Crystalline Difucosyllactose via Aqueous Alcohol Crystallization
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Solution Overview
Problem
Current methods are inefficient and costly for producing large volumes of fucosylated lactoses, particularly difucosyllactose (DFL), due to the difficulty in isolating and purifying it from human milk and the lack of crystalline forms, which are crucial for industrial applications.
Innovation Solution
A method is developed to crystallize DFL by dissolving non-crystalline DFL in a solvent system of C1-C4 alcohols and water, followed by cooling and optionally adding seeding crystals, resulting in the formation of crystalline DFL with specific X-ray powder diffraction patterns and high purity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If DFL is isolated from human milk using current methods, then DFL can be obtained, but the process is difficult, expensive, and inefficient due to the presence of many similar oligosaccharides
Solution Approach 1:
The patent applies parameter changes by optimizing crystallization conditions including solvent composition (water/ethanol or water/isopropanol ratios), temperature (cooling from dissolution temperature to room temperature or lower), and pH to achieve selective crystallization of DFL from complex milk oligosaccharide mixtures, thereby simplifying purification and enabling large-scale production
Solution Approach 2:
The patent utilizes phase transitions through controlled crystallization where DFL transitions from dissolved state in aqueous alcohol solvent to solid crystalline form by cooling and solvent composition adjustment, enabling efficient separation from other oligosaccharides that remain in solution
2Ease of manufacture
If DFL is produced through chemical synthesis or biotechnology, then DFL can be made, but there is no known crystalline form and current methods are costly
Solution Approach 1:
The patent extracts DFL from complex biological matrices (human milk) or production mixtures using crystallization, separating the target compound from contaminants and enabling cost-effective large-scale production without requiring expensive purification chromatography methods
Solution Approach 2:
The patent optimizes crystallization parameters including solvent type (water/ethanol or water/isopropanol), solvent ratio, temperature, and pH to control DFL crystallization efficiency, enabling scalable production at lower cost compared to previous methods
3Manufacturing precision
If crystallization is used to separate DFL from contaminants, then pure crystalline DFL can be obtained, but specific solvent systems and conditions must be precisely controlled
Solution Approach 1:
The patent defines specific parameter ranges for crystallization including water/ethanol or water/isopropanol solvent ratios, temperature ranges for dissolution and cooling, and pH conditions that optimize DFL crystallization while maintaining simplicity and reproducibility of the process
Solution Approach 2:
The patent uses water/ethanol or water/isopropanol solvent systems as intermediaries to facilitate selective crystallization of DFL, where the solvent composition acts as a mediator that promotes DFL crystallization while keeping other oligosaccharides in solution
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 enables the production of high-purity crystalline DFL, suitable for pharmaceutical and nutritional uses, with controlled impurity levels and minimal solvent content, facilitating its application in infant formulas and food supplements.
Implementation Method 1
dissolving non-crystalline DFL in a solvent system of C1-C4 alcohols and water between room temperature (ca. 25 °C) and 80 °C to form a mixture
Implementation Method 2
stirring the mixture obtained in step a) and allowing it to cool, preferably to room temperature... then collecting and drying DFL crystals which precipitate from the mixture
Implementation Method 3
crystalline DFL with specific X-ray powder diffraction patterns
Data Source
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AI summary
Crystalline difucosyllactose, useful in a pharmaceutical composition and a nutritional composition is disclosed. Also disclosed is a method of obtaining crystalline difucosyllactose by crystallisation from a mixture of water and one or more C1 - C4 alcohols and a method of synthesising difucosyllactose from suitably protected lactose and a glycosyl donor.