Thrombolytic agents

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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A61K 31415

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active

059326034

DESCRIPTION:

BRIEF SUMMARY
DESCRIPTION

1. Technical Field
The present invention relates to a thrombolytic agent capable of being orally administered, said agent comprising 6-amidino-2-naphthyl acceptable acid addition salt thereof.
2. Background Art
A clot formed by coagulation of blood in the heart or the blood vessel is called a thrombus, and a pathological process associated with the formation of said thrombus is called thrombosis. Thrombosis includes a variety of pathological states such as cerebral infarction, myocardial infarction, pulmonary infarctionm etc.
The formation of thrombus is originally a mechanism that serves to prevent the potential leakage of blood from the injured part of the blood vessel when it is injured for some reason. The formation of thrombus is closely associated with variation in blood components, abnormal blood circulation, and changes in properties of the walls of blood vessels. That is, when a blood vessel is injured for some reason, blood platelets adhere to the injured site and aggregate to form an aggregated mass in order to prevent bleeding therefrom. Furthermore, platelets, by aggregating to one another, release substances that activate coagulation factors present in the blood to promote thrombus formation leading to the formation of more rigid thrombi. There are a number of coagulation factors, which constitute the complex mechanism of activation in which the reaction proceeds in a cascade manner by one enzyme activating the next (the blood coagulation system). Also, some coagulation factors are directly activated by wounds or injured tissues, and the coagulation proceeds in a variety of ways. However, there are a lot of substances present in the blood that suppress the progress of coagulation, thereby suppressing the enhancement of abnormal coagulation. Blood clots are formed as needed but are lysed by the enzymes (the fibrinolytic enzymes) that dissolve clots in the blood when the hemostatic action becomes no longer needed and the blood vessel returns to the original state (the fibrinolytic system).
Thus, thrombus formation involves a variety of factors. However, the factors that are most directly involved in thrombus formation are platelets, coagulation factors, fibrinolytic factors and the like, and conventionally drugs affecting the above mentioned blood components have been developed and used for treatment of thrombosis that are caused by the presence of abnormal thrombi.
The methods of treatment of thrombosis are roughly divided into two groups by the mechanism of action: the anti-thrombotic therapy that prevents formation of thrombi, and the thrombolytic therapy that dissolves the formed thrombi.
The anti-thrombotic therapy has further been classified into two: the anti-platelet therapy and the anti-coagulation therapy.
The anti-platelet therapy is intended to suppress the functions of platelets involved in the early stages of thrombus formation and drugs such as classical aspirin and many other drugs that can be administered orally have been developed. They are now used to prevent recurrence of cerebral infarction, myocardial infarction, etc., to prevent occlusion after various bypass surgeries, to prevent restenosis after coronary angioplasty, and the like. Thus, they are used more as prophylactic drugs against thrombus formation than as therapeutic drugs. They have the problem of the presence of individual variation in appearance of efficacy, and of bleeding tendency because of the need for prolonged administration.
The anti-coagulation therapy is intended to inhibit thrombus formation by suppressing coagulation factors and is classified into the drugs for inhibiting activity of coagulation factors and the drugs for suppressing formation of coagulation factors. The former includes heparin, enzyme inhibitors, and the like. Since they are injections, they show anti-coagulation activity by intravenous administration. However, they have to be used under the supervision of a physician and also have the problem of bleeding tendencies and the like. The latter is a method that suppresses th

REFERENCES:
patent: 4777182 (1988-10-01), Fujii et al.
Ethical Drugs, Pharmaceutical Drugs in Japan, Aug. 1995, cover sheet and one-page description concerning the uses of the products(*) listed in the Oct. 1996 Drugs in Japan; Ethical Drugs publication.
Drugs in Japan; Ethical Drugs, published by Yakugyo Jiho Co., Ltd., Tokyo, Japan, Oct. 1996 Parts Only.
One-page translation of Table 2 in the 1994 Journal of Japanese College of Angiology.
Journal of Japanese College of Angiology, 1994, vol. 34, No. 6, including a one-page summary in English on p. 6 of the Journal.

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