Control of degradation profile of bioabsorbable poly(l-lactide) scaffold

Abstract

Methods of controlling the degradation profile of a biodegradable stent scaffolding are disclosed. Disclosed methods include controlling features of the degradation profile including the time to loss of radial strength and the degradation time of the stent.

1 . (canceled) 
     
     
         2 . A method of making a bioabsorbable stent,
 said stent having:
 a number average molecular weight (Mn) at onset of loss of radial strength (Mn, Tr) from 45 kDa to 52 kDa; 
 a desired minimum patency time of 3 months; 
 an Mn(0) greater than or equal to an Mn(0) that is determined from a kinetic model of formula Mn(t)/Mn(0)=exp(−kt), said Mn(0) being that in which Mn(t)=Mn,Tr, at a desired patency time (t), 
   the method comprising:
 providing a resin of bioabsorbable polymer of PLLA, with a nominal amount of L-lactide monomer content or with an added pre-determined amount of L-lactide monomer content; 
 extruding the resin to form a tube while controlling the L-lactide monomer content in the extruded tube, in such a way that a degradation rate constant (k) according to the model is determined for adjusting the Mn(t) at desired patency time (t) to a value within the Mn,Tr range or higher, and for adjusting the Mn(0) to that that leads to this Mn(t); and 
 making a stent scaffolding from the tube; 
 wherein Mn(0) is the initial number average molecular weight at time of degradation t=0 of the scaffolding, Mn(t) is the number average molecular weight at time t, and k is the degradation rate constant. 
   
     
     
         3 . The method of  claim 1 , further comprising adjusting the molecular weight of the bioabsorbable polymer of PLLA during making of the stent so that the stent scaffolding has the Mn(0) greater than or equal to the determined Mn(0). 
     
     
         4 . The method of  claim 3 , wherein the molecular weight is adjusted through exposure to radiation of the bioabsorbable polymer or through hydrolytic pre-degradation. 
     
     
         5 . The method of  claim 1 , wherein the Mn of the PLLA of the scaffolding is at least about 250 kDa; and wherein the method further comprises performing a sterilization step comprising exposing the PLLA scaffolding to a radiation dose between 31 to 75 kGy which reduces the Mn of the PLLA scaffolding to no less than the determined Mn(0). 
     
     
         6 . The method of  claim 5 , wherein the radiation dose reduces the Mn of the PLLA scaffolding to the Mn(0). 
     
     
         7 . The method of  claim 6 , wherein the monomer content of L-lactide of the sterilized scaffolding is 0.2 wt % or less and the radiation dose reduces the Mn of the PLLA scaffolding to 66 kDa. 
     
     
         8 . The method of  claim 1 , wherein the polymer tube has an Mn of at least 250 kDa, wherein the method comprises:
 laser cutting the polymer tube to form the scaffolding;   exposing the laser cut scaffolding to a first radiation dose prior to crimping to reduce the Mn;   crimping the exposed scaffolding to a reduced diameter over a delivery balloon; and   exposing the crimped scaffolding to a second radiation dose of 20-31 kGy for sterilization which reduces the Mn to the Mn(0) which provides a degradation time of 16-20 months and the time of loss of radial strength of at least about 3 months.   
     
     
         9 . The method of  claim 8 , wherein the monomer content of L-lactide of the sterilized scaffold is 0-0.1 wt %, 0.1-0.2 wt %, 0.2-0.5 wt %, or 0.5-1 wt %, and the Mn after the final sterilization is 55-110 kDa. 
     
     
         10 . The method of  claim 8 , wherein the first radiation dose is 6-50 kGy. 
     
     
         11 . The method of  claim 1 , wherein the Mn of the PLLA of the scaffolding is at least about 250 kDa; and wherein the method further comprises exposing the scaffolding to radiation for sterilization, wherein the radiation reduces the Mn of the scaffolding to 70 kDa or less, wherein the Mn of the exposed scaffolding provides a degradation time of the exposed scaffold of less than 18 months and the time to loss of radial strength is at least 3 months. 
     
     
         12 . The method of  claim 11 , wherein the monomer L-lactide concentration of the scaffold is up to 0.2 wt %. 
     
     
         13 . The method of  claim 1 , wherein the polymer tube is radially expanded; wherein the method comprises radiation sterilizing the scaffolding; and wherein at least one of the following is hydrolytically pre-degraded to reduce its Mn: resin, the extruded tube; or the radially expanded tube. 
     
     
         14 . The method of  claim 1 , wherein the Mn of the PLLA stent scaffolding is greater than 250 kDa; and wherein the method further comprises:
 hydrolytically pre-degrading the PLLA stent scaffolding prior to radiation sterilization to reduce the Mn of the scaffolding to 100 kDa or less,   
       wherein the pre-degradation provides a degradation time of the scaffolding of less than 18 months.