Stabilized PVA-Borate Hydrogel for Wound Care

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Solution Overview

Problem

PVA-borate hydrogels used in wound treatment are prone to instability, leading to changes in viscosity and appearance, making them unsuitable for long-term storage and use, as they separate into phases and lose clarity, which affects their effectiveness and shelf life.

Innovation Solution

Formulating PVA-borate hydrogels with less than 5% w/w acetic acid using a PVA grade with a molecular weight between 145,000 and 300,000 Daltons and a degree of hydrolysis of 98-100%, incorporating a modulator like D-mannitol to stabilize the gel and maintain its cohesive integrity and bioadhesive properties, allowing for sterilization and extended shelf life.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If PVA-borate hydrogels are formulated for wound treatment, then they display unique flow properties that allow filling wound cavity, but they are prone to instability with changes in viscosity and appearance on storage

Engineering Contradiction:
Improveflow propertiesVSAvoidviscosity stability
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by optimizing the PVA molecular weight to 145,000-300,000 Daltons and degree of hydrolysis to 98-100%, controlling acetic acid content below 5% w/w, and adjusting pH to 4.5-8.5. These parameter optimizations resolve the contradiction by maintaining stable viscosity while preserving the gel's flow properties for wound cavity filling.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses composite materials by formulating PVA-borate hydrogels with specific cross-linking agents and stabilizers. The composite structure of PVA chains cross-linked with borate ions, combined with stabilizing agents, creates a system that maintains both flow properties and viscosity stability over extended storage periods.

Inventive Principle:
Principle #40Composite materials

2Reliability

If PVA-borate hydrogels are used to deliver drugs to wound cavity, then they provide ideal platform for drug delivery, but they separate into two phases making it unachievable to remove gel from wound in one intact unit

Engineering Contradiction:
Improvedrug delivery effectivenessVSAvoidphase stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent resolves phase separation by changing the chemical parameters of the hydrogel system. By controlling the PVA degree of hydrolysis (98-100%) and acetic acid content (<5% w/w), the patent maintains homogeneous phase structure that prevents separation, ensuring the gel can be removed as an intact unit while maintaining drug delivery effectiveness.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces stabilizing agents as intermediaries that mediate between the PVA polymer chains and borate cross-linking agents. These intermediaries prevent phase separation by maintaining uniform distribution of components, allowing the gel to retain structural integrity for intact removal while effectively delivering drugs to the wound cavity.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Stability of the object's composition

If PVA-borate hydrogels are formulated with high stability, then they can achieve sufficient shelf life, but they may lose their mouldability and flow properties

Engineering Contradiction:
Improvestorage stabilityVSAvoidmouldability
Core Design Contradiction:
Stability of the object's compositionVSEase of operation

Solution Approach 1:

The patent applies dynamics by creating a hydrogel system with time-dependent and condition-dependent properties. The gel exhibits mouldability and flow properties under wound conditions (low shear stress, physiological temperature) while maintaining storage stability under ambient conditions. This dynamic behavior resolves the contradiction between stability and ease of operation.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent utilizes phase transitions by designing the hydrogel to undergo reversible changes in physical state. The gel transitions from a mouldable, flowable state during application to a more stable, structured state during storage. This phase transition capability allows the gel to maintain both mouldability when needed and stability during storage.

Inventive Principle:
Principle #36Phase transitions

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 stabilized PVA-borate hydrogels retain their clear appearance and viscosity for over two years, ensuring stability and effectiveness in wound treatment, with the ability to deliver active ingredients like lidocaine hydrochloride effectively.

Implementation Method 1

PVA subjected to reversible or partially reversible cross-linking

Methodology Applied
Scientific EffectCross-linking: Chemical Bonding

Implementation Method 2

PVA-Borate hydrogels display unique flow properties

Methodology Applied
Scientific EffectHydrogel formation: Gel

Implementation Method 3

a low molecular weight sugar alcohol that is capable of binding borate or PVA in aqueous solution through a mono-diol or di-diol formation

Methodology Applied
Scientific EffectDiol-borate complexation: Chemical Bonding

Implementation Method 4

These gels will flow under low shear to fill the wound cavity and can be removed as a solid mass post treatment due to their shear thickening properties

Methodology Applied
Scientific EffectShear thickening: Shear Thickening

Data Source

PatentEP3716947B1Stable wound care formulation
Publication Date: 2024.12.04 JENARRON THERAPEUTICS LTD
  • EP3716947B1 patent drawingFigure 1A~1F
  • EP3716947B1 patent drawingFigure 2
  • EP3716947B1 patent drawingFigure 3A~3F

AI summary

The present invention relates to a sterile gel formulation suitable for use in filling a wound cavity and delivering an active ingredient thereto, the gel further having a pH range of 4.5 to 8.5, low bioadhesive strength and cohesive integrity and being formed from a polymer selected from among the group consisting of poly(vinyl) alcohol (PVA) polymer and a PVA-polyvinyl acetate copolymer, a cross-linker being a salt form of boron that produces borate ions in aqueous solution, at least one compound which has a beneficial effect as an active ingredient in the wound and at least one modulator, the modulator being a low molecular weight species that is capable of binding borate or PVA in aqueous solution through a mono-diol or di-diol formation and reduces the pH of PVA-borate hydrogels; wherein the gel is heat and/or gamma sterilised and contains less than 5% acetic acid and the polymer has a degree of hydrolysis of between 98% and 100% and a molecular weight of from 100,000 to 300,000 Daltons.