Apparatus and Method for Delivery of Mitomycin Through an Eluting Biocompatible Implantable Medical Device

Abstract

The present invention is an apparatus and a method for delivery of mitomycin through an eluting biocompatible implantable medical device. A biocompatible drug release matrix comprises a biocompatible drug release matrix and a drug incorporated into the biocompatible drug release matrix. The drug has antibiotic and anti-proliferative properties and is an analogue related to the quinone-containing alkylating agents of a mitomycin family. The drug is initially released from the biocompatible drug release matrix at a faster rate followed by a release at a slower rate. The drug release rate maintains tissue level concentrations of the drug for at least two weeks after implantation of the medical device. The present invention provides a coating for a vascular prosthesis that elutes the drug at a controlled rate to inhibit proliferation of smooth muscle cells causing restenosis.

1 . A biocompatible medical device for delivering a drug to a treatment area in a vasculature of a body comprising:
 a tubular body having a proximal end, a distal end and a longitudinal axis therebetween;   a proximal end band at the proximal end of the tubular body, a distal end band at the distal end of the tubular body and a plurality of intermediate bands between the proximal end band and the distal end band;   a plurality of circumferential rows of links engaging the proximal end band, the plurality of intermediate bands and the distal end band to form the tubular body; and   an elution layer comprising a biocompatible drug release matrix applied to the surface of the biocompatible medical device, the biocompatible drug release matrix having a biocompatible polymer matrix co-solubilized with the drug in a solvent to form a solution and the solvent is evaporated from the solution,   wherein the drug is released from the biocompatible drug release matrix after implantation of the biocompatible medical device to prevent restenosis.   
   
   
       2 . The biocompatible medical device of  claim 1  further comprising a primer layer surrounding a strut of the biocompatible medical device. 
   
   
       3 . The biocompatible medical device of  claim 1  further comprising a burst control layer surrounding the elution layer. 
   
   
       4 . The biocompatible medical device of  claim 1  wherein the proximal end band, the distal end band and the plurality of intermediate bands are arranged axially end to end, extending from the proximal end to the distal end of the biocompatible medical device. 
   
   
       5 . The biocompatible medical device of  claim 1  wherein the biocompatible polymer matrix comprises a mixture of hydrophilic and hydrophobic polymers selected from the group consisting of polyurethanes, polyvinyl pyrrolidone, poly methyl methracrylate (PMMA), hydroxyetyl methacrylate and cellulose esters. 
   
   
       6 . The biocompatible medical device of  claim 1  wherein the solvent is selected from the group consisting of water, saline, tetrahydrofuran, methanol, acetone, butyl acetate, cyclohexane, carbon tetrachloride, ether, chloroform, benzene, ethanol, toluene, dimethyl sulfoxide, petroleum ethers, other hydrocarbons and other organic solvents. 
   
   
       7 . The biocompatible medical device of  claim 1  wherein the elution layer releases the drug at a rate sufficient to produce surrounding tissue level concentrations of the drug from about 0.01 micrograms per milliliter to about 25 micrograms per milliliter after implantation of the biocompatible medical device. 
   
   
       8 . The biocompatible medical device of  claim 1  wherein the drug has antibiotic properties and anti-proliferative properties. 
   
   
       9 . The biocompatible medical device of  claim 1  wherein the drug is an analogue related to the quinone-containing alkylating agents of a mitomycin family. 
   
   
       10 . The biocompatible medical device of  claim 1  wherein the drug is mitomycin C. 
   
   
       11 . The biocompatible medical device of  claim 1  wherein a total dosage of about 0.5 micrograms to about 50 micrograms of the drug per millimeter of a length of the biocompatible medical device is coated on the biocompatible medical device. 
   
   
       12 . The biocompatible medical device of  claim 1  wherein the biocompatible drug release matrix coated on the surface of the biocompatible medical device is between about 5 microns to about 120 microns thick. 
   
   
       13 . The biocompatible medical device of  claim 1  wherein an initial dose of between about 10 percent and about 60 percent of the drug is delivered to the vasculature in the first few days after implantation of the biocompatible medical device. 
   
   
       14 . The biocompatible medical device of  claim 1  wherein initially the drug is released from the biocompatible polymer matrix at a faster rate followed by a release of the drug at a slower rate. 
   
   
       15 . A biocompatible implantable stent comprising:
 a tubular body having a proximal end, a distal end and a longitudinal axis therebetween;   a plurality of circumferential bands arranged axially end to end, extending from the proximal end to the distal end of the tubular body;   a plurality of circumferential rows of links engaging adjacent circumferential bands to form the tubular body; and   an elution layer applied to the surface of the biocompatible implantable stent, the elution layer comprising a biocompatible erodible polymer matrix co-solubilized with a mitomycin family drug in a solvent to form a solution and the solvent is evaporated from the solution,   wherein the mitomycin family drug is released from the biocompatible erodible polymer matrix after implantation of the biocompatible implantable stent to prevent restenosis.   
   
   
       16 . The biocompatible implantable stent of  claim 15  further comprising a burst control layer surrounding the elution layer. 
   
   
       17 . The biocompatible implantable stent of  claim 15  wherein the erodible polymer matrix is selected from the group consisting of polyactide, polyactide with glycolide, polyester-amides, polyurethanes, poly(ethylene-urethane), poly(ester-urethane) and poly(ether-polyester-urethane), amino-acid based polyurethanes, polycaprolactone based polyurethanes, polyurethanes synthesized from poly(butylene succinate) polyol, poly(ethylene glycol), and 4,4′-methylenebis(cyclohexyl isocyanate), fat, carbohydrates and protein compounds. 
   
   
       18 . A biocompatible delivery device comprising:
 a biocompatible polymer matrix co-solubilized with a mitomycin family drug in a solvent to form a biocompatible drug release matrix applied to the delivery device to form an elution layer on the delivery device.   
   
   
       19 . The biocompatible delivery device of  claim 18  wherein the mitomycin family drug is released from the biocompatible polymer matrix to prevent restenosis. 
   
   
       20 . A method of inhibiting the growth of smooth muscle cells to inhibit restenosis comprising:
 providing a biocompatible medical device;   preparing a biocompatible polymer matrix;   co-solubilizing the biocompatible polymer matrix with a mitomycin family drug in a solvent to form a biocompatible drug release matrix;   applying the biocompatible drug release matrix to the biocompatible implantable medical device to form an elution layer of the biocompatible drug release matrix on the biocompatible implantable medical device; and   implanting the biocompatible implantable medical device into a vasculature of a body.   
   
   
       21 . A method of inhibiting restenosis comprising:
 preparing a biocompatible polymer matrix;   co-solubilizing the biocompatible polymer matrix with a mitomycin family drug in a solvent to form a biocompatible drug release matrix; and   applying the biocompatible drug release matrix to a delivery device to form an elution layer of the biocompatible drug release matrix on the delivery device.