Halogenated Salicylanilides for Resistant Gram-Positive Bacterial Infections

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current antibiotics are ineffective against resistant strains of Gram-positive bacteria such as Staphylococcus aureus and Streptococcus pyogenes, leading to increased resistance and limited treatment options for infections like impetigo and wounds.

Innovation Solution

Topical use of halogenated salicylanilides, specifically niclosamide and its derivatives, which exhibit reduced frequency of spontaneous resistant mutants, effectively treating and preventing infections caused by these bacteria without promoting resistance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If commonly used topical antibiotics (fusidic acid, mupirocin) are used to treat Gram-positive bacterial infections, then initial treatment effectiveness is achieved, but resistance develops rapidly leading to treatment failure

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidresistance development time

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent applies parameter changes by using halogenated salicylanilides (niclosamide and derivatives) which have different chemical structures and mechanisms of action compared to conventional antibiotics like fusidic acid and mupirocin. This structural and mechanistic parameter change results in bacteria that have not developed resistance, thereby maintaining treatment effectiveness against resistant strains

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention employs composite chemical structures in the form of halogenated salicylanilides with specific substitutions (chloro, nitro, hydroxy groups) that create a novel antibiotic agent. This composite molecular structure provides effectiveness against Gram-positive bacteria while avoiding the resistance issues associated with single-mechanism conventional antibiotics

Inventive Principle:

Principle #40Composite materials

2Adaptability or versatility

If new antibiotics are developed to replace resistant strains, then treatment options are expanded, but the frequency of resistant mutants increases

Engineering Contradiction:

Improvetreatment optionsVSAvoidresistance frequency

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies inversion by using an older, less commonly used antibiotic class (halogenated salicylanilides originally used as anthelmintics) for antibacterial purposes. This reverse approach exploits the fact that bacteria have not adapted to this drug class, resulting in low resistance frequency while providing a new treatment option for resistant Gram-positive infections

Inventive Principle:

Principle #13The other way round (Inversion)

Data Source

PatentEP3338783B1Antibacterial use of halogenated salicylanilides

Publication Date: 2024.01.24 UNION THERAPEUTICS AS

Figure 1
Figure 2
Figure 3

AI summary

The invention relates to a halogenated salicylanilide selected from closantel, rafoxanide, oxyclozanide and niclosamide and derivatives thereof including salts, hydrates, esters and the like for use in the topical treatment or prevention of infections caused by Gram-positive bacteria such as Staphylococcus, in particular Staphylococcus aureus, and Streptococcus, in particular Streptococcus pyogenes. Gram positive bacteria treated with the halogenated salicylanilides exhibit a very low frequency of appearance of resistant mutants compared to commonly used topical antibiotics.