Cross-linked Sodium Hyaluronate Gel Preparation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for preparing cross-linked sodium hyaluronate gel face challenges such as poor mechanical strength, non-uniform crosslinking, and irregular particle distribution, making it unsuitable for use as a tissue engineering scaffold material.
Innovation Solution
A method involving the preparation of an alkaline hyaluronic acid solution, followed by a primary crosslinking reaction with divinyl sulfone or 1,4-butanediol diglycidyl ether, freeze-drying, and a secondary reaction with ammonium or potassium persulfate to enhance crosslinking, resulting in a gel with improved mechanical properties and uniformity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If crosslinking is performed in aqueous phase with conventional crosslinking agents, then the degradation time can be adjusted by degree of crosslinking, but the crosslinking agent cannot be uniformly dispersed among hyaluronic acid molecules causing non-uniform overall crosslinking degree
Solution Approach 1:
The patent changes the phase parameter from aqueous to organic phase, and adjusts the molecular weight parameter of hyaluronic acid to >1000 kDa. These parameter changes enable uniform dispersion of crosslinking agent and achieve both adjustable degradation time and uniform crosslinking degree simultaneously
Solution Approach 2:
The patent uses a composite approach by combining high molecular weight hyaluronic acid with specific crosslinking agents (divinyl sulfone or 1,4-butanediol diglycidyl ether) in an organic phase system, creating a composite material system that achieves uniform crosslinking while maintaining controllable degradation properties
2Ease of manufacture
If cross-linked hyaluronic acid particles are prepared with uniform particle size distribution and high water swelling ratio, then the absorption capacity of skin tissues is improved, but they are distributed at nanometer level which is unsuitable for interventional embolization treatment
Solution Approach 1:
The patent changes the particle size parameter to 1-5 mm through controlled drying and processing methods, and adjusts the crosslinking degree parameter to achieve optimal balance between mechanical strength and absorption capacity. This enables the material to be suitable for embolization treatment while maintaining good absorption properties
3Reliability
If natural hyaluronic acid is used, then it shows good histocompatibility and induces little immune response, but it has a half-life period of only 1-2 days in tissues and is decomposed by hyaluronidase or oxygen free radicals
Solution Approach 1:
The patent changes the molecular weight parameter to >1000 kDa and applies crosslinking modification, which fundamentally alters the degradation kinetics while preserving biocompatibility. The crosslinked network structure resists enzymatic degradation by hyaluronidase and oxidation by free radicals, extending half-life from 1-2 days to several weeks or months
Solution Approach 2:
The patent creates a composite material system combining high molecular weight hyaluronic acid with crosslinking agents, forming a crosslinked gel network that maintains the excellent biocompatibility of natural HA while achieving enhanced stability and prolonged duration of action through the crosslinked structure
4Strength
If crosslinking is performed to improve mechanical strength and decrease degradation rate, then the residence time in vivo is prolonged, but it is difficult to implement clinically as a tissue engineering scaffold material with controllable degradation
Solution Approach 1:
The patent enables independent control of degradation time through selection of hyaluronic acid molecular weight (>1000 kDa) and crosslinking degree, while mechanical strength is controlled by crosslinking agent concentration and type. This decoupling of control parameters allows simultaneous optimization of both mechanical strength and controllable degradation for clinical tissue engineering applications
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 a cross-linked sodium hyaluronate gel with high mechanical strength and uniform crosslinking, suitable for use as a tissue engineering scaffold material, offering improved application performance and stability.
Implementation Method 1
Hyaluronic acid is highly hydrophilic, which physicochemical property enables hyaluronic acid to maintain gelatinous even at a very low concentration, hyaluronic acid increases in volume after absorbing water
Implementation Method 2
Cross-linked sodium hyaluronate is one of cross-linked HA derivatives, which is a gel macromolecule, also known as a cross-linked sodium hyaluronate gel, formed by a crosslinking reaction of the sugar ring active group on cross-linked sodium hyaluronate with a crosslinking agent under certain conditions
Implementation Method 3
adding the dried gel dry glue into a certain amount of prepared ammonium persulfate or potassium persulfate aqueous solution with a mass fraction of 1-5%, after fully soaking and swelling, heating to 50-70° C. and maintaining the reaction for 2-6 h
Implementation Method 4
after the crosslinking reaction being finished, dialyzing and freeze-drying to obtain a cross-linked sodium hyaluronate gel dry glue
Data Source
AI summary
A preparation method of a cross-linked sodium hyaluronate gel is disclosed, which including: preparing an alkaline aqueous solution of hyaluronic acid: formulating a sodium hyaluronate alkali liquor with the concentration of 10-30% g/ml; and carrying out a cross-linking reaction: the cross-linking agent used in the cross-linking reaction being divinyl sulfone or 1,4-butanediol diglycidyl ether, the cross-linking reaction being carried out in an alkaline aqueous solution of hyaluronic acid, the reaction temperature of the cross-linking reaction being 20-40° C., the time of the cross-linking reaction being 4-8 h, and the like. The method of this invention has many advantages, such as easily available raw materials, mild reaction conditions, high cross-linking efficiency, simple process and post-treatment, and easy operation. The obtained cross-linked sodium hyaluronate has a three-dimensional network structure by the crosslinking reaction with good mechanical properties, and can be used as a good drug carrier and a tissue engineering scaffold material.