Methods and implantable devices and systems for long term delivery of a pharmaceutical agent

Abstract

Implantable devices and osmotic pump and catheter systems for delivering a pharmaceutical agent to a patient at selectable rates include an impermeable pump housing and a moveable partition disposed within the housing, the partition dividing the housing into an osmotic driving compartment having an open end and a pharmaceutical agent compartment having a delivery orifice. A plurality of semi permeable membranes may be disposed in the open end of the osmotic driving compartment and a number of impermeable barriers may seal selected ones of the plurality of semi permeable membranes from the patient until breached. Breaching one or more of the impermeable barriers increases the surface area of semi permeable membrane exposed to the patient and controllably increases the delivery rate of the pharmaceutical agent through the delivery orifice and catheter. Each of the plurality of semi permeable membranes may have a selected surface area, composition and/or thickness, to allow a fine-grained control over the infusion rate while the pump is implanted in the patient.

What is claimed is:  
     
         1 . An implantable osmotic pump for delivering a pharmaceutical agent to a patient, comprising: 
 a pump housing;    a moveable partition disposed within the housing, the partition dividing the housing into an osmotic driving compartment having an open end and a pharmaceutical agent compartment having a delivery orifice;    a first semi permeable membrane disposed in the open end of the osmotic driving compartment, the first semi permeable membrane being exposed to the patient;    a second semi permeable membrane disposed in the open end of the osmotic driving compartment, and    a first impermeable barrier disposed over the second semi permeable membrane, the second semi permeable membrane being sealed from the patient until the first barrier is breached, wherein breaching the first barrier increases the surface area of semi permeable membrane exposed to the patient and increases a delivery rate of the pharmaceutical agent through the delivery orifice.    
     
     
         2 . The pump of  claim 1 , wherein the first impermeable barrier includes at least one of titanium and stainless steel.  
     
     
         3 . The pump of  claim 1 , further comprising a saturated solution including NaCl between the first impermeable barrier and the second semi permeable membrane.  
     
     
         4 . The pump of  claim 1 , wherein the first and second semi permeable membranes have a same composition.  
     
     
         5 . The pump of  claim 1 , wherein the first and second semi permeable membranes have a same thickness.  
     
     
         6 . The pump of  claim 1 , wherein the first and second semi permeable membranes have mutually different compositions.  
     
     
         7 . The pump of  claim 1 , wherein the first and second semi permeable membranes have mutually different thickness.  
     
     
         8 . The pump of  claim 1 , further including: 
 a third semi permeable member, and    a second impermeable barrier nested within the first impermeable barrier, the second impermeable barrier being disposed over the third semi permeable membrane, the third semi permeable membrane being sealed from the patient until the second impermeable barrier is breached, wherein breaching the second barrier increases the surface area of semi permeable membrane exposed to the patient and increases a delivery rate of the pharmaceutical agent through the delivery orifice.    
     
     
         9 . The pump of  claim 8 , further comprising a saturated solution including NaCl between the second barrier and the third semi permeable membrane.  
     
     
         10 . The pump of  claim 1 , wherein the pharmaceutical agent compartment contains sufentanil.  
     
     
         11 . The pump of  claim 10 , wherein the sufentanil is at a concentration selected between about 200 μg/mL and about 15,000 μg/mL.  
     
     
         12 . The pump of  claim 1 , wherein the daily delivery rate of the pharmaceutical agent through the delivery orifice is selected from about: 
 0.5 micrograms per day to about 25 micrograms per day when the pump is configured to be implanted intraventricularly;    0.5 micrograms per day to about 50 micrograms per day when the pump is configured to be implanted intrathecally;    5 micrograms per day to about 300 micrograms per day when the pump is configured to be implanted epidurally, and 10 micrograms per day to about 300 micrograms per day when the pump is configured to be implanted subcutaneously.    
     
     
         13 . The pump of  claim 1 , wherein the first and second semi permeable membranes include cellulose acetate.  
     
     
         14 . The pump of  claim 1 , wherein the first semi permeable membrane is shaped as a torus and is disposed adjacent an outer periphery of the first impermeable barrier and wherein the second semi permeable membrane is disposed in a center opening of the torus.  
     
     
         15 . The pump of  claim 1 , further comprising a catheter coupled to the delivery orifice.  
     
     
         16 . The pump of  claim 15 , wherein the catheter has an inner diameter of between about 0.001 inches and about 0.010 inches.  
     
     
         17 . The pump of  claim 15 , wherein the catheter includes a guidewire lumen and a pharmaceutical agent infusion lumen.  
     
     
         18 . The pump of  claim 17 , wherein the pharmaceutical agent infusion lumen has an inner diameter selected between about 0.001 inches to about 0.010 inches.  
     
     
         19 . The pump of  claim 15 , wherein the catheter and the pump are dimensioned to infuse a volume of pharmaceutical agent of between about 1 μL/day and about 10 μL/day over a treatment period.  
     
     
         20 . The pump of  claim 15 , wherein the catheter and the pump are dimensioned to infuse a dose of pharmaceutical agent of between about 0.5 μg/day and about 300 μg/day over a treatment period.  
     
     
         21 . The pump of  claim 15 , wherein at least a portion of the catheter is radiopaque.  
     
     
         22 . The pump of  claim 17 , wherein the guidewire lumen includes a valve to prevent back flow of fluid into the guidewire lumen.  
     
     
         23 . A method for achieving an analgesic effect in a patient, the method comprising the step of administering a therapeutically effective dose of a sufentanil-containing analgesic to the patient using a device that is fully implanted in the patient.  
     
     
         24 . The method of  claim 23 , wherein the dose is administered one of intravascularly, subcutaneously, epidurally, intrathecally and intraventricularly.  
     
     
         25 . The method of  claim 23 , further comprising the step of selectively increasing the dose in a stepwise manner over a treatment period without removing the device from the patient.  
     
     
         26 . The method of  claim 25 , wherein the dose is administered using an implanted osmotic pump that includes a first semi permeable membrane exposed to the patient and a second semi permeable membrane initially not exposed to the patient and wherein the increasing step includes a step of exposing the second semi permeable membrane to the patient.  
     
     
         27 . The method of  claim 26 , wherein the second semi permeable membrane exposing step includes a step of breaching an impermeable barrier sealing the second semi permeable membrane from the patient.  
     
     
         28 . The method of  claim 27 , wherein the breaching step includes a step of puncturing the impermeable barrier using a lancet while the pump remains implanted in the patient.  
     
     
         29 . The method of  claim 23 , wherein the therapeutically effective dose is selected within the range of about 0.5 μg/day to about 300 μg/day.  
     
     
         30 . A method for achieving an analgesic effect in a patient, the method comprising intraspinal administration of a therapeutically-effective dose of an analgesic to the patient by an osmotic pump and catheter integrated combination, the pump including a first semi permeable membrane across which an osmotic pressure gradient develops when the pump is implanted in the patient.  
     
     
         31 . The method of  claim 30 , further including the step of selectively increasing a surface area of semi permeable membrane exposed to the patient in a stepwise manner.  
     
     
         32 . The method of  claim 30 , wherein the analgesic includes sufentanil.  
     
     
         33 . The method of  claim 30 , further including a second semi permeable membrane and wherein the surface area of semi permeable membrane exposed to the patient is increased by breaching an impermeable barrier initially sealing the second semi permeable membrane from the patient.  
     
     
         34 . The method of  claim 33 , wherein the impermeable barrier is breached by puncturing the impermeable barrier.  
     
     
         35 . The method of  claim 31 , wherein the dose is increased in a stepwise manner by sequentially breaching one of a plurality of nested impermeable barriers disposed over a corresponding plurality of the semi permeable membranes, each sequential breach exposing additional surface area of semi permeable membrane to the patient.  
     
     
         36 . The method of  claim 35 , wherein each of the plurality of nested barriers is configured to be breached by a lancet, an outer diameter of the lancet determining which of the plurality of nested barriers is breached.  
     
     
         37 . The method of  claim 30 , wherein the analgesic is administered one of intravascularly, subcutaneously, epidurally and intrathecally.  
     
     
         38 . The method of  claim 33 , wherein the second semi permeable membrane has one of a same and different composition as the first semi permeable membrane.  
     
     
         39 . The method of  claim 33 , wherein the second semi permeable membrane has one of a same and different thickness as the first semi permeable membrane.  
     
     
         40 . An integrated implantable pump and catheter system for delivering a dose of sufentanil to a patient over a treatment period, comprising: 
 a pump housing;    a moveable partition disposed within the housing, the partition dividing the housing into an driving engine compartment and a pharmaceutical agent compartment having a delivery orifice;    a catheter coupled to the delivery orifice, and a preloaded amount of sufentanil in the pharmaceutical agent compartment.    
     
     
         41 . The system of  claim 40 , wherein the pump and catheter are dimensioned to deliver sufentanil at an infusion rate of about 0.5 μg/day to about 300 μg/day over a treatment period.  
     
     
         42 . The system of  claim 40 , wherein the system further includes a mechanical infusion rate selection structure configured to allow the infusion rate of the pump to be increased while the system is implanted in the patient.  
     
     
         43 . The system of  claim 40 , wherein the infusion rate selection feature includes a plurality of semi permeable membranes across each of which osmotic pressure develops when selectively and sequentially exposed to the patient.  
     
     
         44 . The system of  claim 43 , wherein each of the plurality of semi permeable membranes has a selected thickness, composition and surface area, the selected thickness, composition and surface area contributing to a rate at which the sufentanil is infused into the patient.  
     
     
         45 . A kit comprising: 
 an osmotic pump;    sufentanil preloaded in the osmotic pump, and    a delivery catheter configured to be coupled to the osmotic pump.    
     
     
         46 . The kit of  claim 45 , wherein the osmotic pump includes a mechanical infusion rate selection structure.  
     
     
         47 . The kit of  claim 45 , and further comprising a lancet configured to act upon the infusion rate selection structure to increase an infusion rate of the sufentanil through the delivery catheter.  
     
     
         48 . The kit of  claim 45 , wherein the pump is configured to deliver sufentanil at an infusion rate of a bout 0.5 μg/day to about 300 μg/day over a treatment period.  
     
     
         49 . The kit of  claim 45 , wherein the catheter includes a guidewire lumen and a sufentanil delivery lumen.  
     
     
         50 . The kit of  claim 49 , further comprising a guidewire.  
     
     
         51 . The kit of  claim 49 , further comprising: 
 a guidewire;    a needle, and    a splittable introducer.    
     
     
         52 . The kit of  claim 51 , wherein the needle is one of a hypodermic needle and a non-coring needle.  
     
     
         53 . A kit comprising: 
 an osmotic pump that includes a mechanical infusion rate selection structure;    an amount of pharmaceutical agent preloaded into the pump, and    a delivery catheter.    
     
     
         54 . The kit of  claim 53 , wherein the pharmaceutical agent includes sufentanil.  
     
     
         55 . The kit of  claim 53 , wherein the infusion rate selection structure is configured to allow the infusion rate to be increased while the pump is implanted into a patient.  
     
     
         56 . The kit of  claim 53 , wherein the infusion rate selection structure includes a plurality of semi permeable membranes, each of which being selectably exposable to the patient to increase a dose of pharmaceutical agent delivered to the patient.  
     
     
         57 . The kit of  claim 56 , wherein each of the plurality of semi permeable membranes has an individually selected thickness, composition and surface area.  
     
     
         58 . A method of delivering a pharmaceutical agent to a patient, comprising the steps of: 
 implanting an osmotic pump within the patient, the osmotic pump including the pharmaceutical agent and a plurality of semi permeable membranes across which osmotic pressure develops when exposed to the patient, and    controlling a surface area of semi permeable membrane exposed to the patient to control an infusion rate of the pharmaceutical agent analgesic to the patient.    
     
     
         59 . The method of  claim 58 , further comprising the step of controlling at least one of a thickness and a composition of each of the plurality of semi permeable membranes.