Thrombolytic subtilisins: 615.273.55

Abstract

Summary. Thrombolytic agents based on serine proteinase-plasminogen activators effectively eliminate critical occlusion in acute myocardial infarction and ischemic stroke. However, their use is limited to a single intravenous injection. The use of serine proteinases-subtilisins significantly expands the horizon of thrombolytic therapy. Almost 80 years have passed since the discovery of subtilisins in 1947, during
which interest in subtilisins has manifested itself in the publication of more than 9,000 scientific articles and the protection of more than 3,000 inventions, one third of which are related to medicine. Long-term chemical, biological and medical research has allowed not only to formulate the concept of using subtilisins, but also to develop original technological solutions for the production of agents based on them. As a result, a new group of agents is emerging — oral thrombolytics, which form the basis of a fundamentally new pharmacological technology that addresses two significant issues of modern pharmacological thrombolysis — the impossibility of prolonged dose-dependent thrombus dissolution and oral administration. Currently, new agents are being developed in three directions — based on subtilisin Carlsberg, nattokinase and lumbrokinase. To date, two thrombolytic subtilisin-based agents have been authorized and introduced into real clinical practice — Trombovazim® and Disolf®, which are successfully used to treat thrombosis. In the Russian Federation, Trombovazim® is approved as an infusion thrombolytic agent for the treatment of acute myocardial infarction and as a thrombolytic agent in the complex treatment of venous diseases. The developers of Disolf® have not yet begun authorization process in Russia. This article presents an analytical review of scientific and practical developments in the field of subtilisin use.

For citation: Madonov P.G., Mishenina S.V., Kikhtenko N.V., Roitman E.V. Thrombolytic subtilisins. Tromboz, gemostaz i reologiya. 2025;(2):53–65. (In Russ.).

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