Combination of a pyrroloquinoline compound and a beta-lactam antimicrobial agent, mupirocin or chlorhexidine
Inventors
Hu, Yanmin • Coates, Anthony R. M.
Assignees
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Publication Number
US-8940723-B2
Publication Date
2015-01-27
Expiration Date
Abstract
This invention relates to the use of 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable derivative thereof in combination with another antimicrobial agent selected from the group consisting of a beta-lactam antimicrobial agent, mupirocin and chlorhexidine or a pharmaceutically acceptable derivative thereof, for the prevention and/or treatment of microbial infections.
Core Innovation
The described invention relates to combinations comprising 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable derivative thereof together with another antimicrobial agent selected from a beta-lactam antimicrobial agent, mupirocin, and chlorhexidine, or pharmaceutically acceptable derivatives thereof. The combinations are positioned for prevention and/or treatment of microbial infections.
The problem addressed is prevention and/or treatment of microbial infections, including achieving improved killing of clinically latent microorganisms and non-multiplying microorganisms. The document emphasizes killing of stationary/non-multiplying microorganisms and clinically latent microorganisms, including MRSA/MSSA and selected fungi, in addition to killing multiplying microorganisms.
The core technical concept is the synergistic antimicrobial activity resulting from combining the 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline (and derivatives) with selected partner antimicrobial agents, specifically beta-lactams, mupirocin, and/or chlorhexidine. The document includes biological testing and in vitro kill-curve/MIC/MBC results that demonstrate synergistic effects for the combinations, including effects reported for stationary-phase MSSA/MRSA, using minimum stationary-cidal concentration (MSC) and minimum dormicidal concentration (MDC) concepts.
Claims Coverage
The claim set covers five independent claim categories, with inventive features centered on a combination of the pyrroloquinoline with a selected co-antimicrobial, manufacturing a medicament by combining the same components, treating a microbial infection by administering the combination, a pharmaceutical composition including an adjuvant/diluent/carrier and the co-antimicrobial, and a product configured for simultaneous, separate or sequential use.
Combination with selected co-antimicrobial
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 and another antimicrobial agent selected from the group consisting of a beta-lactam antimicrobial agent, mupirocin and chlorhexidine or a pharmaceutically acceptable derivative thereof.
Manufacturing a medicament by combining active components
A method of manufacturing a medicament comprising combining 4 methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable derivative thereof with another antimicrobial agent selected from the group consisting of a beta-lactam antimicrobial agent, mupirocin and chlorhexidine or a pharmaceutically acceptable derivative thereof.
Treating microbial infection by administering the combination
A method of treating a microbial infection comprising administering to a patient a combination of 4 methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable derivative thereof and another antimicrobial agent selected from the group consisting of a beta-lactam antimicrobial agent, mupirocin and chlorhexidine or a pharmaceutically acceptable derivative thereof.
Pharmaceutical composition with adjuvant, diluent, or 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 derivative thereof, another antimicrobial agent selected from the group consisting of a beta-lactam antimicrobial agent, mupirocin and chlorhexidine or a pharmaceutically acceptable derivative thereof, and a pharmaceutically acceptable adjuvant, diluent or carrier.
Combined preparation for simultaneous, separate, or sequential use
A product comprising 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable derivative thereof and another antimicrobial agent selected from the group consisting of a beta-lactam antimicrobial agent, mupirocin and chlorhexidine or a pharmaceutically acceptable derivative thereof, as a combined preparation for simultaneous, separate or sequential use in the treatment of a microbial infection.
Across the independent claims, the inventive coverage is anchored on forming a combination, and corresponding medicament, composition, or product, in which 4-methyl-8-phenoxy-1-(2-phenylethyl)-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline or a pharmaceutically acceptable derivative is paired with a selected antimicrobial co-agent from beta-lactams, mupirocin, and chlorhexidine or derivatives, and then using or administering that paired combination for manufacturing, treating microbial infections, and pharmaceutical formulations or simultaneous, separate, or sequential use.
Stated Advantages
Improved killing of log-phase (multiplying) microorganisms.
Improved killing of non-multiplying and stationary microorganisms.
Improved killing of clinically latent microorganisms.
Synergistic antimicrobial activity when combined with the selected partner antimicrobial agents.
Demonstrated synergistic effects with reduced CFU counts and increased killing rates for combinations, including for stationary-phase MSSA/MRSA.
Documented Applications
Prevention and/or treatment of microbial infections.
Treatment of a microbial infection in a patient by administering the combination.
Use in killing non-multiplying microorganisms associated with a microbial infection.
Treatment of bacterial infections.
Treatment of fungal infections.
Treatment of infections caused by Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Histoplasma capsulatum, or Pneumocystis jiroveci.
Treatment of a broad range of human diseases and infections, including tuberculosis and many named bacterial and fungal infections, including infections with MSSA, MRSA, and Staph. epidermidis, as well as infections involving other listed bacterial and fungal conditions.
Pharmaceutical compositions formulated for oral, inhaled, or topical administration.
Treatment of a microbial infection using a combined preparation for simultaneous, separate or sequential use.
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