Abstract:
An implantable drug delivery device is provided with a passive flow control device is provided in the form of a valve which may assume two flow states. Flow control is achieved by duty cycling the valve using a control module which generates appropriate signals in response to an input telemetry signal corresponding to a desired flow rate. In another embodiment, a passively controlled bolus delivery device is provided to deliver a bolus of drug in addition to normal dosage.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to implantable apparatus for delivering beneficial agents, including drugs to a living body. More particularly, the present invention relates to implantable flow control devices for controlling delivery of beneficial agents to a living body. 
     2. Description of the Related Art 
     It is known to provide implanted drug infusion pumps to deliver a controlled, sustained dosage of beneficial agent or drug to the living human body. Such infusion pumps are generally classified as fixed rate infusion pumps or variable rate infusion pumps. Fixed rate infusion pumps deliver drug-carrying fluid at a preset flow rate, which cannot be changed after manufacture. Variable flow rate implantable pumps permit adjustment of the flow rate, but only prior to implantation. Readjustment of the flow rate of variable rate pumps requires removal of the pump from the patient&#39;s body and related surgery. Because of the surgical intrusiveness typically required for flow rate changes for both fixed rate and adjustable rate pumps, there has developed a trend towards selectable-rate pumps, which permit flow adjustment while the pump remains implanted in the living body. 
     Flow control in selectable rate pumps, however, is complicated by the need to limit or minimize the power consumption. To this end, there have been efforts to provide passive flow control elements on selectable rate pumps for minimizing power consumption while providing flow control. 
     For example, U.S. Pat. No. 5,820,589, to Torgerson and McMullen, the subject matter of which is incorporated herein, in its entirety, discloses the concept of an implantable pump, which is provided with a passive regulator in the form of a manifold communicating with a restrictor network, with a number (n) of bi-stable valves with two flow states, or a number (n) of multi-stable valves with a number (m) of flow states. With the bi-stable valve configuration, the combination overall allows for 2 n  flow rate options. With the multi-stable valves, the system has m n  flow rate options. Ideally, such bi-stable or multi-stable valves would have no requirement for power except during flow state changes. Power is typically provided via RF signal with suitable electronic implements provided on the pump for providing an induced voltage from the RF signal. While such known passive flow control systems provide variability in flow rates, the number of attainable flow configurations is somewhat limited. It would therefore be desirable to provide an implantable pump with a passive flow control system which provides increased adjustability in flow rates over known systems. 
     In drug infusion applications, it is frequently desirable to provide for the introduction of a drug bolus to the patient. Bolus dosage may be required, for example, when a patient&#39;s activity results in increased pain that is not adequately controlled with normal dosage. Known passive control systems do not provide for the administering of a drug bolus. Thus, there is a need to provide an implantable pump with a passive flow control system which permits the metering and delivery of a bolus of drug. 
     SUMMARY OF THE INVENTION 
     The present invention solves the aforementioned problems and others by providing an implantable drug infusion pump with a passive flow control device with increased variability in flow settings over heretofore known devices. In a preferred embodiment, the invention provides a bi-stable valve which is duty-cycled by a control module to achieve a desired average flow rate over time. The control module provides appropriate signals at appropriate times to open and close the valve to achieve a desired average flow rate over time. A flow restrictor may be provided downstream of the valve as a safety feature to limit flow or to achieve a desired flow rate range. 
     The invention also provides a drug infusion pump with a passive flow control device which provides for metering and delivery of a bolus of drug. In a preferred embodiment, a flow conduit communicates with the pressurized reservoir and with a first normally closed, bi-stable valve. The first bi-stable valve is in fluid communication with an accumulator for accumulating a bolus of drug. A second bi-stable valve isolates the drug supply stored in the accumulator from a drug delivery catheter. To meter a drug bolus into the accumulator, a control module provides an appropriate signal to open and close the first valve and permit ingress of a desired amount of drug to the accumulator. The inlet valve is closed after the bolus has accumulated. When a bolus delivery is desired, the control module delivers appropriate signals to the second valve to release the bolus from the accumulator. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     The invention will be described with reference to the drawings, which form a part of this specification. Those of ordinary skill will understand that the invention is not intended to be limited to these exemplary embodiments illustrated in the drawings, of which: 
     FIG. 1 is a diagrammatic illustration of a fluid control system according to a preferred embodiment of the invention; 
     FIG. 2 is a diagrammatic illustration of a fluid control system according to another preferred embodiment of the invention; 
     FIG. 3, is a graph of a duty cycling signal associated with the embodiment of FIG. 2; and 
     FIG. 4 is a diagrammatic illustration of a fluid control system and bolus delivery device according to another preferred embodiment of the invention. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     FIG. 1 illustrates diagrammatically the components of an implantable pump incorporating a passive flow control device  100  according to a preferred embodiment of the present invention. A pressurized reservoir  12  is provided with beneficial agent in a carrier fluid and communicates with an inlet manifold  30  for conveying fluid to a plurality of inlet branches  32  and a like plurality of valves  102 . While five valves are represented in FIG. 1, it will be understood by those of ordinary skill that any number of valves may be provided to achieve a desired range of flow rates. Associated with each valve is a fluid restrictor  104 , which is designed to provide a predetermined flow rate, usually proportional to the pressure differential across the restrictor  104 . In fluid communication with each restrictor is an outlet manifold  34  which collects the fluid flow exiting each restrictor  104  and conveys the cumulative flow through a delivery conduit  36  to a catheter (not shown) for delivery to a desired location within the body. 
     In accordance with the invention, each valve V 1 -V 5  is provided with a respective control signal along a signal path from the control module  50 . Consistent with known telemetry techniques, control module  50 , in conjunction with radio frequency (RF) receiver  16 , provides power, in the form of a voltage signal to the respective valves V 1 -V 5 . The voltage signals are preferably in the form of impulses of sufficient duration and magnitude to change the state of the valves V 1 -V 5 . Control module  50  thus generates respective signals to each of valves V 1 -V 5 , based on signals received from RF receiver  16  corresponding to a particular desired one of the available flow rate settings. 
     In accordance with the invention, the respective flow rates for restrictors R 1 -R 5  are selected to provide a desired range of flows. Typically, a flow rate range between 10 and 2000 μL/day (microliters per day) are practical for most drug administering applications. Preferably, the flow rates of restrictors R 1 -R 5  are related to provide a uniform interval of flow rate increase or decrease for changed states of valves V 1 -V 5 . For example, each restrictor may be adapted to provide twice the flow rate of the adjacent and lower flowing restrictor: restrictor R 1  may be adapted to provide a flow rate of 10 μL/day, restrictor R 2  a flow rate of 20 μL/day, restrictor R 3  a flow rate of 40 μL/day, restrictor R 4  a flow rate of 80 μL/day and restrictor R 5  a flow rate of 160 μL/day. range of 10 to 2000 μL/day, with adjustment intervals of 10 μL/day, eight restrictors and corresponding bi-stable valves would be required. 
     As will be appreciated by those of ordinary skill, the valves  102  of flow control device  100  may be implemented in micromachinery as detailed, for example, in U.S. Pat. No. 5,839,467 to Saaski et al, the subject matter of which is incorporated herein by reference in its entirety. Similarly, restrictors  104  may be provided as micromachined elements or capillary tubes, for example. Alternatively, valves  102  may be macromachined bi-stable elements, including but not limited to solenoid valves, piezoelectric operated valves, or shape memory alloy actuated valves incorporating NITONOL, for example. 
     Referring now to FIGS. 2 and 3, in accordance with another aspect of the invention, a passive flow control device provides for duty cycling a valve  202  to achieve a desired flow rate. Control module  250  is adapted to provides intermittent signals to change to state of valve  202  to achieve desired time-average flow rates. Valve  202  may be a micromachined bi-stable valve as described above with reference to FIG.  1 . Valve  202  is capable of being configured to one of two states by an appropriate electrical signal. These two states may correspond to an “open” and “closed” condition, or may correspond to two different flow rates. A flow restrictor  204  may be provided to reduce the flow through valve  202 . 
     In accordance with the present invention, control module  250  provides signals to periodically change the state of valve  202  to achieve a desired flow rate. Referring to FIG. 3, a first signal  252  is provided from control module  250  to change the state of the bi-stable valve to an open-state. For a time period, t open , the valve  202  remains open and fluid is permitted to pass at a predetermined rate to the patient&#39;s body. Then, after t open  has expired, a second signal  254  is sent by control module  250  to change the state of the bi-stable valve  202  to a closed-state, in which the valve  250  will remain for a period t closed . In accordance with the invention, the duration of the open and closed states of valve  202  are chosen to achieve a desired average flow rate over a large time interval, T. The flow restrictor  204  may be employed to reduce the flow through valve  202 , to thereby provide for more accurate control of the flow rate when the time intervals t open  and t closed  would otherwise be too small to be accurately controlled by signals from control module  250 . 
     Those of ordinary skill will recognize that a virtually infinite number of average flow rates may be selected by appropriate selection of the duration of time that the valve  202  remains in each of the two states. It will be appreciated that the duty cycling described with respect to FIGS. 2 and 3 may be used in conjunction with a number of valves in a flow control network such as that described above with respect to FIG. 1 while still falling within the scope of the invention described herein. 
     Referring now to FIG. 4, another aspect of the invention provides a passive flow control system  300  for metering and delivering a drug bolus. In addition to the flow control network described above with respect to FIG. 1, a bolus delivery component  301  in fluid communication with reservoir  12  may be employed to meter and deliver a bolus of drugs. An inlet passage  302  is provided to direct flow of drug-carrying fluid from the reservoir  12  to an inlet valve  304 . An accumulator  306  is in fluid communication with an outlet end of inlet valve  304  to permit the ingress of fluid. An outlet valve  308 , is provided at an outlet end of accumulator  306 . Inlet valve  304  and outlet valve  308  may be bi-stable valves adapted to remain in their closed positions in the absence of a signal from control module  320 . 
     In operation, upon appropriate telemetry to RF receiver  16  indicating that an operator, or the patient, has requested a bolus of drug, control module  320  provides a first signal to inlet valve  304  to maintain inlet valve  304  in an open state for a predetermined time, corresponding to the amount of drug to be included in the bolus. Under pressure from reservoir  12 , drug flows into accumulator. When the predetermined period of time has expired, inlet valve  304  closes. Subsequently, control module  320  initiates a control signal to outlet valve  308  and holds outlet valve  308  in an open state to permit the bolus of drug, which is pressurized within the accumulator, to be delivered to the outlet conduit  310 . 
     Although the preferred embodiment of this invention has been described above in some detail, it should be appreciated that a variety of embodiments will be readily apparent from the foregoing description to persons of ordinary skill. The description is intended to be illustrative of the preferred embodiment of this invention and not intended to be limiting to the scope of protection sought by the applicants, which scope is defined by the appended claims.