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Methods of bladder cancer treatment with ciclopirox, ciclopirox olamine, or a ciclopirox prodrug

A technique for ciclopirox amine and bladder cancer, which is applied in the field of treating bladder cancer with ciclopirox, ciclopirox amine or prodrug of ciclopirox

Pending Publication Date: 2017-09-26
UNIVERSITY OF KANSAS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

High-grade Ta and T1, and Tis tumors have a higher recurrence rate, with moderate to high risk of progression to MIBC

Method used

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  • Methods of bladder cancer treatment with ciclopirox, ciclopirox olamine, or a ciclopirox prodrug
  • Methods of bladder cancer treatment with ciclopirox, ciclopirox olamine, or a ciclopirox prodrug
  • Methods of bladder cancer treatment with ciclopirox, ciclopirox olamine, or a ciclopirox prodrug

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Experimental program
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Embodiment approach

[0124] The data in the Figures and Tables demonstrate that the ciclopirox-POM prodrugs described herein are an improvement for administration to subjects. It was found that ciclopirox-POM is an improvement in chemical formulation when ciclopirox is readily bioavailable when administered IV as a prodrug compared to ciclopirox amine administered IV to mice, rats and dogs. However, after oral administration to mice, the bioavailability was low, 21% after administration of ethanolamine salt and 12% after oral administration of ciclopirox-POM prodrug. Therefore, ciclopirox is readily bioavailable when administered IV in prodrug form. Since the prodrug was undetectable in plasma and urine following IV, oral, subcutaneous, and intraperitoneal administration, it appears that when the prodrug reaches the systemic circulation, it is rapidly and completely metabolized to ciclopirox. Therefore, the ciclopirox-POM prodrug has advantages over ciclopirox amine from the viewpoint of physicoc...

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Abstract

A method of treating bladder cancer is provided. The method of treating bladder cancer can include: providing a pharmaceutical composition having ciclopirox or ciclopirox olamine or a ciclopirox-POM prodrug having a structure of one of the formulae provided herein or derivative thereof or stereoisomer thereof or pharmaceutically acceptable salt thereof; and administering the pharmaceutical composition to a subject having the bladder cancer. The ciclopirox or ciclopirox olamine or a ciclopirox-POM prodrug can be administered in a therapeutically effective amount.

Description

[0001] Cross References to Related Applications [0002] This patent application claims priority to US Provisional Patent Application 62 / 134,747, filed March 18, 2015. This patent application also claims priority to US Provisional Patent Application 62 / 078,069, filed November 11, 2014. The foregoing provisional application is hereby incorporated by reference in its entirety by specific reference. Background technique [0003] The molecule 6-cyclohexyl-1-hydroxy-4-methylpyridin-2(1H)-one, also known as ciclopirox, is a commercially available topical antifungal agent. Ciclopirox has been used to treat superficial mycosis and tinea versicolor. Commercially available topical drug products contain the olamine salt of ciclopirox. Following oral administration to humans, ciclopirox olamine is completely absorbed followed by rapid and complete drug elimination. The oral bioavailability of ciclopirox olamine in humans has not been reported. However, in animals, the absolute bioava...

Claims

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Application Information

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IPC IPC(8): A61K31/661A61K31/663A61P35/00
CPCA61K31/661A61K31/663A61K31/4418A61K31/675A61P13/10A61P35/00
Inventor S.J.韦尔S.南特
Owner UNIVERSITY OF KANSAS
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