Casein-Lactoferrin Complexes Resist Sterilization Denaturation

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Solution Overview

Problem

Bioactive proteins like lactoferrin are sensitive to harsh treatments such as high heat, making it difficult to incorporate them into industrial products like infant formula without denaturation, and existing methods for stabilization are costly or unsuitable for all types of casein, including micellar casein.

Innovation Solution

A process involving specific heating, cooling, and holding steps to form robust complexes of high isoelectric point proteins with casein, specifically ramping up temperature to 85-95°C, holding for 30 seconds, and then cooling to below 5°C over 30 minutes, which results in stable coacervates that can withstand environmental changes and harsh conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If lactoferrin is added in solid form by dry-mixing after base powder production, then sterility can be achieved, but the process becomes challenging and requires expensive sterilization techniques and specific aseptic dosing equipment

Engineering Contradiction:
ImprovesterilityVSAvoidprocess complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines lactoferrin with casein to form stable complexes that can be processed together with other infant formula ingredients through wet mixing and standard sterilization processes, eliminating the need for separate sterile handling equipment and complex aseptic dosing systems

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

Casein acts as an intermediary carrier that protects lactoferrin during processing. The casein-lactoferrin complex allows lactoferrin to withstand harsh sterilization conditions and mechanical stress that would otherwise require special equipment to prevent

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If lactoferrin is subjected to high heat sterilization, then sterility is achieved, but denaturation of lactoferrin occurs

Engineering Contradiction:
ImprovesterilityVSAvoidprotein stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

Casein serves as a protective intermediary that shields lactoferrin from thermal denaturation during sterilization. The complex structure allows the mixture to withstand high heat treatment while maintaining lactoferrin's biological activity

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical state of lactoferrin from native protein to complexed form with casein, which fundamentally alters its thermal stability parameters and allows it to withstand sterilization temperatures without denaturation

Inventive Principle:
Principle #35Parameter changes

3Ease of manufacture

If lactoferrin is added during wet mixing of infant formula blend, then it can be processed with other ingredients, but protein unfolding denaturation and refolding occurs resulting in instability and increased viscosity

Engineering Contradiction:
Improveprocessing easeVSAvoidprotein stability
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

By merging lactoferrin with casein in a stable complex, the patent enables both proteins to undergo wet mixing and heat treatment together without the lactoferrin experiencing harmful unfolding and refolding cycles, maintaining its stability throughout processing

Inventive Principle:
Principle #5Merging (Combining)

4Reliability

If membrane filtration is used for sterilization, then sterility is achieved, but the process becomes costly and requires specific equipment

Engineering Contradiction:
ImprovesterilityVSAvoidequipment requirements
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent changes the sterilization approach from requiring sophisticated membrane filtration equipment to using standard thermal processing equipment. The casein-lactoferrin complex enables conventional heat sterilization to achieve the same sterility level without specialized equipment

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 process produces stable complexes that can resist heat sterilization, pH changes, and mechanical stress without the need for additional cross-linking agents, allowing for the inclusion of lactoferrin and other proteins in infant formula and other products, enhancing their stability and usability.

Implementation Method 1

A process involving specific heating, cooling, and holding steps to form robust complexes of high isoelectric point proteins with casein

Methodology Applied
Scientific EffectComplex coacervation: Coacervate

Implementation Method 2

ramping up the temperature from the denaturation temperature of the protein having an isoelectric point of 7 or more to a temperature in the range of 85 to 95°C

Methodology Applied
Scientific EffectHeat treatment: Heat Treatment

Data Source

PatentEP3723496B1Complexes of high isoelectric point proteins with casein
Publication Date: 2023.05.31 SOCIETE DES PRODUITS NESTLE SA
  • EP3723496B1 patent drawingFigure 1
  • EP3723496B1 patent drawingFigure 2A~2B
  • EP3723496B1 patent drawingFigure 3A~3B

AI summary

The present invention provides a process for producing complexes of high isoelectric point proteins with casein comprising a specific sequence of heating, cooling and holding steps. Also provided are the complexes obtained by such process and their use, in particular their use in methods of therapy.