Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
2001-03-14
2003-06-17
Weber, Jon P. (Department: 1651)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
Reexamination Certificate
active
06579851
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to inhibiting antro-duodenal motility with GLP-1 and methods to alleviate discomfort during endoscopy and to alleviate symptoms of gastrointestinal disorders.
2. Description of the Related Art
Glucagon has been widely used to cause a variable reduction in gastroduodenal motility. The effect of glucagon appears to be dose-dependent with a minimally effective dose being 0.5 mg. Glucagon, however, does not facilitate colonoscopic evaluation (Norfleet, Gastrointest. Endosc., 24, 164-5, 1978), and at doses as high as 2 mg glucagon does not reduce contractions in the antrum (Gregerson et al., Scand. J. Gastroenterol. 23 (Supp 152), 42-47 (1988)). Furthermore, glucagon is contraindicated in persons with diabetes (Paul & Freyschmidt, ROFO Rortschr. Geb. Rontgenstr. Nuklearmed., 125, 31-7 (1996)), is expensive and its efficacy has been questioned.
Side effects associated with the use of glucagon include nausea and vomiting. The effects are dose-dependent and can appear at a dose of 1 mg (Larsen et al., Scand. J. Gastroenterol. 21, 634-640, 1986; Gregersen et al., supra, Diamant Handbook Experimental Pharm, Lefevre ed., Vol. 66/2, 611-643, 1983). As dosages required to sufficiently reduce motility frequently exceed 1 mg, side effects from glucagon use are common. Such side effects render the patient extremely uncomfortable and often cause the endoscopic procedure to be interrupted or aborted.
Hyoscamine sulfate has antispasmodic activity and been used for treatment of irritable bowel syndrome and also has adverse side effects (Lahoti et al., Gastrointest. Endosc. 46, 139-142 (1997)). Otreocide, a somatostatin analog, has also been used and proven effective in treating clinically significant diarrhea during rapid detoxification and postoperative dumping syndrome, but is associated with an unacceptable incidence of bradycardia; its long-term use is limited by side effects.
The proglucagon-derived glucagon-like peptide-1(7-36)amide (GLP-1) is a gastrointestinal hormone that is released postprandially from the L-cells of the gut (Göke et al.,
Eur. J. Clin. Invest.
21, 135-44 (1991); Schirra et al.,
J. Clin. Invest.
97, 92-103 (1996)). Previous studies in humans have shown synthetic GLP-1 to substantially retard gastric emptying of liquid and solid meals (Schirra et al.,
J. Endocrinol,
156, 177-86 (1998); Wettergren et al.,
Dig. Dis. Sci.
38, 665-673 (1993); Schirra et al.,
Proc. Assoc. Am. Physicians
109, 84-97 (1997)). Transpyloric pulsatile flow regulated by the motility of the antro-pyloro-duodenal region is a major mechanism of gastric emptying (Malbert & Mathis,
Gastroenterol.
107, 37-46 (1994); Anvari et al.,
J. Physiol
. (
London
) 488, 193-202 (1995)). Antral contractions, and especially antro-duodenal coordinated ones, were shown to be associated with the gastric emptying rate of liquids (Schirra et al.,
J. Clin. Invest.
97, 92-103 (1996); Camilleri et al.,
Am J Physiol
249, G580-585 (1985); Houghton et al.,
Gastroenterol.
94, 1276-84 (1988)) and solids (Fraser et al.,
Am. J. Physiol.
264, G195-201 (1993)). Tonic and localized phasic pressure increases generated by the pylorus provide an important braking mechanism, diminishing gastric outflow (Anvari et al.,
J. Physiol
. (
London
) 488, 193-202 (1995); Heddle et al.,
Dig. Dis. Sci.
38, 856-69 (1993); Heddle et al.,
Gut
29, 1349-57 (1988); Tougas et al.,
Gut
33, 466-471 (1992)).
SUMMARY
It is therefore an object of the present invention to provide a method for inhibiting antro-duodenal motility with an effective, therapeutic composition that has minimal side effects. It is well known that GLP-1 does not cause hypoglycemia—and it did not cause hypoglycemia during the experiments discussed in the present application, nor did it cause any other side effects. Accordingly, a dosage unit comprising a GLP-1 molecule and a pharmaceutically suitable excipient is also disclosed.
In a related vein, the present invention also encompasses a method for premedicating in endoscopic procedures, comprising administering a GLP-1 molecule prior to or during an endoscopic procedure.
Another embodiment of the present invention is a method for treating or preventing gastrointestinal disorders, including but not limited to, irritable bowel syndrome, non-infectious acute and chronic diarrhea and post-operative dumping syndrome, that comprises administering to the patient therapeutically effective amount of a GLP-1 molecule.
Further encompassed by this invention is a method for treating or preventing symptoms associated with narcotics withdrawal, by administering a GLP-1 molecule as described above.
In another embodiment, the invention includes a method for inhibiting pyloric motility in a patient in need thereof that comprises administering to the patient a therapeutically effective amount of an antagonist to a GLP-1 molecule.
REFERENCES:
patent: 98/39022 (1998-09-01), None
patent: 99/64060 (1999-12-01), None
Schirra et al., “Gastric-Emptying and Release of Incretin Hormones After Glucose-Ingestion in Humans” (Jan. 1, 1996) Journal Of Clinical Investigation, 97(1),92-103.*
Schirra et al., “Mechanisms of the Antidiabetic Action of Subcutaneous Glucagon-like Peptide-1(7-36) Amide in Non-Insulin Dependent Diabetes Mellitus” (1998) J. Endocrinol., 156, 177-185.*
Aros et al., “Effetos del Glucagón-like Peptide-1 (GLP-1) en la Acomodación Y Vaciado Y la Saciedad en Humanos” (Jun. 16-20, 2001) XXVIII Congreso Nacional de la Sociedad Española de Patologia Digestiva, accessed Oct. 4, 2002 at http://www.congressreview.co.*
Anvari et al., “Effects of GLP-1 on Gastric Emptying, Antropyloric Motility, and Transpyloric Flow in Response to a Nonnutrient Liquid,”Digestive Diseases and Sciences43(6):1133-1140 (1998).
Anvari et al., “Effect of GLP-1 on Gastric Emptying, Antropyloric Motility, Transpyloric Flow and Gastric Emptying of Non-nutrient Liquids in Conscious Dogs,”Gastroenterology108(4 Suppl.):A563 (1995).
Anvari et al., “Sites of Action of GLP-1 to Inhibit Transpyloric Flow and Gastric Emptying of Non-nutrient Liquids in Conscious Dogs,”Clinical and Investigative Medicine18(4 Suppl.):B56 (1995).
Chang et al., “A Randomized Study Comparing Glucagon and Hyoscine N-butyl Bromide Before Endoscopic Retrograde Cholangiopancreatography,”Scandinavian Journal of Gastroenterology30(3):283-286 (1995).
Giralt et al., “Sympathetic Pathways Mediate GLP-1 Actions in the Gastrointestinal Tract of the Rat,”Regulatory Peptides74(1):19-25 (1998).
Moses et al., “Suppression of Duodenal Motility During ERCP by L-Hyoscyamine Versus Glucagon: A Randomized Prospective, Double Blinded Trial,”Gastroenterology114(4 Part 2):A533 (1998).
Näslund et al., “Distal Small Bowel Hormones: Correlation with Fasting Antroduodenal Motility and Gastric Emptying,”Digestive Diseases and Sciences43(5):945-952 (1998).
Nauck, “Is Glucagon-like Peptide 1 an Incretin Hormone?,”Diabetologia42(3):373-379 (1999).
Quigley, “Gastroduodenal Motility,”Current Opinion in Gastroenterology, 15(6):481-491 (1999).
Qvigstad et al., “Comparison of Glucagon Atropine and Placebo as Pre Medication for Endoscopy of the Upper Gastro Intestinal Tract,”Scandinavian Journal of Gastroenterology, Database Accession No. PREV197968075464, Abstract (1979).
Schirra et al., “Differential Effects of Subcutaneous GLP-1 on Gastric Emptying, Insulin Release and Exocrine Pancreatic Secretion in Man,”Gastroenterology108(4):A1003 (1995).
Schirra et al., “Effects of GLP-1 on Human Antro Pyloro-duodenal Motility,”Gastroenterology110(4):A1116 (1996).
Schirra et al., “Effects of Glucagon-like Peptide-1(7-36) amide on Antro-pyloro-duodenal Motility in the Interdigestive State and With Duodenal Lipid Perfusion in Humans,”Gut46(5):622-631 (2000).
Schirra et al., “Differential Effects of Subcutaneous GLP-1 on Gastric Emptying, Antroduodenal Motility, and Pancreatic Function in Men,”Proceedings of the Association of American Physicians109(1):84-97 (1997).
Schirra et al., “Endogenous GLP-1(7-36) Amide Controls Endocrine Pancreatic Secre
Goeke Burkhard
Schirra Joerg
Amylin Pharmaceuticals Inc.
McKee Voorhees & Sease, P.L.C.
Weber Jon P.
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