New anticoagulant hirudin-polyvinyl lactam conjugates - for treating e.g. myocardial infarction, peripheral arterial occlusion disorders, deep venous thrombosis and pulmonary embolism

摘要

Conjugates of formula (I), made from polyvinyl lactams and hirudin, desulphatohirudin or coagulation-inhibiting hirudin muteins are new. A = H, OH or CH3. n = 2-4; m = 50-500. B = -CO-, -CH=, -CH2-, -CH2-X-CO-, -CH2-X-Z-CO-, -CH2-X-CO-NH-Z-NH-CO-, -CH2-X-CH2-(1,4-Ph)-N2-, -CH2-X-CH2-CH(OH)-CH2-(1,4-Ph)-N2-, -CH2-X-CO-CH2-CH2-CO or -CH2-X-(4-W-(1,3,5-triazin-2,6-yl)). X = -S-, -O-, -NH-, -N(CH3)- or -N(C2H5)-. Z = 1-6C alkylene or p-phenylene. W = H, Cl or OH. Hir = the hirudin, desulphatohirudin or hirudin mutein, which is bound to B via the serine, threonine or lysine side chain(s). USE/ADVANTAGE - For the treatment and prevention of thromboembolic disorders (e.g. myocardial infarction), peripheral arterial occlusion disorders, deep venous thrombosis and pulmonary embolism. (I) can be used to prevent reocclusion after re-opening of arterial blood vessels by mechanical methods of lysis. Administration is i.v. or i.m. (I) have longer in vivo half life (1-100 hours) than hirudin alone (50 minutes) or even than hirudin-dextran conjugates (7 hours).