Mast Cell Stabilization for Safe Thrombolysis

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Solution Overview

Problem

Current thrombolytic treatments for conditions like acute ischemic stroke are associated with significant risks of hemorrhagic complications and brain edema due to mast cell degranulation, with no effective clinical methods to mitigate these risks.

Innovation Solution

Administration of mast cell degranulation-blocking or activation-blocking agents, such as cromoglycate, to prevent mast cell degranulation and stabilize the blood-brain barrier, reducing the severity of cerebral complications during and after thrombolytic therapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If thrombolytic therapy is administered to dissolve arterial thrombi, then the occlusion is removed and blood flow is restored, but hemorrhagic complications and brain edema occur due to mast cell degranulation

Engineering Contradiction:

Improvethrombus dissolution efficiencyVSAvoidhemorrhagic complications and brain edema

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces mast cell degranulation-blocking agents (such as cromolyn sodium, ketotifen, and loratadine) as intermediary substances that mediate between the thrombolytic therapy and the mast cells. These agents block the degranulation process, preventing the release of vasoactive and proteolytic substances that cause hemorrhage and edema, thereby allowing safe administration of thrombolytics

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent applies preliminary anti-action by administering mast cell stabilizing agents before or concomitantly with thrombolytic therapy. This pre-blockade of mast cell degranulation prevents the subsequent harmful effects (hemorrhage and edema) that would otherwise occur during thrombus dissolution, enabling the thrombolytic treatment to proceed safely

Inventive Principle:

Principle #9Preliminary anti-action

2Speed

If thrombolytic substances are used to treat acute ischemic stroke, then reperfusion is achieved, but reperfusion injury and enhanced brain edema occur

Engineering Contradiction:

Improvereperfusion speedVSAvoidreperfusion injury and brain edema

Core Design Contradiction:

SpeedVSObject-generated harmful factors

Solution Approach 1:

Mast cell degranulation-blocking agents serve as intermediary substances that intervene in the reperfusion process. By blocking mast cell degranulation during reperfusion, these agents prevent the release of substances that amplify reperfusion injury and edema formation, allowing rapid reperfusion to occur without the harmful consequences

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent converts the potentially harmful mast cell degranulation response into a beneficial effect by using mast cell stabilizing agents. The same mast cells that would normally cause harm during reperfusion are instead stabilized to protect the brain tissue, transforming the pathological response into a protective mechanism that reduces reperfusion injury and edema

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Loss of time

If thrombolytic therapy is administered rapidly to prevent limb necrosis or brain damage, then treatment effectiveness increases, but the risk of serious intracranial hemorrhage increases

Engineering Contradiction:

Improvetreatment time delayVSAvoidsafety from intracranial hemorrhage

Core Design Contradiction:

Loss of timeVSReliability

Solution Approach 1:

Mast cell degranulation-blocking agents act as intermediary substances that enable rapid thrombolytic administration by protecting against the hemorrhagic complications. These agents create a safety mechanism that allows the thrombolytic therapy to be administered quickly without compromising patient safety from intracranial hemorrhage

Inventive Principle:

Principle #24Intermediary (Mediator)

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

Significant reductions in hemorrhagic complications and brain edema, with up to 40% reduction in ischemic edema and 74% decrease in hemorrhage area, demonstrating the effectiveness of mast cell stabilization in enhancing the safety of thrombolytic treatments.

Implementation Method 1

Administration of mast cell degranulation-blocking or activation-blocking agents, such as cromoglycate, to prevent mast cell degranulation and stabilize the blood-brain barrier

Methodology Applied

Scientific EffectMast cell stabilization:

Data Source

PatentUS8163734B2Use of a mast cell activation or degranulation blocking agent in the manufacture of a medicament for the treatment of a patient subjected to thrombolyses

Publication Date: 2012.04.24 LINDSBERG PERTTU J

AI summary

The invention concerns the use of a mast cell activation- or degranulation-blocking agent in the manufacture of a medicament for preventing and treating cerebral complications caused by thrombolytic treatment. The invention also relates to treatment of patients suffering from cerebral complications associated with thrombolysis. Further, the invention provides thrombolytic compositions comprising a mast cell degranulation-blocking and/or mast cell activation-blocking agent present in a therapeutically effective amount to prevent or reduce any cerebral complications caused by the active thrombolytic component.