Dual-Mechanism Antibacterial Composition for Broad pH Efficacy

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Solution Overview

Problem

Existing antibacterial agents based on 2-phenylbenzimidazole compounds are ineffective in acidic and neutral environments where V-ATPase expression is low or absent, limiting their applicability.

Innovation Solution

Combining a 2-phenylbenzimidazole-based compound with a salicylanilide-based compound to create an antibacterial composition that inhibits Na+-transporting V-ATPase and F-ATPase activities across various pH environments.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a 2-phenylbenzimidazole-based compound is used as an antibacterial agent, then it effectively inhibits V-ATPase in alkaline environments, but it becomes ineffective in acidic and neutral environments where V-ATPase is not expressed

Engineering Contradiction:
Improveantibacterial efficacyVSAvoidenvironmental adaptability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines a 2-phenylbenzimidazole-based compound (V-ATPase inhibitor) with a salicylanilide-based compound (protonophore) to create a composite antibacterial composition. The 2-phenylbenzimidazole component targets V-ATPase in alkaline environments, while the salicylanilide component acts as a protonophore in acidic and neutral environments, allowing the combination to effectively cover all pH conditions where pathogenic bacteria may be present.

Inventive Principle:
Principle #5Merging (Combining)

2Object-affected harmful factors

If the antibacterial agent targets V-ATPase specifically, then it achieves selective inhibition of pathogenic bacteria, but it fails to function in environments where V-ATPase expression is low or absent

Engineering Contradiction:
Improveselective antibacterial actionVSAvoidpH range coverage
Core Design Contradiction:
Object-affected harmful factorsVSAdaptability or versatility

Solution Approach 1:

The antibacterial composition achieves multi-functionality by incorporating two compounds with different mechanisms: the 2-phenylbenzimidazole-based compound specifically inhibits V-ATPase in alkaline environments, while the salicylanilide-based compound functions as a protonophore across all pH ranges. This dual-mechanism approach ensures the composition remains effective regardless of environmental pH conditions.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 combined composition effectively inhibits bacterial proliferation in a wide pH range, including acidic and neutral environments, targeting drug-resistant bacteria and maintaining antibacterial efficacy.

Implementation Method 1

a 2-phenylbenzimidazole-based compound exhibits an activity inhibitory function of Na + -transporting V-ATPase

Methodology Applied
Scientific EffectIon transport inhibition:

Implementation Method 2

a protonophore containing a salicylanilide-based compound

Methodology Applied
Scientific EffectProtonophore activity:

Implementation Method 3

the V-ATPase has a function to hydrolyze ATP and to transfer intracellular sodium ions

Methodology Applied
Scientific EffectATP hydrolysis: Hydrolysis

Implementation Method 4

transports ions between the inside and outside of the membrane while rotating a specific detail unit in the membrane by ATP hydrolysis energy

Methodology Applied
Scientific EffectIon transport:

Data Source

PatentEP4652995A1Antibacterial composition, pharmaceutical agent, and antibacterial method
Publication Date: 2025.11.26 THE JAPAN SCI & TECH AGENCY
  • EP4652995A1 patent drawingFigure 1
  • EP4652995A1 patent drawingFigure 2
  • EP4652995A1 patent drawingFigure 3

AI summary

The present invention provides an antibacterial composition containing a 2-phenylbenzimidazole-based compound and a salicylanilide-based compound. In addition, the present invention provides an antibacterial method for inhibiting proliferation of bacteria using the antibacterial composition, the method including: administering the 2-phenylbenzimidazole-based compound and the salicylanilide-based compound to bacteria having Na+-transporting V-ATPase and F-ATPase; and binding the 2-phenylbenzimidazole-based compound to the V-ATPase of the bacteria to inhibit activity of the V-ATPase, and breaking a proton concentration gradient by the F-ATPase with the salicylanilide-based compound to inhibit activity of the F-ATPase.