Drug delivery system. DDS of thrombolytic agents.

Recently, a remarkable progress has been done in thrombolytic therapy. The progress mainly depends on the newly develped route of administration (for example, intracoronary), and the development of more fibrin-specific fibrinolytic agents. The newly developed thrombolytic drugs, called as the “third generation” agents are t-PA(tissue-type plasminogen activator), which is fibrin-specific, scu-PA(single-chain urokinase-type plasminogen activator), which is activated on fibrin surface, and APSAC(acylated plasminogen-streptokinase activator complex), which has rather long in vivo half-life. The physiological half-lives of these agents in the circulation are short except a kind of acylated plasminogen-streptokinase activator complex (RBL 33575). Plasmin(“first generation” agent)is not used because of its extremely short half-life(0.1 sec)and its lack of fibrin-specificity. However, the “second” and the “third” generation drugs are useful notwithstanding their relatively short half-lives, because fibrinolytic agents must be administered as quick as possible before the development of organ failure due to disturbances of circulation. Quite recently, the drugs with more increasing fibrin selectivity have begun to be designed. These are mutants of the scu-PA, kimeras of these drugs with plasminogen, and hybrids of fibrinolytic agents and anti-fibrin antibody. Moreover, fibrotide, which inhibits activity of PAI, which neutralizes t-PA and urokinase.