Cannabinoid Purification via Cyclohexane CPC

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Solution Overview

Problem

Current methods for extracting cannabinoids, such as THC and CBD, from cannabis extracts using Centrifugal Partition Chromatography (CPC) face challenges in achieving high purity and yield, with prior art methods achieving maximum purities of around 93.1% and requiring multiple steps, while also using neurotoxic solvents like hexane.

Innovation Solution

A method utilizing a two-phase solvent system with cyclohexane, n-heptane, or iso-octane as the stationary phase and acetonitrile as the mobile phase, with optional addition of t-butyl methyl ether, which enhances separation performance, achieving purities over 95% and reducing the need for additional chromatographic steps, and allows for easy renewal of the stationary phase.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If hexane is used as the stationary phase in CPC, then the separation process can be performed, but the purity achieved is limited to maximum 93.1% and hexane is neurotoxic

Engineering Contradiction:
Improvepurity of cannabinoidsVSAvoidneurotoxicity of hexane
Core Design Contradiction:
Manufacturing precisionVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical parameters of the stationary phase by replacing hexane with cyclohexane, n-heptane, or iso-octane. This substitution maintains the functional properties needed for separation while eliminating the neurotoxicity issue, and simultaneously improves purity from 93.1% to over 95%

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent treats the stationary phase as a disposable component that can be easily renewed by distillation. Each run completely renews the stationary phase, eliminating the need for complex regeneration processes and allowing simple replacement of toxic solvents with safer alternatives

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

2Manufacturing precision

If a two-phase system based on hexane is used, then separation can be achieved, but additional chromatographic steps are required and yields are low

Engineering Contradiction:
Improvepurity of cannabinoidsVSAvoidyield and number of process steps
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent modifies the phase system parameters by using cyclohexane, n-heptane, or iso-octane as stationary phase with acetonitrile as mobile phase. This parameter change achieves purities over 95% in a single step, eliminating the need for multiple chromatographic steps and significantly increasing yield

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent extracts and removes the problematic hexane-based system and replaces it with an improved solvent system. The new system extracts cannabinoids with higher efficiency in a single step, taking out the need for additional purification steps

Inventive Principle:
Principle #2Taking out (Extraction)

3Productivity

If the stationary phase is used multiple times, then process efficiency is maintained, but deposits accumulate requiring regeneration or removal of interfering components

Engineering Contradiction:
Improveprocess efficiencyVSAvoidpurity of cannabinoids
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent treats the stationary phase as a disposable component that is completely renewed after each run through simple distillation. This approach maintains high process efficiency while ensuring consistent purity over 95%, as each run starts with a fresh, deposit-free stationary phase

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

Solution Approach 2:

The patent discards the used stationary phase after each run and recovers it through simple distillation for complete renewal. This process eliminates deposit accumulation and interfering components, maintaining both high productivity and purity without complex regeneration procedures

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 and yield of cannabinoids, often exceeding 95%, with reduced process stages and minimal eluent consumption, enabling efficient industrial-scale extraction with minimal solvent toxicity and no deposition on the stationary phase.

Implementation Method 1

CPC is a liquid-liquid chromatography method that typically uses a two-phase solvent system. In these chambers, arranged directly one after the other, the substances contained in the plant extract are distributed between the mobile and stationary phases.

Methodology Applied
Scientific EffectLiquid-liquid partition chromatography: Chromatography

Implementation Method 2

The partition coefficient K of the desired substance between the two phases should be between 0.7 and 4.5. At lower K values, the substance elutes too quickly, making separation impossible. At higher K values, however, the retention time becomes too long

Methodology Applied
Scientific EffectPartition coefficient distribution: Liquid-Liquid Extraction

Implementation Method 3

The system is set into rapid rotation (up to 2,500 rpm) during the separation process. This not only retains the desired phase in the CPC rotor, depending on the flow direction, but also accelerates the separation of the two phases through centrifugal force.

Methodology Applied
Scientific EffectCentrifugal force: Centrifugal Force

Implementation Method 4

The density and viscosity of cyclohexane, n-heptane and iso-octane are greater than the density/viscosity of n-hexane, so that a more stable two-phase system is produced compared to a second mobile phase such as acetonitrile, for example, enabling better retention of the stationary phase

Methodology Applied
Scientific EffectDensity difference: Density Gradient

Data Source

PatentEP3978095B1Cpc partition chromatography of cannabinoids
Publication Date: 2024.11.06 CANDORO ETHICS GMBH
  • EP3978095B1 patent drawingFigure 1~3
  • EP3978095B1 patent drawingFigure 4~6
  • EP3978095B1 patent drawingFigure 7~9

AI summary

The invention relates to the isolation and purification of cannabinoids by means of centrifugal partition chromatography.