Malonate Salt Use to Limit Stroke Reperfusion ROS Injury
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Solution Overview
Problem
Current treatments for ischemic stroke reperfusion injury are inadequate, as they either cause harm in hemorrhagic stroke or require time-consuming diagnostic imaging, leading to prolonged ischemic time and extensive tissue damage.
Innovation Solution
The use of malonate salts, particularly disodium malonate, which are administered before or during reperfusion to inhibit succinate oxidation by succinate dehydrogenase, reducing reactive oxygen species production and mitigating reperfusion injury.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If emergency imaging is performed to determine stroke type, then diagnostic accuracy is improved, but time loss increases and ischemic time is prolonged
Solution Approach 1:
The patent applies preliminary action by administering malonate salt before the diagnostic imaging is completed and before reperfusion therapy is initiated. The malonate salt is given as a preliminary protective measure that activates before the harmful reperfusion injury can occur, thus preventing tissue damage without waiting for stroke type confirmation.
Solution Approach 2:
The patent applies preliminary anti-action by using malonate salt to preemptively inhibit succinate dehydrogenase and prevent ROS production before reperfusion injury can occur. This counteracts the potential harmful effect of reperfusion in advance, protecting ischemic tissue without requiring certain knowledge of stroke type.
2Reliability
If clot-dissolving drugs are administered, then ischemic tissue salvage is improved, but harm increases in hemorrhagic stroke
Solution Approach 1:
The patent applies parameter changes by using malonate salt, which has a different mechanism of action compared to traditional clot-dissolving drugs. Malonate salt inhibits succinate dehydrogenase and prevents ROS production, providing protective effect without the bleeding risks associated with thrombolytic agents. This changes the therapeutic parameter from direct clot dissolution to metabolic inhibition.
Solution Approach 2:
The patent applies the intermediary principle by using malonate salt as a mediator between ischemia and reperfusion. Rather than directly dissolving clots or stopping ischemia, malonate salt acts as an intermediary protective agent that prevents the harmful metabolic effects of reperfusion, thus protecting tissue without interfering with clotting mechanisms.
3Productivity
If reperfusion therapy is initiated, then blood flow restoration is improved, but reperfusion injury increases
Solution Approach 1:
The patent applies preliminary anti-action by administering malonate salt before reperfusion therapy to preemptively inhibit the harmful metabolic effects. Malonate salt blocks succinate dehydrogenase and prevents ROS production before reperfusion occurs, thus counteracting the potential injury while allowing beneficial blood flow restoration to proceed.
Solution Approach 2:
The patent applies the blessing in disguise principle by converting the harmful effect of reperfusion (ROS production and tissue damage) into a beneficial outcome. By using malonate salt to inhibit succinate dehydrogenase, the patent transforms the potentially harmful reperfusion process into a protected, beneficial revascularization event that restores blood flow without causing injury.
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
Malonate salts effectively penetrate tissues and mitochondria, minimizing reperfusion injury by reducing ROS production, thus protecting ischemic tissue and allowing for rapid administration before stroke diagnosis, regardless of stroke type.
Implementation Method 1
inhibit succinate oxidation by succinate dehydrogenase, reducing reactive oxygen species production
Implementation Method 2
inhibit succinate oxidation by succinate dehydrogenase
Implementation Method 3
Malonate salts effectively penetrate tissues and mitochondria
Data Source
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AI summary
The present invention relates to salts and compositions for use in the treatment of ischaemic stroke reperfusion (IR) injury. In particular, the present invention relates to a salt of formula (I) for use in treating or preventing ischaemic stroke reperfusion injury, wherein X, Y, n, m, Z, A and B are as defined herein.