Substituted Cyclodextrins as Procoagulants for NOAC Reversal
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Solution Overview
Problem
Current anticoagulant therapies, particularly non-vitamin K-dependent oral anticoagulants (NOACs), lack effective reversal agents, posing a significant barrier to their widespread use due to the risk of bleeding complications during emergencies, surgeries, or overdoses, as there are no rapid and safe antidotes available to counteract their anticoagulant effects.
Innovation Solution
Development of substituted cyclodextrins with procoagulant properties that can reverse anticoagulant effects and stimulate blood coagulation, applicable regardless of the specific anticoagulant type, providing a rapid and safe solution for emergency situations and bleeding disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If non-vitamin K-dependent oral anticoagulants (NOACs) are used for long-term anticoagulation therapy, then the anticoagulant effect is stable and predictable with few drug-drug interactions, but the risk of bleeding increases and there is no effective reversal agent available
Solution Approach 1:
The patent introduces a procoagulant agent as an intermediary substance that counteracts the anticoagulant effect of NOACs. This mediator restores the coagulation balance by promoting clot formation, effectively reversing the therapeutic effect when bleeding occurs or surgery is needed, without interfering with the primary anticoagulant mechanism during normal therapy
Solution Approach 2:
The patent establishes a preliminary counter-measure by developing a procoagulant reversal agent that can be administered in advance or at the time of bleeding emergencies, surgery, or overdose. This preliminary anti-action prepares the system to quickly neutralize the anticoagulant effect before severe bleeding complications occur
2Adaptability or versatility
If traditional anticoagulants like unfractionated heparin or vitamin K antagonists are used, then reversal agents are available (protamine sulfate or vitamin K), but frequent monitoring is required and the reversal process takes significant time
Solution Approach 1:
The patent employs preliminary action by administering the procoagulant reversal agent that rapidly activates coagulation pathways without requiring the extended synthesis time of vitamin K-dependent factors. The procoagulant agent is prepared and ready to act immediately upon administration, eliminating the 12-24 hour waiting period associated with vitamin K reversal
Solution Approach 2:
The patent changes the kinetic parameter of reversal by using a procoagulant mechanism that acts within minutes rather than hours. This parameter change transforms the reversal timeline from a slow biochemical synthesis process (vitamin K pathway) to a rapid physiological response (procoagulant activation), dramatically reducing the time loss in emergency situations
3Speed
If selective antidotes like dabigatran-specific reversal agents are developed, then rapid reversal is achieved for that specific anticoagulant, but the solution is not applicable to other anticoagulant types
Solution Approach 1:
The patent applies universality by designing a procoagulant agent that functions as a broad-spectrum reversal mechanism applicable to multiple anticoagulant classes including NOACs, heparins, and vitamin K antagonists. This single multi-functional agent can be used across different anticoagulant therapies, eliminating the need for multiple selective antidotes and providing versatile coverage for various bleeding emergencies
Data Source
AI summary
The invention relates to substituted cyclodextrins and pharmaceutically acceptable salts thereof, pharmaceutical compositions, kits of parts and their use as procoagulants. The invention further relates to methods of reversing an anticoagulant effect of an anticoagulant in a subject, methods for reducing or preventing bleeding in a subject and methods for the treatment or prevention of a blood coagulation disorder.