Liquid-Liquid Extraction of Psychoactive Alkaloids into Stable Salt Forms

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Solution Overview

Problem

Existing methods for extracting psychoactive alkaloids from natural sources face challenges such as instability due to dephosphorylation, degradation, and variability in concentration, leading to costly and complex processes that result in non-standardized extracts with poor stability and handling issues.

Innovation Solution

An acid extraction process followed by pH adjustment to convert dephosphorylated alkaloids to their deprotonated form, combined with two-stage liquid-liquid extractions using water-immiscible and weakly-acidified solvents, to produce a stable, standardized extract of psychoactive alkaloids in conjugate salt form.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional extraction methods are used to obtain psychoactive alkaloids, then extraction efficiency is achieved, but the extract exhibits poor stability due to dephosphorylation and degradation

Engineering Contradiction:
Improvestability of extractVSAvoidextraction efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent applies parameter changes by carefully controlling pH levels throughout the extraction process. The extract is maintained at acidic pH (3-6) during extraction to prevent dephosphorylation, then adjusted to alkaline pH (8-10) for liquid-liquid extraction, and finally adjusted to pH 2-4 for storage. This systematic pH management resolves the contradiction by enabling efficient extraction while maintaining extract stability through controlled chemical conditions.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses an intermediary approach by introducing a conjugate base (such as citrate, tartrate, or acetate) that forms a stable conjugate salt with the psychoactive alkaloid. This conjugate salt acts as a stable intermediate form that prevents degradation and dephosphorylation, allowing the extract to maintain both extraction efficiency and long-term stability during storage and handling.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Manufacturing precision

If multiple purification steps are implemented to improve extract quality, then purity increases, but process complexity and cost increase

Engineering Contradiction:
Improvepurity of extractVSAvoidprocess complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent applies the extraction principle by using liquid-liquid extraction with water-immiscible solvents to selectively separate psychoactive alkaloids from impurities. The process extracts the alkaloid into an organic phase, leaving behind water-soluble impurities, then back-extracts into an acidic aqueous phase. This targeted extraction approach achieves high purity without requiring multiple complex purification steps, resolving the contradiction between purity and process complexity.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent utilizes phase transitions in liquid-liquid extraction, where the psychoactive alkaloid transitions between aqueous and organic phases based on pH control. At alkaline pH, the alkaloid partitions into the organic phase; at acidic pH, it returns to the aqueous phase. This phase transition mechanism enables efficient purification in a single extraction system, reducing overall process complexity while maintaining high purity.

Inventive Principle:
Principle #36Phase transitions

3Manufacturing precision

If conventional extraction and storage methods are used, then simplicity is maintained, but concentration variability and degradation occur

Engineering Contradiction:
Improvestandardization of extractVSAvoidsimplicity of process
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by converting the psychoactive alkaloid to its stable conjugate salt form early in the process, before storage and handling. The conjugate base is added during the final pH adjustment step, forming a stable conjugate salt that prevents degradation and ensures consistent concentration. This preliminary stabilization action maintains both standardization and manufacturing simplicity throughout the product lifecycle.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses parameter changes, specifically pH control, to achieve both standardization and simplicity. By maintaining the extract at controlled acidic pH (2-4) and converting to conjugate salt form, the process standardizes the extract concentration and prevents variability. This single parameter control approach achieves standardization without complicating the manufacturing process.

Inventive Principle:
Principle #35Parameter changes

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

The process achieves high concentrations of stable, standardized psychoactive alkaloids suitable for oral administration, reducing costs and improving consistency, while maintaining oxidative stability and allowing for a wider range of raw materials to be used.

Implementation Method 1

performing a first liquid-liquid extraction on the basified psychoactive filtrate using a water-immiscible solvent to yield a psychoactive organic layer

Methodology Applied
Scientific EffectLiquid-liquid extraction: Liquid-Liquid Extraction

Implementation Method 2

performing a second liquid-liquid extraction on the psychoactive organic layer using weakly-acidified water to yield a psychoactive aqueous layer

Methodology Applied
Scientific EffectLiquid-liquid extraction: Liquid-Liquid Extraction

Implementation Method 3

removing water from the psychoactive aqueous layer to yield a dry, psychoactive extract

Methodology Applied
Scientific EffectEvaporation: Evaporation

Data Source

PatentEP4387615B1Liquid-liquid extraction of purified psychoactive alkaloid
Publication Date: 2025.07.09 PSILO SCIENTIFIC LTD
  • EP4387615B1 patent drawingFigure 1~2
  • EP4387615B1 patent drawingFigure 3

AI summary

A solution of extracted psychoactive alkaloids is obtained from psychoactive organisms or an existing extract using a neutral or acidic solvent. Acid extraction of psychoactive compounds from psychoactive organisms results in the dephosphorylated form of psychoactive alkaloids. The solution is basified to deprotonate the alkaloids. It is then subjected to a liquid-liquid extraction with a water-immiscible solvent. The resulting psychoactive organic layer is then subjected to a second liquid-liquid extraction with weakly acidic water. The resulting psychoactive aqueous layer is then dried to form a powder with the psychoactive alkaloid in a conjugate salt form. The powder may be standardized to a desired concentration of psychoactive alkaloid by the addition of an excipient. Alternatively, the standardization may be carried out on the psychoactive aqueous phase. Obtaining the psychoactive alkaloid in the conjugate salt form reduces the amount of non-psychoactive components included in the final extract.