Low Odor Choline Ellagate Salt Preparation via Inert Atmosphere

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Solution Overview

Problem

Commercial preparations of choline ellagate and other choline salts often have an unpleasant amine odor due to impurities and degradation, affecting consumer acceptance and bioavailability.

Innovation Solution

A method involving a liquid suspension of ellagic acid and choline in methanol at a pH of 6.95 to 8, under reduced oxygen, followed by cooling and drying, to produce choline ellagate salts with higher purity and reduced odor, increasing solubility and bioavailability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional methods are used to prepare choline ellagate salts, then the production process is simple, but the product has unpleasant amine odor and lower purity

Engineering Contradiction:
Improvepurity of choline ellagate saltVSAvoidamine odor
Core Design Contradiction:
Manufacturing precisionVSObject-generated harmful factors

Solution Approach 1:

The patent applies inert atmosphere by conducting the reaction under nitrogen or argon gas to prevent oxidation of choline and formation of odorous degradation products. The reaction vessel is purged with inert gas before and during the reaction to maintain an oxygen-free environment, thereby producing higher purity choline ellagate salt with minimal amine odor.

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

Solution Approach 2:

The patent changes key reaction parameters including maintaining pH between 6.95-8.0, controlling temperature between 20-40°C, and using specific molar ratios of choline to ellagic acid (1.05:1 to 1.2:1). These parameter optimizations prevent choline degradation and minimize odorous byproduct formation while ensuring complete reaction.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If conventional preparation methods are used, then the manufacturing process is straightforward, but the solubility and bioavailability of the product are reduced

Engineering Contradiction:
Improvesolubility and bioavailabilityVSAvoidcomplexity of preparation process
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent optimizes reaction parameters including pH control (6.95-8.0), temperature (20-40°C), and molar ratios (choline:ellagic acid = 1.05:1 to 1.2:1) to produce choline ellagate salt with enhanced solubility and bioavailability. These controlled conditions ensure complete reaction and high purity product that dissolves more readily in biological systems.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs continuous stirring throughout the reaction process to ensure complete mixing and reaction between choline and ellagic acid. The reaction is maintained under continuous inert gas flow and controlled temperature to ensure consistent product quality and maximum solubility without requiring complex post-processing steps.

Inventive Principle:
Principle #20Continuity of useful action

3Stability of the object's composition

If conventional methods are used to produce choline salts, then production time is shorter, but the stability and degradation resistance of the product is lower

Engineering Contradiction:
Improvestability of choline ellagate saltVSAvoidproduction time
Core Design Contradiction:
Stability of the object's compositionVSProductivity

Solution Approach 1:

The patent conducts the entire reaction and workup process under inert atmosphere (nitrogen or argon) to prevent oxidation of choline and formation of degradation products. The inert gas protects the choline ellagate salt throughout synthesis, isolation, and storage, significantly enhancing product stability without requiring extended reaction times.

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

Solution Approach 2:

The patent prepares solutions of choline and ellagic acid separately under inert atmosphere before mixing, ensuring both starting materials are free from oxidation. The reaction vessel is purged with inert gas before adding reagents, and the entire process is maintained under positive pressure of inert gas to prevent degradation during the relatively short reaction time.

Inventive Principle:
Principle #10Preliminary action

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 method results in choline ellagate salts with lower odor, higher stability, and increased bioavailability, enhancing absorption and metabolite production in subjects compared to conventional methods.

Implementation Method 1

cooling the liquid suspension of step (b) to 20 °C to -80 °C

Methodology Applied
Scientific EffectCooling: Cooling

Implementation Method 2

cooling the liquid suspension containing the choline ellagate salt(s) in the dark and protected from moisture and oxygen

Methodology Applied
Scientific EffectPrecipitation: Precipitation

Implementation Method 3

drying the isolated choline ellagate salt(s)

Methodology Applied
Scientific EffectDrying: Desiccation

Data Source

PatentEP3478091B1Method of preparing a low odor dicholinium ellagate salt and other low odor organic salts of choline
Publication Date: 2024.03.20 HALO LIFE SCIENCE LLC
  • EP3478091B1 patent drawingFigure 1
  • EP3478091B1 patent drawingFigure 2

AI summary

Methods of making low odor choline salts of an organic compound, for example, choline ellagate compound(s), and uses and formulations thereof.