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Method for monitoring, evaluating, and controlling cyclic chromatographic purification process

一种工艺、吸附器的技术，应用在用于监测、评估和控制循环色谱纯化工艺领域，能够解决阻碍实际应用等问题，达到稳健运行的效果

Active Publication Date: 2020-06-30
CHROMACON
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The complexity of these setups hampered their practical application and led to the development of alternative processes for ternary separations utilizing the countercurrent principle
Furthermore, the SMB process cannot use linear solvent gradients, which are important for the separation of compounds with similar adsorption properties

Method used

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  • Method for monitoring, evaluating, and controlling cyclic chromatographic purification process
  • Method for monitoring, evaluating, and controlling cyclic chromatographic purification process
  • Method for monitoring, evaluating, and controlling cyclic chromatographic purification process

Examples

Experimental program
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Effect test

Embodiment 1

[0152] Example 1 [ Figure 9 ]:

[0153] The Contichrom system (ChromaCon AG) was operated using the control method (A). Two columns packed with different cation exchange stationary phases (Fractoprep SO3(M) and Gigacap SO3) were packed into a column with an internal diameter of 0.5 cm and a bed height of 10 cm. Two different resins were used to simulate columns with different column packing qualities. The system's operating software was programmed to continuously monitor the A280 UV signal at both column outlets and based on knowledge of the designed chromatogram set the UV threshold to start the product collection phase at 0.1 AU (=100 mAU). The duration of the product elution phase was fixed at 5.5 minutes.

[0154] The loading material was lysozyme solution, and the buffers used were buffer A: 25 mM phosphate, pH 6.0; buffer B: 25 mM phosphate, pH 6.0, 1 M NaCl; washing solution: 1 M NaOH. Figure 9 A shows the chromatogram of the cyclic operation of the MCSGP process ...

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Abstract

A method for monitoring, evaluating and controlling a cyclic chromatographic purification process is proposed involving at least two adsorbers, wherein the method comprises at least the following steps: a) monitoring of the chromatogram including the measurement of at least one current concentration-proportional signal in the liquid; b) evaluation of the chromatogram including a comparison of at least one of said current concentration-proportional signals measured in step (a) with a threshold value thereof; c) controlling the chromatographic purification process by adapting the termination ofthe currently running phase as a function of the comparison of step (b) and initiating the next phase, wherein the sequence a)-c) is carried out in given order at least twice.

Description

technical field [0001] The present invention relates to methods for monitoring, evaluating and controlling cyclic chromatographic purification processes. Background technique [0002] Chromatographic processes are used to purify products from complex mixtures. [0003] In the case of "difficult" chromatographic separations, the target product is accompanied by by-compounds (impurities) with very similar adsorption behaviour. In traditional single-adsorber chromatography chromatography, this results in overlapping portions of product and various by-compounds in the front and back of the product peak, necessitating center-cut purification. This purification is also known as a three-way separation challenge because in chromatography, the compounds to be separated can be divided into three classes, early eluting (weakly adsorbing) impurities / by-compounds, intermediate eluting "products" and late eluting (strongly adsorbing) adsorption) impurities / by-compounds. Overlapping fra...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): B01D15/18G01N30/60G01N30/86
CPCB01D15/1807B01D15/1864G01N30/6034G01N30/8624B01D15/1871
Inventor 拉尔斯·奥曼托马斯·米勒-斯佩思迈克尔·巴万德
Owner CHROMACON
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