Thermolysin Liquid Preparation Stability at High pH
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Solution Overview
Problem
Current methods for preparing thermolysin liquid preparations are limited by stability restrictions at pH levels between 5.0 to 9.0, which restrict industrial production and are not suitable for examining stability at higher pH levels, and autodigestion occurs within this pH range, limiting the potential for improved stability.
Innovation Solution
A thermolysin liquid preparation with a concentration of 0.1 mg/mL or higher and a pH adjusted to 9.5 to 11.5, potentially containing sodium chloride or calcium chloride, is developed to enhance stability and suppress autodigestion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If thermolysin is prepared at pH 5.0 to 9.0 to maintain stability, then stability is improved, but autodigestion occurs and productivity is limited
Solution Approach 1:
The patent applies parameter changes by shifting the pH range from the conventional 5.0-9.0 to a higher range of 9.0-11.5. This fundamental parameter change resolves the contradiction by finding a new pH window where thermolysin exhibits both high stability and suppressed autodigestion, thereby improving both stability and reducing harmful self-digestion simultaneously
2Stability of the object's composition
If pH is adjusted to 5.0 to 9.0 to obtain stable thermolysin liquid, then stability is improved, but manufacturing flexibility and productivity are restricted
Solution Approach 1:
The patent changes the pH parameter from the conventional 5.0-9.0 range to 9.0-11.5, which expands the operational window for thermolysin preparation. This enables more flexible manufacturing processes and higher productivity while maintaining stability, as the enzyme remains stable across this broader alkaline range
3Stability of the object's composition
If pH is restricted to 5.0 to 9.0 based on conventional knowledge, then stability is maintained, but examination of higher pH stability is prevented
Solution Approach 1:
The patent applies inversion by challenging the conventional wisdom that thermolysin is only stable at pH 5.0-9.0. Instead of accepting this limitation, the inventors explored the opposite pH range (9.0-11.5) and discovered that thermolysin maintains high stability and suppressed autodigestion in this previously unexplored alkaline range, thereby expanding adaptability
Data Source
AI summary
A thermolysin solution has further improved stability as a result of the thermolysin solution containing thermolysin at a concentration that is 0.1 mg/mL or higher and the thermolysin solution having a pH that is adjusted to higher than 9.0. The thermolysin solution preferably has a pH in the range of 9.5-11.5.

