Plasminogen Thrombolysis Without Bleeding Side Effects
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Solution Overview
Problem
Current thrombolytic therapies, such as those using plasminogen activators, suffer from limitations including short half-life, non-specific activation leading to bleeding side effects, and reduced effectiveness on old thrombi, necessitating the development of a more effective and safer thrombolytic agent.
Innovation Solution
Utilizing plasminogen, which has a long half-life and can specifically dissolve both fresh and old thrombi without causing bleeding, by modulating the thrombolytic reaction substrate, allowing for controlled thrombolytic activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If plasminogen activators are used for thrombolytic therapy, then thrombolytic activity is achieved, but the half-life is short and bleeding side effects occur
Solution Approach 1:
Instead of activating plasminogen to plasmin (the conventional approach), the patent uses plasminogen directly as the thrombolytic agent. This inversion of the thrombolytic pathway allows plasminogen to dissolve thrombus without being converted to active plasmin, thereby avoiding the bleeding side effects associated with plasmin activation while maintaining thrombolytic efficacy and achieving a longer half-life
Solution Approach 2:
The patent employs plasminogen as an intermediary substance that mediates thrombolysis through a different mechanism than conventional plasminogen activators. By using plasminogen itself rather than its activators, the system achieves thrombolytic activity through plasminogen's direct action on thrombus components, bypassing the need for plasmin generation and its associated bleeding risks
2Reliability
If plasminogen activators are used, then thrombolytic effect is achieved, but effectiveness on old thrombi is reduced
Solution Approach 1:
The patent changes the key parameter from using active plasmin or plasminogen activators to using inactive plasminogen. This parameter change enables the system to effectively degrade old, organized thrombi that are resistant to conventional thrombolytic agents, as plasminogen can directly interact with and dissolve fibrin structures in chronic thrombus without being inhibited by the organized nature of old clots
3Strength
If plasmin is activated for direct thrombolysis, then strong thrombolytic activity is achieved, but specificity is lost and bleeding occurs
Solution Approach 1:
The patent inverts the conventional thrombolytic approach by using inactive plasminogen instead of active plasmin. This inversion maintains sufficient thrombolytic activity to dissolve thrombus while preserving specificity, as plasminogen does not exhibit the uncontrolled proteolytic activity of active plasmin that leads to systemic bleeding complications
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Plasminogen effectively dissolves thrombi with a longer duration of action, reduced side effects, and improved specificity, particularly effective for old thrombi, making it a promising new strategy for thrombolytic treatment.
Implementation Method 1
Plasmin is a broad-spectrum protease that can hydrolyze several components of the extracellular matrix (ECM), including fibrin
Data Source
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AI summary
The present invention relates to the use of plasminogen in the dissolution of fresh and old thrombus. Compared with other existing thrombolytic drugs, the plasminogen of the present invention can specifically dissolve thrombus without causing side effects such as bleeding. The drug of the present invention also has the advantages of dissolving both fresh and old thrombus, with a long half-life and controllable thrombolytic strength. Therefore, plasminogen may become a brand-new strategy for dissolving thrombus in vivo.