US20100278895A1 - Antioxidants and antimicrobial accessories including antioxidants - Google Patents

Abstract

An antimicrobial accessory may include a polymer an antimicrobial mixed in the polymer, and an antioxidant. The antioxidant may include, for example, at least one of citric acid, maltol, kojic acid, malic acid, or vitamin A. In some examples, the antioxidant may include an ascorbate peroxidase in combination with ascorbic acid, a glutathione peroxidase in combination with glutathione, or a superoxide dismutase in combination with a metal such as Ni, Cu, Mn, or Fe. In some examples, the antimicrobial accessory may include at least three polymer layers. For example, the antimicrobial accessory may include a first layer comprising a biodegradable polymer and an antimicrobial. The antimicrobial accessory may further include a sacrificial diffusion layer formed on a surface of the first layer. The sacrificial diffusion layer may include a biodegradable polymer, which may be the same biodegradable polymer as in the first layer or may be a different biodegradable polymer. The antimicrobial accessory may also include a topcoat formed on the sacrificial diffusion layer. The topcoat may include a biodegradable polymer and at least one antioxidant mixed in the biodegradable polymer.

Description

• This application claims the benefit of U.S. Provisional Application No. 61/174,349, entitled, “ANTIOXIDANTS AND ANTIMICROBIAL ACCESSORIES INCLUDING ANTIOXIDANTS,” filed on Apr. 30, 2009, and U.S. Provisional Application No. 61/174,411, entitled, “ANTIOXIDANTS AND ANTIMICROBIAL ACCESSORIES INCLUDING ANTIOXIDANTS,” filed on Apr. 30, 2009, the entire contents of which are incorporated herein by reference.
TECHNICAL FIELD
• The disclosure relates to implantable medical devices and, more particularly, to methods of reducing risk of post-implantation infection.
BACKGROUND
• Implantable medical devices (IMDs) include a variety of devices that provide therapy (such as electrical stimulation or drug delivery) to a patient, monitor a physiological parameter of a patient, or both. IMDs typically include a number of functional components encased in a housing. An IMD may also include a lead or catheter extending from the housing. The housing and lead or catheter is implanted in a body of the patient. For example, the housing may be implanted in a pocket created in a torso of a patient. The housing, lead, and/or catheter may be constructed of biocompatible materials, such as titanium, silicone, polyurethane, or the like. While the housing, lead and catheter are biocompatible, there may still be a risk of infection to the patient as a result of the implantation procedure or the presence of the IMD in the body.
SUMMARY
• In general, the disclosure is directed to an antimicrobial accessory for use with an implantable medical device (IMD). The antimicrobial accessory may be configured to be attached to or implanted adjacent to the IMD to reduce or substantially eliminate risk of post-implant infection to a patient in which the IMD is implanted. In some examples, the antimicrobial accessory may be formed integrally with the IMD, such as a housing of the IMD, a lead body, or a catheter.
• The antimicrobial accessory may include a polymer, an antimicrobial mixed in the polymer, and an antioxidant mixed in the polymer. The antioxidant may generally be a naturally occurring compound with antioxidant properties. The antioxidant may include multiple conjugated double bonds, e.g., may be a highly conjugated compound, may be a relatively low molecular weight compound, or both. For example, the antioxidant may include at least one of citric acid, maltol, kojic acid, malic acid, or vitamin A. When an antioxidant compound is highly conjugated and relatively low molecular weight, the antioxidant may be an efficient electron or free radical scavenger on a per weight basis. Additionally, an antioxidant having a relatively low molecular weight may facilitate mixing of the antioxidant into the polymer. In some embodiments, the antioxidant includes an enzyme and a substrate on which the enzyme acts, such as, for example, an ascorbate peroxidase in combination with ascorbic acid, a glutathione peroxidase in combination with glutathione, or a superoxide dismutase in combination with a metal such as Ni, Cu, Mn, or Fe. The enzyme catalyzes oxidation of the substrate, and may provide improved oxidation protection to the polymer and/or antimicrobial than an antioxidant substrate alone.
• In some examples, the antimicrobial accessory may include multiple layers. For example, the antimicrobial accessory may include a first layer comprising a biodegradable polymer and an antimicrobial. The antimicrobial accessory may further include a sacrificial diffusion layer formed on a surface of the first layer. The sacrificial diffusion layer may include a biodegradable polymer, which may be the same biodegradable polymer as in the first layer or may be a different biodegradable polymer. The antimicrobial accessory may also include a topcoat formed on the sacrificial diffusion layer. The topcoat includes a biodegradable polymer and an antioxidant.
• The sacrificial diffusion layer may reduce or substantially eliminate contamination of the antimicrobial disposed in the first layer with the antioxidant or impurities formed from oxidation of the antioxidant disposed in the topcoat. At least one of the thickness of the sacrificial diffusion layer and the material from which the sacrificial diffusion layer is formed may be selected so that the topcoat and sacrificial diffusion layer degrade before mixing of the antioxidant and the antimicrobial occurs in the sacrificial diffusion layer.
• In one aspect, the disclosure is directed to an antimicrobial accessory comprising a polymer, an antimicrobial mixed in the polymer, and an antioxidant mixed in the polymer. According to this aspect of the disclosure, the antioxidant is selected from the group consisting of citric acid, maltol, kojic acid, malic acid, vitamin A, an ascorbate peroxidase in combination with ascorbic acid, a glutathione peroxidase in combination with glutathione, a superoxide dismutase in combination with a metal, or combinations thereof.
• In another aspect, the disclosure is directed to a system comprising an implantable medical device and an antimicrobial accessory. According to this aspect of the disclosure, the antimicrobial accessory includes a polymer, an antimicrobial mixed in the polymer, and an antioxidant mixed in the polymer. The antioxidant is selected from the group consisting of citric acid, maltol, kojic acid, malic acid, vitamin A, an ascorbate peroxidase in combination with ascorbic acid, a glutathione peroxidase in combination with glutathione, a superoxide dismutase in combination with a metal, or combinations thereof.
• The details of one or more examples of the disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the disclosure will be apparent from the description and drawings, and from the claims.
BRIEF DESCRIPTION OF DRAWINGS
• FIG. 1 is a cross-sectional diagram illustrating an example of an antimicrobial accessory including a first layer comprising a biocompatible polymer, an antimicrobial, and an antioxidant, and an adhesive layer formed on the first layer.
• FIG. 2 is a conceptual diagram of an example of an antimicrobial accessory attached to a housing of an implantable medical device.
• FIG. 3 is a conceptual diagram of an example of an antimicrobial accessory including a pouch enclosing an implantable medical device.
• FIG. 4 is a conceptual diagram of an example of an antimicrobial accessory including a sleeve fitted around a housing of an implantable medical device.
• FIG. 5 is a cross sectional diagram of an example of a lead body including an outer jacket comprising an antimicrobial accessory.
• FIG. 6 is a cross-sectional diagram illustrating an example of an antimicrobial accessory including a first layer comprising a biodegradable polymer and an antimicrobial, a sacrificial diffusion layer comprising a biodegradable polymer formed on the first layer, and a topcoat comprising a biodegradable polymer and an antioxidant formed on the sacrificial diffusion layer.
• FIG. 7 is a conceptual diagram illustrating an example of diffusion of an antimicrobial out of a first layer and into a sacrificial diffusion layer, and diffusion of an antioxidant out of a topcoat and into the sacrificial diffusion layer and the surrounding environment.
• FIG. 8 is a cross-sectional diagram illustrating another example of an antimicrobial accessory including a first layer, a first sacrificial diffusion layer formed on a first surface of the first layer, a topcoat formed on the first sacrificial diffusion layer, a second sacrificial diffusion layer formed on a second surface of the first layer, and a base layer formed on the second sacrificial diffusion layer.
• FIG. 9 is a flow diagram illustrating an example of a technique for forming an antimicrobial accessory including a first layer, a sacrificial diffusion layer formed on the first layer, and a topcoat formed on the sacrificial diffusion layer.
DETAILED DESCRIPTION
• In general, the disclosure is directed to an antimicrobial accessory that may be implanted in a body of a patient. The patient may be, but will not always be, a human. In some examples, the antimicrobial accessory may be configured to be implanted proximate to or attached to an implantable medical device (IMD). For example, the antimicrobial accessory may be utilized with an implantable cardioverter/defibrillator, a pacemaker, an implantable drug delivery device, an implantable monitoring device that monitors one or more physiological parameter of a patient, an implantable neurostimulator (e.g., a spinal cord stimulator, a deep brain stimulator, a pelvic floor stimulator, a peripheral nerve stimulator, or the like), a cardiac or neurological lead, a catheter, an orthopedic device such as a spinal device, or the like. In general, the antimicrobial accessory may be attached to or implanted proximate to any medical device configured to be implanted in a body of a patient.
• In other examples, the antimicrobial accessory may be formed integrally with the IMD. For example, the antimicrobial accessory may form a portion of a housing of an IMD, or may form a portion of a lead body or catheter body. In any of these examples, the antimicrobial accessory may reduce or substantially eliminate risk of infection proximate to an implant site at which the antimicrobial accessory is implanted in a body of a patient. The antimicrobial accessory may include a polymer, an antimicrobial, and an antioxidant.
• Because the antimicrobial accessory is configured to be implanted in a body of a patient, the antimicrobial accessory may be sterilized after being formed and prior to being packaged or prior to being implanted in the patient. The antimicrobial accessory may be sterilized using, for example, ethylene oxide, an electron beam, a gamma beam, autoclaving, or the like. In some examples, a method of sterilization may initiate degradation of the polymer from which the antimicrobial accessory is formed, which may adversely affect the mechanical properties of the polymer. In some examples, the method of sterilization may adversely affect the antimicrobial in addition or alternative to affecting the polymer. The antimicrobial accessory includes an antioxidant to combat the degradation of the polymer and/or antimicrobial. The antioxidant may be more easily oxidized than the polymer and/or the antimicrobial, and may reduce or substantially prevent the oxidation of the polymer and/or the antimicrobial. For example, the antioxidant, when oxidized, may form a relatively stable free radical, which has a significantly lower reactivity than a free radical formed by reaction of the polymer or antimicrobial. As another example, the antioxidant, when oxidized, may form a compound that is not a free radical, and which is relatively non-reactive. In this way, even if the sterilization process initiates oxidation of the polymer or antimicrobial, the antioxidant may react with the oxidized polymer or antimicrobial and slow or substantially stop propagation of oxidation reactions. Alternatively or additionally, the antioxidant may react with and be oxidized by other free radical species or oxidizing species present in the antimicrobial accessory (e.g., a sterilization agent such as ethylene oxide) and may slow or substantially stop the oxidation of the polymer or antimicrobial.
• In some examples, the antimicrobial and the antioxidant are mixed in the same layer of polymer to form a substantially homogeneous layer including the polymer, antimicrobial, and antioxidant. In other examples, the antimicrobial accessory includes at least three distinct layers. A first layer of the antimicrobial accessory may include a biodegradable polymer and an antimicrobial mixed in the biodegradable polymer. The antimicrobial accessory may further include a sacrificial diffusion layer formed on the first layer. The sacrificial diffusion layer may include a biodegradable polymer, which may be the same biodegradable polymer as in the first layer, or may be a different biodegradable polymer. The antimicrobial accessory may also include a topcoat including a biodegradable polymer and an antioxidant formed on the sacrificial diffusion layer. The sacrificial diffusion layer may substantially prevent mixing in the antimicrobial accessory of the antimicrobial and the antioxidant or a product of oxidation of the antioxidant.
• FIG. 1 is a cross-sectional diagram of an example of anantimicrobial accessory10 including afirst layer12 comprising a biocompatible polymer, an antimicrobial mixed in the biocompatible polymer, and an antioxidant mixed in the biocompatible polymer. In some examples, as illustrated inFIG. 1,antimicrobial accessory10 further includes anadhesive layer14 formed on afirst surface16 of thefirst layer12. In other examples, antimicrobial accessory does not includeadhesive layer14.
• In some examples, the biocompatible polymer is biodegradable or bioabsorbable, such thatfirst layer12 ofantimicrobial accessory10 breaks down or is absorbed by a body of a patient over time after being implanted in the patient. This may facilitate release of substantially all of the antimicrobial, which may reduce risk of bacteria developing resistance to the antimicrobial inantimicrobial accessory10. Anantimicrobial accessory10 including a biodegradable polymer may also mitigate or prevent growth of bacteria onantimicrobial accessory10 after the antimicrobial has eluted from theaccessory10. For example, the biodegradable polymer may break down over time after being implanted in the patient. In some examples, the biodegradable polymer may comprise poly(lactic-co-glycolic acid) (PLGA), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(ethylene oxide) (PEO), poly(ortho ester) (POE), poly(dioxanone), a hydrophilic hydrogel, a hydrophobic hydrogel, a polyanhydride, an amino acid polymer such as a tyrosine polymer, or the like.
• In other examples, the biocompatible polymer is not biodegradable and may remain implanted in the body of the patient indefinitely. For example, the polymer may include silicone, polyurethane, an epoxy, nylon, a polyester, blends of these polymers, co-copolymers of these polymers, or the like.
• The antimicrobial may include, for example, an antibiotic such as minocycline, rifampin, clindamycin, tigecycline, daptomycin, gentamicin, or another fluoroquinolone, an antiseptic, an antimicrobial peptide, a quaternary ammonium, or the like. In some examples, the antimicrobial may be provided in a salt form, e.g., minocycline HCl. The antimicrobial may be selected to provide efficacious prevention or treatment of any infection which may be present proximate to the implant site at which the IMD is implanted. In some examples, the antimicrobial accessory may include at least two antimicrobials, and the combination of the at least two antimicrobials may be selected to efficaciously treat or prevent any infection present proximate to the implant site of the IMD. One example of two antimicrobials that may be used together is minocycline and rifampin.
• In general, the antimicrobial may be mixed intofirst layer12 to a concentration of less than about 50 weight percent (wt. %). In some preferred examples, the antimicrobial may be mixed intofirst layer12 to a concentration of between about 5 wt. % and about 50 wt. %. In other preferred examples, the antimicrobial may be mixed intofirst layer12 to a concentration of between about 10 wt. % and about 20 wt. %. The concentration to which the antimicrobial is mixed intofirst layer12 may depend on, for example, the method of formingantimicrobial accessory10, the efficacy of the antimicrobial, the geometry ofantimicrobial accessory10, the desired elution profile of the antimicrobial fromantimicrobial accessory10, the desired duration of elution of the antimicrobial fromantimicrobial accessory10, or the like.
• The antioxidant may include, for example, a naturally occurring compound that possesses antioxidant properties. In other words, the compound is capable of mitigating or eliminating oxidation of other molecules, such as the polymer and/or antimicrobial inantimicrobial accessory10. In many oxidation reactions, a free radical is formed as an intermediate in the oxidation reaction or as a product of the oxidation reaction. The antioxidant may react with the free radical and thus inhibit further reactions. In many cases, the antioxidant may contain one or more phenyl rings, conjugated double bonds, or carboxyl groups. In some examples, the antioxidant may be lipid soluble, may be a biological compound, or both.
• In some examples, the antioxidant may include a compound that contains multiple conjugated double bonds, e.g., a highly conjugated compound, a relatively low molecular weight compound, or both. A highly conjugated compound may be a more effective antioxidant than a compound including fewer conjugated double bonds. When an antioxidant compound is highly conjugated and relatively low molecular weight, the antioxidant may be an efficient electron or free radical scavenger on a per weight basis. Additionally, an antioxidant with a relatively low molecular weight may facilitate mixing of the antioxidant into the polymer. Examples of antioxidants that are highly conjugated, relatively low molecular weight, or both are shown below in Formulas 1-5.
• In some examples, the antioxidant includes an enzyme and a substrate on which the enzyme acts. The enzyme catalyzes oxidation of the substrate, and may provide improved oxidation protection to the polymer and/or antimicrobial than an antioxidant substrate alone. Examples of antioxidants including an enzyme and a substrate on which the enzyme acts are shown below in Reactions 1-3.
• In one example, the antioxidant includes citric acid, also referred to as 3-hydroxypentanedioic acid-3-carboxylic acid. The structure of citric acid is shown in Formula. 1.
• 
• Citric acid contains three carboxyl groups, which may be oxidized by removal of a hydrogen atom. The resulting free radical is stabilized by resonance of the lone electron between the adjacent carbon-oxygen bonds. Citric acid has a molecular weight of approximately 192.12 g/mol.
• In another example, the antioxidant includes maltol. Maltol includes conjugated double bonds, and has a molecular weight of approximately 126.11 g/mol. The structure of maltol is shown in Formula 2.
• 
• In another example, the antioxidant includes kojic acid, which also is referred to as 5-hydroxy-2-(hydroxymethyl)-4-pyrone or 2-hydroxymethyl-5-hydroxy-γ-pyrone. Kojic acid includes conjugated double bonds and has a molecular weight of approximately 142.11 g/mol. The chemical structure of kojic acid is shown below in Formula 3.
• 
• In another example, the antioxidant includes malic acid. The chemical structure of malic acid is shown below in Formula 4.
• 
• Malic acid includes two carboxyl groups that may be easily oxidized by removal of a hydrogen atom. The oxidized malic acid may be stabilized by resonance of the free electron between the adjacent carbon-oxygen bonds of the carboxyl groups. Malic acid has a molecular weight of approximately 134.09 g/mol.
• The antioxidant may also include vitamin A, the structure of which is shown below in Formula 5. Vitamin A includes five of conjugated double bonds and has a molecular weight of approximately 286.45 g/mol.
• 
• In some examples, the antioxidant includes an enzyme and a substrate antioxidant on which the enzyme acts. The use of an enzyme may catalyze the oxidation of the substrate antioxidant, and may increase the efficacy with which the substrate antioxidant protects the polymer and/or antimicrobial from oxidation.
• In some examples, the antioxidant may include an ascorbate peroxidase (or APX1) in combination with an ascorbate. Ascorbate peroxidases are enzymes that detoxify peroxides using ascorbate as a substrate. Ascorbate peroxidases catalyze transfer of electrons from ascorbate to a peroxide. The transfer of the electrons produces dehydroascorbate and water. One such reaction catalyzed by ascorbate peroxidases is shown below in Reaction 1. In Reaction 1, ascorbate peroxidase catalyzes oxidation of ascorbic acid to dehydroascorbic acid and reduction of hydrogen peroxide to water. Ascorbate peroxidases may provide general antioxidant activities by catalyzing the reaction of ascorbate with other free radicals or free radical generating compounds in a similar manner.
• 
• The antioxidant may also include a glutathione peroxidase in combination with a glutathione. Glutathione peroxidase is an enzyme family that reduces peroxides using glutathione as a substrate. One example of a reaction catalyzed by glutathione peroxidase is shown below in Reaction 2. Glutathione peroxidase may provide more general antioxidant activities by catalyzing the reaction of glutathione with other free radicals or free radical generating compounds in a similar manner.
• 
• In some examples, the antioxidant may include a superoxide dismutase (SOD) and a metal, such as copper, manganese, iron, or nickel. Superoxide dismutases are enzymes that catalyze the dismutation of superoxide into oxygen and hydrogen peroxide using a metal substrate. The dismutation of superoxide may be represented as two half-reactions, shown below in Reaction 3.
• 
  M⁽ⁿ⁺¹⁾-SOD+O₂⁻→Mⁿ⁺-SOD+O₂
• 
  Mⁿ⁺-SOD+O₂⁻+2H⁺→M⁽ⁿ⁺¹⁾-SOD+H₂O₂  Reaction 3
• where M=Cu (n=1), Mn (n=2), Fe (n=2), or Ni (n=2).
• Depending on the antioxidant used,antimicrobial accessory10, and more specificallyfirst layer12, may include a range of antioxidant concentrations. In some examples,first layer12 may include less than about 15 volume percent (vol. %) antioxidant. In other examples,first layer12 may include less than about 9 vol. % antioxidant. In some preferred examples,first layer12 may include between about 2 vol. % and about 9 vol. % antioxidant, or between about 5 vol. % and about 9 vol. % antioxidant. In examples in which the antioxidant includes both an enzyme and a substrate antioxidant, the combined concentration of the enzyme and substrate antioxidant infirst layer12 may be as great as about 30 vol. %. In some examples, the combined concentration of the enzyme and the substrate antioxidant in first layer may be as greater as about 15 vol. %. The amount of antioxidant infirst layer12 may be selected by considering, for example, a radiation level to whichantimicrobial accessory10 will be exposed, a desired shelf-life ofantimicrobial accessory10, a thickness ofantimicrobial accessory10, or which antioxidant is being used inantimicrobial accessory10.
• The polymer, antioxidant, and antimicrobial may be mixed in a solvent, such as tetrahydrofuran (THF) to form a solution or suspension. The solution or suspension may then be spray coated onto a substrate, such as a release liner, to formantimicrobial accessory10. In other examples, the solution or suspension may be coated onto a release liner using another coating technique, such as, for example, knife coating, air knife coating, gap coating, gravure coating, slot die coating, metering rod coating, doctor blade, or the like.
• In some examples, the antioxidant and/or the antimicrobial may be mixed directly into a polymer melt and extruded, casted, or molded to formantimicrobial accessory10. In examples in which the antioxidant and/or antimicrobial is mixed into a polymer melt, the melt temperature, mixing shear rate, and residence time may be balanced to prevent degradation of the antimicrobial and/or antioxidant. For example, lower temperatures, shear rates, and/or residence times may reduce or substantially eliminate degradation of the antioxidant and/or antimicrobial. In various examples, one, two, or all three of the melt temperature, mixing shear rate, and residence time may be controlled or selected to mitigate or eliminate degradation of the antimicrobial and/or antioxidant.
• In some examples, as illustrated inFIG. 1,antimicrobial accessory10 includes aadhesive layer14, such as, for example, a silicone, acrylic, or polyisobutylene PSA, applied onfirst surface16 offirst layer12.Adhesive layer14 may be applied tofirst surface16 offirst layer12 by, for example, spray coating, knife coating, air knife coating, gap coating, gravure coating, slot die coating, metering rod coating, doctor blade, or the like.
• In other examples,antimicrobial accessory10 does not include anadhesive layer14. For example,antimicrobial accessory10 may be attached to an IMD by other means, such as a suture or staple. In other examples,antimicrobial accessory10 is not be attached to an IMD in any manner, and is simply implanted in a patient proximate to an IMD. These methods may be advantageous whenfirst layer12 includes a biodegradable polymer, because no adhesive residue will be left on a surface of the IMD. In some examples, the suture may also be biodegradable. In other examples,antimicrobial accessory10 may be formed integrally with a housing of an IMD, or may form a portion of a lead body, catheter, or the like. In such examples,antimicrobial accessory10 may not include anadhesive layer14 or any other means of attachment. Instead,antimicrobial accessory10 may be a portion of the IMD, lead, or catheter.
• In examples in whichantimicrobial accessory10 includes anadhesive layer14,antimicrobial accessory10 may be disposed on a release liner, such as a fluoropolymer release liner, to provide a convenient article for storing, shipping, and providing to the implanting clinician. In some examples, anantimicrobial accessory10 disposed on a release liner may be packaged in a foil package or other substantially air and water impermeable package that is vacuum sealed or backfilled with an inert gas.
• Antimicrobial accessory10 may then be sterilized using, for example, an electron beam, a gamma beam, ethylene oxide, autoclaving, or the like. As described above, in some examples the sterilization may initiate degradation of one or both of the polymer and antimicrobial inantimicrobial accessory10 through oxidation reactions. The presence of the antioxidant may slow or substantially stop the oxidation of the polymer and/or the antimicrobial.
• Antimicrobial accessory10 may be formed into one of a variety of form factors, including, for example, a disk, a sheet, or a film. As illustrated inFIG. 2, animplantable system20 may include anIMD22 and a disk-shapedantimicrobial accessory24. Disk-shapedantimicrobial accessory24 may be adhered to a housing ofIMD22 by an adhesive layer (e.g.,adhesive layer14,FIG. 1), or may be attached toIMD22 by a suture or staple. In some examples, disk-shapedantimicrobial accessory24 may be sutured to a polymer connector block ofIMD22 or an aperture defined in the connector block. In other examples,antimicrobial accessory10 may not be attached toIMD22 in any manner, and may simply be implanted in a patient proximate toIMD22. These non-adhesive attachment methods may be advantageous when disk-shapedantimicrobial accessory24 includes a biodegradable polymer, because no adhesive residue will be left on a surface ofIMD22. In some examples, the suture may also be biodegradable.
• An antimicrobial accessory also may be constructed in other, different form factors, such as an extruded cylinder, a paste, or a clip. In some examples, an antimicrobial accessory26 may include a sheet or film, which may be adhered toIMD22. The sheet, film, or disk-shapedantimicrobial accessory24 may be applied to a single surface ofIMD22, or may be applied to two or more surfaces ofIMD22. The sheet or film may include a thickness similar to those described with respect to disk-shapedantimicrobial accessory24. Further, the sheet or film may be manufactured by similar processes to disk-shapedantimicrobial accessory24, and may be packaged and sterilized similarly.
• In other examples, as illustrated inFIG. 3, anantimicrobial accessory32 includes apouch32 that at least partially encloses a housing ofIMD22. In the example illustrated inFIG. 3,pouch32 substantially fully encloses the housing ofIMD22. As used herein, substantially fully enclosing refers to apouch32 that fully encloses the housing ofIMD22, but which may define at least one aperture that permits a lead, catheter, or other probe to extend fromIMD22 and out ofpouch32. In some examples,pouch32 may be attached to the housing ofIMD22 by an adhesive34.Adhesive34 may also function to close an opening inpouch32 through whichIMD22 is inserted intopouch32. In other examples,pouch32 simply fits around the housing ofIMD22. In some examples, the opening inpouch32 through whichIMD22 is inserted may be closed by welding, melting, or adhering two portions ofpouch32 together to form a substantiallycontinuous pouch32.Pouch32 may be sized and configured to fit intimately over the housing ofIMD22, or may be sized and configured to fit more loosely over the housing. In addition,pouch32 may be customized for anindividual IMD22 or a type or class ofIMD22, or may be formed more generically and may fit over a wider range of IMDs.
• In other examples, as illustrated inFIG. 4, an antimicrobial accessory may be formed into asleeve42.Sleeve42 may be sized and configured to fit over a housing of theIMD22. Theantimicrobial sleeve42 may include a polymer, an antioxidant, and at least one antimicrobial. In some examples,sleeve42 may form a friction fit with the housing of theIMD22, which maintains the sleeve substantially in position relative to the housing ofIMD22.Sleeve42 may also be adhered to theIMD22 by an adhesive, either additionally or instead of being friction fit around the housing.
• An antimicrobial accessory also may be formed integral with an IMD, catheter, or lead body. For example, an antimicrobial accessory may form an integral portion of a catheter, a housing of an IMD, a polymeric connector block of an IMD, or the like. In other examples, as illustrated inFIG. 5, an antimicrobial accessory includes anantimicrobial sheath52 that forms an integral portion of alead body50.FIG. 5 is a cross section oflead body50, and also illustrates aninner sheath54 that defines aninner lumen58 through which a stylet may be introduced to stiffen and guidelead body50 during implantation in a patient. Leadbody50 also includes a coiledconductor56 disposed in an annulus formed betweenantimicrobial sheath52 andinner sheath54. In some examples,antimicrobial sheath52 forms substantially the entire portion of an external sheath of thelead body50, e.g.,antimicrobial sheath52 may extend substantially from a proximal end oflead body50 to a distal end oflead body50. In other examples,antimicrobial sheath52 forms only a portion of an external sheath of thelead body50, andlead body50 includes an external sheath that includes at least one portion that is not anantimicrobial sheath52, i.e., does not include an antimicrobial.
• Although the preceding disclosure has been directed to an antimicrobial accessory including a single layer into which the antimicrobial and antioxidant are mixed, in some examples it may be beneficial to prevent mixing between the antimicrobial and the antioxidant (or products of the oxidation of the antioxidant). For example, the antioxidant may react to form impurities that negatively affect the efficacy of the antimicrobial. For this reason, an antimicrobial accessory may include in some examples a first layer comprising the antimicrobial, a sacrificial diffusion layer formed on a surface of the first layer, and a topcoat comprising the antioxidant formed on the sacrificial diffusion layer.
• FIG. 6 is a cross-sectional diagram that illustrates an example of such anantimicrobial accessory60.Antimicrobial accessory60 includes afirst layer62 including afirst surface68. Asacrificial diffusion layer64 is formed onfirst surface68 offirst layer62.Sacrificial diffusion layer64 includes opposite first surface68 asecond surface70, on which atopcoat66 is formed.
• Each offirst layer62,sacrificial diffusion layer64, andtopcoat66 may be formed of a biocompatible, biodegradable polymer. For example, each offirst layer62,sacrificial diffusion layer64, andtopcoat66 may be formed of at least one of poly(lactic-co-glycolic acid) (PLGA), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(ethylene oxide) (PEO), poly(ortho ester) (POE), poly(dioxanone), a hydrophilic hydrogel, a hydrophobic hydrogel, a polyanhydride, an amino acid polymer such as a tyrosine polymer, or the like. In some examples, at least two offirst layer62,sacrificial diffusion layer64, andtopcoat66 are formed of the same polymer, while in other examples, each offirst layer62,sacrificial diffusion layer64, andtopcoat66 are formed of different polymers.
• First layer62 may include an antimicrobial mixed into the biodegradable polymer. As described above, the antimicrobial may include at least one of minocycline, rifampin, clindamycin, tigecycline, daptomycin, gentamicin, or another fluoroquinolone, an antiseptic, an antimicrobial peptide, a quaternary ammonium, or the like. In some examples, the antimicrobial may be provided in a salt form, e.g., minocycline HCl. The antimicrobial may be selected to provide efficacious prevention or treatment of any infection that may be present proximate to the implant site at which the IMD is implanted. In some examples, the antimicrobial accessory includes at least two antimicrobials, and the combination of the at least two antimicrobials is selected to efficaciously treat or prevent any infection present proximate to the implant site of the IMD. One example of two antimicrobials that may be used together is minocycline and rifampin.
• In general,first layer62 may include less than about 50 wt. % of antimicrobial. In some preferred examples,first layer62 includes between about 5 wt. % and about 50 wt. % of antimicrobial. In other preferred examples,first layer62 includes between about 10 wt. % and about 20 wt. % of antimicrobial. The concentration of antimicrobial whichfirst layer62 includes may depend on, for example, the method of formingantimicrobial accessory60, the efficacy of the antimicrobial, the geometry ofantimicrobial accessory60, the desired elution profile of the antimicrobial fromantimicrobial accessory60, the desired duration of elution of the antimicrobial fromantimicrobial accessory60, or the like.
• In some examples,first layer62 may not be exposed to the external environment, e.g., a bodily fluids, upon implantation ofantimicrobial accessory60 in the body of a patient. For example,first layer62 may be an inner layer of an antimicrobial sheath52 (FIG. 5), may be located adjacent to or attached to a housing of an IMD22 (FIG. 2,3, or4), or may be oriented as an inner surface of a housing of a medical device. In such examples,first layer62 may only be exposed to bodily fluids oncetopcoat66 andsacrificial diffusion layer64 degrade and are removed. This may serve to only allow release of the antimicrobial infirst layer62 throughfirst surface68.
• Topcoat66 may include an antioxidant mixed into a biodegradable polymer. In some examples, the antioxidant may include at least one of citric acid (3-hydroxypentanedioic acid-3-carboxylic acid), maltol, kojic acid (5-hydroxy-2-(hydroxymethyl)-4-pyrone or 2-hydroxymethyl-5-hydroxy-γ-pyrone), malic acid, or vitamin A. The antioxidant may also include an ascorbate peroxidase in combination with an ascorbate, a glutathione peroxidase in combination with glutathione, or a superoxide dismutase in combination with a metal such as Cu, Mn, Fe, or Ni.
• Depending on the antioxidant used,topcoat66 may include a range of antioxidant concentrations. In some examples,topcoat66 may include less than about 15 vol. % antioxidant. In other examples,topcoat66 may include less than about 9 vol. % antioxidant. In some preferred examples,topcoat66 may include between about 2 vol. % and about 9 vol. % antioxidant, or between about 5 vol. % and about 9 vol. % antioxidant. In examples in which the antioxidant includes both an enzyme and a substrate antioxidant, the combined concentration of the enzyme and substrate antioxidant intopcoat66 may be as great as about 30 vol. %. In some examples, the combined concentration of the enzyme and the substrate antioxidant intopcoat66 may be as great as about 15 vol. %. The amount of antioxidant intopcoat66 may be selected by considering, for example, a radiation level to whichantimicrobial accessory60 will be exposed, a desired shelf-life ofantimicrobial accessory60, a thickness ofantimicrobial accessory60, or which antioxidant is being used inantimicrobial accessory60.
• Sacrificial diffusion layer64 may be formed of a biodegradable polymer that degrades over time after being implanted in a body of a patient. At least one of the biodegradable polymer and the thickness ofsacrificial diffusion layer64 may be selected to substantially prevent interdiffusion (i.e., mixing) of the antioxidant or products of oxidation of the antioxidant and the antimicrobial in sacrificial diffusion layer64 (e.g., prior to degradation and removal of sacrificial diffusion layer64).
• As illustrated inFIG. 7, the antimicrobial may diffuse fromfirst layer62 intosacrificial diffusion layer64. The diffusion of the antimicrobial fromfirst layer62 is represented by a first set ofarrows78. Similarly, the antioxidant or product of oxidation of the antioxidant may diffuse fromtopcoat66 intosacrificial diffusion layer64, as represented by a second set ofarrows76. The antioxidant or product of oxidation of the antioxidant may also diffuse fromtopcoat66 into the surrounding environment, as represented by a third set ofarrows74.
• Sacrificial diffusion layer64 may function to substantially prevent diffusion of the antioxidant and antimicrobial from proceeding to the extent that the antioxidant and the antimicrobial mix in thesacrificial diffusion layer64. More particularly, the thickness and/or material from whichsacrificial diffusion layer64 is formed may be selected so thattopcoat66 andsacrificial diffusion layer64 degrade before mixing of the antioxidant and antimicrobial occurs insacrificial diffusion layer64.
• The material from whichsacrificial diffusion layer64 is formed may affect the rate at which the antioxidant and the antimicrobial diffuses into and throughsacrificial diffusion layer64. Different materials may have different permeabilities to the antioxidant and the antimicrobial. By formingsacrificial diffusion layer64 of a material that has a lower permeability to at least one of the antimicrobial and the antioxidant, the rate at which the antimicrobial and/or the antioxidant diffuses throughsacrificial diffusion layer64 may be lowered. This may more effectively prevent mixing of the antioxidant and antimicrobial than a material with a higher permeability to at least one of the antimicrobial and the antioxidant.
• The material from whichsacrificial diffusion layer64 is formed may also affect the rate at which thesacrificial diffusion layer64 degrades once implanted in the body of the patient. Thus, the selection of the material for formingsacrificial diffusion layer64 may be based on consideration of the permeability of the material to the antimicrobial and/or antioxidant being used, and also the degradation rate of the material.
• The thickness ofsacrificial diffusion layer64 may also affect the efficacy of thesacrificial diffusion layer64 in preventing mixing of the antimicrobial and antioxidant. In particular, although a thickersacrificial diffusion layer64 may take a longer time to fully degrade, the thickersacrificial diffusion layer64 may emphasize a difference between the degradation rate and diffusion rates of the antimicrobial and/or the antioxidant. When the degradation rate ofsacrificial diffusion layer64 is faster than the diffusion rate of the antioxidant and/or the antimicrobial, an increase in the thickness of thelayer64 serves to increase the total time over which diffusion and degradation will occur in thelayer64, and thus lead to a greater difference in the progression of degradation of thelayer64 and diffusion of the antimicrobial and/or the antioxidant through thelayer64. In this way, a thickersacrificial diffusion layer64 may in some examples better prevent mixing of the antioxidant and the antimicrobial in thelayer64.
• The thickness and/or composition ofsacrificial diffusion layer64 may also affect the release profile of the antimicrobial fromfirst layer62 into the body of a patient. In some examples, the antimicrobial will not be released into the body until thetopcoat66 andsacrificial diffusion layer64 have degraded to the point that polymer including the antimicrobial mixed therein is exposed to the surrounding body environment. The polymer may include a portion ofsacrificial diffusion layer64 into which the antimicrobial has diffused, or may includefirst layer62 ifsacrificial diffusion layer64 has degraded before substantial diffusion of the antimicrobial intosacrificial diffusion layer64 has occurred. Because of this, the time required for degradation oftopcoat66 andsacrificial diffusion layer64 to degrade to expose the antimicrobial to the surrounding environment may affect the release profile of the antimicrobial.
• In some examples, the thickness ofsacrificial diffusion layer64 may be defined with reference to a thickness offirst layer62. For example, the thickness ofsacrificial diffusion layer64 may be between 0.5 times as thick and 5 times as thick asfirst layer62. In other examples,sacrificial diffusion layer64 may be thinner than 0.5 times as thick as first layer62 (i.e., less than half as thick as first layer62) or greater than 5 times as thick asfirst layer62.
• In some examples, in order to hasten the release of the antimicrobial, material may be selectively removed fromtopcoat66 and, optionally,sacrificial diffusion layer64 to form channels in thetopcoat66 and, optionally, thesacrificial diffusion layer64. The channels may hasten release of the antimicrobial by increasing the degradation rate of thetopcoat66 and/orsacrificial diffusion layer64 by increasing the surface area exposed to the external environment (e.g., bodily fluids). In some embodiments, the channels may also provide paths for bodily fluids to contactfirst layer62 immediately after implant, which may facilitate release of the antimicrobial prior to degradation and removal oftopcoat66 andsacrificial diffusion layer64. In some examples, the material intopcoat66 and, optionally,sacrificial diffusion layer64 may be removed by laser ablation, selective chemical etching, or the like. In other examples, the channels may be formed intopcoat66 and, optionally,sacrificial diffusion layer64 during formation ofantimicrobial accessory60 by, for example, molding, casting, or the like.
• The release profile of the antimicrobial may also be affected by selection of the biodegradable polymer from whichfirst layer62 is formed. As described above, certain biodegradable polymers may permit faster diffusion of the antimicrobial, which may lead to a faster release of the antimicrobial oncefirst layer62 is exposed to the surrounding environment. For example, formingfirst layer62 of hydrogel may lead to relatively fast release, or burst release, of the antimicrobial fromfirst layer62. Other biodegradable polymers may slow diffusion of the antimicrobial, which may lead to slower release of the antimicrobial oncefirst layer62 is exposed to the surrounding environment. By selecting appropriate materials forfirst layer62 andsacrificial diffusion layer64, control may be exercised over the release of antimicrobial fromantimicrobial accessory60.
• In some examples, as illustrated inFIG. 8, anantimicrobial accessory80 may include more than three layers. For example, in addition tofirst layer62, a firstsacrificial diffusion layer64, andtopcoat66,antimicrobial accessory80 may include a secondsacrificial diffusion layer82 formed on asecond surface86 offirst layer62 and abase layer84 formed on asurface88 of secondsacrificial diffusion layer82.
• In some examples,base layer84 may comprise a biodegradable polymer and an antioxidant, similar totopcoat66. As described above, the biodegradable polymer may comprise, for example, poly(lactic-co-glycolic acid) (PLGA), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(ethylene oxide) (PEO), poly(ortho ester) (POE), poly(dioxanone), a hydrophilic hydrogel, a hydrophobic hydrogel, a polyanhydride, an amino acid polymer such as a tyrosine polymer, or the like. In some examples,topcoat66 andbase layer84 may include the same biodegradable polymer, while in other examples,topcoat66 andbase layer84 may include different biodegradable polymers. The antioxidant inbase layer84 may include, for example, at least one of citric acid, maltol, kojic acid, malic acid, or vitamin A. In some examples, the antioxidant may include an enzyme and an antioxidant substrate, such as ascorbate peroxidase in combination with ascorbic acid, a glutathione peroxidase in combination with glutathione, or a superoxide dismutase in combination with a metal such as Ni, Cu, Mn, or Fe. The antioxidant inbase layer84 may be the same or different than the antioxidant intopcoat66.
• In other examples,base layer84 may comprise an adhesive, and may be configured to adhereantimicrobial accessory80 to a housing of an IMD (e.g.,IMD22 shown inFIG. 2,3, or4), a catheter body, a lead body, or a connector block of an IMD. The adhesive may be a pressure sensitive adhesive (PSA), such as a silicone, acrylic, or polybutadiene PSA.Base layer84 including an adhesive may be applied to surface88 of secondsacrificial diffusion layer82 by, for example, spray coating, knife coating, air knife coating, gap coating, gravure coating, slot die coating, metering rod coating, doctor blade, or the like.
• Secondsacrificial diffusion layer82 may function similar to firstsacrificial diffusion layer64, and may substantially prevent diffusion of antimicrobial infirst layer62 intobase layer84, or may substantially prevent mixing of the antimicrobial and the antioxidant inbase layer84. Secondsacrificial diffusion layer82 may comprise a biodegradable polymer, such as, for example, poly(lactic-co-glycolic acid) (PLGA), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(ethylene oxide) (PEO), poly(ortho ester) (POE), poly(dioxanone), a hydrophilic hydrogel, a hydrophobic hydrogel, a polyanhydride, an amino acid polymer such as a tyrosine polymer, or the like. Secondsacrificial diffusion layer82 may comprise the same polymer as firstsacrificial diffusion layer64 or may comprise a different polymer than firstsacrificial diffusion layer64.
• FIG. 9 is a flow diagram of an exemplary method of forming an antimicrobial accessory, which will be described with concurrent reference toantimicrobial accessory60 depicted inFIG. 6. Initially,first layer62 including a biodegradable polymer and an antimicrobial may be formed (102).
• First layer62 may be formed by mixing the biodegradable polymer and the antimicrobial in a solvent, such as tetrahydrofuran (THF) to form a solution or suspension. The solution or suspension may then be spray coated onto a substrate, such as a release liner, to formfirst layer62. In other examples, the solution or suspension may be coated onto a release liner using another coating technique, such as, for example, knife coating, air knife coating, gap coating, gravure coating, slot die coating, metering rod coating, doctor blade, or the like.
• In some examples, the antimicrobial may be mixed directly into a melt of the biodegradable polymer and the melt blend may be extruded, casted, or molded to formfirst layer62. In examples in which the antimicrobial is mixed into a melt of the biodegradable polymer, the melt temperature, mixing shear rate, and residence time must be balanced to prevent degradation of the antimicrobial. For example, lower temperatures, shear rates, and residence times may reduce or substantially eliminate degradation of the antimicrobial. In various examples, one, two, or all three of the melt temperature, mixing shear rate, and residence time may be controlled or selected to mitigate or eliminate degradation of the antimicrobial.
• In other examples,first layer62 may initially be formed as a layer including substantially only the biodegradable polymer. The layer may be formed by, for example, extrusion, casting, molding, spray coating, knife coating, air knife coating, gap coating, gravure coating, slot die coating, metering rod coating, doctor blade coating, or the like. Thefirst layer62 including substantially only the biodegradable polymer may then be submerged in a solution or suspension of the antimicrobial in a solvent, such as THF. Submersion of the biodegradable polymer in the solution or suspension may result in impregnation of the polymer with the antimicrobial. The solvent may then be removed by a drying process, such as, for example, vacuum drying.
• Once thefirst layer62 is formed, thesacrificial diffusion layer64 may be formed onfirst surface68 of first layer62 (104). As described above, in some examples,sacrificial diffusion layer64 may comprise the same biodegradable polymer asfirst layer62. In other examples,sacrificial diffusion layer64 may comprise a different biodegradable polymer thanfirst layer62.
• Sacrificial diffusion layer64 may be formed onfirst layer62 by a variety of processes. For example, the biodegradable polymer from whichsacrificial diffusion layer64 is formed may be dissolved in a solvent and coated on first layer using spray coating, knife coating, air knife coating, gap coating, gravure coating, slot die coating, metering rod coating, doctor blade coating, or the like.Sacrificial diffusion layer64 may also be extruded ontofirst layer62, or molded or casted ontofirst layer62.
• Next, thetopcoat66 may be formed on the sacrificial diffusion layer64 (106).Topcoat66 may include a biodegradable polymer and an antioxidant, as described above. In some examples,topcoat66 may comprise the same biodegradable polymer as at least one offirst layer62 andsacrificial diffusion layer64. In other examples,topcoat66 may comprise a different biodegradable polymer thanfirst layer62 andsacrificial diffusion layer64.
• In some examples,topcoat66 may be formed by first mixing the biodegradable polymer and the antioxidant in a solvent, such as tetrahydrofuran (THF) to form a solution or suspension. The solution or suspension may then be spray coated ontosacrificial diffusion layer64 to formtopcoat66. In other examples, the solution or suspension may be coated ontosacrificial diffusion layer64 using another coating technique, such as, for example, knife coating, air knife coating, gap coating, gravure coating, slot die coating, metering rod coating, doctor blade, or the like.
• In some examples, the antioxidant may be mixed directly into a melt of the biodegradable polymer and the melt blend may be extruded, casted, or molded ontosacrificial diffusion layer64 to formtopcoat66. In examples in which the antimicrobial is mixed into a melt of the biodegradable polymer, the melt temperature, mixing shear rate, and residence time must be balanced to prevent degradation of the antioxidant. For example, lower temperatures, shear rates, and residence times may reduce or substantially eliminate degradation of the antioxidant. In various examples, one, two, or all three of the melt temperature, mixing shear rate, and residence time may be controlled or selected to mitigate or eliminate degradation of the antioxidant.
• In other examples,topcoat66 may initially be formed onsacrificial diffusion layer64 as a layer including substantially only the biodegradable polymer. The layer may be formed by, for example, extrusion, casting, molding, spray coating, knife coating, air knife coating, gap coating, gravure coating, slot die coating, metering rod coating, doctor blade coating, or the like. Thetopcoat66 including substantially only the biodegradable polymer may then be submerged in or washed with a solution or suspension of the antimicrobial in a solvent, such as THF. Submersion or washing of the biodegradable polymer in the solution or suspension may result in impregnation of the polymer with the antimicrobial. The solvent may then be removed by a drying process, such as, for example, vacuum drying, leaving atopcoat66 that includes a biodegradable polymer mixed with or impregnated with the antioxidant.
• Onceantimicrobial accessory60 has been formed, theaccessory60 may be sterilized (108). In some examples,antimicrobial accessory60 may be sterilized prior to being packaged, while in other examples,antimicrobial accessory60 may be sterilized after being packaged.Antimicrobial accessory60 may be sterilized using, for example, an electron beam, a gamma beam, ethylene oxide, autoclaving, or the like. As described above, in some examples the sterilization may initiate degradation of one or both of the polymer and antimicrobial inantimicrobial accessory60. The presence of the antioxidant intopcoat66 may slow or substantially stop the oxidation of the polymer and/or the antimicrobial.
• Antimicrobial accessory60 may be packaged in a foil package or other substantially air and water impermeable package that is vacuum sealed or backfilled with an inert gas.
• Antimicrobial accessory60 may be provided to the implanting physician in different ways. For example,antimicrobial accessory60 may be provided alone, and may be configured to be used with a variety of IMDs, such as different models of ICDs, pacemakers, drug delivery devices, neurostimulators, or monitoring devices. The implanting physician may determine that a patient may benefit fromantimicrobial accessory60 and may attachantimicrobial accessory60 to an IMD prior to implanting the IMD in the patient.
• In other examples,antimicrobial accessory60 may be bundled together in a kit with an IMD, but may be provided physically separately from the IMD, e.g., may require the implanting clinician to attachantimicrobial accessory60 to the IMD before implantation. This may provide convenience of having anantimicrobial accessory60 provided with an IMD, but may still permit an implanting clinician to elect if he or she wishes to utilize theantimicrobial accessory60 on a patient-by-patient basis.
• In other examples, an IMD may be provided to the implanting clinician withantimicrobial accessory60 already attached. This may provide the most straightforward implementation, as the implanting physician is not required to decide whether theantimicrobial accessory60 is desired, and does not need to attachantimicrobial accessory60 to the IMD prior to implanting the IMD in the patient.
• Although certain features of the antioxidants, antimicrobials, polymer, or antimicrobial accessories have been described with reference to different Figures or examples within this disclosure, the various features of the antioxidants, antimicrobials, polymer, or antimicrobial accessories may be used together in combinations other than explicitly described herein. Other combinations of such features will be apparent to one of ordinary skill, and are within the scope of the following claims.
• Various examples have been described in the disclosure. These and other examples are within the scope of the following claims.

Claims (20)

1. An antimicrobial accessory comprising:

a polymer;

an antimicrobial mixed in the polymer; and

an antioxidant mixed in the polymer, wherein the antioxidant is selected from the group consisting of citric acid, maltol, kojic acid, malic acid, vitamin A, an ascorbate peroxidase in combination with ascorbic acid, a glutathione peroxidase in combination with glutathione, a superoxide dismutase in combination with a metal, or combinations thereof.

2. The antimicrobial accessory ofclaim 1, wherein the antioxidant is selected from the group consisting of an ascorbate peroxidase in combination with ascorbic acid, a glutathione peroxidase in combination with glutathione, a superoxide dismutase in combination with a metal, or combinations thereof.

3. The antimicrobial accessory ofclaim 1, further comprising an adhesive layer formed on a surface of the polymer.

4. The antimicrobial accessory ofclaim 1, wherein the antimicrobial is selected from the group consisting of minocycline, rifampin, clindamycin, tigecycline, daptomycin, gentamicin, another fluoroquinolone, an antiseptic, an antimicrobial peptide, a quaternary ammonium, or combinations thereof.

5. The antimicrobial accessory ofclaim 1, wherein the polymer comprises a biodegradable polymer.

6. The antimicrobial accessory ofclaim 1, wherein the polymer is selected from the group consisting of poly(lactic-co-glycolic acid), poly(lactic acid), poly(glycolic acid), poly(ethylene oxide), poly(ortho ester), poly(dioxanone) a hydrophilic hydrogel, a hydrophobic hydrogen, a polyanhydride, an amino acid polymer, or combinations thereof.

7. The antimicrobial accessory ofclaim 1, wherein the polymer comprises poly(lactic-co-glycolic acid).

8. The antimicrobial accessory ofclaim 1, wherein the antimicrobial accessory comprises less than approximately 9 vol. % antioxidant.

9. The antimicrobial accessory ofclaim 1, wherein the antimicrobial accessory comprises between approximately 10 wt. % antimicrobial and approximately 20 wt. %.

10. A system comprising:

an implantable medical device; and

an antimicrobial accessory comprising:

a polymer,

an antimicrobial mixed in the polymer, and

an antioxidant mixed in the polymer, wherein the antioxidant is selected from the group consisting of citric acid, maltol, kojic acid, malic acid, vitamin A, an ascorbate peroxidase in combination with ascorbic acid, a glutathione peroxidase in combination with glutathione, a superoxide dismutase in combination with a metal, or combinations thereof.

11. The system ofclaim 10, wherein the antioxidant is selected from the group consisting of an ascorbate peroxidase in combination with ascorbic acid, a glutathione peroxidase in combination with glutathione, a superoxide dismutase in combination with a metal, or combinations thereof.

12. The system ofclaim 10, wherein the antimicrobial accessory is attached to the implantable medical device.

13. The system ofclaim 10, wherein the antimicrobial accessory further comprises an adhesive layer, and the adhesive layer adheres the antimicrobial accessory to the implantable medical device.

14. The system ofclaim 10, wherein the antimicrobial accessory is formed integrally with the implantable medical device.

15. The system ofclaim 14, wherein the implantable medical device comprises a lead body, and wherein the antimicrobial accessory is formed integrally with the lead body.

16. The system ofclaim 14, wherein the implantable medical device is selected from the group consisting of an implantable cardioverter/defibrillator, a pacemaker, an implantable drug delivery device, an implantable monitoring device that monitors one or more physiological parameter of a patient, or an implantable neurostimulator, and wherein the antimicrobial accessory is formed integrally with a housing of the implantable medical device.

17. The system ofclaim 10, wherein the polymer comprises a biodegradable polymer.

18. The system ofclaim 17, wherein the polymer is selected from the group consisting of poly(lactic-co-glycolic acid), poly(lactic acid), poly(glycolic acid), poly(ethylene oxide), poly(ortho ester), poly(dioxanone) a hydrophilic hydrogel, a hydrophobic hydrogen, a polyanhydride, an amino acid polymer, or combinations thereof.

19. The system ofclaim 18, wherein the polymer comprises poly(lactic-co-glycolic acid).

20. The system ofclaim 10, wherein the antimicrobial is selected from the group consisting of minocycline, rifampin, clindamycin, tigecycline, daptomycin, gentamicin, another fluoroquinolone, an antiseptic, an antimicrobial peptide, a quaternary ammonium, or combinations thereof.

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