Method for manufacturing of drug-releasing stent coated with titanium-oxide thin film

Abstract

Disclosed is a method for manufacturing a drug-releasing stent, including: coating a titanium dioxide or nitrogen-doped titanium dioxide thin film on a metal stent; and attaching a drug on the surface of the titanium oxide thin film. More specifically, the method for manufacturing a drug-releasing stent includes: coating a titanium dioxide or nitrogen-doped titanium dioxide thin film on a metal stent, which can be inserted into the blood vessel, by plasma enhanced chemical vapor deposition (PECVD); modifying the surface of the titanium oxide thin film with hydroxyl groups by low-temperature plasma; and chemically attaching a drug such as an antithrombotic drug or a neointimal hyperplasia inhibitor, so that the drug may be released in the blood vessel in a sustained manner.

1 . A drug-releasing stent comprising:
 a titanium oxide layer coated with TiO 2  or nitrogen-doped titanium oxide (TiO 2-x N x ; x is from 0.001 to 1) on a metal stent; and   a drug coated layer with a drug attached on the titanium oxide layer.   
     
     
         2 . The drug-releasing stent according to  claim 1 , wherein the metal stent is made of a biocompatible metal selected from a group consisting of chromium, cobalt and an alloy thereof. 
     
     
         3 . The drug-releasing stent according to  claim 2 , wherein the titanium oxide layer has a thickness of 10 to 500 nm. 
     
     
         4 . The drug-releasing stent according to  claim 3 , wherein the drug is one or more selected from an anticancer drug, an anti-inflammatory drug, a smooth muscle cell growth inhibitor and an antithrombotic drug having one or more functional groups selected from carboxyl, aldehyde and hydroxyl groups. 
     
     
         5 . The drug-releasing stent according to  claim 4 , wherein one or more of the drug is independently attached on the titanium oxide layer of the drug-releasing stent. 
     
     
         6 . The drug-releasing stent according to  claim 5 , wherein the drug is one or more selected from heparin, ReoPro (abciximab), α-lipoic acid, sirolimus (rapamycin), actinomycin, molsidomine, linsidomine and paclitaxel. 
     
     
         7 . The drug-releasing stent according to  claim 4 , wherein two or more of the drug are attached on the titanium oxide layer of the drug-releasing stent as bound chemically or physically to each other. 
     
     
         8 . The drug-releasing stent according to  claim 7 , wherein the drug is one or more selected from heparin, ReoPro (abciximab), α-lipoic acid, sirolimus (rapamycin), actinomycin, molsidomine, linsidomine and paclitaxel. 
     
     
         9 . The drug-releasing stent according to  claim 1 , wherein the drug-releasing stent releases the drug in the body in a sustained manner. 
     
     
         10 . A method for manufacturing a drug-releasing stent, comprising:
 providing a titanium precursor, a carrier gas and a reactant gas in a plasma vacuum chamber and generating a plasma for 1 to 6 hours to form a titanium oxide thin film on the surface of a stent;   providing steam or oxygen and hydrogen in the plasma vacuum chamber and generating a low-temperature plasma for 10 minutes to 2 hours to modify the surface of the titanium oxide thin film; and   reacting the titanium oxide thin film of the stent with a drug in an acidic solution and under an inert gas atmosphere at room temperature to 100° C. for 30 minutes to 4 hours to attach the drug.   
     
     
         11 . The method for manufacturing a drug-releasing stent according to  claim 10 , wherein the titanium precursor is one or more selected from a group consisting of titanium butoxide, tetraethylmethylamino titanium, titanium ethoxide, titanium isopropoxide and tetramethylheptadiene titanium. 
     
     
         12 . The method for manufacturing a drug-releasing stent according to  claim 10 , wherein the carrier gas is one or more selected from a group consisting of argon and helium. 
     
     
         13 . The method for manufacturing a drug-releasing stent according to  claim 10 , wherein the reactant gas is one or more selected from a group consisting of steam, ozone and oxygen. 
     
     
         14 . The method for manufacturing a drug-releasing stent according to  claim 13 , wherein nitrogen gas is added to the reactant gas to form nitrogen-doped titanium oxide (TiO 2-x N x ; x is from 0.001 to 1). 
     
     
         15 . The method for manufacturing a drug-releasing stent according to  claim 10 , wherein the drug is one or more selected from a group consisting of heparin, ReoPro (abciximab), α-lipoic acid, sirolimus (rapamycin), actinomycin, molsidomine, linsidomine and paclitaxel.