Macroporous Resin Purification of Cyclic Lipopeptides

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Solution Overview

Problem

Current methods for purifying the cyclolipopeptide compound of Formula I are inefficient due to the use of large amounts of organic solvents and silica gel, leading to environmental pollution and unsuitability for large-scale production, while also failing to achieve high purity.

Innovation Solution

A process involving loading crude compound Formula I onto a macroporous adsorption resin, followed by washing and elution using water or a mixed solvent solution, utilizing resins such as XAD-16 or SP207, which reduces solvent usage and improves purity without the need for silica gel.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If active coal column and silica gel column are used for purification, then the purity of compound Formula I is improved, but the amount of organic solvent increases and the materials cannot be recycled

Engineering Contradiction:
Improvepurity of compound Formula IVSAvoidorganic solvent and adsorbent recycling
Core Design Contradiction:
Manufacturing precisionVSLoss of substance

Solution Approach 1:

The patent changes the purification parameters by replacing traditional silica gel and active coal columns with macroporous adsorption resin columns. This substitution allows for reduced organic solvent usage while maintaining purification effectiveness, and the macroporous resin can be regenerated and reused, addressing both purity requirements and substance loss concerns

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements a recovery system where the macroporous adsorption resin, after purification, is regenerated through washing and drying processes. This allows the adsorbent material to be recovered and reused multiple times, eliminating the need to discard expensive adsorbents and reducing waste

Inventive Principle:
Principle #34Discarding and recovering

2Quantity of substance

If great amount of organic solvent and silica gel are used, then the purification capacity is improved, but the environmental pollution increases and it is harmful to operators

Engineering Contradiction:
Improvepurification capacityVSAvoidenvironmental pollution and operator health
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the purification system parameters by replacing silica gel with macroporous adsorption resin and reducing organic solvent quantities. This parameter change maintains adequate purification capacity while significantly reducing environmental pollution and health hazards associated with large amounts of organic solvents and silica dust

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces expensive, non-recoverable materials (silica gel, active coal) with more economical, regenerable macroporous resin. This substitution reduces the need for continuous disposal and replacement of purification materials, thereby reducing environmental impact and operational costs

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

3Manufacturing precision

If traditional purification method is used, then the purification effect is achieved, but it is not suitable for large-scale production due to high solvent consumption

Engineering Contradiction:
Improvepurification effectVSAvoidsuitability for large-scale production
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent optimizes purification parameters for large-scale production by using macroporous adsorption resin columns with controlled flow rates and solvent concentrations. This approach maintains effective purification while reducing solvent consumption to levels suitable for economical large-scale manufacturing

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements preliminary concentration of the crude solution before loading onto the macroporous resin column. This preliminary action reduces the volume of solution requiring purification, thereby reducing solvent consumption and making the process more suitable for large-scale production while maintaining purification effectiveness

Inventive Principle:
Principle #10Preliminary action

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 purifies the compound with minimal solvent use, reducing environmental impact and enabling high-purity production suitable for large-scale production while maintaining high yields and purity levels.

Implementation Method 1

loading the crude compound of Formula I onto a macroporous adsorption resin

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

washing the macroporous adsorption resin using water, an organic solvent or a mixed solution of an organic solvent and water as the washing liquid

Methodology Applied
Scientific EffectWashing:

Implementation Method 3

eluting the compound of Formula I from the macroporous adsorption resin using water, an organic solvent or a mixed solution of an organic solvent and water as eluent

Methodology Applied
Scientific EffectElution: Desorption

Data Source

PatentEP2623511B1Process for purifying cyclic lipopeptide compounds or salts thereof
Publication Date: 2016.04.06 SHANGHAI TECHWELL BIOPHARMACEUTICALS CO LTD
  • EP2623511B1 patent drawingFigure 1~2
  • EP2623511B1 patent drawing
  • EP2623511B1 patent drawing

AI summary

A process for purifying cyclic lipopeptide compounds or salts thereof comprising the steps of: (1) charging a crude compound of Formula I onto a macroporous adsorption resin; (2) washing the macroporous adsorption resin using water, an organic solvent or a mixed solution of an organic solvent and water as a washing liquid; and (3) eluting the compound of Formula I from the macroporous adsorption resin using water, an organic solvent or a mixed solution of an organic solvent and water as an eluent. The purification method has the advantages of using a small amount of organic solvents, using no silica gel, and causing little damage to the environment; the purity of the collected compound of formula I is also improved as compared with the methods previously disclosed.