Capsular Polysaccharide Production Without pH Adjustment
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Solution Overview
Problem
Existing methods for producing capsular polysaccharides of pneumococcal serotypes require pH adjustment for protein precipitation, which complicates the process and can modify the polysaccharides, generating harmful substances.
Innovation Solution
A method involving cultivating bacterial cells without pH adjustment until the culture broth reaches a pH of 5.5 or lower, allowing natural acidification products to facilitate protein precipitation, eliminating the need for a pH adjuster and simplifying the process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If pH adjustment is performed for protein precipitation, then protein removal efficiency is improved, but process complexity increases and capsular polysaccharide modification occurs
Solution Approach 1:
The culture broth system automatically lowers its own pH through natural acidification by metabolic byproducts (lactic acid, acetic acid) during extended cultivation, eliminating the need for external pH adjusters. The bacteria themselves serve the function of acidifying the medium for protein precipitation.
Solution Approach 2:
The harmful metabolic byproducts (organic acids) that accumulate during cultivation and lower pH are converted into a beneficial tool for protein precipitation. The naturally produced acidification, originally a waste product, becomes the mechanism for simplifying the purification process.
2Manufacturing precision
If pH adjuster is used for protein precipitation, then protein precipitation is achieved, but harmful substances are generated
Solution Approach 1:
The system uses its own metabolic byproducts (lactic acid, acetic acid) to achieve protein precipitation, eliminating the need for external chemical pH adjusters that would introduce harmful substances into the capsular polysaccharide product.
Solution Approach 2:
Metabolic byproducts that were previously considered waste or harmful are converted into the precipitating agent, eliminating the introduction of external harmful chemicals while achieving the same protein precipitation effect.
3Ease of manufacture
If additional cultivating is performed without pH adjustment, then pH reaches 5.5 or lower naturally, but cultivation time increases
Solution Approach 1:
The cultivation process continues uninterrupted without pH adjustment interventions, allowing the natural acidification to proceed continuously until the desired pH is reached. This eliminates the need for stopping and adjusting pH, maintaining continuous productive action.
Solution Approach 2:
The pH parameter changes naturally over time during cultivation due to metabolic activity, transitioning from initial pH to final pH of 5.5 or lower without external intervention. This temporal parameter change replaces the need for active pH control.
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
This approach minimizes polysaccharide modification and harmful substance generation, simplifying the production process while maintaining stringent protein and nucleic acid content specifications for vaccine production.
Implementation Method 1
cell lysis is carried out using a lysing agent such as sodium deoxycholate (DOC)
Implementation Method 2
protein precipitation by acidification of the cell lysate to a pH of less than 5.5
Data Source
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AI summary
The present invention provides an improved method of producing a capsular polysaccharide having a pneumococcal serotype. The method according to the present invention includes a step of additionally culturing bacterial cells producing a pneumococcal serotype without pH adjustment, thereby removing a protein precipitation process by acidification with a pH adjuster.