Implantable or insertable medical device resistant to microbial growth and biofilm formation

• US 9,034,346 B2
• Filed: 01/24/2012
• Issued: 05/19/2015
• Est. Priority Date: 02/08/2002
• Status: Active Grant

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Inventors: Miller, Kathleen M., Sydney, Gregory T., Geitz, Kurt, Dayton, Peter L., Sahatjian, Ronald A.
• Primary Examiner(s): Azpuru, Carlos
• Assistant Examiner(s): HAGOPIAN, CASEY SHEA
• Application Number:
  US13/357,033
• Publication Number:
  US 20120121665A1
• Time in Patent Office: 1,211 Days
• Field of Search: None
• US Class Current: 424/400
• CPC Class Codes: A61L 2/232 layered or coated
• CPC Class Codes: A61L 2300/202 with halogen atoms, e.g. triclosan, povidone-iodine
• CPC Class Codes: A61L 2300/206 Biguanides, e.g. chlorohexidine
• CPC Class Codes: A61L 2300/21 Acids
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: Y10T 428/1334 Nonself-supporting tubular film or bag [e.g., pouch, envelope, packet, etc.]
• CPC Class Codes: Y10T 428/1352 Polymer or resin containing [i.e., natural or synthetic]
• CPC Class Codes: Y10T 428/1372 Randomly noninterengaged or randomly contacting fibers, filaments, particles, or flakes
• CPC Class Codes: Y10T 428/1379 Contains vapor or gas barrier, polymer derived from vinyl chloride or vinylidene chloride, or polymer containing a vinyl alcohol unit
• CPC Class Codes: Y10T 428/1386 Natural or synthetic rubber or rubber-like compound containing
• CPC Class Codes: Y10T 428/1393 Multilayer [continuous layer]

Abstract

Disclosed are implantable or insertable medical devices that provide resistance to microbial growth on and in the environment of the device and resistance to microbial adhesion and biofilm formation on the device. In particular, the invention discloses implantable or insertable medical devices that comprise at least one biocompatible matrix polymer region, an antimicrobial agent for providing resistance to microbial growth and a microbial adhesion/biofilm synthesis inhibitor for inhibiting the attachment of microbes and the synthesis and accumulation of biofilm on the surface of the medical device. Also disclosed are methods of manufacturing such devices under conditions that substantially prevent preferential partitioning of any of said bioactive agents to a surface of the biocompatible matrix polymer and substantially prevent chemical modification of said bioactive agents.

Claims

1. An implantable medical device comprising (a) at least one biocompatible matrix polymer region that comprises a radio-opacifying agent selected from bismuth subcarbonate, bismuth oxychloride and bismuth trioxide and least one of an antimicrobial agent or microbial attachment/biofilm synthesis inhibitor and (b) a barrier layer at least partially covering said at least one matrix polymer region, wherein said matrix polymer region and said barrier layer each comprises a biocompatible non-biodegradable polymer, wherein said non-biodegradable polymer is an ethylene vinyl acetate copolymer, and wherein said medical device is selected from a ureteral stent, a urethral stent, a urinary catheter, a biliary stent, a pancreatic stent, a tracheal stent, a gastrointestinal stent, an esophageal stent, and a peritoneal access device.

2. The medical device of claim 1, wherein said device is adapted to remain implanted for a period of greater than about 30 days.

5. The implantable medical device of claim 1, wherein said device is selected from a ureteral stent, a urethral stent and a urinary catheter.

7. The implantable medical device of claim 1, wherein said device is a ureteral stent.

3. An implantable medical device comprising (a) at least one biocompatible matrix polymer region that comprises a biocompatible non-biodegradable polymer and bismuth subcarbonate as a radio-opacifying agent and least one of an antimicrobial agent or microbial attachment/biofilm synthesis inhibitor and (b) a barrier layer comprising said biocompatible non-biodegradable polymer at least partially covering said at least one matrix polymer region, wherein said medical device is selected from a ureteral stent, a urethral stent, a urinary catheter, a biliary stent, a pancreatic stent, a tracheal stent, a gastrointestinal stent, an esophageal stent, and a peritoneal access device.

6. The implantable medical device of claim 3, wherein said device is selected from a ureteral stent, a urethral stent and a urinary catheter.

8. The implantable medical device of claim 3, wherein said device is a ureteral stent.

4. A ureteral stent comprising (a) a biocompatible matrix polymer region that comprises an ethylene vinyl acetate copolymer, bismuth subcarbonate as a radio-opacifying agent and least one of an antimicrobial agent or microbial attachment/biofilm synthesis inhibitor, and (b) a barrier layer that at least partially covers said matrix polymer region, said barrier layer comprising an ethylene vinyl acetate copolymer.