Simulated Moving Bed Chromatography for Cannabinoid Isomer Separation

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Solution Overview

Problem

Current methods for purifying cannabinoid compounds, such as trans-(-)-delta-9-tetrahydrocannabinol and trans-(-)-delta-9-tetrahydrocannabivarin, are inefficient and costly, particularly in achieving high purity levels on a large scale due to the structural similarity of isomers which complicates separation.

Innovation Solution

The use of simulated moving bed chromatography (SMB) in combination with additional extraction steps to separate and purify cannabinoid compounds, allowing for the simultaneous continuous separation and purification of desired compounds with reduced eluant usage and minimal material loss.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional chromatography methods are used to purify cannabinoid compounds, then separation of isomers can be achieved, but the process becomes time-consuming and expensive, particularly at large scale

Engineering Contradiction:
Improvepurity levelVSAvoidpurification time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The patent applies simulated moving bed chromatography where the stationary phase is dynamically switched between different regions (loading, separation, elution, regeneration) through periodic valve switching. This dynamic operation allows continuous purification at industrial scale, resolving the contradiction between achieving high purity and reducing purification time.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The SMB system enables continuous operation where multiple columns work in sequence to maintain continuous purification flow. The feed stream continuously enters the system and pure product continuously exits, eliminating the batch processing time losses associated with conventional chromatography while maintaining high purity levels.

Inventive Principle:
Principle #20Continuity of useful action

2Manufacturing precision

If conventional chromatography methods are used to purify cannabinoid compounds, then separation of isomers can be achieved, but the process becomes costly and complex

Engineering Contradiction:
Improvepurity levelVSAvoidprocess complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The purification system is divided into multiple identical chromatography columns arranged in series, with each column performing a specific function in the cyclic process. This segmentation allows the complex purification function to be distributed across simpler, identical units, reducing overall system complexity while maintaining high purification performance.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system uses periodic valve switching to cycle through different operational modes (loading, separation, elution, regeneration) for each column. This periodic action simplifies control by using repeated cyclic operations rather than continuous complex control, making the system more manageable while achieving high purity separation.

Inventive Principle:
Principle #19Periodic action

3Manufacturing precision

If traditional purification methods are used, then isomer separation can be achieved, but material loss increases and eluant consumption is high

Engineering Contradiction:
Improveisomer separationVSAvoidmaterial loss
Core Design Contradiction:
Manufacturing precisionVSLoss of substance

Solution Approach 1:

The SMB system recovers and reuses the mobile phase (eluant) throughout the cyclic operation. The eluant that has passed through the columns is collected and reused in subsequent cycles, significantly reducing material loss and eluant consumption compared to conventional methods where eluant is continuously consumed and discarded.

Inventive Principle:
Principle #34Discarding and recovering

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 achieves high purity levels with isomers below detection limits, enabling large-scale production while reducing costs and time, as demonstrated by the successful purification of delta-9-THC and delta-9-THCV with minimal residual impurities.

Implementation Method 1

purifying cannabinoid compounds via simulated moving bed chromatography

Methodology Applied
Scientific EffectChromatography: Chromatography

Implementation Method 2

the cannabinoid compound(s) is/are obtained in the extract and/or the raffinate with the total amount of isomeric impurities being below detection level

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentEP3455213B1Method for purifying cannabinoid compounds via simulated moving bed chromatography
Publication Date: 2021.11.24 SYMRISE GMBH & CO KG
  • EP3455213B1 patent drawingFigure 1a~1b
  • EP3455213B1 patent drawingFigure 2a~2b
  • EP3455213B1 patent drawingFigure 3

AI summary

The present invention relates to methods for purifying one or two cannabinoid compounds using simulated moving bed chromatography, wherein the cannabinoid compound(s) is/are obtained in the extract and/or the raffinate with the total amount of isomeric impurities being below detection level. In particular, the present invention relates to methods for the purification of cannabidiol, trans-(-)-delta-9-tetrahydrocannabinol, cannabidivarin, trans-(-)-delta-9-tetrahydrocannabivarin and cannabigerol which have been obtained by enantiopure synthesis.