Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10653717-B2
Publication Date
2020-05-19
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 a pharmaceutical antibiotic composition in a unit dosage form comprising a silver-containing agent and an organoselenium agent, wherein the organoselenium agent comprises ebselen in an amount effective for treating a bacterial infection. The compositions are described as synergistic antimicrobial formulations that combine silver ions with ebselen or related selenazol compounds, and as providing broad antibacterial activity against Gram-negative bacteria, including MDR pathogens.
The described compositions provide enhanced antibacterial potency, including major in vitro growth inhibition, bactericidal effects, and improved MIC and IC50 values against multiple Gram-negative organisms such as Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae, and Escherichia coli. The document also reports activity against vancomycin-resistant enterococci, selective synergistic toxicity versus mammalian cells, including HeLa cells, and microbial biofilm penetration and dissolution activity.
Synergistic activity is supported by mechanistic evidence described in the document, including depletion of bacterial glutathione, inhibition of thioredoxin/thioredoxin reductase, elevation of ROS including H2O2, loss of TrxR/Trx activity, decreased functional GSH, and increased protein S-glutathionylation. The document further reports efficacy in a mouse peritonitis model, including reduced bacterial load and improved survival, with no mortality at tested doses.
Claims Coverage
The provided claim coverage includes two independent claims. One claim covers a unit dosage form pharmaceutical antibiotic composition comprising a silver-containing agent and an organoselenium agent comprising ebselen, and the other covers a method of making the composition by contacting a silver-containing agent with an ebselen-containing organoselenium agent.
Unit dosage pharmaceutical antibiotic composition with silver and ebselen
A pharmaceutical antibiotic composition in a unit dosage form comprising a silver-containing agent and an organoselenium agent, wherein the organoselenium agent comprises ebselen in an amount effective for treating a bacterial infection.
Silver agent identity as silver nitrate
The pharmaceutical antibiotic composition where the silver-containing agent is silver nitrate.
AgNO3/ebselen molar ratio constraint
The silver-containing agent and the organoselenium agent are present in a molar ratio of about 1:2 to about 1:20.
Liquid dosage form with specified AgNO3 and ebselen amounts
A liquid pharmaceutical antibiotic composition comprising about 5 μM AgNO3 and about 40 μM ebselen.
Organoselenium concentration range
A pharmaceutical antibiotic composition that includes an organoselenium agent at a concentration of about 30 to about 200 μM.
Potency threshold against Gram-negative bacteria using IC50
A pharmaceutical antibiotic composition that has an IC50 value of about 50 nM or lower to one or more Gram-negative bacteria.
Making by contacting silver-containing agent with ebselen organoselenium agent
A method of making a pharmaceutical antibiotic composition comprising contacting a silver-containing agent and an organoselenium agent, wherein the organoselenium agent comprises an ebselen in an amount effective for treating a bacterial infection.
Overall, the claim set covers a unit dosage pharmaceutical antibiotic composition combining a silver-containing agent with an ebselen-containing organoselenium agent for treating a bacterial infection, with dependent refinements specifying silver nitrate, liquid dosage and AgNO3/ebselen amounts, molar-ratio constraints, organoselenium concentration range, and an IC50 potency threshold against Gram-negative bacteria; it also covers making the composition by contacting the silver-containing agent with the ebselen-containing organoselenium agent.
Stated Advantages
Selective synergistic toxicity versus mammalian cells.
Major in vitro growth inhibition and bactericidal effects.
Biofilm penetration and dissolution activity.
In vivo efficacy with reduced bacterial load and improved survival in a murine peritonitis model.
Combination safety with no mortality at tested doses.
Enhanced antibacterial potency against Gram-negative MDR pathogens, as indicated by MIC/IC50 improvements.
Synergistic bacteriostatic and synergistic bactericidal effects.
Synergistic activity supported by mechanisms including glutathione depletion, inhibition of thioredoxin/thioredoxin reductase, and ROS elevation, including H2O2.
Limited synergistic toxicity to mammalian cells (HeLa).
Documented Applications
Treating a bacterial infection using the pharmaceutical antibiotic composition in a unit dosage form.
Activity against bacterial pathogens including Gram-negative bacteria such as Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae, and Escherichia coli.
Assessment and support of synergy in a mouse peritonitis model.
Treating a bacterial infection, including infections involving multidrug-resistant bacteria and Gram-negative MDR nonsusceptible to multiple antimicrobial categories, as supported by the reported in vitro activity and the murine peritonitis model.
Interested in licensing this patent?