40-O-(2-hydroxy)ethyl-rapamycin coated stent

Abstract

A method and coating for reducing the release rate of an active agent from an implantable device, such as a stent, is disclosed.

1 . A stent for implantation in a human being having a vascular medical condition, comprising a radially expandable body and a coating covering at least a portion of the body, the coating containing 40-O-(2-hydroxy)ethyl-rapamycin, or an analog or derivative thereof, wherein the amount of the 40-O-(2-hydroxy)ethyl-rapamycin, or the analog or derivative thereof, released in 24 hours after the implantation of the stent in a blood vessel of a human being is less than about 50% of the total amount of 40-O-(2-hydroxy)ethyl-rapamycin, or an analog or derivative thereof, contained in the coating.  
     
     
         2 . The stent of  claim 1 , wherein the derivative or analogue of 40-O-(2-hydroxy)ethyl-rapamycin includes 40-O-(3-hydroxy)propyl-rapamycin and 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin.  
     
     
         3 . The stent of  claim 1 , wherein the coating comprises an ethylene vinyl alcohol copolymer.  
     
     
         4 . The stent of  claim 1 , wherein the coating is made from a polymer including a first region having a first degree of crystallinity and a second region having a second degree of crystallinity, the second degree of crystallinity being greater than the first degree of crystallinity.  
     
     
         5 . The stent of  claim 4 , wherein the second region is positioned over the first region.  
     
     
         6 . A method of inhibiting or eliminating the development of vascular restenosis in a human being following a stent placement procedure, comprising implanting in a blood vessel of the human being a stent which releases 40-O-(2-hydroxy)ethyl-rapamycin, or an analog or derivative thereof, at an amount of less than 50% of the total amount of the 40-O-(2-hydroxy)ethyl-rapamycin, or an analog or derivative thereof, carried by the stent in a 24 hour period following the implantation procedure in the blood vessel of the human being.  
     
     
         7 . The method of  claim 6 , wherein the 40-O-(2-hydroxy)ethyl-rapamycin, or an analog or derivative thereof, is contained in a polymer coating on the stent.  
     
     
         8 . The method of  claim 6 , wherein the stent carries about 50 μg to about 500 μg of 40-O-(2-hydroxy)ethyl-rapamycin, or analog or derivative thereof.  
     
     
         9 . A method of providing drug delivery capability for a stent, comprising coating a stent with a layer of polymer containing 40-O-(2-hydroxy)ethyl-rapamycin, or analog or derivative thereof, wherein the coating has an in vivo release rate of less than 50% of the total amount of the 40-O-(2-hydroxy)ethyl-rapamycin, or analog or derivative thereof, in a 24 hour period.  
     
     
         10 . The method of  claim 9 , wherein the release rate of the 40-O-(2-hydroxy)ethyl-rapamycin, or an analog or derivative thereof, from the coating is adjusted by exposing a the coating to sufficient temperature which causes modifications to the polymer so as to reduce the rate of release of the 40-O-(2-hydroxy)ethyl-rapamycin, or an analog or derivative thereof.  
     
     
         11 . A method of treating a coating comprising a polymer on a stent to reduce the rate of release of a drug from the coating, comprising exposing the coating to a temperature of a sufficient degree to cause modifications in the structure of the polymer which allows for the reduction of the release rate of the drug through the polymer.  
     
     
         12 . The method of  claim 11 , wherein the temperature increases the crystallinity of the polymer in at least a portion of the coating.  
     
     
         13 . The method of  claim 11 , wherein the temperature is above the glass transition temperature and below the melting temperature of the polymer.  
     
     
         14 . The method of  claim 11 , wherein the coating includes an additive for shifting the glass transition temperature or the melting temperature of the polymer to a temperature different than the actual glass transition temperature or the melting temperature of the polymer without the additive.  
     
     
         15 . A method of treating a coated stent containing a therapeutic substance to reduce the rate of release of the therapeutic substance from a coating, comprising subjecting the coating to a stimuli so as to change the property of at least a region of the coating such that the change of the property of the region of the coating causes the therapeutic substance to be released more slowly from the region that has the changed property.  
     
     
         16 . The method of  claim 15 , wherein the stimuli does not significantly affect the properties of the therapeutic substance to make the therapeutic substance not useful for the intended purpose of the substance.  
     
     
         17 . (canceled)  
     
     
         18 . (canceled)  
     
     
         19 . A method of preparing a coated stent containing 40-O-(2-hydroxy)ethyl-rapamycin, or analog or derivative thereof, for an implantation procedure comprising sterilizing the stent while maintaining the peak purity of the 40-O-(2-hydroxy)ethyl-rapamycin, or analog or derivative thereof, at a level greater than 90%.  
     
     
         20 . The method of  claim 19 , wherein the coating is of a type that protects the purity from dropping to a level below 90%.  
     
     
         21 . The stent of  claim 1 , wherein the coating comprises a release rate-limiting barrier layer on top of a layer containing the 40-O-(2-hydroxy)ethyl-rapamycin, or an analog or derivative thereof.  
     
     
         22 . The stent of  claim 1 , wherein the coating comprises a primer layer between the surface of the stent and a layer containing the 40-O-(2-hydroxy)ethyl-rapamycin, or an analog or derivative thereof.  
     
     
         23 . The stent of  claim 1 , wherein the coating comprises a biocompatible finishing layer.  
     
     
         24 . The stent of  claim 21 , wherein the release rate-limiting barrier layer is substantially free of the 40-O-(2-hydroxy)ethyl-rapamycin, or an analog or derivative thereof.  
     
     
         25 . The method of  claim 1 , wherein the stent carries about 50 μg to about 500 μg of 40-O-(2-hydroxy)ethyl-rapamycin, or analog or derivative thereof.