Osmotic pump drug delivery systems and methods

Abstract

Implantable osmotic pump devices and systems include multiple osmotic pumps and/or semipermeable membranes to extend the useful life cycle and functionality of the drug delivery system. Use of an implantable system including multiple implantable osmotic pumps allows different drugs to be administered from the same implanted system. One or more of the semipermeable membranes of the system may be initially sealed by an overlying impermeable membrane upon implantation of the system into the patient. When the patient develops a tolerance to a first drug or to a first dose of the first drug, the impermeable membrane may be breached, to expose the underlying semipermeable membrane to the osmotic pressure of the patient at the implant site. This causes the infusion rate to increase, thereby providing the patient with the needed relief and/or other desired therapeutic effect. In the case of a multiple pump system, breaching an impermeable membrane may cause the infusion of a second drug. The second drug may potentiate a therapeutic effect (such as an analgesic effect) of the first drug, as is the case with Sufentanil and Clonidine.

What is claimed is:  
     
         1 . An implantable osmotic pump system, comprising: 
 a first osmotic pump including a first semipermeable membrane;    a second osmotic pump including a second semipermeable membrane, and    a single catheter attached to both the first and the second osmotic pumps.    
     
     
         2 . The pump system of  claim 1 , wherein the catheter includes a first lumen and a second lumen, the first lumen being connected to the first osmotic pump and the second lumen being connected to the second pump.  
     
     
         3 . The pump system of  claim 1 , wherein the catheter includes a single lumen with two side arms, one of the two side arms being attached to the first pump and the other of the two side arms being attached to the second pump, each of two side arms including an internal lumen that feeds into the single lumen.  
     
     
         4 . The pump system of  claim 1 , wherein the second semipermeable membrane is sealed by an impermeable membrane.  
     
     
         5 . The pump system of  claim 4 , wherein the impermeable membrane is disposed over and away from said one of the first and second semipermeable membranes so as to define a fluid tight compartment therewith, the fluid tight compartment being filled with a saturated saline solution.  
     
     
         6 . The pump system of  claim 4 , wherein the impermeable membrane is adapted to be punctured with a lancet when the pump system is implanted in a patient.  
     
     
         7 . The pump system of  claim 4 , wherein the impermeable membrane comprises at least one of titanium, stainless steel, platinum, platinum-iridium, polyethylene, PET and PETG.  
     
     
         8 . The pump system of  claim 1 , wherein the first and second pumps are preloaded with at least one pharmaceutical agent.  
     
     
         9 . The pump system of  claim 1 , wherein the first pump is preloaded with a first pharmaceutical agent at a first therapeutically effective concentration and wherein the second pump is preloaded with a second pharmaceutical agent at a second therapeutically effective concentration.  
     
     
         10 . The pump system of  claim 9 , wherein the first pharmaceutical agent is a same pharmaceutical agent as the second pharmaceutical agent.  
     
     
         11 . The pump system of  claim 10 , wherein the first concentration is a same concentration as the second concentration.  
     
     
         12 . The pump system of  claim 9 , wherein the first pharmaceutical agent is a different pharmaceutical agent than the second pharmaceutical agent.  
     
     
         13 . The pump system of  claim 9 , wherein the first pharmaceutical agent potentiates a therapeutic property of the second pharmaceutical agent.  
     
     
         14 . The pump system of  claim 9 , wherein the first pharmaceutical agent is an opioid and wherein the second pharmaceutical agent includes a drug that potentiates an analgesic property of the first pharmaceutical agent.  
     
     
         15 . The pump system of  claim 14 , wherein the first pharmaceutical agent includes Sufentanil and wherein the drug includes an alpha 2-adrenoreceptor agonist.  
     
     
         16 . The pump system of  claim 15 , wherein the alpha 2-adrenoreceptor agonist includes at least one of Clonidine and derivatives of Clonidine  
     
     
         17 . The pump system of  claim 4 , wherein the first and second pumps are preloaded with at least one pharmaceutical agent.  
     
     
         18 . The pump system of  claim 4 , wherein the first pump is preloaded with a first pharmaceutical agent at a first therapeutically effective concentration and wherein the second pump is preloaded with a second pharmaceutical agent at a second therapeutically effective concentration.  
     
     
         19 . The pump system of  claim 18 , wherein the first pharmaceutical agent is a same pharmaceutical agent as the second pharmaceutical agent.  
     
     
         20 . The pump system of  claim 19 , wherein the first concentration is a same concentration as the second concentration.  
     
     
         21 . The pump system of  claim 18 , wherein the first pharmaceutical agent is a different pharmaceutical agent than the second pharmaceutical agent.  
     
     
         22 . The pump system of  claim 18 , wherein the first pharmaceutical agent potentiates a therapeutic property of the second pharmaceutical agent.  
     
     
         23 . The pump system of  claim 18 , wherein the first pharmaceutical agent is an opioid and wherein the second pharmaceutical agent includes a drug that potentiates an analgesic property of the first pharmaceutical agent.  
     
     
         24 . The pump system of  claim 23 , wherein the first pharmaceutical agent includes Sufentanil and wherein the drug includes an alpha 2-adrenoreceptor agonist.  
     
     
         25 . The pump system of  claim 24 , wherein the alpha 2-adrenoreceptor agonist includes Clonidine.  
     
     
         26 . The pump system of  claim 4 , wherein the first pump is preloaded with a first opioid and wherein the first pump is adapted to infuse the first opioid at a first therapeutically effective range of concentration and wherein the second pump is preloaded with a second opioid and wherein the second pump is adapted to infuse the second opioid at a second therapeutically effective range of concentration after the semipermeable membrane is breached.  
     
     
         27 . The pump system of  claim 26 , wherein the first opioid includes one of Fentanyl and Sufentanil and wherein the second opioid includes one of Fentanyl and Sufentanil.  
     
     
         28 . The pump of  claim 26 , wherein the first opioid is a same opioid as the second opioid and wherein the second pump is adapted to infuse the second opioid at the first therapeutically effective range when the first pump is out of the first opioid, upon breaching the impermeable membrane.  
     
     
         29 . A kit, comprising: 
 a first osmotic pump including a first semipermeable membrane;    a second osmotic pump including a second semipermeable membrane, and    a single catheter adapted to attach to both the first and the second osmotic pumps.    
     
     
         30 . The kit of  claim 29 , wherein the catheter includes a first lumen and a second lumen, the first lumen being adapted to connect to the first osmotic pump and the second lumen being adapted to connect to the second pump.  
     
     
         31 . The kit of  claim 29 , wherein the catheter includes a single lumen with two side arms, one of the two side arms being adapted to attach to the first pump and the other of the two side arms being adapted to attach to the second pump, each of two side arms including an internal lumen that feeds into the single lumen.  
     
     
         32 . The kit of  claim 29 , wherein the second semipermeable membrane is sealed by an impermeable membrane.  
     
     
         33 . The kit of  claim 32 , wherein the impermeable membrane is disposed over and away from the said one of the first and second semipermeable membrane so as to define a fluid tight compartment therewith, the fluid tight compartment being filled with a saturated saline solution.  
     
     
         34 . The kit of  claim 32 , further including a lancet configured to breach the impermeable membrane.  
     
     
         35 . The kit of  claim 29 , wherein the first osmotic pumps is preloaded with a first pharmaceutical agent and wherein the second pump is preloaded with a second pharmaceutical agent.  
     
     
         36 . The kit of  claim 35 , wherein the first pharmaceutical agent is a same pharmaceutical agent as the second pharmaceutical agent.  
     
     
         37 . The kit of  claim 35 , wherein the first pharmaceutical agent is a different pharmaceutical agent as the second pharmaceutical agent.  
     
     
         38 . A drug delivery method, comprising the steps of: 
 infusing a first drug at a first therapeutically effective range of concentration from a first implanted osmotic pump;    infusing a second drug at a second therapeutically effective range of concentration from a second implanted osmotic pump;    preventing the first and second drugs from mixing until both the first and second drugs reach an intended delivery site.    
     
     
         39 . The method of  claim 38 , wherein the preventing step is carried out by attaching a catheter having a first and a second lumen to the first and second osmotic pumps, the first lumen being in fluid communication with the first osmotic pump and the second lumen being in fluid communication with the second osmotic pump, a free end of the catheter being disposed at the intended delivery site.  
     
     
         40 . The method of  claim 38 , wherein the first and second drugs are therapeutically effective for at least one therapy selected from pain therapy, hormone therapy, gene therapy, angiogenic therapy, anti-tumor therapy, chemotherapy and/or other pharmaceutical therapies.  
     
     
         41 . An implantable osmotic pump system, comprising: 
 a first osmotic pump, including a first semipermeable membrane; a first impermeable membrane initially sealing the first semipermeable membrane; a second semipermeable membrane and a second impermeable membrane initially sealing the second semipermeable membrane, and    a second osmotic pump, including a third semipermeable membrane; a third impermeable membrane initially sealing the third semipermeable membrane; a fourth semipermeable membrane and a fourth impermeable membrane initially sealing the fourth semipermeable membrane.    
     
     
         42 . The pump system of  claim 41 , wherein each of the first and second pumps includes a proximal end, a distal end and a side wall and wherein at least one of the first and second initially sealed semipermeable membranes is fitted to a side wall of the first pump and wherein at least one of the third and fourth initially sealed semipermeable membranes is fitted to a side wall of the second pump.  
     
     
         43 . The pump system of  claim 41 , wherein each of the first and second pumps includes a proximal and a distal end, and wherein a catheter is attached to the distal end of the first pump is and to the distal end of the second pump.  
     
     
         44 . The pump system of  claim 43 , wherein the catheter includes a first lumen and a second lumen, the first lumen being in fluid communication with a pharmaceutical agent compartment of the first pump and the second lumen being in fluid communication with a pharmaceutical agent compartment of the second pump.  
     
     
         45 . The pump system of  claim 43 , wherein the catheter includes a single lumen with two side arms, one of the two side arms being attached to the first pump and the other of the two side arms being attached to the second pump, each of two side arms including an internal lumen that feeds into the single lumen.  
     
     
         46 . The pump system of  claim 41 , wherein each of the first to fourth impermeable membranes is disposed over and away from the first to fourth semipermeable membranes, respectively, so as to define a first to fourth fluid tight compartment therewith, respectively, each of the first to fourth fluid tight compartments being filled with a saturated saline solution.  
     
     
         47 . The pump system of  claim 46 , wherein each of the first to fourth impermeable membranes is adapted to be punctured with a lancet when the pump system is implanted in a patient.  
     
     
         48 . The pump system of  claim 41 , wherein each of the first to fourth impermeable membranes comprises at least one of titanium, stainless steel platinum-iridium, polyethylene, PET and PETG.  
     
     
         49 . The pump system of  claim 41 , wherein the first and second pumps are preloaded with at least one pharmaceutical agent.  
     
     
         50 . The pump system of  claim 41 , wherein the first pump is preloaded with a first pharmaceutical agent at a first therapeutically effective concentration and wherein the second pump is preloaded with a second pharmaceutical agent at a second therapeutically effective concentration.  
     
     
         51 . The pump system of  claim 50 , wherein the first pharmaceutical agent is a same pharmaceutical agent as the second pharmaceutical agent.  
     
     
         52 . The pump system of  claim 51 , wherein the first concentration is a same concentration as the second concentration.  
     
     
         53 . The pump system of  claim 50 , wherein the first pharmaceutical agent is a different pharmaceutical agent than the second pharmaceutical agent.  
     
     
         54 . The pump system of  claim 50 , wherein the first pharmaceutical agent potentiates a therapeutic property of the second pharmaceutical agent.  
     
     
         55 . The pump system of  claim 50 , wherein the first pharmaceutical agent is an opioid and wherein the second pharmaceutical agent includes a drug that potentiates an analgesic property of the first pharmaceutical agent.  
     
     
         56 . The pump system of  claim 55 , wherein the first pharmaceutical agent includes Sufentanil and wherein the drug includes an alpha 2-adrenoreceptor agonist.  
     
     
         57 . The pump system of  claim 56 , wherein the alpha 2-adrenoreceptor agonist includes Clonidine.  
     
     
         58 . The pump system of  claim 50 , wherein the first pharmaceutical agent includes a first opioid and wherein the second pharmaceutical agent includes a second opioid.  
     
     
         59 . The pump system of  claim 58 , wherein the first opioid includes one of Fentanyl and Sufentanil and wherein the second opioid includes one of Fentanyl and Sufentanil.  
     
     
         60 . The pump system of  41 , wherein the first pump is adapted to deliver a dose of Fentanyl of about 10 to about 300 milligrams per day and wherein the second pump is adapted to deliver a dose of Sufentanil of about 1 to about 25 micrograms per day.  
     
     
         61 . The pump system of  claim 59 , wherein the second opioid includes a combination of Sufentanil and Fentanyl.  
     
     
         62 . The pump system of  claim 56 , wherein the drug includes a combination of Sufentanil and the alpha 2-adrenoreceptor agonist.  
     
     
         63 . The pump system of  claim 62 , wherein the alpha 2-adrenoreceptor agonist includes Clonidine.  
     
     
         64 . The pump system of  41 , wherein the first pump is adapted to deliver a dose of Sufentanil of about 1 to about 25 micrograms per day and wherein the second pump is adapted to deliver a dose of Clonidine of about 25 to about 150 micrograms per day.  
     
     
         65 . Method of using the pump system of  claim 50 , comprising the steps of: 
 breaching the first impermeable membrane;    implanting the pump system into a patient to start infusion of the first pharmaceutical agent at a first therapeutically effective dose;    breaching the second impermeable membrane to start infusion of the first pharmaceutical agent at a second therapeutically effective dose when the patient develops a tolerance to the first dose;    breaching the third impermeable membrane to start infusion of the second pharmaceutical agent at a third therapeutically effective dose when the patient develops a tolerance to the first pharmaceutical agent, and    breaching the fourth impermeable membrane to start infusion of the second pharmaceutical agent at a fourth therapeutically effective dose when the patient develops a tolerance to the third dose.    
     
     
         66 . The method of  claim 65 , wherein the breaching steps are carried out by puncturing the first to fourth impermeable membranes with a lancet.  
     
     
         67 . An implantable osmotic pump, comprising: 
 a pump housing having a proximal end, a distal end and a sidewall, the pump housing defining a pharmaceutical agent compartment and an osmotic agent compartment, the pharmaceutical agent compartment being separated from the osmotic agent compartment by a movable piston;    a first semipermeable membrane fitted to the proximal end and a second semipermeable membrane fitted to a portion of the sidewall defining the osmotic engine compartment, both the first and second semipermeable membranes being adapted to allow water to cross into the osmotic engine compartment;    an impermeable membrane sealing the second semipermeable membrane, and    an integrated lancet adapted to breach the impermeable membrane.    
     
     
         68 . The pump of  claim 67 , wherein the integrated lancet mechanism is adapted to breach the impermeable membrane upon a manual application of force on the mechanism.  
     
     
         69 . The pump of  claim 67 , wherein the lancet mechanism includes a spring biasing a lancet away from the impermeable membrane.  
     
     
         70 . The pump of  claim 67 , wherein the integrated lancet mechanism includes a plurality of through holes, the through holes allowing water into the mechanism and in contact with the second semipermeable membrane when the impermeable membrane is breached.  
     
     
         71 . The pump of  claim 67 , wherein the pharmaceutical agent compartment is preloaded with a pharmaceutical agent and wherein the pump is configured to infuse the pharmaceutical agent at a first rate based upon a composition, thickness and surface area of the first semipermeable membrane when the impermeable membrane is intact and is configured to infuse the pharmaceutical agent at a second infusion rate when the impermeable membrane has been breached.  
     
     
         72 . The pump of  claim 71 , wherein the second rate is based upon a composition, thickness and surface area of the first and the second semipermeable membranes.  
     
     
         73 . The pump of  claim 71 , wherein the pharmaceutical agent includes Fentanyl.  
     
     
         74 . The pump of  claim 73 , wherein each of the first and second rates is selected within the range of about 10 to about 300 milligrams per day.  
     
     
         75 . The pump of  claim 71 , wherein the pharmaceutical agent includes a combination of Fentanyl and Sufentanil.  
     
     
         76 . The pump of  claim 75 , wherein each of the first and second rates is selected within the range of about 1 to about 25 micrograms per day for Sufentanil and within the range of about 10 to about 30 milligrams per day of Fentanyl.  
     
     
         77 . The pump of  claim 71 , wherein the pharmaceutical agent includes a combination of Sufentanil and Clonidine.  
     
     
         78 . The pump of  claim 77 , wherein each of the first and second rates is selected within a range of about 1 to about 25 micrograms per day for Sufentanil and within a range of about 25 to about 150 micrograms per day for Clonidine.  
     
     
         79 . The pump of  claim 67 , wherein the pharmaceutical agent compartment is preloaded with at least one pharmaceutical agent that is therapeutically effective for at least one therapy selected from a group including pain management, hormone therapy, gene therapy, angiogenic therapy, anti-tumor therapy, chemotherapy and/or other therapies.  
     
     
         80 . A method of delivering a pharmaceutical agent, comprising the steps of: 
 implanting an osmotic pump including a first and a second semipermeable membrane, the second impermeable membrane being initially sealed by an impermeable membrane, the pump including an integrated lancet mechanism adapted to breach the impermeable membrane;    infusing the pharmaceutical agent at a first infusion rate based upon a composition, thickness and surface area of the first semipermeable membrane;    applying force to the lancet mechanism to cause the mechanism to breach the impermeable membrane and expose the initially sealed second semipermeable membrane, and    infusing the pharmaceutical agent at a second infusion rate that is higher than the first infusion rate, the second infusion rate being based upon a composition, thickness and surface area of the first and the second semipermeable membranes.    
     
     
         81 . The method of  claim 80 , wherein the force applying step is carried out while the pump is implanted.  
     
     
         82 . The method of  claim 80 , further including a step of palpating or imaging the implanted pump to locate the integrated lancet mechanism thereof prior to the force-applying step.  
     
     
         83 . An implantable osmotic pump system, comprising: 
 a pump housing having a proximal end, a distal end and a sidewall, the pump housing defining a pharmaceutical agent compartment and an osmotic agent compartment, the pharmaceutical agent compartment being separated from the osmotic agent compartment by a movable piston;    a first semipermeable membrane fitted to a portion of the sidewall defining the osmotic engine compartment, the first semipermeable membrane being adapted to allow water to cross into the osmotic engine compartment;    a first sealing member covering and sealing the first semipermeable membrane.    
     
     
         84 . The system of  claim 83 , further comprising a catheter attached to the distal end of the pump housing, the catheter being in fluid communication with the pharmaceutical agent compartment.  
     
     
         85 . The system of  claim 83 , wherein the proximal end of the pump housing is impermeable to water.  
     
     
         86 . The system of  claim 83 , wherein the first sealing member includes a spacer fitted to the sidewall, the spacer including an impermeable membrane that is adapted to be breached by a lancet.  
     
     
         87 . The system of  claim 86 , wherein the pump housing and the spacer are configured to allow the spacer to be screwed on the sidewall.  
     
     
         88 . The system of  claim 86 , wherein the spacer is fitted to the pump housing by an ultrasonic weld.  
     
     
         89 . The system of  claim 86 , wherein the impermeable membrane includes at least one of titanium and stainless steel, platinum-iridium, polyethylene, PET and PETG.  
     
     
         90 . The system of  claim 83 , further comprising: 
 at least one second semipermeable membrane fitted to the portion of the sidewall defining the osmotic engine compartment, the at least one second semipermeable membrane being adapted to allow water to cross into the osmotic engine compartment;    at least one second sealing member covering and sealing a respective one of the at least one second semipermeable membrane.    
     
     
         91 . The system of  claim 90 , wherein the first and the at least one second sealing members each include a spacer fitted to the sidewall, the spacer including an impermeable membrane that is adapted to be breached by a lancet.  
     
     
         92 . The system of  claim 91 , wherein the impermeable membrane is visible under fluoroscopy.  
     
     
         93 . The system of  claim 83 , wherein at least the portion of the sidewall defining the osmotic engine compartment is substantially flat.  
     
     
         94 . The system of  claim 83 , wherein the pump housing has a generally rectangular shape with rounded atraumatic edges.  
     
     
         95 . The system of  claim 83 , wherein the first sealing member includes a first integrated lancet mechanism attached thereto, the integrated lancet mechanism being adapted to breach the first sealing member to expose the first semipermeable membrane.  
     
     
         96 . The system of  claim 83 , wherein the pharmaceutical agent compartment is preloaded with a pharmaceutical agent and wherein the pharmaceutical agent includes Fentanyl.  
     
     
         97 . The system of  claim 96 , wherein the pump system is configured to infuse Fentanyl within a range of about 10 to about 300 milligrams per day.  
     
     
         98 . The system of  claim 96 , wherein the pump system is configured to infuse Sufentanil within a range of about 1 to about 25 micrograms per day.  
     
     
         99 . The system of  claim 83 , wherein the pharmaceutical agent compartment is preloaded with a pharmaceutical agent and wherein the pharmaceutical agent includes a combination of Fentanyl and Sufentanil.  
     
     
         100 . The system of  claim 99 , wherein the pump system is configured to infuse the combination of Fentanyl within a range of about 10 to about 300 micrograms per day and Sufentanil within a range of about 1 to about 25 micrograms per day.  
     
     
         101 . The system of  claim 83 , wherein the pharmaceutical agent compartment is preloaded with a pharmaceutical agent and wherein the pharmaceutical agent includes a combination of Sufentanil and Clonidine, the Sufentanil being infused at within a range of about 1 to about 25 micrograms per day and the Clonidine being infused within a range of about 25 to about 150 micrograms per day.  
     
     
         102 . The system of  claim 83 , wherein the pharmaceutical agent compartment is preloaded with at least one pharmaceutical agent that is therapeutically effective for at least one therapy selected from a group including pain management, hormone therapy, gene therapy, angiogenic therapy, anti-tumor therapy, chemotherapy and/or other therapies.  
     
     
         103 . The kit of  claim 37 , wherein the first pharmaceutical agent includes Fentanyl and the second pharmaceutical agent includes Sufentanil.  
     
     
         104 . The kit of  claim 37 , wherein the first pharmaceutical agent includes Sufentanil and the second pharmaceutical agent includes Clonidine.