Liquid Block Copolymer Peptide Delivery System
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Solution Overview
Problem
Biodegradable polymer compositions used for drug delivery, particularly peptides, face challenges with stability and extended release due to acid degradation and high viscosity issues, leading to local irritation and limited duration of drug delivery beyond 14 days.
Innovation Solution
A biodegradable liquid block copolymer system comprising D,L-lactide, ε-caprolactone, and polyethylene glycol (PEG) with specific molar ratios and divalent cations like magnesium and zinc, which remains liquid at body temperature and stabilizes peptides, allowing for extended release without forming solid implants.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If solid biodegradable polymers are used to form implants, then extended drug delivery is achieved, but the polymers must be formed outside the body and inserted surgically, increasing procedure complexity
Solution Approach 1:
The patent changes the physical state parameter of the polymer from solid to liquid by controlling molecular weight and composition. This allows the polymer to be injected through standard needles as a liquid solution that forms an implant in situ, eliminating surgical formation procedures while maintaining extended drug delivery capability
Solution Approach 2:
The patent replaces the mechanical surgical formation process with a chemical solution injection process. The liquid polymer solution is injected through a syringe and needle, where it automatically forms the implant structure in the body without requiring external mechanical formation tools or surgical procedures
2Ease of operation
If solid polymers are dissolved in biocompatible solvents to enable injection, then ease of administration is improved, but the solutions become highly viscous requiring large bore needles and considerable injection force
Solution Approach 1:
The patent changes the viscosity parameter by using low molecular weight liquid polymers instead of dissolving solid high molecular weight polymers. This reduces the solution viscosity to levels that can be injected through standard gauge needles with minimal force, while still forming effective implants in situ
Solution Approach 2:
The patent uses low molecular weight polymers that are essentially disposable after injection - they degrade in the body over time to provide extended drug delivery. This shorter-lived material approach allows for lower viscosity formulations that are easier to administer compared to long-lived solid polymer systems
3Productivity
If viscous polymer solutions are injected into muscle tissue, then drug delivery is achieved, but local irritation of muscular tissue occurs
Solution Approach 1:
The patent changes the viscosity parameter of the polymer solution to a lower range that reduces mechanical irritation to tissues during injection. The optimized viscosity allows for smoother injection through standard needles and reduces the mechanical stress and irritation caused to muscle tissue, while still enabling effective drug delivery
4Ease of operation
If liquid polymer compositions are used for extended drug delivery, then ease of injection is improved, but peptide stability is compromised due to acid degradation from polymer hydrolysis
Solution Approach 1:
The patent introduces divalent cations (such as calcium or zinc ions) as intermediary substances that buffer the acidic environment created by polymer hydrolysis. These cations complex with the carboxylic acid groups released during degradation, neutralizing the acid and preventing peptide degradation, thus maintaining peptide stability in the liquid polymer composition
Solution Approach 2:
The patent creates a composite formulation combining the liquid polymer, peptide drug, and divalent cation buffer system. This composite material approach allows the acidic polymer to coexist with the peptide without causing degradation, as the divalent cation component actively neutralizes the acid, enabling both ease of injection and peptide stability
5Ease of operation
If the polymer solution viscosity is reduced for easier injection, then ease of administration is improved, but the extended release duration beyond 14 days is limited
Solution Approach 1:
The patent optimizes the molecular weight parameter of the liquid polymer to a specific low range that simultaneously achieves low enough viscosity for easy injection through standard needles and sufficient polymer mass to provide extended drug release beyond 14 days. This precise parameter control resolves the contradiction between ease of administration and release duration
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 system provides improved stability and extended release of peptides over a longer period, reducing local irritation and enabling consistent drug delivery for therapeutic windows, with enhanced stability and reduced degradation.
Implementation Method 1
A liquid polymer composition is provided that includes a biodegradable liquid block copolymer and a divalent cation or metal salt... divalent cations like magnesium and zinc, which remains liquid at body temperature and stabilizes peptides
Implementation Method 2
which remains liquid at body temperature... a viscosity of the biodegradable liquid block copolymer does not spontaneously increase with an increase in temperature
Implementation Method 3
provides both an initial burst and extended release of the drug... provides improved stability and extended release of peptides over a longer period
Data Source
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AI summary
Liquid polymer pharmaceutical compositions with a biodegradable liquid polymer, a biocompatible solvent or combination or mixture of solvents and/or cosolvents, and an active pharmaceutical agent comprising a peptide are useful to provide extended long-term release of the drug to a subject and/or to improve the stability of the active pharmaceutical agent. In embodiments, the polymer may be initiated with a low-molecular weight polyethylene glycol and/or may be a block copolymer comprising a low-molecular weight polyethylene glycol block. In further embodiments, the liquid polymer pharmaceutical composition may include a divalent cation, which may be provided in the form of a metal salt.