Medical device having anti-infective and contraceptive properties

• US 6,939,569 B1
• Filed: 06/18/1999
• Issued: 09/06/2005
• Est. Priority Date: 06/19/1998
• Status: Expired due to Term

• Current Assignee: Oxibio, Inc.
• Original Assignee: Oxibio, Inc.
• Inventors: Fellman, Jack, Green, Terrence R.
• Primary Examiner(s): Clardy, S. Mark
• Assistant Examiner(s): CHOI, FRANK I
• Application Number:
  US09/336,392
• Time in Patent Office: 2,272 Days
• Field of Search: 424/667, 424/448, 424/449, 424/405, 424/409, 424/422, 424/423, 424/486, 424/607, 424/613, 424/661, 424/668, 424/669, 424/670, 424/718, 424/671, 216/17, 514/552, 514/557, 514/772.3, 514/953
• US Class Current: 424/667
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• CPC Class Codes: A61L 2300/106 Halogens or compounds thereof, e.g. iodine, chlorite
• CPC Class Codes: A61L 2300/11 Peroxy compounds, peroxides, e.g. hydrogen peroxide
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic 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: A61M 2025/0056 provided with an antibacterial agent, e.g. by coating, residing in the polymer matrix or releasing an agent out of a reservoir

Abstract

There is disclosed a medical device for implantation that acts to prevent transmission of infectious agents. Specifically, the present invention provides implantable devices, such as catheters or living skin matrices or wound dressings, for insertion into various body cavities or over wound sites to confer to the site microbicidal or virucidal activity. Devices in the disclosure designed as vaginal inserts also exhibit contraceptive spermicidal activity. The coated devices or devices having the inventive polymeric material interspersed throughout are formed into appropriate shapes according to their contemplated uses (such as catheters or Foley catheters). Further, the present invention provides devices for providing therapeutic anti-microbial activity into an infected body cavity or on an infected wound site.

Claims

1. An implantable anti-infective medical device selected from the group consisting of catheters, prostheses, shunts, stents, and leadwires, said device comprising a solid polymeric matrix selected from the group selected from a two component elastomer formulation, room temperature vulcanization elastomers, thermoplastic polymers, and hydrogels, containing within the matrix solid particles of an oxidant-producing component comprising a reducing agent, an oxidizing agent consisting of anhydrous alkali iodine oxide salts, inorganic and organic peracids, iodine pentoxide, an oxidase enzyme, and combinations thereof, that, when wetted, causes the formation of an oxidant and sustained release of the thus-formed oxidant into and about the polymeric matrix so that the matrix serves as an anti-infective reservoir;

wherein the oxidant is iodine generated at a quantity sufficient so that free-iodine concentration near a surface of the device should reach a level of at least 5 ppm;

wherein the polymeric matrix is formed from room temperature vulcanization elastomers when the oxidizing agent is selected to be the oxidase enzyme;

wherein the device further comprises an iodide salt when the oxidizing agent is inorganic and organic peracids or the oxidase enzyme.

2. The anti-infective medical device of claim 1 where the oxidant is elemental iodine.

3. The anti-infective medical device of claim 1 where the oxidant-producing component further comprises a proton donor that, in combination with the reducing agent and the oxidizing agent, forms solid particles dispersed within the polymeric matrix in sufficient amount to provide anti-infective activity to the medical device.

4. The anti-infective medical device of claim 3 where the proton donor is selected from the group consisting of organic acids, inorganic acids, iodine pentoxide, and other acid anhydrides.

5. The anti-infective medical device of claim 4 where the proton donor is selected from the group consisting of perborates and organoperoxy acids.

6. The anti-infective medical device of claim 5 where the proton donor has a concentration of from about 0.01% to about 16% by weight of the polymeric material.

7. The anti-infective medical device of claim 3 wherein the polymeric matrix is the room temperature vulcanization elastomers and where the proton donor is a hydrogen peroxide-generating oxidase enzyme selected from the group consisting of glucose oxidase and diamine oxidase.

8. The anti-infective medical device of claim 7 where the glucose oxidase has a specific activity of from about 2,000 IU/g to about 200,000 IU/g, the diamine oxidase has a specific activity of from about 50 U/g to about 800 IU/g, and the concentration of the glucose oxidase or diamine oxidase is from about 0.01% to about 2.5% by weight of the polymeric material.

9. The anti-infective medical device of claim 7 further comprising a peroxidase enzyme, where the glucose oxidase or diamine oxidase concentration is at least about 0.01% by weight of the polymeric matrix, the peroxidase enzyme is present at a concentration of at least about 0.01% by weight of the polymeric matrix, and the sum concentration of the oxidase and peroxidase enzymes is from of about 0.02% to about 2.5% by weight of the polymeric matrix.

10. The anti-infective medical device of claim 1 where the reducing agent is a water soluble iodide salt.

11. The anti-infective medical device of claim 10 where the reducing agent is an alkali iodide salt.

12. The anti-infective medical device of claim 11 where the alkali iodide salt has a concentration of about 0.01% to about 16% by weight of the polymeric matrix.

13. The anti-infective medical device of claim 1 where the oxidizing agent is selected from the group consisting of anhydrous alkali iodate salts, iodine pentoxide, and mixtures thereof.

14. The anti-infective medical device of claim 1 where the polymeric matrix comprises a hydrophobic polymer selected from the group consisting of polyureas, polyurethanes, poly(ethylene/-vinyl acetate), polyvinylchloride, polyesters, polyamides, polycarbonate, polyethylene, polypropylene, polystyrenes, polytetrafluoroethylene, and silicone polymers.

15. The anti-infective medical device of claim 14 where the oxidant is elemental iodine.

16. The anti-infective medical device of claim 14 where the oxidant-producing component further comprises a proton donor that, in combination with the reducing agent and the oxidizing agent, forms solid particles dispersed within the polymeric matrix in sufficient amount to provide anti-infective activity to the medical device.

17. The anti-infective medical device of claim 14 where the reducing agent is a water soluble iodide salt.

18. The anti-infective medical device of claim 17 where the reducing agent is an alkali iodide salt.

19. The anti-infective medical device of claim 18 where the alkali iodide salt has a concentration of about 0.01% to about 16% by weight of the polymeric matrix.

20. The anti-infective medical device of claim 14 where the oxidizing agent is selected from the group consisting of anhydrous alkali iodine oxide salts, iodine pentoxide, inorganic and organic peracids, and combinations thereof.

21. The anti-infective medical device of claim 20 where the oxidizing agent is selected from the group consisting of anhydrous alkali iodate salts, iodine pentoxide, and mixtures thereof.

22. The anti-infective medical device of claim 16 where the proton donor is selected from the group consisting of organic acids, inorganic acids, iodine pentoxide, and other acid anhydrides.

23. The anti-infective medical device of claim 22 where the proton donor is selected from the group consisting of perborates and organoperoxy acids.

24. The anti-infective medical device of claim 23 where the proton donor has a concentration of from about 0.01% to about 16% by weight of the polymeric material.

25. The anti-infective medical device of claim 16 where the polymeric matrix is the room temperature vulcanization elastomers when the proton donor is a hydrogen peroxide-generating oxidase enzyme selected from the group consisting of glucose oxidase and diamine oxidase.

26. The anti-infective medical device of claim 25 where the glucose oxidase has a specific activity of from about 2,000 IU/g to about 200,000 IU/g, the diamine oxidase has a specific activity of from about 50 IU/g to about 800 IU/g, and the concentration of the glucose oxidase or diamine oxidase is from about 0.01% to about 2.5% by weight of the polymeric material.

27. The anti-infective medical device of claim 25 further comprising a peroxidase enzyme, where the glucose oxidase or diamine oxidase concentration is at least about 0.01% by weight of the polymeric matrix, the peroxidase enzyme is present at a concentration of at least about 0.01% by weight of the polymeric matrix, and the sum concentration of the oxidase and peroxidase enzymes is from of about 0.02% to about 2.5% by weight of the polymeric matrix.

28. The anti-infective medical device of claim 1 selected from the group consisting of catheters and prostheses.

29. An implantable anti-infective medical device selected from the group consisting of catheters, prostheses, shunts, stents, and leadwires, comprising a solid polymeric matrix, comprising a solid polymeric matrix selected from the group consisting of room temperature vulcanization elastomers that contain within the matrix solid particles of an oxidant-producing component comprising an iodide salt and an oxidizing agent consisting of substrate oxidoreductases which, when allowed to contact oxidoreductase substrates in body fluids causes the formation of an oxidant and sustained release of the thus-formed oxidant into and about the polymeric matrix so that the matrix serves as an anti-infective reservoir;

wherein the oxidant is iodine generated at a quantity sufficient so that free-iodine concentration near a surface of the device should reach a level of at least 5 ppm.

30. An implantable anti-infective medical device selected from the group consisting of catheters, prostheses, shunts, stents, and leadwires, comprising a solid polymeric matrix selected from the group consisting of thermoplastic polymers and thermosetting polymers, containing within the matrix solid particles of a non-enzyme, oxidant-producing component comprising an oxidizing agent and an iodide salt which, when allowed to contact body fluids, generates an oxidant and sustained release of the thus-formed oxidant into and about the polymeric matrix so that the matrix serves as an anti-infective reservoir, wherein the oxidant is iodine generated at a quantity sufficient so that free-iodine concentration near a surface of the device should reach a level of at least 5 ppm.