Lacticaseibacillus Paracasei pH Adaptation for Gastric and Bile Resistance

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Solution Overview

Problem

Existing methods for enhancing the resistance of Lacticaseibacillus paracasei to gastric acid and bile acid are either complex or limited in applicability, and the use of Tween 80 does not improve bile acid resistance in Lacticaseibacillus paracasei.

Innovation Solution

A method involving co-culturing Lacticaseibacillus paracasei with specific lactic acid bacteria in a controlled pH environment, adjusting the pH to specific ranges at different culture periods, or culturing Lacticaseibacillus paracasei in skim milk with pH adjustments, to enhance resistance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If Lacticaseibacillus paracasei is cultured in a culture medium containing Tween 80 excessively, then the bile acid-resisting property improves, but the method does not work for Lacticaseibacillus paracasei and causes a decrease in resistance

Engineering Contradiction:
Improvebile acid-resisting propertyVSAvoidapplicability to Lacticaseibacillus paracasei
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the chemical parameter of the culture medium from Tween 80 to oleic acid or its salts, which fundamentally alters the mechanism of improving gastric acid/bile acid resistance. This parameter change makes the method effective specifically for Lacticaseibacillus paracasei where Tween 80 failed.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If genetic engineering methods are used to enhance gastric acid/bile acid-resisting property by disrupting hrcA gene, then the resistance improves, but the method requires complicated genetic engineering procedures

Engineering Contradiction:
Improvegastric acid/bile acid-resisting propertyVSAvoidcomplicated genetic engineering method
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces complex genetic engineering operations with a simple cultural method using oleic acid or its salts in the culture medium. This substitutes biochemical manipulation with a more straightforward nutritional approach, eliminating the need for gene disruption techniques.

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

3Reliability

If enteric-coated capsules are used to encapsulate lactic acid bacterium, then the viability improves by avoiding direct contact with gastric juice, but the method has restrictions on dosage form

Engineering Contradiction:
ImproveviabilityVSAvoidrestrictions on dosage form
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the approach from physical encapsulation in enteric-coated capsules to biochemical adaptation through culturing in oleic acid-containing medium. This allows the bacteria to inherently resist gastric acid and bile acid, enabling versatile application across different dosage forms without capsule restrictions.

Inventive Principle:
Principle #35Parameter changes

4Object-affected harmful factors

If Lacticaseibacillus paracasei is exposed to digestive fluids containing gastric acid and bile acid, then the microorganisms suffer serious damages such as death or loss of colony-forming activity, but protection techniques are either complex or limited in applicability

Engineering Contradiction:
Improvedamage from digestive fluidsVSAvoidprotection technique complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by pre-adapting Lacticaseibacillus paracasei to gastric acid and bile acid resistance through culturing in oleic acid-containing medium before the bacteria encounter digestive fluids in the body. This preliminary biochemical adaptation provides inherent protection without requiring complex protection techniques during administration.

Inventive Principle:
Principle #10Preliminary action

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

Significantly improves the viability of Lacticaseibacillus paracasei to gastric acid and bile acid, allowing for higher delivery of viable cells to the intestines and enhancing health benefits.

Implementation Method 1

when Lacticaseibacillus paracasei and a lactic acid bacterium are co-cultured... in which, when a precultured bacterial solution of the lactic acid bacterium is inoculated in a culture medium, pH becomes in specific ranges after specific periods of time

Methodology Applied
Scientific EffectFermentation: Fermentation

Data Source

PatentEP4624566A1Method for improving gastric acid/bile acid-resisting properties of lacticaseibacillus paracasei
Publication Date: 2025.10.01 YAKULT HONSHA KK
  • EP4624566A1 patent drawingFigure 1~2
  • EP4624566A1 patent drawingFigure 3~4
  • EP4624566A1 patent drawingFigure 5~6

AI summary

A method for improving gastric acid/bile acid-resisting property of Lacticaseibacillus paracasei characterized by co-culturing with a lactic acid bacterium in which, when a precultured bacterial solution of the lactic acid bacterium is inoculated at 0.01 mass% in a 10 mass% skim milk culture medium and static cultured in a thermostatic chamber at 37°C, the pH is 6.0 to 6.5 after the culture period of four hours, the pH is 5.0 to 6.0 after the culture period of eight hours, the pH is 4.5 to 5.5 after the culture period of 12 hours, and the pH is 4.0 to 4.5 after the culture period of 24 hours, and Lacticaseibacillus paracasei; or a method for improving gastric acid/bile acid-resisting property of Lacticaseibacillus paracasei characterized by inoculating a precultured bacterial solution of Lacticaseibacillus paracasei in a culture medium containing skim milk at 0.1 to 20 mass% and culturing while adjusting the pH in such a manner that the pH becomes 5.5 to 6.25 after the culture period of eight hours, the pH becomes 4.25 to 5.5 after the culture period of 16 hours, and the pH becomes 4.0 to 4.75 after the culture period of 24 hours: is a novel method for improving resistance of Lacticaseibacillus paracasei to gastric acid or bile acid.