Methods of stabilizing molecular weight of polymer stents after sterilization

Abstract

Methods of stabilizing the molecular weight of polymer stents scaffolds after E-beam sterilization are disclosed. The molecular weight of the polymer of the irradiated scaffolds is stabilized through exposure to gas containing oxygen.

1 . (canceled) 
     
     
         2 . A method of making a stent, comprising:
 providing a polymeric stent scaffolding disposed on a catheter;   exposing the scaffolding to E-beam radiation for sterilization, wherein the scaffolding is exposed to a gas containing oxygen during the exposure, wherein the exposure to the gas containing oxygen is performed at least until a free radical concentration of the gas is less than 5×10 7  DI/mg and/or at least until the number average molecular weight (Mn) of the scaffolding is stabilized, wherein an oxygen content of the gas is 1% or greater; and followed by   packaging the scaffolding in an inert gas environment.   
     
     
         3 . The method of  claim 2 , wherein the oxygen-containing gas is air. 
     
     
         4 . The method of  claim 2 , an oxygen content of the gas is 1 to 10%. 
     
     
         5 . The method of  claim 2 , wherein the inert gas environment has an oxygen content of less than 0.002%. 
     
     
         6 . The method of  claim 2 , wherein the polymeric stent scaffolding is exposed 8 to 24 hr to the oxygen-containing gas after the E-beam exposure. 
     
     
         7 . The method of  claim 2 , wherein during sterilization, the scaffolding is within a package that allows permeation of air into the package. 
     
     
         8 . The method of  claim 2 , wherein a dose of the radiation exposure is between 20-50 kGy. 
     
     
         9 . The method of  claim 2 , wherein stabilizing comprises less than a 10% change in Mn over a selected time period. 
     
     
         10 . The method of  claim 9 , wherein the selected time period is at least 30 days, 30 to 60 days, or greater than 60 days. 
     
     
         11 . The method of  claim 2 , wherein:
 prior to E-beam exposure:   the scaffolding is sealed in a package permeable to and comprising air, wherein oxygen in the air quenches free radicals generated by the radiation exposure, and   after the radiation exposure:   the package is disposed in a gas impermeable package,   the air is removed from the packages, and   the packages are filled with an inert gas and sealed.   
     
     
         12 . A method of making a stent, comprising:
 providing a polymeric stent scaffolding;   exposing the scaffolding to E-beam radiation for sterilization, wherein the scaffolding is exposed to an inert gas environment during sterilization;   exposing the irradiated scaffolding to air to quench free radicals generated by the radiation exposure and stabilize a molecular weight of the scaffolding polymer,   wherein the exposure to the air is performed at least until the free radical concentration is less than 5×10 7  DI/mg and/or the stabilized scaffolding polymer has less than a 10% change in Mn over a selected time period; and   after stabilizing, packaging the scaffolding in an inert gas environment.   
     
     
         13 . The method of  claim 12 , wherein the radiation exposure is between 20-50 kGy. 
     
     
         14 . The method of  claim 12 , wherein the selected time period is at least 30 days, 30 to 60 days, or greater than 60 days. 
     
     
         15 . A method of making a stent, comprising:
 packaging a polymeric stent scaffolding in a sealed gas impermeable package for storage until use, wherein the package contains a mixture of inert gas and oxygen and a content of the oxygen in the gas mixture is 0.5% to 2%; and   exposing the packaged scaffolding to E-beam radiation for sterilization,   wherein the oxygen in the gas mixture quenches free radicals in the scaffolding polymer generated during radiation exposure and stabilizes the molecular weight of the scaffolding polymer such that a number average molecular weight (Mn) of the stabilized scaffolding polymer changes less than 10% during storage.   
     
     
         16 . The method of  claim 15 , wherein the free radical concentration is less than 5×10 7  DI/mg in less than 2 days after exposure. 
     
     
         17 . A method of making a stent, comprising:
 disposing a polymeric stent scaffolding in a gas-impermeable package;   vacuum evacuating the package followed by backfilling of the package with an inert gas;   repeating the evacuation and backfill process to further reduce oxygen content in the package;   exposing the package to E-beam radiation for sterilization of the scaffolding, wherein an oxygen content in the package during the exposing is 0.5 to 3%; and   releasing the sterilized package for storage and/or shipping.   
     
     
         18 . The method of  claim 17 , wherein a required dose of the radiation for sterilization is 20-50 kGy. 
     
     
         19 . The method of  claim 17 , wherein the package is exposed to a required dose for sterilization in multiple passes of E-beam exposure. 
     
     
         20 . The method of  claim 17 , wherein the scaffolding comprises PLLA.