Medical devices having improved antimicrobial/antithrombogenic properties

• US 6,273,875 B1
• Filed: 08/17/1998
• Issued: 08/14/2001
• Est. Priority Date: 08/17/1998
• Status: Expired due to Term

• Current Assignee: Edwards Lifesciences Corporation
• Original Assignee: Edwards Lifesciences Corporation
• Inventors: Dove, Jeff, Siman, Jaime
• Primary Examiner(s): Sykes, Angela D.
• Assistant Examiner(s): Bianco, Patricia
• Application Number:
  US09/135,873
• Time in Patent Office: 1,093 Days
• Field of Search: 604/264-66, 604/20-21, 604/523, 523/112, 623/1, 428/35.7, 428/36.9, 424/422
• US Class Current: 604/264
• CPC Class Codes: A61L 2300/102 Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
• CPC Class Codes: A61L 2300/236 Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• 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: A61L 33/0011 Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
• CPC Class Codes: A61L 33/0023 using a quaternized group or a protonated amine group of the substrate
• CPC Class Codes: A61N 1/05 for implantation or insertion into the body, e.g. heart electrode A61N1/06 takes precedence

Abstract

An enhanced antimicrobial antithrombogenic medical device is formed by using an oligodynamic metal and a noble metal with a polymer, and forming the mixture into a device. By using low concentrations of conductive polymers or ionophoric compounds, non-conductive, or highly plasticized polymers can be likewise blended into an iontophoretic-capable composition. The surface of the device may be treated with a solvent to remove the top surface of the polymer and create surface voids in the composition in order to expose previously encapsulated iontophoretic materials. This surface treatment results in a larger reaction area of the iontophoretic capable composition that produces larger yields of bacteriostatic oligodynamic ions for a longer duration thereby increasing the antimicrobial effectiveness of the composition. The surface of the antimicrobial composition may be treated with an anticoagulant such as heparin or heparin complexed with a quaternary ammonium salt for an added bacteriostatic effect.

Claims

1. A medical device comprising a non-conductive plasticized polymer body, said polymer body comprising at least one iontophoretic compound, said polymer body further comprising an ionophore selected from the group consisting of metal ionophores, halide ionophores, proton ionophores and electron ionophores.

2. The medical device according to claim 1 wherein said polymer body comprises a metal ionophore, a halide ionophore, a proton ionophore and an electron ionophore wherein each of said ionophores is present in an amount of between about 0.1 and 2.0 weight percent of said polymer body.

3. The medical device according to claim 1 wherein said iontophoretic compound is a galvanic metal.

4. The medical device according to claim 1 further comprising the addition of a conductive polymer.

5. The medical device according to claim 4 wherein said conductive polymer is present in an amount of between about 1 to 5 weight percent of said polymer body.

6. The medical device according to claim 1 wherein said polymer body comprises polyvinyl chloride.

7. The medical device according to claim 1 which comprises an anticoagulent attached to said polymer body.

8. The medical device according to claim 7 wherein said anticoagulent comprises heparin.

9. The medical device of claim 1 comprising a surface and a polymer matrix located within said polymer body under said surface and wherein said polymer body is treated with a sufficient amount of an exposure enhancing reagent for a sufficient time to expose at least a portion of an unexposed active ingredients located within said polymer body surface and/or polymer matrix.

10. The medical device of claim 9 wherein said exposure enhancing agent is a solvent for said polymer matrix.

11. The medical device of claim 9 wherein said exposure enhancing agent is a swelling agent.

12. The medical device of claim 9 wherein said exposure enhancing agent is tetrahydrofuran.

13. The medical device of claim 1, wherein the ionophore chelates with a charged species of the iontophoretic compound and allows electro-migration of the charged species in the polymer body.

14. The medical device of claim 1, wherein the ionophore is a metal ionophore selected from the group consisting of:

diphenyl sulfide;

6-oxa-3, 9 dithiabicyclo 9.3.1 pentadeca 1(15), 11-13 triene; and

S,S methylenebis (diisobutyldithiocarbamate).

15. The medical device of claim 1, wherein the ionophore is a halide ionophore consisting essentially of meso-tetraphenylporphorin magnesium chloride.

16. The medical device of claim 1, wherein the ionophore is a proton ionophore selected from the group consisting of:

tridodecyl amine; and

4-nonadecyl pyridine.

17. The medical device of claim 1, wherein the ionophore is an electron or general ionophore selected from the group consisting of:

vitamin B12;

di tert butyl tartrate;

bis triphenylphosphoanylidene ammonium chloride;

tetradodecylammonium nitrate; and

tetraphenylphosphonium tetraphenylborate.

18. A medical device comprising a non-conductive plasticized polymer body, said polymer body comprising at least one iontophoretic compound, said polymer body further comprising an ionophore selected from the group consisting of metal ionophores, halide ionophores, proton ionophores and electron ionophores, and wherein:

said polymer body comprises a surface and a polymer matrix located within said polymer body under said surface, wherein at least a portion of the iontophoretic compound is exposed iontophoretic compound which is located at said surface and wherein at least a portion of the iontophoretic compound is unexposed iontophoretic compound which is also located at said surface but within said polymer matrix, said iontophoretic compound further including unexposed iontophoretic compound located deeper within said polymer matrix, wherein the medical device is made by;

treating said polymer body with a sufficient amount of an exposure enhancing reagent for a sufficient time to expose at least a portion of the unexposed iontophoretic compound located within said polymer body surface and/or polymer matrix.

19. A medical device comprising a non-conductive highly plasticized polymer body, said polymer body comprising at least one iontophoretic compound, said polymer body further comprising a conductive polymer wherein said polymer body has a glass transition temperature between ambient and body temperature.

20. The medical device according to claim 19 wherein said iontophoretic compound is a galvanic metal.

21. The medical device according to claim 19 wherein said polymer body comprises a conductive polymer which is present in an amount of between about 1 to 5 weight percent of said polymer body.

22. The medical device according to claim 19 wherein said polymer body comprises polyvinyl chloride.