Cerebrospinal fluid shunt having long term anti-occlusion agent delivery

Abstract

The invention includes a shunt for at least partial implantation into a patient that includes an elongated conduit having at least one lumen therethrough, that includes a proximal end for receipt of bodily fluids for flow through the shunt and a distal end for discharge of the bodily fluids from the shunt, and a long term source of at least one occlusion resistant agent, wherein said at least a portion of the at least one occlusion resistant agent can permeate through at least a portion of the elongated conduit. The invention also includes kits and systems.

1 . A shunt for at least partial implantation into a patient comprising:
 an elongated conduit having at least one lumen therethrough, wherein said elongated conduit comprises a proximal end for receipt of bodily fluids for flow through said shunt and a distal end for discharge of said bodily fluids from said shunt; and   a long term source of at least one occlusion resistant agent, wherein said at least a portion of said at least one occlusion resistant agent can permeate through at least a portion of the elongated conduit.   
   
   
       2 . The shunt according to  claim 1  wherein the long term source comprises a refill port that is in fluid communication with the lumen of the elongated conduit. 
   
   
       3 . The shunt according to  claim 2 , wherein the refill port includes a percutaneous access port. 
   
   
       4 . The shunt according to  claim 1  wherein said elongated conduit comprises at least two lumens therethrough. 
   
   
       5 . The shunt according to  claim 4 , wherein said at least two lumens comprise:
 a fluid conduit that functions as a conduit for the at least one occlusion resistant agent;   and a drainage conduit that functions as a conduit for CSF drainage.   
   
   
       6 . The shunt according to  claim 5 , wherein the fluid conduit comprises a surface through which the at least one occlusion resistant agent can permeate. 
   
   
       7 . The shunt according to  claim 5  further comprising a refill port that is in fluid communication with the fluid conduit. 
   
   
       8 . The shunt according to  claim 7 , wherein the refill port includes a percutaneous access port. 
   
   
       9 . The shunt according to  claim 5 , wherein at least a portion of the fluid conduit contains at least one absorptive agent and the at least one occlusion resistant agent. 
   
   
       10 . The shunt according to  claim 9 , wherein the absorptive agent is alumina, silica, activated charcoal, cross-linked polystyrene beads, high molecular weight gels, silicone polyurethanes, open-celled foams or some combination thereof. 
   
   
       11 . The shunt according to  claim 4 , wherein at least a portion of the fluid conduit contains a saturated solution that includes the at least one occlusion resistant agent. 
   
   
       12 . The shunt according to  claim 11 , wherein the at least one occlusion resistant agent has a solubility of less than 1 mg/mL in water. 
   
   
       13 . The shunt according to  claim 11 , wherein the at least one occlusion resistant agent is rapamycin. 
   
   
       14 . The shunt of  claim 1  further comprising at least one valve. 
   
   
       15 . The shunt of  claim 1  wherein the occlusion-resistant material comprises an immunosuppressive, an anti-inflammatory, an anti-neoplastic, a radiation emitting material, an anti-angiogenic, an anti-coagulant, an anti-proliferative, an anti-thrombogenic, an anti-oxidant, a cyclooxygenase inhibitor, a calcium entry blocker, an anti-neoplastic, an anti-mitotic, an anti-microbial, a nitric oxide donor, a cell cycle inhibitor, an anti-cancer agent, an anti-arthritis agent, an anti-diabetic agent, a thrombin inhibitor, a thrombolytic, an antibiotic, an antiviral agent, a gene therapy agent, or some combination thereof. 
   
   
       16 . The shunt of  claim 15  wherein the occlusion-resistant material includes a material selected from the group consisting of beta-radiation emitting isotopes, dexamethasone, beclomethasone, cortisone, hydrocortisone, prednisone, methylprednisone, fluorometholone, tranilast, ketoprofen, curcumin, cyclosporin A, deoxyspergualin, FK506, sulindac, myriocin, 2-aminochromone (U-86983), colchicines, pentosan, antisense oligonucleotides, mycophenolic acid, paclitaxel, etoposide, actinomycin D, camptothecin, carmustine, methotrexate, adriamycin, mitomycin, cis-platinum, mitosis inhibitors, vinca alkaloids, tissue growth factor inhibitors, platinum compounds, cytotoxic inhibitors, alkylating agents, antimetabolite agents, tacrolimus, rapamycin, azathioprine, recombinant or monoclonal antibodies to interleukins, T-cells, B-cells, and receptors, bisantrene, retinoic acid, tamoxifen, compounds containing silver, doxorubicin, azacytidine, homoharringtonine, selenium compounds, superoxide-dismutase, interferons, heparin, rapamycin ABT-578 and analogs, homologs, derivatives or combinations of the above group. 
   
   
       17 . The shunt of  claim 16  wherein the occlusion resistant material includes a material selected from the group consisting of mycophenolic acid, rapamycin, rapamycin ABT-578, derivatives or combinations thereof. 
   
   
       18 . The shunt of  claim 16  wherein the occlusion resistant material includes mycophenolic acid. 
   
   
       19 . The shunt of  claim 16  wherein the occlusion resistant material includes a combination of mycophenolic acid and, rapamycin or rapamycin ABT-578. 
   
   
       20 . The shunt of  claim 15  wherein the occlusion-resistant material permeates at different rates at different portions of the shunt. 
   
   
       21 . A shunt for at least partial implantation into a patient comprising:
 an elongated conduit having a fluid conduit and a drainage conduit, wherein said elongated conduit comprises a proximal end for receipt of bodily fluids for flow through said shunt and a distal end for discharge of said bodily fluids from said shunt; and   a long term source of at least one occlusion resistant agent, wherein said at least a portion of said at least one occlusion resistant agent can permeate through at least a portion of the elongated conduit,   wherein said fluid conduit functions as a conduit for the at least one occlusion resistant agent and the drainage conduit functions as a conduit for CSF drainage, and   wherein at least a portion of the fluid conduit contains at least one absorptive agent and the at least one occlusion resistant agent.   
   
   
       22 . The shunt according to  claim 21 , wherein the absorptive agent is alumina, silica, activated charcoal, cross-linked polystyrene beads, high molecular weight gels, silicone polyurethanes, open-celled foams or some combination thereof. 
   
   
       23 . The shunt according to  claim 21 , wherein at least a portion of the fluid conduit contains a saturated solution that includes the at least one occlusion resistant agent. 
   
   
       24 . The shunt according to  claim 23 , wherein the at least one occlusion resistant agent has a solubility of less than 1 mg/mL in water. 
   
   
       25 . The shunt according to  claim 23 , wherein the at least one occlusion resistant agent is rapamycin. 
   
   
       26 . The shunt of  claim 21  further comprising at least one valve. 
   
   
       27 . A kit comprising:
 a shunt for at least partial implantation into a patient comprising:
 an elongated conduit having at least one lumen therethrough, wherein said elongated conduit comprises a proximal end for receipt of bodily fluids for flow through said shunt and a distal end for discharge of said bodily fluids from said shunt; and 
 a long term source of at least one occlusion resistant agent, wherein said at least a portion of said at least one occlusion resistant agent can permeate through at least a portion of the elongated conduit; 
   a valve; and   a distal catheter.   
   
   
       28 . The kit according to  claim 27 , wherein the long term source comprises a refill port that is in fluid communication with the lumen of the elongated conduit. 
   
   
       29 . The kit according to  claim 28 , wherein the refill port includes a percutaneous access port. 
   
   
       30 . The kit according to  claim 27  wherein said elongated conduit comprises at least two lumens therethrough. 
   
   
       31 . The kit according to  claim 30 , wherein said at least two lumens comprise:
 a fluid conduit that functions as a conduit for the at least one occlusion resistant agent;   and a drainage conduit that functions as a conduit for CSF drainage.   
   
   
       32 . The kit according to  claim 31 , wherein the fluid conduit comprises a surface through which the at least one occlusion resistant agent can permeate. 
   
   
       33 . The kit according to  claim 31  further comprising a refill port that is in fluid communication with the fluid conduit. 
   
   
       34 . The kit according to  claim 33 , wherein the refill port includes a percutaneous access port. 
   
   
       35 . The kit according to  claim 31 , wherein at least a portion of the fluid conduit contains at least one absorptive agent and the at least one occlusion resistant agent. 
   
   
       36 . The kit according to  claim 35 , wherein the absorptive agent is alumina, silica, activated charcoal, cross-linked polystyrene beads, high molecular weight gels, silicone polyurethanes, open-celled foams or some combination thereof. 
   
   
       37 . The kit according to  claim 30 , wherein at least a portion of the fluid conduit contains a saturated solution that includes the at least one occlusion resistant agent. 
   
   
       38 . The kit according to  claim 37 , wherein the at least one occlusion resistant agent has a solubility of less than 1 mg/mL in water. 
   
   
       39 . The kit according to  claim 37 , wherein the at least one occlusion resistant agent is rapamycin.