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Antifungal combination therapy

a combination therapy and antifungal technology, applied in the field of antifungal combination therapy, can solve the problem that none of these studies have demonstrated the results found

Inactive Publication Date: 2006-02-14
MERCK SHARP & DOHME CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention relates to a combination therapy for antifungal treatment that involves the use of known antifungal agents such as azoles or polyenes in combination with a pneumocandin derivative antifungal agent. This combination therapy has been shown to be effective against various opportunistic pathogens such as Cryptococcus, Candida, Aspergillus, and others. The use of pneumocandins, which are related to echinocandins, has been shown to have potent in vivo activity against these fungal pathogens. The invention provides an effective treatment option for these infections that previously had limited treatment options.

Problems solved by technology

However, none of these studies have demonstrated the results found using Compound I as the pneumocandin derivative.

Method used

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[0014]It has been found that combination therapy of Compound I with AmB and FCZ against C. neoformans results in enhanced activity against strains of C. neoformans in vitro. It has also been found that combination therapy of Compound I with AmB against C. albicans and A. fumigatus results in enhanced activity in vitro. This has been shown using a broth microdilution technique which is the standard method for antifungal susceptibility testing proposed by the NCCLS (protocol M27-T). Sub-inhibitory concentrations of Compound I in combination with sub-inhibitory concentrations of AmB and sub-inhibitory concentrations of FCZ were employed. The minimal inhibitory concentrations (MICS) for AmB and Compound I were defined as the lowest drug concentration at which there was an absence of growth. FCZ MIC was defined as the lowest drug concentration which resulted in a visual turbidity less than or equal to 80% inhibition compared with that produced by the control without antifungal agent.

[001...

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Abstract

There is described antifungal combination therapy comprising the use of known antifungal agents such as the azoles or polyenes in combination with a pneumocandin derivative antifungal agent. More particularly, the invention relates to antifungal combination therapy comprising the use of azoles such as fluconazole, voriconazole, itraconazole, ketoconazole, miconazole, ER 30346, SCH 56592; polyenes such as amphotericin B, nystatin or liposomal and lipid forms thereof such as Abelcet, AmBisome and Amphocil; purine or pyrimidine nucleotide inhibitors such as flucytosine; or polyoxins such as nikkomycins, in particular nikkomycin Z or other chitin inhibitors, elongation factor inhibitors such as sordarin and analogs thereof, mannan inhibitors such as predamycin, bactericidal / permeability-inducing (BPI) protein products such as XMP.97 or XMP.127 or complex carbohydrate antifungal agents such as CAN-296 in combination with a pneumocandin derivative as described herein.

Description

[0001]“This application claims the benefit of U.S. Provisional Application No. 60 / 026,327, filed Sept. 12, 1996.”FIELD OF THE INVENTION[0002]The present invention relates to antifungal combination therapy comprising the use of known antifungal agents such as the azoles or polyenes in combination with a pneumocandin derivative antifungal agent. More particularly, the invention relates to antifungal combination therapy comprising the use of azoles such as fluconazole (hereinafter referred to as FCZ), voriconazole, itraconazole, ketoconazole, miconazole, ER 30346, SCH 56592; polyenes such as amphotericin B (hereinafter referred to as AmB), nystatin or liposomal and lipid forms thereof such as Abelcet, AmBisome and Amphocil; purine or pyrimidine nucleotide inhibitors such as flucytosine; or polyoxins such as nikkomycins, in particular nikkomycin Z or other chitin inhibitors, elongation factor inhibitors such as sordarin and analogs thereof, mannan inhibitors such as predamycin, bacteric...

Claims

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): A61K38/00A61K31/45A61K31/70A61K38/12A61K38/17
CPCA61K38/12A61K38/1709A61K38/1751A61K31/00A61K2300/00
Inventor ABRUZZO, GEORGE K.BARTIZAL, KENNETH F.FLATTERY FEIGHNER, AMY M.
Owner MERCK SHARP & DOHME CORP
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