Research On The Quality Control Of Low Molecular Weight Heparin

This paper is mainly studying and researching Low molecular weight heparinstandards.Low molecular weight heparin(LMWH),produced from unfractioned heparin(UFH)by chemical or enzymatic depolymerization methods,are a new type ofanticoagulants.Compared with UFH,LMWH have the similar parent structure with UFHbut involve higher antithrombotic activity,better subcutaneous bioavailability,longerhalf-time,better oral absorption and may slightly lower the risk of bleedingcomplications,so LMWH have a trend of replacing UFH in the future.The manufacturesof LMWH products at home and abroad continue to increase,and there are increasingresearch and development of the new LMWH products,in addition,clinical indicationsenlarge gradually, so it′s particularly important to assure the quality control.Butcurrently,LMWH aren’t the remedies of Ch.P,the active standard has much room forimprovement.This paper refers foreign pharmacopoeia and combines the particularsituation of our LMWH products to research the active standard.This paper has four sections,respectively are molecular weight and its distribution,1,6-anhydro derivatives of Enoxaparin sodium assay，impurities testing and activitydetermination.The first part,molecular weight and molecular weight distribution.It’s one of themost important quality control targets and it’s closely related to activity.There are manydetermining methods of molecular weight,but HPSEC is the most commonly usedmethod. This method needs the reference standard,but there aren’t our own LMWHmolecular weight reference standard,so this part is aimed at providing research idea andreference datas.The research idea is establishing the national LMWH molecular weightreference standard similar to WHO LMWH molecular weight reference standard,whichhas the broad molecular weight range,using the single RI detector and common GPCsoftware to complete the test.This part picked out three LMWH molecular weightreference standards waiting for calibration.The second part,1,6-anhydro derivatives of Enoxaparin sodium assay.1,6-anhydroderivatives are the unique characteristics of Enoxaparin sodium.USP began to recordthis item from the32rd edition,EP draft also began to record this item,but Ch.P didn’trecord the item so far.So this part established the assay method of1,6-anhydro derivatives of Enoxaparin sodium.The third part, the impurities testing.The impurities testing methods aren’t perfectand have the low detection sensitivities in the active standard,so the impurities testingmethods of the active standard need to be perfect.This part established residual solventsand other impurities testing methods.The fourth part,activity determination.Activity is the other one of the mostimportant quality control targets.Anti-Factor Ⅹa activity and anti-Factor Ⅱa activityare the essential element playing anticoagulation into fullplay.The active standard aboutactivity determination(assay) is a unified standard,only meeting EP or BP LMWH profilerequirements. This part utilizes chromophoric substrate method to test the three LMWHproducts respectively,which can provide data reference for quality control respectively..This subject studied these four parts according to active standard.This paper pickedout three molecular weight standards waiting for calibration,providing research idea andreference data of establishing the national LMWH molecular weight standard,established1,6-anhydro derivatives of Enoxaparin sodium assay method,which is reported for thefirst time at home, established and improved impurities testing methods and respectivelytested anti-Factor Ⅹa and anti-Factor Ⅱa activity of three LMWHs to provide datareference for quality control respectively.At the same time,this paper has made up a draftof three LMWHs quality standards.