Disulfide-Crosslinked Hyaluronan Hydrogel for Durable Thin-Needle Injection
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Solution Overview
Problem
Existing hyaluronan-based soft tissue fillers face challenges in achieving both extended residence time in the body and ease of injection through thin needles, leading to issues like short duration of effect and patient discomfort.
Innovation Solution
A sterile hydrogel composition comprising a crosslinked polymer, which is an oxidation product of thiol-modified hyaluronan, with a specific degree of thiol modification and molecular weight, crosslinked via disulfide bonds, allowing for extended in vivo residence time and injectability through thin needles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If chemical crosslinking agents like BDDE are used to extend residence time, then durability is improved, but genotoxicity and immunogenicity increase
Solution Approach 1:
The patent changes the chemical parameters of the crosslinking agent from synthetic epoxides (BDDE) to natural disulfide bonds formed through controlled oxidation of thiol-modified hyaluronan. This parameter change maintains crosslinking functionality while eliminating genotoxic effects, achieving extended residence time through safe biochemical crosslinking
Solution Approach 2:
The patent uses transient oxidizing agents (oxygen, hydrogen peroxide) that decompose into safe byproducts, replacing persistent synthetic crosslinkers. The crosslinking bonds (disulfide bonds) are designed to be metabolically stable yet biodegradable, providing extended but not permanent residence time
2Duration of action of stationary object
If high molecular weight hyaluronan is used to extend residence time, then durability is improved, but viscosity increases making injection difficult
Solution Approach 1:
The patent modifies the molecular weight parameters by using thiol-modified hyaluronan with controlled chain lengths and introducing crosslinking that creates a three-dimensional network. This transforms the linear high-viscosity polymer into a gel structure with optimized rheological properties, achieving extended residence time while maintaining injectability through needle
Solution Approach 2:
The patent creates a composite hydrogel structure combining thiol-modified hyaluronan chains crosslinked via disulfide bonds. This composite network structure provides both the molecular weight necessary for extended residence time and the gel consistency required for easy injection, resolving the contradiction between durability and operability
3Productivity
If crosslinking is performed at high temperature to achieve desired crosslinking degree, then crosslinking efficiency is improved, but hyaluronan degradation increases
Solution Approach 1:
The patent replaces thermal energy input with chemical energy input for crosslinking. Instead of using high temperature to drive crosslinking reactions, the system uses controlled oxidation chemistry (oxygen or hydrogen peroxide) to form disulfide bonds at physiological temperatures, eliminating thermal degradation while maintaining crosslinking efficiency
Solution Approach 2:
The patent employs controlled oxidation using oxygen or hydrogen peroxide to accelerate disulfide bond formation. This oxidation-driven crosslinking proceeds efficiently at low temperatures, achieving desired crosslinking degree without the thermal degradation that would occur with conventional heating methods
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 hydrogel composition provides a sustainable effect for at least 3 months after a single treatment, eliminating the need for multiple sessions, with improved injectability and favorable toxicological safety.
Implementation Method 1
the crosslinked polymer is an oxidation product of a thiol-modified hyaluronan
Implementation Method 2
crosslinked via disulfide bonds
Data Source
Figure 1~2D
AI summary
A sterile hydrogel composition comprising a crosslinked polymer, wherein the crosslinked polymer is an oxidation product of a thiol-modified hyaluronan and wherein the thiol- modified hyaluronan has a degree of modification of hyaluronan with thiol moietiesof more than about 80 µmol per gram polymer, wherein the thiol-modified hyaluronan has a degree of modification of hyaluronan with thiol moieties of less than about 280 µmol per gram polymer, and wherein the thiol-modified hyaluronan has a mean molecular weight of at least 400 kDa.