LC-MS Detection of Beta-Casein Proteose Peptones in Infant Formula

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Solution Overview

Problem

Current methods fail to efficiently detect and quantify β-casein derived proteose peptones such as PP-5, PP8s, and PP8f in dairy products, which are associated with digestive issues in humans, and there is a need for nutritional compositions with reduced levels of these proteose peptones to mimic human breast milk and prevent abdominal pain and stool inconsistency in infants.

Innovation Solution

A method using liquid chromatography-mass spectrometry analysis to determine and quantify β-casein derived proteose peptones by detecting compounds of defined m/z values or deconvoluting mass spectrometry spectra to calculate monoisotopic masses, allowing for the production of whey protein fractions with reduced β-casein derived proteose peptone content, which are then used to create nutritional compositions with minimized A1 β-casein or its proteose peptones.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional detection methods are used, then the analysis is simpler, but the detection precision and quantification accuracy of β-casein derived proteose peptones is insufficient

Engineering Contradiction:
Improvedetection and quantification precision of proteose peptonesVSAvoidcomplexity of liquid chromatography-mass spectrometry system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces conventional mechanical detection methods (such as UV detection in HPLC) with mass spectrometry detection. This substitution enables precise identification and quantification of β-casein derived proteose peptones based on their unique mass-to-charge ratios, achieving high measurement precision despite the increased complexity of the analytical system.

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

Solution Approach 2:

The patent utilizes the unique mass-to-charge ratio parameter of proteose peptones to achieve specific detection. By monitoring characteristic m/z values (such as m/z 1072.5 for PP-5 and m/z 1112.6 for PP8s), the method achieves high precision quantification without requiring complex separation procedures, thus resolving the contradiction between detection precision and system complexity.

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If whey protein fraction is produced without selection, then the production process is simpler, but the proteose peptone content remains high causing digestive issues

Engineering Contradiction:
Improvedigestive issues from proteose peptonesVSAvoidsimplicity of whey protein fraction production
Core Design Contradiction:
Object-affected harmful factorsVSEase of manufacture

Solution Approach 1:

The patent implements preliminary detection and quantification of proteose peptone content in whey protein fractions before final product formulation. By measuring the proteose peptone content early in the production process using LC-MS analysis, manufacturers can select or adjust whey protein fractions to ensure low proteose peptone content in the final nutritional composition, thereby preventing digestive issues while maintaining production efficiency.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent establishes a feedback mechanism where proteose peptone content is measured and used to control the whey protein fraction selection process. The quantification data from LC-MS analysis provides feedback that guides the selection of whey protein fractions with appropriate proteose peptone levels, ensuring the final product meets safety criteria for infant nutrition.

Inventive Principle:
Principle #23Feedback

3Quantity of substance

If A1 β-casein is used in nutritional compositions, then the protein content is higher, but BCM-7 formation increases causing abdominal pain and stool inconsistency

Engineering Contradiction:
Improveprotein content in nutritional compositionVSAvoidabdominal pain and stool inconsistency from BCM-7
Core Design Contradiction:
Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent applies the principle of extraction by removing or minimizing A1 β-casein and its derived proteose peptones from nutritional compositions intended for infants. By selecting whey protein fractions with low proteose peptone content and verifying through LC-MS analysis, the harmful BCM-7 precursors are effectively extracted from the final product while maintaining adequate protein content through alternative protein sources.

Inventive Principle:
Principle #2Taking out (Extraction)

Data Source

PatentEP3897184B1Determination and quantification of proteose peptone content and/or beta-casein content and nutritional compositon with reduced beta-casein derived proteose peptone content
Publication Date: 2024.06.26 SOCIETE DES PRODUITS NESTLE SA
  • EP3897184B1 patent drawingFigure 1~2
  • EP3897184B1 patent drawingFigure 3~3C
  • EP3897184B1 patent drawingFigure 4~4B

AI summary

The present invention relates to a method for determining and quantifying β-casein derived proteose peptones and/or β -casein, said method comprising the steps of (i) providing a dairy-based product to be analysed; (ii) subjecting said product using liquid chromatography - mass spectrometry analysis; (iii) determining and/or quantifying said β -casein derived proteose peptones and/or β -casein in said product by detecting compounds of defined m/z values or deconvoluting the mass spectrometry spectra to calculate monoisotopic masses. The present invention also relates to nutritional compositions having a reduced content of β -casein derived proteose peptones and the uses hereof for e.g. treating, preventing and/or ameliorating abdominal pain in an infant.