Process for extracting crude heparin sodium through nanofiltration membrane concentration

Abstract

The invention relates to the technical field of heparin sodium production, and discloses a process for extracting crude heparin sodium through nanofiltration membrane concentration, wherein the process comprises the following steps: S1, carrying out enzymolysis and high-temperature inactivation on animal viscera, and cooling to obtain an inactivated solution; S2, transferring the inactivated solution into a stirrer for stirring, adding an inorganic settling agent at the same time, and continuously stirring; S3, adding an alkaline material, stirring, and standing; S4, pumping the supernate into a middle liquid storage tank, filtering a settling layer through a plate-and-frame filter press to obtain residual clear liquid, and pumping the residual clear liquid into the middle liquid storage tank; and S5, fully stirring and mixing the clear liquid in the intermediate liquid storage tank, filtering out a small amount of suspended matters through a security filter, concentrating through a nanofiltration membrane, and carrying out alcohol precipitation and drying on the concentrated solution to obtain a crude heparin sodium product. The process is characterized in that an inorganic settling agent is adopted to remove turbid substances in the inactivated solution, a disc tube type nanofiltration membrane is adopted to remove salt and small molecular impurities in the clear liquid, heparin sodium is concentrated, and then the heparin sodium crude product is obtained through alcohol precipitation and drying processes.

Description

technical field [0001] The invention relates to the technical field of heparin sodium production, in particular to a process for concentrating and extracting crude heparin sodium through a nanofiltration membrane. Background technique [0002] Heparin is the first anticoagulant to be discovered and isolated for medical use. It has been more than one hundred years since the discovery of heparin sodium, and it is one of the oldest drugs still used clinically. So far, there is no Synthetic products can completely replace it, and it is still the most important anticoagulant and antithrombotic drug, which can only be extracted from animal tissues. Heparin sodium can prevent and treat arterial and venous thrombosis and pulmonary embolism, and can be used as an anticoagulant drug during artificial heart-pulmonary, peritoneal dialysis or hemodialysis treatment. In recent years, studies have proved that heparin sodium also has blood lipid-lowering, anti-cancer, anti-viral, anti-infla...

AI Technical Summary

Problems solved by technology

CN111888941A adopts membrane integration process: preliminarily treats the heparin sodium intermediate flat product after salt hydrolysis and enzymolysis, removes macromolecular impurities such as protein through a 50nm ceramic membrane, and obtains a permeate and a concentrate. The permeate contains heparin sodium and For small molecular salt products, the concentrated solution contains macromolecular impurities such as protein, so as to realize the preliminary separation of heparin and other organic substances, but the ceramic membrane has defects such as high cost, easy clogging of the membrane, and difficult control of heparin sodium filtration.

The way CN111909287A handles the enzymolysis solution is to first use coarse filters with 100-200 mesh apertures, including tubular filters, bag filters, plate and frame filters, plug-in filters or centrifuges, etc. to carry out coarse filtration, and then use The tubular ceramic membrane with a pore size of 200-500nm is used for microfiltration to remove water-soluble and insoluble proteins and other organic molecules in the enzymatic hydrolysis solution, which has the disadvantages of complex process, low efficiency and large investment

CN111138565A has carried out 68-76 purpose filter cloth to remove filter residue to the liquid after secondary enzymolysis, can not remove finer insoluble particle and water-soluble protein nucleic acid etc., the effect of alleviating resin adsorption pressure is limited

CN109293801A filters with 90-100 order nylon cloth, collects filtrate, can't remove smaller insoluble particle and water-soluble protein nucleic acid etc. equally

CN109517092A heats and stirs the enzymolysis solution quickly to 85°C, then slowly heats to 90-92°C after the temperature rises to 85°C, and then keeps warm for 30-60 minutes until the liquid in the enzymolysis tank is separated, the upper layer is protein, and the lower layer is Clarified enzymolysis solution, separation of protein and enzymolysis solution, there is a problem that the protein suspension layer occupies a relatively large volume and the post-treatment process is complicated

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