Frozen-Medium Crosslinking for Stable Injectable Hyaluronic Acid Hydrogels
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing hyaluronic acid-based gels for soft tissue filling degrade rapidly and require high levels of crosslinking agents like 1,4-butanediol diglycidyl ether (BDDE) to achieve mechanical stability, which can lead to unstable products that are not cohesive and fail to withstand sterilization, making them unsuitable for soft tissue applications.
Innovation Solution
A method for crosslinking polysaccharides, such as hyaluronic acid, under conditions that prevent water sublimation at temperatures above the eutectic point but below the freezing point, using specific crosslinking agents with functional groups, reducing the amount of crosslinking agent needed and maintaining mechanical properties suitable for soft tissue filling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If the quantity of crosslinking agent is reduced to minimize modification, then biocompatibility is improved, but mechanical properties and cohesiveness deteriorate
Solution Approach 1:
The patent changes the physical state parameter of the reaction medium from liquid to solid (frozen state) to enable crosslinking at low temperatures with reduced crosslinking agent quantities. This parameter change allows the crosslinking reaction to proceed while maintaining the polysaccharide's natural structure and reducing the need for high concentrations of crosslinking agents.
Solution Approach 2:
The patent utilizes the phase transition of water from liquid to solid state by cooling the reaction medium below its freezing point. This phase transition creates a frozen reaction medium that enables crosslinking reactions to occur at low temperatures, thereby reducing the quantity of crosslinking agent required while maintaining mechanical properties.
2Object-affected harmful factors
If the quantity of crosslinking agent is reduced, then biocompatibility is improved, but stability during sterilisation deteriorates
Solution Approach 1:
The patent changes the temperature parameter to below the freezing point of water, creating a frozen reaction medium. This temperature parameter change enables crosslinking to occur under milder conditions, producing gels that are more stable during subsequent sterilization processes even with reduced crosslinking agent quantities.
Solution Approach 2:
By utilizing the frozen phase of the reaction medium, the patent enables crosslinking reactions to proceed at low temperatures. This phase transition approach creates a more stable crosslinked structure that can withstand sterilization conditions without degrading, thereby improving reliability while maintaining low crosslinking agent usage.
3Object-affected harmful factors
If crosslinking is performed at low temperature with reduced crosslinking agent, then biocompatibility is improved, but cohesiveness deteriorates
Solution Approach 1:
The patent employs the frozen phase of the reaction medium to enable crosslinking at low temperatures. This phase transition creates a unique environment where crosslinking reactions can occur with minimal crosslinking agent while maintaining the cohesiveness and structural integrity of the resulting gel, thus improving biocompatibility without sacrificing composition stability.
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 method produces biocompatible, injectable hydrogels with improved mechanical properties and stability, allowing for effective soft tissue filling without migration, while minimizing the use of crosslinking agents and ensuring compatibility with sterilization processes.
Implementation Method 1
crosslinking the polysaccharide: d1) by reacting the polysaccharide with the one or more crosslinking agents; or d2) by sol-gel reaction of the functionalised polysaccharide... carried out under conditions not allowing sublimation of water, at a pressure P and at a temperature T greater than the temperature of the eutectic point of the reaction medium as measured at pressure P and less than the temperature of the freezing point of the reaction medium as measured at pressure P
Implementation Method 2
providing at least one crosslinking agent and/or at least one functionalisation agent, the functionalisation agent enabling crosslinking of the polysaccharide by sol-gel reaction
Data Source
AI summary
The present invention relates to a method for producing a hydrogel comprising a crosslinked polysaccharide, in particular, a method for producing an injectable hydrogel comprising crosslinked hyaluronic acid. The hydrogel has mechanical properties suitable for filling soft tissues. The present invention also relates to a hydrogel, preferably injectable, that can be obtained by the method and a composition containing the hydrogel.