Paul A Diamantopoulos, 771163 Morgantown Rd, Morgantown, PA 19543

4956181, Sep 11, 1990

Jun 7, 1988

7/203774

Gerald W. Bayer - Rochester NY
Paul A. Diamantopoulos - Rochester NY
Hans W. Osterhoudt - Spencerport NY
Paul F. Schmit - Rochester NY

Eastman Kodak - Rochester NY

A61F 1340

424448

Method and device for treating angina pectoris and preventing tolerance to nitrate drugs which takes into account the frequent need to provide the patient with relief from or prevention of pre-waking or early morning angina. The treatment comprises administering a daily unit dose of the nitrate before bedtime in a dosage form that (1) provides a washout period of 3 to 12 hours by sufficiently retarding delivery of the nitrate to the patient during the washout period so as to provide a rate of delivery of nitrate from the patch that is so low as to be insufficient to cause tolerance to said nitrate in said patient; (2) at the end of the washout period and at least 30 minutes before the patient expects to awaken, initiates an effective delivery period during which the dosage form provides an initial effective delivery rate sufficient to provide an antianginally effective concentration of nitrate in the blood stream of the patient; and (3) thereafter, during a ramp-up delivery period, delivers the nitrate at an increasing rate until a final delivery rate is achieved, which is from 125% to 1,000% of the initial effective delivery rate. At the end of the ramp-up period, delivery is exhausted or otherwise terminated. A new unit dose is administered at bedtime, and the cycle is repeated.