L-Citrulline Purification by Continuous Chromatography and Crystallization

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Solution Overview

Problem

Existing methods for producing high-purity L-citrulline through fermentation processes require multiple purification steps, leading to reduced yield and the use of chemical solvents, which are environmentally unfriendly and fail to meet food-grade purity standards.

Innovation Solution

A method utilizing continuous chromatography and crystallization to purify L-citrulline without organic solvents, involving a continuous chromatography process using strong acid cation exchange resin to separate impurities, followed by concentration and cooling crystallization to form easy-to-separate anhydrous crystals.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If multiple purification steps are used to obtain high-purity citrulline through fermentation process, then purity is improved, but recovery yield decreases

Engineering Contradiction:
ImprovepurityVSAvoidrecovery yield
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent combines multiple purification operations (chromatography, filtration, concentration, crystallization) into an integrated continuous processing system where the fermentation broth is directly processed through a chromatography column followed by sequential filtration and crystallization steps, eliminating the need for separate intermediate purification stages while maintaining high purity (98.5% or more) and improving recovery yield

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent implements a continuous processing workflow where the fermentation broth flows continuously through the chromatography column, then through filtration systems, and into concentration and crystallization vessels without interruption, maintaining continuous useful action throughout the purification process to improve both purity and recovery yield efficiency

Inventive Principle:
Principle #20Continuity of useful action

2Manufacturing precision

If resin columns and organic solvents are used for purification, then purity is improved, but environmental friendliness deteriorates

Engineering Contradiction:
ImprovepurityVSAvoidenvironmental friendliness
Core Design Contradiction:
Manufacturing precisionVSObject-affected harmful factors

Solution Approach 1:

The patent changes the parameters of the purification process by using a continuous chromatography system with controlled flow rates and a continuous crystallization process with controlled temperature and concentration parameters, achieving high purity (98.5% or more) without requiring organic solvents or traditional resin column methods, thereby improving environmental friendliness

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces the chemical-based purification method (using organic solvents and resin columns) with a physical-based continuous processing system involving chromatography, filtration, and crystallization, eliminating harmful chemical substances while achieving the required purity level for food-grade citrulline

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

3Manufacturing precision

If more purification steps are added, then purity is improved, but process complexity increases

Engineering Contradiction:
ImprovepurityVSAvoidprocess complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent segments the purification process into distinct functional units (chromatography column, filtration system, concentration vessel, crystallization vessel) that operate in sequence, where each unit performs a specific purification function, simplifying the overall process complexity while achieving high purity (98.5% or more) through the coordinated action of these segmented steps

Inventive Principle:
Principle #1Segmentation

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

Achieves high-purity L-citrulline production with reduced steps and energy consumption, meeting food-grade purity standards while being environmentally friendly.

Implementation Method 1

a continuous chromatography process using strong acid cation exchange resin to separate impurities

Methodology Applied
Scientific EffectIon exchange: Ion Exchange

Implementation Method 2

followed by concentration and cooling crystallization to form easy-to-separate anhydrous crystals

Methodology Applied
Scientific EffectCrystallization: Crystallisation

Data Source

PatentEP4660312A1Method and apparatus for preparing l-citrulline
Publication Date: 2025.12.10 CJ CHEILJEDANG CORP
  • EP4660312A1 patent drawingFigure 1
  • EP4660312A1 patent drawingFigure 2
  • EP4660312A1 patent drawingFigure 3

AI summary

The present disclosure relates to a preparation method for L-citrulline, comprising: Step 1 of preparing a fermentation broth comprising L-citrulline; Step 2 of performing a continuous chromatography process on the fermentation broth to obtain a purified citrulline process liquid; and Step 3 of crystallizing and separating L-citrulline in the purified citrulline process liquid. According to the present disclosure, high purity L-citrulline crystals can be obtained in high yield from the fermentation broth.