Abstract:
According to one aspect, the invention pertains to a ureteral stent that includes a proximal retention structure configured for retaining the proximal portion in the urinary bladder, which contains a balloon reservoir for storing a pressurized fluid that contains a urologically beneficial drug. In another aspect, a ureteral stent is provided that includes a reservoir for storing a pressurized fluid that comprises a urologically beneficial drug and an outlet remote from the reservoir, wherein the outlet includes a hydrogel material that, upon implantation of the ureteral stent, shrinks as the salinity of surrounding urine drops and expands as the salinity of surrounding urine increases. In other aspects, the invention pertains to a system for introducing a urinary stent into the body of a patient. In yet other aspects, the invention pertains to methods for treating patients.

Description:
STATEMENT OF RELATED APPLICATION 
       [0001]    This application claims the benefit of U.S. Ser. No. 61/622,073, filed Apr. 10, 2012 and entitled “URETERAL STENT WITH DRUG DELIVERY RESERVOIR,” which is hereby incorporated by reference in its entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    This invention generally relates to urological medical devices and more particularly to ureteral stents for drug delivery. 
       BACKGROUND 
       [0003]    Ureteral stents are used to create a pathway for urinary drainage from the kidney to the bladder in patients with ureteral obstruction or injury or to protect the integrity of the ureter in a variety of surgical manipulations, among other uses. A number of clinical conditions can produce interruption in urine flow including, for example, intrinsic obstruction of the ureter due to tumor growth, stricture or stones, compression of the ureter due to extrinsic tumor growth, stone fragment impaction in the ureter following extracorporeal shock wave lithotripsy (ESWL), and ureteral procedures such as ureteroscopy and endopyelotomy. Stents may thus be used to treat or prevent obstructions of the ureter that disrupt the flow of urine from the corresponding kidney to the urinary bladder, which obstructions can cause urine to back up into the kidney, threatening renal function. 
       SUMMARY OF THE INVENTION 
       [0004]    According to one aspect, the invention pertains to a ureteral stent that includes a proximal portion, a distal portion, a central portion, and a proximal retention structure configured for retaining the proximal portion in the urinary bladder. The proximal retention structure includes at least one balloon reservoir for storing at least one pressurized fluid that contains a urologically beneficial drug. The central portion is configured to fit the ureter of a human patient, and the distal portion is configured to stay in the renal pelvis and prevent stent migration. The stent is a multi-lumen device that includes a urine drainage lumen and at least one drug lumen. The urine drainage lumen extends from the proximal portion to the distal portion. At least one drug lumen is in fluid communication with at least one balloon reservoir. At least one drug lumen is also in fluid communication with the exterior of the device via at least one outlet. 
         [0005]    For instance, in some specific embodiments, at least one drug lumen extends from the proximal portion to just the distal portion of the device, and the distal portion is provided with at least one outlet that provides fluid communication between at least one drug lumen and the exterior of the distal portion (i.e., the renal pelvis, when implanted). 
         [0006]    In other specific embodiments, at least one drug lumen extends from the proximal portion to just the central portion of the device, and the central portion is provided with one or more outlets that provide fluid communication between at least one drug lumen and the exterior of the central portion (i.e., the ureter, when implanted). 
         [0007]    In still other specific embodiments, at least one drug lumen extends from the proximal portion to both the central and the distal portions of the device, with the central portion being provided with one or more outlets that provide fluid communication between at least one drug lumen and the exterior of the central portion (i.e., the ureter, when implanted) and the distal portion being provided with one or more outlets that provide fluid communication between at least one drug lumen and the exterior of the distal portion (i.e., the renal pelvis, when implanted). 
         [0008]    In other aspects, the invention pertains to a system for introducing a urinary stent into the body of a patient. The system may contain, for example, (a) a urinary stent like that described above and (b) a device containing an inflation lumen for introducing into the balloon reservoir a pressurized fluid that contains a urologically beneficial drug. 
         [0009]    In yet other aspects, the invention pertains to methods for treating patients. Such methods may include, for example, (a) inserting a urinary stent like that described above into the urinary tract of a patient and (b) deploying the proximal retention structure in the urinary bladder by inflation of the balloon reservoir with a pressurized fluid that contains a urologically beneficial drug. As a result, the proximal portion is retained in the bladder and drug-containing fluid is delivered to the patient. 
         [0010]    Still other aspects of the invention pertain to a ureteral stent comprising a proximal portion, a distal portion and a central portion. The ureteral stent comprises at least one reservoir for storing at least one pressurized fluid that comprises a urologically beneficial drug, at least one outlet remote from at least one reservoir, and at least one drug delivery lumen that provides fluid communication between at least one reservoir and at least one outlet, wherein at least one outlet comprises a hydrogel material that, upon implantation of the ureteral stent, shrinks as the salinity of surrounding urine drops, thereby enlarging the size of at least one outlet, and expands as the salinity of surrounding urine increases, thereby reducing the size of at least one outlet. 
         [0011]    The above and other aspects, embodiments and advantages of the present invention will become immediately apparent to those of ordinary skill in the art upon review of the Detailed Description and any claims to follow. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0012]      FIG. 1  is a plan view of a ureteral stent and a pusher tube according to one embodiment of the invention. 
           [0013]      FIG. 2A  is a cross-sectional view of the pusher tube illustrated in  FIG. 1 , taken along line A-A. 
           [0014]      FIG. 2B  is a cross-sectional view of the ureteral stent illustrated in  FIG. 1 , taken along line B-B. 
           [0015]      FIG. 2C  is a cross-sectional view of the ureteral stent illustrated in  FIG. 1 , taken along line C-C. 
           [0016]      FIG. 2D  is a cross-sectional view of the ureteral stent illustrated in  FIG. 1 , taken along line D-D. 
           [0017]      FIG. 2E  is a cross-sectional view of the ureteral stent illustrated in  FIG. 1 , taken along line E-E. 
           [0018]      FIGS. 3A and 3B  are alternatively cross-sectional views to the cross-sectional view of  FIG. 2B . 
           [0019]      FIG. 4  illustrates a clinical application of the ureteral stent according to one embodiment of the invention. 
       
    
    
     DETAILED DESCRIPTION 
       [0020]    A more complete understanding of the present disclosure is available by reference to the following detailed description of numerous aspects and embodiments. The detailed description which follows is intended to illustrate but not limit the invention. 
         [0021]    The disclosure generally concerns a drainage device that facilitates the drainage of urine from the kidney through the ureter and into the urinary bladder and also includes a drug reservoir. 
         [0022]    Ureteral stents typically are tubular in shape, terminating in two opposing ends: a distal (kidney) end and a proximal (urinary bladder) end. One or both of the ends of the stent may have a retention structure. A distal (kidney) retention structure is designed to retain the distal end of the stent within the renal pelvis and to prevent stent migration down the ureter toward the urinary bladder. A proximal (urinary bladder) retention structure is designed to retain the proximal end of the stent within the urinary bladder and to prevent stent migration up the ureter toward the kidney. In the present disclosure, the proximal retention structure may also act as a reservoir for drugs, which may be delivered to the bladder, the ureter, the kidney or combinations thereof, including the bladder and ureter in combination, the bladder and kidney in combination, the ureter and kidney in combination, and the bladder, ureter and kidney in combination. The bladder retention structure may also be used to aid in retrieval and removal of the stent, among other uses. 
         [0023]    Throughout the discussion of the illustrative embodiments herein, it is to be understood that in the figures, like reference characters generally refer to the same parts throughout different views. 
         [0024]    Referring now to  FIG. 1 , a ureteral stent system comprising a ureteral stent  5  and pusher tube  7  in accordance with an embodiment of the present disclosure is shown. The stent  5  is suitable for use with the pusher tube  7  for implantation within the ureter of a patient, and includes a proximal portion  9 , a distal portion  12 , and a central portion  15  which extends between the proximal portion  9  and the distal portion  12 . As seen from  FIG. 4 , upon implantation, the proximal portion  9  is positioned within the bladder, distal portion  12  is positioned within the renal pelvis, and a central portion  15  is positioned within the ureter. 
         [0025]    A proximal retention structure  20  is attached to the proximal portion  9 , and the distal portion  12  comprises a retention structure  25 . Both the stent  5  and the pusher tube  7  are dimensioned to fit the anatomical requirements of each application within the body. 
         [0026]    Typically, in a ureteral application, the length of the central portion  15  ranges between about 12 cm to 35 cm, more typically about 14 cm to 30 cm. The central portion  15  typically has an outside diameter of at least about 1.0 mm to 3.3 mm, more typically about 1.3 mm to 2.7 mm (or French size 4-8). 
         [0027]    As seen further from  FIG. 4 , the proximal retention structure  20  is attached to the proximal portion  9  of sent 5 and serves to retain the proximal portion  9  of stent  5  within the urinary bladder  30 . 
         [0028]    Referring again to  FIG. 1 , the proximal retention structure  20  may be integral with, or detachable from the proximal portion  9  of the stent  5 . The proximal retention structure  20  comprises a balloon  33  and mechanism for introducing fluid into the balloon  33  such as a valve  36  as shown, or a septum, among other mechanisms. In one embodiment, the proximal retention structure  20  may at least partially surround the proximal end  23  of proximal portion  9  of stent  5 , and in other embodiments, the proximal portion  9  of stent  5  may be disposed relative to the proximal retention structure  20  such that the proximal retention structure  20  is located from between 0 and 10 mm from a proximal end  23  of the proximal portion  9  of stent  5 . 
         [0029]    In some embodiments, the proximal retention structure  20  partially surrounds the proximal portion  9  of stent  5  as shown in  FIG. 2B . In other embodiments, the proximal retention structure  20  completely surrounds the proximal portion  9  of stent  5  (see, e.g.,  FIG. 3A ). 
         [0030]    One embodiment in which the proximal retention structure  20  partially surrounds the proximal portion  9  of stent  5  is shown in  FIG. 2B , which is a cross-section taken along line B-B in  FIG. 1 . In  FIG. 2B , the proximal retention structure  20  includes a balloon  33  asymmetrically surrounding a portion of the proximal portion  9  of the stent  5 . The multi-lumen stent body  27  within the proximal portion  9  of the stent  5  may include a drainage lumen  17  which allows urine to flow along the length of the stent between the kidney and bladder. The multi-lumen stent body  27  may also include one or more inlet orifices  18   i ,  19   i  that provide fluid communication between an interior of balloon  33  and multiple drug lumens  18 ,  19  within the multi-lumen stent body  27 . As described in more detail below, in the embodiment shown, drainage lumen  17  assists with urine drainage from the kidney to the bladder, drug lumen  18  can be used to deliver drug to the ureter, and drug lumen  19  can be used to deliver drug to the kidney. Moreover, in some embodiments, a single lumen can be used to deliver drug to both the kidney and the bladder. 
         [0031]    In an alternative embodiment to  FIG. 2B  shown in  FIG. 3A , the proximal retention structure  20  includes a balloon  33  that symmetrically surrounds a portion of the proximal portion  9  of the stent  5 . For example, the balloon  33  may be in the shape of a toroid. As in  FIG. 2B , the multi-lumen stent body  27  includes a drainage lumen  17  which allows urine to flow along the length of the stent between the kidney and bladder. Moreover, the multi-lumen stent body  27  within the proximal portion  9  of the stent  5  may include one or more inlet orifices  18   i ,  19   i  that provide fluid communication between an interior of balloon  33  and one or more drug lumens  18 ,  19  within the multi-lumen stent body  27 . 
         [0032]    In another alternative embodiment to  FIG. 2B  shown in  FIG. 3B , the proximal retention structure  20  includes at least two balloons  33   a  and  33   b , each partially surrounding a portion of the proximal portion  9  of the stent  5 . As in  FIGS. 2B and 3A , the multi-lumen stent body  27  includes a drainage lumen  17  which allows urine to flow along the length of the stent between the kidney and bladder. Moreover, the multi-drug lumen stent body  27  includes multiple drug lumens  18 ,  19  and multiple in inlet orifices  18   i ,  19   i . In this embodiment, however, inlet orifice  18   i  provides fluid communication between drug lumen  18  and the interior of balloon  33   a , whereas inlet orifice  19   i  provides fluid communication between drug lumen  19  and the interior of a separate balloon  33   b . In this way, a first drug can be delivered from balloon  33   a  to drug lumen  18  and a second drug can be delivered from balloon  33   b  to drug lumen  19 . As an alternative, a first drug can be delivered at a first pressure from balloon  33   a  to drug lumen  18  and the same drug can be delivered at a second pressure from balloon  33   b  to drug lumen  19 . As another alternative, a first drug can be delivered at a first concentration from balloon  33   a  to drug lumen  18  and the same drug can be delivered at a second concentration from balloon  33   b  to drug lumen  19 . As another alternative, a sequence of drugs or drug concentrations can be delivered, first from one balloon and then from another after the erosion of one or more disintegrable plugs made of materials described below, among other materials, from the lumen(s) and/or orifice(s) associated with the second balloon. 
         [0033]    Other embodiments of the balloon  33  and multi-lumen stent construction  27  are also contemplated and the disclosure is not limited to the embodiments illustrated in FIGS.  2 B and  3 A- 3 B. 
         [0034]    Referring again to  FIG. 1 , the retention structure valve  36  may be, for example, a self-sealing valve or bi-directional valve or a uni-directional valve that is configured to receive fluid into the balloon and to prevent backflow of the fluid out of the balloon. In one embodiment, the retention structure valve  36  is biodisintegrable. In one embodiment, the retention structure valve  36  comprises a valve inlet  41  for inflation and deflation of balloon  33  with a suitable therapeutic-agent containing-fluid. With continued reference to  FIG. 1  and  FIG. 2A  (a cross-sectional view of the pusher tube illustrated in  FIG. 1 , taken along line A-A), the pusher tube  7  has two lumens, a primary pusher tube lumen  43  and an inflation lumen  45 . A port  46  is disposed at one end of the inflation lumen  45  and engages valve inlet  41  of the retention structure valve  36  for delivery of a therapeutic-agent containing-fluid into balloon  33 . Valve inlet  41  opens when engaged by port  46  of pusher tube  7 , and valve  41  will close when port  46  of pusher tube  7  is disengaged from valve inlet  41 . In another embodiment, a syringe may be used for delivery of a therapeutic-agent containing-fluid into the balloon  33  via valve inlet  41  or another mechanism, for example, via a septum (not shown). The valve inlet  41  may also be opened in some embodiments by pulling deflation suture  57  to deflate balloon  33  and allow removal of stent  5 . 
         [0035]    With continued reference to  FIG. 1 , the balloon  33  may be filled via the inflation lumen  45  of pusher tube  7  with a drug-containing fluid (e.g., a fluid containing a urologically beneficial drug such as those disclosed below, among others). In this embodiment, the balloon serves the dual function of retaining the proximal portion  9  of the stent  5  within the urinary bladder  30  and acting as a reservoir for the controlled delivery of a drug into the urinary bladder  30 . 
         [0036]    In some embodiments, drug-containing fluid contained within balloon  33  may be released into the bladder  30  through various means. For example, a small exit orifice  60  may be perforated through balloon  33  as illustrated in  FIG. 1 . In another embodiment, balloon  33  may contain a plurality of perforated orifices. In a further embodiment, balloon  33  may be constructed from a semi-permeable membrane to effect the controlled released of the contents of balloon  33  into bladder  30  by diffusion, resulting from a pressure gradient between the inside of balloon  33  and bladder  30 . In another embodiment, controlled release may be effected through valve inlet  41  of retention structure valve  36 . In still other embodiments, drug-containing fluid contained within balloon  33  is not released directly into the bladder  30 . 
         [0037]    The drug-containing fluid may also be delivered to the central portion  15  of stent  5  (and thus to the ureter) and/or to the distal portion  12  of stent  5  (and thus to the kidney). 
         [0038]    With reference to  FIGS. 2B-2E , as noted above in conjunction with  FIGS. 2B ,  3 A and  3 B, a first drug-containing fluid may be supplied to first drug lumen  18  through first inlet orifice  18   i  and a second drug-containing fluid may be supplied to second drug lumen  19  through second inlet orifice  19   i . The second drug-containing fluid may be the same as the first drug-containing fluid. Alternatively, the second drug-containing fluid may differ from the first drug-containing fluid in one or more respects, for example, selected from one or more of the following, among others: (a) the type of drug in the drug-containing fluid, (b) the concentration of drug in the drug-containing fluid and (c) the pressure of the drug-containing fluid. 
         [0039]    Drug-containing fluid is transported through drug lumens  18 ,  19  in multi-lumen stent body  27  of stent  5  in a proximal-to-distal direction. Conversely, when implanted, urine is transported through drainage lumen  17  in the multi-lumen stent body  27  of the stent  5  in a distal-to-proximal (kidney-to-bladder) direction. 
         [0040]      FIG. 2C  is a cross-section taken along line C-C in  FIG. 1  and illustrates the drainage lumen  17  and drug lumens  18 ,  19  in multi-lumen stent body  27  within the central portion  15  of stent  5 . 
         [0041]      FIG. 2D  is a cross-section taken along line D-D in  FIG. 1  at a position distal to that of  FIG. 2C . At this point, an exit orifice  18   o  in stent  5  provides fluid communication between the drug lumen  18  and the exterior of the device. Because drug lumen  18  extends from inlet orifice  18   i  to exit orifice  18   o , drug can be delivered from the balloon  33  to the exterior of the device at orifice  18   o , which corresponds to the ureter region when the stent  5  is positioned in vivo. In the embodiment shown, drug lumen  18  terminates in the multi-lumen stent body  27  at the orifice  180 . In other embodiments (not shown), drug lumen  18  extends through the multi-lumen stent body  27  to the distal portion  12  of the stent  5 . 
         [0042]    In the embodiment shown, a single exit orifice  18   o  is provided in the lateral wall of multi-lumen stent body  27 , whereas in other embodiments (not shown) multiple exit orifices can be provided (e.g., along the length of the multi-lumen stent body  27 ). In other embodiments (not shown), multiple exit orifices are provided in the lateral walls of the central portion  15  and/or distal portion  12  of multi-lumen stent body  27  (e.g., along the length of the multi-lumen stent body  27 ). 
         [0043]    Drug lumen  19  and drainage lumen  17  extend through the multi-lumen stent body  27  to the distal portion  12  of the stent  5 , more specifically, to the distal tip  26  of the stent  5 .  FIG. 2E  is a cross-section taken along line E-E in  FIG. 1  and illustrates the continued progress of drug lumen  19  and drainage lumen  17  through multi-lumen stent body  27  of stent  5  in the direction of the distal tip  26 . Drug lumen  19  opens at the distal tip  26  of the stent  5 . Because the drug lumen  19  extends from inlet orifice  19   i  to the distal tip  26  of stent  5 , drug can be delivered from the balloon  33  to the distal tip  26 , which corresponds to a position in the kidney when the stent  5  is positioned in vivo. 
         [0044]    Drainage lumen  27  also opens at distal tip  26  of stent  5 , allowing urine to pass into stent  5 . Because drainage lumen  27  extends from distal tip  26  to the proximal tip  23  of the stent, urine is allowed to pass through the length of the stent  5 . Thus, when implanted in vivo, urine is allowed to pass from the kidney through the length of the stent  5  to the bladder. 
         [0045]    In many embodiments, various components of the ureteral stent system of the disclosure (e.g., stent, balloon, valve, suture, pusher tube, etc.) are formed at least partially from polymeric materials. Polymeric materials are materials that comprise one or more polymers. Polymers may be selected, for example, from suitable members of the following, among others: polycarboxylic acid polymers and copolymers including polyacrylic acids; acetal polymers and copolymers; acrylate and methacrylate polymers and copolymers (e.g., n-butyl methacrylate); cellulosic polymers and copolymers; polyoxymethylene polymers and copolymers; polyimide polymers and copolymers such as polyether block imides, polyamidimides, polyesterimides, and polyetherimides; polysulfone polymers and copolymers including polyarylsulfones and polyethersulfones; polyamide polymers and copolymers including nylon 6,6, nylon 12, polyether-block co-polyamide polymers (e.g., Pebax® resins), polycaprolactams and polyacrylamides; polycarbonates; polyacrylonitriles; polyvinylpyrrolidones; polymers and copolymers of vinyl monomers including polyvinyl alcohols, polyvinyl halides such as polyvinyl chlorides, ethylene-vinylacetate copolymers (EVA), polyvinylidene chlorides, polyvinyl ethers such as polyvinyl methyl ethers, vinyl aromatic polymers and copolymers such as polystyrenes, styrene-maleic anhydride copolymers, vinyl aromatic-hydrocarbon copolymers including styrene-butadiene copolymers, styrene-ethylene-butylene copolymers (e.g., a polystyrene-polyethylene/butylene-polystyrene (SEBS) copolymer, available as Kraton® G series polymers), styrene-isoprene copolymers (e.g., polystyrene-polyisoprene-polystyrene), acrylonitrile-styrene copolymers, acrylonitrile-butadiene-styrene copolymers, styrene-butadiene copolymers and styrene-isobutylene copolymers (e.g., polyisobutylene-polystyrene block copolymers such as SIBS), polyvinyl ketones, polyvinylcarbazoles, and polyvinyl esters such as polyvinyl acetates; polybenzimidazoles; ionomers; polyalkyl oxide polymers and copolymers including polyethylene oxides (PEO); polyesters including polyethylene terephthalates, polybutylene terephthalates and aliphatic polyesters such as polymers and copolymers of lactide (which includes lactic acid as well as d-,l- and meso lactide), epsilon-caprolactone, glycolide (including glycolic acid), hydroxybutyrate, hydroxyvalerate, para-dioxanone, trimethylene carbonate (and its alkyl derivatives), 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, and 6,6-dimethyl-1,4-dioxan-2-one (a copolymer of polylactic acid and polycaprolactone is one specific example); polyether polymers and copolymers including polyarylethers such as polyphenylene ethers, polyether ketones, polyether ether ketones; polyphenylene sulfides; polyisocyanates; polyolefin polymers and copolymers, including polyalkylenes such as polypropylenes, polyethylenes (low and high density, low and high molecular weight), polybutylenes (such as polybut-1-ene and polyisobutylene), polyolefin elastomers (e.g., santoprene), ethylene propylene diene monomer (EPDM) rubbers, poly-4-methyl-pen-1-enes, ethylene-alpha-olefin copolymers, ethylene-methyl methacrylate copolymers and ethylene-vinyl acetate copolymers; fluorinated polymers and copolymers, including polytetrafluoroethylenes (PTFE), poly(tetrafluoroethylene-co-hexafluoropropenes) (FEP), modified ethylene-tetrafluoroethylene copolymers (ETFE), and polyvinylidene fluorides (PVDF); silicone polymers and copolymers; polyurethanes; p-xylylene polymers; polyiminocarbonates; copoly(ether-esters) such as polyethylene oxide-polylactic acid copolymers; polyphosphazines; polyalkylene oxalates; polyoxaamides and polyoxaesters (including those containing amines and/or amido groups); polyorthoesters; biopolymers; as well as blends and further copolymers of the above. 
         [0046]    The stent and distal retention structure are beneficially formed from a biostable polymeric material, for example, selected from suitable polymers set forth above. Some specific examples include the following polymers: polyurethanes (polyester polyurethanes, polyether polyurethanes, polycarbonate polyurethanes polyolefin polyurethanes, etc.), polyether-block-polyamide copolymers (e.g., poly[tetramethylene oxide]-b-polyamide-12 block copolymer, available from Elf Atochem as PEBAX), polycarbonates (e.g., bisphenol A polycarbonate), silicones (e.g., siloxanes such as polydimethylsiloxane, polydiethylsiloxane, polymethylethylsiloxane, polymethylphenylsiloxane, and polydiphenylsiloxane, etc., which are commonly covalently crosslinked), polytetrafluoroethylene, and ethylene copolymers such as ethylene-vinyl acetate copolymers (EVA), among others. 
         [0047]    For the balloon, a compliant material with a high percentage of elongation at break (e.g., at least 100%) is preferred in some embodiments. In some embodiments, a thermoplastic elastomer is used for the balloon material. Examples of thermoplastic elastomers include styrenic block copolymers, polyolefin blends, elastomeric alloys, thermoplastic polyurethanes, thermoplastic copolyesters and thermoplastic polyamides. More specific examples include polyester-based polyurethanes, polyether-based polyurethanes, polyolefin-based polyurethanes, polyester-polyether copolymers such as poly[dimethyl terephthalate]-poly[tetramethylene ether glycol] block copolymers and poly[butylene terephthalate]-poly[tetramethylene oxide] block copolymers, and polystyrene-polyolefin block copolymers such as poly(styrene-b-polyethylene/butylene-b-polystyrene) (SEBS) and poly(styrene-b-isobutylene-b-styrene)triblock copolymers (SIBS), and polyether-polyamide block copolymers such as poly[tetramethylene oxide]-block-polyamide-12 block copolymers. 
         [0048]    In some embodiments, a crosslinked elastomer (e.g., via vulcanization or another suitable process) is used for the balloon material, examples of which include silicone rubber, natural and synthetic polyisoprene, polybutadiene, chloroprene rubber, butyl rubber, halogenated butyl rubber, styrene-butadiene rubber, nitrile rubber, halogenated nitrile rubber, EPM rubber (ethylene-propylene rubber), EPDM rubber (ethylene-propylene-diene), epichlorohydrin rubber, polyacrylic rubber, fluorosilicone rubber, fluoroelastomers, perfluoroelastomers, polyether block amides, chlorosulfonated polyethylene and ethylene-vinyl acetate. 
         [0049]    Referring again to  FIGS. 1 and 4 , a clinical application of ureteral stent  5  according to the disclosure is depicted. In one embodiment of the disclosure, pusher tube  7  is used to deliver the stent  5  through a cytoscope, over a guide wire (not shown) and into the ureter  50 . In another embodiment, stent  5  is introduced endoscopically without the use of pusher tube  7 . Before stent  5  is inserted into the body, the deflated/collapsed balloon is substantially the same diameter in this deflated form as the proximal portion  9  of stent  5 . After insertion into the body, the port  46  of the inflation lumen  45 , is detachably coupled to the valve inlet  41  of retention structure valve  36  and a therapeutic-agent containing-fluid is introduced through the inflation lumen  45  to inflate balloon  33  to a suitable diameter, for instance, 10 to 60 mm, more typically about 20 to 50 mm, for retention of the proximal portion  9  of stent  5  within the urinary bladder  30 . 
         [0050]    With continued reference to  FIGS. 1 and 4 , once inflated, balloon  33  is positioned adjacent to the bladder wall  53  thereby minimizing migration of stent  5  within the ureter  50  and maintaining the central portion  15  in situ. For removal of stent  5 , a deflation suture  57  of retention structure valve  36  is pulled by an operator, thereby opening the retention structure valve  36 , dispensing the contents of balloon  33  into the urinary bladder  30 , and restoring the diameter of balloon  33  to substantially the same diameter as the proximal portion  9  of stent  5 . Further pulling of deflation suture  57  will remove stent  5  from the patient. If a substantial volume of drug remains in the balloon  33  at removal, a pusher tube  7  can be reengaged with the stent  5  over a guidewire (not shown) and the contents can be drained outside the body through inflation lumen  45 . 
         [0051]    A distal retention structure  25  may be formed by bending distal portion  12  of the stent  5  into a non-linear (e.g., curvilinear) configuration to retain the distal portion  12  of the stent  5  in the renal pelvis  70  of the kidney  65 , as depicted in  FIG. 4 . For example, the distal portion  12  may be bent into a planar or substantially planar spiral configuration, for instance, a planar spiral coil formed with one or more turns wound concentrically within the same plane. In another embodiment, a retention structure  25  is formed by shaping distal portion  12  into a helical coil formed with at least one turn. In another embodiment, a retention structure  25  is formed by shaping distal portion  12  into a curvilinear shape having less than one turn (e.g., a quarter-turn or more), such as J-shape, among many other possibilities. 
         [0052]    In one embodiment, with continued reference to  FIG. 4 , multi-lumen stent body  27  passes through the center of balloon  33  permitting drainage of urine from the kidney  65  directly into the urinary bladder  30  via the drainage lumen within the multi-lumen stent body  27 . A proximal drainage lumen valve may be disposed within proximal portion  9  of stent  5  to further enhance the comfort of the stent  5  by preventing or reducing ureteral reflux during patient voiding. The proximal drainage lumen valve may serve to prevent or reduce reflux of urine back up the ureter due to retrograde pressure that occurs during patient voiding. The proximal drainage lumen valve may be, for example, a unidirectional valve such as “duck-bill” of ball-type valve that permits fluid to flow only substantially in the distal-to-proximal direction. 
         [0053]    As previously described, one or more drugs can be delivered can be delivered using any combination of the following: 1. One or more drugs may be delivered from the balloon  33  to the bladder  30 , for example, through one or more pores in the balloon, among other routes. 2. One or more drugs can be delivered from the balloon  33  to the ureter  50 , for example, through one or more drug lumens terminating in one or more orifices in the lateral wall of multi-lumen stent body  27  within the central portion  15  of stent  5 , among other routes. 3. One or more drugs can be delivered from the balloon  33  to the kidney  65 , for example, through one or more drug lumens terminating, for example, at the distal end of the retention structure  25  or through one or more drug lumens terminating in one or more orifices in the lateral wall of multi-lumen stent body  27  within the distal portion  12  of stent  5 , among other routes. 
         [0054]    With regard to delivery to the kidney, in some embodiments, in order to increase the comfort of the patient in whom a stent is implanted or in order to treat an upper tract condition (e.g., an upper tract urothelial tumor), it is desirable to deliver drugs into the renal pelvis. A drug released in the kidney would then drain through the entire urinary tract providing increased therapy compared to delivery in the bladder alone. 
         [0055]    Because the balloon is positioned in the bladder, it is possible to provide increased delivery of drug (e.g., anesthetic agent) during voiding. Pressure increases in the bladder during voiding in order to empty the bladder. A patient with a ureteral stent implanted may experience flank pain due to urine reflux from the bladder to the kidney causing temporary hydronephrosis. Increased delivery of a discomfort reducing agent (e.g., a fast-acting anesthetic) to the kidney by an increase in pressure on the balloon reservoir during voiding may help alleviate any reflux pain. 
         [0056]    In certain embodiments, a sufficient quantity of drug is retained in balloon  33  until removal of stent  5  to hold the proximal portion  9  of stent  5  comfortably within the urinary bladder  30 . Any remaining drug may be released by the medical practitioner during removal of stent  5 , for example, by pulling the deflation suture  57 , which in turn opens valve inlet  41  of retention structure valve  36 , among other mechanisms. The surplus volume of the drug may be flushed and drained from the urinary bladder  30 , for example, through a cystoscopic sheath. 
         [0057]    Drug delivery rates will be determined by a several factors including one or more of the following factors, among others: balloon pressure, the size and number of inlet orifices, the size and number of exit orifices, and the size and number of drug lumens. 
         [0058]    In certain embodiments, the device may be configured to provide a higher rate of drug delivery immediately after implantation when the reservoir is full (e.g., when patient need for pain relief is higher), then tapering off as the reservoir empties and the pressure is lowered (e.g., as the patient accommodates to the implant). For this purpose, the balloon may be formed from a compliant material such as a thermoplastic elastomer or a chemically cross-linked elastomer selected from as those described above, among others. The particular compliance of the balloon reservoir wall may be selected to provide the desired temporal variation in drug delivery rate. 
         [0059]    In certain embodiments, the reservoir may be configured to provide a relatively constant pressure to provide a relatively continuous rate of drug delivery, for example, by selecting a highly compliant reservoir material under low elongation. 
         [0060]    The rate of delivery can also be modified over time by variation over time in the width of the drug fluid delivery path(s) within the device, for example, the width of the drug inlet orifice(s), the drug delivery lumen(s) and/or the drug exit orifices(s) in the device. 
         [0061]    In certain embodiments, the drug inlet orifice(s), the drug delivery lumen(s) and/or the drug exit orifices(s) of the device may be lined with a disintegrable material which decreases in thickness over time, thereby increasing drug release over time. An increase in lumen diameter may also be useful in offsetting a reduction pressure in the reservoir over time. Examples of disintegrable materials include disintegrable small molecule materials such as a sugars (e.g., sucrose, lactose, and the like), fatty acids and fatty acid esters, disintegrable biopolymers such as a polysaccharides and polypeptides (e.g., starch, gelatin, heparin, albumin, hyaluronic acid, and the like), and biodisintegrable synthetic polymers such as polyesters (e.g., polylactic acid, polyglycolic acid, poly(lactic acid-co-glycolic acid), etc.), poly(ortho esters) and polyanhydrides, among others. Additional disintegrable materials may be selected from suitable members of the polymers listed above. 
         [0062]    In certain embodiments, the drug inlet orifice(s), the drug delivery lumen(s) and/or the drug exit orifices(s) of the device may be lined with a hydrophilic material that increases in thickness over time, reducing drug release over time. Examples of such materials include hydrogels that comprise one or more of the following materials, among many others: polyacrylic acid, polyacrylamide, poly(polyethylene oxide), polyhydroxyethyl methacrylate, polyvinyl alcohol, polyvinyl pyrollidone, polycaprolactone, polyethylene glycol, poloxamers, and polyesters, among others. Additional materials for hydrogel formation may be selected from suitable members of the polymers listed above. 
         [0063]    In certain embodiments, the drug inlet orifice(s), the drug delivery lumen(s) and/or the drug exit orifices(s) of the device may be lined with a degradable hydrophilic material which initially increases in thickness over time (due to swelling), reducing drug release, followed by a decrease in thickness over time (due to disintegration), increasing drug release. Examples of such materials include those mentioned above and variations and modifications of the same, among others. 
         [0064]    In some embodiments, multiple layers may be selected for use from the preceding embodiments to tailor delivery characteristics. For example, alternating layers of swelling hydrogel material and disintegrating polymer material (e.g., 2 to 4 to 6 or more layers) could result in a pseudo-pulsatile drug delivery profile. 
         [0065]    Materials (e.g., hydrogels) that react to changes in the specific gravity or ionic strength of the surrounding urine by swelling or shrinking may also provide an increase or decrease in drug delivery rate based on the hydration status or urine production rate of the patient. Selected or custom hydrogels can be designed to react to an osmotic imbalance by absorbing water and swelling, or by releasing water and shrinking. For example, such hydrogels may be disposed in an exit orifice such that the orifice is reduced in size or closed upon expansion of the hydrogel and such that the orifice is opened or enlarged upon shrinkage of the hydrogel. A hydrogel could be configured to open or enlarge an exit orifice as the salinity of the surrounding urine drops (due to increased urine production from systemic hydration), or reduce or close an exit orifice as the salinity of the surrounding urine increases (due to decreased urine production from systemic dehydration). This could act to keep a drug concentration in the urinary tract more consistently within a therapeutic range thereby providing improved efficacy of the treatment. 
         [0066]    As specific examples of hydrogels for this purpose, it is noted that anionic and cationic hydrogels (e.g., hydrogels based on acidic and basic monomers) are sensitive to ionic strength (and thus urine salinity), because such ionic hydrogels can exchange ions with surrounding solution, when the ionic strength of the solution is increased or decreased. In addition, hydrogels can be sensitive to pH, particularly in the case of hydrogels based on weakly acidic and basic monomers, because the degree of ionization is controlled by pH. Monomers employed within cationic hydrogels, which are commonly crosslinked for stability, include homopolymers and copolymers based on one or more of the following: acrylamide and its derivatives such as dimethylaminopropyl acrylamide, N-isopropylacrylamide, and N,N-dimethylacrylamide, as well as allyl amine and ethylene imine, among others. Monomers employed for anionic hydrogels, which are commonly crosslinked for stability, include homopolymers and copolymers based on one or more of the following: acrylic acid and its derivatives and methacrylic acid and its derivatives, among others. 
         [0067]    As noted above, fluids comprising urologically beneficial drugs are employed in the present disclosure. In some embodiments, the drug itself may be in fluid form at room and body temperature. In other embodiments, the drug is provided in a liquid vehicle that comprises water, organic solvent, or both. The drug may be dissolved or suspended in the liquid vehicle. 
         [0068]    Urologically beneficial drugs for use in the present disclosure include agents that reduce pain and/or discomfort (also referred herein as “discomfort reducing agents”), antimicrobial agents, anti-cancer drugs, genes and gene vectors, growth factors, and combinations thereof. 
         [0069]    Discomfort reducing agents include antispasmodic agents, alpha-adrenergic blockers, corticosteroids, narcotic analgesic agents, non-narcotic analgesic agents, local anesthetic agents, and combinations thereof. 
         [0070]    Antispasmodic agents may be selected, for example, from suitable members of the following: alibendol, ambucetamide, aminopromazine, apoatropine, bevonium methyl sulfate, bietamiverine, butaverine, butropium bromide, n-butylscopolammonium bromide, caroverine, cimetropium bromide, cinnamedrine, clebopride, coniine hydrobromide, coniine hydrochloride, cyclonium iodide, difemerine, diisopromine, dioxaphetyl butyrate, diponium bromide, drofenine, emepronium bromide, ethaverine, feclemine, fenalamide, fenoverine, fenpiprane, fenpiverinium bromide, fentonium bromide, flavoxate, flopropione, gluconic acid, guaiactamine, hydramitrazine, hymecromone, leiopyrrole, mebeverine, moxaverine, nafiverine, octamylamine, octaverine, oxybutynin chloride, pentapiperide, phenamacide hydrochloride, phloroglucinol, pinaverium bromide, piperilate, pipoxolan hydrochloride, pramiverin, prifinium bromide, properidine, propivane, propyromazine, prozapine, racefemine, rociverine, spasmolytol, stilonium iodide, sultroponium, tiemonium iodide, tiquizium bromide, tiropramide, trepibutone, tricromyl, trifolium, trimebutine, n,n-1trimethyl-3,3-diphenyl-propylamine, tropenzile, trospium chloride, and xenytropium bromide, among others, as well as combinations and pharmaceutically acceptable salts, esters and other derivatives of the same. 
         [0071]    Examples of alpha-adrenergic blockers for use in the present disclosure may be selected from suitable members of the following: alfuzosin, amosulalol, arotinilol, dapiprazole, doxazosin, ergoloid mesylates, fenspiride, idazoxan, indoramin, labetalol, manotepil, naftopidil, nicergoline, prazosin, tamsulosin, terazosin, tolazoline, trimazosin, and yohimbine, among others, as well as combinations and pharmaceutically acceptable salts, esters and other derivatives of the same. Of these, tamsulosin, alfuzosin, doxazosin, prazosin, tamsulosin and terazosin are alpha-1-adrenergic blockers, of which tamsulosin and alfuzosin are selective alpha-1-adrenergic blockers. 
         [0072]    Examples of corticosteroids for use in the present disclosure may be selected from suitable members of the following: betamethasone, cortisone, dexamethasone, deflazacort, hydrocortisone, methylprednisolone, prednisolone, prednisone and triamcinolone, among others, as well as combinations and pharmaceutically acceptable salts, esters and other derivatives of the same. 
         [0073]    Examples of narcotic analgesic agents for use in the present disclosure may be selected from suitable members of the following: codeine, morphine, fentanyl, meperidine, propoxyphene, levorphanol, oxycodone, oxymorphone, hydromorphone, pentazocine, and methadone, among others, as well as combinations and pharmaceutically acceptable salts, esters and other derivatives of the same. 
         [0074]    Examples of non-narcotic analgesic agents for use in the present disclosure may be selected from suitable members of the following: analgesic agents such as acetaminophen, and non-steroidal anti-inflammatory drugs such as aspirin, diflunisal, salsalate, ibuprofen, ketoprofen, naproxen, indomethacin, celecoxib, valdecoxib, diclofenac, etodolac, fenoprofen, flurbiprofen, ketorolac, meclofenamate, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, sulindac, tolmetin, and valdecoxib, among others, as well as combinations and pharmaceutically acceptable salts, esters and other derivatives of the same. 
         [0075]    Examples of local anesthetic agents for use in the present disclosure may be selected from suitable members of the following: benzocaine, cocaine, lidocaine, mepivacaine, and novacaine, among others, as well as combinations and pharmaceutically acceptable salts, esters and other derivatives of the same. 
         [0076]    The term “antimicrobial agent” as used herein means a substance that kills microbes and/or inhibits the proliferation and/or growth of microbes, particularly bacteria, fungi and yeast. Antimicrobial agents, therefore, include biocidal agents and biostatic agents as well as agents that possess both biocidal and biostatic properties. In the context of the present disclosure, the antimicrobial agent kills microbes and/or inhibits the proliferation and/or growth of microbes on and around the surfaces of the implanted or inserted urological medical device, and can therefore inhibit biofilm formation (encrustation) in some cases. 
         [0077]    Antimicrobial agents may be selected, for example, from triclosan, chlorhexidine, nitrofurazone, benzalkonium chlorides, silver salts and antibiotics, such as rifampin, gentamicin and minocycline, and combinations thereof, among others. 
         [0078]    Further antimicrobial agents may be selected, for example, from suitable members of the following: the penicillins (e.g., penicillin G, methicillin, oxacillin, ampicillin, amoxicillin, ticarcillin, etc.), the cephalosporins (e.g., cephalothin, cefazolin, cefoxitin, cefotaxime, cefaclor, cefoperazone, cefixime, ceftriaxone, cefuroxime, etc.), the carbapenems (e.g., imipenem, metropenem, etc.), the monobactems (e.g., aztreonem, etc.), the carbacephems (e.g., loracarbef, etc.), the glycopeptides (e.g., vancomycin, teichoplanin, etc.), bacitracin, polymyxins, colistins, fluoroquinolones (e.g., norfloxacin, lomefloxacin, fleroxacin, ciprofloxacin, enoxacin, trovafloxacin, gatifloxacin, etc.), sulfonamides (e.g., sulfamethoxazole, sulfanilamide, etc.), diaminopyrimidines (e.g., trimethoprim, etc.), rifampin, aminoglycosides (e.g., streptomycin, neomycin, netilmicin, tobramycin, gentamicin, amikacin, etc.), tetracyclines (e.g., tetracycline, doxycycline, demeclocycline, minocycline, etc.), spectinomycin, macrolides (e.g., erythromycin, azithromycin, clarithromycin, dirithromycin, troleandomycin, etc.), and oxazolidinones (e.g., linezolid, etc.), among others, as well as combinations and pharmaceutically acceptable salts, esters and other derivatives of the same. 
         [0079]    Examples of anticancer drugs include alkyating agents such as mechlorethamine, nitrosoureas (carmustine, lomustine), melphalan, cyclophosphamide, busulfan and procarbazine, antimetabolites such as methotrexate, 6-thioguanine, 5-fluorouracil, 6-mercaptopurine, cytosine arabinoside, gemcitabine, fludarabine and capecitabine, antimitotics such as vincristine, vinblastine, paclitaxel and docetaxel, hormones such as estrogens, prednisone, goserelin, anti-estrogen (tamoxifen), flutamide, leuprolide, immunosuppressives such as azathioprine, tacrolimus (FK506), cyclosporin a, natural products such as dactinomycin, bleomycin, camptothecin and analogs (e.g., irinotecan and topotecan), daunorubicin, mitomycin C, doxorubicin, etoposide (VP-16), and other agents such as hydroxyurea, asparaginase, amsacrine, cisplatin, carboplatin, mitoxantrone and imatinib. 
         [0080]    It is will be apparent to those skilled in the art that various modifications and variations can be made to the structure and methodology of the present invention without departing from the scope or spirit of the invention.