Reduced Coenzyme Q10 Form I Crystal Production

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Solution Overview

Problem

The production of reduced coenzyme Q10 crystals is hindered by the presence of metastable Form I crystals, which can contaminate with stable Form II crystals, affecting bioavailability and stability, and existing methods fail to efficiently produce Form I crystals alone.

Innovation Solution

A method involving holding a solution containing reduced coenzyme Q10 at a temperature exceeding 47°C for at least 60 minutes, followed by crystallization, using solvents like hydrocarbons, fatty acid esters, or alcohols, and controlling temperature variations to produce Form I crystals substantially free of Form II crystals.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional crystallization methods are used to produce reduced coenzyme Q10, then reduced coenzyme Q10 crystals can be obtained, but the crystals are contaminated with metastable Form I crystals instead of being pure stable Form I crystals

Engineering Contradiction:
Improvecrystal form purityVSAvoidcrystal form stability
Core Design Contradiction:
Manufacturing precisionVSReliability

Solution Approach 1:

The patent applies parameter changes by precisely controlling temperature (maintaining 47-50°C for at least 60 minutes) and solvent composition (using specific ratios of alcohol, ketone, and water) to guide the crystallization process toward forming pure stable Form I crystals while preventing metastable Form I crystal formation

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies preliminary action by pre-heating the solution to the specific temperature range of 47-50°C before initiating crystallization and maintaining this temperature for at least 60 minutes to ensure complete dissolution and prevent premature crystal formation, thereby ensuring pure Form I crystal production

Inventive Principle:
Principle #10Preliminary action

2Manufacturing precision

If temperature control is not strictly maintained during crystallization, then the production process is simpler, but the crystal form becomes uncontrollable and may produce unwanted polymorphs

Engineering Contradiction:
Improvecrystal form controlVSAvoidtemperature control system
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent specifies precise parameter ranges (temperature: 47-50°C, time: at least 60 minutes, solvent composition: specific alcohol-ketone-water ratios) that balance manufacturing precision with practical implementability, allowing standard equipment to achieve reliable Form I crystal production

Inventive Principle:
Principle #35Parameter changes

3Reliability

If existing crystallization methods are used, then reduced coenzyme Q10 can be produced, but the bioavailability and stability are compromised due to crystal polymorph contamination

Engineering Contradiction:
Improveproduct stabilityVSAvoidproduction complexity
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent changes key parameters including temperature (47-50°C range), time (at least 60 minutes), and solvent composition (specific ratios of alcohol, ketone, and water) to achieve reliable production of stable Form I crystals with improved bioavailability while maintaining practical manufacturability

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

This method ensures the consistent production of Form I crystals with controlled crystal polymorph, enhancing bioavailability and stability, and is scalable for industrial production.

Implementation Method 1

a method involving holding a solution containing reduced coenzyme Q10 at a temperature exceeding 47°C for at least 60 minutes, followed by crystallization

Methodology Applied
Scientific EffectCrystallization: Crystallisation

Implementation Method 2

holding a solution containing reduced coenzyme Q10 at a temperature exceeding 47°C for at least 60 minutes, and a step of crystallization thereafter

Methodology Applied
Scientific EffectPhase change: Phase Change

Data Source

PatentUS9440901B2Method for producing reduced coenzyme Q10
Publication Date: 2016.09.13 KANEKA CORP

AI summary

Provided is a production method of Form I crystal of reduced coenzyme Q10 or a crystalline solid thereof, which is substantially free of Form II crystal, including a step of holding a solution containing reduced coenzyme Q10 at a temperature exceeding 47° C. for at least 60 minutes, and a step of crystallization thereafter.