Decoloration method of enoxaparin sodium

Abstract

The invention discloses a decoloration method of enoxaparin sodium. The method includes dissolving an intermediate of the enoxaparin sodium to be discolored into an ammonium sulfate solution to obtain an enoxaparin sodium solution; when a hydrophobic chromatographic column is balanced by the ammonium sulfate solution, loading the enoxaparin sodium solution to the hydrophobic chromatographic column, and collecting penetration solution; when an anion exchange chromatographic column is balanced by purified water, diluting the penetration solution with the purified water, loading the penetration fluid to the anion exchange chromatographic column, washing the column with the purified water and a sodium chloride solution with a low concentration sequentially after the loading, eluting the column with a sodium chloride solution with a high concentration, and collecting the eluent; subjecting the eluent to nanofiltration, desalination and concentration until the concentration of the enoxaparin sodium in the concentrated solution is 5wt%-20wt%; and precipitating and drying the concentrated solution to obtain the finished product of the enoxaparin sodium. According to the decoloration method, the decoloration effect is good, the color of the finished product is lighter than that of a color solution BY6, the finished product conforms to the provision of European Pharmacopoeia 7.0, and the method is high in safety and easy to control.

Description

technical field [0001] The invention relates to a decolorization method, in particular to a decolorization method of enoxaparin sodium. Background technique [0002] Enoxaparin sodium is a benzyl ester derivative of heparin-benzethonium chloride salt obtained from heparin sodium derived from pig intestinal mucosa through salt formation and esterification, and then undergoes beta-elimination reaction cleavage under alkaline conditions to form low Molecular weight heparin sodium, and then decolorized to obtain the finished product. Its main feature is that it has 4-enolpyranonic acid at the non-reducing end of the sugar chain and 1,6-anhydrous structure at the reducing end of the sugar chain, and the latter accounts for 15wt% to 25wt% of all sugars. Enoxaparin Sodium is mainly used to prevent deep vein thrombosis and pulmonary embolism; treat existing venous thrombosis; prevent thrombosis in extracorporeal circulation during hemodialysis, etc. [0003] The product of heparin...

AI Technical Summary

Problems solved by technology

[0006] The decolorization method disclosed in this document has the following deficiencies: (1) Decolorization with activated carbon is likely to produce microcrystals that cannot be filtered, which makes the product have certain safety risks, and activated carbon will also adsorb certain active ingredients while adsorbing pigments, reducing the yield.

(2) If some macroporous resins are used for decolorization, impurities such as benzene, toluene, xylene, and styrene may remain, and there are certain safety risks