Method of fabricating an implantable medical device comprising a rapamycin derivative

摘要

This invention relates to an method of manufacture of an implantable medical device comprising an oxygen-sensitive rapamycin derivative that is protected by addition of an antioxidant during the manufacturing process where the amount of antioxidant added at the outset of the processing is such that when the device is fully fabricated, sterilized and packaged the amount of antioxidant has reduced to a minimal, preferably non-detect, amount.

主权项

1. A method of fabricating an implantable medical device comprising a rapamycin derivative drug, the method comprising:
synthesizing a rapamycin derivative drug; purifying the rapamycin derivative drug using a technique that results in a substantially pure rapamycin derivative drug dissolved in a solvent, wherein:
the solvent used in the purification technique is used for preparation of a coating composition comprising the rapamycin derivative drug; determining the percent by weight of the rapamycin derivative drug in the solvent; adjusting the amount of the solvent such that the weight percent of the rapamycin derivative drug in the solvent is that desired in the coating composition to be applied to an implantable medical device; adding a desired weight percent, based on the weight of the rapamycin derivative drug, of an pharmaceutically acceptable antioxidant stabilizer to form the coating composition; and disposing the coating composition on the implantable medical device to form a drug reservoir layer; wherein the substantially pure rapamycin derivative drug is not isolated as a dry solid after the purifying step and before the disposing step.