Drug eluting stents with prolonged local elution profiles with high local concentrations and low systemic concentrations

Abstract

A drug eluting stent can include a stent body having a polymeric coating with a lipophilic and/or hydrophilic element. A drug that has a bioactivity that inhibits cell proliferation can be disposed in the polymeric coating. The drug can be present in the polymer at an amount greater than or equal to about 150 ug/cm 2 . The polymeric coating and drug are configured to cooperate so as to form a diffusion pathway with tissue when the stent is disposed in a body lumen such that the drug preferentially diffuses into the tissue over a body fluid passing through the body lumen such that a maximum systemic blood concentration of the drug is less than about 40 ng/ml.

1 . A drug eluting stent comprising:
 a stent body;   a polymeric coating disposed on the stent body;   a drug disposed in the polymeric coating, said drug being present at an amount greater than or equal to about 150 ug/cm 2 ; and   wherein the polymeric coating and drug cooperate to form a diffusion pathway with tissue when the stent is disposed in a body lumen such that the drug preferentially diffuses into the tissue over a body fluid passing through the body lumen such that a maximum systemic blood concentration of the drug is less than about 40 ng/ml.   
   
   
       2 . A stent as in  claim 1 , wherein the polymer includes a lipophilic component, and the drug is lipophilic and is present in an amount greater than or equal to about 200 ug/cm 2 . 
   
   
       3 . A stent as in  claim 1 , wherein the maximum systemic blood concentration of the drug is less than about 4 ng/ml per milligram of total drug on the stent. 
   
   
       4 . A stent as in  claim 1 , wherein the maximum systemic blood concentration of the drug is less than about 15 pg/ml per millimeter of stent length. 
   
   
       5 . A stent as in  claim 1 , wherein maximum systemic blood concentration is from about 0.6 ng/ml to about 15 ng/ml. 
   
   
       6 . A stent as in  claim 1 , wherein the polymeric coating ranges from about 2 um to about 50 um. 
   
   
       7 . A stent as in  claim 6 , wherein the polymeric coating includes a primer layer disposed on the stent body, a drug-loaded layer disposed on the primer layer, and a topcoat layer disposed on the drug-loaded layer so as to control elution of the drug. 
   
   
       8 . A stent as in  claim 7 , wherein the polymeric coating is characterized by at least one of the following:
 the primer layer being from about 1% to about 20% of the total coating thickness;   the drug-loaded layer being from about 25% to about 90% of the total coating thickness; or   the topcoat being from about 5% to about 50% of the total coating thickness.   
   
   
       9 . A stent as in  claim 1 , wherein the stent body is nitinol, the drug is everolimus, and the polymer is an ethylenevinylalcohol copolymer. 
   
   
       10 . A drug eluting stent comprising:
 a stent body comprising a superelastic alloy;   an ethylenevinylalcohol polymeric coating disposed on the stent body;   a therapeutically effective amount of everolimus disposed in the polymeric coating, said drug being present at an amount greater than or equal to about 150 ug/cm 2 ; and   wherein the polymer coating and everolimus cooperate to form a lipophilic diffusion pathway with tissue when the stent is disposed in a body lumen such that the everolimus preferentially diffuses into the tissue over a body fluid passing through the body lumen such that a maximum systemic blood concentration of everolimus is less than about 40 ng/ml.   
   
   
       11 . A stent as in  claim 10 , wherein the everolimus is present in an amount greater than or equal to about 220 ug/cm 2 . 
   
   
       12 . A stent as in  claim 10 , wherein the maximum systemic blood concentration of the everolimus is less than about 4 ng/ml per milligram of total everolimus on the stent. 
   
   
       13 . A stent as in  claim 10 , wherein the maximum systemic blood concentration of the everolimus is less than about 15 pg/ml per millimeter of stent length. 
   
   
       14 . A stent as in  claim 10 , wherein maximum systemic blood concentration is from about 0.6 ng/ml to about 15 ng/ml. 
   
   
       15 . A stent as in  claim 10 , wherein the polymeric coating ranges from about 2 um to about 50 um. 
   
   
       16 . A stent as in  claim 15 , wherein the polymeric coating includes a primer layer disposed on the stent body, a drug-loaded layer disposed on the primer layer, and a topcoat layer disposed on the drug-loaded layer so as to control elution of the drug. 
   
   
       17 . A stent as in  claim 17 , wherein the polymeric coating is characterized by at least one of the following:
 the primer layer being from about 1% to about 20% of the total coating thickness;   the drug-loaded layer being from about 25% to about 90% of the total coating thickness; or   the topcoat being from about 5% to about 50% of the total coating thickness.   
   
   
       18 . A method of inhibiting occlusion of a body lumen in a subject, the method comprising:
 providing a drug eluting stent comprising:
 a stent body; 
 a polymeric coating having a lipophilic element disposed on the stent body; 
 a lipophilic drug that inhibits cell proliferation disposed in the polymeric coating, said drug being present at an amount greater than or equal to about 150 ug/cm 2 ; and 
 wherein the polymeric coating and drug cooperate to form a lipophilic diffusion pathway with tissue when the stent is disposed in a body lumen such that the lipophilic drug preferentially diffuses into the tissue over a body fluid passing through the body lumen such that a maximum systemic blood concentration of the drug is less than about 40 ng/ml; and 
   deploying the drug eluting stent into the body lumen.   
   
   
       19 . A method as in  claim 18 , wherein the drug is present in an amount greater than or equal to about 200 ug/cm 2 . 
   
   
       20 . A method as in  claim 19 , wherein the maximum systemic blood concentration of the drug is less than about 4 ng/ml per milligram of total drug on the stent. 
   
   
       21 . A method as in  claim 20 , wherein the maximum systemic blood concentration of the drug is less than about 15 pg/ml per millimeter of stent length. 
   
   
       22 . A method as in  claim 21 , wherein maximum systemic blood concentration is from about 0.6 ng/ml to about 15 ng/ml. 
   
   
       23 . A method as in  claim 22 , wherein the polymeric coating ranges from about 2 um to about 50 um. 
   
   
       24 . A method as in  claim 23 , wherein the polymeric coating includes a primer layer disposed on the stent body, a drug-loaded layer disposed on the primer layer, and a topcoat layer disposed on the drug-loaded layer so as to control elution of the drug. 
   
   
       25 . A method as in  claim 24 , wherein the polymeric coating is characterized by at least one of the following:
 the primer layer being from about 1% to about 20% of the total coating thickness;   the drug-loaded layer being from about 25% to about 90% of the total coating thickness; or   the topcoat being from about 5% to about 50% of the total coating thickness.   
   
   
       26 . A method as in  claim 25 , wherein the stent body is nitinol, the drug is everolimus, and the polymer is an ethylenevinylalcohol copolymer.