Chernyshenko V. Search and study of the mechanisms of action of biologically active compounds acting on the blood coagulation

The thesis is devoted to the search of the way to control the blood coagulation: stimulation of the extravascular and prevention of the intravascular clotting. Effective extravascular thrombus formation is the important for effective termination of bleeding and prevention of blood loss. On the other hand, intravascular thrombosis is the pathological process leading to the ischemia of important tissues and organs. That is why the aim of the thesis being focused on biotechnological aims finally achieves the medical goals. Author performed the analysis of molecular mechanisms of extravascular and intravascular coagulation that allowed selecting the platelet aggregation and fibrin polymerization as the most promising targets of antithrombotic action; the prothrombin conversion to thrombin was selected as the main object of procoagulant action of hemostatics. Several biologically active compounds and biomaterials were selected as the platelet effectors. In particular, metabolites of lignans (entherodiol and entherolacton), epigallocatechin gallate, N-stearoylethanolamine, integrin receptors antagonists were shown to inhibit platelet activation and aggregation; silica dioxide and Е1-containing fragments of fibrin enhanced platelet aggregation; nanodiamonds and fullerene C-60 as well as some biomaterials (PU and PVC) did not act on platelets directly. The antithrombotіc and proangiogenic action of calix[4]arene C-145 were found in studies in vivo. The modification of different biomaterials by enzyme prothrombin activator was proposed for the increasing of their hemostatic properties. The ‘Carbohemostat’ based on the activated carbon adsorptive material, procoagulant collagen matrix and autologuous fibrin composite were developed. The efficacy of such modification was proved in studies in vitro and in vivo. The unique way to thrombin preparation was developed.