SU802290A1 - Method of preparing carboxyl-containing chitosan derivatives - Google Patents

Description

(54) METHOD FOR OBTAINING CARBOXYL CONTAINING - .HACHING CHITOSAN DERIVATIVES

one

The invention relates to a method for producing carboxyl-containing chitosan derivatives and can be used in the chemical and food industries, as well as in medicine.

A method is known which consists in acylation of the chitosan amino groups with dicarboxylic acid anhydrides 1J. The chitosan acylation reaction according to this method is carried out by adding to the aqueous solution of chitosan salts, alternately and in portions, in several stages of a dilute alkali solution (to release the amio groups of chitosan and neutralizing carboxyl groups formed during the reaction) and dicarboxylic anhydride.

The main disadvantage of this method is that the acylated reaction proceeds under heterogeneous conditions, since the addition of enough water causes the precipitation of chitosan from the solution. At the same time, the acylation reaction is sharply slowed down, and the rate of the side reaction of hydrolysis of dicarboxylic anhydride significantly exceeds the rate of the main reaction, which makes it difficult to carry out quantitatively. and acylation reactions (yield

the acylation stages vary between 70 and 87%).

The resulting carboxyl-containing chitosan derivative is a compositionally heterogeneous product, or more precisely, a range of products that are non-uniform in the degree of acylation and with a non-uniform distribution of the added carboxyl groups. The alternate addition of alkali and acidifying medium anhydride leads to drastic changes in pH values, which also makes it difficult to obtain a compositionally uniform, reproducible in composition standard product. In addition, multiple repetitions of the alternate addition of alkali and anhydride greatly prolong the reaction time and complicate the process, making it difficult to automate.

The aim of the invention is to increase the degree of acylation and homogeneity of carboxyl-containing chitosan derivatives.

The goal is achieved in that chitosan is acylated with dicarboxylic acid anhydrides in a ratio of 0.51.0 0 mol of anhydride to 1 mol of amino groups of chitosan at pH 4.0-5.5 with subsequent processing of the resulting polymfolit with carboxylic acid anhydrides in 0.5-2 , 0 mol of anhydride per 1 mol of amino groups of chitoane at pH 7.5-10. To a solution of chitosan in acidic aqueous buffer with vigorous stirring, add a solution of dicarbic acid anhydride in an organic solvent that is well miscible with water (for example, methanol, dioxane, etc. By varying the excess anhydride, you can get polyampholytes with a given amino ratio and carboxyl groups. Thus, in the interaction of chitosan with an equimolar amount of maleic anhydride, it is possible to obtain a polyampholyte with an almost stoichiometric ratio of acidic and basic groups, the content of which determines with potentiometric titration. This makes it possible to use polyampholytes of this kind as amphoteric ion exchange resins. To obtain a polyampholyte capable of dissolving in alkaline media, it is sufficient to process chitosan with 0.5 molar dicarboxylic acid anhydride per 1 mole of chitosan amino groups. As acidic An aqueous buffer with a pH value of 4.0-5.5, for example, an acetate buffer, is used to buffer the reaction medium. In some cases, at the stage of polyampholyte production, it is acceptable to use acidic aqueous-organic (e.g. water-alcohol, water-dioxane, etc.) homogeneous solutions of chitosan, however, the products of chitosan acidification under these conditions give non-flowing, elastic gels in the whole solution volume, which is extremely difficult There is no further modification or isolation of the polyampholytes obtained. Depending on the method of healing and the structure of polyampholytes, they can be obtained in various ionized forms: in the form of acidic salts with mineral and organic acids (chlorohydrates, hydroxide phosphates, formates, etc.), in the form of basic salts with various mineral and organic acids. Organic bases (such as, for example, NaOH, KOH, ammonia, triethylamines, etc.), as well as in the form of internal salts. The anhydrides of unsaturated dicarboxylic acids, for example, maleic, citraconic, etc., and the acid anhydrides of fixed dicarboic acids, for example succinic, glutamic, hydrochloric acid, hydraboxylic anhydrides, are used as anhydrides of dicarboxylic acids, for example, maleic, citraconic and the like; anhydrides savages. Boone acids are carried out under homogeneous conditions in an alkaline medium at constant pH values taken in the range of 7.5-10. As an alkaline medium for conducting: acylation, water buffers (e.g., phosphate, borate, etc.) are generally used. For the subsequent acylation of polyampholyte by dicarboxylic acid anhydrides under alkaline homogeneous conditions, it is possible to bring the pH to the desired value by adding alkali and to carry out the acylation, maintaining the set pH value by automatic alkalinization of the medium using a pH-stat. Dicarboxylic anhydride can be added either as a solution in an inert organic solvent or in a solid state. For the quantitative acylation of all amino groups of a polyampholyte, 1 mole of anhydride per mole of the starting chitosan is sufficient. In order to obtain carboxyl-containing chitosan derivatives with superficially-affective properties, alkaline solutions and polyampholytes are treated under homogeneous conditions with hydrogenated anhydrides or anhydrides of fatty carboxylic acids with long hydrocarbon radicals (e.g. Example 1. To a solution of 1.0 g of chitosan in 100 ml of acetate buffer pH 5.5, with vigorous stirring, add a solution of the calculated amount (1 mol per 1 mol of the amino groups of chitosan) maleic anhydride in a minimum volume of absolute methanol. After 15 min, the reaction mass was poured into methanol. The white powdered product is washed with methanol, acetone, dried in vacuo. The polymer obtained is a polyampholyte, well soluble: 1st in both acidic and alkaline media and not swelling in water. It is dissolved in 100 ml of 0.1N. NaOH and dialyzed against 0.1N. NaOH for a day, then a solution of Vyliviot in ethanol, the precipitated sodium salt of polyampholyte is filtered off, washed with methanol, acetone, dried in vacuum over molecular sieves. 1.2 g of the sodium salt of polyhypholite are obtained. According to potentiometric titration data, 48% of all free amino groups of chitosan were procylated. Example 2. According to the method described in example 1, the sodium salt of polyampholyte is obtained. The only difference is that the reaction is carried out in an acetate buffer with a pH of 4.0 and succinic anhydride is used instead of maleic anhydride. The degree of conversion is 45%. Example 3. To a solution of 1.0 g of chitosan in a mixture of 20 ml of 1.5 n hydroxyacetic acid and 80 MP of methanol (pH 5.5), the calculated amount is added with vigorous stirring

(1 mol per 1 mol of amino groups: chitosan) glutaric,. Anhydride in the minimum volume of methanol. After 1 hour, the gelatinous reaction product, Fractional, is suspended in acetone, then the polymer is washed on the filter with acetone, methanol, acetone. Dry in vacuo over molecular sieves. The dried polymer is dissolved in 0.1 N NaOH and dialysis comfort versus 0.1 n. NaOH during the day. Then the solution is poured into ethanol. The precipitated sodium salt of polyampholyte is filtered off, washed with methanol, acetone. Dried over molecular sieves. The degree of conversion is 52%.

Example 4. To a solution of 1, O g of chitosan in 100 ml of acetate buffer pH 5.0, with vigorous stirring, add a solution of the calculated amount (1 mol per 1 mol of the amino groups of chitosan) maleic anhydride in the minimum amount of absolute methanol. After 10 min, the reaction mass was poured into methanol. The white powdered product is washed with methanol, acetone, dried in vacuo. The resulting polyampholyte is then dissolved in 100 ml of borate buffer with a pH of 9.0, and maleic anhydride (1 mol per 1 molar amino groups of the starting chitosan) dissolved in a minimum volume of methanol is added to the solution with vigorous stirring. The solution is stirred for 1 hour, then transferred to a cellophane bag and dialyzed for 24 hours against 0.1 g. NaOH. From the resulting solution, the polymer is precipitated in ethanol, filtered and washed with methanol with acetone. Dry in vacuum. 1.6 g of sodium salt of carboxyl-containing chitosan derivative are obtained. The resulting compound is soluble in water and alkali, insoluble in acids. Quantitative acylation of all a and diogroup chitosan was confirmed by conductometric titration.

Example 5. According to the procedure described in Example 4, the sodium salt of the carboxyl-containing chitosan derivative was obtained. The only difference is that succinic anhydride is added to the reaction with chitosan. Quantitative acylation of all amino groups of chitosan was confirmed by conductometric titration.

Example 6. According to the procedure described in Example 4, the sodium salt of the carboxyl-containing chitosan derivative was obtained. The cast is only that instead of the acetate buffer, maleate buffer with a pH of 5.4 is used. The resulting product in its physical properties is identical to the product described in example 4.

Lymer 7. To a solution of 1.0 g of chitosan in 100 ml of acetate buffer with pH 5.0 with vigorous stirring

NIIs add a solution of maleic anhydride (0.5 mol per 1 mol of the amino groups of chitosan) in a minimum volume of absolute methanol. After 15 minutes, the pH of the reaction medium was adjusted to 8.5 by the addition of 4 n. Maon. Maleic anhydride solution (1 mol per 1 mol of chitosan amino groups) in a minimum volume of dioxane is added to the resulting solution with stirring, as it is pH 8.5-9.0 by automatically adding 4N.NaOH using a pH-stat. After 1 hour, the solution is transferred to a plastic bag and dialyzed against 0.1N. NaOH during the day. 1.7 g of the sodium salt of the carboxyl-containing chitosan derivative is obtained. Quantitative acylation of all amino groups of chnozane confirmed by conductometric titration

Example 8. To a solution of 1.0 g of the sodium salt of polyampholyte prepared according to the procedure described in Example 1 in 100 ml of phosphate buffer pH 7.5, the calculated amount is added with vigorous stirring (1 mole per mole of polyampholyte amino groups) maleic anhydride, dissolved in a minimum volume of dioxane. The solution is stirred for 1 h, then transferred to a plastic bag and dialyzed with a solution of 0.1 N NaOH for 24 hours. From the resulting solution, the polymer is precipitated in ethanol, filtered and washed with methanol, acetone. Dry in a vacuum over molecular sieves. The physicochemical properties of the sodium salt of the carboxyl-containing chitosan derivative are identical to the product described in Example 4.

 Example 9. To a solution of 200 mg of sodium salt of polysl "1) olite prepared according to the procedure described in example 2, in 20 ml of borate buffer with pH 9.0, a solution of acid chloride of capric acid (2 mol per 1 mol of amino groups source chitosan) in the minimum amount of dioxane. The reaction mass is stirred for 6 hours, maintaining the pH 9-10 by the automatic addition of 4 n. NaOH using a pH-stat. The polymer is planted in methanol, washed with methanol, acetone, ether, dried in vacuum. 0.26 g of polymer is obtained.

,, Found:%: C 52.0, H 7.23;

N 5.32,

j Calculated:%: C 52.50, H 7.330,

N 5.07.

Example 10. By the method,. described in example 9, get carboryl derivative of chitosan. The only difference is that lauric anhydride is used instead of capric acid chloride.

. Found,%: C 53.91, H 7.48 / N 4.51.

,, Calculated;% C 54.40; H 7.62 {; N 4.70.

The proposed method makes it possible to obtain compositionally homogeneous carboxyl-containing chitosan derivatives with a high degree of acylation.

The use of alkali-soluble polyampholyte allows the range of reactions to be extended over the amino group of chitosan carried out in a homogeneous medium.

In this case, the synthesis of chitosan modifiers is based on the use of readily available and inexpensive reagents with their small excess. The proposed method is simple and technologically convenient.

Claims (1)

1. For France of France No. 2137684, cl. C 08, pub. 1965.