ANTIMICROBIAL HOUSING AND COVER FOR A MEDICAL DEVICE

• US 20100197817A1
• Filed: 04/13/2010
• Published: 08/05/2010
• Est. Priority Date: 07/20/2007
• Status: Active Grant

• Current Assignee: Baxter Healthcare SA (Baxter International Inc.), Baxter International Inc.
• Original Assignee: Baxter Healthcare SA (Baxter International Inc.), Baxter International Inc.
• Inventors: Bui, Tuan, Lamb, David, Yardimci, Ozlem, Nordhaus, Mark, Sanders, Paul, Hai, Ton That, Jiang, Cong
• Granted Patent: US 9,125,973 B2
• Time in Patent Office: Days
• US Class Current: 521/53
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/442 Colorants, dyes
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/14 Materials characterised by their function or physical properties , e.g. lubricating compositions
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 39/045 pre-slit to be pierced by blunt instrument
• CPC Class Codes: A61M 39/16 having provision for disinfection or sterilisation A61M39/143 takes precedence; methods or apparatus for disinfection or sterilisation A61L2/00
• CPC Class Codes: C07D 213/30 Oxygen atoms
• CPC Class Codes: C08J 2207/10 Medical applications, e.g. biocompatible scaffolds
• CPC Class Codes: C08J 2309/06 Copolymers with styrene
• CPC Class Codes: C08J 2345/00 Characterised by the use of homopolymers or copolymers of compounds having no unsaturated aliphatic radicals in side chain, and having one or more carbon-to-carbon double bonds in a carbocyclic or in a heterocyclic ring system; Derivatives of such polymers of cyclic anhydrides or imides C08J2335/00; of cyclic esters of polyfunctional acids C08J2331/00
• CPC Class Codes: C08J 2367/00 Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain of polyester-amides C08J2377/12; of polyester-imides C08J2379/08; Derivatives of such polymers
• CPC Class Codes: C08J 2369/00 : Characterised by the use of polycarbonates; Derivatives of polycarbonates
• CPC Class Codes: C08J 2375/04 : Polyurethanes
• CPC Class Codes: C08J 2377/00 : Characterised by the use of polyamides obtained by reactions forming a carboxylic amide link in the main chain of polyhydrazides C08J2379/06; of polyamide-imides or polyamide acids C08J2379/08; Derivatives of such polymers
• CPC Class Codes: C08J 9/36 : After-treatment C08J9/22 takes precedence

Abstract

A method for immobilizing dyes and antimicrobial agents on a polymeric cover or housing for a medical device is disclosed and described. The surface may be that of a catheter, a connector, a drug vial spike, a bag spike, a prosthetic device, an endoscope, a surface of an infusion pump, a key pad, a touch screen or a handle. The surfaces may also be one or more of those associated with a infusion of a medicament or dialysis treatment, such as peritoneal dialysis or hemodialysis, where it is important that the working surface for the dialysis fluid be sterile. These surfaces include connectors for peritoneal dialysis sets or for hemodialysis sets, bag spikes, dialysis catheters, and so forth. A method for determining whether a surface has been sterilized, and a dye useful in so indicating, is also disclosed.

Claims

1. A method for providing a cover or housing for a medical device, the method comprising:

providing a medical device cover or a housing made from a polymer, the polymer optionally comprising a porous surface;

treating a surface of the cover or housing with a plurality of functional groups;

attaching a linking group to the functional groups; and

attaching an antimicrobial agent to the functional group or to the linking group.

2. The method of claim 1, further comprising attaching an effective amount of a solvatochromic dye or a tetrazolium salt to the functional group or the linking group.

3. The method of claim 1, wherein the functional groups on the surface are provided by reacting the surface with an acid, washing, and drying or non-thermal plasma discharge processing.

4. The method of claim 1, wherein the linking group is provided by poly(N-succinimidyl acrylate) (PNSA), polyethyleneimine, polyallylimine, or a polymer with an aldehyde functional group, a epoxide functional group, or a halogenoalkyl group.

5. The method of claim 1, further comprising masking the surface and directing the antimicrobial agent to a desired location on the surface.

6. The method of claim 1, further comprising swabbing the surface or the porous surface with a disinfecting solution, whereupon a color or an appearance of the surface changes reversibly.

7. The method of claim 6, further comprising allowing the disinfecting solution to evaporate, whereupon the color or the appearance of the surface or the porous surface changes back to the color or the appearance that existed before swabbing.

8. The method of claim 1, wherein the cover is a removable membrane or a film.

9. The method of claim 1, wherein the cover or housing is made from a polymer having an index of refraction from about 1.25 to about 1.6.

10. The method of claim 1, further comprising attaching an effective amount of an alkyl-amino containing compound selected from the group consisting of heparin, proteins, chitosan Factor VIII or other anti-clotting Factor, polysaccharides, peptides, polmyxins, hyaluronic acid, condroitin sulfate, and derivatives of each of these.

11. A method of treating a medical device, the method composing:

treating a surface or porous surface of a polymeric cover or a polymeric housing for a medical device with a strong acid or plasma discharge to provide a plurality of functional groups on the surface;

reacting the functional groups with a linking agent to form attachment sites, the linking agent selected from the group consisting of poly(N-succinimidyl acrylate) (PNSA), polyethyleneimine, polyallylimine, and polymers with an aldehyde functional group; and

attaching a solvatochromic dye, an antimicrobial agent, or an alkyl-amino containing compound to the attachment sites.

12. The method of claim 11, wherein the alkyl-ammo containing compound is selected from the group consisting of peptides, proteins, Factor VIII or other anti-clotting Factor, polysaccharides, polymyxins, hyaluronic acid, heparin, chitosan, and derivatives of each of these.

13. The method of claim 11, wherein the polymeric cover or housing has an index of refraction from about 1.25 to about 1.6.

14. The method of claim 11, further comprising treating the surface or porous surface to induce amine functional groups.

15. The method of claim 11, wherein the solvatochromatic dye is selected from the group consisting of 4,6-dichloro-2-[2-(6-aminohexyl-4-pyridinio)-vinyl] phenolate and derivatives, Reichardt'"'"'s dye, its salts and derivatives, merocyanine dyes and their derivatives, and tetrazolium compounds and their derivatives.

16. The method of claim 11, further comprising stabilizing the surface or porous surface by converting unreacted carboxyl attachment sites to a salt.

17. The method of claim 11, wherein the surface or porous surface comprises a membrane or a coating for attachment to the medical device.

18. The method of claim 11, wherein treating a nylon surface with a strong acid results in amino attachment sites, treating a polycarbonate surface with chlorosulfonic acid results in sulfonyl chloride attachment sites, and treating a polyester surface or polycarbonate surface with an acrylic or methacrylic acid results in carboxyl attachment sites.

19. A polymeric cover or housing, comprising:

a polymer in a form of a cover or a housing for a medical device;

a plurality of attachment sites on an least an outer surface of the polymer;

optionally, a plurality of functional groups attached to the attachment sites; and

at least one of an antimicrobial compound and a solvatochromic dye, attached to the attachment sites or to the functional groups, wherein the outer surface is configured to reversibly change from a first appearance to a second appearance when the outer surface is swabbed with a disinfecting solution.

20. The medical device according to claim 19, wherein the polymer surface is porous and is made from a polymer having an index of retraction from about 1.25 to about 1.6.

21. The medical device according to claim 19, wherein the polymer is a discrete membrane, a foamed article, a thin film, a casting, a molding, or a coating.

22. The medical device according to claim 19, wherein the antimicrobial compound comprises an effective amount of a compound selected from the group consisting of:

chlorhexidine, its salts and derivates;

an antimicrobial agent bearing an aminoalkyl group;

chloroxyphenol;

triclosan;

triclocarban and derivatives;

chitosan and chitosan derivatives; and

a quaternary ammonium compound.

23. The medical device surface, according to claim 19, wherein the polymeric cover or housing further comprises an effective amount of an oligodynamic compound or an antimicrobial compound.

24. A medical device, comprising:

a porous polymeric surface or cover for a medical device;

a plurality of attachment sites on the polymeric surface;

optionally, a plurality of functional groups attached to the attachment sites;

a solvatochromic dye, attached to the attachment sites or to the functional groups, wherein the porous polymeric surface is configured to reversibly change from a first appearance to a second appearance when the porous polymeric surface is swabbed with a disinfecting solution; and

optionally an antimicrobial compound, attached to the attachment sites or to the functional groups, wherein the antimicrobial compound is configured to be cidal to, or to resist growth of, microorganisms on the polymeric surface.

25. The medical device according to claim 24, wherein the medical device surface or cover is selected from the group consisting of a cover for a catheter, a drug vial spike, a connector, a vascular access devices, a luer access device, an access port, a medication port, a pigtail connector, a prosthetic, an endoscope, a bronchoscope, a stethoscope, an infusion pump, a key pad, a touch screen, and a handle.

26. The medical device according to claim 24, wherein the porous polymeric surface has an index of refraction from about 1.25 to about 1.6.

27. The medical device according to claim 24, wherein the solvatochromic dye is selected from the group consisting of 4,6-dichloro-2-[2-(6-aminohexyl-4-pyridinio)-vinyl] phenolate and derivatives. Reithardt'"'"'s dye, its salts and derivatives, merocyanine dyes and their derivatives, and tetrazolium compounds and their derivatives.

28. The medical device of claim 24, wherein the polymer is selected from the group consisting of elastomers, acrylic, COC, nylon, methacrylic, polycarbonate, ABS, polyurethane, polyester, and vinylester.

29. The medical device according to claim 24, wherein the attachment sites comprise at least one of carboxyl groups, amine groups, and amide groups.

30. The medical device according to claim 24, wherein the polymer comprises a discrete membrane cut from a sheet, a foamed article, a film, a casting, a molding, or a coating.

31. The medical device according to claim 24, wherein the antimicrobial compound comprises an effective amount of compound selected from the group consisting of chlorhexidine, its salts and den sates, an antimicrobial agent bearing an aminoalkyl group, chloroxyphenol, triclosan and triclocarban and derivatives, chitosan and chitosan derivatives, and a quaternary ammonium compound.

32. The medical device according to claim 24, wherein the surface further comprises an effective amount of an oligodynamic or an antimicrobial material.

33. A medical device, comprising:

a cover or housing for a medical device made from a polymer;

a plurality of attachment sites on to surface of the cover or housing;

optionally, a plurality of functional groups attached to the attachment sites;

a solvatochromic dye, attached to the attachment sites or to the functional groups, wherein the surface is configured to reversibly change from a first appearance to a second appearance when the porous polymeric surface is swabbed with a disinfecting solution; and

an amino-alkyl containing compound selected from the group consisting of peptides, proteins, Factor VIII or other anti-clotting Factor, polysaccharides, polymyxins, hyaluronic acid, heparin, condroitin sulfate, chitosan, and derivatives of each of these, to the attachment sites.

34. The medical device according to claim 33, further comprising an antimicrobial compound, attached to the attachment sites or to the functional groups, wherein the antimicrobial compound is configured to be cidal to, or to resist growth of, microorganisms on the surface of the device.

35. The medical device according to claim 33, wherein the medical device is selected from the group consisting of catheters, drug vial spikes, connectors, vascular access devices, luer access devices, access ports, medication ports, pigtail connectors, prosthetics, endoscopes, bronchoscopes, stethoscopes, infusion pumps, key pads, touch screens, and handles.