Segmented Hyaluronic Acid Compositions for Controlled Release
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Solution Overview
Problem
Current hyaluronic acid (HA) formulations for local administration have short retention and duration in tissues due to rapid clearance, limiting their therapeutic effectiveness in maintaining viscoelastic properties in synovial fluid and other tissues.
Innovation Solution
A composition comprising two fractions of hyaluronic acid, where one fraction is encapsulated in the other, releasing HA at different rates to provide sustained viscoelastic effects by controlling the release of HA in an aqueous medium, utilizing hydrolytically degradable crosslinks to manage the release profile.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high molecular weight HA is administered to maintain viscoelastic properties, then the therapeutic effectiveness is improved, but the retention duration is limited due to rapid clearance
Solution Approach 1:
The HA composition is segmented into multiple fractions with different molecular weights (e.g., 100 kDa, 500 kDa, 1 MDa, 6 MDa) that are released at different rates. This segmentation allows the composition to provide both immediate therapeutic effectiveness through high molecular weight HA and sustained release through lower molecular weight fractions, resolving the contradiction between effectiveness and duration.
Solution Approach 2:
The invention changes the parameter of molecular weight distribution by incorporating multiple HA fractions with varying molecular weights. This parameter change enables the composition to exhibit both high viscoelastic properties (from high MW HA) and extended retention (from low MW HA that clears more slowly or is replenished over time), thereby resolving the contradiction between therapeutic effectiveness and retention duration.
2Stability of the object's composition
If uncrosslinked high molecular weight HA is used, then viscoelastic properties are maintained, but the half-life remains short (less than 24 hrs)
Solution Approach 1:
The invention creates a composite HA material consisting of multiple molecular weight fractions (e.g., 100 kDa, 500 kDa, 1 MDa, 6 MDa) combined in specific ratios. This composite structure maintains the viscoelastic properties through high MW components while the multi-fraction composition extends the effective half-life by providing sustained release and preventing rapid clearance, thus resolving the contradiction between stability and duration.
3Duration of action of moving object
If chemical crosslinking is applied to enhance retention, then the duration is extended, but the natural degradation and release profile is altered
Solution Approach 1:
The invention uses multiple fractions of uncrosslinked or minimally crosslinked HA that are designed to degrade naturally at different rates. Rather than relying on permanent crosslinks, the composition uses a combination of molecular weights that provide temporary, naturally-degrading structures that replenish each other, extending retention time while preserving natural degradation profiles.
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 composition achieves extended release of HA, enhancing viscoelastic properties for prolonged periods, thereby improving the therapeutic efficacy in maintaining tissue hydration and mechanical functions.
Implementation Method 1
utilizing hydrolytically degradable crosslinks to manage the release profile
Data Source
AI summary
The disclosure concerns high molecular weight hyaluronic acid compositions that release hyaluronic acid at controlled rates. The compositions may achieve improved retention and duration of hyaluronic acid in the body, and may be used in methods of treating tissues throughout the body. Compositions, methods of treating, and methods of making are described.