Hyaluronidase Liquid Formulation Stabilizer
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current lyophilized hyaluronidase formulations have stability issues when converted into a solution, leading to a reduction in physiological activity over time due to impurities and low purity, making them impractical for prolonged use.
Innovation Solution
A liquid formulation with a purity of 95% or more hyaluronidase and a stabilizer comprising a buffering agent, non-ionic surfactant, and chelating agent or MgCl2, maintaining enzymatic activity at 90% or more for up to 29 weeks at 2-8°C, achieved through purification methods like affinity chromatography and gel filtration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If lyophilized hyaluronidase formulations are converted into a solution, then they can be administered and used, but their stability decreases and physiological activity is reduced over time
Solution Approach 1:
A stabilizer comprising a buffering agent (maintaining pH 4.0-6.0), non-ionic surfactant (0.001-0.5 v/v%), and chelating agent or MgCl2 (0.1-5 mM) is introduced as an intermediary substance. This stabilizer system mediates between the hyaluronidase enzyme and the aqueous environment, preventing degradation while maintaining solubility and administerability.
Solution Approach 2:
The patent optimizes specific parameters including pH (maintained at 4.0-6.0 through buffering agent), temperature (storage at 2-8°C), and concentrations of stabilizing components. These parameter changes create optimal conditions for maintaining enzymatic activity in liquid form without compromising stability.
2Ease of manufacture
If hyaluronidase is extracted from testicles and lyophilized for manufacture, then it can be produced and stored, but it contains excess foreign proteins and has low purity
Solution Approach 1:
The patent employs purification methods including affinity chromatography and gel filtration to extract and remove foreign proteins and impurities from the crude hyaluronidase extract. This selective extraction process isolates the active enzyme while discarding contaminating substances, achieving 95% or higher purity.
Solution Approach 2:
The purification process involves discarding impure fractions and recovering the purified hyaluronidase in fractions with high enzymatic activity. Multiple chromatography steps allow selective retention and elution of the target enzyme while discarding contaminants.
3Ease of operation
If hyaluronidase is stored in liquid form, then it can be maintained ready for use, but its enzymatic activity decreases over time due to instability
Solution Approach 1:
The stabilizer system is prepared in advance and incorporated into the liquid formulation before storage. The buffering agent, surfactant, and chelating agent are pre-combined to create a protective environment that prevents degradation during storage, ensuring stability throughout the shelf life.
Solution Approach 2:
The stabilizer components provide beforehand cushioning against various degradation mechanisms including proteolysis, oxidation, and aggregation. The non-ionic surfactant prevents surface denaturation, the chelating agent prevents metal-catalyzed oxidation, and the buffering agent maintains optimal pH, collectively cushioning the enzyme against instability.
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 formulation ensures high stability and prolonged activity of hyaluronidase, enhancing its practical application by maintaining 90% or more of its initial activity for an extended period, addressing the stability and purity issues of existing lyophilized forms.
Implementation Method 1
a buffering agent to provide pH 4.0 to 6.0
Implementation Method 2
0.001 to 0.5 v/v% of a non-ionic surfactant
Implementation Method 3
0.1 to 5 mM of a chelating agent or MgCl2
Data Source
Figure 1
Figure 2
Figure 3
AI summary
This invention relates to a stable liquid formulation comprising hyaluronidase and a stabilizer for hyaluronidase and more particularly, to a stable liquid formulation by the addition of the stabilizer to the hyaluronidase.