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Combination comprising zidovudine and an antimicrobial compound

An anti-microbial, zidovudine technology, used in the field of treating microbial infections and killing proliferating microorganisms associated with microbial infections, can solve the problems of unpredictable and unpredictable synergy

Pending Publication Date: 2021-01-12
HELPERBY THERAPEUTICS LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] However, when two active substances are used in combination, the synergistic effect is neither predictable nor expected

Method used

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  • Combination comprising zidovudine and an antimicrobial compound
  • Combination comprising zidovudine and an antimicrobial compound
  • Combination comprising zidovudine and an antimicrobial compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0150] Example 1: In Vitro Synergy of Zidovudine (AZT) and Nitrofurantoin

[0151] The tessellation method used in Example 1 followed the protocol detailed in Antimicrob Chemo (2013) 68, 374-384. Zidovudine and nitrofurantoin were obtained from commercial sources. The bacterium used was E. coli k12; E. coli k12 is a susceptible strain which is considered sensitive to all antibiotics against Gram-negative bacteria. Such strains were obtained from commercial sources and the bacteria were grown in log phase using methods known in the art.

[0152] The effect of the combinations of the present invention is examined by calculating the Fractional Inhibitory Concentration Index (FICI) of each combination, as follows:

[0153] (MIC of drug A tested in combination) / (MIC of drug A tested alone)+(MIC of drug B tested in combination) / (MIC of drug B tested alone).

[0154]Interactions for combinations were defined as showing synergy if FICI 0.5 but 4.0.

[0155]

[0156] FICI valu...

Embodiment 2

[0157] Example 2: In vitro synergistic effect of the combination of zidovudine and faropenem

[0158] Method and bacterial strain are identical with embodiment 1. Zidovudine and faropenem were obtained from commercial sources. The effect of the combination of the present invention was examined in the same manner as in Example 1 by calculating the MIC of each drug alone and in combination.

[0159]

[0160] The FICI values ​​indicate that zidovudine (AZT) and faropenem have a synergistic effect against log-phase E. coli k12 when used in combination at various concentrations.

Embodiment 3

[0161] Example 3: In Vitro Synergy of Combination of Zidovudine and Mecillin

[0162] Method and bacterial strain are identical with embodiment 1. Zidovudine and mecillin were obtained from commercial sources. The effect of the combination of the present invention was examined in the same manner as in Example 1 by calculating the MIC of each drug alone and in combination.

[0163]

[0164] FICI values ​​indicate that zidovudine (AZT) and mecillin are synergistic against log-phase E. coli k12 when used in combination at various concentrations.

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Abstract

The invention provides a combination comprising zidovudine or a pharmaceutically acceptable derivative thereof and an antimicrobial compound selected from nitrofurantoin, mecillinam, fosfomycin, cephalexin and faropenem, or a pharmaceutically acceptable derivative or prodrug thereof. These combinations are particularly useful for the treatment of microbial infections.

Description

technical field [0001] The present invention relates to the combination of zidovudine or a pharmaceutically acceptable derivative thereof and an antibiotic compound selected from the group defined herein or a pharmaceutically acceptable derivative or prodrug thereof. The invention also relates to the use of these combinations for the treatment of microbial infections. In particular, the invention relates to the use of such combinations for killing proliferating (ie, log phase) microorganisms associated with microbial infections, such as Gram-negative bacterial infections, including urinary tract infections. Background technique [0002] Before the introduction of antibiotics, patients with acute microbial infections such as tuberculosis or pneumonia had low chances of survival. For example, tuberculosis has a mortality rate of approximately 50%. While the introduction of antimicrobials in the 1940s and 1950s rapidly changed the scenario, bacteria have responded by graduall...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4178A61K31/431A61K31/545A61K31/55A61K31/665A61K31/7072A61P31/00
CPCA61K31/4178A61K31/431A61K31/545A61K31/55A61K31/665A61K31/7072A61P31/00Y02A50/30A61P31/04A61K2300/00
Inventor A·科茨胡彦民
Owner HELPERBY THERAPEUTICS LTD
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