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Effects of glucagon-like peptide-1 (7-36) on antro-pyloro-duodenal motility

A technique of duodenum and gastric antrum pylorus is applied in the field of the influence of glucagon-like peptide 1 (7-36) on gastric antrum pylorus and duodenum motility, and can solve adverse side effects, long-term use, internal Problems such as interruption or abort of speculum operation

Inactive Publication Date: 2004-04-07
AMYLIN PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

These side effects are very uncomfortable for the patient and often result in the endoscopic procedure having to be interrupted or discontinued
[0004] Hyoscyamine sulfate has antispasmodic properties and is used in the treatment of irritable bowel syndrome, but is also associated with adverse side effects [Lahoti et al., Gastrointest. Endosc. 46: pp. 139-142, (1997)]
Otreocide, a somatostatin analog, has also been used to treat clinically severe diarrhea and postoperative dumping syndrome in rapid detoxification, and has been proven to be effective, but unacceptable bradycardia will occur, due to There are these side effects, so it should not be taken for a long time

Method used

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  • Effects of glucagon-like peptide-1 (7-36) on antro-pyloro-duodenal motility
  • Effects of glucagon-like peptide-1 (7-36) on antro-pyloro-duodenal motility
  • Effects of glucagon-like peptide-1 (7-36) on antro-pyloro-duodenal motility

Examples

Experimental program
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Effect test

preparation example Construction

[0067] Preparation of Dosage Units

[0068] Another embodiment of the present invention provides a dosage unit for inhibiting antral duodenal motility in a patient, which comprises GLP-1 and a pharmaceutically suitable excipient. The dosage unit is preferably about 0.4 to 2.4 pmol·kg -1 min -1 range between. And the dosage unit is preferably about 0.8 to 1.2 pmol·kg -1 min -1 range between. In the present invention, the term about is defined as ±10%. For example, the dosage unit is about 0.4 to 2.4 pmol·kg -1 min -1 range, that is, between 0.196 and 2.64pmol·kg -1 min -1 between.

[0069] The compositions of the present invention can be administered orally or parenterally for systemic or topical use. In addition, the composition can also be administered by intravenous infusion or subcutaneous injection. For the convenience of doctors or patients, the composition can be made into a dosage unit form containing a certain amount of GLP-1 molecules, for example, GLP-1...

Embodiment 1

[0099] Example 1 Motility Records and Blood Samples Obtained from Patients

[0100] A total of 11 healthy male volunteers participated in this study, aged from 23 to 28, and all within 10% of their ideal body weight. None of them were taking medication or suffering from gastrointestinal symptoms or systemic diseases.

[0101] All studies were performed after an overnight fast. There was at least one week between the two experiments, and the subjects took the semi-recumbent position during the experiment. An indwelling catheter is inserted in the antecubital vein for IV infusion. Arterialized venous blood was withdrawn by a second catheter retrogradely inserted in the dorsal vein of the contralateral hand [Schirra et al., Proc. Assoc. Am. Physicians, 109: pp. 84-97, (1997)].

[0102] Each experiment was preceded by a base period of at least 30 minutes, the last 15 minutes of which showed lower motor activity (less than 5 contractions per 10 minutes). During the interdiges...

Embodiment 2

[0104] Example 2 Motility recording of gastric antrum pyloric duodenal area

[0105] Perfusion pressures were recorded with a nine-lumen duodenal sleeve / side port catheter (Dentsleev, South Australia, Australia). The manometry device consisted of a 4.5 cm long sleeve sensor, two gastric antrum side holes (2 cm apart), and three duodenal side holes (2 cm apart), starting from the proximal and distal ends of the sleeve, respectively. Set two more side holes 1.5cm apart in the sleeve. An additional lumen was set 12cm away from the sleeve sensor for duodenal perfusion.

[0106] Duodenal probes with transpyloric cuff arrays were examined by fluoroscopy before each experiment as described in previous studies [Schirra et al., J. Clin Invest, 97:92-103, (1996)]. The correct position of the ostium was monitored throughout each study by measuring the transmucosal potential difference between the distal gastric antral ostium and the proximal duodenal ostium. A potential difference o...

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Abstract

The present invention provides an effective method for inhibiting antro-duodenal motility in healthy subjects and patients suffering from various disorders, without the side effects associated with other pharmaceutical compositions. GLP-1 slows antro-duodenal motility and may be used for the treatment or prevention of gastrointestinal disorders such as diarrhea, postoperative dumping syndrome and irritable bowel syndrome, and also premedication in endoscopic procedures.

Description

technical field [0001] The present invention relates to the use of glucagon-like peptide-1 (GLP-1 for short) to inhibit the motility of gastric antrum, pylorus and duodenum, and to relieve discomfort and gastrointestinal dysfunction during endoscopic examination. method. Background technique [0002] Extensive use of glucagon can cause varying degrees of reduction in gastroduodenal motility. The effect of glucagon is dose-related, and the minimum effective dose is 0.5mg. However, glucagon is not conducive to colonoscopy detection [Norfleet, Gastrointest. Endosc., 24:164-5 pages, (1978)], at doses up to 2 mg, glucagon does not reduce gastric antrum contraction [Gregerson et al., Scand. J. Gastroenterol. 23 (supp 152), pp. 42-47, (1988)]. In addition, glucagon is contraindicated for diabetic patients [Paul and Freyschmidt, ROFO Rortschr. It has never been confirmed. [0003] Side effects of taking glucagon include nausea and vomiting. Side effects are dose-dependent and ...

Claims

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Application Information

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IPC IPC(8): A61K38/00A61K38/12A61K38/26A61P1/00A61P1/12A61P25/24A61P25/36
CPCA61K38/00A61K38/26A61P1/00A61P1/12A61P25/24A61P25/30A61P25/36A61P41/00
Inventor B·格克J·斯基拉
Owner AMYLIN PHARMA INC
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