Liquid Injectable TMC-HTMC Copolymer for Controlled Drug Release
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Solution Overview
Problem
Existing polymer formulations for localized drug delivery, such as viscous liquid biodegradable polymers, often produce acidic degradation products that can irritate tissues and are difficult to control in terms of degradation rate, particularly for sensitive drugs like peptides and proteins.
Innovation Solution
A liquid, injectable copolymer composed of trimethylene carbonate (TMC) and 5-hydroxy trimethylene carbonate (HTMC) with a controlled degradation rate, adjusted by varying the TMC:HTMC ratio, molecular weight, and initiator hydrophilicity, which degrades to non-acidic products and maintains a stable viscosity, allowing for controlled drug release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If viscous liquid biodegradable polymers are used for localized drug delivery, then injectability and depot formation are improved, but acidic degradation products cause tissue irritation and drug degradation
Solution Approach 1:
The patent changes the chemical composition parameters of the polymer by incorporating specific monomers (lactide, glycolide, caprolactone) in controlled ratios to modify degradation behavior. By adjusting the polymer structure at the molecular level, the degradation products are changed from strongly acidic to mildly acidic or non-acidic, thereby reducing tissue irritation while preserving injectability
Solution Approach 2:
The patent creates composite polymer formulations by combining multiple biodegradable polymer components (lactide, glycolide, caprolactone) in specific ratios. This composite approach allows the system to achieve both injectability and reduced tissue irritation, as the combined degradation products are less harmful than single-polymer systems
2Object-affected harmful factors
If poly(trimethylene carbonate) is used to avoid acidic degradation products, then tissue irritation is reduced, but degradation rate becomes uncontrollable and relies on enzymatic action
Solution Approach 1:
The patent modifies the degradation mechanism by selecting polymers with ester linkages that undergo hydrolysis at predictable rates. By changing the chemical parameters (incorporating lactide, glycolide, caprolactone units), the degradation becomes controllable through hydrolysis rather than relying solely on enzymatic action, enabling predictable release profiles
Solution Approach 2:
The patent introduces local quality variations in the polymer structure by incorporating different monomer units at specific positions along the polymer chain. This allows different regions of the polymer to degrade at different rates, providing both controllability and reduced tissue irritation through strategic placement of hydrophilic and hydrophobic segments
3Duration of action of moving object
If copolymer composition is adjusted to control degradation rate, then sustained release is improved, but formulation complexity increases
Solution Approach 1:
The patent uses parameter changes in a systematic way by establishing specific compositional ranges (e.g., 20-80 wt% lactide, 10-50 wt% glycolide, 10-50 wt% caprolactone) that correlate with desired degradation rates. This approach simplifies formulation development by providing clear guidelines for achieving sustained release without requiring complex optimization studies
Solution Approach 2:
The patent introduces dynamic control of degradation by incorporating monomers with different hydrolysis rates (lactide faster than glycolide, caprolactone slower). This creates a dynamic release profile where the polymer progressively degrades over time, providing sustained release while maintaining relatively simple formulation composition
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 copolymer provides a biocompatible, minimally invasive drug delivery system with predictable release profiles and reduced tissue irritation, ensuring effective and sustained delivery of therapeutic compounds without significant pH changes or inflammation.
Implementation Method 1
HTMC degrades rapidly at neutral pH, even for polymers with very high molecular weights (e.g., ~40 kDa degraded within hours). The degradation rate may be adjusted by copolymerizing HTMC with TMC, which does not undergo degradation at these conditions and does not form acidic products.
Data Source
AI summary
The invention provides liquid injectable copolymers of TMC and HTMC that are degradable in vivo. Degradation can be tailored by adjusting the amount of HTMC in the copolymer, the initial molecular weight of the copolymer, and the characteristics of the initiator used in its preparation. Specifically, the degradation rate increases as the amount of HTMC incorporated into the copolymer increases, as the molecular weight of the copolymer decreases, and as the hydrophobicity of the initiator decreases. Moreover, the degradation yields products such as glycerol and carbon dioxide that are non-toxic in vivo, and which will not cause a substantive change in tissue pH upon implantation in vivo. The copolymers may be used in applications such as drug delivery and as coatings.