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Publication Number
US-11801262-B2
Publication Date
2023-10-31
Expiration Date
Abstract
Disclosed herein are antibiotic compositions, for example compositions that comprise a metal-containing agent and an organoselenium agent, and uses thereof.
Core Innovation
The invention relates to an antibiotic composition for use on a non-biological surface. The antibiotic composition comprises a metal-containing agent comprising silver and an organoselenium agent comprising ebselen or ebselen diselenide.
The antibiotic composition is present in an amount effective for killing or inhibiting one or more bacteria when the one or more bacteria contact the non-biological surface. The disclosed approach includes silver ions (Ag+) with an organoselenium agent, with potency expressed as IC50 and constrained against one or more Gram-negative bacteria.
The patent describes selective synergistic antimicrobial activity of silver plus ebselen against Gram-negative bacteria, including multidrug-resistant Gram-negative bacteria. It also targets bacterial redox systems, including thioredoxin (Trx/TrxR) and glutathione (GSH), with associated increases in ROS and related signaling.
Claims Coverage
The claims coverage centers on a coated non-biological surface and an antibiotic composition containing silver and an organoselenium agent, with the composition effective for killing or inhibiting bacteria upon contact. Six inventive features are identified across the independent and dependent claim content.
Non-biological contact killing or inhibition coating
A non-biological surface coated with an antibiotic composition that comprises a metal-containing agent comprising silver and an organoselenium agent comprising ebselen or ebselen diselenide, wherein the antibiotic composition is present in an amount effective for killing or inhibiting one or more bacteria when the one or more bacteria contact the non-biological surface.
Silver-to-organoselenium molar ratio
The non-biological surface coated with the antibiotic composition comprises a metal-containing agent comprising silver and an organoselenium agent in a molar ratio ranging from about 1:2 to about 1:20.
Named silver compound forms
The metal-containing agent comprises silver in one or more specified silver compounds.
Surgical equipment surface
The non-biological surface is a surface of surgical equipment.
Ebselen diselenide organoselenium selection
The organoselenium agent is ebselen diselenide.
Gram-negative potency threshold
The non-biological surface coated with the antibiotic composition exhibits an IC50 value of about 50 nM or lower to one or more Gram-negative bacteria.
Overall, the claim set requires a silver plus ebselen or ebselen diselenide antibiotic composition on a non-biological surface, with dependent claims narrowing coverage through molar ratio, specified silver compound forms, surgical equipment surface context, selection of ebselen diselenide, and an IC50 threshold against Gram-negative bacteria.
Stated Advantages
Selective synergistic antimicrobial activity of Ag+ with ebselen against Gram-negative bacteria, including MDR Gram-negative bacteria.
In vitro bactericidal synergy and quantitative MIC decreases are reported for the silver plus ebselen combination.
In vivo efficacy is reported in mouse peritonitis models, including bacterial load reduction and survival rate observations.
Synergistic selective bactericidal or toxic profiles are described for combinations of silver-containing agent with an organoselenium compound.
The combinations are described as reducing mammalian (HeLa) toxicity relative to silver-containing agent alone.
The combinations are described as providing effective killing or inhibition against Gram-negative bacteria, including MDR Gram-negative bacteria.
Documented Applications
Non-biological surface coatings for killing or inhibiting bacteria upon contact, including surgical equipment surfaces.
Treatment of MDR Gram-negative bacterial infections is described through targeting bacterial redox systems.
Use on non-biological surfaces is described, including surgical equipment surfaces.
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