Method for treating bronchitis with uridine triphosphates and related compounds

A compound, bronchial technology, applied in the direction of carbohydrate active ingredients, drug combinations, organic chemistry, etc., can solve the problems of increasing the clearance of residual mucous secretions, unsuccessful, etc.

Inactive Publication Date: 2003-07-23
MERCK & CO INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

None of these treatments were successful in increasing the clearance of residual mucus secretions

Method used

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  • Method for treating bronchitis with uridine triphosphates and related compounds
  • Method for treating bronchitis with uridine triphosphates and related compounds
  • Method for treating bronchitis with uridine triphosphates and related compounds

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Study on Sheep Tracheal Mucus

[0049] Use the following steps to study UTP and U 2 P 4 Effects on tracheal mucus velocity (TMV): Nasal passages of conscious adult ewes were anesthetized with 2% lidocaine solution. After local anesthesia was produced, a modified endotracheal tube was inserted 7.5 mm such that the cuff was clamped below the vocal cords (as determined by fluoroscopy). Inhaled air is warmed and humidified. The endotracheal tube's cuff was inflated only during administration of the test compound to minimize possible TMV injury from the cuff. Test compounds were administered by spray, 4ml administered over 10-12 minutes.

[0050] TMV was determined by fluoroscopy. Put 10-20 small radiopaque dishes (Teflon  / bismuth trioxide; diameter 1mm, thickness 0.8mm, weight 1.8mg) with a stream of compressed air (3-4L / min) into the trachea through a modified air suction catheter. Record the speed of a single disc on videotape in a portable i...

Embodiment 2

[0053] Study on Mucociliary Clearance in Sheep

[0054] In this study, healthy adult ewes were given 99m Tc-labeled human serum albumin ( 99m Tc-HSA) nebulized aerosol. Administer by nasotracheal tube within 5 minutes 99m Tc-HSA (20mCi), the cannula was inserted under local anesthesia with 2% lidocaine. 99m After Tc-HSA, animals were given test compounds: UTP or U 2 P 4 . The test compound is administered by spray, 4ml given over 10-12 minutes. The dose of test compound was 400 μmol. Following administration of the test compound, the catheter is removed from the animal. The clearance of radiolabeled particles was monitored with a gamma camera. Measurements were taken at 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 76, 90, 105 and 120 minutes. Initial results (n=7) showed that both test compounds enhanced clearance of radiolabeled particles (compared to saline control). The results are shown in Figure 4 middle.

[0055] UTP and U 2 P 4 Enha...

Embodiment 3

[0057] Treatment of humans with mild chronic bronchitis

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Abstract

A method of promoting clearance of retained mucous secretions in the bronchi, bronchioles and small terminal airways of a subject in need of such treatment is disclosed. The method comprises administering to the bronchi of the subject a uridine phosphate such as uridine 5' triphosphate (UTP), or P1,P4-di(uridine-5') tetraphosphate (U2P4), an analog of UTP, or any other analog, in an amount effective to promote mucociliary clearance and / or cough clearance of retained fluid in the bronchi, bronchioles and small terminal airways. Methods of administering the same would include; aerosol inhalation, any liquid suspension (including nasal drops or spray), oral form (liquid or pill), injected, intra-operative instillation or suppository form.

Description

[0001] This application is a partial continuation of US Application No. 08 / 744,3673 filed on Nov. 7, 1996, which is hereby incorporated by reference. technical field [0002] The present invention relates to methods of removing retained mucus secretions from the bronchi, bronchioles and small terminal airways of a subject by using uridine triphosphate and other purine receptor agonists. Background of the invention [0003] Chronic bronchitis (CB) is a profuse production of mucus in the bronchial tubes, accompanied by regularly repeated coughs lasting at least three months over a period of at least two consecutive years. CB is an important non-asthmatic lung disease. The condition affects approximately 14 million Americans and is the leading cause of death in the United States. Many different factors, including smoking, environmental pollution, chronic infection, and various genetic abnormalities, trigger bronchitis. Among these factors, smoking is the most important. Path...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H19/10A61KA61K9/08A61K9/10A61K9/12A61K31/70A61K31/7024A61K31/7068A61K31/7072A61K31/7076A61K31/7084A61P11/00A61P11/10A61P11/12C07D473/00C07H19/20C07H19/207
CPCA61K31/7072A61K31/7076A61P11/00A61P11/10A61P11/12A61K31/70
Inventor C·L·谢弗R·C·鲍彻J·L·赖德奥特K·M·雅格布斯
Owner MERCK & CO INC
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