Comparison of Low-Molecular-Weight Heparins Prepared From Bovine Lung Heparin and Porcine Intestine Heparin

Yudong Guan, Xiaohui Xu, Xinyue Liu, Anran Sheng, Lan Jin, Robert J. Linhardt, Lianli Chi

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Currently porcine intestine is the only approved source for producing pharmaceutical heparin in most countries. Enoxaparin, prepared by benzylation and alkaline depolymerization from porcine intestine heparin, is prevalent in the anticoagulant drug market. It is predicted that porcine intestine heparin-derived enoxaparin (PIE) will encounter shortage, and expanding its production from heparins obtained from other animal tissues may, therefore, be inevitable. Bovine lung heparin is a potential alternative source for producing enoxaparin. Critical processing parameters for producing bovine lung heparin-derived enoxaparin (BLE) are discussed. Three batches of BLEs were prepared and their detailed structures were compared with PIEs using modern analytical techniques, including disaccharide composition, intact chain mapping by liquid chromatography-mass spectrometry and 2-dimensional nuclear magnetic resonance spectroscopy. The results suggested that the differences between PIEs and BLEs mainly result from N-acetylation differences derived from the parent heparins. In addition, bioactivities of BLEs were about 70% of PIEs based on anti-factor IIa and Xa chromogenic assays. We conclude that BLE has the potential to be developed as an analogue of PIE, although some challenges still remain.

Original languageEnglish
Pages (from-to)1843-1850
Number of pages8
JournalJournal of Pharmaceutical Sciences
Issue number6
StatePublished - 1 Jun 2016
Externally publishedYes


  • LC-MS
  • NMR spectroscopy
  • bioanalysis
  • bovine lung
  • enoxaparin
  • glycosaminoglycans
  • heparin
  • molecular weight determination
  • porcine intestine
  • processing


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