Preparation of low molecular weight heparins from bovine and ovine heparins using nitrous acid degradation

Shaoshuai Xie, Yudong Guan, Peipei Zhu, Fei Li, Mengqi Yu, Robert J. Linhardt, Lianli Chi, Lan Jin

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Low molecular weight heparins (LMWHs) are important anticoagulant drugs. Nitrous acid degradation is a major approach to produce LMWHs, such as dalteparin. Due to the foreseeable shortage of porcine intestinal mucosa heparin and other potential risks, expansion of other animal tissues for heparin preparation is necessary. Heparins from different tissues differ in structure and bioactivity potency, and these variations may be carried over to the LMWH products. Sophisticated analytical techniques have been applied to compare various versions of dalteparins produced from porcine intestinal, bovine lung and ovine intestinal heparins to elucidate the effects of different animal tissues starting materials and processing conditions on the properties of final dalteparin products. With adjusted depolymerization conditions, versions of dalteparins that qualify under the European Pharmacopeia (EP) specifications were manufactured using non-porcine heparins. Dissimilarities among the three interspecies animal tissue heparin-derived dalteparins regarding fine structures are also disclosed, and their origins are discussed.

Original languageEnglish
Pages (from-to)83-91
Number of pages9
JournalCarbohydrate Polymers
Volume197
DOIs
StatePublished - 1 Oct 2018
Externally publishedYes

Keywords

  • Biosimilar
  • Bovine lung heparin
  • Dalteparin
  • LMWHs
  • Ovine intestinal heparin
  • Porcine intestinal heparin

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