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Publication Number
US-10736888-B2
Publication Date
2020-08-11
Expiration Date
Abstract
The invention provides a combination comprising 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable derivative thereof, mupirocin or a pharmaceutically acceptable derivative thereof and neomycin or a pharmaceutically acceptable derivative thereof. This triple combination is particularly useful for the treatment and/or prevention of microbial infections.
Core Innovation
The invention relates to a triple combination antimicrobial regimen comprising 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline (HT61; and pharmaceutically acceptable derivatives), together with mupirocin and neomycin. The regimen is presented for preventing and/or treating microbial infections by killing multiplying, non-multiplying, and clinically latent microorganisms.
The regimen is described as providing improved or synergistic antimicrobial activity over each agent alone. Synergy is assessed using a Fractional Inhibitory Concentration Index (FICI) and chequerboard technique, together with time-kill methods.
The disclosures further compare the longer-lasting activity of the triple combination versus existing topical products including Bactroban® and Naseptin®. The patent narrative supports the regimen with formulations and antimicrobial testing concepts including Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), Minimum Stationary-cidal Concentration (MSC), and Minimum Dormicidal Concentration (MDC), applied to clinically relevant microorganisms.
Claims Coverage
The partial claim set includes three independent claims. Across these independent claims, the inventive subject matter is centered on combining a specific HT61 compound with mupirocin and neomycin, optionally as a pharmaceutical composition with pharmaceutically acceptable adjuvant, diluent, or carrier, and using the combination to treat a microbial infection in a mammal.
Triple combination comprising HT61, mupirocin, and neomycin
A combination comprising 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable salt and/or solvate thereof, mupirocin or a pharmaceutically acceptable salt and/or solvate thereof and neomycin or a pharmaceutically acceptable salt and/or solvate thereof.
Administering triple combination to treat microbial infection in a mammal
A method of treating a microbial infection in a mammal, wherein the method comprises administering a combination comprising 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable salt and/or solvate thereof, mupirocin or a pharmaceutically acceptable salt and/or solvate thereof and neomycin or a pharmaceutically acceptable salt and/or solvate thereof.
Pharmaceutical composition containing HT61, mupirocin, neomycin, and a pharmaceutically acceptable carrier
A pharmaceutical composition comprising 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable salt and/or solvate thereof, mupirocin or a pharmaceutically acceptable salt and/or solvate thereof and neomycin or a pharmaceutically acceptable salt and/or solvate thereof, and a pharmaceutically acceptable adjuvant, diluent or carrier.
Collectively, the independent claims cover the triple combination of HT61 with mupirocin and neomycin, administering that combination to treat a microbial infection in a mammal, and a pharmaceutical composition containing the three actives plus a pharmaceutically acceptable adjuvant, diluent, or carrier.
Stated Advantages
Improved or synergistic antimicrobial activity versus each agent alone.
Longer-lasting antimicrobial activity versus existing topical products including Bactroban® and Naseptin®.
Documented Applications
Preventing and/or treating microbial infections by killing multiplying, non-multiplying, and clinically latent microorganisms.
Treating a microbial infection in a mammal by administering the triple combination.
Treatment or prevention using topical products for comparison, including Bactroban® and Naseptin®.
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