RU2592617C1 - Method of oxidised dextran producing - Google Patents

Abstract

FIELD: technological processes.

SUBSTANCE: invention relates to method of oxidised dextran producing. Method involves oxidation of aqueous solution of dextran with molecular weight of 20-75 kDa with potassium permanganate solution in medium of acetic acid, settling and filtering solution from impurities, separation of oxidised dextran with ethanol and drying. At that, initial dextran in form of 20-25 % acetic acid aqueous solution in concentration of 32-34 % in amount of 0.005-0.1 % of initial volume of dextran solution, potassium permanganate solution in concentration of 2 % in amount of 20-25 % of weight of dry dextran in solution, and ethanol is in concentration of 95-96 % with ethanol to liquid ratio of (1.4-1.6):1. Preferably dextran oxidation is carried out at temperature of 60-70 °C, filtering of oxidised dextran solution from impurities is carried out on membrane micro filter, and drying of oxidised dextran is carried out in vacuum oven at temperature of 60-85 °C.

EFFECT: invention enables to obtain oxidized dextran with higher output due to creation of conditions for maximum possible release of all fractions of oxidised dextran, not only medium and high-molecular but and low-molecular ones, eliminating loss of oxidised dextran and simultaneously increase organoleptic properties of oxidised dextran and its solubility in water.

4 cl, 3 ex

Description

The invention relates to a method for producing oxidized dextran containing aldehyde groups, which can be used as a carrier and modifier of biologically active substances and pharmaceutical substances.

The prior art method for producing dialdehydedextran according to the patent of the Russian Federation No. 2087146 (publ. 08/20/1997), including the oxidation of dextran.

Oxidation of dextran is carried out with sodium periodate, which leads to the formation of iodine-containing impurities in dialdehydedextran, which have a toxic effect and reduce the effectiveness of the use of dialdehydedextran in the composition of the drug. In addition, this method is multistage and time-consuming, which limits the prospects for its use for industrial implementation.

Known adopted for the prototype method for producing dialdehydedextran according to the Eurasian patent No. 011718 (published on April 28, 2009), including the oxidation of an aqueous solution of dextran with a molecular weight of 20-75 kDa with a solution of potassium permanganate in acetic acid when heated, sedimentation and filtering the solution from impurities , the selection of oxidized dextran with ethanol and drying.

The disadvantages of this method are: low productivity due to the use of a low concentrated stock solution of dextran; large product losses up to 25%, which are formed when scaling the known method in an industrial environment; excess acetic acid gives the product a characteristic odor for acetic acid, indicating the presence of unreacted acid; the product is poorly soluble in water; the use of a paper filter does not provide the required degree of purification of a solution of dialdehydedextran from manganese dioxide; the use of high temperatures in the allocation of ethanol reduces the safety of the process due to the presence of alcohol vapor; due to the fact that this process requires the use of a large amount of ethanol per unit of output, the cost of production is very high and requires the development of new solutions to reduce it; incomplete selection of all fractions of oxidized dextran (only medium and high molecular weight), which leads to insufficiently high yield of the target product.

The objective of this technical solution is to develop a high-performance, economically attractive and safer method of producing oxidized dextran, suitable for use in both laboratory and industrial conditions, allowing to obtain oxidized dextran, applicable in the pharmaceutical, cosmetic and food industries, with a higher yield by creating the conditions for the maximum possible allocation of all fractions of oxidized dextran, not only medium and high molecular weight but also low molecular weight, excluding the loss of oxidized dextran, while increasing the organoleptic properties of oxidized dextran and its solubility in water.

The problem is solved by the method of producing oxidized dextran, including the oxidation of an aqueous solution of dextran with a molecular weight of 20-75 kDa with a solution of potassium permanganate in an acetic acid medium when heated, sedimenting and filtering the solution from impurities, isolating the oxidized dextran with ethanol and drying. The peculiarity is that the initial dextran is used in the form of a 20-25% aqueous solution, acetic acid in a concentration of 32-34% in an amount of 0.005-0.1% of the initial volume of a dextran solution, a solution of potassium permanganate in a concentration of 2% in an amount of 20 -25% by weight of dry dextran in solution, and ethanol at a concentration of 95-96% with a ratio of ethanol to liquid (1.4-1.6): 1.

In particular, to reduce energy consumption and improve safety, the oxidation of dextran is carried out at a temperature of 60-70 ° C. In particular, to improve cleaning, filtering the solution of oxidized dextran from impurities is carried out on a membrane microfilter. In particular, it is preferable to dry the oxidized dextran in a vacuum oven at a temperature of 60-85 ° C, since this reduces the temperature of evaporation of moisture, and the capture of alcohol-containing vapors increases the safety of the process.

The inventive method allows to fully isolate not only medium and high molecular weight fractions of oxidized dextran, but also low molecular weight (determined in accordance with FSP 42-0088063400), which increases the yield of the target product by 20% compared with the prototype, in industrial conditions provides an increase in the productivity of the process 2.5 times, a decrease in ethanol consumption per unit of product by 60%, a reduction in the cost of the product by 30%, allows to obtain easily soluble oxidized dextran (in the prototype - sparingly soluble) and Exclude odor characteristic of acetic acid.

Modes of implementation of the proposed method are optimal to achieve the full range of claimed benefits.

A decrease in the concentration of an aqueous solution of dextran will lead to a decrease in the productivity of the method. With an increase in the concentration of an aqueous solution of dextran above the declared upper limit, due to the high viscosity of the solution, the process of dissolution of dextran, oxidation and filtering will not be feasible.

The decrease in the content of acetic acid below the lower limit from the initial dextran solution will not allow to provide the desired pH of the solution. An increase in the content of acetic acid above the higher declared limit will result in the presence of unreacted acid in the oxidized dextran, and the product will have a characteristic acetic odor.

If you use a ratio of ethanol to liquid less than 1.4: 1, then the selection will be the loss of oxidized dextran associated with its incomplete deposition. If the ratio is greater than 1.6: 1, then there will be an overrun of ethanol and a rise in price of the target product.

A solution of potassium permanganate concentration of 2% is added in an amount of 20-25% by weight of dry dextran in solution. If you add a solution of potassium permanganate less than 20% by weight of dry dextran in the solution, the oxidation reaction will not pass, if more than 25%, then an excessive amount of unreacted potassium permanganate will contaminate the product.

It is a 2% potassium permanganate solution that is convenient to use because dry potassium permanganate in this volume is readily soluble. If you prepare a more concentrated solution with a lower water content, then potassium permanganate is difficult to dissolve. If you prepare a less concentrated solution with a high water content, this will reduce manufacturability due to the need to use larger containers.

Information confirming the possibility of implementing the proposed method.

Example 1. In a beaker, a 20% dextran solution with a molecular weight of 20-75 kDa is prepared and heated in a water bath to 60 ° C. Acetic acid with a concentration of 33% in the amount of 0.005% of the volume of the initial dextran solution was added to the solution. An aqueous solution of potassium permanganate with a concentration of 2% is added in an amount of 20-25% by weight of dry dextran in the solution. The oxidation process is carried out at a temperature of 60 ° C. After a brownish-black precipitate formed, the reaction mixture was settled, then the clarified part was poured into a vacuum filter for filtration, where a microfiltration membrane was used as a filter material. At the end, the precipitate is filtered off. The selection of oxidized dextran from an aqueous solution of 20% is carried out with ethanol 95% in a ratio of ethanol to liquid of 1.6: 1, while the allocation temperature is 40 ° C. Drying of the target product is carried out in a vacuum oven at a temperature of 60 ° C. Dry oxidized dextran is ground in a mill to a powder with particles of the desired size. The yield of the target product is 96%, the product is readily soluble in water (determined by OFS 42-0049-07) and does not have a characteristic odor for acetic acid.

Example 2. In the apparatus with a stirrer, prepare a 23% solution of dextran with a molecular weight of 20-75 kDa and heat it to 65 ° C. Acetic acid with a concentration of 34% in an amount of 0.01% of the volume of the initial dextran solution was added to the solution. An aqueous solution of potassium permanganate with a concentration of 2% is added in an amount of 25% by weight of dry dextran in the solution. The oxidation process is carried out at a temperature of 65 ° C. After a brownish-black precipitate formed, the reaction mixture was settled, then the clarified part was poured into a vacuum funnel for filtering, where a microfiltration membrane was used as a filter material. At the end, the precipitate is filtered off. The separation of oxidized dextran from an aqueous solution of 23% is carried out with ethanol 96% in a ratio of ethanol to liquid of 1.5: 1, while the allocation temperature is 40 ° C. The drying of the target product is carried out in a vacuum oven at a temperature of 75 ° C. Dry oxidized dextran is ground in a mill to a powder with particles of the desired size. The yield of the target product is 95%, the product is readily soluble in water (determined by OFS 42-0049-07) and does not have a characteristic odor for acetic acid.

Example 3. In the apparatus with a stirrer, a 25% solution of dextran with a molecular weight of 20-75 kDa is prepared and heated to 70 ° C. Acetic acid with a concentration of 32% in the amount of 0.007% of the volume of the initial dextran solution is added to the solution. An aqueous solution of potassium permanganate with a concentration of 2% is added in an amount of 23% by weight of dry dextran in the solution. The oxidation process is carried out at a temperature of 70 ° C. After a brownish-black precipitate formed, the reaction mixture was settled, then the clarified part was poured into a vacuum funnel for filtering, where a microfiltration membrane was used as a filter material. At the end, the precipitate is filtered off. The selection of oxidized dextran from an aqueous solution of 25% is carried out with ethanol 96% in a ratio of ethanol to liquid of 1.4: 1, while the allocation temperature is 40 ° C. The drying of the target product is carried out in a vacuum oven at a temperature of 85 ° C. Dry oxidized dextran is ground in a mill to a powder with particles of the desired size. The yield of the target product is 95.5%, the product is readily soluble in water (determined by OFS 42-0049-07) and does not have a characteristic odor for acetic acid.

In the examples, the molecular weight range of the starting dextran is indicated, since the entire range of molecular weight values is present in the starting dextran, and not just one specific value.

The proposed method for producing oxidized dextran is practically feasible, technologically feasible and can satisfy a long-standing need for solving the problem.

Claims (4)

1. The method of producing oxidized dextran, including the oxidation of an aqueous solution of dextran with a molecular weight of 20-75 kDa with a solution of potassium permanganate in an acetic acid medium when heated, settling and filtering the solution from impurities, the selection of oxidized dextran with ethanol and drying, characterized in that the source dextran is used in the form of a 20-25% aqueous solution, acetic acid in a concentration of 32-34% in an amount of 0.005-0.1% of the initial volume of a solution of dextran, a solution of potassium permanganate in a concentration of 2% in an amount of 20-25% by weight of dry dextran solution and ethanol in a concentration of 95-96% with the ratio of ethanol and liquid (1.4-1.6): 1. 2. The method according to p. 1, characterized in that the oxidation of dextran is carried out at a temperature of 60-70 ° C. 3. The method according to p. 1, characterized in that the filtration of the solution of oxidized dextran from impurities is carried out on a membrane microfilter. 4. The method according to p. 1, characterized in that the drying of oxidized dextran is carried out in a vacuum oven at a temperature of 60-85 ° C.