Stimuli-Responsive Block Copolymers for DMSO-Free Embolization
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Solution Overview
Problem
Existing liquid embolic systems for neural and peripheral diseases face issues due to the toxicity of DMSO, causing tissue necrosis and vessel spasm, and require additional patient consent for side effects, while aqueous-based systems lack effective alternatives with drug loading and biocompatibility.
Innovation Solution
Compositions comprising block copolymers with poly(N-isopropylamino acrylamide) and poly(2-(di-(C3-5)alkylamino)ethyl methacrylate) blocks, which form gels in vivo upon pH and temperature changes, combined with anionic polymers and imaging/therapeutic agents, providing a biocompatible and drug-delivery capable embolic solution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If DMSO solvent based embolic systems are used, then embolization effectiveness is achieved, but tissue necrosis and vessel spasm occur due to toxicity
Solution Approach 1:
The patent extracts and removes the toxic DMSO solvent from the embolic system, replacing it with water as the base solvent. This eliminates the harmful effects of DMSO (tissue necrosis and vessel spasm) while maintaining the embolization functionality through alternative mechanisms using water-soluble polymers and pH/temperature-responsive gelation.
Solution Approach 2:
The patent changes the chemical parameter of the solvent from DMSO to water, and utilizes pH and temperature parameter changes to trigger gelation of the embolic material in vivo. The composition transitions from liquid at room temperature to gel at physiological conditions, providing both safety and effectiveness.
2Object-affected harmful factors
If aqueous based embolic systems are used, then biocompatibility and ease of use are improved, but effective alternatives with drug loading capability are lacking
Solution Approach 1:
The patent creates a multi-functional aqueous-based embolic system that simultaneously provides biocompatibility, embolization capability, and drug loading functionality. The pH/temperature-responsive block copolymer serves multiple purposes: as the embolic agent itself, as a drug carrier, and as a gelation trigger, eliminating the need for separate DMSO-based systems and enabling versatile therapeutic applications.
Solution Approach 2:
The patent employs composite materials consisting of block copolymers with specific functional blocks (pH-responsive and temperature-responsive segments) combined with anionic polymers. This composite structure enables both the aqueous biocompatibility and the drug loading capability through the polymer's ability to form gel networks that can encapsulate therapeutic agents.
3Object-affected harmful factors
If block copolymers forming gels in vivo are used, then toxicity is reduced and embolization effectiveness is improved, but system complexity increases
Solution Approach 1:
The patent segments the polymer structure into distinct functional blocks: pH-responsive blocks that trigger initial gelation and temperature-responsive blocks that provide secondary stabilization at physiological temperature. This segmentation allows each block to perform its specific function independently, simplifying the design logic despite the overall molecular complexity.
Data Source
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AI summary
In various embodiments, the present disclosure pertains to compositions for medical use. In some embodiments, the compositions comprise an aqueous solution of a block copolymer that comprises one or more poly(N-isopropylamino acrylamide) blocks and one or more poly(2-(di-(C1-5)alkylamino) (C1-5)alkyl methacrylate) blocks. In some embodiments, the compositions are in liquid form at 25°C. Other embodiments pertain to methods that comprise delivering such compositions to a patient.