Investigation On Purification Technology Of Heparin Sodium

It is composed of polymers of alternating derivatives of ?-D-glucosamine(N-sulfated,O-sulfated,or N-acetylated)and uronic acid(?-L-iduronic acid or ?-D-glucuronic acid)joined by glycosidic linkages,white or almost white,hygroscopic powder,freely soluble in water,insoluble in organic solvents such as acetone,ethanol.Heparin has many significant effects in treating thromboembolic disease,in addition to the anticoagulant effect,heparin has regulating blood lipid,anti-inflammatory,antitumor,antiviral,allergy,and other else biological functions.The purpose of the topic is based on the analysis of the relationship between crude heparin and heparin sodium products about quality control index,and then formulate the quality control indicators of crude heparin which is considered as starting materials.Do further research on the pretreatment process and refining process of heparin sodium,in the end determine the key process parameters of each process step.Depending on the analytical investigation,formulate the quality control indicators of crude heparin : white or almost white,gray or brown,hygroscopic powder or granular,the color should be uniform;The potency of crude heparin should be 50 IU/mg or more;specific rotation should be equal or greater than +40°;After injecting trichloroacetic acid solution,there should have precipitation or turbidity occur;The origin of crude heparin should be made from pigs;Through the control of quality indicators of the crude heparin,using existing production technology for production,the amount of oxidant to reduce the 1/4,the production cycle reduce the 1/6,and the product yield increased by 10%.In the pretreatment process of Heparin sodium,there are some effect in potency of heparin sodium,for example: solution temperature,salt concentration,thermal denaturation time and dosage of hydrogen peroxide which is the most important affect.The potency of heparin reduced gradually with the temperature is rising,the best solution temperature of raw heparin is 40?;In the process of salt solution,with salt concentration is rising the potency of heparin sodium showed a trend of rising first and then reduced,the best salt solution concentration is 0.35 mol/L;Heat changes over time,the heparin titer also presents rising before reducing,the best time of thermal denaturation is 10 mins;With the continuous increasing in the amount of hydrogen peroxide,heparin sodium potency reduced after rising first,the best dosage of hydrogen peroxide is 1%(volume with hydrogen peroxide solution volume).Heparin sodium refining process is made of three parts : ion exchange,precipitation and dry,experiment study: D254 resin adsorption capacity and the desorption rate is good which is suitable for heparin sodium adsorption and desorption of anion resin;The optimal adsorption parameters of static adsorption is:1.5mol/L NaCl concentration,temperature 45?,pH 8.5.Sample is 4 times the amount of resin,flow rate of 2.0 BV/h for the dynamic adsorption;In 4 mol/L eluent of NaCl concentration,flow velocity of 1.5 BV/h for dynamic elution best conditions;Ethanol concentration in the process of heparin sodium precipitation respectively: a deposit 30%,the secondary precipitation 60%;Among baking oven drying,spray drying,freeze drying the freeze drying method as the best way which dryassaying the fineness of product and high potency and low content of residual ethanol.From dissolution,filtration,oxidation to resin purification,ethanol precipitation,dry until the last,the whole process of removing impurity,heparin sodium production yield increased by 10%.