heparin family leader in anticoagulation ~ enoxaparin sodium

2022-01-13 13:51:36

in recent years, when it comes to anticoagulants, it is no surprise that the industry will be small molecule chemical drugs such as rivaroxaban, apixaban, dabigatran ester, etc., but in terms of practical clinical applications, heparin and low molecular weight heparin are still anticoagulants with high usage rates for many years, accounting for a higher proportion of the market share of anticoagulants, which is difficult to replace. the clinical efficacy of low molecular weight heparin is better than that of heparin, which is more indisputable, and among the many low molecular weight heparin drugs that have been listed, enoxaparin sodium is definitely the leader in heparin drugs with its efficacy advantages of being listed for many years and has maintained sales above the blockbuster level.

1. introduction to enoxaparin sodium

Enoxaparin sodium, originally developed by the French Rhone-Poulenc Rorer (later merged with the German Hoechst to form Sanofi), is a heparin sodium extracted from the mucosa of the porcine intestine, a derivative of heparin benzyl ester sodium obtained after esterification, and then a low molecular weight heparin sodium generated by alkali cleavage. Structurally, it consists of many complex undefined oligosaccharides. According to current understanding, most oligosaccharides have 4-enol pyranoic acid at the non-reducing end of the sugar chain, and 1,6-dehydrated structure at the reducing end of the sugar chain accounting for 15 to 25% of all sugars.

The weight average molecular weight of enoxaparin sodium is between 3800 and 5000, the mass percentage of oligosaccharides with a molecular weight < 2000 is between 12 and 20%, the mass percentage of oligosaccharides with a molecular weight of 2000 to 8000 is 68 to 82%, the titer of anti-Xa factor per milligram is 90 to 125 IU according to dry products, and the ratio of anti-Xa to anti-IIa is between 3.3 and 5.3.

2. enoxaparin sodium ~ mechanism of action

Enoxaparin sodium is a low molecular weight heparin after β-elimination and chemical cleavage by mother heparin, and its active site is a unique 1,6-dehydrated cyclic dicyclic structure, which has pharmacological properties that distinguish it from other low molecular weight heparins. Enoxaparin, by binding to antithrombin III (AT-III), catalyzes the inactivation of coagulation factors IIa, Xa, IXa, XIa and XIIa, of which, mainly by inhibiting Xa, exerts an anticoagulant effect.

Low molecular weight heparin, the role of Xa, IIa is mainly related to the length of the molecular chain, usually the molecular chain of heparin reaches more than 18 sugar units, while it has the effect of inactivating IIa and Xa, while most of the molecular chains of low molecular weight heparin are less than 18 sugar units, the effect of inactivating Xa is stronger, and the effect on coagulation factor IIa is smaller. Therefore, the average molecular weight of enoxaparin sodium is 4500Da anti-Xa/IIa ratio of 41, which is significantly higher than the average molecular weight of unfractionated heparin 15000Da.

3. summary

enoxaparin sodium, perhaps the biggest regret is that the dosage form is single, can only be made into injections... but there is no way, the entire heparin family of products is like this, which is also due to its macromolecular structure. but even so, its contribution to the field of anti-condensation cannot be ignored. from the initial heparin, to today's widely used low molecular weight heparin, and then to the ultra-low molecular weight heparin in the development process, whether in technology or in terms of efficacy, the development of heparin drugs has been greatly developed and product innovation, and with its irreplaceable clinical status, the glory of heparin drugs is believed to continue!