Yellow Reduced PQQ Crystals via Ascorbic Acid Reduction

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Solution Overview

Problem

Conventional methods for producing reduced pyrroloquinoline quinone (PQQ) crystals face challenges such as toxicity from reducing agents, explosive hydrogen use, high costs, low water solubility, and difficulty in forming light-colored crystals suitable for food and pharmaceutical applications.

Innovation Solution

A method involving the reduction of pyrroloquinoline quinone using ascorbic acid at controlled temperatures and pH, resulting in yellow reduced PQQ crystals with enhanced solubility and stability, and a composition with cyclodextrin for improved dispersibility and solubility.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional reducing agents (sodium borohydride, sodium dithionite) are used to reduce oxidized PQQ, then reduced PQQ can be obtained, but toxicity is introduced requiring additional removal steps

Engineering Contradiction:
ImprovesafetyVSAvoidprocess complexity
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent uses ascorbic acid, a safe and inexpensive reducing agent that can be easily removed from the final product, replacing toxic reducing agents like sodium borohydride and sodium dithionite that require complex removal steps. Ascorbic acid's short-lived nature in the reaction allows for simple purification by filtration and washing, eliminating the need for sophisticated toxicity removal facilities.

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

2Reliability

If hydrogen gas is used as reducing agent with platinum catalyst, then reduced PQQ can be obtained, but explosive hazards require special facilities

Engineering Contradiction:
ImprovesafetyVSAvoidfacility requirements
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces hydrogen gas with ascorbic acid as the reducing agent. Ascorbic acid is a stable, non-explosive solid that can be handled safely without special facilities. The reduction reaction proceeds under mild conditions at room temperature, eliminating the need for expensive hydrogen handling equipment, catalysts, and specialized explosion-proof facilities.

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

3Reliability

If conventional recrystallization with dimethyl sulfoxide and acetonitrile is used, then reduced PQQ crystals can be obtained, but organic solvent residues remain requiring additional treatment

Engineering Contradiction:
ImprovepurityVSAvoidprocess simplicity
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent changes the crystallization parameters by using water as the solvent instead of organic solvents like dimethyl sulfoxide and acetonitrile. The reduced PQQ is recrystallized from aqueous solution at controlled temperatures (0-25°C), yielding pure yellow crystals free from organic solvent residues. This parameter change eliminates the need for additional solvent removal treatment and allows direct use in food and pharmaceutical applications.

Inventive Principle:
Principle #35Parameter changes

4Quantity of substance

If conventional black reduced PQQ crystals are used, then they can be obtained through simple reduction, but they have low solubility in water and alcohol making them difficult to use in liquid forms

Engineering Contradiction:
ImprovesolubilityVSAvoidapplication versatility
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent changes the crystallization parameters including temperature control (0-25°C), pH adjustment (2.0-4.0), and solvent selection (water-based) to produce yellow reduced PQQ crystals with enhanced solubility. These yellow crystals exhibit significantly higher solubility in water (0.04-0.20 mg/mL) and alcohol compared to conventional black crystals, enabling direct use in liquid food and pharmaceutical formulations without requiring aprotic solvents like dimethyl sulfoxide.

Inventive Principle:
Principle #35Parameter changes

5Illumination intensity

If conventional black reduced PQQ crystals are used, then they can be obtained, but their dark color makes them unsuitable for food and cosmetic applications

Engineering Contradiction:
Improvecolor brightnessVSAvoidapplication suitability
Core Design Contradiction:
Illumination intensityVSEase of manufacture

Solution Approach 1:

The patent changes the crystallization parameters including temperature (0-25°C), pH (2.0-4.0), and oxidation potential control to produce yellow reduced PQQ crystals instead of black crystals. The yellow color results from controlled crystallization conditions that prevent over-oxidation and aggregation. This color improvement makes the product suitable for food, cosmetic, and pharmaceutical applications where appearance is critical.

Inventive Principle:
Principle #35Parameter changes

6Reliability

If column chromatography is used for purification, then reduced PQQ can be obtained, but expensive facilities and large amounts of extraction solution are required

Engineering Contradiction:
ImprovepurityVSAvoidfacility cost
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and purifies reduced PQQ through simple filtration and washing steps instead of using column chromatography. The reduced PQQ crystals are filtered directly from the aqueous reaction mixture and washed with water to remove impurities. This extraction approach eliminates the need for expensive column chromatography facilities and large amounts of organic extraction solvents, significantly reducing production costs while maintaining high purity.

Inventive Principle:
Principle #2Taking out (Extraction)

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 produces yellow reduced PQQ crystals with high solubility and stability, suitable for food and pharmaceutical applications, avoiding the limitations of conventional methods and ensuring safety and cost-effectiveness.

Implementation Method 1

a method involving the reduction of pyrroloquinoline quinone using ascorbic acid

Methodology Applied
Scientific EffectRedox reactions: Redox Reactions

Implementation Method 2

a composition with cyclodextrin for improved dispersibility and solubility

Methodology Applied
Scientific EffectInclusion complex formation: Absorption (physical)

Data Source

PatentUS9732079B2Yellow reduced pyrroloquinoline quinone crystal and method of producing the same, and food, pharmaceutical, gel, composition and method of producing composition
Publication Date: 2017.08.15 MITSUBISHI GAS CHEM CO INC
  • US9732079B2 patent drawing
  • US9732079B2 patent drawing
  • US9732079B2 patent drawing

AI summary

A yellow reduced pyrroloquinoline quinone crystal having a solubility in water of 0.040 to 0.20 (mg/mL).