Poloxamer Purification via Counter-Current Chromatography
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Solution Overview
Problem
Current methods for purifying poloxamers, such as poloxamer 188, are inefficient in removing low molecular weight (LMW) and high molecular weight (HMW) impurities, resulting in high costs and low productivity, and do not achieve high purity levels effectively for commercial applications.
Innovation Solution
A sequential multi-column size exclusion chromatography process using a counter-current moving bed mode, where a feed mixture of poloxamers is separated across multiple chromatographic columns, with a first eluent portion enriched in the purified target block copolymer and a second eluent portion depleted of it, allowing for the recovery and recycling of the depleted eluent, effectively removing LMW and HMW impurities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If batch chromatographic methods are used for poloxamer purification, then purification is achieved, but productivity is below 0.1 kg treated product per kg stationary phase per day and dilution exceeds 1500 L solvent per kg product
Solution Approach 1:
The patent applies dynamic operation by implementing continuous chromatography with simulated moving bed technology, where the stationary phase is periodically switched between columns to create a moving bed effect. This dynamic operation mode enables continuous processing instead of batch processing, significantly improving productivity from below 0.1 kg/kg/day to above 1 kg/kg/day while reducing solvent consumption through efficient eluent recycling.
Solution Approach 2:
The invention implements continuous operation mode where the chromatographic separation process runs continuously without interruption. Multiple columns are operated in sequence with continuous feed introduction and continuous product collection, eliminating the idle time between batches. This continuous useful action maintains high productivity while the closed-loop eluent recycling system minimizes solvent consumption by recovering and reusing the mobile phase.
2Manufacturing precision
If adsorption methods with mixed bed resin are used, then purification is achieved, but adsorbent regeneration is not reported and process cost is considerably high
Solution Approach 1:
The patent implements eluent recovery and recycling by collecting the mobile phase after chromatographic separation and reusing it as fresh eluent in subsequent cycles. This recovery system eliminates the need for expensive adsorbent regeneration processes while maintaining high purification quality. The recycled eluent is filtered and returned to the system, significantly reducing process costs compared to methods requiring adsorbent regeneration or replacement.
Solution Approach 2:
The chromatographic system performs self-regeneration through the continuous flow mechanism where fresh eluent automatically displaces bound impurities from the stationary phase as the moving bed progresses through the columns. This self-service mechanism eliminates the need for separate regeneration steps or additional chemicals, reducing both process complexity and cost while maintaining consistent purification quality.
3Manufacturing precision
If extraction methods are used to remove LMW impurities, then gel point shift towards body temperature is achieved, but complete depletion of target impurity is not achieved and product recovery is below 80%
Solution Approach 1:
The patent segments the impurity removal process into distinct chromatographic zones within the simulated moving bed system. Different column sections are optimized for separating specific molecular weight ranges, with LMW impurities separated in one zone and HMW impurities in another. This segmented approach achieves complete depletion of target impurities while minimizing product loss through optimized separation conditions in each zone, achieving product recovery above 80%.
Solution Approach 2:
The system employs periodic switching of column inlet and outlet connections to create a moving bed effect that periodically refreshes the separation zones. This periodic action allows the stationary phase to be continuously regenerated as it moves through different functional zones, enabling complete impurity removal while maintaining high product recovery through optimized periodic elution cycles that minimize co-elution of product with impurities.
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 process achieves high purity levels of poloxamers with improved productivity and reduced solvent usage, effectively addressing the limitations of prior art by enabling cost-effective and efficient removal of impurities, including LMW and HMW species, thereby enhancing the quality and yield of the purified product.
Implementation Method 1
a process for purification of polyether block copolymers comprising polyoxyethylene and polyoxypropylene moieties using sequential multi-column size exclusion chromatography apparatus, operated in a counter current simulated or actual moving bed mode
Implementation Method 2
providing a feed mixture comprising the block copolymers dissolved in an eluent in a feed vessel
Data Source
Figure 1(a)~1(c)
Figure 2
Figure 3A
AI summary
A process for purification of polyether block copolymers comprising polyoxyethylene and polyoxypropylene moieties using sequential multi-column size exclusion chromatography apparatus operated as a counter current moving bed wherein a process cycle comprises the steps of.