Cyclic Lipopeptide Purification via Macroporous Resin

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Solution Overview

Problem

Existing methods for purifying the cyclolipopeptide compound of Formula I are environmentally harmful due to the use of large amounts of organic solvents and silica gel, making them unsuitable for large-scale production and inadequate in achieving high purity.

Innovation Solution

A process involving the use of macroporous adsorption resins, where the fermentation liquid is extracted with an organic solvent, diluted, and then loaded onto the resin, followed by washing and elution with water or organic solvents, reducing solvent usage and improving purity without silica gel.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If traditional purification methods using acetone extraction, ethyl acetate washing, n-butanol extraction, and silica gel chromatography are employed, then the compound of Formula I can be purified, but large amounts of organic solvents and silica gel are consumed, causing environmental pollution and health hazards

Engineering Contradiction:
Improvepurity of compound of Formula IVSAvoidenvironmental pollution and health hazards
Core Design Contradiction:
Manufacturing precisionVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes the harmful components (silica gel and large amounts of organic solvents) from the purification process. Instead of using silica gel chromatography, the invention employs a filtration step that eliminates silica gel entirely. The organic solvent system is replaced with water-based extraction using n-butanol, significantly reducing solvent consumption and environmental impact while maintaining effective purification of the compound of Formula I

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the fundamental parameters of the purification system by transitioning from organic solvent-based extraction (acetone, ethyl acetate) to a water-based system with n-butanol. This parameter change reduces the toxicity and environmental harm of the process while achieving the same purification objective. The flow rate parameter is also optimized to 0.1-10 column volumes per hour to enhance efficiency

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If traditional purification methods with multiple extraction steps and silica gel chromatography are used, then purification can be achieved, but the process is complex and not suitable for large-scale production

Engineering Contradiction:
Improvepurity of compound of Formula IVSAvoidcomplexity of purification process
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent segments the purification process into distinct, simplified stages: filtration to remove mycelia, water extraction, n-butanol extraction, concentration, and silica gel-free filtration. This segmentation eliminates the need for complex silica gel chromatography while maintaining purification effectiveness. Each step is independent and can be easily scaled up for industrial production

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent replaces expensive and environmentally persistent silica gel with a disposable filtration approach using common filter materials. This substitution simplifies the process equipment needed and makes the method more suitable for large-scale production where cost-effectiveness and ease of operation are critical

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Manufacturing precision

If traditional purification methods are employed, then the compound can be obtained, but great amounts of organic solvents are needed, increasing production costs and environmental burden

Engineering Contradiction:
Improvepurity of compound of Formula IVSAvoidamount of organic solvent consumed
Core Design Contradiction:
Manufacturing precisionVSQuantity of substance

Solution Approach 1:

The patent fundamentally changes the solvent system parameters by replacing acetone and ethyl acetate with water and n-butanol. This substitution reduces the total volume of organic solvents required while maintaining effective extraction and purification. The water-based system is more environmentally friendly and reduces disposal costs

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent extracts and eliminates the need for large volumes of organic solvents by implementing a concentrated n-butanol extraction step followed by efficient concentration. This approach minimizes solvent usage while achieving high purity, directly addressing the issue of excessive solvent consumption in traditional methods

Inventive Principle:
Principle #2Taking out (Extraction)

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 method effectively reduces environmental pollution, lowers production costs, and achieves high purification yields, facilitating large-scale production of high-purity cyclolipopeptide compounds.

Implementation Method 1

loading extract 2 onto a macroporous adsorption resin

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

the fermentation liquid is extracted by acetone

Methodology Applied
Scientific EffectLiquid-liquid extraction: Liquid-Liquid Extraction

Data Source

PatentEP2623611B1Method for purifying cyclic lipopeptide or salt thereof
Publication Date: 2016.07.13 SHANGHAI TECHWELL BIOPHARMACEUTICALS CO LTD
  • EP2623611B1 patent drawingFigure 1~2
  • EP2623611B1 patent drawing
  • EP2623611B1 patent drawing

AI summary

A method for purifying a cyclic lipopepteide or a salt thereof is provided. The method comprises the steps: (1) extracting a fermentation broth containing a compound of formula I or a salt thereof, to obtain an extract 1 after filtration or centrifugation; (2) diluting or concentrating the extract 1 under vacuum to decrease the content of the organic solvent, to obtain an extract 2; (3) loading the extract 2 onto a macroporous absorption resin; (4) washing the macroporpous adsorption resin with water, an organic solvent, or a mixture of water and an organic solvent as a washing solution; and (5) eluting the compound of formula I off from the macroporous adsorption resin with water, an organic solvent, or a mixture of water and an organic solvent as a washing solution as an eluant. Compared with the prior art, the purification method has the advantages that fewer organic solvent is used, no silica gel is used, the harm to the environment is less, and the purity of the collected compound of formula I is improved.