Polyester Copolymer Drug Loading via Ester Bonding

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Solution Overview

Problem

Current biodegradable and biocompatible polymers face challenges in achieving high loading and controlled release of pharmaceutical compounds, particularly interleukin inhibitors, due to limited reactive sites and solvent compatibility issues, leading to low loading yields and unsustained release profiles.

Innovation Solution

The development of polyester copolymers formed by combining an alcohol-pharmaceutical conjugate with a polyol and an acid monomer, using methods that include heating and removing water to produce a polymeric material with high loading of pharmaceutical compounds, such as salicylic acid, which is incorporated into the polymer structure through ester bonds, allowing for a controlled release mechanism.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional biodegradable polymers are used to deliver pharmaceutical compounds, then biocompatibility is maintained, but pharmaceutical loading levels remain low due to limited reactive sites

Engineering Contradiction:
Improvepharmaceutical loading levelVSAvoidpolymer structure complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The polymer structure is segmented into multiple functional regions: hydrophobic domains for drug incorporation, reactive ester bond sites for pharmaceutical attachment, and biodegradable segments for controlled release. This segmentation allows high pharmaceutical loading while maintaining processable polymer characteristics.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention creates a composite polymer system combining hydrophobic and hydrophilic segments, reactive and inert regions, and biodegradable and structurally stable components. This composite approach enables simultaneous achievement of high drug loading, biocompatibility, and controlled release kinetics.

Inventive Principle:
Principle #40Composite materials

2Duration of action of moving object

If pharmaceutical compounds are incorporated into biodegradable polymers, then controlled release is achieved, but release profiles are unsustained due to rapid degradation

Engineering Contradiction:
Improverelease durationVSAvoidpolymer degradation rate
Core Design Contradiction:
Duration of action of moving objectVSStability of the object's composition

Solution Approach 1:

The polymer degradation rate is made dynamic and controllable through adjustable ester bond density and cross-linking degree. The system transitions from rapid initial degradation to sustained controlled degradation, matching the pharmaceutical release profile requirements and extending therapeutic action duration.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

Key parameters including ester bond concentration, hydrophobic segment length, and cross-linking density are optimized to control degradation kinetics. These parameter adjustments enable sustained release profiles while maintaining biocompatibility and preventing premature drug release.

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If high loading of pharmaceutical compounds is achieved, then therapeutic efficacy is improved, but solvent compatibility issues arise during polymer synthesis

Engineering Contradiction:
Improvepharmaceutical loading levelVSAvoidsynthesis process complexity
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

An intermediary step is introduced where pharmaceutical compounds are first activated or pre-complexed with facilitating agents before incorporation into the polymer matrix. This intermediary approach resolves solvent compatibility issues during synthesis while enabling high pharmaceutical loading in the final product.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

Pharmaceutical compounds undergo preliminary processing including activation, protection group addition, or pre-complexation before polymer incorporation. This preliminary action ensures compatibility with polymer synthesis conditions and enables high loading levels without compromising the ease of manufacture.

Inventive Principle:
Principle #10Preliminary action

4Productivity

If reactive sites are increased to improve pharmaceutical loading, then drug incorporation efficiency improves, but polymer stability and biocompatibility are compromised

Engineering Contradiction:
Improvedrug incorporation efficiencyVSAvoidpolymer stability
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

Reactive sites are distributed non-uniformly throughout the polymer structure, with higher concentrations in specific regions designated for drug incorporation and lower concentrations in regions requiring structural stability. This local quality differentiation maintains both high drug incorporation efficiency and polymer reliability.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

Different segments of the polymer are assigned different functional qualities: some segments provide reactive sites for drug attachment, while other segments maintain structural integrity and biocompatibility. This spatial differentiation of quality allows simultaneous optimization of productivity and reliability.

Inventive Principle:
Principle #3Local quality

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 resulting polyester-pharmaceutical copolymers achieve high loading levels of up to 25% pharmaceutical compounds by weight, maintaining similar physical and chemical characteristics to the pure polymer, with a sustained controlled release of the pharmaceutical compound through degradation, providing a therapeutic delivery system for interleukin inhibitors.

Implementation Method 1

The alcohol-pharmaceutical conjugate includes a pharmaceutical compound having at least one carboxyl group attached to the polyol by an ester bond

Methodology Applied
Scientific EffectEster bond formation: Chemical Bonding

Implementation Method 2

combining an alcohol-pharmaceutical conjugate, a polyol, and an aqueous liquid in a vessel; adding an acid monomer to the vessel and heating and removing water from the vessel to produce the polymeric material

Methodology Applied
Scientific EffectCondensation polymerization:

Implementation Method 3

heating and removing water from the vessel to produce the polymeric material

Methodology Applied
Scientific EffectEvaporation: Evaporation

Data Source

PatentEP3652234B1Poly(glycerol sebacate)-interleukin inhibitor copolymers and methods of making
Publication Date: 2021.04.14 SECANT GROUP LLC
  • EP3652234B1 patent drawingFigure 1
  • EP3652234B1 patent drawingFigure 2
  • EP3652234B1 patent drawingFigure 3

AI summary

A method includes combining an alcohol-pharmaceutical conjugate, a polyol, and an aqueous liquid in a vessel. The alcohol-pharmaceutical conjugate includes a pharmaceutical compound having at least one carboxyl group attached to the polyol by an ester bond. The method also includes adding an acid monomer to the vessel and heating and removing water from the vessel to produce the polymeric material. The polymeric material includes a polyester copolymer of the acid monomer and the polyol and the pharmaceutical compound.