Low-Dose DC009 Dosing for Acute Ischemic Stroke Treatment
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Solution Overview
Problem
Current treatments for acute ischemic stroke, such as alteplase, have limited efficacy and are associated with a high risk of bleeding and a narrow therapeutic window, necessitating the development of safer and more effective therapies.
Innovation Solution
Administration of a low dose of DC009, a peptide-tetrahydroisoquinoline conjugate, at 0.01-0.075 mg/kg/dose, with a plasma Cmax of less than 200 ng/mL, to treat acute ischemic stroke, allowing for a potentially extended treatment time window and minimizing bleeding risks.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If thrombolytic therapy is administered, then recanalization of occluded vessels is improved, but risk of hemorrhage and other complications increases
Solution Approach 1:
The treatment is divided into two distinct phases: first mechanical thrombectomy to physically remove the clot, then targeted thrombolytic therapy only at the distal site. This segmentation allows recanalization to be achieved through mechanical means while minimizing systemic thrombolytic exposure and associated hemorrhage risks.
Solution Approach 2:
A catheter-based delivery system acts as an intermediary to transport thrombolytic agents directly to the distal occlusion site. This targeted delivery mechanism ensures the thrombolytic drug is applied precisely where needed, reducing systemic circulation of the drug and thereby lowering hemorrhage risk while maintaining effective recanalization.
2Reliability
If endovascular thrombectomy is performed, then mechanical clot removal is improved, but procedural complexity and time requirements increase
Solution Approach 1:
The catheter system is designed with multi-functionality, capable of performing both mechanical thrombectomy and delivering thrombolytic agents through the same device platform. This universal design reduces the need for multiple separate devices and procedures, thereby simplifying the overall procedural complexity while maintaining effective clot removal.
Solution Approach 2:
The patent combines mechanical thrombectomy and pharmacological thrombolysis into a single integrated procedure. By merging these two approaches into one coordinated intervention, the patent reduces the number of separate procedural steps and device exchanges, thereby reducing overall procedural complexity and time requirements.
3Reliability
If thrombolytic agents are used, then fibrin clot dissolution is improved, but treatment time and drug dosage requirements increase
Solution Approach 1:
Mechanical thrombectomy is performed first as a preliminary action to remove the bulk of the occluding clot before administering thrombolytic agents. This preliminary mechanical clearance reduces the clot burden that the thrombolytic drug must dissolve, thereby accelerating the overall recanalization process and reducing treatment time.
Solution Approach 2:
The patent uses mechanical thrombectomy to perform the majority of the clot removal work, with thrombolytic agents providing only partial assistance for residual clot dissolution. This approach of relying primarily on mechanical action rather than excessive thrombolytic dosage reduces both treatment time and drug requirements while achieving effective recanalization.
Data Source
Figure 1A~1B
Figure 2
Figure 3~4
AI summary
The present invention is directed to a method of treating acute ischemic stroke in a human comprising administering one of more low doses of DC009, wherein the dose is about 0.01-0.075 mg/kg/dose. The low dose administration is safe and effective in treating acute ischemic stroke in a human subject.