DiNAC Thrombolysis of VWF-Platelet Clots Without Bleeding

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Solution Overview

Problem

Current thrombolytic agents, such as tPA, are ineffective against arterial thrombi composed of von Willebrand Factor (VWF) and platelets, and are associated with high bleeding risks due to hyperfibrinolytic states, necessitating a safer and more efficacious treatment for ischemic strokes and myocardial infarctions.

Innovation Solution

Administration of cystine, specifically N,N′-diacetyl-cystine (DiNAC), which effectively induces thrombolysis in arterial thrombi rich in VWF and platelets, reducing thrombus size and surface area without causing significant bleeding complications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If tPA is used for thrombolysis, then thrombus clearance is improved, but bleeding risk increases due to hyperfibrinolytic state

Engineering Contradiction:

Improvethrombus clearance rateVSAvoidbleeding risk

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the fundamental mechanism parameter from fibrinolytic activation (tPA) to direct thrombus degradation (cystine). This parameter change allows thrombus clearance without triggering the hyperfibrinolytic state that causes bleeding, thus resolving the contradiction between thrombus clearance and bleeding risk

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent substitutes the biochemical mechanism (enzymatic fibrinolysis by tPA) with a direct chemical degradation mechanism (cystine-mediated thrombus breakdown). This substitution eliminates the need for systemic fibrinolytic activation, thereby clearing thrombi without increasing bleeding risk

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Productivity

If tPA is used for thrombolysis, then thrombus dissolution is improved, but efficacy against VWF-platelet-rich arterial thrombi is insufficient

Engineering Contradiction:

Improvethrombus dissolution rateVSAvoidefficacy on arterial thrombi

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent changes the target specificity parameter from fibrin-specific degradation to broad thrombus component degradation. Cystine can degrade both fibrin and VWF-platelet complexes, making it effective against arterial thrombi that are resistant to tPA while maintaining efficient thrombus dissolution

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies universality by using cystine as a multi-functional agent that can degrade multiple thrombus components (fibrin, VWF, platelet aggregates) simultaneously. This multi-functionality ensures reliable efficacy across different thrombus types, particularly VWF-platelet-rich arterial thrombi where tPA fails

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20230372272A1Use of cystine and derivatives thereof as Anti-thrombotic and thrombolytic agents

Publication Date: 2023.11.23 GEORGIA TECH RES CORP

AI summary

The present invention provides compositions that have anti-thrombotic and thrombolytic activity. These compositions are useful, e.g., in the treatment of diseases or disorders associated with thrombus formation, such as stroke and myocardial infraction, and for other uses.