Activated factor X(FXa) stimulants as new antihemorrhagic agents for topical use

Abstract

The activated coagulation Factor X (FXa) stimulating agents may be used in the treatment of hemorrhages in a subject. Compounds and combinations are described which are particularly useful for the topical treatment of hemorrhaging in healthy subjects or in patients with hemorrhagic diathesis.

Description

Stimulators of activated factor X (FXa) as new topical antihemorrhagic agents field of invention The present invention relates to the topical treatment of bleeding in an individual through the use of FXa stimulators. The present invention is based on the discovery that lipidated tissue factor (TF) exhibits a novel regulatory action that stimulates all proteolytic activity of both forms of FXa, soluble FXa and FXa bound to the prothrombinase complex (amidolytic activity and prothrombin hydrolytic activity). Background of the invention 1. Physiology of coagulation Hemostasis is the mechanism by which an organism responds to bleeding that involves the participation of two processes that act immediately after injury and remain active for long periods of time. The first process, known as primary hemostasis, is characterized by vasoconstriction and formation of platelet aggregates at the site of vascular injury. The second process is called secondary hemostasis, during which...

AI Technical Summary

Problems solved by technology

(2) Administration requires special equipment

(4) Unable to provide appropriate or convenient treatment for specific bleeding events

(5) Lack of acute effect

(6) Fibrin clot instability

(7) The side effects are very dangerous

In this patent application, the inventors demonstrated that phospholipids (phosphatidylserine and phosphatidylcholine in different percentages and molar concentrations) do not enhance the procoagulant effect mediated by lipidated TF (Table 21), which indicates that U.S. Patent No. 4,721,618 No. and WO02 / 086118 the claimed synergy is limited to serine protease-activated coagulation factors and does not apply to membrane receptors such as TF

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