METHOD FOR OBTAINING DRUG WITH ANTI-COAGULANT ACTIVITY Russian patent published in 2021 - IPC C08B37/10 

FIELD: pharmaceutical industry.

SUBSTANCE: invention relates to a method for producing an active pharmaceutical ingredient of sodium heparin. The method includes extraction of the crushed mucous membrane of the small intestine of pigs with a 0.5-0.6 M sodium chloride solution, the addition of subtilisin to a final concentration of 0.2-0.4 vol.%, Enzymatic hydrolysis at 50-70°C and pH 7.0 -9.0 for 6 hours, followed by inactivation of the enzyme at 90°C for 30 minutes. The extract is centrifuged and ballast impurities are precipitated at pH 2.5-4.5 and 70°C for 30 minutes. Separation and sorption of the heparin intermediate from the clarified extract are carried out on an anion-exchange chromatographic sorbent pre-equilibrated with 0.6 M sodium chloride solution, washing with 0.6 M sodium chloride solution, removal of ballast substances from the sorbent with 0.9 M sodium chloride solution and desorption with sodium chloride solution with a concentration of 1.4 M. The eluate is diafiltered with water for injection, ultrafiltered on cassettes with a cut-off limit of 5 kDa with the addition of sodium acetate until the latter content is 3.0-6.0 wt.%. The solution of the intermediate product after ultrafiltration is subjected to sterilizing filtration and precipitation with methanol until the final mass fraction of the latter is 35-38%. The semi-finished product is kept at a temperature of 5 ± 3°C for 18 ± 0.5 h, centrifuged and dried in a vacuum drying oven.

EFFECT: increased yield of sodium heparin fractions with anticoagulant activity.

1 cl, 3 ex, 2 dwg