, add and dissolve a basic substance sufficient to completely dissolve the oxycarboxylic acid type cellulose derivative. A method for purifying an oxycarboxylic acid type cellulose derivative according to claim 1 or 2, characterized by: 5 The solid content concentration of the oxycarboxylic acid type cellulose derivative in the final homogeneous aqueous solution system is 5 wt% or more, and the added amount of lower alkanol or acetone having 1 to 3 carbon atoms to be coexisting is 1 to 30% of the above solution amount.
% by weight and a granular purified product having a particle size of 1 mm or more is obtained. 5. A method for purifying an oxycarboxylic acid type cellulose derivative according to any one of claims 1 to 4.