WO2023102436A1 - Polymères ioniques pour applications à des dispositifs médicaux - Google Patents

Polymères ioniques pour applications à des dispositifs médicaux Download PDF

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Publication number
WO2023102436A1
WO2023102436A1 PCT/US2022/080679 US2022080679W WO2023102436A1 WO 2023102436 A1 WO2023102436 A1 WO 2023102436A1 US 2022080679 W US2022080679 W US 2022080679W WO 2023102436 A1 WO2023102436 A1 WO 2023102436A1
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WIPO (PCT)
Prior art keywords
polymer
medical device
active agent
ionic
chlorhexidine
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Application number
PCT/US2022/080679
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English (en)
Inventor
He Bai
James Joseph Semler
Original Assignee
Becton, Dickinson And Company
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Publication date
Priority claimed from US17/991,937 external-priority patent/US20230166007A1/en
Application filed by Becton, Dickinson And Company filed Critical Becton, Dickinson And Company
Publication of WO2023102436A1 publication Critical patent/WO2023102436A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/08—Materials for coatings
    • A61L29/085—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A61L29/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
    • A61L2300/206—Biguanides, e.g. chlorohexidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A61L2300/406—Antibiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602—Type of release, e.g. controlled, sustained, slow
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606—Coatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/06—Coatings containing a mixture of two or more compounds

Definitions

  • Embodiments of the disclosure generally relate to medical devices and methods of manufacture. More particularly, embodiments of the disclosure are directed to medical devices having ionic polymers ionically bonded to an active agent.
  • the active agent may be an antimicrobial agent and/or an antithrombogenic agent.
  • Infusion therapy medical devices such as syringe cannulas and catheters used for sampling or medicament administration, typically have components that are in direct contact with infusion fluid and/or bodily fluid that can cause infection.
  • catheter-related bloodstream infections may be caused by colonization of microorganisms, which can occur in patients whose treatment includes intravascular catheters and I.V. access devices. These infections can lead to illness and excess medical costs.
  • Impregnating and/or coating catheters and I.V. access devices with various antimicrobial agents e.g., chlorhexidine, silver, or other antibiotics
  • Some blood contact devices have the potential to generate thrombus.
  • thrombus When blood contacts a foreign material, a complex series of events occur. These involve protein deposition, cellular adhesion and aggregation, and activation of blood coagulation schemes.
  • Thrombogenicity has conventionally been counteracted by the use of anticoagulants, such as heparin. Attachment of heparin to otherwise thrombogenic polymeric surfaces may be achieved with various surface coating techniques.
  • Impregnating catheters and/or I.V. access devices directly with antimicrobial and/or antithrombogenic agents does not create chemical bonding between active agents and polymer substrates, thus devices would lose antimicrobial/antifouling efficacy in a short time.
  • One or more embodiments are directed a medical device comprising: an ionic polymer ionically bonded to an active agent, the ionic polymer comprising one or more of an anionic polymer, a cationic polymer, and a zwitterionic polymer; and an optional nonionic base polymer, wherein the anionic polymer comprises a functional group selected from one or more of carboxylate (-COO ), sulfonate (-SO3 ), organosulfate (-O-SO3 ), organophosphate (-O- PO3 R 1 or -O-PO3 2 "), phenolate (-CeFU-O ), and thiolate (—S'), wherein the cationic polymer comprises a functional group selected from one or more of phosphonium (-P + (R 1 )(R 2 )(R 3 )), imidazolium, pyridinium, sulfonium, guanidinium, thiazolium, and
  • An additional embodiment is directed to method of manufacturing a medical device, the method comprising: ionically bonding an ionic polymer and an active agent, and, optionally, a nonionic base polymer, the ionic polymer comprising one or more of an anionic polymer, a cationic polymer, and a zwitterionic polymer, wherein the anionic polymer comprises a functional group selected from one or more of carboxylate (-COO ), sulfonate (- SO3"), organosulfate (-O-SO3 ), organophosphate (-O-PO3 R 1 or -O-PO3 2 "), phenolate i-CefU- O ), and thiolate (—S'), wherein the cationic polymer comprises a functional group selected from one or more of phosphonium (-P + (R 1 )(R 2 )(R 3 )), imidazolium, pyridinium, sulfonium, guani
  • FIG. 1 is a plan view of an exemplary medical device
  • FIG. 2 illustrates an elution profile of a medical device according to one or more embodiments of the disclosure
  • FIG. 3 illustrates an elution profile of a medical device according to one or more embodiments of the disclosure.
  • FIG. 4 illustrates an elution profile of a medical device according to one or more embodiments of the disclosure.
  • An ionic polymer is a polymer which contains both covalent bonds and ionic bonds in its molecular structure.
  • the ionically charged functional group of an ionic polymer may include one or more of a cationic functional group and an anionic functional group to form one or more of a cationic polymer, an anionic polymer, or a zwitterionic polymer.
  • Cationic polymers are macromolecules that have positive charges, which can be intrinsically present in the polymer backbone and/or in sidechains.
  • Anionic polymers are macromolecules that have electronegative groups, which can be intrinsically present in the polymer backbone and/or in sidechains.
  • Zwitterionic polymers are macromolecules that have both positive and negative charges incorporated into their polymer backbone and/or in sidechains.
  • An antimicrobial agent is a substance that kills microorganisms or stops their growth.
  • Antimicrobial agents that can be used for bonding with cationic and/or anionic functional groups of the ionic polymer include any anionic antibiotics, e.g., cloxacillin salt, cefoxitin salt, cefazolin salt, penicillin salt, or derivatives thereof, and cationic antiseptics, e.g., chlorhexidine acetate, chlorhexidine gluconate, silver sulfadiazine, benzalkonium chloride, cetylpyridinium chloride, or derivatives thereof.
  • quaternary ammonium-containing biocides, guanidine-containing biocides, cationic antimicrobial polymers, antimicrobial peptides or peptide-mimics, antifouling phospholipids or phospholipid-mimics, and derivatives thereof can also be ionically bonded with anionic functional groups of the ionic polymer to actively and/or passively provide advantages of enhanced surface properties including antimicrobial and/or anti-fouling.
  • An antithrombogenic agent is a substance which prevents the formation of a blood clot.
  • Anionic antithrombogenic agents e.g., heparin salt, or derivatives thereof can be ionically bonded with cationic functional groups of the ionic polymer to provide antithrombotic properties.
  • anionic and/or cationic biocides and anticoagulants of either small molecules or macromolecules can also be used for bonding with cationic and/or anionic functional groups of the ionic polymer.
  • the term "active agent” refers to an antimicrobial agent, an antithrombotic agent, or combinations thereof, which is an anionic, cationic, or zwitterionic compound that can bind to an ionic polymer. Accordingly, in some embodiments, the active agent provides antimicrobial activity, antifouling activity, or a combination thereof.
  • Principles and embodiments of the present disclosure relate generally to ionic polymer devices having improved properties, and methods of preparing and using them.
  • medical articles for example, catheter tubing, that have antimicrobial and/or antifouling characteristics by ionically bonding and stabilizing active agents to provide desirable material properties, including antimicrobial, anti-fouling, and/or antithrombogenicity.
  • ionic polymers that are ionically bonded to antimicrobial/antithrombogenic agents to achieve controlled release of said antimicrobial/antithrombogenic agents from a medical device, e.g., catheter, extensions, IV tubing, catheter adapter, Luer port, connector body, device housing, a component thereof, combinations thereof, and the like, in order to prevent blood stream infections and blood clots, such as deep vein thrombosis (DVT) and thrombosis- induced catheter occlusions.
  • a medical device e.g., catheter, extensions, IV tubing, catheter adapter, Luer port, connector body, device housing, a component thereof, combinations thereof, and the like, in order to prevent blood stream infections and blood clots, such as deep vein thrombosis (DVT) and thrombosis- induced catheter occlusions.
  • DVD deep vein thrombosis
  • FIG. 1 an exemplary medical device in the form of a catheter is illustrated.
  • Tubing made from an ionic polymer ionically bonded to an active agent as disclosed herein forms the catheter, which is shaped as needed to receive other components for forming vascular access devices.
  • Catheter 10 comprises a primary conduit 12, which is tubing in its as- extruded form.
  • a tip 14 is formed by a tipping process.
  • a flange 16 is formed as needed for receipt of other components including but not limited to catheter adapters.
  • Exemplary vascular access devices may include a needle further to the catheter for access to blood vessels.
  • the medical device is in the form of a catheter, an extension, an IV tubing, a catheter adapter, a luer port, a connector body, a device housing, a component thereof, or a combination thereof.
  • the catheter comprises a peripherally inserted central catheter (PICC), a peripheral intravenous catheter (PIVC), or a central venous catheter (CVC).
  • PICC peripherally inserted central catheter
  • PIVC peripheral intravenous catheter
  • CVC central venous catheter
  • controlled release of the ionically bonded active agent prevents blood stream infections and deep vein thrombosis.
  • the medical device comprises an ionic polymer ionically bonded to an active agent.
  • the ionic polymer is selected from one or more of a cationic polymer, an anionic polymer and a zwitterionic polymer.
  • the ionic bond between the active agent and the ionic polymer allows non-leaching and/or controlled release of the active agent.
  • a nonionic base polymer may also be included in the medical article.
  • the medical device passively reduces thrombus formation and/or bacterial biofilm formation due to ionic repulsion of bacteria, protein, and blood components.
  • the ionic polymer includes one or more cationic and/or anionic functional group.
  • the anionic polymer comprises an anionic functional group.
  • the anionic polymer comprises at least one anionic functional group, at least two anionic functional groups, or at least three anionic functional groups.
  • the anionic polymer comprises more than one anionic functional group, more than two anionic functional groups, or more than three anionic functional groups.
  • the cationic polymer comprises a cationic functional group.
  • the cationic polymer comprises at least one cationic functional group, at least two cationic functional groups, or at least three cationic functional groups.
  • the cationic polymer comprises more than one cationic functional group, more than two cationic functional groups, or more than three cationic functional groups.
  • the zwitterionic polymer comprises an anionic functional group and a cationic functional group. In some embodiments, the zwitterionic polymer comprises at least one anionic functional group, at least two anionic functional groups, or at least three anionic functional groups. In some embodiments, the zwitterionic polymer comprises at least one cationic functional group, at least two cationic functional groups, or at least three cationic functional groups. In some embodiments, the zwitterionic polymer comprise more than one anionic functional group, more than two anionic functional groups, or more than three anionic functional groups. In some embodiments, the zwitterionic polymer comprise more than one cationic functional group, more than two cationic functional groups, or more than three cationic functional groups.
  • the cationic functional group may comprise any suitable cationic functional group known to the skilled artisan.
  • the cationic functional group is selected from one or more of quaternary ammonium (-N + (R 1 )(R 2 )(R 3 )), phosphonium (- P + (R 1 )(R 2 )(R 3 )), imidazolium, pyridinium, sulfonium, guanidinium, thiazolium, and quinolinium, where R 1 , R 2 , and R 3 independently comprise hydrogen, halogen, alkyl, and aryl.
  • the ionic polymer is a cationic polymer that does not include a quaternary ammonium group.
  • the cationic polymer includes one or more cationic functional group selected from phosphonium (- P + (R 1 )(R 2 )(R 3 )), imidazolium, pyridinium, sulfonium, guanidinium, thiazolium, and quinolinium, where R 1 , R 2 , and R 3 independently comprise hydrogen, halogen, alkyl, and aryl.
  • the ionic polymer is a cationic polymer that has two or more quaternary ammonium groups (-N + (R 1 )(R 2 )(R 3 )), where the quaternary ammonium groups are different from one another.
  • two or more cationic functional groups are present in the cationic polymer or the zwitterionic polymer.
  • the two or more cationic functional groups may be selected from quaternary ammonium (-N + (R 1 )(R 2 )(R 3 )), phosphonium (-P + (R 1 )(R 2 )(R 3 )), imidazolium, pyridinium, sulfonium, guanidinium, thiazolium, and quinolinium, where R 1 , R 2 , and R 3 independently comprise hydrogen, halogen, alkyl, and aryl.
  • the anionic functional group may comprise any suitable anionic functional group known to the skilled artisan.
  • the anionic functional group comprises one or more of carboxylate (-COO ), sulfonate (-SO3 ), organosulfate (-O-SO3 ), organophosphate (- O-PO3 R 1 or -O-PO3 2 "), phenolate (-Cetk-O ), and thiolate (—S'), where R 1 comprises hydrogen, halogen, alkyl, and aryl.
  • the ionic polymer is an anionic polymer.
  • the anionic polymer may comprise any suitable anionic polymer known to the skilled artisan.
  • the anionic polymer includes a carboxylate (-COO ) functional group.
  • the anionic polymer is selected from the group consisting of carboxylated polyurethane (Becton, Dickinson and Company) and poly(ethylene-co- methacrylic acid) copolymer (e.g., ionomer under the commercial name SurlynTM).
  • the anionic polymer includes a sulfonate (-SO3 ) functional group.
  • the anionic polymer is selected from the group consisting of sulfonated polyurethane (Becton, Dickinson and Company) and perfluorosulfonic acid/polytetrafluoroethylene copolymer (e.g., ionomer under the commercial name NafionTM).
  • the ionic polymer is a zwitterionic polymer, containing both cationic and anionic functional groups.
  • the zwitterionic polymer comprises two or more functional groups selected from carboxylate (-COO ), sulfonate (-SO3 ), organosulfate (-O-SO3 ), organophosphate (-O-PO3 R 1 or -O-PO3 2 "), phenolate (-Cetk-O ), thiolate (-S’), quaternary ammonium (-N + (R 1 )(R 2 )(R 3 )), phosphonium (-P + (R 1 )(R 2 )(R 3 )), imidazolium, pyridinium, sulfonium, guanidinium, thiazolium, and quinolinium, where R 1 , R 2 , and R 3 independently comprise hydrogen, halogen, alkyl, and ary
  • the ionic polymer is ionically bonded to an active agent.
  • the active agent may be any suitable active agent known to the skilled artisan.
  • the active agent is a cationic active agent.
  • the active agent is an anionic active agent.
  • the active agent may be an anionic active agent or a cationic active agent, or both.
  • the active agent is selected from one or more of an anionic active agent and a cationic active agent.
  • the cationic active agent may be selected from one or more of chlorhexidine acetate, chlorhexidine gluconate, silver sulfadiazine, benzalkonium chloride, cetylpyridinium chloride, a quaternary ammonium-containing biocide, a guanidine-containing biocide, a cationic antimicrobial polymer, an antimicrobial peptide or peptide-mimics, an antifouling phospholipid or phospholipid- mimics, and derivatives thereof.
  • the anionic active agent may be selected from one or more of cloxacillin salt, cefoxitin salt, cefazolin salt, penicillin salt, heparin salt, and derivatives thereof.
  • anionic and/or cationic biocides and anticoagulants of either small molecules or macromolecules can also be used for bonding with cationic and/or anionic functional groups of the ionic polymer.
  • the medical device releases or is configured to release the active agent in a range of from 4 hours to 90 days. In some embodiments, the medical device releases or is configured to release the active agent over a span of at least 4 hours, at least 8 hours, at least 12 hours, at least 24 hours, at least 48 hours, at least 72 hours, at least 96 hours, at least 120 hours, or at least 144 hours. In some embodiments, the medical device releases or is configured to release the active agent over a span of at least 3 days, at least 7 days, at least 14 days, at least 21 days, at least 30 days, at least 60 days, or at least 90 days.
  • the medical device comprises an optional nonionic base polymer.
  • the nonionic base polymer is included in the medical device. In other embodiments, the nonionic base polymer is not included in the medical device.
  • the non-ionic base polymer may comprise any suitable nonionic polymer known to the skilled artisan.
  • the nonionic base polymer comprises one or more of polyurethane, copolyester, polyolefin, polyvinyl chloride, polycarbonate, acrylic -based copolymer, acetal copolymer, cellulose acetate propionate, acrylonitrile butadiene styrene copolymer, high impact polystyrene, thermoplastic elastomer, synthetic rubber, and silicone elastomer.
  • a coating including the ionically bonded ionic polymer and the active agent is coated on a body of the medical device.
  • the coating comprises one or more ionic polymers ionically bonded to one or more active agents.
  • the coating also includes one or more nonionic base polymers.
  • the coating is formed by co-dissolving an ionic polymer and an active agent in a solvent system to form an ionic bond between the ionic polymer and the active agent.
  • the solvent system is optimized to prevent damage to the medical device during the coating process.
  • the solvent system is optimized such that flashing off of solvents after coating of the medical device results in a final surface coating layer with a controlled coating thickness.
  • the solvent system for the coating may be any suitable solvent system known to the skilled artisan.
  • the solvent system dissolves both the ionic polymer and the active agent.
  • the solvent system does not cause damage to the medical device substrate during the coating process.
  • the solvent system may be flashed off after coating.
  • the solvent system includes methyl ethyl ketone, tetrahydrofuran, acetone, ethyl formate, methyl formate, 1,3 -dioxolane, ethyl acetate, 2-propanol, ethanol, methanol, or mixtures thereof.
  • polymer carriers containing at least one ionic polymer can be co-dissolved with at least one active agent in a solvent system to form an ionic bond between the ionic polymer and the active agent.
  • polymer carriers containing at least one ionic polymer can be co-dissolved with more than one active agent in a solvent system to form an ionic bond between the ionic polymer and the active agent.
  • the coating can then be applied to the surface of the medical device or medical device component.
  • the body of the device includes one or more ionic polymers, and the body of the device is imbibed with one or more active agents.
  • the body of the device may also comprise one or more nonionic base polymers.
  • imbibing may result in loading of the active agent onto the medical device or medical device component by diffusion in addition to ionic bonding.
  • the medical device comprises a compounded mixture.
  • the compounded mixture comprises the ionic polymer and the active agent.
  • the compounded mixture comprises the one or more ionic polymers ionically bonded to the one or more active agents.
  • the compounded mixture further comprises one or more nonionic base polymers.
  • the compounded mixture can be molded or extruded into medical devices or medical device components.
  • the medical device comprises at least one excipient.
  • the at least one excipient is selected from one or more of thermal stabilizers, light stabilizers, anti-blocking agents, antioxidants, antistatic agents, impact modifiers, reinforcing agents, flame retardants, mold release agents, blowing agents, colorants, radiopaque fillers, lubricating agents, and the like.
  • the medical device may comprise an excipient in an amount in the range of from 0.01 to 50 % w/w.
  • the method comprises ionically bonding the ionic polymer and the active agent, and, optionally, the nonionic base polymer.
  • the ionic bonding can be achieved by any suitable technique known in the art.
  • suitable techniques include a bulk mixing technique and an imbibing technique.
  • the bulk mixing technique comprises a solvent mixing technique and a thermal compounding technique.
  • the body of the device includes the ionic polymer and ionically bonding involves imbibing the body of the medical device with the active agent.
  • the body of the device also includes the nonionic base polymer.
  • the body of the device also includes the excipient.
  • the body of the device includes the ionic polymer in an amount of greater than or equal to: 0.01 % w/w, 0.1 % w/w, 0.5 % w/w, 1 % w/w, 1.5 % w/w, 2 % w/w, 3 % w/w, 4 % w/w, 5 % w/w, 10 % w/w, 25 % w/w, 50 % w/w, 75 % w/w, or 100 % w/w.
  • the body of the device includes the ionic polymer in an amount of less than or equal to: 100 % w/w, 75 % w/w, 50 % w/w, 25 % w/w, 10 % w/w, 8.0 % w/w, 6.0 % w/w, 4 % w/w, 2 % w/w, or 1.0 % w/w.
  • the body of the device includes the ionic polymer in an amount ranging from greater than or equal to 0.01 to less than or equal to 100 % w/w, and all values and subranges therebetween, including greater than or equal to 0.5 to less than or equal to 75 % w/w, greater than or equal to 1 to less than or equal to 50 % w/w, and all values and subranges there between; including: greater than or equal to: 0.01 % w/w, 0.1 % w/w, 0.5 % w/w, 1 % w/w, 1.5 % w/w, 2 % w/w, 3 % w/w, 4 % w/w, 5 % w/w, or 10 % w/w to less than or equal to: 100 % w/w, 75 % w/w, 50 % w/w, or 25 % w/w.
  • the body of the device includes the ionic polymer for bonding of active agents and advantageously does not require priming (e.g., chemical or plasma treatments) of the device. Accordingly, in some embodiments, when the body of the device includes ionic functionalities, the medical device manufacturing process is simplified, and conversion costs are significantly reduced. As used herein, the term “conversion cost” refers to the cost required to load the device with the active agent.
  • imbibing advantageously provides a medical device where the active agent is ionically bonded on a surface of the medical device and in the body of the device. In one or more embodiments, imbibing provides continuous and long-term supply of the active agent from the device.
  • the medical device comprising the ionic polymer is effective to passively reduce thrombus formation and/or bacterial biofilm without imbibing treatment. In one or more embodiments, passive reduction of thrombus formation and/or bacterial biofilm of the ionic polymer is due to ionic repulsion of bacteria, protein, and blood components.
  • the method further comprises pre- swelling the body of the device. In some embodiments, the method further comprises deionizing the ionic polymer. In some embodiments, an ionic bond between the ionic polymer and the active agent is formed using the imbibing technique. Accordingly, in some embodiments, the imbibing technique includes deionizing the ionic polymer prior to imbibing the body of the device in a solution of the active agent. In some embodiments, the imbibing technique includes pre-swelling the body of the device before deionizing the ionic polymer and imbibing the body of the device in a solution of the active agent.
  • process parameters for imbibing method may be tuned to optimize loading and elution of the active agent. Accordingly, in some embodiments, the process parameters include process temperatures, process time, a concentration of the active agent, a selection of the solvent system, or combinations thereof.
  • ionically bonding the ionic polymer and the active agent involves preparing a polymer formulation including the active agent.
  • the polymer formulation comprises the ionic polymer and the active agent.
  • the polymer formulation further comprises nonionic base polymer.
  • the polymer formulation comprises the ionic polymer in an amount of greater than or equal to: 0.01 % w/w, 0.1 % w/w, 0.5 % w/w, 1 % w/w, 1.5 % w/w, 2 % w/w, 3 % w/w, 4 % w/w, 5 % w/w, 10 % w/w, 25 % w/w, 50 % w/w, 75 % w/w, or 99.9 % w/w.
  • the polymer formulation comprises the ionic polymer in an amount of less than or equal to: 99.9 % w/w, 75 % w/w, 50 % w/w, 25 % w/w, 10 % w/w, 8.0 % w/w, 6.0 % w/w, 4 % w/w, 2 % w/w, or 1.0 % w/w.
  • the polymer formulation comprises the ionic polymer in an amount ranging from greater than or equal to 0.01 to less than or equal to 99.9 % w/w, and all values and subranges therebetween, including greater than or equal to 0.5 to less than or equal to 75 % w/w, greater than or equal to 1 to less than or equal to 50 % w/w, and all values and subranges there between; including: greater than or equal to: 0.01 % w/w, 0.1 % w/w, 0.5 % w/w, 1 % w/w, 1.5 % w/w, 2 % w/w, 3 % w/w, 4 % w/w, 5 % w/w, or 10 % w/w to less than or equal to: 99.9 % w/w, 75 % w/w, 50 % w/w, or 25 % w/w.
  • the polymer formulation comprises the active agent in an amount of greater than or equal to: 0.1 % w/w, 0.5 % w/w, 1 % w/w, 1.5 % w/w, 2 % w/w, 3 % w/w, 4 % w/w, 5 % w/w, 10 % w/w, 25 % w/w, 50 % w/w, or 75 % w/w.
  • the polymer formulation comprises the active agent in an amount of less than or equal to: 75 % w/w, 50 % w/w, 25 % w/w, 10 % w/w, 8.0 % w/w, 6.0 % w/w, 4 % w/w, 2 % w/w, or 1.0 % w/w.
  • the polymer formulation comprises the active agent in an amount ranging from greater than or equal to 0.1 to less than or equal to 75 % w/w, and all values and subranges therebetween, including greater than or equal to 0.5 to less than or equal to 50 % w/w, greater than or equal to 1 to less than or equal to 25 % w/w, and all values and subranges there between; including: greater than or equal to: 0.1 % w/w, 0.5 % w/w, 1 % w/w, 1.5 % w/w, 2 % w/w, 3 % w/w, 4 % w/w, or 5 % w/w to less than or equal to: 75 % w/w, 50 % w/w, 25 % w/w, 10 % w/w, 8.0 % w/w, or 6.0 % w/w.
  • preparing the polymer formulation may include compounding the ionic polymer and active agent, and, optionally, the nonionic base polymer to form an ionically bonded compounded mixture.
  • the compounded mixture comprises the ionic polymer in an amount of greater than or equal to: 0.01 % w/w, 0.1 % w/w, 0.5 % w/w, 1 % w/w, 1.5 % w/w, 2 % w/w, 3 % w/w, 4 % w/w, 5 % w/w, 10 % w/w, 25 % w/w, 50 % w/w, 75 % w/w, or 99.9 % w/w.
  • the compounded mixture comprises the ionic polymer in an amount of less than or equal to: 99.9 % w/w, 75 % w/w, 50 % w/w, 25 % w/w, 10 % w/w, 8.0 % w/w, 6.0 % w/w, 4 % w/w, 2 % w/w, or 1.0 % w/w.
  • the compounded mixture comprises the ionic polymer in an amount ranging from greater than or equal to 0.01 to less than or equal to 99.9 % w/w, and all values and subranges therebetween, including greater than or equal to 0.5 to less than or equal to 75 % w/w, greater than or equal to 1 to less than or equal to 50 % w/w, and all values and subranges there between; including: greater than or equal to: 0.01 % w/w, 0.1 % w/w, 0.5 % w/w, 1 % w/w, 1.5 % w/w, 2 % w/w, 3 % w/w, 4 % w/w, 5 % w/w, or 10 % w/w to less than or equal to: 99.9 % w/w, 75 % w/w, 50 % w/w, or 25 % w/w.
  • the compounded mixture comprises the active agent in an amount of greater than or equal to: 0.1 % w/w, 0.5 % w/w, 1 % w/w, 1.5 % w/w, 2 % w/w, 3 % w/w, 4 % w/w, 5 % w/w, 10 % w/w, 25 % w/w, 50 % w/w, or 75 % w/w.
  • the compounded mixture comprises the active agent in an amount of less than or equal to: 75 % w/w, 50 % w/w, 25 % w/w, 10 % w/w, 8.0 % w/w, 6.0 % w/w, 4 % w/w, 2 % w/w, or 1.0 % w/w.
  • the compounded mixture comprises the active agent in an amount ranging from greater than or equal to 0.1 to less than or equal to 75 % w/w, and all values and subranges therebetween, including greater than or equal to 0.5 to less than or equal to 50 % w/w, greater than or equal to 1 to less than or equal to 25 % w/w, and all values and subranges there between; including: greater than or equal to: 0.1 % w/w, 0.5 % w/w, 1 % w/w, 1.5 % w/w, 2 % w/w, 3 % w/w, 4 % w/w, or 5 % w/w to less than or equal to: 75 % w/w, 50 % w/w, 25 % w/w, 10 % w/w, 8.0 % w/w, or 6.0 % w/w.
  • compounding advantageously provides a medical device where the active agent
  • compounding of the polymer formulation is processed through a twin-screw compounder. Accordingly, in some embodiments, a ratio of one or more of the ionic polymer, the active agent, the nonionic base polymer, and the excipient can be controlled and adjusted by a gravimetric multiple-feeder system.
  • the mixture (conveying through multiple heating and mixing zones) can be continuously passed through a die, a quench tank, and is subsequently cut into regular-sized pellets by a puller-pelletizer.
  • the pellets of the compounded polymer formulation can be used for molding and/or extrusion to form medical devices or medical device components.
  • the twin-screw compounder process conditions are optimized to achieve uniform mixing of the active agent in the polymer formulation. In some embodiments, uniform mixing is correlated to a desirable elution profile of the active agent from the medical device.
  • the process parameters of the twin-screw compounder include zone temperatures, screw design, and screw revolutions per minute (RPM).
  • the method further comprises molding and/or extruding the compounded polymer formulation into the medical device. In some embodiments, the medical device is molded and/or extruded by injection molding and/or extrusion technique.
  • preparing the polymer formulation may include solvent-mix the ionic polymer and active agent, and, optionally, the nonionic base polymer to form an ionically bonded coating formulation.
  • the coating formulation comprises the ionic polymer in an amount of greater than or equal to: 0.01 % w/w, 0.1 % w/w, 0.5 % w/w, 1 % w/w, 1.5 % w/w, 2 % w/w, 3 % w/w, 4 % w/w, 5 % w/w, 10 % w/w, 25 % w/w, 50 % w/w, 75 % w/w, or 99.9 % w/w.
  • the coating formulation comprises the ionic polymer in an amount of less than or equal to: 99.9 % w/w, 75 % w/w, 50 % w/w, 25 % w/w, 10 % w/w, 8.0 % w/w, 6.0 % w/w, 4 % w/w, 2 % w/w, or 1.0 % w/w.
  • the coating formulation comprises the ionic polymer in an amount ranging from greater than or equal to 0.01 to less than or equal to 99.9 % w/w, and all values and subranges therebetween, including greater than or equal to 0.5 to less than or equal to 75 % w/w, greater than or equal to 1 to less than or equal to 50 % w/w, and all values and subranges there between; including: greater than or equal to: 0.01 % w/w, 0.1 % w/w, 0.5 % w/w, 1 % w/w, 1.5 % w/w, 2 % w/w, 3 % w/w, 4 % w/w, 5 % w/w, 10 % w/w, or 25 % w/w to less than or equal to: 99.9 % w/w, 75 % w/w, or 50 % w/w.
  • the coating formulation comprises the active agent in an amount of greater than or equal to: 0.1 % w/w, 0.5 % w/w, 1 % w/w, 1.5 % w/w, 2 % w/w, 3 % w/w, 4 % w/w, 5 % w/w, 10 % w/w, 25 % w/w, 50 % w/w or 75 % w/w.
  • the coating formulation comprises the active agent in an amount of less than or equal to: 75 % w/w, 50 % w/w, 25 % w/w, 10 % w/w, 8.0 % w/w, 6.0 % w/w, 4 % w/w, 2 % w/w, or 1.0 % w/w.
  • the coating formulation comprises the active agent in an amount ranging from greater than or equal to 0.1 to less than or equal to 75 % w/w, and all values and subranges therebetween, including greater than or equal to 0.5 to less than or equal to 50 % w/w, greater than or equal to 1 to less than or equal to 25 % w/w, and all values and subranges there between; including: greater than or equal to: 0.1 % w/w, 0.5 % w/w, 1 % w/w, 1.5 % w/w, 2 % w/w, 3 % w/w, 4 % w/w, or 5 % w/w to less than or equal to: 75 % w/w, 50 % w/w, 25 % w/w, 10 % w/w, 8.0 % w/w, or 6.0 % w/w.
  • the method further comprises applying the coating formulation onto the surface of medical device or medical device component.
  • such ionically bonded coating formulation advantageously simplifies the medical device manufacturing process and significantly reduces conversion costs.
  • coating advantageously allows loading of an active agent onto the surface of traditional medical devices.
  • process parameters for coating formulation method may be tuned to optimize loading and elution of the active agent. Accordingly, in some embodiments, the process parameters include process temperatures, process time, ingredient concentrations, a selection of the solvent system, or combinations thereof.
  • Table 1 lists the non-ionic (control) polymers and ionic polymers used in this work. Both ribbon sheet and one- lumen tubing configurations were prepared and tested.
  • each sample was then soaked in 10 mL of methanol for 1 minute at room temperature to rinse off the Tris-Base buffer solution. Each sample was then soaked in 10 mL of loading solution.
  • the loading solution comprised an active agent in 30/70 v/v% of methanol/water and used at 37 °C for 24 hours.
  • the active agent comprised chlorhexidine acetate (100 mM)/sodium citrate (1 mM).
  • Each sample was placed on an Orbital Shaker during this loading process. After the loading process, each sample was soaked in 10 mL of methanol for 1 minute at room temperature to rinse off the loading solution. After rinsing, each sample was dried in a fume hood at room temperature overnight to flash off the residue methanol solvent.
  • Chlorhexidine elution is defined as the mass of chlorhexidine eluted per unit area of sample in the unit of pg/cm 2 .
  • Chlorhexidine Post-Elution Extraction After elution testing, the remaining chlorhexidine in each sample was completely extracted using the extraction media comprising 0.3/70/30 v/v/v% of trifluoroacetic acid/acetonitrile/water at 37 °C for 24 hours (on Orbital Shaker @ 150 RPM), followed by analysis and quantification of remaining chlorhexidine in each sample by HPLC.
  • the chlorhexidine remaining is defined as the mass of chlorhexidine remained per unit area of sample in the unit of pg/cm 2 .
  • Chlorhexidine Loadins Calculation Chlorhexidine initial loading on the sample can be calculated by adding total chlorhexidine elution (adding up all elution time points) and the chlorhexidine remain (by post-elution extraction).
  • Table 2 shows the chlorhexidine initial loading data (average of 3 replicates) of both the control polymers without ionic functionalities and the ionic polymers by the above imbibing approach.
  • Table 2 shows that control polymers without ionic functionalities (Cl and C2) both exhibited low chlorhexidine loading (only ⁇ 50 pg/cm 2 ) after imbibing, which is nonbonded free chlorhexidine trapped within the polymer matrix during imbibing.
  • ionic polymers Rl, R2, R7, R8 and T4 exhibited much higher chlorhexidine loading after imbibing, due to ionic interactions between the anionic functional group and chlorhexidine.
  • Table 3 shows the chlorhexidine elution in human serum and remain data (average of 3 replicates) of both the control polymers without ionic functionalities and the ionic polymers.
  • FIG. 2 shows the chlorhexidine accumulated elution in human serum over a period of time of both the control polymers without ionic functionalities and the ionic polymers.
  • Table 3 and FIG. 2 show the chlorhexidine elution profiles of both the control polymers without ionic functionalities and the ionic polymers.
  • control polymers without ionic functionalities Cl and C2
  • majority of loaded chlorhexidine eluted out in the first 24 h and minimum amount of chlorhexidine left within the polymer matrix after Day 1.
  • the polymers do not show a controlled release.
  • ionic polymers Rl, R2, R7, R8 and T4
  • only small portion of loaded chlorhexidine eluted out in the first 24 h which presumably to be the non-bonded and/or weakly bonded chlorhexidine trapped within the polymer matrix. The remaining chlorhexidine was ionically bonded within the polymer matrix and showed a slow release.
  • Example 3 [0069] Samples Rl, R2, R4, R7, R8 and T4 (as listed in Table 1) were tested following below procedures. Different as Example 2, chlorhexidine acetate (400 mM) in methanol was used as the imbibing solution instead of chlorhexidine acetate (100 mM)/sodium citrate (1 mM) in 30/70 v/v% of methanol/water.
  • the loading solution comprised chlorhexidine acetate (400 mM) in methanol and used at 37 °C for 24 hours. Each sample was placed on an Orbital Shaker during this loading process. After the loading process, each sample was soaked in 10 mL of methanol for 1 minute at room temperature to rinse off the loading solution. After rinsing, each sample was dried in a fume hood at room temperature overnight to flash off the residue methanol solvent.
  • Chlorhexidine Elution in Human Serum Each sample loaded with chlorhexidine, as described above, was soaked in the elution media comprising 60/40 v/v% of human serum/phosphate buffered saline at 37 °C (on Orbital Shaker @ 150 RPM) for time intervals of 3 hours to 21 days. At each designated time interval, the previous elution media was removed for chlorhexidine elution analysis and quantification by high-performance liquid chromatography (HPLC) and fresh elution media was used for the next time interval. Chlorhexidine elution is defined as the mass of chlorhexidine eluted per unit area of sample in the unit of pg/cm 2 .
  • Chlorhexidine Post-Elution Extraction After elution testing, the remaining chlorhexidine in each sample was completely extracted using the extraction media comprising 0.3/70/30 v/v/v% of trifluoroacetic acid/acetonitrile/water at 37 °C for 24 hours (on Orbital Shaker @ 150 RPM), followed by analysis and quantification of remaining chlorhexidine in each sample by HPLC. The chlorhexidine remaining is defined as the mass of chlorhexidine remained per unit area of sample in the unit of pg/cm 2 .
  • Chlorhexidine Loadins Calculation Chlorhexidine initial loading on the sample can be calculated by adding total chlorhexidine elution (adding up all elution time points) and the chlorhexidine remain (by post-elution extraction).
  • Table 4 shows the chlorhexidine initial loading data (average of 3 replicates) of the ionic polymers by the above imbibing approach.
  • Table 4 shows that using chlorhexidine acetate (400 mM) in methanol as the imbibing solution instead of chlorhexidine acetate (100 mM)/sodium citrate (1 mM) in 30/70 v/v% of methanol/water, chlorhexidine loading of perfluorosulfonic acid/ polytetrafluoroethylene copolymer (R8 and T4) does not change significantly; however chlorhexidine loading of carboxylated polyurethane (R1 and R2) and poly(ethylene-co- methacrylic acid) copolymer (R7) significantly increased.
  • Table 5 shows the chlorhexidine elution in human serum and remain data (average of 3 replicates) of the ionic polymers.
  • FIG. 3 shows the chlorhexidine accumulated elution in human serum over a period of time of the ionic polymers.
  • Table 5 and FIG. 3 show the chlorhexidine elution profiles of the ionic polymers. Data show that using chlorhexidine acetate (400 mM) in methanol as the imbibing solution instead of chlorhexidine acetate (100 mM)/sodium citrate (1 mM) in 30/70 v/v% of methanol/water, chlorhexidine elution of perfluorosulfonic acid/ polytetrafluoroethylene copolymer (R8 and T4) does not change significantly; however, chlorhexidine elution of carboxylated polyurethane (R1 and R2) significantly improved.
  • Chlorhexidine Elution in Human (or Bovine ⁇ Serum Each sample loaded with chlorhexidine, as described above, was soaked in the elution media comprising 60/40 v/v% of human (or bovine) serum/phosphate buffered saline at 37 °C (on Orbital Shaker @ 150 RPM) for time intervals of 3 hours to 60 days. At each designated time interval, the previous elution media was removed for chlorhexidine elution analysis and quantification by high-performance liquid chromatography (HPLC) and fresh elution media was used for the next time interval. Chlorhexidine elution is defined as the mass of chlorhexidine eluted per unit area of sample in the unit of pg/cm 2 .
  • Chlorhexidine Post-Elution Extraction After elution testing, the remaining chlorhexidine in each sample was completely extracted using the extraction media comprising 0.3/70/30 v/v/v% of trifluoroacetic acid/acetonitrile/water at 37 °C for 24 hours (on Orbital Shaker @ 150 RPM), followed by analysis and quantification of remaining chlorhexidine in each sample by HPLC.
  • the chlorhexidine remaining is defined as the mass of chlorhexidine remained per unit area of sample in the unit of pg/cm 2 .
  • Chlorhexidine Loading Calculation Chlorhexidine initial loading on the sample can be calculated by adding total chlorhexidine elution (adding up all elution time points) and the chlorhexidine remain (by post-elution extraction). [0087] Table 6 shows the chlorhexidine initial loading data (average of 3 replicates) of both the control polymer without ionic functionalities and the ionic polymers by the above imbibing approach.
  • Table 6 shows that the control polymer without ionic functionalities (C3) exhibited low chlorhexidine loading after imbibing, which is nonbonded free chlorhexidine trapped within the polymer matrix during imbibing.
  • ionic polymers Rl, R2, R3, R4, R5, R6, Tl, T2 and T3 exhibited much higher chlorhexidine loading after imbibing, due to ionic interactions between the anionic functional group and chlorhexidine. Since these ionic polymers are all polyurethane-based materials, higher anionic content generally resulted in higher chlorhexidine loading.
  • Table 6 also shows that even without pre-swelling and de-protonation steps, very desirable chlorhexidine loading was still achieved with a single step imbibing process. Thus, the imbibing process can be significantly simplified.
  • Table 6 shows that for the same ionic polymer, tubing configuration
  • Table 7 shows the chlorhexidine elution in human (or bovine) serum and remain data (average of 3 replicates) of both the control polymer without ionic functionalities and the ionic polymers.
  • FIG. 4 shows the chlorhexidine accumulated elution in human (or bovine) serum over a period of time of both the control polymer without ionic functionalities and the ionic polymers.
  • Table 7 and FIG. 4 show the chlorhexidine elution profiles of both the control polymer without ionic functionalities and the ionic polymers. Similar as previously observed, the control polymer without ionic functionalities (C3) does not show a controlled release due to the low chlorhexidine loading. However, ionic polymers (Rl, R2, R3, R4, R5, R6, Tl, T2 and T3) showed very desirable and controlled release profiles up to 60 days. Since these ionic polymers are all polyurethane-based materials, higher anionic content generally resulted in higher chlorhexidine loading as well as higher chlorhexidine daily release.
  • tubing configuration i.e., Tl, T2 and T3
  • ribbon sheet configuration i.e., Rl, R4 and R6
  • Antimicrobial Testing The antimicrobial efficacy of the imbibed coupons (Rl, R2, R3, R4 and R6) against Candida albicans (yeast), Coagulase Negative Staphylococcus epidermidis (gram-positive), and Klebsiella pneumoniae (gram- negative) were tested after 1, 3, 7, and 14 days of preconditioning.
  • the testing method can quantitatively measure the microbial colonization on and around the sample coupons (both control and imbibed test coupons).
  • the coupon samples were assembled into the testing devices and sterilized by ethylene oxide prior to testing.
  • the preconditioning of coupon samples was performed up to 14 days using 60% Human Serum (HS) in phosphate buffered saline (PBS) at 37 ⁇ 2 °C with constant agitation and the preconditioning solution was changed daily with fresh sterile 60% HS in PBS.
  • HS Human Serum
  • PBS phosphate buffered saline
  • the coupon samples (both control and imbibed test coupons) were challenged with 3 different microbial organisms: i) Candida albicans (yeast, ⁇ 1.0 x 10 5 CFU/device) in 20% Mueller Hinton Broth (MHB) in Butterfield’s Phosphate Buffer, ii) Coagulase Negative Staphylococcus epidermidis (grampositive, ⁇ 1.0 x 10 5 CFU/device) in 20% Nutrient Broth (NB) in Butterfield’s Phosphate Buffer, and iii) Klebsiella pneumoniae (gram- negative, ⁇ 1.0 x 10 5 CFU/device) in 10% Nutrient Broth (NB) in Butterfield’s Phosphate Buffer.
  • the challenge was incubated at 37 ⁇ 2 °C for 24 hours with constant agitation. Testing was performed in triplicate for each microbial organism challenge at each time point.
  • Biofilm Recovery After 24 hours of microbial challenge, the coupon samples were rinsed with sterile saline and placed in D/E Neutralizing Broth. Then, the coupon samples were sonicated to recover biofilms adhered to the coupons. The recovered biofilm suspensions were quantified by serially diluting and plating on prepared Tryptic Soy Agar (TSA) plates. The plates were incubated at 37 ⁇ 2 ° C and counted after approximately 16-24 hours of incubation. Data was evaluated as total CFU recovered/device. Logio Reduction is compared to control sample (Cl) counts.
  • TSA Tryptic Soy Agar
  • Logio CFU/device Logio (CFU/device + 1) Equation (1)
  • Logio Reduction (Logio CFU/device control) - (Logio CFU/device test)
  • % Kill (((CFU/device control) - (CFU/device test)) -? (CFU/device control)) x 100 Equation (3)
  • Table 8 shows a summary of the antimicrobial testing results for both planktonic and biofilm reductions of all three microbial organisms after 1, 3, 7, and 14 days of HS preconditioning.
  • Table 8 shows that after 1, 3, and 7 days of HS preconditioning, all these imbibed ionic polymers (Rl, R2, R3, R4 and R6) presented very desirable antimicrobial performance (both planktonic and biofilm reductions) against all three microbial organisms due to their desirable chlorhexidine elution at Day 1, Day 3, and Day 7.
  • high ionic content imbibing samples (R2, R4 and R6) still presented very desirable antimicrobial performance (both planktonic and biofilm reductions) against all three microbial organisms due to their high chlorhexidine loading as well as continued high chlorhexidine elution at Day 14;
  • low ionic content imbibing samples (Rl and R3) still presented desirable antimicrobial performance (both planktonic and biofilm reductions) against Staphylococcus epidermidis, but start to loose antimicrobial efficacy against Candida albicans and/or Klebsiella pneumoniae due to their relatively lower chlorhexidine loading as well as relatively lower chlorhexidine elution at Day 14.
  • this technology is very efficient for long-term antimicrobial applications (e.g., indwell catheters).

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Abstract

Des articles médicaux formés par liaison ionique d'un polymère ionique et d'un agent actif fournissent des propriétés améliorées. Le polymère ionique peut être un ou plusieurs parmi un polymère anionique, un polymère cationique et un polymère zwitterionique. Le dispositif peut également comprendre un polymère non ionique. Les articles médicaux de la présente invention ont des caractéristiques antimicrobiennes, anti-salissures et/ou antithrombotiques.
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WO2024076460A1 (fr) * 2022-10-04 2024-04-11 Becton, Dickinson And Company Composés ioniques pour applications relatives à des dispositifs médicaux
WO2024076459A1 (fr) * 2022-10-04 2024-04-11 Becton, Dickinson And Company Composés ioniques pour applications de dispositif médical

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