Тромболитические субтилизины
Bibliographic record
Abstract
Тромболитические препараты на основе сериновых протеиназ – активаторов плазминогена эффективно устраняют критическую окклюзию при остром инфаркте миокарда и ишемическом инсульте. Однако их применение ограничено однократным внутривенным введением. Использование сериновых протеиназ–субтилизинов существенно расширяет горизонт тромболитической терапии. С момента открытия субтилизинов в 1947 г. прошло почти 80 лет, в течение которых интерес к субтилизинам проявился в публикации более 9000 научных статей и защите более 3000 изобретений, треть из которых относится к области медицины. Многолетние химические, биологические и медицинские исследования позволили не только сформулировать концепцию применения субтилизинов, но и разработать оригинальные технологические решения по производству лекарственных препаратов на их основе. В результате возникает новая группа лекарственных препаратов – пероральные тромболитики, составляющие основу принципиально новой фармакологической технологии, которая устраняет 2 существенные проблемы современного фармакологического тромболизиса – невозможность пролонгированного дозозависимого растворения тромба и невозможность перорального применения. В настоящее время разработка новых препаратов идет в 3 направлениях – на основе субтилизина типа Carlsberg, наттокиназы и люмброкиназы. На сегодняшний день зарегистрированы и внедрены в реальную клиническую практику 2 тромболитических лекарственных препарата на основе субтилизинов – Тромбовазим® и Disolf®, которые успешно применяются для лечения тромбозов. В Российской Федерации лекарственный препарат Тромбовазим® зарегистрирован в качестве инфузионного тромболитика для лечения острого инфаркта миокарда и как тромболитический агент в комплексном лечении заболеваний вен. Разработчики препарата Disolf® пока не приступили к регистрации в нашей стране. В данной статье представлен аналитический обзор научно-практических разработок в области применения субтилизинов. 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".