Abstract:
An implantable beneficial agent infusion device featuring a unique safety valve assembly is disclosed. In one embodiment of the present invention, a seal in the safety valve assembly is normally closed and only opens upon a deflectable or moveable member to which the seal is attached being electrically, magnetically or electromagnetically activated. The valve assembly is preferably small in size and made of corrosion resistant materials. The valve assembly may be employed in either a passive or an active implantable drug or beneficial agent infusion system.

Description:
RELATED APPLICATION 
     This application is a continuation in part of application Ser. No. 09/017,195, filed Feb. 2, 1998. 
     This patent application is a continuation-in-part of U.S. patent application Ser. No. 09/017,195 to Haller et al. Entitled “Implantable Drug Infusion Device Having a Safety Valve Assembly”, the disclosure of which is hereby incorporated by reference herein in its entirety. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates to the field of implantable medical devices, and more particularly to a safety valve assembly for an implantable drug infusion device. 
     BACKGROUND OF THE INVENTION 
     Implantable drug infusion devices are used to provide patients with a constant and long term dosage or infusion of a drug or any other therapeutic agent. Essentially such device may be categorized as either active or passive. 
     Active drug or programmable infusion devices feature a pump or a metering system to deliver the drug into the patient&#39;s system. An example of such an active drug infusion device currently available is the Medtronic SynchroMed programmable pump. Such pumps typically include a drug reservoir, a peristaltic pump to pump out the drug from the reservoir, and a catheter port to transport the pumped out drug from the reservoir via the pump to a patient&#39;s anatomy. Such devices also typically include a battery to power the pump as well as an electronic module to control the flow rate of the pump. The Medtronic SynchroMed pump further includes an antenna to permit the remote programming of the pump. 
     Passive drug infusion devices, in contrast, do not feature a pump, but rather rely upon a pressurized drug reservoir to deliver the drug. Thus such devices tend to be both smaller as well as cheaper as compared to active devices. An example of such a device includes the Medtronic IsoMed™. This device delivers the drug into the patient through the force provided by a pressurized reservoir. In particular, this reservoir is pressurized with a drug to between 20-40 psi through a syringe capable of delivering the fluid between 35-55 psi. 
     Regardless of whether the device is an active or passive drug infusion device, the overriding concern for all drug infusion devices is to ensure patient safety. This includes, among many other things, that only the exact intended amount of drug is delivered to the patient. Thus, one drawback to active devices which feature pumps that are not normally closed, such as those seen in U.S. Pat. Nos. 5,277,556; 5,224,843 and 5,219,278, is that if the device malfunctions or changes occur in the fluid pathway, then more drug than intended may reach the patient. Similar risks are inherent in passive devices which, should the flow regulator fail or the pressure reservoir be over pressurized, may lead to more drug than intended to reach the patient. 
     Thus there is a need for a drug infusion system which features a safety valve assembly which will provide an additional margin of safety to the patient. 
     SUMMARY OF THE INVENTION 
     The present invention is an implantable beneficial agent or drug infusion device, which features a unique safety valve assembly. In one embodiment of the present invention, the safety valve assembly comprises a seal which is normally closed and opens only upon being a deflectable or moveable member to which the seal is attached being electrically, magnetically or electro-magnetically activated. The valve assembly is preferably small in size and made of corrosion resistant materials. The valve assembly may be employed in either a passive or an active drug or beneficial agent implantable infusion system. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a block diagram of the present invention. 
     FIG. 2A is a side view of one embodiment of a safety valve assembly of the present invention in a closed position. 
     FIG. 2B shows the safety valve assembly of FIG. 2B in an open position, thereby permitting fluid egress from the reservoir thereof. 
     FIGS. 3A and 3B disclose an alternative embodiment of the safety valve assembly of the present invention. 
     FIG. 4 is a schematic diagram of one embodiment of a driver circuit employed to control a piezo-electric embodiment of the lower member shown in FIGS. 2A and 2B which recollects energy stored on a piezo-electric substrate when the voltage on the piezo-electric member is switched off. 
     FIG. 5 is a timing diagram of the operation of the driver circuit shown in FIG.  4 . 
     FIG. 6 depicts an alternative driver circuit for a piezo-electric member. 
     FIG. 7 is a timing diagram of the circuit shown in FIG.  6 . 
     The Figures are not necessarily to scale. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     This patent application hereby incorporates by reference into the specification hereof each of the following patent applications, each in its respective entirety: (1) U.S. patent application Ser. No. 09/239,306 to Haller et al. entitled “System for Locating Implantable Medical Device”; (2) U.S. patent application Ser. No. 09/014,196 to Haller et al. entitled “Implantable Drug Infusion Device Having a Flow Regulator”; and (3) U.S. patent application Ser. No. 09/017,194 to Haller et al. entitled Implantable Drug Infusion Device Having an Improved Valve”. 
     FIG. 1 shows a block diagram of the present invention. As seen, such a system  1  comprises a reservoir  2 , safety valve assembly  3  assembly, pump  4 , electronic controls  10 , battery  11 , telemetry assembly  12  and outlet catheter  5 . Outlet catheter may be of any model desired and suited to the patient&#39;s requirements. Safety valve  3  assembly is coupled to the reservoir and also to pump  4 . Pump may be of any suitable design, including a roller-type pump as found in the SynchroMed™ or a micro-machined pump, for example. Pump  4  is coupled, in turn to outlet catheter  5 , such that fluid form reservoir  2  may be pumped through safety valve assembly and out to outlet catheter. Pump is controlled by electronic controls  10 . These controls include, among other devices, an efficient circuit to drive the membranes used in safety valve assembly  3 . The device may be refilled through injection port  5  through the use of a needle  6  as is well known. This refill procedure may be further enhanced through the use of the system as described in the above-referenced &#39;306 patent application to Haller. Surrounding all components of the implantable pump other than the outlet catheter is a hermetic closure  13  as is well known in the art. The device may further feature, if desired, a flow regulator, such as that shown in the &#39;196 patent application to Haller. 
     FIG. 2A shows a cross-sectional view of one embodiment of safety valve assembly  3  of the present invention in the closed position. Hermetically sealed collapsible reservoir  2  is filled with a desired beneficial agent, drug, medicament, or pharmaceutical such as by needle refilling through a reservoir fill port and self-sealing septum know in the art. Examples of the beneficial agents, drugs, medicaments, and pharmaceuticals that may be infused into a patient&#39;s body with the device and method of the present invention include, but are not limited to, gene therapeutic agents, protein- or peptide-based drugs, morphine, BACLOFEN®, antibiotics, and nerve growth factors. 
     Bellows  26  form the sidewalls of reservoir  2 , and are preferably formed from titanium in a manner similar to that employed to form the titanium bellows employed, for example, in the MEDTRONIC® SYNCHROMED® infusion system. Of course, materials other than titanium may be employed to form bellows  26 . When formed of titanium, bellows  27  are most preferably about 50 microns to about 75 microns thick. 
     Propellant  27  is disposed in the volume existing between the outwardly-facing walls of bellows  26  and the inwardly-facing walls of outer walls  28  (within which most of safety valve assembly  3  is disposed). An appropriate formulation of bi-phasic fluorocarbon may be employed as propellant  27 , and may be obtained from 3M Corporation in St. Paul, Minn. Propellant  27  is intended to cause a relatively constant pressure to be exerted against the outwardly-facing walls of bellows  26  when held at a temperature at or near human body temperature (e.g., 35-39 degrees Celsius). 
     Safety valve assembly  3  further includes deflectable upper member or membrane  20 , seal  22  mounted on or attached to intermediate member or cap  33 / 34 , first substrate  25 , second substrate  14 , deflectable or moveable lower member  21 , and shoulder  19 . Upper membrane  20  is preferably formed of titanium metal and has a thickness ranging between about 25 microns and about 50 microns, but may be thicker (e.g., up to 100 microns) or thinner (e.g., 20 microns). Upper membrane  20  may alternatively be formed of silicone, in which case its thickness would range between about 10 microns and about 20 microns. Upper membrane  20  is preferably 6 to about 15 mm in diameter. Seal  22  most preferably forms an o-ring structure and comprises a deformable material such as silicone rubber, polyimide, TEFLON (PTFE or polytetranfluoroethylene), a polymeric substance, or any other suitable material. Seal  22  preferably has a diameter ranging between 1 and 3 mm, or between about 25 and about 50 microns. Shoulder  19  may be formed of titanium, silicon, or any other suitable material. 
     Depending on the composition of shoulders  23 / 24  and first substrate  25 , shoulders  23 / 24  may be attached to substrate  25  by connecting means such as brazing, welding, anodic bonding, or silicon fusion bonding, such means being selected on the basis of the materials forming shoulders  23 / 24  and first substrate  25 . Cap  32 / 33  is most preferably about 1 mm in height, about one-half the diameter of seal  22  (e.g., between about 0.5 mm and about 1.5 mm), and most preferably comprises nipple  32  formed of silicon, silicone rubber, or titanium or any other suitable material, and end cap  33  formed of glass, silicon, silicone rubber, or titanium or any other suitable material. The height of intermediate member or cap  32 / 33  is preferably determined by the thicknesses of first substrate  25  and shoulder  19 . Cap  32 / 33  may be glued or otherwise attached to member  31 , or alternatively may form a single piece or component in respect of member  31  or lower member  21 . 
     Fluid in reservoir  2  exerts a pressure or force F on the top surface of membrane  20 , thereby pushing membrane  20  down, onto and against the upper surface of seal  22 . To aid in preventing the undesired opening of safety valve assembly  3 , it is preferred that membrane  20 , connecting shoulders  23  and  24 , seal  22 , cap  32 / 33 , and deflectable or moveable lower member  21  be configured and cooperate with one another such that membrane  20  is under mechanical tension and stretched over seal  22 , even in the absence of force or pressure provided by fluid disposed in reservoir  2 . 
     The ends of membrane  20  are attached to shoulders  23  and  24  by any of a number of known connecting means such as brazing, welding, anodic bonding, or silicon fusion bonding, such means being selected on the basis of the materials forming upper membrane  20  and shoulders  23  and  24 . In the closed position of safety valve assembly  3 , the lower surface of seal  22  is pushed down against substrate  25  by upper membrane  20 . Cap  32 / 33  may be formed of two portions, nipple  33  and end cap  34 , or may comprise a single portion. The upper surface of cap  32 / 33  is attached to seal  22 , while the lower surface of cap  32 / 33  is attached to the upper surface of member  31 . Connecting member  31 , in turn, is preferably attached to deflectable or moveable lower member  21  by electrically conductive epoxy  34  or other suitable means. 
     The ends of connecting member  31  are attached to substrate  14  by any of a number of known connecting means such as brazing, welding, anodic bonding, or silicon fusion bonding, such means being selected on the basis of the materials forming connecting member  31 . Alternatively, connecting member  31  may form a single contiguous piece of material extending laterally away from the edges or perimeter of lower member  21 . The upper surface of lower member  21  is preferably attached to connecting member  31  by means of electrically conductive epoxy, the ends of lower member  21  not being attached to second substrate  14 . Deflectable or moveable lower member  21  is most preferably formed from a suitable piezo-electric or piezo-crystal material such as PZT (lead zirconium titanate) or PMN (lead magnesium niobate). A piezo-electric material is preferred for deflectable or moveable member  21  because piezo-electric materials are capable of undergoing relatively large displacements when subjected to an electric field. Other embodiments of lower member  21  are contemplated in the present invention, however, such as electrostatic, electro-capacitive and solenoid embodiments of lower member  21 , where motion and displacement are imparted to member  21  by means of electric or magnetic fields, or the flow of electrical current. 
     Integrated circuit  37  is shown as being disposed on the underside of second substrate  14 , and preferably receives electrical power from a battery (not shown in FIG.  2 A). Integrated circuit  37  comprises a driving circuit, which receives electrical power from a battery or other power source and transforms it into a signal appropriate to cause lower member  21  to move upwardly in response to the application of an electrical filed. It is preferred that integrated circuit  37  provide an output voltage ranging between about +80 and +150 Volts. Wire bonds  38  and  39  provide the electrical connections required to permit such an output voltage to be applied across the top and bottom surfaces of lower member  21 . Other electrical connection techniques may be employed than wire bonds to provide the output signal to the lower member including, but not limited to, flextape, solder and the like. Wire bond  39  is most preferably held at ground and electrically connected to electrically conductive epoxy  34  via an electrical connector in feedthrough  36  disposed in second substrate  14 . Alternatively, the top end of the electrical connector in feedthrough  36  may be electrically connected to another type of electrically conductive coating or member disposed on the upper surface of deflectable or moveable lower member  21 , such as an evaporated, vacuum deposited, electrochemically plated or other electrically conductive plating or member. Wire bond  38  is most preferably switched to a voltage ranging between about +80 and +150 Volts when it is desired to move lower member  21  and seal  22  into the open position. 
     FIG. 2B shows the safety valve assembly of FIG. 2A in the open position, where deflectable or moveable member  21  has moved upwardly in response to an electrical voltage being applied thereacross by integrated circuit  37 . Seal  22 , the underside of which is connected to lower member  21  via cap  32 / 33 , member  31  and glue  34 , has moved upwardly such that the top surface thereof has engaged and pushed up against the underside of membrane  20  to cause membrane  20  to be deflected upwardly. Fluid present in reservoir  2  and residing in intermediate volume  17  (after having passed through membrane passageway  15 ) now flows into exit passageway  35  for eventual delivery to the patient. Via catheter and pump means (not shown). Once the voltage applied across lower member  21  is withdrawn, lower member  21  returns to the position illustrated in FIG.  2 A and further delivery of the fluid contained in reservoir  2  is terminated. 
     It is an advantage of the present invention that safety valve assembly  3  is maintained in the closed position when power is withdrawn or lost from the implantable medical device within which it is disposed (e.g., the battery thereof becoming depleted below a certain voltage, etc.), when reservoir  2  is overfilled during refilling, or when external factors such as changes in temperature or pressure occur such that reservoir  2  becomes overpressurized. 
     The various components of safety valve assembly  3  (e.g., member or membrane  20 , seal  22 , lower member  21 , cap  32 / 33 , etc.) may be configured mechanically such that seal  22  cannot be pushed into the open position, and lower member  21  cannot move upwardly sufficiently to cause seal  22  to open, when a nominal output voltage is applied across lower member  21  and when reservoir  2  has been overfilled to the point of excessive fluid pressures having developed within reservoir  2 . That is, the various components of safety valve assembly  3  may be configured such that seal  22  can move into the open position only so long as the pressure or force applied to the upper surface thereof by the fluid contained in reservoir  2  does not exceed a predetermined amount or limit. Such a design prevents the inadvertent and unintended delivery of excessive amounts of the drug contained within reservoir  2  to the patient. 
     It is contemplated in the present invention that the specific configuration of upper member  20 , lower member  21 , and seal  22  presented in the drawings hereof be modified such that upper membrane  20  is deflected in response to the provision of an output signal thereto while lower membrane  21  and seal  22  remain in relatively fixed positions. 
     FIGS. 3A and 3B disclose an alternative embodiment of the safety valve assembly of the present invention. Such an embodiment features shape memory alloy membranes as opposed to the piezo-electric membranes disclosed above. This embodiment features a superior membrane  40  and an inferior membrane  41 . Membrane  40  is biased in an upward direction while membrane  41  is biased in a downward direction. The respective biasing strengths of these membranes control membrane  40  to normally close the valve when no energy is provided to membrane  41 . Upon energizing the membrane  41 , however, the shape memory alloy undergoes a reorganization of the crystalline structure. As constructed, this removes the bias to membrane  41 . Membrane  40  will, in turn, overcome the bias provided by membrane  41  and thus move the seal assembly  42  upwardly and away from seal footing  43  mounted on substrate  44  thereby creating a fluid passage from cavity  45  to passageway  50 . As seen, membrane  40  is mounted across shoulder elements  50  and  51  and includes center portion  52 . The shoulder and center portions are preferably constructed of glass. As further seen, membrane  41  is disposed on the downward surface of shoulder and center portion and further mounted to bases  53  and  54 . Bases as well as seal assembly  42  are also constructed from glass. This entire assembly is further mounted to substrate  44  through contacts  60  and  61 . Contacts  60  and  61  are preferably constructed from silicone. Substrate  44  is preferably constructed of glass while footing  43  is constructed of silicone. Membranes are preferably constructed from Nitinol, although other shape memory alloys may also be used. Moreover, the areas of substrate and membranes in contact with any drug or fluid are further preferably coated with diamond or diamondlike carbon so as to inhibit any interactions between the drug or fluid and the materials. Such coatings may be selected according to the particular drug or fluid to be infused, and may include also tantalum or titanium, for example. 
     Essentially, the operation of this embodiment may be seen in compared FIGS. 3A and 3B. At rest, or when no energy is provided to membranes, the particular bias to membranes causes seal assembly  42  to snugly engage against footing  43 . Once energy is provided to the membranes, the energy or electric current causes the material to heat up and thereby ending the phased transformation, i.e., the crystalline structure is reorganized. Thus seal assembly  42  is caused to disengage against footing  43  and thereby opens a fluid pathway from cavity  45  into passageway  50 . Of course, although in this embodiment a double membrane design is shown, other embodiments may feature a single, biased membrane as well as three or more membranes, depending upon the exact fluid pathway required. 
     One difficulty with all battery powered implantable devices is that they must operate with as little energy drain as possible. A problem typically associated with prior art piezo-electric membranes is that driver circuits typically dissipated the charge built up after a voltage was applied across the membrane. This, of course, wasted energy, and particularly such built-up charge. Another feature of the present invention is the use of a driver circuit which minimizes the energy used. In. particular, the present invention further features a driver circuit which recollects the stored energy on the piezo when the voltage on the piezo is turned to zero. 
     FIG. 4 is a schematic diagram of a driver circuit used to control the piezo membrane of the embodiment shown in FIGS. 2A and 2B which recollects the stored energy on the piezo when the voltage on the piezo is turned to zero. FIG. 5 is a timing diagram of the operation of the driver circuit shown in FIG.  4 . Each of these FIGS. will now be described together. As seen, the circuit consists of a 3V power supply, four N-MOS switches with low ohms resistance, 1 P-MOS switch, a storage capacitor and inductor and a piezo membrane. M 1  and M 2  are high voltage devices while M 3 -M 5  are low voltage devices. At its initial condition, all switches are closed except M 5 . In step  1  (with reference also to FIG.  5 ,) M 3  and M 4  are opened and M 5  is closed to thereby charge capacitor C 2  through inductor L 1 . In step  2 , M 2  is opened and M 3  is closed to thereby connecting inductor L 1  to piezo. The current in L 1  is maintained and a voltage is developed on the drain of M 2 , as best illustrated by line  99  in FIG. 5, and a voltage is thereby developed across piezo. Once voltage in piezo (or L 1 ) reaches a maximum level step  3  begins. As seen in this step M 1  is opened and M 2  is closed thereby shorting L 1  and maintaining the charge on piezo. Charge actuates the piezo and may be maintained on the piezo for as long as actuation is desired. In steps  4 ,  5  and  6  the process is reversed. In step  4 , M 2  is opened, M 1  is closed thereby discharging the piezo voltage through the inductor. In step  5  M 3  is opened and M 2  is closed and the current through L 1  is flowed through C 2  thereby discharging C 2 . Finally in step  6 , M 5  is opened and M 3  and M 4  are closed, thereby returning to initial conditions. In such a manner the piezo may be driven through a minimal amount of energy. As seen the amount of energy delivered to piezo is determined by the amount of energy delivered to L 1 , which may be determined by the time which elapses between step  1  and step  2 . Of course, if C 1  is not completely charged full, then operation is slightly changed, and in step  2  M 5  opened, M 4  opened and M 3  closed. Thereafter the operation remains as described although in step  5  M 5  is closed. Additional functionality to monitor voltages or current or both and determine the proper timing for closing the switches is not shown, but would be performed in block  10  of FIG. 1, labeled control system. 
     FIG. 6 depicts an alternative driver circuit for the piezo membrane of FIG.  2 . FIG. 7 is a timing diagram of the circuit shown in FIG.  6 . Each of these FIGS. will now be described together. As seen, this circuit consists of a 3V power supply, a storage capacitor—C 1 , a piezo model capacitor—C 2 , an inductor—L 1 , and four N-MOS switches—M 1 -M 4 . The pulses S 1 -S 3  are 10V square wave pulses created by the pulse generation circuit. 
     The first step in creating the piezo drive pulse is to charge the storage capacitor, C 1 , to the voltage level of the power supply by closing switches M 1  and M 3 /M 4 . After C 1  is fully charged to the supply voltage, the inductor, L 1 , is charged with current by discharging the stored energy in C 1 . This is done by simultaneously opening M 1  while closing M 2  and keeping M 3 /M 4  closed. Then M 2  is reopened while M 3 /M 4  remains closed to charge the piezo, C 2 , with the stored current. The voltage on C 2  rises to 150V and all switches are opened while the pulse remains high. 
     After the high pulse on the piezo is finished, M 3 /M 4  is closed to drain the energy from the piezo into the inductor L 1 . After the piezo is drained switch M 2  is closed, while M 3 /M 4  remains closed, to charge C 2  with the energy stored in the inductor L 1 . The cycle begins again with another rising edge on M 1 . The following timing diagram displays the timing sequence for closing of switches M 1 , M 2 , and M 3 /M 4  where time units are in seconds. 
     Although a specific embodiment of the invention has been disclosed, this is done for purposes of illustration and is not intended to be limiting with regard to the scope of the invention. It is contemplated various substitutions, alterations and/or modifications may be made to the disclosed embodiment without departing from the spirit and scope of the invention. Such modifications may include substituting elements or components which perform substantially the same function in substantially the same way to achieve substantially the same result for those described herein. 
     In the claims, means-plus-function clauses are intended to cover the structures described herein as performing the recited function and not only structural equivalents but also equivalent structures. Thus, although a nail and a screw may not be structural equivalents in that a nail employs a cylindrical surface to secure wooden parts together, whereas a screw employs a helical surface, in the environment of fastening wooden parts a nail and a screw are equivalent structures. 
     All patents and printed publication referenced hereinabove are hereby incorporated by reference herein, each in its respective entirety.