MOLECULAR-WEIGHT AND BIOCHEMICAL PROFILE OF A CHEMICALLY MODIFIED HEPARIN DERIVATIVE, SULEPAROIDE(R)

Recently, a new chemically modified derivative of heparin (Suleparoide(R), Syntex Laboratories Buenos Aires, Argentina) was introduced for the prophylaxis of thrombosis and treatment of vascular disorders. This agent is claimed to contain a depolymerized, chemically modified, heparin derivative with similar biologic actions as heparan sulfate. To study the pharmacologic profile of this agent, we have defined its molecular weight distribution profile, utilizing a computerized gel permeation chromatographic system equipped with ultraviolet and refractive index detectors. Suleparoide(R) exhibited a normal molecular distribution profile with no contaminants. It exhibited a weight average of 9.3 K DA and an apparent peak MW of 8.0 K DA. Approximately 50% of the molecular components were < 5.0 K DA and 40% > 5.0 K DA. The results from these studies on the mechanisms show that Suleparoide(R) has anticoagulant activity primarily mediated through Heparin Cofactor-II (HC-II) and because of its novel mechanism of action, further investigations on the biochemical profile of Suleparoide(R) are carried out. Global clotting tests such as Activated Partial Thromboplastin Time (APTT), Heptest and Thrombin Time (TT) revealed a concentration dependent effect in all assays. Plasma samples supplemented with Suleparoide(R) exhibited no significant anti-Xa and anti-IIa activities, However, in the HC-II mediated inhibitory assay for IIa, Suleparoide(R) exhibited significant activity. In contrast, the Antithrombin-III (AT-III) mediated inhibition of IIa was much weaker.