METHOD OF MANUFACTURING AN IMPLANTABLE PRESSURE-ACTUATED DRUG DELIVERY SYSTEM

摘要

Implantable pressure-actuated systems to deliver a drug and/or other substance in response to a pressure difference between a system cavity and an exterior environment, and methods of fabrication and use. A pressure-rupturable membrane diaphragm may be tuned to rupture at a desired rupture threshold, rupture site, with a desired rupture pattern, and/or within a desired rupture time. Tuning may include material selection, thickness control, surface patterning, substrate support patterning. The cavity may be pressurized above or evacuated below the rupture threshold, and a diaphragm-protective layer may be provided to prevent premature rupture in an ambient environment and to dissipate within an implant environment. A drug delivery system may be implemented within a stent to release a substance upon a decrease in blood pressure. The cavity may include a thrombolytic drug to or other substance to treat a blood clot.

主权项

1. A method of fabricating an implantable, pressure-actuated drug delivery system, the method comprising:
fabricating a frangible layer of one or more materials over a substrate surface; forming a cavity within the substrate, including an opening through the substrate surface to expose at least a portion of the frangible layer to the cavity; disposing a drug within a cavity of the substrate; sealing the cavity; pressurizing the cavity; and fabricating a substantially non-frangible layer of an implant-environment-dissipative material over the frangible layer to prevent premature rupture of the frangible layer an at an ambient environment pressure and to dissipate within the implant environment, wherein the frangible layer is fabricated to have a rupture threshold within a range of approximately 200 millimeters of mercury (mmHg) to 1200 mmHg, and a rupture time of at least 15 seconds, and wherein the pressurized cavity is pressurized to a pressure that exceeds the rupture threshold by a rupture pressure within a range of approximately 20 mmHg to 50 mmHg relative to one atmosphere to cause the frangible layer to rupture when the implant environment pressure falls below and remains below the rupture pressure for at least 15 seconds.