Method of detecting lung disease

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai

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536 2853, 536 261, 536124, 5361231, 436 63, A01N 4304, C07H 1906, C07H 1904, C07G 1700

Patent

active

06133247&

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

This application concerns lung diagnostic assays in general, and particularly concerns a lung diagnostic assay in which lung mucus secretions are hydrated to facilitate collection thereof.


BACKGROUND OF THE INVENTION

The analysis of sputum samples is particularly important in the treatment and diagnosis of many lung disorders, including lung cancer and tuberculosis (TB).
In particular, microbial infections of the lung are a serious problem in patients afflicted with acquired immune deficiency syndrome (AIDS). Two particularly problematic infections are Pneumocystis carinii pneumonia infections and mycobacterial infections.
Pneumocystis carinii pneumonia infections are typically referred to as "PCP" infections. It is now estimated that approximately 70 percent of patients afflicted with AIDS will contract this disease. PCP may be treated with pentamidine isethionate, but an unfortunate side effect of this treatment is its toxicity. Accordingly, there is a continued need for techniques which permit the rapid and convenient screening of AIDS patients for this disease, and for the rapid, early, and accurate diagnosis thereof.
Mycobacteria are a large, diverse, and widely distributed family of aerobic, nonsporulating, nonmotile bacilli that have a high cell-wall lipid content and a slow growth rate. Some Mycobacteria are harmless, while others are significant pathogens. The pathogenic Mycobacterium include M. tuberculosis, responsible for tuberculosis, as well as non-tuberculosis Mycobacteria such as M. avium, responsible for Mycobacterium Avium complex infections.


SUMMARY OF THE INVENTION

A first aspect of the present invention is a method of facilitating the obtaining of a mucus sample from at least one lung of a subject. The method comprises administering a physiologically acceptable salt to at least one lung of the subject in an amount effective to hydrate lung mucus secretions therein, and concurrently administering to said at least one lung of the subject, in an amount effective to hydrate lung mucous secretions, and/or stimulate mucus secretions therein, and/or stimulate ciliary beat frequency therein, a compound of Formula (I) below, or a pharmaceutically acceptable salt thereof: ##STR1## wherein: X.sub.1, X.sub.2, and X.sub.3 are each independently selected from the group consisting of OH and SH; dihalomethylene; and
The method is accompanied or followed by the step of collecting a mucus sample from said at least one lung of said subject (e.g., by said subject expectorating a sputum sample).
Also disclosed is a method of facilitating the obtaining of a mucus sample from at least one lung of a subject, comprising administering to at least one lung of said subject, in an amount effective to hydrate lung mucous secretions, and/or stimulate mucus secretions therein, and/or stimulate ciliary beat frequency therein, a compound of Formula (I) as given above, or a pharmaceutically acceptable salt thereof, and then collecting a mucus sample from said at least one lung of said subject. The mucus samples collected may then be analyzed for the presence or absence of lung disease (e.g., microbial infection, cancer, etc.) in said subject.
A second aspect of the present invention is pharmaceutical composition useful for facilitating the collecting of a mucus sample from at least one lung of a subject, said composition comprising, alone or in combination, a physiologically acceptable salt in an amount effective to hydrate lung mucus secretions; and a compound of Formula (I) as given above, or a pharmaceutically acceptable salt thereof, in an amount effective to hydrate lung mucus secretions. The composition may be a liquid composition or a dry powder composition.


DETAILED DESCRIPTION OF THE INVENTION

Compounds illustrative of the compounds of Formula (I) above (also referred to as "active compounds" herein) include: (a) uridine 5'-triphosphate (UTP); (b) uridine 5'-O-(3-thiotriphosphate) (UTP.gamma.S); and (c) 5-bromo-uridine 5'-triphosphate (5-BrUTP). One preferred compound of Formula

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Boucher et al.; Mechanisms and Therapeutic Actions of Uridine Triphosphate in the Lung, Adenosine and Adenine Nucleotides Mol. Biol. To Integr. Physiol. (Proc. Int. Symp.) 5.sup.th 1994 (Pub. 1995), 525-32, edited by Belardinelli et al. Month not available.
Boucher et al.; Mechanisms and Therapeutic Actions of Uridine Triphosphate in the Lung, Chem Abstracts, 123 Nov. 20, 1995, Abstract No. 274934z.
M.I. Lethem et al,; Nucleotide Regulation of Goblet Cells in Human Airway Epithelial Explants: Normal Exocytosis in Cystic Fibrosis, Am. J. Respir. Cell. Mol. Biol. 9, 315-322 (1993).
K.N. Olivier, Acute Safety and Effects on Mucociliary Clearance of Awrosolized Clearance of Aerosolized Uridine 5'-Triphosphate .+-. Amiloride in Normal Human Adults, Am. J. Respir. Crit. Care Med. 154, 217-223 (1996).
Knowles et al., New England J. Med, vol. 325(8), pp. 533-538, Aug. 1991.

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