Catalyst-Free Polyurethane Excipient for Biostable Drug Release
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Solution Overview
Problem
Existing polyurethane excipients for medical devices may cause cytotoxicity due to catalyst use, are hydrophobic, and poorly solubilize water-soluble drugs, with aromatic hard segments potentially forming harmful methylenedianiline, limiting their biostability and drug release efficacy.
Innovation Solution
A biostable polyurethane composed of aliphatic diisocyanate, aliphatic diols with poly(ethylene oxide) and polycarbonate moieties, and a chain extender, formed without catalysts, allowing for improved solubility of water-soluble drugs and reduced melting points for controlled drug release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If catalysts are used in polyurethane synthesis, then the polymerization reaction proceeds efficiently, but cytotoxicity is caused
Solution Approach 1:
The patent removes catalysts from the polyurethane synthesis process entirely, using catalyst-free polymerization conditions. This extraction of the harmful element (catalyst) eliminates cytotoxicity while maintaining polymerization efficiency through optimized reaction conditions and stoichiometry.
Solution Approach 2:
The patent employs transient, non-catalytic basic sites that are consumed during the reaction process rather than persistent catalysts. These short-living basic sites facilitate polymerization temporarily and then degrade, leaving no toxic residue in the final polyurethane product.
2Reliability
If polyurethane is made hydrophobic, then biostability is improved, but solubility for water-soluble drugs deteriorates
Solution Approach 1:
The patent creates local hydrophilic regions within the polyurethane matrix by incorporating polar functional groups (carboxylic acid, hydroxyl, amine) at specific locations in the polymer chain. These localized polar sites provide drug solubility while the overall polyurethane structure maintains biostability.
Solution Approach 2:
The patent creates a composite polyurethane structure combining hydrophobic segments (for biostability) with hydrophilic functional groups (for drug solubility). This composite approach integrates materials with complementary properties to simultaneously achieve biostability and drug compatibility.
3Strength
If aromatic hard segments are used in polyurethane, then mechanical strength is improved, but formation of harmful methylenedianiline occurs
Solution Approach 1:
The patent converts the potential harm of aromatic segment degradation into a benefit by deliberately selecting aliphatic diisocyanates that do not form toxic degradation products. The aliphatic structure, while potentially less strong than aromatic, provides the advantage of biocompatibility and eliminates methylenedianiline formation.
Solution Approach 2:
The patent changes the chemical composition parameter of the hard segments from aromatic to aliphatic diisocyanates. This parameter change fundamentally alters the degradation pathway to eliminate toxic byproducts while maintaining adequate mechanical properties through optimized polymer architecture.
4Duration of action of moving object
If melting point is reduced for controlled drug release, then drug release control is improved, but thermal stability deteriorates
Solution Approach 1:
The patent creates local crystalline regions with specific melting points through controlled phase separation of hard and soft segments. These localized crystalline domains provide controlled drug release at physiological temperatures while the overall polymer structure maintains thermal stability through its crosslinked network and biostable backbone.
Data Source
AI summary
In an embodiment, a polyurethane comprises the residues of i. an aliphatic diisocyanate, ii. an aliphatic diol comprising a poly(ethylene oxide) moiety, iii. an aliphatic diol comprising a polycarbonate moiety, and iv. a chain extender, wherein the polyurethane has a melting temperature of 140° C. or less and has a weight average molecular weight of from 100,000 to 500,000 g/mol. In an embodiment, the polyurethane is substantially devoid of catalyst. In an embodiment, the polyurethane is formed by reactive extrusion. In an embodiment, a medical device comprises the polyurethane and a bioactive agent. The medical devices, methods, and polyurethanes may exhibit benefits in end-product biostability, drug release profile, health and safety, and processing speed or reproducibility.