SU166356A1 - WAY OF OBTAINING RIBOFLAVIP-5'-SODIUM PHOSPHATE - Google Patents

Description

There are known methods for producing a therapeutic preparation of sodium riboflavin-5-phosphate by phosphorylation of riboflavin with dimethylphosphochloride. These methods provide for the isolation of riboflavin-3-phosphate intermediate dimethyl ether, which considerably complicates the process and does not allow to obtain the target product with a satisfactory yield.

In order to simplify the process and increase the drug yield of riboflavin-5-phosphate dimethyl ether, without isolating it from riboflavin phosphorylation products, it is hydrolyzed into riboflavin-5-phosphate, which is precipitated with butanol or isobutanol, converted into the sodium salt by known methods and purified by fractional separation with thickening of the solution.

In order to obtain sodium riboflavin-5-phosphate, riboflavin at 40-50 ° C is treated with an excess of dimethylphosphochloridate followed by hydrolysis of the riboflavin-5-phosphate dimethyl ester formed by decomposition. The obtained riboflavin-5-phosphate is precipitated with butyl or isobutyl alcohol, dissolved in water and alkalinized with sodium hydroxide solution to a pH of 5.1-5.2. Purification of the obtained preparation was performed by fractionated separation of impurities during evaporation of the concentrated solution.

Example. When moving and cooling for 1 hour, 140 ml of anhydrous methyl alcohol is poured into 160 liters of phosphorus oxychloride, maintaining the temperature at 16-24 ° C. Stirring at room temperature is continued for another 20 hours, after which the dimethylphosphochlochloride is added to the resulting

50 g of riboflavin and heated for 1 hour at 40-45 ° C. Then the mixture is cooled, carefully with stirring, the excess phosphorylation mixture is decomposed with 120 ml of water, heated for 1 hour at 60-65 ° C, cooled,

add 1000 ml n. butyl alcohol and allowed to crystallize for 14 hours at -3 ° C. 54 g of riboflavin-5 phosphate are obtained with an mp. 183--184 ° C, which is dissolved in a 20-fold amount of water, is transferred for 1 hour, alkalinized with 1% -11% sodium hydroxide solution to a pH of 5.1-5.2 and kept for 20 hours. After that, the solution is subjected to fractional purification, for which the insoluble precipitate is filtered off, evaporated

the filtrate is up to 1/4 of the initial volume, the precipitate is filtered off again and by adding a double volume of ethyl alcohol, riboflavin5-sodium phosphate is precipitated from the filtrate, completely soluble in

The proposed method is quite simple and allows to obtain a highly water-soluble highly active drug that can be used to treat eye diseases and dermatoses.

Subject invention

The method of producing riboflavin-5-phosphate sodium by phosphorylation of riboflavin with dimethylphosphochloride, characterized in that, in order to obtain a therapeutic preparation, riboflavin-5-phosphate dimethyl ether, without isolating it from the riboflavin phosphorylation products, is subjected to the hydrofluoride dimethyl ether-iphosphate-5-phosphate dimethylphosphinate iphosphine dimethylphosphorin-5-phosphate phosphorinate; butanol or isobutanol, is converted into the sodium salt by known methods and purified by fractionated separation of impurities when the solution is concentrated.