Human Milk Oligosaccharide Spray-Drying for Stability

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Solution Overview

Problem

Human milk oligosaccharides (HMOs) synthesized by catalytic hydrogenolysis are contaminated with organic solvent residues and are unstable and difficult to dissolve, limiting their use in nutritional and therapeutic formulations, especially for infants, due to residual contaminants and poor storage stability.

Innovation Solution

A method involving spray-drying of HMOs or their precursors in an aqueous solution at high temperatures to remove water and organic solvent residues, converting them into an amorphous form with a higher glass transition temperature, enhancing stability and bioavailability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If HMOs are synthesized by catalytic hydrogenolysis, then HMOs can be produced efficiently, but organic solvent residues contaminate the product

Engineering Contradiction:
ImproveHMO production efficiencyVSAvoidorganic solvent residues
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and removes organic solvent residues from HMO products through a multi-step purification process including filtration, concentration, and lyophilization. This separates the harmful solvent components from the desired HMO product while maintaining production efficiency.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent discards organic solvent residues through controlled evaporation and lyophilization processes, recovering pure HMO products. The solvents are removed and discarded while the valuable HMOs are retained and purified.

Inventive Principle:
Principle #34Discarding and recovering

2Temperature

If HMOs are stored at elevated temperatures, then storage conditions are improved, but HMO stability decreases

Engineering Contradiction:
Improvestorage temperatureVSAvoidHMO stability
Core Design Contradiction:
TemperatureVSStability of the object's composition

Solution Approach 1:

The patent changes the physical state parameter of HMOs from crystalline to amorphous form through controlled drying processes. This parameter change enables the HMOs to maintain stability at elevated storage temperatures where crystalline forms would degrade.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite amorphous structures by combining HMOs with suitable excipients or carriers during the lyophilization process. This composite approach enhances thermal stability while maintaining the functional properties of HMOs.

Inventive Principle:
Principle #40Composite materials

3Manufacturing precision

If HMOs are crystallized from organic solvents, then pure crystalline HMOs are obtained, but residual solvents remain and require additional costly processing

Engineering Contradiction:
ImproveHMO purityVSAvoidprocessing steps
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent replaces traditional mechanical filtration and multiple recrystallization steps with a streamlined process using lyophilization (freeze-drying). This substitution achieves equivalent or superior purity with fewer processing steps and reduced complexity.

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

Solution Approach 2:

The patent utilizes phase transitions (freezing and sublimation) during lyophilization to purify HMOs. The phase change from frozen to vapor state removes solvents and impurities efficiently, achieving high purity without multiple mechanical processing steps.

Inventive Principle:
Principle #36Phase transitions

4Manufacturing precision

If HMOs are produced with high purity, then product quality is improved, but production cost increases due to additional processing

Engineering Contradiction:
ImproveHMO purityVSAvoidproduction cost
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent merges multiple purification functions (filtration, concentration, solvent removal, and drying) into a single integrated lyophilization process. This consolidation achieves high purity while reducing the number of separate processing steps and associated costs.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The lyophilization process serves multiple functions simultaneously: it removes organic solvents, concentrates the HMO solution, removes water, and creates the final stable powder form. This multi-functionality reduces the need for separate processing equipment and operations.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 significantly reduces organic solvent residues and improves the stability and bioavailability of HMOs, allowing them to be stored at elevated temperatures without degradation and easily mixed with other ingredients for formulations.

Implementation Method 1

spray-drying of HMOs or their precursors in an aqueous solution at high temperatures to remove water

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 2

spray-drying of HMOs or their precursors in an aqueous solution at high temperatures to remove water and organic solvent residues

Methodology Applied
Scientific EffectEvaporation: Evaporation

Data Source

PatentUS9896470B2Enhancing the stability and purity and increasing the bioavailability of human milk oligosaccharides or precursors or blends thereof
Publication Date: 2018.02.20 GLYCOM AS

AI summary

The present application discloses a method for enhancing the stability of a human milk oligosaccharide (HMO) or a HMO precursor or a HMO blend when stored for extended periods at temperatures above 25° C. by spray-drying an aqueous solution of the HMO or HMO precursor to remove at least 90% of the water and providing a HMO or a HMO precursor or a HMO blend with a specific glass transition temperature. Also disclosed is a method for removing organic solvent residues from a human milk oligosaccharide (HMO) or a HMO precursor or a HMO blend by spray drying. Also disclosed is a method of enhancing the bioavailability of a human milk oligosaccharide (HMO) or a HMO precursor or a HMO blend by spray drying.