Bioactive agent release coating and controlled humidity method

Abstract

A coating composition in the form of a one or multi-part system, and method of applying such a composition under conditions of controlled humidity, for use in coating device surfaces to control and/or improve their ability to release bioactive agents in aqueous systems. The coating composition is particularly adapted for use with medical devices that undergo significant flexion and/or expansion in the course of their delivery and/or use, such as stents and catheters. The composition includes the bioactive agent in combination with a first polymer component such as polyalkyl(meth)acrylate, polyaryl(meth)acrylate, polyaralkyl(meth)acrylate, or polyaryloxyalkyl(meth)acrylate and a second polymer component such as poly(ethylene-co-vinyl acetate).

1 . A method for selecting a bioactive release rate from a coated composition to be positioned in vivo, the method comprising the steps of:
 (a) providing a composition comprising a bioactive agent in combination with a plurality of polymers, including a first polymer component comprising at least one polymer selected from the group consisting of polyalkyl(meth)acrylates, polyaryl(meth)acrylates, polyaralkyl(meth)acrylates, and polyaryloxyalkyl(meth)acrylates, and a second polymer component comprising poly(ethylene-co-vinyl acetate);   (b) coating the composition on a plurality of surfaces, wherein the coating is applied to the surfaces at differing humidity levels;   (c) determining the release profiles of the bioactive agent from the plurality of surfaces; and   (d) correlating the release profiles to the humidity level at which the coating is applied.   
     
     
         2 . A method according to  claim 1 , wherein increasing the humidity level accelerates the release of the bioactive agent and decreasing the humidity level decreases the release of the bioactive agent. 
     
     
         3 . A method according to  claim 1 , wherein the humidity level is altered by a method selected from controlling the humidity at which the device is coated with the coating composition, controlling the water content of the coating composition, or a combination thereof. 
     
     
         4 . A method according to  claim 1  wherein the aromatic poly(meth)acrylates are selected from the group consisting of polyaryl(meth)acrylates, polyaralkyl(meth)acrylates, and polyaryloxyalkyl(meth)acrylates. 
     
     
         5 . A method according to  claim 1  wherein the first polymer component is selected from:
 polyaryl(meth)acrylates, polyaralkyl(meth)acrylates, and polyaryloxyalkyl(meth)acrylates with aryl groups having from 6 to 16 carbon atoms, the first polymer component having a weight average molecular weight of about 50 to about 900 kilodaltons, and wherein the vinyl acetate content is between about 20% and about 40% by weight. 
 
     
     
         6 . A method according to  claim 1  wherein the total combined concentrations of both polymers in the composition is between about 0.05% and about 70% by weight. 
     
     
         7 . A method according to  claim 1 , wherein the composition further comprises a solvent in which the polymers form a true solution. 
     
     
         8 . A method according to  claim 1  wherein the bioactive agent is selected from the group consisting of thrombin inhibitors, antithrombogenic agents, thrombolytic agents, fibrinolytic agents, vasospasm inhibitors, calcium channel blockers, vasodilators, antihypertensive agents, antimicrobial agents, antibiotics, inhibitors of surface glycoprotein receptors, antiplatelet agents, antimitotics, microtubule inhibitors, anti secretory agents, actin inhibitors, remodeling inhibitors, antisense nucleotides, anti metabolites, antiproliferatives, anticancer chemotherapeutic agents, anti-inflammatory steroid or non-steroidal anti-inflammatory agents, immunosuppressive agents, growth hormone antagonists, growth factors, dopamine agonists, radiotherapeutic agents, peptides, proteins, enzymes, extracellular matrix components, ACE inhibitors, free radical scavengers, chelators, antioxidants, anti polymerases, antiviral agents, photodynamic therapy agents, and gene therapy agents. 
     
     
         9 . A method according to  claim 1 , wherein the concentration of bioactive agent is about 0.01 to about 90 percent, by weight, based on the weight of the coating composition. 
     
     
         10 . A method according to  claim 1 , wherein the coating composition thickness is about 0.1 micrometers to about 100 micrometers. 
     
     
         11 . A method according to  claim 1  wherein the composition is provided in a form selected from a solution, emulsion, mixture, dispersion or blend. 
     
     
         12 . A method according to  claim 1 , wherein the surface is provided by a device that comprises a catheter or stent. 
     
     
         13 . A combination according to  claim 12 , wherein the catheter is selected from urinary catheters and intravenous catheters.