Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – Coated – impregnated – or colloidal particulate
Reexamination Certificate
1999-04-16
2001-07-24
Dudash, Diana (Department: 1619)
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
Coated, impregnated, or colloidal particulate
C424S001330, C424S001650, C424S001810, C424S001130, C514S023000, C514S024000, C514S025000, C435S024000, C435S034000, C435S035000, C435S039000
Reexamination Certificate
active
06264913
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a method for monitoring bacterial overgrowth of the small intestine. More specifically, the invention relates to administering labeled sorbitol or sorbitol derivatives to an individual and assessing labeled carbon dioxide in one or more specimens from the individual to determine bacterial overgrowth of the small intestine.
2. Description of the Prior Art
Normally, the human small intestine contains only small amounts of bacteria compared to the colon. Many structural or functional disorders of the gastrointestinal tract can lead to bacterial overgrowth of the small intestine. Small bowel bacterial overgrowth is characterized by steatorrhea (fat malabsorption), diarrhea, vitamin deficiencies, and carbohydrate malabsorption. Optimum care of patients with bacterial overgrowth requires adequate evaluation and proper antibiotic therapy. Unfortunately, bacterial overgrowth is difficult to diagnose with accuracy. Unlike many other illnesses, bacterial overgrowth is never cured but requires constant monitoring and therapy.
The current diagnostic “gold standard” for identifying small intestinal bacterial overgrowth is a quantitative culture of small bowel fluid aspirate. Jejunal fluid is collected through a small tube that is swallowed by the patient and positioned by a physician under fluoroscopic (x-ray) guidance. The jejunal fluid aspiration is cultured for the presence of bacteria. There are many limitations to this technique as a diagnostic test of small bowel bacterial overgrowth. These limitations include (1) discomfort of placing orointestinal tubes, (2) exposure to x-rays, (3) high medical costs (about $700) (4) culturing the aspirate is time consuming and (5) the poor diagnostic sensitivity of single aspirations.
The need for a reliable screening test for bacterial overgrowth fostered the development of non-invasive breath tests. These tests utilized radioactive
14
C and nonradioactive
13
C substrates, such as cholyl-[
14
C]-glycine (bile acid breath test) and
14
C and
13
C-xylose, or relied on bacterial metabolism of glucose or lactulose to evolve hydrogen gas in the breath. With the exception of the xylose breath test, all the other non-invasive screening tests have been shown to be unreliable to screen for bacterial overgrowth because of poor sensitivity and specificity of these tests. Recent clinical experience with the xylose breath test, however, has suggested a decrease in the sensitivity and specificity, perhaps due to the altered ability of intestinal bacteria to metabolize xylose.
These and other disadvantages of the prior art are overcome by the present invention. As shown herein, we provide a novel test for assessing bacterial overgrowth of the small intestine.
SUMMARY OF THE INVENTION
The present invention overcomes the limitations of the prior art and provides a method and kit for the assessment of bacterial overgrowth of the small intestine.
Provided herein is a method of assessing bacterial overgrowth of the small intestine in a subject comprising the steps of: a) administering to said subject an effective amount of carbon-labeled sorbitol or carbon-labeled sorbitol derivative to said subject; b) collecting expired breath from said subject; and c) measuring the amount of label in said expired breath to assess bacterial overgrowth of the small intestine in said subject. The label is a carbon label. Preferably the labeled compound administered is
13
C sorbitol or a
13
C sorbitol derivative, or mixtures thereof. Alternatively, the compound is
14
C sorbitol or a
14
C sorbitol derivative. The labeled sorbitol derivative is any sorbitol derivative that would be known to those skilled in the art and which would not be readily absorbed; thus, any increase in CO
2
enrichment would be due to bacteria rather than endogenous metabolism. The carbon-labeled compound may comprise a plurality of labeled carbons. Preferably, the sorbitol derivative is D-sorbitol, but L-sorbitol or a racemic mixture of the two also function.
In an alternative embodiment, provided herein is a method of assessing bacterial overgrowth of the small intestine in a subject comprising the steps of: a) administering to said subject an effective amount of carbon-labeled sorbitol or carbon-labeled sorbitol derivative to said subject; b) collecting blood from said subject; and c) measuring the amount of label in said blood to assess bacterial overgrowth of the small intestine in said subject.
The method further comprises comparing said amount of expired labeled carbon with a standard, whereby said comparing yields a measure of bacterial overgrowth of the small intestine. The standard comprises the mean value of expired label in a control population without bacterial overgrowth of the small intestine, or the mean value of expired label in a control population with bacterial overgrowth of the small intestine.
The label may be measured by techniques commonly used for measuring the presence of labeled species. Isotopic measurement of label is selected from the group consisting of mass spectrometric measurement, laser measurement, infrared detection, nuclear magnetic resonance and liquid scintillation counting of labeled carbon.
The present invention also provides a kit for assessing bacterial overgrowth of the small intestine comprising carbon-labeled sorbitol or carbon-labeled sorbitol derivative in a pharmaceutically acceptable carrier, and optionally a means for collecting expired breath and/or blood and/or blood treating agents.
The advantages of the present invention may be gleaned from the following detailed description.
REFERENCES:
patent: 4830010 (1989-05-01), Marshall
patent: 5458910 (1995-10-01), Gruetzmacher et al.
Chang et al. Eur J Nucl Med; 22: 1118-1122, 1995.*
Rosenburg et al. Gastroenterology; 86: 1356, 1984.*
Martindale, the Extra Pharmacoppeia, p. 780, 1993.*
American Hospital Formulary Services, p. 1893, 1994.*
L.H. Adcock et al., The Metabolism of Sorbitol in the Human Subject,Journal Title Unknown,, vol. 65, p. 554-560, Aug. 13, 1956.
C.E. King et al., Small Intestine Bacterial Overgrowth,Gastroenterology, vol. 76, No. 5, p. 1035-1040, May 1979.
C.E. King et al., Comparison of the One-Gram d-[14C]Xylose Breath Test to the [14C]Bile Acid Breath Test in Patients with Small-Intestine Bacterial Overgrowth,Digestive Diseases and Sciences, vol. 25, No. 1, p. 53-58, Jan. 1980.
C.E. King et al., Comparison of the 1-Gram [14C]Xylose, 10-Gram Lactulose-H2, and 80-Gram Glucose-H2, Breath Tests in Patients with Small Intestine Bacterial Overgrowth,Gastroenterology, vol. 91, No. 6, p. 1447-1451, 1986.
C.E. King et al., Detection of Small Intestine Bacterial Overgrowth by Means of a14C-D-Xylose Breath Test,Gastroenterology, vol. 77, No. 1, p. 75-82, 1979.
N.W. Solomons et al., Application of a stable isotope (13C)-labeled glycocholate breath test to diagnosis of bacterial overgrowth and ileal dysfunction,J. Lab. Clin. Med., vol. 90, No. 3, p. 431-439, 1977.
P.P. Toskes et al., Xylose Catabolism in the Experimental Rat Blind Loop Syndrome,Gastroenterology, vol. 74, No. 4, p. 691-697, 1978.
S.M. Riordan et al., Factors Influencing the 1-g14C-D-Xylose Breath Test for Bacterial Overgrowth,The American Journal of Gastroenterology, vol. 90, No. 9, p. 1445-1460, 1995.
Dudash Diana
Jenkens & Gilchrist A Professional Corporation
Metabolic Solutions, Inc.
Sharareh Shahnam
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