Synthesis and anticoagulant activity of sodium alginate sulfates

Sodium alginate sulfates prepared from sodium alginate through reaction with an uncommon sulfating agent (N (SO3Na)3) which was synthesized by sodium bisulfite and sodium nitrite in aqueous solution. The factors that could affect the degree of substitution (DS) of sodium alginate sulfates were investigated in detail. A sodium alginate sulfate with DS of 1.87 was obtained under optimal conditions. The structures of the derivatives were characterized by FTIR and 13C NMR. FTIR spectra showed the characteristic absorptions of sulfate ester bonds at 1249 cm−1 and 873 cm−1. The in vitro coagulation assay of human plasma containing the sodium alginate sulfates was determined with respect to activated partial thromboplastin time (APTT), thrombin time (TT) and prothombin time (PT). These activities strongly depended on the DS, molecular weight (Mw) and the concentration of sodium alginate sulfates. The introduction of sulfate groups to hydroxyl groups greatly prolonged the APTT and TT. Low S% and concentration sodium alginate sulfates showed little anticoagulant activity. The high DS and concentration could inhibit the activity of IIa and Xa to prolong APTT and TT. The low molecular weight resulted in higher anti-factor Xa activity to promote anticoagulant activity. Generally, the introducing of sulfate groups could not increase PT, it had little effect on coagulation factors in the extrinsic pathway.