Antimicrobial catheters

Abstract

Antimicrobial catheters and medical devices are provided. In some aspects, a low durometer aliphatic polyether polyurethane may be impregnated with a first antimicrobial agent (e.g., minocycline and rifampin) and coated with a second antimicrobial agent (e.g., chlorhexidine, gendine, or gardine). The antimicrobial catheters may display improved flexibility and resistance to kinking. Methods of producing the antimicrobial catheters are also provided.

1 . A medical device comprising an aliphatic polyether polyurethane polymer having a durometer of A or B wherein the polyurethane is impregnated with minocycline and rifampin. 
     
     
         2 . The medical device of  claim 1 , wherein the aliphatic polyether polyurethane polymer has a durometer of A. 
     
     
         3 . The medical device of any one of  claims 1 - 2 , wherein the polyurethane is coated or impregnated with a guanidium compound. 
     
     
         4 . The medical device of  claim 3 , wherein the guanidium compound is chlorhexidine. 
     
     
         5 . The medical device of any one of  claims 1 - 4 , wherein said coating further comprises a dye. 
     
     
         6 . The medical device of  claim 5 , wherein the dye is gendine or gardine. 
     
     
         7 . The medical device of any one of  claims 1 - 3 , wherein the polyurethane is coated with gendine, gardine, or chlorohexidine. 
     
     
         8 . The medical device of  claim 7 , wherein the polyurethane is coated with gendine, gardine, and chlorohexidine. 
     
     
         9 . The medical device of  claim 3 , wherein the guanidium compound is chlorhexidine. 
     
     
         10 . The medical device of any one of  claims 1 - 4 , further comprises a dye impregnated into the polyurethane. 
     
     
         11 . The medical device of  claim 10 , wherein the dye is gendine or gardine. 
     
     
         12 . The medical device of any one of  claims 1 - 3 , wherein the polyurethane is impregnated with gendine, gardine, or chlorohexidine. 
     
     
         13 . The medical device of  claim 12 , wherein the polyurethane is impregnated with gendine, gardine, and chlorohexidine. 
     
     
         14 . The medical device of  claim 3 , wherein the coating comprises a lower alcohol. 
     
     
         15 . The medical device of any one of  claims 1 - 14 , wherein the polyurethane is impregnated with or coated with a fatty acid. 
     
     
         16 . The medical device of  claim 15 , wherein the fatty acid is caprylic acid (octanoic acid), caproic acid, lauric acid, or decanoic acid. 
     
     
         17 . The medical device of any one of  claims 1 - 16 , wherein the aliphatic polyether polyurethane polymer has a repeating unit of the formula: [—O(CH 2 ) n ] m —OC(O)NH—(CH 2 ) x —NHC(O)—; wherein n=1-4, x=1-12, m is 1-100; wherein the repeating unit repeats 1-250 times, and the terminus of the polymer is hydrogen. 
     
     
         11 . The medical device of  claim 17 , wherein m=1-50. 
     
     
         18 . The medical device of  claim 17 , wherein x=1-10. 
     
     
         19 . The medical device of  claim 17 , wherein the polymer further comprises a polymer coating comprising chlorohexidine, gendine, or gardine. 
     
     
         20 . The medical device of  claim 19 , wherein the polymer coating further comprises a polyurethane, a silicone, a vinyl, a fluoropolymer, an olefin, or a polymer blend or copolymer thereof. 
     
     
         21 . The medical device of  claim 20 , wherein the polymer coating is a polyurethane coating. 
     
     
         22 . The medical device of  claim 21 , wherein the polyurethane coating is an aliphatic polyether polyurethane. 
     
     
         23 . The medical device of  claim 21 , wherein the polyurethane coating has a durometer of A or D, or the coating comprises a blend of A and D durometer aliphatic polyether polyurethanes. 
     
     
         24 . The medical device of  claim 19 , wherein the polyurethane coating comprises a blend of A and D durometer aliphatic polyether polyurethanes. 
     
     
         25 . The medical device of any one of  claims 1 - 24 , wherein the aliphatic polyether polyurethane is comprised in a coating on the medical device. 
     
     
         26 . The medical device of any one of  claims 1 - 24 , wherein the aliphatic polyether polyurethane is not comprised in a coating on the medical device. 
     
     
         27 . The medical device of any one of  claims 1 - 24 , wherein the medical device does not comprise a penetrating or alkalizing agent. 
     
     
         28 . The medical device of any one of  claims 1 - 27 , wherein the medical device is a catheter, an endotracheal tube, a nephrostomy tube, a biliary stent, an orthopedic device, a valve, a prosthetic valve, a drainage tube, a drain, a shunt, a staple, a clip, a mesh, a film, a blood exchanging device, a port, a cardiovascular device, a defibrillator, a pacemaker lead, a wire coating, an ocular implant, an auditory implant, a cochlear implant, a dental implant, a stimulator, a drug delivery depot, a filter, a membrane, a vascular access port, a stent, an envelope, a bag, a sleeve, intravenous or other tubing, a bag, a dressing, a patch, a fiber, a pin, a vascular graft, a suture, a cardiovascular suture, or an implantable prosthesis. 
     
     
         29 . The medical device of  claim 28 , wherein the medical device is a catheter. 
     
     
         30 . The medical device of  claim 29 , wherein the catheter is a vascular catheter, a urinary catheter, an intracranial catheter, an intraspinal catheter, a peritoneal catheter, a central nervous system catheter, a cardiovascular catheter, a drainage catheter, a soaker catheter, an aspirating catheter, an intrathecal catheter, a neural catheter, a stimulating catheter, or an epidural catheter. 
     
     
         31 . The medical device of  claim 30 , wherein the catheter is a vascular catheter. 
     
     
         32 . The medical device of  claim 31 , wherein the vascular catheter is a central venous catheter, an arterial line, an pulmonary artery catheter, a peripheral venous catheter, an intravenous catheter, or an intraarterial catheter. 
     
     
         33 . The medical device of  claim 1 , wherein a surface of the polyurethane is coated with gendine, gardine, or chlorohexidine in a lower alkyl alcohol solvent. 
     
     
         34 . The medical device of  claim 1 , wherein said minocycline and rifampin have been impregnated in the polyurethane using a solution that does not comprise a penetrating or alkalizing agent. 
     
     
         35 . The medical device of  claim 1 , wherein the medical device does not comprise a penetrating or alkalizing agent. 
     
     
         36 . The medical device of any one of  claims 1 - 35 , wherein the polyurethane further comprises an additional therapeutic agent. 
     
     
         37 . The medical device of  claim 36 , wherein the additional therapeutic agent is impregnated in the polyurethane. 
     
     
         38 . The medical device of  claim 36 , wherein the additional therapeutic agent is coated on a surface of the polyurethane. 
     
     
         39 . The medical device of  claim 36 , wherein the therapeutic agent is an antimicrobial agent. 
     
     
         40 . The medical device of  claim 39 , wherein the antimicrobial agent is chlorhexidine, gendine, or gardine. 
     
     
         41 . The medical device of  claim 36 , wherein the additional therapeutic agent is a thrombin inhibitor, a platelet inhibitor, an anti-inflammatory agent, an anti-fibrotic agents, or a vasodilator. 
     
     
         42 . The medical device of  claim 41 , wherein the additional therapeutic agent is argatroban, dipyridamole, a glyceryl nitrate or mercaptoethane sulfonate (MeSNA). 
     
     
         43 . The medical device of  claim 36 , wherein the additional therapeutic agent is calcium channel blocker, or an anti-arrhythmia drug. 
     
     
         44 . The medical device of  claim 43 , wherein the additional therapeutic agent is verapamil or thioridazine. 
     
     
         45 . The medical device of any one of  claims 1 - 44 , wherein the at least a portion of the medical device is coated with a hydrogel polyetherurethane. 
     
     
         46 . The medical device of  claim 45 , wherein the hydrogel polyetherurethane is a TECOPHILIC, TECOFLEX, or a polyurethane copolymer. 
     
     
         47 . The medical device of any one of  claims 1 - 46 , wherein the medical device comprises polytetrafluoroethylene. 
     
     
         48 . The medical device of any one of  claims 1 - 46 , wherein a surface of the medical device is coated or the device is impregnated with a chelator. 
     
     
         49 . The medical device of  claim 48 , wherein the chelator is calcium disodium EDTA. 
     
     
         50 . The medical device of  claim 49 , wherein the calcium disodium EDTA is comprised in an amount of about 0.01-1.5% EDTA in a coating solution. 
     
     
         51 . The medical device of any one of  claims 1 - 49 , wherein the medical device is a catheter. 
     
     
         52 . The medical device of  claim 51 , wherein the catheter is a drainage catheter or a vascular catheter. 
     
     
         53 . The medical device of  claim 51 , wherein the catheter is impregnated or coated with chlorhexidine. 
     
     
         54 . The medical device of any one of  claims 1 - 53 , wherein the aliphatic polyether polyurethane polymer is coated on the surface of the medical device. 
     
     
         55 . A medical device comprising an aliphatic polyether polyurethane polymer having a durometer of A or B wherein the polyurethane is impregnated with chlorhexidine, gendine, or gardine. 
     
     
         56 . The medical device of  claim 55 , wherein the aliphatic polyether polyurethane is coated with a second polymer. 
     
     
         57 . The medical device of  claim 56 , wherein the second polymer is a polyurethane. 
     
     
         58 . The medical device of any one of  claims 55 - 57 , wherein the aliphatic polyether polyurethane is impregnated with chlorhexidine and gardine. 
     
     
         59 . The medical device of any one of  claims 55 - 57 , wherein the aliphatic polyether polyurethane is impregnated with chlorhexidine and gendine. 
     
     
         60 . The medical device of any one of  claims 55 - 57 , wherein the aliphatic polyether polyurethane is impregnated with chlorhexidine, gendine, and gardine. 
     
     
         61 . The medical device of any one of  claims 55 - 60 , wherein the second polymer comprises minocycline and rifampin. 
     
     
         62 . The medical device of  claim 61 , wherein the polymer is a polyurethane. 
     
     
         63 . The medical device of  claim 61 , wherein the polyurethane is an aliphatic polyether polyurethane. 
     
     
         64 . The medical device according to any one of  claims 55 - 61 , wherein the second polymer has a durometer of A or D, or the coating comprises a blend of A and D durometer aliphatic polyether polyurethanes. 
     
     
         65 . The medical device of  claim 55 , wherein the polyurethane coating comprises a blend of A and D durometer aliphatic polyether polyurethanes. 
     
     
         66 . The medical device of  claim 55 , wherein the medical device is a catheter. 
     
     
         67 . The medical device of any one of  claims 55 - 66 , wherein the at least a portion of the medical device is coated with a hydrogel polyetherurethane. 
     
     
         68 . The medical device of  claim 67 , wherein the hydrogel polyetherurethane is a TECOPHILIC, TECOFLEX, or a polyurethane copolymer. 
     
     
         69 . The medical device of any one of  claims 55 - 68 , wherein a surface of the medical device is coated or impregnated with a chelator. 
     
     
         70 . The medical device of  claim 69 , wherein the chelator is calcium disodium EDTA. 
     
     
         71 . The medical device of any one of  claims 55 - 70 , wherein the medical device is a catheter. 
     
     
         72 . The medical device of  claim 71 , wherein the catheter is a drainage catheter or a vascular catheter. 
     
     
         73 . The medical device of  claim 71 , wherein the catheter is impregnated or coated with chlorhexidine. 
     
     
         74 . The medical device of any one of  claims 55 - 73 , wherein the aliphatic polyether polyurethane polymer is coated on the surface of the medical device. 
     
     
         75 . A medical device, comprising a polymer impregnated with minocycline and rifampin, wherein a surface of the polymer is coated with a polymer coating comprising a fatty acid or a guanidium compound. 
     
     
         76 . The medical device of  claim 75 , wherein the polymer coating comprises a polyurethane, a silicone, a vinyl, a fluoropolymer, an olefin, or a polymer blend or copolymer thereof. 
     
     
         77 . The medical device of  claim 75 , wherein the polymer is polytetrafluoroethylene. 
     
     
         78 . The medical device of  claim 75 , wherein the polymer coating is a polyurethane coating. 
     
     
         79 . The medical device of  claim 78 , wherein the polyurethane coating has a durometer of A or D, or the coating comprises a blend of A and D durometer aliphatic polyether polyurethanes. 
     
     
         80 . The medical device of  claim 78 , wherein the polyurethane comprises chlorhexidine. 
     
     
         81 . The medical device of  claim 78 , wherein the fatty acid is caprylic acid (octanoic acid), caproic acid, lauric acid, or decanoic acid. 
     
     
         82 . The medical device of  claim 81 , wherein the fatty acid is capyrlic acid. 
     
     
         83 . The medical device of  claims 75 - 82 , wherein the polymer coating further comprises mercaptoethane sulfonate (MeSNA). 
     
     
         84 . The medical device of  claim 83 , wherein the medical device further comprises a thrombin inhibitor, a platelet inhibitor, an anti-inflammatory agent, an anti-fibrotic agents, or a vasodilator. 
     
     
         85 . The medical device of  claim 75 , wherein the medical device further comprises a thrombin inhibitor, a platelet inhibitor, an anti-inflammatory agent, an anti-fibrotic agents, or a vasodilator. 
     
     
         86 . The medical device of  claim 75 , wherein the polymer is polyurethane, silicone, a polyvinyl chloride (PVC), a fluoropolymer, or a polyester, or a copolymer or blend thereof. 
     
     
         87 . The medical device of any one of  claims 75 - 86 , wherein the at least a portion of the medical device is coated with a hydrogel polyetherurethane. 
     
     
         88 . The medical device of  claim 87 , wherein the hydrogel polyetherurethane is a TECOPHILIC, TECOFLEX, or a polyurethane copolymer. 
     
     
         89 . The medical device of any one of  claims 1 - 88 , wherein the medical device comprises polytetrafluoroethylene. 
     
     
         90 . The medical device of  40 - 50 . 3 , wherein the polytetrafluoroethylene is TEFLON. 
     
     
         91 . The medical device of any one of  claims 1 - 90 , wherein a surface of the medical device is coated or impregnated with a chelator. 
     
     
         92 . The medical device of  claim 91 , wherein the chelator is calcium disodium EDTA. 
     
     
         93 . The medical device of any one of  claims 1 - 92 , wherein the medical device is a catheter. 
     
     
         94 . The medical device of  claim 93 , wherein the catheter is a drainage catheter or a vascular catheter. 
     
     
         95 . The medical device of  claim 93 , wherein the catheter is impregnated or coated with chlorhexidine. 
     
     
         96 . The medical device of any one of  claims 1 - 96 , wherein the aliphatic polyether polyurethane polymer is coated on the surface of the medical device. 
     
     
         97 . An antimicrobial catheter, wherein the body of the catheter comprises an A durometer aliphatic polyether polyurethane polymer, wherein the polyurethane is impregnated either with
 (i) minocycline and rifampin; or   (ii) chlorhexidine, gendine, or gardine.   
     
     
         98 . The catheter of  claim 97 , wherein the aliphatic polyether polyurethane polymer has a repeating unit of the formula: [—O(CH 2 ) n ] m —OC(O)NH—(CH 2 ) x —NHC(O)—; wherein n=1-4, x=1-10, m is less than 100, m is greater than x, the repeating unit repeats 1-250 times, and the terminus of the polymer is hydrogen. 
     
     
         99 . The catheter of  claim 98 , wherein the repeating unit repeats 1-100 times. 
     
     
         100 . The catheter of any one of  claims 97 - 99 , wherein the at least a portion of the medical device is coated with a hydrogel polyetherurethane. 
     
     
         101 . The catheter of  claim 99 , wherein the hydrogel polyetherurethane is a TECOPHILIC or a polyurethane copolymer. 
     
     
         102 . The catheter of any one of  claims 97 - 101 , wherein a surface of the medical device is coated or impregnated with a chelator. 
     
     
         103 . The catheter of  claim 102 , wherein the chelator is calcium disodium EDTA or a citrate. 
     
     
         104 . The catheter of  claim 97 - 103 , wherein the catheter is impregnated or coated with chlorhexidine. 
     
     
         105 . The catheter of any one of  claims 97 - 104 , wherein the aliphatic polyether polyurethane polymer is coated on the surface of the medical device. 
     
     
         106 . The catheter according to any one of  claims 97 - 98 , wherein the polyurethane further comprises a polyurethane coating comprising an additional therapeutic agent. 
     
     
         107 . The catheter of  claim 106 , wherein the additional therapeutic agent is an antimicrobial agent. 
     
     
         108 . The catheter of  claim 107 , wherein the antimicrobial agent is chlorhexidine, gendine, or gardine. 
     
     
         109 . The catheter of  claim 107 , wherein the coating comprises chlorhexidine and gendine. 
     
     
         110 . The catheter of  claim 107 , wherein the coating comprises chlorhexidine and gardine. 
     
     
         111 . The catheter of  claim 107 , wherein the antimicrobial agent is minocycline or rifampin. 
     
     
         112 . The catheter of  claim 107 , wherein the coating comprises minocycline and rifampin. 
     
     
         113 . The catheter of  claim 106 , wherein the additional therapeutic agent is a thrombin inhibitor, a platelet inhibitor, or a vasodilator. 
     
     
         114 . The catheter of  claim 113 , wherein the additional therapeutic agent is argatroban, dipyridamole, a glyceryl nitrate or a thrombin inhibitor. 
     
     
         115 . The catheter according to any one of  claims 97 - 114 , wherein the catheter is a vascular catheter, a urinary catheter, an intracranial catheter, an intraspinal catheter, or an epidural catheter. 
     
     
         116 . The catheter of  claim 115 , wherein the catheter is a vascular catheter. 
     
     
         117 . The catheter of  claim 116 , wherein the vascular catheter is a central venous catheter, an arterial line, an pulmonary artery catheter, a peripheral venous catheter, an intravenous catheter, or an intraarterial catheter. 
     
     
         118 . A method of catheterization comprising inserting a catheter of any one of  claims 97 - 117  into a subject. 
     
     
         119 . The method of  claim 118 , wherein the subject is a mammal. 
     
     
         120 . The method of  claim 119 , wherein the subject is human. 
     
     
         121 . A method of producing an antimicrobial polymer, comprising:
 (a) contacting an aliphatic polyether polyurethane with a solution comprising a first lower alcohol and at least one antimicrobial agent for an amount of time sufficient to impregnate the at least one antimicrobial agent in the aliphatic polyether polyurethane; wherein the solution does not contain a penetrating agent or an alkalizing agent; and   (b) substantially drying the aliphatic polyether polyurethane.   
     
     
         122 . The method of  claim 121 , wherein the at least one antimicrobial agent is minocycline and rifampin. 
     
     
         123 . The method of  claim 121 , wherein the at least one antimicrobial agent is chlorhexidine. 
     
     
         124 . The method of  claim 123 , wherein the at least one antimicrobial agent further comprises gendine or gardine. 
     
     
         125 . The method of  claim 121 , wherein the lower alcohol is a C 1-6  alcohol. 
     
     
         126 . The method of  claim 125 , wherein the C 1-6  alcohol is methanol, ethanol, propanol, butanol, or isopropanol. 
     
     
         127 . The method of  claim 126 , wherein the lower alcohol is methanol. 
     
     
         128 . The method of  claim 121 , wherein the solution consists of the lower alcohol. 
     
     
         129 . The method of  claim 121 , further comprising:
 (c) subsequent to step (a), coating at least a portion of a surface of the aliphatic polyether polyurethane with a second solution comprising: a second lower alcohol, a second organic solvent, and an additional therapeutic compound.   
     
     
         130 . The method of  claim 129 , wherein said coating is applied to substantially all of the external surfaces of the aliphatic polyether polyurethane. 
     
     
         131 . The method of  claim 129 , wherein the second organic solvent is an aliphatic ether solvent or a chlorinated solvent. 
     
     
         132 . The method of  claim 131 , wherein the chlorinated solvent is methylene chloride or chloroform. 
     
     
         133 . The method of  claim 131 , wherein the aliphatic ether solvent is tetrahydrofuran or diethyl ether. 
     
     
         134 . The method of  claim 129 , wherein the second lower alcohol is the same alcohol as the first lower alcohol. 
     
     
         135 . The method of  claim 134 , wherein the second lower alcohol is a C 1-6  alcohol. 
     
     
         136 . The method of  claim 135 , wherein the second lower alcohol is methanol, ethanol, propanol, butanol, or isopropanol. 
     
     
         137 . The method of  claim 136 , wherein the lower alcohol is methanol. 
     
     
         138 . The method of  claim 129 , wherein the solvent is tetrahydrofuran and the second lower alcohol is methanol. 
     
     
         139 . The method of  claim 129 , wherein the additional therapeutic compound is a second antimicrobial agent. 
     
     
         140 . The method of  claim 139 , wherein the second antimicrobial agent is chlorhexidine, gendine, gardine, minocycline, or rifampin. 
     
     
         141 . The method of  claim 129 , wherein the additional therapeutic agent is a thrombin inhibitor, a platelet inhibitor, an anti-inflammatory agent, an antifibrotic agent, or a vasodilator. 
     
     
         142 . The method of  claim 141 , wherein the additional therapeutic agent is argatroban, or dipyridamole. 
     
     
         143 . The method of  claim 129 , wherein the additional therapeutic agent is calcium channel blocker or an anti-arrhythmia drug. 
     
     
         144 . The method of  claim 143 , wherein the additional therapeutic agent is verapamil or thioridazine. 
     
     
         145 . The method of  claim 129 , wherein said coating has a durometer of A or D, or the coating comprises a blend of A and D durometer aliphatic polyether-urethanes. 
     
     
         146 . The method of  claim 121 , wherein the aliphatic polyether polyurethane has a repeating unit of the formula: [—O(CH 2 ) n ] m —OC(O)NH—(CH 2 ) x —NHC(O)—; wherein n=1-4, x=1-10, m is less than 500, m is greater than x, the repeating unit repeats 1-250 times, and the terminus of the polymer is hydrogen. 
     
     
         147 . The method of  claim 146 , wherein m is 1-250. 
     
     
         148 . The method of  claim 146 , wherein the repeating unit repeats 1-100 times. 
     
     
         149 . The method of  claim 146 , wherein the resulting polyether polyurethane has a durometer of A or B. 
     
     
         150 . The method of  claim 121 , wherein the aliphatic polyether urethane polymer is comprised in a medical device or a catheter. 
     
     
         151 . The method of  claim 150 , wherein the aliphatic polyether urethane polymer is comprised in an endotracheal tube, a vascular catheter, a urinary catheter, a nephrostomy tube, a biliary stent, a peritoneal catheter, an epidural catheter, a central nervous system catheter, an intracranial catheter, an intraspinal catheter, an epidural catheter, an orthopedic device, a prosthetic valve, or a medical implant. 
     
     
         152 . The method of  claim 151 , wherein the catheter is a vascular catheter. 
     
     
         153 . The method of  claim 152 , wherein the vascular catheter is a central venous catheter, an arterial line, a pulmonary artery catheter, and a peripheral venous catheter, an intraarterial catheter, or intravenous (i.v.) tubing. 
     
     
         154 . A method of producing an antimicrobial polymer, comprising:
 (a) contacting a polymer with a solution comprising a lower alcohol, minocycline, rifampin, and an alkalizing agent for an amount of time sufficient to impregnate the minocycline and rifampin in the aliphatic polyether polyurethane;   (b) exposing the polymer to a neutralizing solution comprising an alkanoic acid for an amount of time sufficient to substantially neutralize the alkalizing agent; and   (c) substantially drying the polymer.   
     
     
         155 . The method of  claim 154 , wherein the alkalizing agent is sodium hydroxide. 
     
     
         156 . The method of  claim 154 , wherein the solution further includes a penetrating agent. 
     
     
         157 . The method of  claim 156 , wherein the penetrating agent is ethyl acetate or butyl acetate. 
     
     
         158 . The method of  claim 154 , wherein the polymer is a polyurethane. 
     
     
         159 . The method of  claim 158 , wherein the polyurethane is an aliphatic polyether polyurethane. 
     
     
         160 . The method of  claim 154 , wherein step (b) comprises neutralizing a majority or substantially all of the alkylating agent. 
     
     
         161 . The method of  claim 154 , wherein the lower alcohol is methanol. 
     
     
         162 . The method of  claim 154 , wherein the alkanoic acid is a C 1-6  alkanoic acid. 
     
     
         163 . The method of  claim 162 , wherein the C 1-6  alkanoic acid is acetic acid, formic acid, propionic or butyric acid. 
     
     
         164 . The method of  claim 163 , wherein the C 1-6  alkanoic acid is acetic acid. 
     
     
         165 . The method of  claim 154 , further comprising:
 (d) subsequent to step (a), coating at least a portion of a surface of the aliphatic polyether polyurethane with a second solution comprising: a second lower alcohol, a second organic solvent, and an additional therapeutic compound.   
     
     
         166 . The method of  claim 165 , wherein said coating is applied to substantially all of the external surfaces of the aliphatic polyether polyurethane. 
     
     
         167 . The method of  claim 165 , wherein the second organic solvent is an aliphatic ether solvent or a chlorinated solvent. 
     
     
         168 . The method of  claim 167 , wherein the chlorinated solvent is methylene chloride or chloroform. 
     
     
         169 . The method of  claim 167 , wherein the aliphatic ether solvent is tetrahydrofuran or diethyl ether. 
     
     
         170 . The method of  claim 165 , wherein the second lower alcohol is the same alcohol as the first lower alcohol. 
     
     
         171 . The method of  claim 165 , wherein the second lower alcohol is methanol. 
     
     
         172 . The method of  claim 165 , wherein the solvent is tetrahydrofuran and the second lower alcohol is methanol. 
     
     
         173 . The method of  claim 165 , wherein the additional therapeutic compound is an antimicrobial agent. 
     
     
         174 . The method of  claim 173 , wherein the antimicrobial agent is chlorhexidine, gendine, or gardine. 
     
     
         175 . The method of  claim 165 , wherein the additional therapeutic agent is a thrombin inhibitor, a platelet inhibitor, an anti-inflammatory agent, an antifibrotic agent, or a vasodilator. 
     
     
         176 . The method of  claim 165 , wherein the additional therapeutic agent is argatroban, or dipyridamole. 
     
     
         177 . The method device of  claim 165 , wherein the additional therapeutic agent is calcium channel blocker or an anti-arrhythmia drug. 
     
     
         178 . The medical device of  claim 177 , wherein the additional therapeutic agent is verapamil or thioridazine. 
     
     
         179 . The method of  claim 165 , wherein said coating has a durometer of A or D, or the coating comprises a blend of A and D durometer aliphatic polyether-urethanes. 
     
     
         180 . The method of  claim 154 , wherein the aliphatic polyether urethane polymer is comprised in a medical device or a catheter. 
     
     
         181 . The method of  claim 154 , wherein the polymer is comprised in an endotracheal tube, a vascular catheter, a urinary catheter, a nephrostomy tube, a biliary stent, a peritoneal catheter, an epidural catheter, a central nervous system catheter, an intracranial catheter, an intraspinal catheter, an epidural catheter, an orthopedic device, a prosthetic valve, or a medical implant. 
     
     
         182 . The method of  claim 181 , wherein the catheter is a vascular catheter. 
     
     
         183 . The method of  claim 182 , wherein the vascular catheter is a central venous catheter, an arterial line, a pulmonary artery catheter, and a peripheral venous catheter, an intraarterial catheter, or intravenous (i.v.) tubing. 
     
     
         184 . A catheter comprising a polymer tubing, wherein the polymer tubing is an aliphatic polyether polyurethane polymer, a polyurethane polymer coated with an aliphatic polyether polyurethane polymer, or a polytetrafluoroethylene polymer coated with an aliphatic polyether polyurethane polymer; wherein the polymer is coated or impregnated with chlorhexidine, gendine, gardine, minocycline, and/or rifampin. 
     
     
         185 . The catheter of  claim 184 , further comprising a second polymer coating on the polymer tubing. 
     
     
         186 . The catheter of  claim 185 , wherein the second polymer coating comprises an aliphatic polyether polyurethane. 
     
     
         187 . The catheter of  claim 186 , wherein the coating comprises chlorhexidine, gendine, gardine, minocycline, and/or rifampin. 
     
     
         188 . The catheter of any one of  claims 184 - 187 , wherein the device further comprises an additional therapeutic agent.