Phenyl Ester Side Chains for Polymer Resorption

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Solution Overview

Problem

There is a need for biocompatible, biodegradable, and resorbable polymers that can be used in medical applications for controlled or sustained drug delivery, with the ability to manipulate drug release profiles and provide greater chemical properties and drug delivery capabilities, while also allowing for the generation of free carboxylic acid groups in vivo.

Innovation Solution

Development of biocompatible, biodegradable polymers with phenyl ester side chains that cleave in situ to generate free carboxylic acid groups, increasing polymer degradation and resorbability, and can be used in pharmaceutical compositions and medical devices, including copolymers and blends with other biocompatible polymers like polyethylene glycol and poly(lactic-co-glycolic acid).

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If biocompatible polymers are used for controlled drug delivery, then drug delivery capability is improved, but polymer resorbability and degradation rate are insufficient

Engineering Contradiction:
Improvedrug delivery capabilityVSAvoidpolymer resorbability
Core Design Contradiction:
Adaptability or versatilityVSDuration of action of moving object

Solution Approach 1:

The patent changes the chemical parameter of the polymer by introducing phenyl ester side chains with specific leaving groups (para-substituted phenyl esters). This chemical modification enables controlled hydrolysis in vivo, transforming the polymer from non-resorbable to resorbable with tunable degradation rates, while preserving drug delivery functionality.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite polymer structures combining a stable polymer backbone with labile phenyl ester side chains. This composite design allows the backbone to maintain mechanical integrity and drug delivery capability while the side chains provide controlled degradation and resorbability through hydrolytic cleavage of the ester bonds.

Inventive Principle:
Principle #40Composite materials

2Productivity

If free carboxylic acid groups are generated in vivo, then polymer degradation is improved, but polymer stability during storage is reduced

Engineering Contradiction:
Improvepolymer degradation rateVSAvoidpolymer stability
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent performs preliminary protection by capping carboxylic acid groups as phenyl ester derivatives during polymer synthesis. This preliminary action prevents premature degradation and maintains polymer stability during storage and handling, while the protected esters are designed to cleave in vivo to generate the desired free carboxylic acid groups and achieve degradation.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The phenyl ester side chains act as intermediary protecting groups that bridge the contradiction between stability and degradability. These intermediates are stable enough to preserve polymer integrity during storage but can be selectively cleaved in vivo through hydrolysis, thereby generating free carboxylic acid groups and enabling controlled degradation at the target site.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Duration of action of moving object

If phenyl ester side chains are used to increase resorbability, then polymer degradation is improved, but manufacturing complexity increases

Engineering Contradiction:
Improvepolymer resorbabilityVSAvoidmanufacturing complexity
Core Design Contradiction:
Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The patent segments the polymer structure into two functionally distinct parts: a stable backbone providing mechanical properties and a modular phenyl ester side chain providing controlled degradability. This segmentation allows independent optimization of each component and simplifies manufacturing by enabling the use of commercially available phenyl ester monomers and standard polymerization techniques.

Inventive Principle:
Principle #1Segmentation

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

These polymers enable controlled and sustained drug release, faster resorption, and manipulation of drug release profiles, improving biocompatibility and reducing side effects, while providing mechanical properties suitable for medical devices and coatings.

Implementation Method 1

these leaving groups are phenyl esters, which upon cleavage in situ, generate free carboxylic acid groups on the polymer to thereby increase polymer degradation and resorbability

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Data Source

PatentEP2166981B1Phenyl ester side chains to increase polymer resorptivity
Publication Date: 2016.09.07 TYRX INC
  • EP2166981B1 patent drawingFigure 1
  • EP2166981B1 patent drawingFigure 2
  • EP2166981B1 patent drawingFigure 3

AI summary

The present invention relates to polymers modified to increase their resorbability. In particular, the polymers of the invention have phenyl ester side chains which are good leaving groups and which thereby increase the resorption rate of the polymer relative to the same polymer, for example, bearing a comparable amount of an alkyl ester side chain. Such polymers are generally water insoluble, but when modified are able to solublize drugs and upon degradation and resorption, release those in a physiological environment in a controlled and/or sustained manner.