The Exploration And Optimizationof Key Parameters For Preparation Of Low Molecular Weight Heparin

Low molecular heparin is a kind of multicomponent biochemical medicine which is anticoagulant and antithrombotic drugs.At present,the molecular weight is difficult to control and the production process is not stable,so domestic low molecular heparin have a great distance between international standard.In this article,we query different production process of low molecular heparin,we explore and optimize the process parameters of lovenox,fragmin and nadroparin calcium.And on this basis,through experiment confirmed that the optimized production technology can produce low molecular heparin products which quality is stable,safe and reliable.In this paper the main research content is as follows:For lovenox,we obtained the weight ratio of heparin and zephiran chloride is1:2.5?m/m?.Heparin benzene chloride amine salt and benzyl chloride in the best weight ratio is 1:0.8?m/v?,by orthogonal test,we optimized the technological parameters of degradation,finally we obtained the optimal parameters for degradation process conditions,10%of NaOH dosage of esterification,temperature of 50-60?,react 60 min.Using this process,our products can reach the standard.For fragmin,we optimized the technological parameters of degradation by orthogonal test,finally we obtained the optimal parameters for degradation process conditions,the dosage of NaNO₂ is 1.9%-2.5%?m/m?of the weight of the heparin sodium,pH 2.5,degradation temperature is 23?,the reaction time is 60-90 min.We optimized the process of ultraviolet radiation,and determine the intensity of uv irradiation for 300 W light works 150 min.For nadroparin calcium,we optimized the technological parameters of degradation by orthogonal test,NaNO₂ dosage is 2.4%-3.0%?m/m?to heparin sodium,degradation temperature is 19-23?,p H 2 to 3,the reaction time of 60-90 min.The dosage of CaCl₂ is 40%to heparin in replacement calcium,time 16-22 h.Using this process,our products can reach the standard EP and USP.The new production process of low molecular heparin in this paper relative to the old production process,process parameters is easy to control,subsequent degradation process is controllable,molecular weight distribution of low molecular weight heparin product stability.New technology of producing low molecular heparin can be very good to meet national quality standards.This paper provides an important reference process for the domestic production of the low molecular heparin production enterprise.