Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1994-02-22
1997-10-28
Weddington, Kevin E.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
A61K 3800
Patent
active
056818165
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/US92/03369 filed Apr. 24, 1992.
The present invention relates to a method for inducing temporary paralysis of the gastrointestinal tract by administering vasoactive intestinal peptide (VIP) to a patient during the course of an endoscopy or other medical procedure.
BACKGROUND OF THE INVENTION
Gastrointestinal endoscopy is a diagnostic and therapeutic procedure which involves visual examination of different portions of the gastrointestinal tract using a long flexible tube known as an endoscope. An endoscope has a lens on one end and an eyepiece or video display system at the opposite end. Endoscopy is performed in moderately sedated patients by inserting the endoscope through the mouth or rectum and positioning the lens in the desired area of observation. Because the gastrointestinal tract is actively contracting during the procedure, the attending physician's visualization of certain regions of the GI tract is impaired or limited. In addition, this natural peristaltic reflex renders difficult the biopsy of certain areas of the GI tract and often interferes with the removal of polyps. In the case of attempted polyp removal, the procedure is made more difficult since the colon may be contracting when the polyps are being snared, cauterized and removed. The esophagus also moves at inopportune times such as when dilated veins known as vatices are being injected.
Attempts to reduce gastrointestinal contractions in endoscopic procedures have involved the use of several different agents over the years. In particular, atropine and glucagon have been employed as premedications for this purpose.
Atropine is a belladonna alkaloid with competitive antimuscarinic actions. In the gastrointestinal tract it is an inhibitor of oral secretion and gastrointestinal motility. However, it is known by practitioners in the field to be only marginally effective as a paralytic agent for use in endoscopic procedures. In fact, controlled studies have failed to demonstrate any beneficial effects of atropine during endoscopies with regard to improvement in patient tolerance or facilitation of endoscopy (Ross, W., Gastrointestinal Endoscopy, Vol.35, No 2, 120-126, 1989). Atropine is also associated with undesirable side effects such as blurred vision, headache, and urinary retention (Goodman and Gilman, The Pharmacological Basis of Therapeutics, 5th Ed., MacMillan, New York, 1975 pp. 514-532) and an increased risk of cardiac arrhymthias (Ross, W., Gastrointestinal Endoscopy, Vol. 35, No. 2, 120-126, 1989). Consequently, atropine is rarely used as a premeditation in endoscopy today.
Glucagon has been demonstrated 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. However, glucagon does not facilitate colonoscopic evaluation (Norfleet, R. G., Gastrointestinal Endoscopy, Vol. 24, 164-5, 1978). In addition, it has been shown that even at doses as high as 2 mg, glucagon does not reduce contractions in the antrum (Gregerson et al., Scan. J. Gastroenterol. 23 (Supp 152) 42-47, 1988).
Glucagon administered intravenously at a dose of 1 mg followed by 2 mg IV over a period of 2 hours does affect, however, antroduodenal activity. That is, the cycle length and time between contractile activity in the duodenum is significantly increased while the mean pressure period is decreased (Larsen et al., Scand. J. Gastroenterol. Vol 21, 634-640, 1986).
Nausea and vomiting are two side effects associated with the use of glucagon. They 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., Scand. J. Gastroent. 23 (Supp 152):42-47, 1988; Diamant Handbook Experimental Parm, Lefevre ed., Vol. 66/2:611-643, 1983). Since dosages required to sufficiently reduce motility frequently exceed 1 mg, side effects from glucagon use are prevalent. Such side effects render the patient extremely uncomfortable and often cause the endoscopic procedure to be interrupte
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