“Supersulfated” heparin fragments, a new type of low-molecular weight heparin: Physico-chemical and pharmacological properties

摘要: Abstract A new type of low-molecular-weight heparin (ss-LMW-H) was prepared (by controlled depolymerization and concurrent sulfation with a mixture sulfuric chlorosulfonic acid), to test the influence extra-sulfate groups on biological properties fragments. The fragments had an average molecular weight ranging from 5000 10,000, sulfate-to-carboxyl molar ratio 2.8–3.1, electrophoretic mobilities NMR spectra distinctly different those parent heparins. Depolymerization oversulfation reduced anticoagulant activity ( ex vivo , in rats) much more than alone, about 10% original APTT 25–30% a.Xa units. By contrast, antithrombotic (venous stasis model, still comparable that heparin, bleeding times were not significantly increased. lipasemic (lipoprotein-lipase-releasing) ss-LMW-H twice heparin. Results are discussed terms contribution charge-density effects activities mechanisms for same