Multi-step Chromatographic PUFA Separation Process

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Solution Overview

Problem

Current chromatographic separation processes face challenges in efficiently purifying polyunsaturated fatty acids (PUFAs) from complex mixtures, particularly in minimizing C18 fatty acids like alpha-linolenic acid (ALA) and gamma-linolenic acid (GLA), which are difficult to remove without using large volumes of aqueous alcohol solvents, and are prone to degradation due to their fragility.

Innovation Solution

A chromatographic separation process using a mixed solvent system, where a feed mixture is purified in a first step with water and a first organic solvent, followed by a second step using a different organic solvent in a simulated or actual moving bed chromatography apparatus, effectively reducing C18 fatty acid impurities and achieving high purity of PUFAs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If distillation is used to purify PUFAs, then separation efficiency is improved, but product degradation increases due to heating and oxidation

Engineering Contradiction:
Improvepurification efficiencyVSAvoidproduct degradation
Core Design Contradiction:
Manufacturing precisionVSObject-affected harmful factors

Solution Approach 1:

The patent replaces thermal distillation with chromatographic separation using supercritical carbon dioxide as a solvent. This substitutes a mechanical/physical separation process (chromatography based on adsorption differences) for a thermal process (distillation), thereby achieving purification without subjecting fragile PUFAs to high temperatures that cause isomerization, peroxidation and oligomerization

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent uses supercritical carbon dioxide as the eluent in the chromatographic separation process. CO2 provides an inert atmosphere that prevents oxidation of PUFAs during separation, eliminating the need for oxygen exclusion measures while maintaining product integrity throughout the purification process

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

2Manufacturing precision

If conventional chromatographic separation is used, then separation is achieved, but large volumes of aqueous alcohol solvents are required to remove C18 fatty acids

Engineering Contradiction:
Improveseparation capabilityVSAvoidsolvent volume
Core Design Contradiction:
Manufacturing precisionVSQuantity of substance

Solution Approach 1:

The patent changes the physical state and chemical properties of the eluent by using supercritical carbon dioxide instead of conventional aqueous alcohol solvents. By adjusting pressure and temperature parameters to achieve supercritical state, the process achieves effective separation of C18 fatty acids from PUFAs while dramatically reducing solvent volume and eliminating the need for large-scale solvent removal operations

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs supercritical CO2 which can be easily evaporated and removed from the final product. The CO2 is used in controlled amounts, performs its separation function, then is completely evaporated leaving no residual solvent in the product, effectively making the solvent 'disposable' without environmental or product contamination concerns

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

3Manufacturing precision

If multiple chromatographic steps are used to reduce C18 fatty acids, then purity is improved, but process complexity increases

Engineering Contradiction:
Improveproduct purityVSAvoidprocess complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent designs a single chromatographic separation system using supercritical CO2 that simultaneously achieves multiple separation objectives: removing C18 fatty acids, separating PUFA fractions, and eliminating solvent residues. This multi-functional approach consolidates what would traditionally require multiple sequential chromatographic steps into one integrated process, reducing overall system complexity while maintaining high purity outcomes

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 (>90%) of PUFAs like EPA and DHA with low levels of C18 fatty acids, such as ALA and GLA, while minimizing solvent usage and preventing product degradation, making it suitable for pharmaceutical and nutraceutical applications.

Implementation Method 1

chromatographic separation process which employs a mixed solvent system

Methodology Applied
Scientific EffectChromatography: Chromatography

Implementation Method 2

purifying the feed mixture in a first chromatographic separation step using as eluent a mixture of water and a first organic solvent

Methodology Applied
Scientific EffectPartitioning: Liquid-Liquid Extraction

Implementation Method 3

The column contains a packing of a porous material (generally called the stationary phase) exhibiting a high permeability to fluids

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 4

Simulated and actual moving bed chromatography are known techniques, familiar to those of skill in the art. The principle of operation involves countercurrent movement of a liquid eluent phase and a solid adsorbent phase

Methodology Applied
Scientific EffectCountercurrent flow: Convection

Data Source

PatentEP3501617B1Multi-step separation process
Publication Date: 2023.02.01 BASF PHARMA CALLANISH
  • EP3501617B1 patent drawingFigure 1
  • EP3501617B1 patent drawingFigure 2
  • EP3501617B1 patent drawingFigure 3

AI summary

The present invention provides a chromatographic separation process for recovering a polyunsaturated fatty acid (PUFA) product from a feed mixture, which comprises: (a) purifying the feed mixture in a first chromatographic separation step using as eluent a mixture of water and a first organic solvent, to obtain an intermediate product; and (b) purifying the intermediate product in a second chromatographic separation step using as eluent a mixture of water and a second organic solvent, to obtain the PUFA product, wherein the second organic solvent is different from the first organic solvent, and wherein the first chromatographic separation step comprises introducing the feed mixture into a stationary bed chromatography apparatus and the second chromatographic separation step comprises introducing the intermediate product into a simulated or actual moving bed chromatography apparatus.