Beta-Lactoglobulin Peptides Probiotic Oral Tolerance

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Solution Overview

Problem

Current infant formulas fail to effectively induce oral tolerance to cow's milk proteins, leading to recurring allergic reactions in infants, as they either avoid allergens too aggressively or do not sufficiently reduce allergenicity.

Innovation Solution

A composition comprising a probiotic and a beta-lactoglobulin-derived peptide with an amino acid sequence corresponding to at least 8 consecutive amino acids of the beta-lactoglobulin protein, optionally combined with a prebiotic, is administered to induce oral tolerance and reduce the risk of cow's milk protein allergy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If extensively hydrolysed proteins or free amino acids are used in infant formula to prevent allergy, then allergic reactions are avoided, but oral immune tolerance cannot be established and allergy recurs upon reintroduction of milk protein

Engineering Contradiction:
Improveallergic reactionsVSAvoidoral immune tolerance establishment
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent applies parameter changes by using partially hydrolysed proteins with controlled molecular weight distribution (average molecular weight 1000-10000 Da) instead of extensive hydrolysis. This moderate hydrolysis level maintains reduced allergenicity while preserving intact epitopes necessary for inducing oral tolerance, resolving the contradiction between allergy prevention and tolerance establishment

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses composite materials by combining partially hydrolysed cow's milk proteins with specific probiotic strains (Bifidobacterium breve, Bifidobacterium longum, Lactobacillus rhamnosus, or Lactobacillus paracasei) and prebiotics (galacto-oligosaccharides or fructo-oligosaccharides). This synbiotic combination enhances both allergy prevention and oral tolerance induction, overcoming the limitations of protein hydrolysates alone

Inventive Principle:
Principle #40Composite materials

2Reliability

If partially hydrolysed proteins are used to reduce allergenicity, then likelihood of tolerogenic response increases, but allergenicity is not sufficiently reduced for clinically safe introduction

Engineering Contradiction:
Improveimmunological tolerogenic responseVSAvoidallergenicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent precisely controls the hydrolysis parameters to achieve proteins with average molecular weight of 1000-10000 Da and specific peptide composition. This optimized parameter range reduces allergenicity to clinically acceptable levels while maintaining immunogenicity sufficient for tolerance induction, balancing both requirements simultaneously

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces probiotics and prebiotics as intermediary substances that mediate between the partially hydrolysed proteins and the infant's immune system. These microorganisms modulate the immune response, enhancing tolerogenic effects while further reducing allergenicity, allowing safe introduction of milk proteins

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentUS11389492B2Method for inducing oral tolerance via administration of beta-lactoglobulin derived peptides in combination with probiotic
Publication Date: 2022.07.19 NV NUTRICIA
  • US11389492B2 patent drawing
  • US11389492B2 patent drawing
  • US11389492B2 patent drawing

AI summary

The invention pertains to the use of a probiotic and a beta-lactoglobulin-derived peptide in the manufacture of a product for use in inducing oral tolerance, and/or treatment, prevention or reducing the risk of allergy in a subject, in particular cow's milk protein allergy.