RGD Peptide Thrombolytic Composition for Vascular Occlusion
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Solution Overview
Problem
Current thrombolytic agents for treating ischemic stroke, such as recombinant tissue plasminogen activator (r-tPA), have limited efficacy in recanalizing occluded arteries and are associated with risks like reperfusion injury, hemorrhage, and reocclusion, while targeting fibrin alone is insufficient due to resistance from platelet-rich thrombi.
Innovation Solution
A composition comprising a peptide with the Arg-Gly-Asp motif, which binds to the platelet glycoprotein IIb/IIIa receptor to dissolve preformed thrombi, potentially offering improved thrombolytic activity and reduced side effects by targeting platelets in addition to fibrin.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If recombinant tissue plasminogen activator (r-tPA) is used for thrombolytic treatment, then fibrin dissolution is achieved, but recanalization success rate remains low and reocclusion risk increases
Solution Approach 1:
The patent combines two distinct thrombolytic mechanisms into a single composition: fibrin dissolution (via tPA or similar agents) and platelet aggregation inhibition (via GPIIb/IIIa antagonists). This dual-action approach addresses both fibrin-rich and platelet-rich thrombus components, thereby improving recanalization success rates while reducing reocclusion risks that plague single-mechanism therapies
2Object-affected harmful factors
If thrombolytic agents targeting fibrin are used, then fibrin dissolution occurs, but resistance from platelet-rich thrombi reduces treatment effectiveness
Solution Approach 1:
The patent segments the thrombus into its two primary components: fibrin matrix and platelet aggregates. By applying separate therapeutic mechanisms targeted at each component (fibrinolytics for the matrix, GPIIb/IIIa antagonists for platelets), the treatment overcomes the resistance that arises when only one component is addressed, thereby improving overall treatment effectiveness
3Productivity
If current thrombolytic treatments are administered, then some recanalization is achieved, but reperfusion injury and hemorrhage risks increase
Solution Approach 1:
The GPIIb/IIIa antagonist acts as an intermediary protective agent that modulates the thrombolytic process. By inhibiting platelet aggregation during fibrin dissolution, it prevents excessive platelet activation and microvascular damage that lead to reperfusion injury and hemorrhage, thereby enabling safer recanalization without compromising recanalization achievement
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
The peptide effectively dissolves preformed thrombi, enhancing recanalization rates and reducing the risk of reocclusion and bleeding complications, thereby improving treatment outcomes for stenotic or occlusive vascular diseases.
Implementation Method 1
The peptide with the Arg-Gly-Asp motif binds to the platelet glycoprotein IIb/IIIa receptor
Data Source
AI summary
The present invention relates to: a composition for dissolving thrombi comprising a peptide comprising the Arg-Gly-Asp motif; a pharmaceutical composition for treating stenotic or occlusive vascular diseases which comprises the same; and a thrombus dissolving method and a method for treating stenotic or occlusive vascular diseases, comprising the step of administering the same. The compositions and methods of the present invention have the advantage that they effectively break down already formed thrombi by adopting the principle of targeting integrin within the thrombus such as platelet surface GPIIb-IIIa, which is not the same as the existing principle of plasminogen activation. Also, the compositions and methods of the present invention have a nerve-protecting function as they effectively open as far as the microvasculature, without the occurrence of restenosis after penetration.