The Improvement Of Post-treatment Technology Of Heparin Production Process And The Study Of Low Molecular Weight Heparin Production Process

Heparin is an anticoagulant extracted from porcine intestinal. Its major biological activity is anticoagulation and antithrombosis. It also has bioactivities of adjusting blood fat levels, anti-inflammatory, anti-alergy and so on. The purpose of this study is to improve the production process of crude heparin by combination of membrane separation and spray drying technology, which can achieve greater production efficiency and reduce production costs. Another part of this study was research for the production process of low molecular weight heparin (LMWH), we also hope membrane separation and spray drying technology can be used in LMWH, so we can design a production route for LMWH production. This thesis mainly contained three parts as followed:(1) Crude heparin produced by Hubei Wurui Biotechnology Corporation were used as original materials,the production process of crude heparin were optimized through single-factor test and multi-factor combination test. The results showed that the best condition for spray drying is 200℃. The appearance and potency of the product were improved by the combination of membrane separation and spray drying. The appearance of the product changed from brown solid into white powder, and the potency raised from 87.19±0.40 IU/mg to 112.93±3.80 IU/mg.(2) Sheep plasma method for the determination of heparin potency was established in our laboratory.We also established chromogenic substrate method for the determination of LMWH anti-IIa and anti-Xa activity and high performance gel permeation chromatography (HPGPC) for the determination of the molecular mass distribution of LMWH in our laboratory.(3) Production process of enoxaparin- the most wildly used LMWH was explored in our laboratory, and enoxaparin was successfully prepared. Meanwhile some conditions of the LMWH production were studied. On the study of membrane separation of low molecular weight heparin,some preliminary results on membrane separation of low molecular heparin were obtained.In this thesis, the membrane separation and spray drying technology was used for the production of crude heparin, and the determination methods of potency and mass distribution were established, preparation of LMWH was also studied as a preliminary research.