METHODS FOR THE TREATMENT OF POST-OPERATIVE ILEUS

Inhibition of intestinal motility, especially colonic motility, is a major complication of abdominal surgery. The condition, called post-operative ileus, delays the normal resumption of food intake after surgery. Ileus can extend a hospital stay by 2-10 days and represents the most common condition that prolongs costly hospitalization. Current approaches to treatment of post-operative ileus are generally ineffective in significantly reducing its duration. A more effective method of treatment would not only acceleraterecovery time, but would also reduce the overall cost of surgery.

UCSF researchers have developed a method for treatment and prevention of ileus involving the administration of compounds effective either in inhibiting mast cell degranulation, or in inhibiting tryptase or chymase. The method is based on the discoveries that proteinase-activated receptor 2 (PAR-2) is expressed in colonic muscle cells, and that activation of PAR-2 inhibits colonic activity. The PAR-2 receptor is activated, at least in part, by tryptase and chymase, produced in the intestinal wall by the infiltration and degranulation of mast cells. Thus, inhibitors of these specific enzymes, or inhibitors of mast cell degranulation may be effective in maintaining colonic motility after surgery.

Intellectual Property:

UCSF has issued US patents 5,958,407 and 5,888,529 covering methods for treating post-operative ileus by preventing mast cell degranulation via administration of specific compounds, or by inhibiting tryptase or chymase.

Selected References:

1) Corvera et al., Mast Cell Tryptase Regulates Rat Colonic Myocytes Through Proteinase-activated Receptor 2. J. Clin. Invest. 1997 September; 100(6):1383-1393.

2) Corvera et al., Thrombin and mast cell tryptase regulate guinea-pig myenteric neurons through proteinase-activated receptors-1 and -2. J. Physiol. 1999; 517(3):741-756.

3) Bunnett and Raybould, Role of Mast Cells in Surgically-induced Gastrointestinal Ileus in Mice. 1998 April 15; 114(4): A729.

If you would like to receive further information about this technology and potential licensing opportunities, please contact:

Joel B. Kirschbaum, Ph.D.
Director & Senior Technology Portfolio Manager
(415) 353-4462 phone
(415) 348-1579 fax
Joel Kirschbaum, Ph.D.

Reference: OTM Case #SF97-138