rPEG Block Copolymers for Low-Immunogenic Medical Particles
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing amphiphilic block copolymers comprising poly(ethylene oxide) (PEO) often trigger an immune response leading to the formation of anti-PEG antibodies, causing adverse reactions and loss of the 'stealth effect', which affects their functionality in medical devices and pharmaceutical applications.
Innovation Solution
Development of block copolymers with randomized polyethylene glycol (rPEG) structures featuring C1 to C3-alkyloxymethyl side chains, which reduce interaction with anti-PEG antibodies, allowing for controlled hydrophilicity and crystallinity, and enhancing miscibility and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If poly(ethylene oxide) (PEO) blocks are used in amphiphilic block copolymers, then hydrophilicity and stealth effect are improved, but immune response and formation of anti-PEG antibodies occur
Solution Approach 1:
The patent introduces C1 to C3-alkyloxymethyl side chains at specific positions (0.5 to 5.0 mol%) within the polyethylene oxide blocks, creating local structural variations that maintain overall hydrophilicity while reducing immunogenicity. This local modification approach preserves the stealth effect while eliminating the harmful immune response.
Solution Approach 2:
The patent modifies the chemical structure of PEO blocks by incorporating small amounts of alkyloxymethyl-substituted ethylene oxide units, changing parameters such as side chain length (C1-C3), substitution position, and frequency. These parameter changes maintain water solubility and stealth properties while reducing antibody formation.
2Reliability
If PEO blocks are used in block copolymers, then hydrophilicity is improved, but water uptake speed and hydrolyzation homogeneity deteriorate
Solution Approach 1:
The introduction of alkyloxymethyl side chains creates local hydrophilic variations that enhance water interaction at the molecular level, accelerating water uptake while maintaining overall block copolymer hydrophilicity. The side chains act as additional hydrophilic sites that facilitate faster water penetration.
Solution Approach 2:
By adjusting the substitution frequency (0.5-5.0 mol%) and side chain length (C1-C3), the patent optimizes the balance between hydrophilicity and water uptake kinetics, achieving both improved hydrophilicity and faster water absorption rates.
3Reliability
If PEO blocks are used in block copolymers, then hydrophilicity is improved, but matrix homogeneity and stability deteriorate due to phase mixing and phase transitions
Solution Approach 1:
The alkyoxymethyl side chains create local structural variations that prevent large-scale phase separation by disrupting the regular packing of PEO chains. This local disruption maintains matrix homogeneity while preserving the hydrophilic character of the blocks.
Solution Approach 2:
The patent creates a composite structure within the PEO blocks by incorporating alkyoxymethyl-substituted units, resulting in a heterogeneous block that maintains overall homogeneity at the macro level while preventing phase transitions through molecular-level diversity.
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 novel block copolymers exhibit improved functionality without immunogenic potential, offering faster water uptake and homogeneous hydrolyzation, while maintaining matrix homogeneity and stability, thus addressing the issues associated with PEO-based copolymers.
Implementation Method 1
The randomized polyethylene glycol) copolymer (rPEG) structure of the block copolymers of the present invention impedes the interaction with anti-PEG antibodies due to the increased spatial requirements of the alkyloxy methyl side chains
Implementation Method 2
Self-organization of the amphiphilic molecules enables self-organization in aqueous media to nano-scaled polymeric micelles. The assemblies (micelles) comprise a hydrophobic polyester core and a hydrophilic polyether corona
Implementation Method 3
The improved hydrophilicity leads to faster uptake of water and degradation caused by hydrolysis
Data Source
Figure 1~2
AI summary
The present invention refers to the use of novel polyoxyalkylene based block copolymers in particles or in medical devices, wherein the particles comprise at least one novel polyoxyalkylene based block copolymer and preferably at least one active agent.