Structural and activity variability of fractions with different charge density and chain length from pharmaceutical heparins
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Heparin is a structurally complex polysaccharide used as a clinical anticoagulant. It is comprised of a heterogeneous mixture of polysaccharide chains having a variety of sequences and lengths. The production methods and regulatory controls of pharmaceutical heparins have changed over the years. This study assesses the structural and activity uniformity of the polysaccharide chains comprising two contemporary heparin products. The heparin fractions with different sizes and charges were separated with size exclusion and ion exchange chromatography. The fractions were analyzed for their molecular weight properties, di- and tetrasaccharide compositions, and anti-factor IIa and anti-factor-Xa activities. The distribution of these properties through chains of different lengths and ones with different charge density were compared. The results demonstrate that with the increase in heparin purity, activity and molecular weight required by the current pharmacopeia, the uniformity of pharmaceutical heparin products have increased.
KeywordsHeparin Chromatography Compositional analysis Anti-factor IIa activity Anti-factor-Xa activity
This work was supported by National Institutes of Health Grants HL125371, GM38060, HL096972 and HL062244 and HL136271.
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflicts of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 2.Toida, T., Yoshida, H., Toyoda, H., Koshiishi, I., Imanari, T., Hileman, R.E., Fromm, J.R., Linhardt, R.: J: structural differences and the presence of unsubstituted amino groups in Heparan Sulphates from different tissues and species. Biochem. J. 322, 499–506 (1997)CrossRefPubMedPubMedCentralGoogle Scholar
- 3.Linhardt, R.: J: heparin: an important drug enters its seventh decade. Chemistry & Industry. 2, 45–50 (1991)Google Scholar
- 4.Keire, D., Mulloy, B., Chase, C., Al-Hakim, A., Cairatti, D., Gray, E., Hogwood, J., Morris, T., Mourāo, P., Soares, M.D.L.C.: Szajek, a: diversifying the global heparin supply chain: reintroduction of bovine heparin in the United States? Pharmaceutical Technol. 39, 2–8 (2015)Google Scholar
- 7.Szajek, A.Y., Chess, E., Johansen, K., Gratzl, G., Gray, E., Keire, D., Linhardt, R.J., Liu, J., Morris, T., Mulloy, B., Nasr, M., Shriver, Z., Torralba, P., Viskov, C., Williams, R., Woodcock, J., Workman, W.: Al-Hakim. A: The US regulatory and pharmacopeia response to the global heparin contamination crisis. Nat. Biotechnol. 34, 625–630 (2016)PubMedGoogle Scholar