Abstract:
An implantable medication delivery device that is highly space efficient and can reliably and safely deliver controlled medication doses to a target site. The system includes a variable volume medication reservoir that is exposed to an ambient pressure equal to the ambient pressure at a system outlet port. A pump/valve subassembly is provided to draw medication from the reservoir and force a medication dose along a fluid transfer passageway to the outlet port. The pump/valve subassembly incorporates a safety mechanism, e.g., a balanced valve, which normally blocks medication flow to the outlet port and opens only in response to a pump induced unbalancing force. A protective shell is also disclosed for protecting the ambient reservoir.

Description:
RELATED APPLICATIONS  
       [0001]     This application claims the benefit of U.S. Application 60/383,237 filed on 22 May 2002. 
     
    
     FIELD OF THE INVENTION  
       [0002]     The present invention is directed to implantable medication delivery devices useful for delivering prescribed medication doses to targeted body sites.  
       BACKGROUND OF THE INVENTION  
       [0003]     Commercially available implantable medication delivery devices are exemplified by a Synchromed product marketed by Medtronic (of Minneapolis, Minn., USA) and a MIP product manufactured by Minimed, now a division of Medtronic. Both of these devices employ a medication reservoir comprising a bellows that contracts as medication is extracted by a pump mechanism. The reservoir volume change is accommodated by a second chamber which contains a propellant such as Freon in a gas/liquid equilibrium. The propellant functions to maintain a constant absolute pressure at body temperature. In the case of the MIP product, the propellant is a liquid at body temperature creating a negative pressure reservoir. In the case of the Syncromed product, the propellant is a gas at body temperature creating a positive pressure reservoir. In both cases, the medication reservoir is maintained at a constant absolute pressure by the propellant. Although the reservoir, and therefore the inlet side of the pump mechanism are at a constant absolute pressure, the tip of an output catheter and thus the outlet of the pump mechanism, are at ambient pressure. Ambient pressure typically varies as a function of environmental conditions including local barometric pressure and altitude, etc. In addition, variations in temperature can produce variations in reservoir pressure. The combined effect of these conditions can produce pressure differences in excess of 500 millibars across the pump mechanism. In order to seal and pump across a pressure difference of this magnitude, these exemplary systems require pumps of a size which are not well suited for implantation in space limited sites, e.g., the brain, eye, or ear.  
       SUMMARY OF THE INVENTION  
       [0004]     The present invention is directed to a medication delivery device comprising an ambient reservoir and housing integrated so as to be highly space efficient for reliably and safely delivering controlled medication doses to a target body site. Devices in accordance with the invention include a mounting structure for supporting a reservoir peripheral wall which includes a movable, e.g., flexible, portion. The reservoir wall has an outer surface exposed to an ambient pressure (equal to the pressure at the tip of an output catheter) which establishes the same pressure within the reservoir interior volume. As a consequence of the reservoir and catheter tip being at the same pressure, the pump size and energy requirements are reduced as compared to the aforementioned exemplary prior art systems.  
         [0005]     In accordance with the invention, the reservoir wall encloses a variable volume for storing medication. The movable reservoir wall portion can be formed of flaccid nonextensible nonporous material or, alternatively, can be formed by a bellows or telescoping tubular sections. The mounting structure for supporting the reservoir wall preferably incorporates a pump/valve subassembly operable to draw medication from the reservoir via a fluid inlet and force medication along a fluid transfer passageway to an outlet port adapted to be coupled to the output catheter.  
         [0006]     In order to reliably use an ambient pressure reservoir, a device in accordance with the invention is configured to prevent medication leakage (or flowthrough), i.e., unintended medication discharge through the outlet port, as a result of reservoir overfill and/or a pressure or force being applied to the reservoir. More particularly, it is unacceptable for medication to be discharged as a result of the reservoir wall being pressed, e.g., as a consequence of the patient being bumped. Thus, in accordance with a first preferred embodiment, the aforementioned pump/valve subassembly incorporates a safety mechanism which functions to normally block unintended fluid flow to the outlet port. One preferred safety mechanism in accordance with the invention uses a balanced valve which responds to a difference between the reservoir pressure and a pump chamber pressure. That is, an increase in reservoir pressure acts in a direction to seal closed the safety mechanism valve whereas an increase in pump chamber pressure acts to open the valve to effectively disable its normal blocking function.  
         [0007]     In accordance with an alternative and/or additional feature for preventing medication flowthrough, a protective substantially rigid shell is mounted around the reservoir wall to prevent the inadvertent application of a force thereto. In order to maintain ambient pressure in the reservoir, the shell is configured to allow body fluid to enter and exit the shell to enable the reservoir to expand (when being filled with medication) and contract (as medication is being discharged). In accordance with a second preferred embodiment, the shell includes a diffusive membrane (e.g., cellulose acetate membrane) that permits body fluid to flow slowly into the shell interior volume but prevents undesirable tissue growth therein. The shell preferably also includes a check valve which permits relatively rapid fluid outflow to permit the reservoir to fill and expand within the shell interior volume.  
         [0008]     A preferred mounting structure in accordance with the invention supports the reservoir wall and functionally integrates the pump/valve subassembly. The pump/valve subassembly includes an inlet port and a fluid passageway extending to an outlet port. A first check valve, permitting fluid inflow only is included in the passageway downstream from the fluid inlet. A pump chamber is included in the passageway between the first check valve and a safety mechanism located upstream from the outlet port. A pump element coupled to the pump chamber is operable to produce (1) a suction for drawing medication past the first check valve into the pump chamber and (2) a pressure for expelling medication from the pump chamber toward said safety mechanism.  
         [0009]     As previously mentioned, the safety mechanism is provided to prevent unintended medication flow to the outlet port. The safety mechanism includes a valve element movable between (1) a flow position and (2) a flow-block position. In a preferred embodiment, the safety valve element is normally in the flow-block position. However, a pressure increase in the pump chamber produced by the pump element acts to move the safety valve element to the flow position thus temporarily disabling the flow blocking function. 
     
    
     BRIEF DESCRIPTION OF THE FIGURES  
       [0010]      FIG. 1  is a schematic block diagram of a basic ambient pressure medication delivery system;  
         [0011]      FIG. 2  is a schematic block diagram similar to  FIG. 1  modified to represent two alternative features for preventing medication discharge as a consequence of a force applied to the medication reservoir, namely (1) a safety mechanism responsive to an applied force for blocking flow to the output port and (2) a protective shell mounted around the reservoir;  
         [0012]      FIG. 3  is an isometric exterior view of a preferred implantable medication delivery system in accordance with the present invention;  
         [0013]      FIG. 4  is a cross-sectional view showing the system of  FIG. 3  implanted at an exemplary site in a patient&#39;s body for infusing medication into the patient&#39;s brain;  
         [0014]      FIG. 5  is an exterior side view of a preferred embodiment showing exemplary dimensions;  
         [0015]      FIG. 6  is a horizontal sectional view taken substantially along the plane  6 - 6  of  FIG. 5 ;  
         [0016]      FIG. 7  is a vertical sectional view taken substantially along the plane  7 - 7  of  FIG. 6 ;  
         [0017]      FIG. 8  is an enlarged sectional view showing a preferred pump/valve assembly in accordance with a first embodiment of the invention;  
         [0018]      FIG. 9  is a plan view of a second embodiment of the invention incorporating a protective shell around the reservoir;  
         [0019]      FIG. 10  is a sectional view taken substantially along the plane  10 - 10  of  FIG. 9 ; and  
         [0020]      FIG. 11  is a sectional view of an alternative preferred embodiment of this invention. 
     
    
     DETAILED DESCRIPTION  
       [0021]     Attention is initially directed to  FIG. 1  which schematically depicts an implantable medication delivery system  20  including a variable volume reservoir  24  for storing medication. The reservoir  24  is preferably refillable, e.g., via a fill device  26  and tube  28  coupled to a reservoir fill port  30 . The fill device  26  preferably defines a conical entrance  32  for guiding the needle of a syringe (not shown) through a self healing septum  34  to a channel  36  and check valve  38 . The outlet of check valve  38  is coupled via nipple  40  to the upstream end of tube  28 . The downstream end of tube  28  is coupled to the reservoir fill port  30 .  
         [0022]     The variable volume reservoir  24  is comprised of a wall  42  including at least a portion supported for movement to enable the reservoir interior volume  44  to expand and contract. Although the reservoir  24  is most simply formed of flexible, or flaccid, nonextensible nonporous material forming a sack, it can also be provided in various alternative configurations. For example, the reservoir  24  can be configured as a bellows, telescoping tubular sections, or as a shaped rubber boot having a stiffened base such that the base lifts and the boot&#39;s sidewall rolls upon itself, as the reservoir interior volume changes.  
         [0023]     The reservoir outlet  46  is coupled via a fluid passageway  48  to a system output port  50 . The system output port  50  is typically coupled to a catheter  52  whose downstream end, or tip  54 , is intended to infuse medication into targeted body tissue, e.g., brain tissue, blood or intraperitoneal space. The fluid passageway  48  is comprised of a first, or upstream, check valve  56  which leads to an entrance port  58  of a pump chamber  60 . A pump chamber exit port  62  is coupled to a second, or downstream, check valve  64  which leads to the aforementioned system output port  50 .  
         [0024]     The pump chamber  60  is defined by a peripheral wall  68  including a movable portion, e.g., a piston or diaphragm  70 . The diaphragm  70  is coupled to an actuator  72  configured to displace the diaphragm  70  reciprocally between a first position which contracts the volume of the pump chamber  60  and a second position which expands the volume of the chamber  60 . Thus, when the diaphragm  70  moves downwardly as represented in  FIG. 1 , the pump chamber  60  will expand in volume creating a negative pressure which draws medication from the interior reservoir volume  44  past the check valve  56  into the pump chamber  60 . On the other hand, when the diaphragm  70  moves upwardly, as represented in  FIG. 1 , a portion, or dose, of the medication in chamber  60  will be expelled through exit port  62  past check valve  64  to the system output port  50 .  
         [0025]     A system of the type represented in  FIG. 1  is intended in accordance with the invention to be implanted in a patient&#39;s body such that the reservoir wall  42  and the catheter tip  54  are both exposed to substantially the same ambient pressure. An isometric exterior view of an exemplary embodiment  80  in accordance with the invention is shown in  FIG. 3 . Note that the embodiment  80  includes a housing  82  carrying an integrated reservoir  84 , analogous to the aforedisccussed reservoir  24 , of  FIG. 1 . Also note that a catheter tube  86 , analogous to the aforementioned catheter tube  52 , extends outwardly from the housing  82 . Further note that a fill device  88 , analogous to aforedisccussed fill device  26 , is coupled to the housing  82  via a fill tube  90 .  
         [0026]      FIG. 4  depicts an exemplary embodiment  80  implanted in a patient&#39;s body in accordance with one significant application of the invention as a cranial pump for delivering medication to brain tissue. Embodiments of the invention can be advantageously used in a variety of other applications, e.g., eye, ear, brain. Note that  FIG. 4  represents a patient&#39;s skull at  100  covered by a patient&#39;s skin  102  and hair  104 . In the contemplated implant procedure for the embodiment  80 , a recess  106  is surgically formed in the patient&#39;s skull for accommodating the housing  82 . The reservoir portion  84  of the embodiment  80  lies beneath the skin  102  as depicted. The fill device  88  is also shown as being subcutaneously implanted. As is well known, the subcutaneous fill device  88  can be used together with a syringe to fill reservoir  84  with fluid medication.  FIG. 4  also depicts the output catheter  86  extending from the device  80  with the catheter tip  87  positioned to infuse medication into the patient&#39;s brain.  
         [0027]     In order to use an ambient pressure reservoir in the medication delivery system exemplified by  FIG. 1  and implanted in the exemplary manner shown in  FIG. 4 , various problems have to be addressed to insure patient safety and device reliability. One such problem is to prevent medication discharge from catheter tip  87  as a consequence of inadvertently overfilling the reservoir and/or unintentionally applying a force to the reservoir wall  42 . That is, it is important in accordance with the invention to prevent flowthrough, i.e., an unintended delivery of medication as a consequence, for example, of a physician over pressurizing the reservoir by introducing too much medication and/or the patient being bumped or pressing the reservoir wall.  
         [0028]     Thus, preferred embodiments of the invention, as detailed in  FIGS. 5-11 , incorporate (1) a safety mechanism for preventing medication flowthrough in the event of a pressure increase in the reservoir, e.g., attributable to a force exerted against the reservoir wall and/or (2) a protective shell around the reservoir to prevent the inadvertent application of a force to the reservoir wall.  FIG. 2  depicts a modification of the ambient pressure reservoir medication delivery system of  FIG. 1  to show the inclusion of an exemplary (1) safety mechanism  110  responsive to reservoir pressure via channel  111  and (2) protective reservoir shell  112 . The safety mechanism  110  and protective shell  112  can be used separately or in combination.  
         [0029]     Attention is now directed to  FIGS. 5-8  which show the details of a first embodiment of the invention, consistent with the exterior representation shown in  FIGS. 3 and 4 , and incorporating the safety mechanism  110  of  FIG. 2 .  FIG. 5  comprises an exterior side view of the embodiment depicted in  FIG. 3  showing exemplary dimensions (inches) for presently contemplated implant applications. The following table shows exemplary specifications for the applications indicated:  
                                                                                                                             Very Small Pump; Very Low Delivery Rate   Small Pump; Low Delivery Rate            Parameter   Typical   Min   Max   Typical   Min   Max                    Medication   3   0.5   5   20   5   40       Reservoir       Volume (ml)       Daily Delivery Rate   0.05   0.03   0.1   0.33   0.1   0.66       (ml/day)       Maximum Delivery   3   1   10   30   5   120       Rate       (ul/minute)       Stroke Volume   0.2   0.05   1   0.5   0.1   5       (microliters)       Maximum Output   14.7   7   100   14.7   7   100       Pressure (psig)       Longevity (years)   8   3   10   8   3   10       Refill Interval (days)   60   30   90   60   30   90            Application (typical)   Tinnitus using lidocaine   Pain using morphine;               Spasticity (CP) using baclofen       Route of Delivery   Intracranial, eye, ear   Intrathecal, epidural,               Intraperitoneal, systemic                  
 
         [0030]     The medication delivery device depicted in  FIGS. 5-8  is comprised of a housing  120  formed by a bowl-shaped wall  122  that includes a horizontally oriented (as viewed in  FIG. 7 ) circular base  124  having a cylindrical side wall  126  extending vertically therefrom. The upper edge of sidewall  126  flairs radially outward to form a horizontal flange  128 . A circular partition plate  130  is supported above the base  124  to form a closed compartment for housing a battery  132  (preferably remotely chargeable). The upper surface of partition plate  130  is preferably used to support an electronic control module  136  and an electrically driven pump actuator  138 , analogous to the aforementioned actuator  72 . A substantially planar pump/valve subassembly  140  is supported on the upper surface of flange  128  above the module  136  and pump actuator  138 .  
         [0031]     The housing  120  and subassembly  140  together form a mounting structure for supporting a reservoir wall  144  of nonextensible nonporous material which extends loosely over the subassembly  140 . The peripheral edge  146  of wall  144  is preferably sealed to the under surface of flange  128  to thus form a closed reservoir volume  148  above the upper surface of subassembly  140  for storing fluid medication.  
         [0032]     The pump/valve subassembly  140  preferably comprises a thin flat structure formed by laminating two or more plates  152 ,  154 . The laminated plates can be formed and assembled using a variety of materials, e.g., titanium, stainless steel, silicon, plastic, etc. and known fabrication techniques appropriate to the materials and the desired dimensions and tolerances.  
         [0033]     With continuing reference to  FIG. 8 , note that upper plate  152  defines an inlet port  160  of a fluid passageway  161  leading to an outlet port  164 . The fluid passageway  161  includes a first check valve  166 , located just downstream form inlet port  160 . Check valve  166  is preferably comprised of spring  170  that normally seals a precision ball  172  against valve seat  174 . The outlet of check valve  166  opens via port  175  to pump chamber  176  whose peripheral wall is defined in part by flexible diaphragm  178 . The pump chamber outlet  179  leads to the inlet of a second check valve  180  preferably comprised of spring  182  normally sealing ball  184  against valve seat  186 .  
         [0034]     The pump diaphragm  178  is mounted for movement, as by coupling it to a stem  188  of the linear actuator  138 . When the actuator  138  pulls the stem downward (as viewed in  FIG. 8 ) to increase the volume of pump chamber  176 , the resulting suction draws medication past check valve  166  into the pump chamber  176 . When the actuator  138  drives the stem  188  upward, the diaphragm  178  produces a positive pressure to expel medication from the pump chamber  176  past the second check valve  180  toward the outlet port  164 . For simplicity of explanation herein, the actuator has been described as pulling the stem downward and driving the stem upward. It should be understood however, that the diaphragm could, in fact, be biased to one position so that the actuator need only move it from the biased position  
         [0035]     The outlet of check valve  180  opens via port  194  to safety valve  196 , analogous to safety mechanism  110  of  FIG. 2 . Safety valve  196  is preferably comprised of a flexible, e.g., elastomeric, valve disc  198  mounted so that its upper surface normally seals against the valve seat  200  (flow-block position) in the absence of a force produced by an upward stroke of diaphragm  178 . More particularly, When the actuator  138  is dormant, the upper face of valve disc  198  is exposed to ambient reservoir pressure via check valves  166  and  168 . The lower face of valve disc  198  is also exposed to ambient reservoir pressure via channel  204 , analogous to channel  111  of  FIG. 2 . Parenthetically, note also that channel  204  defines a path from fill nipple  206 , analogous to input  30  of  FIG. 1 , to the reservoir volume interior  148 .  
         [0036]     Under normal conditions with the actuator  138  dormant, ambient reservoir pressure is applied to both faces of valve disc  198  and it remains in a flow-block position sealed against valve seat  200  so as to block outflow from check valve  180  to output port  164 . If the reservoir pressure increases, e.g., attributable to the patient being bumped or pressing the reservoir wall, the pressure will increase equally on both faces of the valve disc  198 , thereby leaving the disc  198  seated. Thus, the inclusion of safety valve  196  upstream from outlet port  164  prevents a failure mode which could, in the absence of the safety valve, unintentionally force medication out through the outlet port  164 . When the actuator  138  is activated, however, the upward movement of diaphragm  178  forces medication from the pump chamber  176  past the check valve  180  to the upper face of valve disc  198 . The resulting unbalanced pressure on valve disc  198  unseats the disc thereby disabling its flow blocking function to permit medication to flow therepast to the outlet port  164 .  
         [0037]     Attention is now directed to  FIGS. 9 and 10  which illustrate a preferred protective shell  240  (corresponding to shell  112  of  FIG. 2 ) configured to protect the reservoir wall  144  from impact, while still exposing it to ambient pressure and allowing it to expand and contract. The shell  240  preferably comprises a dome-shaped rigid or semi-rigid frame  242  including a hub  244  and radial arms  246  extending to an outer ring  248 . The outer ring  248  carries inwardly extending flange portions  250  configured to mount around housing flange  128 . The shell  240  is shaped and dimensioned to define an interior volume  252  able to snugly accommodate reservoir wall  144  in its fully expanded state.  
         [0038]     In order to expose the reservoir wall  144  to ambient pressure and permit it to expand and contract within the shell interior volume  252 , means are provided to allow body fluid to enter into and exit from the interior volume  252 . More particularly, a diffusive membrane  258  preferably formed of a cellulose acetate or similar material, is mounted between the hub  244  and outer ring  248 . The diffusive membrane material is preferably selected to permit slow diffusion of body fluids into the volume  252  while preventing the in-growth of body tissue. A slow rate of fluid inflow is acceptable because, in typical applications, the reservoir will contract at a maximum rate of only about 40 milliliters per month.  
         [0039]     On the other hand, when the reservoir is refilled via fill nipple  206 , a greater rate of outflow from the volume  252  is required. Accordingly, an outflow check valve  264  is preferably mounted in the hub  244  to allow the reservoir to expand relatively rapidly and force fluid out of the volume  252 . Check valve  264  is comprised of a stem  266  carrying a retention rod  268  on its lower end and a sealing disc  270  on its upper end. When the reservoir expands, it increases the pressure in volume  252  to lift disk  270  permitting the outflow of fluid through opening  272  around stem  266 .  
         [0040]     Attention is now directed to  FIG. 11  which schematically illustrates an alternative preferred medication delivery device  300  in accordance with the present invention. The device  300  is comprised of a housing  302  including a top cover plate  304  and a bottom plate  306 . The spaced plates  304 ,  306  define an interior compartment  308  for housing a battery  310 , electronics  312 , and a pump  314 . The housing  302  and plate  306  form a mounting structure for supporting a flexible membrane  316 . The membrane  316  preferably comprises flaccid nonextensible nonporous material which acts as a peripheral wall  318  enclosing an interior reservoir volume  320 .  
         [0041]     The spaced plates  304 ,  306  support a reservoir fill port  324  which includes a self healing septum  326 . The reservoir volume  320  can be filled by a hypodermic needle (not shown) penetrating the septum  326  and discharging medication through chamber  328  and ports  329  formed in plate  306 .  
         [0042]     The plate  306  functions as part of a pump/valve subassembly  330  which includes a fluid transfer passageway for coupling reservoir volume  320  to outlet port  332 . More particularly, plate  306  defines inlet port  336  opening via check valve  338  into pump chamber  340 . Pump chamber  340  exits past outlet check valve  342  to safety valve  348 . Safety valve  348  includes a valve element or diaphragm  350  having one face  352  exposed via port  354  to the pressure in reservoir volume  320 . A second face  354  of diaphragm  350  is exposed via check valve  342  to the pressure produced in pump chamber  340 .  
         [0043]     When the reservoir pressure exceeds the pump chamber pressure, it forces diaphragm  350  in a direction to seal against valve seat  360  to thereby block unintended fluid flow from the reservoir to the outlet port  332 . On the other hand, when it is intended to flow fluid from the reservoir to the outlet port, the pump chamber pressure is increased to unseat diaphragm  350 . When diaphragm  350  is unseated, medication is able to flow through the passageway from the pump chamber  340  to the outlet port  332 .  
         [0044]     From the foregoing, it should now be apparent that an implantable ambient pressure medication delivery system has been described including means for preventing the unintended discharge of medication into the patient&#39;s body. The described means includes a safety mechanism depicted primarily in the embodiments of  FIGS. 5-8  and  11  and a protective shell depicted primarily in  FIGS. 9 and 10 . Although distinctly discussed, it should be understood that these two techniques can be employed separately or in combination.  
         [0045]     It should also be understood that although specific implementations have been described herein, it is recognized that variations and modifications will occur to those skilled in the art coming within the spirit and intended scope of the invention. Thus, for example only, it is pointed out that the check valves and safety valve illustrated could take many alternative forms using different valve elements and different mechanisms for producing the seating force, e.g., magnetic.