Glutamic Acid Crystallization via Two-Step pH Control

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Solution Overview

Problem

Current methods for producing α-form glutamic acid crystals are challenging due to difficulties in storing seed crystals without transformation to β-form, controlling supersaturation, and the introduction of impurities, which hinders reproducibility and purification.

Innovation Solution

A two-step neutralization crystallization method is employed, where a glutamic acid salt solution is first supersaturated by adding acid to achieve a pH of 1.3 to 2.0, followed by a second supersaturation step to shift the pH toward the isoelectric point, all without adding seed crystals or impurities, to preferentially deposit α-form crystals.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If seed crystals are added to produce α-form crystals, then crystallization can be initiated, but the seed crystals are difficult to store without transforming to β-form crystals

Engineering Contradiction:
Improvecrystallization initiationVSAvoidcrystal form stability
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent creates a supersaturated solution state before crystallization occurs by adjusting pH to 1.3-2.0, preparing the system in advance so that when crystallization begins, α-form crystals form spontaneously without requiring stable seed crystals that would need to be stored and handled separately

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system uses its own supersaturated state to trigger and sustain crystallization of α-form crystals without external intervention from pre-prepared seed crystals, allowing the solution to crystallize autonomously while maintaining the desired crystal form

Inventive Principle:
Principle #25Self-service

2Productivity

If acid is added rapidly to create supersaturation, then crystallization rate increases, but β-form crystals deposit due to excessive supersaturation

Engineering Contradiction:
Improvecrystallization rateVSAvoidcrystal form control
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent carefully controls the pH parameter, adjusting it to a specific range of 1.3-2.0 to create optimal supersaturation conditions. This parameter control enables the system to achieve high crystallization rates while preventing excessive supersaturation that would lead to β-form crystal deposition

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs a dynamic two-step pH adjustment process: first rapidly adjusting pH to create initial supersaturation for high crystallization rate, then slowly adjusting pH toward the isoelectric point to maintain supersaturation at appropriate levels and prevent β-form crystal formation

Inventive Principle:
Principle #15Dynamics

3Ease of manufacture

If amino acids or sugars are added to produce α-form crystals, then crystallization can occur, but impurities are introduced to the system

Engineering Contradiction:
Improvecrystallization capabilityVSAvoidimpurity introduction
Core Design Contradiction:
Ease of manufactureVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and eliminates the need for adding external additives like amino acids or sugars by using pure pH adjustment with acid. This approach maintains the purity of the crystallization system while still enabling α-form crystal formation through controlled supersaturation

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses a simple, inexpensive acid additive that can be easily removed or neutralized, replacing the need for more complex and potentially contaminating additives like amino acids or sugars, thereby maintaining system purity

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

4Quantity of substance

If pH is adjusted to lower than prescribed value, then supersaturation increases, but β-form crystals deposit due to high rate of supersaturation

Engineering Contradiction:
Improvesupersaturation levelVSAvoidcrystal form control
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent establishes an optimal pH range of 1.3-2.0 for initial supersaturation creation, and then dynamically adjusts pH toward the isoelectric point. This parameter control strategy maintains sufficient supersaturation for high crystallization rate while preventing excessive supersaturation that would cause β-form crystal deposition

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 allows for stable and reproducible production of α-form glutamic acid crystals, avoiding the deposition of β-form crystals and minimizing impurity addition, resulting in high-quality α-form crystals suitable for further processing.

Implementation Method 1

forming a first supersaturated state of a glutamic acid salt solution having a rate of supersaturation of 1.0 to 1.7

Methodology Applied
Scientific EffectSupersaturation: Supersaturation

Implementation Method 2

depositing α-form crystals while forming supersaturation

Methodology Applied
Scientific EffectCrystallization: Crystallisation

Implementation Method 3

adding an acid at once to lower pH of the solution beyond isoelectric point of glutamic acid to pH 1.3 to 2.0

Methodology Applied
Scientific EffectNeutralization: Chemical Bonding

Data Source

PatentEP2163539B1METHOD FOR PRECIPITATING alpha-CRYSTALS OF GLUTAMIC ACID
Publication Date: 2016.06.22 AJINOMOTO CO INC
  • EP2163539B1 patent drawingFigure 1
  • EP2163539B1 patent drawingFigure 2~3
  • EP2163539B1 patent drawingFigure 4

AI summary

This invention has an object to provide a crystallization of α-form crystals preferentially which are metastable crystals without depositing β-form crystals which are stable crystals in the polymorphism of glutamic acid crystals existing two forms, and, allows to deposit α-form crystals which are metastable crystals by combining (a) the process of forming supersaturation by mixing an acidic solution with an aqueous solution containing glutamic acid to arrange to a pH region at the isoelectric point of glutamic acid or lower than that, and (b) the process of, after forming the supersaturation of (a), and after elapsed a certain time, adding the aqueous glutamic acid solution again to add a second supersaturation.