Abstract:
A tool for refilling an implantable pump having at least one reservoir. The tool includes a plurality of independent fluid channels; a fluid reservoir in fluid communication with a first one of the fluid channels; at least one pump fluidly coupled to the fluid channels, the at least one pump and the independent fluid channels differing from each other in number, wherein (i) a pump is configured to apply positive pressure to the first fluid channel so as to drive fluid from the fluid reservoir therethrough, and (ii) a pump is configured to apply negative pressure to the second fluid channel; and a connector for removably connecting the fluid channels to the at least one reservoir.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims priority to and the benefit of, and incorporates herein by reference in its entirety, U.S. Provisional Patent Application No. 61/452,399, which was filed on Mar. 14, 2011. 
     
    
     FIELD OF THE INVENTION 
       [0002]    In various embodiments, the present invention relates, generally, to implantable drug pump devices, and in particular to systems and methods for refilling such devices. 
       BACKGROUND 
       [0003]    Medical treatment often requires the administration of a therapeutic agent (e.g., medicament, drugs, etc.) to a particular part of a patient&#39;s body. As patients live longer and are more frequently diagnosed with chronic and often debilitating ailments, the result will be an increase in the need to place protein therapeutics, small-molecule drugs and other medications into targeted areas throughout the body. Some maladies, however, are difficult to treat with currently available therapies and/or require administration of drugs to anatomical regions to which access is difficult to achieve. 
         [0004]    A patient&#39;s eye is a prime example of a difficult-to-reach anatomical region, and many vision-threatening diseases, including retinitis pigmentosa, age-related macular degeneration (AMD), diabetic retinopathy, and glaucoma, are incurable and yet difficult to treat with currently available therapies. For example, oral medications have systemic side effects; topical applications may sting and engender poor compliance; injections require a medical visit, can be painful and risk infection; and sustained-release implants must typically be removed after their supply is exhausted (and generally offer limited ability to change the dose in response to the clinical situation). Another example is cancer, such as breast cancer or meningiomas, where large doses of highly toxic chemotherapies such as rapamycin or irinotecan (CPT-11) are typically administered to the patient intravenously, resulting in numerous undesired side effects outside the targeted area. Yet another example is drug delivery to the knee, where drugs often have difficulty penetrating the avascular cartilage tissue for diseases such as osteoarthritis. 
         [0005]    Implantable drug delivery systems, which may have a refillable drug reservoir, cannula and check valve, etc., generally allow for controlled delivery of pharmaceutical solutions to a specified target. As drug within the drug reservoir depletes, the physician can refill the reservoir with, for example, a syringe, via a refill port while leaving the device implanted within the patient&#39;s body. This approach can minimize the surgical incision needed for implantation and avoids future or repeated invasive surgery or procedures. 
         [0006]    Conventionally, the drug pump is refilled manually using, for example, a handheld syringe. This approach can be both inconvenient and dangerous. It is typically difficult to monitor the pressure in the syringe, and a large pressure may be generated inadvertently particularly when small volumes are involved and the syringe plunger is of small diameter. Excessive pressures can damage the pump and/or cause improper drug expulsion. Additionally, refilling the implantable pump may represent a difficult manual task. For example, the pump&#39;s refill port, which is usually located on the pump surface to facilitate post-implantation access, may be inaccessible or inconvenient to access due to the recipient&#39;s internal anatomy. This makes the refill procedure uncomfortable for the recipient and, once again, risks damage to the pump. Refilling difficulties are especially acute if the therapeutic procedure involves a multiple-drug administration which requires several cycles of needle insertion and withdrawal as different fluids are removed and injected into the pump, causing stress for both the patient and doctor and creating wear on the refill port. 
         [0007]    Consequently, there is a need for a refilling system that can monitor the pressure during drug administration and reduce the insertion frequency into the implanted pump. 
       SUMMARY 
       [0008]    In accordance with various embodiments of the invention described herein, a dedicated instrument is used to automatically facilitate a filling or refilling therapeutic procedure via, for example, a self-sealing needle-accessible refill port in an implanted drug pump. The procedure may include, for example, emptying, rinsing, and filling the drug reservoir. An instrument in accordance with the current invention may be configured such that only a single needle insertion in the fluid access refill port is required to direct multiple fluids to the implanted pump. Additionally, the instrument may include a valve, a pressure sensor and/or a flow sensor to detect and control the pressure therein. The automation and/or pressure-control of the refilling process protects pump components (e.g., the refill port or the reservoir) from potential damage and ensures reliable and repeatable drug filling. 
         [0009]    Accordingly, in one aspect, the invention pertains to a tool for refilling an implantable pump having at least one reservoir. In various embodiments, the tool includes: (i) multiple independent fluid channels, (ii) a fluid reservoir in fluid communication with a first fluid channel, and (iii) a connector for removably connecting the fluid channels to the at least one reservoir. The tool may include one or more pumps that are fluidly coupled to the fluid channels. The pump(s) may be configured to apply positive pressure to the first fluid channel so as to drive fluid from the fluid reservoir therethrough, and to apply negative pressure to a second fluid channel. 
         [0010]    The pump(s) and the independent fluid channels may differ from each other in number. For example, when there are one pump and at least two independent fluid channels, the pump may be configured to generate suction through a first one of the channels and to drive a fluid through a second one of the channels. If there is a third independent fluid channel connected to the pump, the pump may be configured to drive a second fluid through the third fluid channel. 
         [0011]    The tool may include a sensor associated with each of the channels for monitoring at least one parameter relating to liquid flowing therethrough. The sensor may be a flow sensor and/or a pressure sensor and the parameter may be a flow rate of the liquid and/or pressure in the channels, respectively. 
         [0012]    Additionally, the tool may include governing circuitry for preventing the monitored parameter from exceeding or falling below a predefined level. Two valves that are responsive to the governing circuitry may be used for controlling fluid flow through the first and second fluid channels. 
         [0013]    In a second aspect, the invention relates to a tool for refilling an implantable pump having a reservoir. The tool may include a refilling kit and a base unit. The refilling kit may have two independent fluid channels connectable at one end thereof to the reservoir. The base, which is removably connectable to the other ends of the fluid channels, may include at least one pump, a sensor for monitoring at least one parameter relating to flow through the fluid channels, and feedback circuitry for controlling flow through the fluid channels based on the monitored parameter(s). 
         [0014]    The refilling kit may be connectable to the reservoir by means, for example, of a needle configured for entering the reservoir. The needle may have separate lumens each fluidly coupled to one of the fluid channels. The tool may further include a locking system that is associated with the refilling kit for preventing injection of an unapproved fluid into the reservoir. 
         [0015]    In a third aspect, the invention relates to a method of filling an implantable drug-delivery pump having at least one reservoir. In some embodiments, the method includes the steps of: (i) fluidly coupling multiple independent fluid channels to the reservoir and (ii) operating a single pump to purge the reservoir via a first one of the multiple channels and pump fluid into the purged reservoir via a second one of the multiple fluid channels. The pump may generate suction through the first fluid channel and drives a fluid through the second fluid channel. The purging step may include causing the single pump to pump fluid into the reservoir through a third independent fluid channel and thereafter provide suction to draw the fluid from the reservoir via the first fluid channel. 
         [0016]    Reference throughout this specification to “one example,” “an example,” “one embodiment,” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the example is included in at least one example of the present technology. Thus, the occurrences of the phrases “in one example,” “in an example,” “one embodiment,” or “an embodiment” in various places throughout this specification are not necessarily all referring to the same example. Furthermore, the particular features, structures, routines, steps, or characteristics may be combined in any suitable manner in one or more examples of the technology. The headings provided herein are for convenience only and are not intended to limit or interpret the scope or meaning of the claimed technology. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0017]    In the drawings, like reference characters generally refer to the same parts throughout the different views. Also, the drawings are not necessarily to scale, with an emphasis instead generally being placed upon illustrating the principles of the invention. In the following description, various embodiments of the present invention are described with reference to the following drawings, in which: 
           [0018]      FIG. 1  schematically illustrates an implantable drug-delivery pump; 
           [0019]      FIG. 2A  schematically illustrates a filling/refilling instrument in accordance with an embodiment of the current invention; 
           [0020]      FIG. 2B  schematically depicts the filling/refilling instrument incorporating valves, sensors and a feedback system; 
           [0021]      FIG. 2C  schematically illustrates a single pump associated with two fluid channels; 
           [0022]      FIG. 2D  schematically depicts a base unit having pumps, sensors, valves and a feedback system and a filling/refilling kit having fluid channels; 
           [0023]      FIG. 3  schematically depicts the wash channel and the filling channel merged into a single channel; and 
           [0024]      FIG. 4  schematically depicts two lumens in the needle that is used to puncture the drug reservoir. 
       
    
    
     DETAILED DESCRIPTION 
       [0025]    Refer first to  FIG. 1 , which illustrates an electrolysis-actuated, implantable drug-delivery pump  100 , as described, for example, in U.S. Ser. No. 12/463,251, the entire disclosure of which is hereby incorporated by reference. As illustrated, the implantable drug pump  100  has a cannula  102  and a pair of chambers  104 ,  106  bounded by an envelope  108 . The top chamber  104  defines a drug reservoir that contains the drug to be administered in liquid form, and the bottom chamber  106  contains a liquid which, when subjected to electrolysis using electrolysis electrodes  110 , evolves a gaseous product. The two chambers are separated by a corrugated diaphragm  112 . The cannula  102  connects the top drug chamber  104  with a check valve  114  inserted at the site of administration. The envelope  108  resides within a shaped protective shell  116  made of a flexible material (e.g., a bladder or collapsible chamber) or a relatively rigid biocompatible material (e.g medical-grade polypropylene). Control circuitry  118 , a battery  120  and an induction coil  122  for power and data transmission are embedded under the parylene chambers (i.e., between the bottom wall of the electrolyte chamber  106  and the floor of the shell  116 ). One or more refill ports  124  are in fluid communication with the drug reservoir  104  and permit the drug reservoir  104  to be refillable by inserting, for example, a refill needle (not shown) therethrough. The refill port  124  may include a self-sealing material such that the needle can puncture the top surface thereof and the surface reseals itself upon removal of the needle. The self-sealing material may be able to withstand multiple punctures by the needle, and is biocompatible. Through the refill port  124 , the existing fluid in the reservoir can be removed, the reservoir washed, and a filling/refilling solution injected. Certain embodiments of the invention involve an external device that can be interfaced to the liquid containing reservoir for the automatic filling/refilling of the reservoir. 
         [0026]      FIG. 2A  depicts an instrument  200  that interfaces with and refills, for example, the implantable drug-delivery pump  100  as show in  FIG. 1  in accordance with an embodiment of the current invention. The instrument  200  may include a needle  210  piercing through the surface of the refill port  124  to facilitate the fluid communication between the drug reservoir  104  in the implantable pump  100  and the instrument  200  that has one or more independent fluid channels  212 ,  214 ,  216 . In various embodiments, the refilling process begins with removing or aspirating an expired and/or remnant fluid from the drug reservoir  104  via the lumen  218  of the needle  210  and the first channel  212  of the instrument  200  using, for example, vacuum suction generated by the first pump  220 . A wash solution in the second channel  214 , handled by the associated second pump  222 , is then drawn to the drug reservoir  104  via the lumen  218  of the needle  210  to wash away and rinse the drug reservoir  104 ; the waste from the wash-removal process is collected using the first waste channel  212  and its connected pump  220 , as described above. The wash-removal process may be repeated as many times as necessary for effectiveness. After the final waste-removal step is complete, the drug refilling solution in the third channel  216  may be injected into the drug reservoir  104  using the associated third pump  224 . As described above, during the filling/refilling process, only a single needle insertion in the fluid access refill port is required; this thus reduces the needle insertion frequency into the drug reservoir  104  of the implanted pump  100 . Additionally, if a refill procedure involves directing multiple fluids to the implanted pump  100 , a single needle insertion using the instrument  200  may suffice. In one embodiment, a drug container  226  (e.g., a vial) directly connects to the third channel  216  such that the drug flows out of the container  226  into the drug reservoir  104  via the third channel  216 , without the risks of contamination or other human error introduced when performing the intermediate step of delivering drug from a vial to the drug reservoir  104  using a needle or other delivery means. 
         [0027]    In some embodiments, as illustrated in  FIG. 2B , the fluid channels  212 ,  214 ,  216  connect to the needle  210  via valves  238 ,  240 ,  242 . Alternatively, or additionally, the valves  238 ,  240 ,  242  may be integral with the fluid channels  212 ,  214 ,  216 , and may be located anywhere along the channels. Prior to a filling/refilling process, all three valves  238 ,  240 ,  242  are initially closed when the needle  210  is inserted into the drug reservoir  104  through the refill port so that the outlet of the needle  210  is in fluid communication with the drug chamber  104  but is isolated from the rest of the system by the valves. In a first step, valve  238  connected to the first waste channel  212  is opened and any fluid that is left in the reservoir  104  is removed using, for example, suction by activating the associated pump  220 . In a second step, valve  238  is then closed and valve  240  is opened to pump a wash solution into the drug chamber  104  via the solution channel  214 ; the waste from the wash step is collected using the method described in step one. In one embodiment, the suction and wash steps are alternately and repeatedly performed (by alternately closing and opening valves  238  and  240 ). Alternatively, valve  238  may be left open during step two such that the suction is left on to perform a continuous rinse of the drug reservoir  104 . In either case, after the final waste-removal step is complete, valves  238  and  240  are closed and valve  242  is opened to fill the reservoir  104  with the drug solution via the solution channel  216  (step three). 
         [0028]    In various embodiments, the refill instrument  200  includes flow sensors  246  and/or pressure sensors  248  to monitor and control the flow rate and/or pressure, respectively, of the fluid injection and suction in each channel  212 ,  214 ,  216 . For example, flow sensors  246 , based upon thermal effects, time-of-flight, and/or pressure, as explained further below, may be employed within the channels to sense the fluidic flow. In one embodiment, flow sensors  246  based on thermal effects use a resistive heater to locally heat the fluid flowing in proximity to the sensors  246 . The temperature of the flowing fluid in the channel then provides an indication of the flow rate. For example, time-of-flight flow sensors  246  generate a tracer pulse in the fluid flowing within the channel, and then measure the time that it takes for this pulse to traverse a certain distance. This measured time is defined as the “time of flight” and corresponds to the linear fluid velocity, which may be translated into a volumetric flow rate. In another embodiment, flow sensors  246  utilize pressure sensing and are employed within the fluid channel to measure the pressure therein and, based thereon, to increase or reduce the fluid flow rate through the channels when necessary. The pressure-based flow sensors  246  may function in any of a variety of ways; for example, capacitive, piezoresistive, and piezoelectric implementations, among others known to those of ordinary skill in the art, may all be employed advantageously. In various embodiments, if one or more pressure sensors  248  are placed inside the channels  212 ,  214 ,  216 , operations of the channels associated pumps  220 ,  222 ,  224  may be adjusted to maintain an optimal pressure or pressure range during the filling/refilling process and thus avoid excess pressure, prevent damage to the pumps, and unwanted ejection of drug into the patient. 
         [0029]    A critical set of values that define the upper and lower bounds of the safe range of pressure and/or flow rate may be determined before the filling/refilling process. If the pressure and/or flow rates exceed or fall below the set critical values during the filling/refilling procedure, an alarm system may be turned on and/or a feedback system may be initiated to control the pressure and flow rate such that the pressure and flow rates inside the fluid channels  212 ,  214 ,  216  and/or the drug reservoir  104  remain within safe operational values; this prevents drug expulsion or damage to the instrument  200  and/or the drug chamber  104 . 
         [0030]    The pumps  220 ,  222 ,  224  that are in fluid communication with the fluid channels  212 ,  214 ,  216  and handle the waste solution, wash solution and filling/refilling solutions may be standard mechanical pumps (e.g., gear, diaphragm, peristaltic, syringe, etc.) or pneumatic systems that create vacuum or adjust pressure in the individual channels. Pneumatic systems may include, but are not limited to, vacuum generators, air compressors, pneumatic motors, and pneumatic actuators, etc. The pumps  220 ,  222 ,  224  work cooperatively with the flow sensors  246 , pressure sensors  248  and/or valves  238 ,  240 ,  242  to control the flow rate and/or pressure in the fluid channel  212 ,  214 ,  216  during the refilling process. In addition, the volume of fluid may be metered to prevent overfilling. If the drug reservoir  104  reaches full capacity such that the internal pressure begins to rise, pumps  220 ,  222 ,  224  may adjust the pressure such that fluid is injected less into the reservoir  104  and/or aspirated more from the reservoir  104 . In one embodiment, the fluid injection pressure is monitored and maintained below a critical value when a liquid is infused into the drug reservoir  104  pneumatically. If the pressure exceeds the critical value, a pressure-release valve (not shown) may be used to reduce the pressure inside the channel. In another embodiment, if the liquid is infused using a mechanical pump, the pressure may be monitored and controlled by a pressure sensor  248  disposed at the point of highest hydraulic pressure; a feedback system  254  (e.g., control circuitry) may then be used to prevent the pressure at this point from exceeding the critical value. In general, the feedback system  254  is typically implemented on a printed circuit board (“PCB”) and may interface with the pumps  220 ,  222 ,  224  associated with the fluid channel  212 ,  214 ,  216 , the flow sensors  246 , the pressure sensors  248  and/or the valves  238 ,  240 ,  242 . In response to the measured flow rates and/or pressures in the fluid channel, the feedback system  254  takes corrective action in order to ensure that the flow rate and/or pressure of the drug delivered through the channels remains within the critical range. For example, when receiving pressure data indicating that the pressure inside the fluid channel is too high, the feedback system  254  can automatically adjust operation of the pumps  220 ,  222 ,  224  and/or valves  238 ,  240 ,  242  to avoid excess pressure and/or maintain an optimal pressure or pressure range, thus preventing harm to the patient. The number of pumps used to drive the fluids in the channels may be different from (e.g., less than) the number of channels. For example, as depicted in  FIG. 2C , one pump  256  may be used to connect to the first waste and second wash channels  212 ,  214 : while one outlet  258  of the pump  256  generates suction such that the fluid in the drug reservoir  104  is removed, another outlet  260  of the pump  256  exerts a pressure to drive the fluid flow into the drug reservoir  104 . 
         [0031]    The feedback system  254 , pumps  220 ,  222 ,  224  that are associated with the fluid channel, the flow sensors  246  and/or the pressure sensors  248 , the valves  238 ,  240 ,  242 , and/or the channels  212 ,  214 ,  216  may be implemented as a single unit or as multiple components. Referring to  FIG. 2D , in one embodiment, the pumps  220 ,  222 ,  224 , sensors  246 ,  248  and valves  238 ,  240 ,  242  are integrated with the feedback system  254  to form a base unit  262  while the fluid channels  212 ,  214 ,  216  are combined (e.g., into a single cartridge structure) to form a filling/refilling kit  264 . The filling/refilling kit  264  may be mated with the base unit  262  and the needle  210  at the time of use. In such implementations, the filling/refilling kit  264  may be a single-use disposable component that is replaced each time a new reservoir is filled. The filling/refilling kit  264  may be provided to the end-user as a pre-filled kit or empty. In the case of an empty filling kit, fluid may be manually transferred to the kit  264  or the procedure may be performed automatically by the base unit  262 . 
         [0032]    In some embodiments, an electronic or mechanical locking system  266  is employed to prevent a user from injecting an unapproved fluid into the reservoir. The locking system may be based on, for example, electronic tags (e.g., RFID, barcodes, etc.) that are associated with the filling/refilling kit  264  described above. If improper tags are sensed, the instrument  200  may be programmed to prevent filling. 
         [0033]    Although described above is a three-channel system, one of ordinary skill in the art will understand that systems may have different numbers of channels that ultimately terminate in the needle  210  and are within the scope of the current invention. For example, fewer independently controlled fluid channels may be utilized in the current invention. Referring to  FIG. 3 , an exemplary system  300  uses two independently controlled fluid channels  310 ,  312 , where the wash channel and filling channel are merged in a single channel  312 . Therefore, instead of using a dedicated wash solution to rinse the drug reservoir  104 , the drug solution itself can be used. As a result, two independent fluid channels  310 ,  312 —channel  312  for infusing the drug and channel  310  for aspirating liquid out of the reservoir  104 —may suffice. 
         [0034]    As described above, the fluid channels may be interfaced to a flow control system ultimately terminating in a needle  210 , which is used to pierce the access port and access the fluid reservoir  104 . In one embodiment, the needle includes one lumen and all fluids from the channels travel in and out of the single lumen, as depicted in  FIGS. 2A-2D  and  3 . In another embodiment, with reference to  FIG. 4 , the needle includes two lumens  410 ,  412 , which provide two parallel, isolated paths for fluid to flow between the channels  414 ,  416 ,  418  and the drug reservoir  104 . One of these lumens, i.e., lumen  410  may be dedicated for aspiration and the other lumen, i.e., lumen  412 , may be used to infuse liquid (e.g., wash and drug solutions). During the filling/refilling procedure, all valves except valve  420  may be closed and the fluid in the reservoir  104  is removed via flowing through lumen  410 . The reservoir  104  is then washed by opening valve  422  and pumping the wash solution through lumen  412 . The waste from the washing step may then be removed through lumen  410 . Finally, after the reservoir  104  is completely washed, valves  420  and  422  may be closed and valve  424  is opened to fill/refill the drug reservoir via lumen  412 . Again, channels  416  and  418  may be merged to a single channel and the drug may serve as a rinse solution; this merged channel thus delivers the same drug solution during the filling/refilling procedure. 
         [0035]    The terms and expressions employed herein are used as terms and expressions of description and not of limitation, and there is no intention, in the use of such terms and expressions, of excluding any equivalents of the features shown and described or portions thereof. In addition, having described certain embodiments of the invention, it will be apparent to those of ordinary skill in the art that other embodiments incorporating the concepts disclosed herein may be used without departing from the spirit and scope of the invention. Accordingly, the described embodiments are to be considered in all respects as only illustrative and not restrictive.