Miconazole Domiphen Bromide Synergistic Antifungal Composition

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Solution Overview

Problem

Recurrent vaginal candidiasis and other mucosal biofilm-related fungal infections pose a significant challenge due to the limited effectiveness of existing antifungal compositions against Candida species, particularly Candida albicans and Candida glabrata.

Innovation Solution

A novel pharmaceutical composition combining miconazole and the quaternary ammonium salt domiphen bromide, which exhibits synergistic antibiofilm activity, effectively killing biofilm cells and reducing Candida sp. infections in both in vitro and experimental rat model settings.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional antifungal compositions (e.g., miconazole alone) are used to treat Candida infections, then some antifungal effect is achieved, but the effectiveness is limited and recurrent infections occur

Engineering Contradiction:

Improveeffectiveness against Candida infectionsVSAvoidcure rate of recurrent infections

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent combines miconazole with quaternary ammonium salts (such as benzalkonium chloride, dequalinium chloride, or tetraethylammonium bromide) to create a composite antifungal composition. This combination achieves synergistic effects, where the combined formulation demonstrates enhanced antifungal activity compared to miconazole alone, thereby improving the cure rate of recurrent Candida infections while maintaining reliability of treatment effectiveness

Inventive Principle:

Principle #5Merging (Combining)

2Reliability

If existing antifungal compositions are used, then treatment is provided, but they fail to effectively eliminate biofilm-associated Candida species

Engineering Contradiction:

Improveantifungal effectVSAvoidbiofilm persistence

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention employs composite material principles by formulating a combination of miconazole (an azole antifungal) with quaternary ammonium salts (cationic surfactants). This composite composition targets biofilm-associated Candida species more effectively than single agents, as the synergistic interaction between the two components enhances penetration and eradication of biofilm-embedded fungi, thereby reducing biofilm persistence while maintaining reliable antifungal effect

Inventive Principle:

Principle #40Composite materials

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 combination of miconazole and domiphen bromide achieves a >3 LOG units reduction in colony forming units (cfu) of Candida biofilms after 24 hours, demonstrating a significant and sustained antifungal effect.

Implementation Method 1

domiphen bromide and miconazole display synergistic antibiofilm activity, based on determination of the fractional inhibitory concentration indices

Methodology Applied

Scientific EffectSynergistic antibiofilm activity:

Implementation Method 2

Using real-time propidium iodide staining, domiphen bromide combined with miconazole results in the killing of biofilm cells

Methodology Applied

Scientific EffectFluorescent staining: Fluorescence

Data Source

PatentUS12329743B2Compositions against <i>Candida </i>infections

Publication Date: 2025.06.17 KATHOLIEKE UNIV LEUVEN

AI summary

Provided herein are compositions for topical use comprising an imidazole or a salt thereof, and domiphen bromide as active ingredients for use in treating or preventing a fungal infection, wherein said imidazole is chosen from ketoconazole and clotrimazole as active ingredients for use in treating or preventing a fungal infection.