Aqueous Oligosaccharide Composition pH Control for Heat Stability

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Solution Overview

Problem

Existing liquid aqueous compositions of human milk oligosaccharides (HMOs) face issues such as isomerization of reducing terminal monosaccharides during heat treatment, degradation over time, and pH levels that can disrupt infant physiology, particularly for preterm or low birth weight infants.

Innovation Solution

Aqueous compositions with a pH ranging from 5.5 to 6.5, specifically 5.8 to 6.3, are used to stabilize oligosaccharides with a glucose unit at the reducing end, preventing isomerization and degradation, and maintaining physiological compatibility for infants.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If aseptic filling or sterilization by retorting is implemented to ensure microbiological safety, then the composition becomes microbiologically safe, but isomerization of the reducing terminal monosaccharides occurs during heat treatment

Engineering Contradiction:
Improvemicrobiological safetyVSAvoidisomerization of reducing terminal monosaccharides
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by adjusting the pH of the aqueous composition to a specific range (5.5-6.5) before heat treatment. This pH modification prevents isomerization of the reducing terminal monosaccharides during subsequent sterilization processes while maintaining microbiological safety. The pH parameter is controlled to stabilize the oligosaccharide structure against base-catalyzed isomerization that would otherwise occur during heat treatment.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If oligosaccharides are concentrated to reach microbiologically safe low water activity, then microbiological safety is improved, but viscosity increases and crystallization occurs

Engineering Contradiction:
Improvemicrobiological safetyVSAvoidfeeding application
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent uses pH parameter changes (maintaining pH 5.5-6.5) to prevent crystallization of oligosaccharides during concentration, enabling the formulation of stable aqueous compositions at lower concentrations (e.g., 1-10% w/v) that remain liquid and easy to administer. The controlled pH prevents the oligosaccharides from reaching saturation and crystallizing, thus maintaining fluidity and ease of feeding application while achieving adequate microbiological safety through the stabilized composition.

Inventive Principle:
Principle #35Parameter changes

3Stability of the object's composition

If pH is lowered to prevent isomerization and degradation, then stability is improved, but infant physiology is disrupted

Engineering Contradiction:
Improvestability of oligosaccharidesVSAvoiddisruption of infant physiology
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent optimizes the pH parameter to a specific range (5.5-6.5) that balances two requirements: it is low enough to prevent base-catalyzed isomerization and degradation of oligosaccharides during storage and heat treatment, yet high enough to be compatible with infant physiology and not cause acidosis. This narrow pH window achieves both compositional stability and physiological compatibility.

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

The solution ensures stability of oligosaccharides during heat treatment and storage, while maintaining a pH suitable for infant administration, supporting digestive and immune maturation without altering infant physiology.

Implementation Method 1

mild acidification at a pH which may range from 5.5 to 6.5, for example from 5.8 to 6.3 or from 5.9 to 6.2, of an aqueous composition comprising at least one oligosaccharide having a glucose unit at the reducing end stabilized such oligosaccharide against isomerization

Methodology Applied
Scientific EffectpH adjustment:

Implementation Method 2

Very surprisingly, mild acidification also prevented hydrolysis during storage

Methodology Applied
Scientific EffectpH-dependent hydrolysis prevention: Hydrolysis

Data Source

PatentEP3893675B1Stable aqueous composition comprising oligosaccharides
Publication Date: 2026.04.15 SOCIETE DES PRODUITS NESTLE SA
  • EP3893675B1 patent drawingFigure 1~2A
  • EP3893675B1 patent drawingFigure 2B~2C
  • EP3893675B1 patent drawingFigure 2D~2E

AI summary

The present invention concerns a stable aqueous composition comprising oligosaccharides having a glucose unit at the reducing end and characterised in that the pH of such aqueous composition ranges from 5.5 to 6.5.5