FIELD: chemical-pharmaceutical industry.
SUBSTANCE: invention relates to method for producing low molecular weight heparin, which can be used in the chemical and pharmaceutical industry. Method includes the steps of: (a) shaping the protection of sulfo groups by the interaction of high molecular weight heparin with benzethonium chloride to form heparinate benzethonium, (b) esterification of the resulting salt by benzylation in an aprotic solvent, (c) isolating an incomplete heparin benzyl ester with removal of the benzethonium protection of the sulfo groups with a saturated solution of sodium acetate in alcohol, (d) cleavage of the macarolecule of heparin by alkaline depolymerization and (e) formation of terminal 1,6-anhydrogroups β-elimination when interacting with a strong reducing agent, and differs in that that at stage (a) the washing of heparinate benzethonium from an excess of unreacted benzethonium chloride is performed by repeated fractional washing with purified water using ultrasound of an operating frequency of 30–40 kHz radiation power of 200–400 W, and at the stage (c) the isolation of the heparin benzyl ester is carried out in two successive operations: the separation of the benzyl ester benzyl ester from solution by precipitation with a methanolic solution of sodium acetate, followed by removal of the benzethonium protection of sulfo groups with a saturated methanol solution of sodium acetate.
EFFECT: new effective method for obtaining low molecular weight heparin with improved purity and yield while reducing water consumption and reducing waste is proposed.
4 cl, 4 ex, 8 dwg, 3 tbl
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Authors
Dates
2018-10-25—Published
2017-12-26—Filed