Patent Abstract:
An anti-microbial component of the IMD that is exposed to body fluids in the pocket is compounded of an anti-microbial metal ion zeolite that elutes metal ions in concentrations exhibiting anti-microbial activity over a substantial period of time of implantation is disclosed. The anti-microbial component is physically attached to the IMD to be retained in close proximity and in a stable location in the subcutaneous pocket. In another embodiment, the anti-microbial component conforms to the shape of the IMD and is attachable to and detachable from the IMD. In another embodiment, the polymeric component includes a connector header of an IPG or a monitor, or a connector sleeve or the sealing rings of a proximal connector assembly of an electrical medical lead coupled with an IPG or monitor that are located in the subcutaneous pocket or in the backing of a subcutaneously implanted cardioversion/defibrillation (C/D) electrode.

Full Description:
FIELD OF THE INVENTION  
         [0001]    The present invention relates generally to implantable medical devices (IMDs), and more particularly to a polymeric member associated with the IMD and compounded from a polymer and an anti-bacterial agent to provide anti-microbial protection during chronic implantation.  
         BACKGROUND OF THE INVENTION  
         [0002]    At present, a wide variety of IMDs are commercially released or proposed for clinical implantation that include a housing that is implanted subcutaneously and typically include elongated medical electrical leads or drug delivery catheters that extend from the subcutaneous site to other subcutaneous sites or deeper into the body to organs or other implantation sites. Typically, the IMD includes a battery-powered implantable pulse generator (IPG) that is coupled with electrical medical leads, a battery-powered implantable monitor that may or may not be coupled with electrical medical leads, a battery-powered drug pump coupled with a drug delivery catheter, etc. Such IMDs include implantable cardiac pacemakers, cardioverter/defibrillators having pacing capabilities, other electrical stimulators including spinal cord, deep brain, nerve, and muscle stimulators, drug delivery systems, cardiac and other physiologic monitors, cochlear implants, etc.  
           [0003]    Typically, the battery-powered component of the IMD is implanted subcutaneously at a surgically prepared site, referred to as a “pocket”, that can be accessed readily when it is necessary to replace the battery-powered component. The surgical preparation and initial and replacement IMD implantations are conducted in a sterile field, and the IMD components are packaged in sterile containers or sterilized prior to introduction into the sterile field. However, despite these precautions, there always is a risk of introduction of microbes into the pocket. Surgeons therefore typically apply disinfectant or antiseptic agents to the skin at the surgical site prior to surgery (e.g., Chlorhexidine, Gluconate, Povidone-Iodine, Isopropyl Alcohol, Ethyl Alcohol), directly to the site before the incision is closed (e.g., gentamicin, vancomycin), and prescribe oral antibiotics for the patient to ingest during recovery (e.g., sefuroxin, gentamicin, rifamycin, vancomycin).  
           [0004]    Resident inflammatory cells in the fibrous tissue surrounding the IPG and lead become weakened or “exhausted” over time, such that at the time of IPG replacement, the amount of bacteria that can cause infection in the pocket is reduced by several orders of magnitude. Once the pocket becomes infected, the infection can migrate along the lead sheath to the heart, and such a migrating infection can become intractable and life-threatening, requiring removal of the IPG and lead and drug treatment to cure the infection. Removal of a chronically implanted lead can be difficult and dangerous, and in some cases could require a thoracotomy.  
           [0005]    There is a long history of the actual or proposed use of certain elemental metals and metal ions that exhibit anti-microbial behavior in association with a wide variety of products, including IMDs or temporarily implanted devices and instruments, particularly catheters. The metal ions that have been shown to possess antibiotic or anti-microbial activity include silver, gold, platinum, palladium, iridium, antimony, arsenic, selenium, copper, zinc, mercury, tin, lead, and bismuth. Anti-microbial metal ions of silver, gold, copper and zinc, in particular, are considered safe for in vivo use. Anti-microbial silver ions have been found to be particularly useful for in vivo use due to the fact that they are not substantially absorbed into the body. The incorporation of elemental metals into IMDs, particularly silver incorporated into heart valve sewing rings, is proposed in U.S. Pat. No. 6,267,782.  
           [0006]    Metallic silver has also been impregnated in the surfaces of medical implants, e.g., catheters, by ion-beam-assisted deposition or implantation as described in U.S. Pat. Nos. 5,474,797 and 5,520,664. The products described in these patents, however, do not exhibit an antibiotic effect for a prolonged period of time because a passivation layer typically forms on the silver metal coating. This layer reduces the release rate of the silver metal from the product, resulting in lower antibiotic effectiveness.  
           [0007]    Various compounds have been developed for coating catheters and other devices that release silver ions into body fluids and tissues. As set forth in U.S. Pat. Nos. 6,123,925 and 6,296,863, antibiotic zeolites are well known and have been prepared by replacing all or part of the ion-exchangeable ions in zeolite with ammonium ions and antibiotic metal ions, as described in U.S. Pat. Nos. 4,923,450, 4,938,958, 4,911,898, and 5,100,671. “Zeolite” is a natural or synthetic aluminosilicate having a three dimensional skeletal structure that is represented by the empirical formula: XM 2/n O—Al 2 O 3 —YSiO 2 —ZH 2 O, wherein M represents an ion-exchangeable ion, generally a monovalent or divalent metal ion, n represents the atomic valency of the (metal) ion, X and Y represent coefficients of metal oxide and silica respectively, and Z represents the number of water of crystallization. Examples of such zeolites include A-type zeolites, X-type zeolites, Y-type zeolites, T-type zeolites, high-silica zeolites, sodalite, mordenite, analcite, clinoptilolite, chabazite and erionite. Such zeolites have been incorporated in antibiotic resins as shown in U.S. Pat. Nos. 4,938,955 and 4,906,464 and polymer articles as shown in U.S. Pat. No. 4,775,585 in concentrations sufficient to effective as an anti-microbial agent. The above-referenced &#39;450 and &#39;671 patents disclose coatings of anti-microbial metal ion zeolites in a polymer, e.g., silicone rubber, on the surface of medical devices, e.g., catheters. In the &#39;925 and &#39;863 patents, particular ones of the above-described antibiotic zeolites are incorporated into coatings applied to porous fabrics used to form implantable vascular grafts and into toothpaste formulations, respectively, in concentrations providing anti-microbial activity.  
           [0008]    However, applying coatings of the types described to surfaces of IMDs intended for long-term implantation can be problematic since the coatings can degrade and slough away over time.  
         BRIEF SUMMARY OF THE INVENTION  
         [0009]    The present invention is directed to providing a simple, effective and long-lasting anti-microbial agent into the subcutaneous implantation pocket that is surgically prepared to receive an IMD of the type described above. In accordance with one aspect of the present invention, an anti-microbial component of the IMD that is exposed to body fluids in the pocket is compounded of an antibiotic zeolite that elutes metal ions in concentrations exhibiting anti-microbial activity over a substantial period of time of implantation. The anti-microbial component is physically attached to the IMD to be retained in close proximity and in a stable location in the subcutaneous pocket.  
           [0010]    In one embodiment, the anti-microbial component conforms to the shape of the IMD and is attachable to and detachable from the IMD. The anti-microbial component includes a polymeric pad or boot that fits around at least a portion of an outer housing of the IMD, wherein the IMD may include an ICD IPG, a pacemaker IPG, a neurostimulator IPG, a muscle stimulator IPG, a monitor, a drug pump, or a subcutaneous electrode or components thereof that implanted subcutaneously. The surgeon can exercise the option of using or not using the anti-microbial component in any particular instance whether based on medical or aesthetic considerations. Moreover, it is not necessary for manufacturers to commit to manufacturing and clinical buyers to stock redundant models of expensive IMDs, one model with the anti-microbial polymeric component and one without the anti-microbial polymeric component.  
           [0011]    In another embodiment, the polymeric component includes a connector header of an IPG or a monitor or the sealing rings of a proximal connector assembly of an electrical medical lead coupled with an IPG or monitor that are located in the subcutaneous pocket or in the backing of a subcutaneously implanted cardioversion/defibrillation (C/D) electrode.  
           [0012]    Polymeric boots have been proven over long-term clinical use to not degrade significantly in the body despite the fact that they are relatively thin. Therefore, it is expected that metal (e.g., silver) silver ions of the anti-microbial agent dispersed through the thin wall of the anti-microbial pad or boot component or other component will be beneficially released over time.  
           [0013]    This summary of the invention has been presented here simply to point out some of the ways that the invention overcomes difficulties presented in the prior art and to distinguish the invention from the prior art and is not intended to operate in any manner as a limitation on the interpretation of claims that are presented initially in the patent application and that are ultimately granted. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0014]    These and other advantages and features of the present invention will be more readily understood from the following detailed description of the preferred embodiments thereof, when considered in conjunction with the drawings, in which like reference numerals indicate identical structures throughout the several views, and wherein:  
         [0015]    [0015]FIG. 1 is a schematic view of an implantable medical device, according to the present invention, implanted subcutaneously in a patient&#39;s thoracic region, having a silicone rubber boot compounded with metal ion zeolite fitted over the device  
         [0016]    [0016]FIG. 2 is a plan view of the silicone rubber boot compounded of metal ion zeolite of FIG. 1;  
         [0017]    [0017]FIG. 3 is a side-cross-section view of the boot taken along lines  3 - 3  of FIG. 2;  
         [0018]    [0018]FIG. 4 is a top view of the boot of FIG. 2;  
         [0019]    [0019]FIG. 5 is a schematic view of an implantable medical device according to the present invention including, implanted subcutaneously in a patient&#39;s thoracic region, having a silicone rubber boot compounded with metal ion zeolite fitted over the device and having a further silicone rubber boot compounded with metal ion zeolite fitted over or attached to the non-conducting side of the device;  
         [0020]    [0020]FIG. 6 is a schematic view of an implantable medical device according to the present invention included two modules implanted subcutaneously across the patient&#39;s thorax and tethered together, each module having a silicone rubber boot compounded with metal ion zeolite fitted over the device;  
         [0021]    [0021]FIG. 7 is a schematic view of an implantable medical device according to the present invention implanted subcutaneously in a patient&#39;s thoracic region having a silicone rubber boot compounded with metal ion zeolite fitted over the device;  
         [0022]    [0022]FIG. 8 is a schematic view of an implantable medical device according to the present invention implanted subcutaneously in a patient&#39;s thoracic region having a silicone rubber boot compounded with metal ion zeolite fitted over the device;  
         [0023]    [0023]FIG. 9 is a schematic view of an implantable medical device according to the present invention implanted subcutaneously in a patient&#39;s thoracic region having a silicone rubber boot compounded with metal ion zeolite fitted over the device;  
         [0024]    [0024]FIG. 10 is a schematic view of an implantable medical device according to the present invention implanted subcutaneously in a patient&#39;s thoracic region having a silicone rubber boot compounded with metal ion zeolite fitted over the device;  
         [0025]    [0025]FIG. 11 is a schematic view of an implantable medical device according to the present invention implanted subcutaneously in a patient&#39;s thoracic region having a silicone rubber boot compounded with metal ion zeolite fitted over the device;  
         [0026]    [0026]FIG. 12 is a schematic partial view of an exemplary implantable medical device according to the present invention depicting a connector header in partial cross-section and an exemplary lead connector assembly adapted to be fitted into a connector bore, wherein selected ones or all of polymeric components of the connector header and/or the lead connector assembly are compounded with metal ion zeolite in accordance with an embodiment of the present invention; and  
         [0027]    [0027]FIG. 13 is a perspective view of a subcutaneously implantable C/D electrode wherein selected ones or all of the polymeric components of the C/D electrode are compounded with metal ion zeolite in accordance with an embodiment of the present invention. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0028]    In the following detailed description, references are made to illustrative embodiments of methods and apparatus for carrying out the invention. It is understood that other embodiments can be utilized without departing from the scope of the invention.  
         [0029]    In the preferred embodiments, an inorganic anti-microbial agent is incorporated into a polymeric component of or a detachable boot that can be optionally fitted against or over the housing of an IMD that is subcutaneously implanted, particularly a monitor, a drug pump, an IPG and subcutaneously implanted electrodes or sensors. The inorganic anti-microbial agent is preferably the antibiotic silver ion zeolite the type designated HealthShield™, which is sold by AgION™ Technologies, Inc., the assignee of the above-referenced &#39;925 and &#39;863 patents.  
         [0030]    This material is basically an anti-microbial zeolite of the types described above having a metal having one or the whole of the metal substituted by at least one kind of an ion exchangeable metal selected from the group consisting of Ag, Cu and Zn. A typical particle size for the agent is between 0.8 and 10 microns. The particles are dispersed in silicone rubber in the quantity of between 0.5 and 20% by weight, more preferably between 0.5 and 15% by weight and most preferably between 0.5 and 10% by weight. The silicone rubber-particle mixture is molded into a desired shape employing conventional medical grade silicone rubber molding techniques. In accordance with the invention, other inorganic anti-microbial metal ions, e.g., gold, platinum, palladium, iridium, antimony, arsenic, selenium, copper, zinc, mercury, tin, lead, bismuth, cadmium, chromium and thallium ions can be employed instead of silver.  
         [0031]    A first embodiment of a detachable, elastic, boot  15  that is compounded of silicone rubber and the preferred anti-microbial metal ion zeolite and molded in a shape to be fitted over an IPG or monitor  50  implanted in patient  10  is depicted in FIGS. 1-4. The boot  15  has first and second major boot sides  20  and  25  joined by a mutual boot edge  30  defining a boot cavity  45 . A side opening  35  through major boot side  20  and an edge opening  40  through a segment of boot edge  30  are provided.  
         [0032]    The boot  15  is fitted over the housing  55  and connector block  60  of the exemplary IPG or monitor and inserted into a subcutaneous pocket  140  at a distance from the heart  100  as shown in FIG. 1. The fitted boot  15  provides the anti-microbial protection in the subcutaneous implantation pocket  140  while leaving at least a portion of the housing  55  of IPG/monitor  50  exposed through side opening  35 . The IPG  50  is depicted in FIG. 1 as a ventricular pacemaker IPG or hemodynamic monitor that is coupled to a cardiac lead  70  extending from a connection with connector block  60  into the heart  100  through a conventional transvenous route. The cardiac lead comprises an active or cathodal pace/sense electrode  80  at the distal end of lead body  75  and optionally comprises a pressure transducer  90  proximal to pace/sense electrode  80  both disposed in this instance in the right ventricle  105  of heart  100 . The housing  55  of IPG  50  is hermetically sealed and formed of a conductive metal that is electrically connected to pacing and/or sensing circuitry within housing  55  to function as an indifferent or anodal pace/sense electrode  85  that is exposed by side opening  35 .  
         [0033]    The housing  55  and connector block  60  of IPG/monitor  50  can take any shape known in the art, and that shape dictates the shape and dimensions of the boot  15 . The specifications and operating modes and other characteristics of the pacemaker IPG and the cardiac lead(s) coupled therewith can correspond to any of those known in the art. The monitor can correspond to the Medtronic® CHRONICLE® IHM that is coupled through a cardiac lead of the type described in commonly assigned U.S. Pat. No. 5,564,434 having capacitive blood pressure and temperature sensors as well as at least one EGM sense electrode.  
         [0034]    The IPG/monitor  50  is slipped through the side opening  35  and the connector block  60  is oriented to be exposed through the edge opening  40 . It will also be understood that the side opening  35  is necessary to expose the housing  55  for use as a remote indifferent pacing and/or sensing electrode in either of a unipolar pacemaker IPG/monitor  50  or in a bipolar pacemaker IPG/monitor also having the capability of monitoring the far field EGM. The boot  15  having such a side opening  35  can still be efficaciously used over a typical bipolar pacemaker IPG/monitor not having such a far field sensing capability. These features of the boot  15  are applicable to the remaining boot embodiments illustrated in FIGS. 5-10.  
         [0035]    A second embodiment of a detachable, elastic, boot  215  that is compounded of silicone rubber and the preferred anti-microbial metal ion zeolite and molded in a shape to be fitted over a rectilinear ICD IPG  250  implanted in patient  10  is depicted in FIG. 5. The boot  215  is also formed of first and second major boot sides joined by a mutual boot edge defining a side opening  235  through major boot side and an edge opening  240  through a segment of the boot edge.  
         [0036]    The boot  215  is fitted over the housing  255  and connector block  260  of the exemplary ICD IPG  250  and inserted into a subcutaneous pocket  140  at a distance from the heart  100  as shown in FIG. 5. The fitted boot  215  provides the anti-microbial protection in the subcutaneous implantation pocket  140  while leaving at least a portion of the housing  255  of ICD IPG  250  exposed through side opening  235 . The exposed portion of the housing  255  may be employed as one C/D electrode.  
         [0037]    The ICD IPG  250  depicted in FIG. 5 is coupled to an exemplary set of C/D leads extending to pace/sense electrodes and C/D electrodes. It will be understood that not all of the depicted C/D leads and that other combinations of C/D leads can be connected to the ICD IPG  250 . In this particular instance, a right ventricular (RV) C/D lead  275  extends from a connection with connector block  260  into the right ventricle  105  of the heart  100  through a conventional transvenous route. The RV C/D lead  275  comprises active or cathodal pace/sense electrode and fixation helix  280  at the distal end of the lead body, a more proximally located, ring-shaped, indifferent or anodal pace/sense electrode  285 , and an elongated C/D electrode  290 . A coronary sinus (CS) C/D lead  225  extends from a connection with connector block  260  to an elongated C/D electrode  230  disposed in the coronary sinus or great vein  115  of the heart  100  through a conventional transvenous route.  
         [0038]    A further C/D lead  265  extends subcutaneously from a connection with connector block  260  to a rectilinear, pad-shaped, C/D electrode  270  disposed in a further subcutaneous pocket  140 ′ selected by the surgeon to optimally apply C/D shock therapies between selected pairs of the C/D electrodes  230 ,  255 ,  270 , and  290 . Typically the rectilinear C/D electrode  270  is formed of a flexible silicone rubber or polyurethane pad supporting a C/D electrode surface or array on one major side disposed toward heart  100  and a non-conductive side disposed toward the skin. A further detachable, elastic, boot  295  that is compounded of silicone rubber and the preferred anti-microbial metal ion zeolite and molded in a shape to be fitted over the non-conductive major side of the rectilinear C/D electrode  270  is shown in FIG. 5. The boot  295  can be affixed by sutures or other means to the silicone rubber or polyurethane pad to ensure that it does not move or detach from the non-conductive side within the pocket  140 ′.  
         [0039]    More recently, it has been proposed that all components of an ICD be implanted subcutaneously distributed between two or more C/D electrode bearing modules implanted in subcutaneous pockets  140 ,  140 ′ around the thorax to deliver C/D shock therapies between them and through the heart. Such ICDs are disclosed in U.S. Pat. Nos. 5,255,692, 5,314,451, and 5,342,407 and in U.S. Patent Application Publication Nos. 2002/0042634 and 2002/0035377. Such an arrangement is depicted in FIG. 6 wherein the ICD  300  comprises first and second schematically depicted, hermetically sealed ICD IPG modules  305  and  310  tethered together by a cable  315 . First and second C/D electrodes  320  and  325  are supported on one side of the ICD IPG modules  305  and  310 , respectively, that are intended to be implanted in the subcutaneous pockets  140 ,  140 ′ facing the heart  100  and one another.  
         [0040]    The hermetically sealed ICD IPG module  305  encloses the electronic sensing, pacing, and C/D circuitry, including the relatively bulky high voltage capacitors that are charged and discharged to deliver C/D shocks, as well as a low voltage battery employed for powering the circuitry and the delivered pacing pulses. The second hermetically sealed ICD IPG module  310  encloses a relatively bulky high power C/D battery as well as a switch to enable selective connection with the high voltage capacitor charging circuitry within the first ICD IPG module  305  in the manner described in the above-referenced &#39;451 patent. The cable  315  encases conductors distributing power from the battery and exchanging signals and commands between circuitry in the first and second ICD IPG modules  305  and  310 .  
         [0041]    First and second detachable, elastic, boots  335  and  340  that are each compounded of silicone rubber and the preferred anti-microbial metal ion zeolite and molded in a shape to be fitted over the respective first and second ICD IPG modules  305  and  310  implanted in patient  10  are also depicted in FIG. 6. The boots  335  and  340  have openings  345  and  350  in the major sides thereof that expose the first and second respective C/D electrodes  320  and  325 .  
         [0042]    The first and second hermetically sealed ICD IPG modules  305  and  310  bearing the first and second detachable, elastic, boots  335  and  340  are preferably implanted subcutaneously in posterior and anterior positions through a single skin incision intermediate the illustrated posterior and anterior positions. Tunneling tools would be employed to displace the tissue and advance the first and second hermetically sealed housings to the depicted sites or other selected sites around the thorax. Tissue adhesive may be employed to secure the first and second hermetically sealed ICD IPG modules  305  and  310  bearing the first and second detachable, elastic, boots  335  and  340  at the sites and prevent migration. Alternatively, the sites may be exposed through minimal surgical exposures, and the first and second hermetically sealed ICD IPG modules  305  and  310  bearing the first and second detachable, elastic, boots  335  and  340  can be sutured at the sites through the boots  335  and  340  to prevent migration.  
         [0043]    Therapeutic administration of pain suppressing electrical stimulation into the intraspinal space, that is to either the epidural space or to the intrathecal space, is also known in the art as illustrated in FIG. 7. Three meningeal sheaths that are continuous with those which encapsulate the brain within the enclosure by the vertebral canal for the spinal cord by the bones of the vertebrae surround the spinal cord. The outermost of these three meningeal sheaths is the dura matter, a dense, fibrous membrane which anteriorally is separated from the periosteum of the vertebral by the epidural space. Posterior to the dura matter is the subdural space. The subdural space surrounds the second of the three meningeal sheaths, the arachnoid membrane, which surround the spinal cord. The arachnoid membrane is separated from the third meningeal sheath, the pia mater, by the subarachnoid or intrathecal space. The subarachnoid space is filled with CSF. Underlying the pia mater is the spinal cord. Thus the progression proceeding inwards or in posterior manner from the vertebra is the epidural space, dura mater, subdural space, arachnoid membrane, intrathecal space, pia matter and spinal cord.  
         [0044]    An exemplary spinal cord stimulation (SCS) system  400  comprising a neurostimulator SCS IPG  450 , an SCS lead  410 , and a detachable, elastic, boot  415  that is each compounded of silicone rubber and the preferred anti-microbial metal ion zeolite and molded in a shape to be fitted over the housing and connector of the neurostimulator IPG  450  is depicted implanted in patient  10  in FIG. 7. The neurostimulator IPG  450  may comprise the Medtronic® Itrel® 3, Synergy™ or Synergy Versitrel™ neurostimulator, and the SCS lead  410  may comprise the Medtronic® Pisces Z Quad lead.  
         [0045]    Therapeutic administration of stimulation of the sacral nerves to control bladder function or treat sexual dysfunction is also alternatively illustrated in FIG. 7 by the sacral nerve stimulation lead  420  depicted in dotted lines extending from the neurostimulator IPG  450  and detachable, elastic, boot  415  into a foramen of the sacrum. In this case, the neurostimulator IPG  450  may comprise the Medtronic® InterStim® Neurostimulator Model 3023. In one embodiment, a sacral nerve stimulation lead  420  bearing one or a plurality of distal stimulation electrodes are percutaneously implanted through the dorsum and the sacral foramen of the sacral segment S 3  for purposes of selectively stimulating the S3 sacral nerve. The distal electrode(s) is positioned using a hollow spinal needle through a foramen (a singular foramina) in the sacrum. The electrode is secured by suturing the lead body in place, and the lead body is tunneled subcutaneously to the implant site of the neurostimulator IPG  450  within the boot  415 .  
         [0046]    The detachable, elastic, boot  415  corresponds to the detachable, elastic, boot  15  described above with respect to FIGS. 1-4. It will be understood that the actual shape of such commercially available neurostimulator IPGs may differ from the exemplary shape of neurostimulator IPG  450  shown in FIG. 7, and that boot  415  is molded to conform to the actual shape. Again, the boot  415  has a major side opening  435  exposing the housing  455  of the IPG  450  that can function as an indifferent stimulation electrode in conjunction with a stimulation electrode or electrodes along the distal end segment of the SCS lead  410  disposed within the intraspinal space and obscured from view. The boot  415  also has an edge opening  440  enabling access to the connector block  460 .  
         [0047]    Therapeutic administration of pain suppression or therapeutic drugs into the intraspinal space as also known in the prior art is illustrated in FIG. 8. Administration of a drug directly to the intrathecal space can be by either spinal tap injection or by catheterization. Intrathecal drug administration can avoid the inactivation of some drugs when taken orally as well and the systemic effects of oral or intravenous administration. Additionally, intrathecal administration permits use of an effective dose that is only a fraction of the effective dose required by oral or parenteral administration. Furthermore, the intrathecal space is generally wide enough to accommodate a small catheter, thereby enabling chronic drug delivery systems. Thus, it is known to treat spasticity by intrathecal administration of baclofen. Additionally, it is known to combine intrathecal administration of baclofen with intramuscular injections of botulinum toxin for the adjunct effect of intramuscular botulinum for reduced muscle spasticity. Furthermore, it is known to treat pain by intraspinal administration of the opioids morphine and fentanyl. A drug pump is required because the antinociceptive or antispasmodic drugs in current use have a short duration of activity and must therefore be frequently re-administered, which re-administration is not practically carried out by daily spinal tap injections. The drug pump is surgically placed under the skin of the patient&#39;s abdomen. One end of a catheter is connected to the pump, and the other end of the catheter is threaded into a CSF filled subarachnoid or intrathecal space in the patient&#39;s spinal cord. The implanted drug pump can be programmed for continuous or intermittent infusion of the drug through the intrathecally located catheter.  
         [0048]    Thus a fully implantable intrathecal drug delivery system  500 , e.g., the Medtronic® SynchroMed® EL Infusion System, comprising a programmable SynchroMed® drug pump  550  and a drug delivery catheter  510 , is depicted in FIG. 8. A detachable, elastic, boot  515  that is compounded of silicone rubber and the preferred anti-microbial metal ion zeolite and molded in a shape to be fitted over the housing and connector of the drug pump  550  is depicted implanted in patient  10  in FIG. 7. Again, the boot  515  has a major side opening  535  in this case exposing a drug fill port  555  for percutaneously refilling a drug chamber within the drug pump  550  in a manner well known in the art. The boot  515  also has an edge opening  540  enabling access to the connector block  560  that the drug delivery catheter  510  is attached to. The drug pump  550  and boot  515  encasing the drug pump  550  are implanted just under the skin of the abdomen in a prepared subcutaneous pocket  140  so that the drug fill port is oriented outward to enable access to the drug fill port  555 .  
         [0049]    Turning to FIG. 9, it schematically illustrates the delivery of Medtronic® Activa® Tremor Control Therapy or Parkinson&#39;s Control Therapy to a patient  10  for controlling essential tremors and those associated with Parkinson&#39;s disease. The Activa® Therapy is delivered by an deep brain stimulator similar to a cardiac pacemaker, that uses mild electrical stimulation delivered by electrodes implanted in the brain to block the brain signals that cause tremor.  
         [0050]    The Activa Tremor Control System stimulates targeted cells in the thalamus—the brain&#39;s message relay center—via electrodes that are surgically implanted in the brain and connected to a neurostimulator IPG implanted near the collarbone. In the treatment of Parkinson&#39;s tremors, the electrodes are located at the subthalamic nucleus (STN) or globus pallidus interna (GPI) that control movement and muscle function. A lead with tiny electrodes is surgically implanted at these sites in the brain and connected by an extension that lies under the skin to a neurostimulator IPG implanted near the collarbone. The electrical stimulation can be non-invasively adjusted to meet each patient&#39;s needs.  
         [0051]    The implanted components of the Activa® System  600  depicted in FIG. 9 include the Medtronic® Itrel® II Model 7424 neurostimulator IPG  650 , a DBS™ lead  670  and an extension  610  that connects the lead  670  to the neurostimulator IPG  650 . The lead  670  is implanted using a stereotactic headframe designed to keep the head stationary and help guide the surgeon in the placement of the lead  670  into the brain  130  to dispose the electrodes  680  at the desired site  135 . The brain  130  and the placement of the lead  670  is imaged using CT (computed tomography) or MRI (magnetic resonance imaging) equipment. The Model 3387 DBS™ lead, with a plurality of widely spaced electrodes, and the Model 3389 DBS™ lead, with a plurality of narrowly spaced electrodes, provide physician options for precise placement and stimulation selectivity. Other components of the Activa® System 60 include a neurostimulator control magnet, neurological test stimulator, physician programmer, lead frame kits, and MemoryMod® software cartridge.  
         [0052]    A detachable, elastic, boot  615  that is compounded of silicone rubber and the preferred anti-microbial metal ion zeolite and molded in a shape to be fitted over the housing and connector block of the neurostimulator IPG  650  is depicted implanted in patient  10  in FIG. 9. Again, the boot  615  has a major side opening  635  and an edge opening  640  enabling access to the connector block  660  that the lead extension  610  is attached to. The neurostimulator IPG  650  and boot  615  encasing the neurostimulator IPG  650   d  are implanted just under the skin of the upper thorax in a prepared subcutaneous pocket  140 . The exposed surface of the bipolar neurostimulator housing  655  can be employed as a stimulation electrode in this instance.  
         [0053]    An implantable infusion pump (IIP) comprising an implantable drug pump and catheter is disclosed in commonly assigned U.S. Pat. Nos. 5,643,207 and 5,782,798 for dispensing pancreatic polypeptide blockers and other drugs that decrease sensations of hunger and increase satiety into particular sites in the brain through a distal catheter segment that is implanted through the skull and extends to the specific sites. The delivery of other appetite influencing drugs directly into the brain for increasing appetite to treat anorexia is also proposed in the &#39;207 patent. The drug that is dispensed from the infusion pump coupled to the catheter through the catheter lumen and into the brain is expected to induce or increase the feeling of satiety to treat obesity by reducing caloric intake or to increase feelings of hunger to treat anorexia by increasing caloric intake. The system of the &#39;798 patent can also be employed to apply electrical stimulation to the brain through catheter borne electrodes and conductors to increase feelings of satiety to treat obesity or to decrease feelings of satiety to treat anorexia presumably either with of without delivery of the identified drugs.  
         [0054]    Such an implantable deep brain drug delivery system  700  is depicted in FIG. 10 comprising an implantable drug pump  750  and catheter  710  for dispensing pancreatic polypeptide blockers and other drugs that decrease sensations of hunger and increase satiety through catheter ports  780  into a particular site  135  in the brain  130  through a distal catheter segment  770  that is implanted through the skull and extends to the specific site  135 . The implantable drug pump  750  can comprise a programmable SynchroMed® drug pump  750 . A detachable, elastic, boot  715  that is compounded of silicone rubber and the preferred anti-microbial metal ion zeolite and molded in a shape to be fitted over the housing and connector of the drug pump  750  is depicted implanted in patient  10  in FIG. 10. Again, the boot  715  has a major side opening  735  in this case exposing a drug fill port  755  for percutaneously refilling a drug chamber within the drug pump  750  in a manner well known in the art. The boot  715  also has an edge opening  740  enabling access to the connector block  760  that the drug delivery catheter  710  is attached to. The drug pump  750  and boot  715  encasing the drug pump  750  are implanted just under the skin of the thorax in a prepared subcutaneous pocket  140  so that the drug fill port is oriented outward to enable access to the drug fill port  755 .  
         [0055]    An implantable EGM monitor for recording the cardiac electrogram from electrodes remote from the heart is disclosed in commonly assigned U.S. Pat. No. 5,331,966 and PCT publication WO 98/02209 and is embodied in the Medtronic® REVEAL® Model 9526 Insertable Loop Recorder having spaced housing EGM electrodes employed with a Model 6191 patient activator and a Model 9790 programmer. Such implantable monitors when implanted in patients suffering from cardiac arrhythmias or heart failure accumulate date and time stamped data that can be of use in determining the condition of the heart over an extended period of time and while the patient is engaged in daily activities. A wide variety of other IMDs have been proposed to monitor many other physiologic conditions as set forth in U.S. Pat. No. 6,221,011.  
         [0056]    Therefore, a REVEAL® Insertable Loop Recorder  850  is depicted in FIG. 11 implanted in a subcutaneous pocket  140  in the thorax of patient  10 . The Insertable Loop Recorder  850  comprises a hermetically sealed housing  855  enclosing the monitoring circuitry, battery, telemetry antenna, and other components and a header  860  that supports a sense electrode  810  coupled to the a sense amplifier via a feedthrough extending through the housing  855  and has a pair of suture holes extending through it. An electrically uninsulated portion of the housing  855  that is coupled with the sense amplifier provides a second sense electrode  820 . A detachable, elastic, boot  815  that is compounded of silicone rubber and the preferred anti-microbial metal ion zeolite and molded in a shape to be fitted over at least the housing  855 . Again, the boot  815  has a major side opening  835  exposing the sense electrode  820  and an edge opening  840  enabling insertion of the housing  855  into the boot  815 . The boot  815  may be shaped to extend over at least the portions of the header  860  having the suture holes to enable using the same sutures to secure the boot to the Insertable Loop Recorder  850  and the Insertable Loop Recorder  850  to subcutaneous tissue.  
         [0057]    Thus, a variety of subcutaneously implanted IMDs have been described having a variety of uses and shapes that are implanted in subcutaneous pockets  140 ,  140 ′ and over which a detachable anti-microbial component characterized as a pad or boot that fits around at least a portion of an outer housing of the IMD is placed. The subcutaneous site is advantageously protected from microbial growth and infections of the types described above by inclusion of the anti-microbial polymeric component that is exposed to body fluids in the pockets  140 ,  140 ′ that is compounded of an antibiotic zeolite that elutes silver ions in concentrations exhibiting anti-microbial activity over a substantial period of time of implantation. In these embodiments depicted in FIGS. 1-11, the anti-microbial component is physically attached to the IMD by fitting it over the IMD. It will be understood that the anti-microbial component can be molded to conform to the shape of any IMD adapted to be implanted subcutaneously that is presently available or may become available in the future, e.g., gastric stimulators and drug pumps, insulin delivery drug pumps, and other body organ, muscle or nerve stimulators and drug delivery devices that are specifically identified herein.  
         [0058]    In another preferred embodiment, the anti-microbial component comprises a permanently attached portion of any of the above-identified IMDs that are implanted into the prepared subcutaneous pocket  140 . For example, a schematic partial view of an exemplary IPG/monitor  950  depicting the connector header  960  in partial cross-section and an exemplary lead connector assembly  915  of an electrical medical lead  910  adapted to be fitted into a connector bore  965 , is depicted in FIG. 12. A bipolar lead  910  is depicted having a connector assembly  915  of conventional bipolar design comprising a connector pin  920  and a connector ring  930  adapted to fit a pin receptacle contact  925  and a ring receptacle contact of schematically depicted connector header  960 . Elastic polymeric sealing rings  940  and  945  are located adjacent to the connector pin  920  and connector ring  930 . A distal portion  985  of the lead connector assembly  915  coupled to the elongated lead body  990  is disposed outside the connector bore  965  when the more proximal portion of the lead connector assembly  915  is fully inserted within the connector bore  965 . Elastic bands  970  and  980  encircle the connector bore opening and a suture can be applied to tighten them against the elastic portion of the connector assembly between the sealing rings  945  and the distal portion  955 . The particular configurations of the connector elements  925  and  935 , the feedthroughs and wire connections, and any setscrews or other fasteners that are encased within the molded polymeric header body  975  for making secure electrical connections can take any of the known configurations and are not important to the practice of the present invention and are not depicted. The depicted IPG/monitor  950  is exemplary of any of the IPG/monitors and components thereof  50 ,  250 ,  305 - 310 ,  450 , and  650 , although the number of connector elements of the lead connector assembly and the connector header and their specific configurations may vary widely.  
         [0059]    Selected ones or all of the polymeric components of the IPG connector header  975  and/or the lead connector assembly  915  are compounded with metal ion zeolite as indicated by the hatching in FIG. 12 in accordance with a further embodiment of the invention. Usually, the lead connector assembly  915  is separately formed and attached to the lead body  990  in manufacture, so it is convenient to mold the polymeric lead connector assembly parts from silicone rubber or polyurethane compounded with the metal ion zeolite. The anti-microbial silver ions can thereby be eluted from the connector header body  975  and/or from the elastic band  970  and or from the lead connector portion  985  that is disposed outside the connector bore  965 . The anti-microbial silver ions can also be eluted from the sealing rings  940  and  945  if they become wet with body fluids over chronic implantation to inhibit any microbial activity within the connector bore/connector assembly interface.  
         [0060]    [0060]FIG. 13 is a perspective view of a subcutaneously implantable C/D electrode, e.g., C/D electrode  275  wherein selected ones or all of the polymeric components of the C/D electrode  275  are compounded with metal ion zeolite in accordance with a further embodiment of the invention. In particular, all or portions of the silicone rubber or polyurethane pad  220  can be molded with the metal ion zeolite as indicated by the hatching in FIG. 13. Again, the silicone rubber or polyurethane pad  220  is separately formed and attached to the lead body of C/D lead  265  in manufacture, so it is convenient to mold the polymeric pad as a single part or as multiple parts, depending on the design, from silicone rubber or polyurethane compounded with the metal ion zeolite.  
         [0061]    Similarly, the polymeric header  860  of the implantable monitor  800 , for example, the subcutaneously tunneled cable  315 , for example, between subcutaneously implanted IMD components, and the polymeric component of the catheter connectors  560  and  760  with the implantable drug pumps  500  and  700 , for example, can be molded from polymers compounded with metal ion zeolite.  
         [0062]    All patents and publications referenced herein are hereby incorporated by reference in their entireties.  
         [0063]    It will be understood that certain of the above-described structures, functions and operations of the above-described preferred embodiments are not necessary to practice the present invention and are included in the description simply for completeness of an exemplary embodiment or embodiments.  
         [0064]    In addition, it will be understood that specifically described structures, functions and operations set forth in the above-referenced patents can be practiced in conjunction with the present invention, but they are not essential to its practice.  
         [0065]    It is therefore to be understood, that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described without actually departing from the spirit and scope of the present invention.

Technology Classification (CPC): 0