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Combination compositions comprising a beta-lactamase inhibitor

A technology for compositions and solvates, applied in the field of combined compositions comprising beta-lactamase inhibitors, can solve problems such as limiting treatment options

Pending Publication Date: 2021-06-22
VENATORX PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The rapid spread of this bacterial resistance mechanism can severely limit β-lactam treatment options in hospitals and the community

Method used

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  • Combination compositions comprising a beta-lactamase inhibitor
  • Combination compositions comprising a beta-lactamase inhibitor
  • Combination compositions comprising a beta-lactamase inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0215] Example 1: In Vitro Efficacy of the Combination Formulation of Compound 1 plus Sulbactam.

[0216] To determine the ability of test compounds to enhance the antibacterial activity of sulbactam (Cat. No. 1623670, USP, Rockville, MD) and the sulbactam combination against Acinetobacter, a classical cell-based broth microdilution MIC assay was employed. A panel of 51 Acinetobacter isolates with elevated sulbactam MICs was used. Of these isolates, 40 were characterized and known to produce OXA-23-like (Ambler D-type carbapenemases) and at least one additional β-lactamase, while the remaining 11 were not characterized. The assay was performed at Cation Adjusted Mueller Hinton Broth (CAMHB, BD #212322, BD Diagnostic Systems, Sparks, MD). Bacterial strains were grown in CAMHB broth for 3-5 hours. In CAMHB, sulbactam, ampicillin (Cat. No. A9518-5G, Sigma, St. Louis, MO), cefepime (Cat. No. 1097636, USP, Rockville, MD) at 2-fold serial dilutions, the following antibodies Bacte...

Embodiment 2

[0222] Example 2: In vitro efficacy of the combination formulation of compound 1 plus sulbactam in the presence of cefepime.

[0223] Table 2 shows the minimum inhibitory concentration of compound 1 / cefepime (FEP) / sulbactam (SUL) / ampicillin (AMP) compared to a group of multidrug resistant Acinetobacter baumannii ( MIC) data. MIC values ​​are provided for the indicated fixed ratios of β-lactam antibiotics.

[0224] Table 2. Minimum inhibitory concentrations (MIC, μg / mL) of cefepime (FEP), ampicillin (AMP), sulbactam (SUL) and combination with compound 1 (fixed at 4 μg / mL). ND, not determined.

[0225]

[0226]

[0227]

Embodiment 3

[0228] Example 3: In Vitro Efficacy of the Combination Formulation of Compound 1 plus Cefiderole.

[0229] To determine the ability of compound 1 to enhance the antibacterial activity of cefdiril (FDC) against β-lactamase producing strains of Enterobacteriaceae, a classical cell-based broth microdilution MIC assay was employed. A panel of 30 characterized Enterobacteriaceae isolates producing Ambler A, B, C and D β-lactamases were used. The assay was performed in Cation Adjusted Mueller Hinton Broth (CAMHB, BD #212322, BD Diagnostic Systems, Sparks, MD) and in parallel in iron depleted media (IDM). IDM was prepared by adding 100 g of chelex (a chelating agent) to 1 L of sterile CAMBH and stirring for 2 hours. The chelex-treated media was then filtered through a 0.2 μm filter and divalent Ca, Mg and Zn were added back at the relevant concentrations. Adjust the pH to 7.2 with HCl and filter the medium again to ensure sterility. This produces a medium that is free of iron but ...

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Abstract

Described herein are combination compositions comprising a beta-lactamase inhibitor. In certain embodiments, the combination compositions described herein are useful in the treatment of bacterial infections.

Description

[0001] cross reference [0002] This application claims the benefit of U.S. Provisional Application Serial No. 62 / 730,289, filed September 12, 2018, which is hereby incorporated by reference in its entirety. [0003] Statement Regarding Federally Funded Research [0004] This invention was made with United States Government support under Contract No. HHSN272201300019C awarded by the National Institutes of Health (NIH). The US Government has certain rights in this invention. technical field [0005] The present invention relates to combination compositions comprising beta-lactamase inhibitors and their use in the treatment of bacterial infections. Background technique [0006] Antibiotics are the most effective drugs clinically used to treat bacterial infectious diseases. They have a large market due to the advantages of good antibacterial effect and limited side effects. Among them, β-lactam antibiotics (eg, penicillins, cephalosporins, and carbapenems) are widely use...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/69A61K31/546A61K31/43A61K31/496A61K9/00
CPCA61K31/546A61K31/43A61K31/69A61K31/496A61K9/0019A61K45/06A61K31/431A61P31/04Y02A50/30A61K2300/00
Inventor 朱迪·哈姆里克克里斯多佛·J·伯恩斯丹尼尔·C·佩维尔路易吉·谢里蒂莫西·亨克尔丹尼斯·戴格尔
Owner VENATORX PHARMA INC
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