Anticoagulant properties of semisynthetic polysaccharide sulfates

Several naturally occurring polysaccharides were purified and subsequently sulfated by chlorosulfonic acid-pyridine complex. These were isolated as the sodium salt and further purified by ECTEOLA cellulose chromatography. Anticoagulant properties of the sulfated polysaccharides were compared with commercial heparin by measuring their in vitro effects on activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using pooled normal human plasma. In general, all the compounds exhibited antithrombic (anti-TT) properties similar to heparin but were less effective than heparin in inhibiting APTT or PT. The in vivo anticoagulant properties were also compared with commercial heparin by injecting rats a single intraperitoneal dose and measuring plasma APTT at 2, 4 and 6 hour intervals. All of the compounds including heparin increased APTT significantly at 2 hours and then gradually returned to near normal value after 6 hours. Larchwood xylan sulfate was almost as active as heparin in inhibiting APTT while the rest of the compounds were less active. Toxicological studies using rats showed wide variations in the LD50 of various compounds. Sulfated xylan and heparin were least toxic while sulfated polysaccharide of locust bean was most toxic. For most of the compounds the LD50 was 5-100 fold higher than the effective dosage.