Crystalline 3-O-fucosyllactose Purification via Phase Transition

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

The synthesis and purification of 3-O-fucosyllactose, an important human milk oligosaccharide, are challenging and costly due to its amorphous form, which affects its properties and makes commercialization difficult.

Innovation Solution

Obtaining crystalline 3-O-fucosyllactose by drying syrupy forms under high vacuum or converting amorphous forms to crystalline using antisolvents, followed by classical crystallization with seeding in alcoholic solvent systems, resulting in high-purity polycrystalline material with specific X-ray powder diffraction patterns and thermal stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If 3-FL is synthesized by enzymatic, biotechnological and chemical processes, then 3-FL can be obtained, but it is isolated as an amorphous material which is costly to purify

Engineering Contradiction:
Improvepurification costVSAvoidcrystalline form
Core Design Contradiction:
Ease of manufactureVSShape

Solution Approach 1:

The patent applies phase transition by converting amorphous 3-FL to crystalline form through controlled crystallization processes. The invention describes methods to induce crystallization from amorphous material by adjusting temperature, solvent composition, and using seeding techniques, thereby transforming the physical state and improving purification efficiency

Inventive Principle:
Principle #36Phase transitions

Solution Approach 2:

The patent employs parameter changes by systematically varying crystallization conditions including temperature gradients, solvent ratios (alcoholic solvents mixed with water), pH levels, and concentration to achieve reliable crystallization of 3-FL. These parameter optimizations enable consistent formation of crystalline material suitable for cost-effective purification

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If 3-FL is isolated from human milk by chromatographic procedures, then pure 3-FL can be obtained, but the process is very costly and complicated

Engineering Contradiction:
ImprovepurityVSAvoidchromatographic procedures
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent applies extraction by removing 3-FL from complex mixtures through selective crystallization. By inducing crystallization of 3-FL from solution while leaving other components in solution, the method extracts pure crystalline 3-FL without requiring complex chromatographic separation procedures

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces complex mechanical chromatographic systems with a simpler crystallization-based purification approach. Instead of using sophisticated chromatographic equipment and procedures, the invention uses controlled crystallization followed by simple filtration to achieve high purity 3-FL

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Stability of the object's composition

If amorphous 3-FL is used, then synthesis is simpler, but it lacks thermodynamic stability and has poor solubility properties

Engineering Contradiction:
Improvethermodynamic stabilityVSAvoidcrystallization process
Core Design Contradiction:
Stability of the object's compositionVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by preparing amorphous 3-FL as an intermediate step and then systematically converting it to the stable crystalline form. The invention describes preliminary drying of syrupy material followed by controlled crystallization to achieve the thermodynamically stable crystalline state with improved properties

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 provides a cost-effective and scalable process for obtaining high-purity crystalline 3-O-fucosyllactose suitable for nutritional and pharmaceutical applications, enhancing its stability and solubility properties.

Implementation Method 1

crystalline 3-FL can be obtained when 3-FL in syrupy form is dried under high vacuum for prolonged time

Methodology Applied
Scientific EffectVacuum drying: Vacuum Distillation

Implementation Method 2

amorphous/precipitated 3-FL can be converted to crystalline material when suspended and stirred in bad solvent(s) for some time

Methodology Applied
Scientific EffectCrystallization: Crystallisation

Implementation Method 3

it can be used as seeding crystals for classical crystallization from solvent system, preferably those comprising an alcoholic solvent

Methodology Applied
Scientific EffectSeeded crystallization: Crystallisation

Data Source

PatentUS9834574B2Crystalline 3-O-fucosyllactose
Publication Date: 2017.12.05 GLYCOM AS
  • US9834574B2 patent drawing
  • US9834574B2 patent drawing
  • US9834574B2 patent drawing

AI summary

Crystalline 3-O-fucosyllactose, useful in a pharmaceutical composition and a nutritional formulation, is disclosed.