Target-Specific Urokinase Microspheres for Sickle Disease Clots
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Solution Overview
Problem
Existing thrombolytic agents like urokinase and tPA are not targeted to specific clots, leading to potential bleeding in non-affected areas and slower clot dissolution, while current anti-infectious agents do not address vaso-occlusive clots effectively.
Innovation Solution
Development of Target-specific Thrombolytic Urokinase Spheres (TTUS) encapsulating urokinase in albumin microspheres, designed to convert plasminogen into plasmin at clot sites, minimizing systemic distribution and enhancing clot dissolution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If thrombolytic agents like urokinase and tPA are administered as solution, then they can actively dissolve clots, but they are distributed all over the body and cause bleeding in non-affected areas
Solution Approach 1:
The patent encapsulates urokinase in albumin microspheres with diameter of 0.1-10 micrometers, enabling the thrombolytic agent to concentrate at the clot site through passive accumulation in the vascular occlusion. This localized delivery ensures that urokinase is released only where the clot is present, dissolving it effectively while minimizing systemic distribution and reducing the risk of bleeding in non-affected areas
Solution Approach 2:
The patent uses albumin microspheres as an intermediary carrier to deliver urokinase to the clot site. The microspheres serve as a targeted delivery vehicle that accumulates in the vascular occlusion and releases the encapsulated urokinase locally, acting as a mediator between the thrombolytic agent and the clot to achieve precise therapeutic effect while avoiding systemic side effects
2Reliability
If heparin is administered to prevent new clots, then it allows the body's own thrombolysis mechanism to work, but it is not always effective against already-formed clots and can cause heparin-induced thrombocytopenia
Solution Approach 1:
The patent extracts the thrombolytic function from systemic anticoagulation by delivering urokinase directly to the clot site through albumin microsphere encapsulation. This localized delivery approach provides reliable clot dissolution without the need for systemic heparin administration, thereby avoiding heparin-induced thrombocytopenia while maintaining effective thrombolysis
3Productivity
If soluble thrombolytic agents are used to dissolve clots, then they can convert plasminogen into plasmin, but the process is slow and causes overall bleeding
Solution Approach 1:
The patent employs albumin microspheres with diameter of 0.1-10 micrometers that passively accumulate in the vascular occlusion, creating a high concentration of urokinase at the clot site. This localized delivery accelerates the conversion of plasminogen to plasmin specifically where the clot is present, rapidly dissolving the clot while minimizing plasmin generation in other areas and reducing overall bleeding risk
Solution Approach 2:
The patent creates a composite delivery system combining albumin microspheres with encapsulated urokinase. This composite structure enables controlled local release of the thrombolytic agent at the clot site, enhancing dissolution speed through concentrated action while the albumin carrier provides targeted delivery to minimize systemic bleeding effects
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 TTUS effectively target and dissolve vaso-occlusive clots with minimal side effects, reducing the risk of bleeding and accelerating clot resolution.
Implementation Method 1
The TTUS including urokinase encapsulated in albumin microspheres... converting plasminogen in blood of the subject into plasmin molecules that dissolve the clot
Data Source
AI summary
A product, composition, suspension and/or method to dissolve vaso-occlusive clots in vivo in a sickle diseased subject utilizing Target-specific Thrombolytic Urokinase Spheres (TTUS). The TTUS can target vaso-occlusive clots in vivo and then lyse the obstructive blood clots with high efficiency can be intravenously administered to a subject in need thereof. The TTUS are configured to dissolve vaso-occlusive clots by converting plasminogen in blood of the subject into plasmin molecules that dissolves the clot. The nanospheres can encapsulate an enzymatically active bioreactive agent, such as urokinase. Since the active enzyme is targeting and binding essentially only to obstructive clots, there is minimal risk of side-effects to the subject. The nanospheres are less than one micron in diameter, resulting in a size much smaller than red blood cells.