Cyclooxygenase inhibitor and calcium channel antagonist compositions and methods for use in urological procedures

a technology of cyclooxygenase inhibitor and composition, applied in the direction of biocide, drug composition, prosthesis, etc., can solve the problems of discontinuation of these medications, not all patients respond to these medications adequately, pain/inflammation and/or spasm, etc., to inhibit pain/inflammation and/or spasm

Inactive Publication Date: 2007-10-25
OMEROS CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0011] A still further aspect of the present invention provides a method of inhibiting pain / inflammation and spasm in the urinary tract during a diagnostic, interventional, surgical or other medical urological procedure, comprising periprocedurally delivering to the urinary tract during a urological procedure a composition including a combination of ketoprofen and nifedipine in a carrier. Ketoprofen and nifedipine are each included in a therapeutically effective amount such that the combination inhibits pain / inflammation and spasm in the urinary tract.

Problems solved by technology

While less invasive than open surgery, these techniques involve procedural irritation and trauma to the urinary tract leading to pain, inflammation and smooth muscle spasm.
However, not all patients respond adequately to these drugs, and side effects may lead to discontinuation of these medications.
These conventional irrigation solutions do not contain active pharmaceutical agents.
This reference does not teach optimized pairings of a pain / inflammation inhibitory agent with an anti-spasm agent for given urological procedures.

Method used

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  • Cyclooxygenase inhibitor and calcium channel antagonist compositions and methods for use in urological procedures
  • Cyclooxygenase inhibitor and calcium channel antagonist compositions and methods for use in urological procedures
  • Cyclooxygenase inhibitor and calcium channel antagonist compositions and methods for use in urological procedures

Examples

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examples

[0107] The present invention may be illustrated by the following studies demonstrating the effects of ketoprofen and other cyclooxygenase inhibitors, nifedipine and combinations of these agents in urological models, and demonstrating the stability of certain formulations of such compositions.

example i

The Effect of COX Inhibitors on Bradykinin Induced PGE2 Production in Rat Bladders

[0108] The following studies evidence that bradykinin induces immediate prostaglandin E2 (PGE2) production in the bladder, and demonstrate the effects of cyclooxygenase inhibitors on this process. Bradykinin was chosen as the activating agonist for testing in this system because its actions on the rat bladder tissue system have been well characterized and because its role as a proinflammatory agent in acute pathophysiology has been studied. Bradykinin is also known to stimulate contraction of smooth muscle of the bladder when delivered intravesically by activation of B1 and B2 receptor subtypes.

1. Introduction

[0109] Acute, localized inflammatory responses in the lower urinary tract, including spasm, are triggered by surgical trauma. In response to tissue injury, multiple inflammatory mediators, including bradykinin and Substance P (SP) are released into the bladder. Exogenous application of these pr...

example ii

Effects of Ketoprofen and Nifedipine Individually on Bradykinin Induced Contractility in Rat Bladder Tissue Strips

[0120] The purpose of this study was to characterize the effects of ketoprofen, a non-selective COX-1 / COX-2 inhibitor, and nifedipine, an L-type Ca2+ channel antagonist, on agonist-stimulated rat bladder contractility using bradykinin as a stimulating agonist.

1. Methods

[0121] Ketoprofen USP and nifedipine USP were dissolved in DMSO prior to dilution to the final concentration. Bladder tissue strips from Wistar derived rats were prepared, transduced and equilibrated using the bladder strip contractility method described in Example I above. Assayed tissue was incubated with the test drugs for 10 minutes before activities were determined.

[0122] A cumulative contraction-response curve to bradykinin was generated through application of 7 bradykinin concentrations in 3-fold increments ranging from 0.001 μM to 1 μM at 1 minute intervals for a total of 7 minutes to establish...

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Abstract

Compositions of a cyclooxygenase inhibitor and a calcium channel antagonist in a liquid carrier. The composition may be administered the the urinary tract during urological diagnostic, interventional, surgical and other medical procedures. One disclosed composition comprises ketoprofen and nifedipine in a liquid irrigation carrier, and includes a solubilizing agent, stabilizing agents and a buffering agent.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] The present application claims the benefit of U.S. Provisional Application No. 60 / 683,488, filed May 20, 2005.FIELD OF THE INVENTION [0002] The present invention relates to pharmaceutical compositions for administration to the urinary tract during urological diagnostic, interventional, surgical and other medical procedures and for therapeutic treatment of urologic structures. BACKGROUND OF THE INVENTION [0003] Many urological procedures are now performed using minimally invasive endoscopic (e.g., cystoscopic or uteroscopic) techniques. These include examination of the urethra, bladder and ureters, therapeutic treatments for benign prostatic hypertrophy, removal or fragmentation of kidney and bladder stones, the placement of urethral or ureteral stents to facilitate the passage of stones, the performance of biopsies and the excision of tumors. While less invasive than open surgery, these techniques involve procedural irritation and traum...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61F2/00A61K31/00A61K31/21A61K31/40A61K31/44A61P13/00
CPCA61K9/0034A61K9/08A61L2300/432A61L2300/41A61L2300/402A61K31/00A61K31/192A61K31/21A61K31/40A61K31/44A61K31/4422A61K31/455A61L31/16A61K2300/00A61P13/00A61P13/02A61P13/06A61P13/10A61P13/12A61P25/00A61P25/04A61P25/08A61P29/00
Inventor DEMOPULOS, GREGORYHERZ, JEFFREY
Owner OMEROS CORP
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