Medical devices having antimicrobial coatings thereon

• US 20050008676A1
• Filed: 12/10/2003
• Published: 01/13/2005
• Est. Priority Date: 12/19/2002
• Status: Abandoned Application

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Lally, John Martin, Kotov, Nicholas, Winterton, Lynn Cook, Qiu, Yongxing
• Application Number:
  US10/732,648
• Publication Number:
  US 20050008676A1
• Time in Patent Office: Days
• US Class Current: 424/429
• CPC Class Codes: A61K 31/14 Quaternary ammonium compounds, e.g. edrophonium, choline betaines A61K31/205
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61L 2300/104 Silver, e.g. silver sulfadiazine
• 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 2300/608 having two or more layers
• CPC Class Codes: A61L 2300/61 containing two or more active agents in different layers
• CPC Class Codes: A61L 2300/624 Nanocapsules
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/106 Inorganic materials other than carbon
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/088 Other specific inorganic materials not covered by A61L31/084 or A61L31/086
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: G02B 1/043 Contact lenses
• CPC Class Codes: Y10T 428/31678 Of metal
• CPC Class Codes: Y10T 428/31681 Next to polyester, polyamide or polyimide [e.g., alkyd, glue, or nylon, etc.]
• CPC Class Codes: Y10T 428/31692 Next to addition polymer from unsaturated monomers

Abstract

The present invention provides a medical device, preferably a contact lens, which a core material and an antimicrobial metal-containing LbL coating that is not covalently attached to the medical device and can impart to the medical device an increased hydrophilicity. The antimicrobial metal-containing coating on a contact lens of the invention has a high antimicrobial efficacy against microorganisms including Gram-positive and Gram-negative bacterial and a low toxicity, while maintaining the desired bulk properties such as oxygen permeability and ion permeability of lens material. Such lenses are useful as extended-wear contact lenses. In addition, the invention provides a method for making a medical device, preferably a contact lens, having an antimicrobial metal-containing LbL coating thereon.

Claims

1. A medical device comprising a core material and an antimicrobial metal-containing LbL coating, wherein the antimicrobial metal-containing LbL coating is not covalently attached to the core material and imparts to the medical device a hydrophilicity characterized by having an averaged contact angle of less than 80 degree.

2. A medical device of claim 1, wherein the antimicrobial metal-containing LbL coating comprises a member selected from the group consisting of:

(a) one layer of charged antimicrobial metal nano-particles;

(b) one layer of charged antimicrobial metal-containing nano-particles;

(c) silver-polyelectrolyte complexes formed between silver ions and a polycationic material having amino groups;

(d) silver-polyelectrolyte complexes formed between silver ions and a polyionic material having sulfur-containing groups;

(e) silver nano-particles; and

(f) combinations thereof.

3. A medical device of claim 2, wherein the medical device further comprises one or more antimicrobial agents selected from the group consisting of polyquats which exhibit antimicrobial activity, furanones, antimicrobial peptides, isoxazolinones, and organic selenium compounds.

4. A medical device of claim 3, wherein said one or more antimicrobial agents are covalently attached to the surface of the core material.

5. A medical device of claim 3, wherein said one or more antimicrobial agents are covalently attached to the antimicrobial metal-containing LbL coating through the reactive sites of the antimicrobial metal-containing LbL coating.

6. A medical device of claim 2, wherein the antimicrobial metal-containing LbL coating comprises one capping layer of a polyionic material.

7. A medical device of claim 2, wherein the antimicrobial metal-containing LbL coating comprises one capping electrolyte bilayer of a positively charged polyionic material and a negatively charged polyionic material or one capping layer of a charged polymeric material and a non-charged polymeric material that can be non-covalently bonded to the charged polymeric material.

8. A medical device of claim 2, wherein the antimicrobial LbL coating comprises at least one layer of an antimicrobial polyquat.

9. A medical device of claim 2, wherein the medical device is a hard or soft contact lens.

10. A contact lens of claim 9, wherein the antimicrobial metal-containing LbL coating comprises:

at least one layer of charged antimicrobial metal nano-particles and/or charged antimicrobial metal-containing nanoparticles; and

at least one layer of a polyionic material having charges opposite of the charges of the charged antimicrobial metal nano-particles and/or charged antimicrobial metal-containing nanoparticles.

11. A contact lens of claim 10, wherein said charged antimicrobial metal nanoparticles are charged silver nanoparticles, and wherein the charged antimicrobial metal-containing nanoparticles are charged silver-containing nanoparticles.

12. A contact lens of claim 9, wherein the antimicrobial metal-containing LbL coating comprises at least one layer of a negatively-charged polyionic material and at least one layer of silver-polyelectrolyte complexes formed between silver ions and a polycationic material having amino groups.

13. A contact lens of claim 9, wherein the antimicrobial metal-containing LbL coating comprises at least one layer of a negatively-charged polyionic material and at least one layer of silver-polyelectrolyte complexes formed between silver cations and a polyionic material having sulfur-containing groups.

14. A contact lens of claim 9, wherein the antimicrobial metal-containing LbL coating comprises at least one layer of a silver-polyelectrolyte complex formed between silver ions and a polyionic material having sulfur-containing groups.

15. A contact lens of claim 9, wherein the antimicrobial metal-containing LbL coating comprises silver nano-particles.

16. A contact lens of claim 15, wherein the silver nano-particles are obtained by first forming a transitional LbL coating composed of at least one layer of a first polyionic material and at least one layer of a second polyionic material having charges opposite of the charges of the first polyionic material, wherein at least one of the first and second polyionic materials is a silver-polyelectrolyte complex formed between silver cations and a positively-charged amino group containing polyionic material, a silver-polyelectrolyte complex formed between silver cations and a polyionic material with sulfur-containing groups;

and then by reducing silver ions in the transitional LbL coating by means of a reducing agent, UV irradiation or heating.

17. A contact lens of claim 9, wherein the contact lens further comprises one or more antimicrobial agents selected from the group consisting of polyquats which exhibit antimicrobial activity, furanones, antimicrobial peptides, isoxazolinones, and organic selenium compounds.

18. A contact lens of claim 17, wherein said one or more antimicrobial agents are covalently attached to the surface of the core material.

19. A contact lens of claim 17, wherein said one or more antimicrobial agents are covalently attached to the antimicrobial metal-containing LbL coating through the reactive sites of the antimicrobial metal-containing LbL coating.

20. A contact lens of claim 9, wherein the contact lens further comprises a plasma coating on top of the antimicrobial metal-containing LbL coating.

21. A medical device of claim 2, wherein the medical device is a case or container for storing an ophthalmic device or an ophthalmic solution.

22. A medical device of claim 21, wherein the case or container further comprises one or more antimicrobial agents selected from the group consisting of polyquats which exhibit antimicrobial activity, furanones, antimicrobial peptides, isoxazolinones, and organic selenium compounds.

23. A medical device of claim 22, wherein said one or more antimicrobial agents are covalently attached to the surface of the core material.

24. A medical device of claim 22, wherein said one or more antimicrobial agents are covalently attached to the antimicrobial metal-containing LbL coating through the reactive sites of the antimicrobial metal-containing LbL coating.

25. A method for preparing a medical device having an antimicrobial metal-containing LbL coating thereon, comprising the steps of:

(a) contacting said medical device with a solution of a first charged material to form a layer of the first charged material on the medical device;

(b) optionally rinsing said medical device by contacting said medical device with a first rinsing solution

(c) contacting said medical device with a solution of a second charged material to form a layer of the second charged material on top of the layer of the first charged material, wherein the second charged material has charges opposite of the charges of the first charged material; and

(d) optionally rinsing said medical device by contacting said medical device with a second rinsing solution,

wherein at least one of the first and second charged material is selected from the group consisting of charged antimicrobial metal nanoparticles, charged antimicrobial metal-containing nano-particles, silver-polyelectrolyte complexes formed between silver ions and a polycationic material having amino groups, silver-polyelectrolyte complexes formed between silver ions and a polyionic material having sulfur-containing groups, and combinations thereof.

26. A method of claim 25, wherein at least one of said contacting occurs by immersion said medical device in a solution.

27. A method of claim 25, wherein at least one of said contacting occurs by spraying a solution onto the medical device.

28. A method of claim 25, wherein said method comprises repeating steps (a) through (d) between 2 to 20 times.

29. A method of claim 25, wherein at least one of the first and second charged material is selected from the group consisting of silver-polyelectrolyte complexes formed between silver ions and a polycationic material having amino groups, silver-polyelectrolyte complexes formed between silver ions and a polyionic material having sulfur-containing groups, and combinations thereof, and wherein the method further comprises a step of reducing the silver ions in the antimicrobial metal-containing LbL coating to form silver nano-particles.

30. A method of claim 29, wherein said reducing occurs by means of a reducing agent.

31. A method of claim 29, wherein said reducing occurs by means of UV irradiation.

32. A method of claim 29, wherein said reducing occurs by means of heating.

33. A method of claim 25, comprising, prior step (a), the step of completely or partially coating the surface of the medical device with at least one antimicrobial agent selected from the group consisting of a polyquat which exhibits antimicrobial activity, furanones, antimicrobial peptides, isoxazolinones, and organic selenium compounds, wherein said at least one antimicrobial agent is covalently attached to the surface of the medical device.

34. A method of claim 25, further comprising the step of covalently attaching at least one antimicrobial agent to the antimicrobial metal-containing LbL coating through the reactive sites of the antimicrobial metal-containing LbL coating, wherein said at least one antimicrobial agent is selected from the group consisting of a polyquat which exhibits antimicrobial activity, furanones, antimicrobial peptides, isoxazolinones, and organic selenium compounds.

35. A method of claim 25, further comprising the step of subjecting the medical device with the antimicrobial metal-containing LbL coating to a plsma treatment to form a plasma coating on top of the antimicrobial metal-containing LbL coating.

36. A method for preparing a medical device having an antimicrobial metal-containing LbL coating thereon, comprising the steps of dipping said medical device in a solution containing a first charged material and a second charged material for a desired period of time so as to obtain the antimicrobial LbL coating characterized by having an average contact angle of about 80 degrees or less, wherein the second charged material has charges opposite of the charges of the first charged material, wherein the first charged material and the second charged material are present in an amount such that the ratio of the charges of the first charged material to the second charged material is from about 3:

1 to about 100;

1, wherein at least one of the first and second charged material is selected from the group consisting of charged antimicrobial metal nanoparticles, charged antimicrobial metal-containing nano-particles, silver-polyelectrolyte complexes formed between silver ions and a polycationic material having amino groups, silver-polyelectrolyte complexes formed between silver ions and a polyionic material having sulfur-containing groups, and combinations thereof.

37. A method of claim 36, wherein at least one of the first and second charged material is selected from the group consisting of silver-polyelectrolyte complexes formed between silver ions and a polycationic material having amino groups, silver-polyelectrolyte complexes formed between silver ions and a polyionic material having sulfur-containing groups, and combinations thereof, and wherein the method further comprises a step of reducing the silver ions in the antimicrobial LbL coating to form silver nano-particles.

38. A method of claim 37, wherein said reducing occurs by means of a reducing agent, UV irradiation, or heating.

39. A method of claim 36, comprising, prior the step of dipping, the step of completely or partially coating the surface of the medical device with at least one antimicrobial agent selected from the group consisting of a polyquat which exhibits antimicrobial activity, furanones, antimicrobial peptides, isoxazolinones, and organic selenium compounds, wherein said at least one antimicrobial agent is covalently attached to the surface of the medical device.

40. A method of claim 36, further comprising the step of covalently attaching at least one antimicrobial agent to the antimicrobial metal-containing LbL coating through the reactive sites of the antimicrobial metal-containing LbL coating, wherein said at least one antimicrobial agent is selected from the group consisting of a polyquat which exhibits antimicrobial activity, furanones, antimicrobial peptides, isoxazolinones, and organic selenium compounds.

41. A method of claim 36, further comprising the step of subjecting the medical device with the antimicrobial metal-containing LbL coating to a pisma treatment to form a plasma coating on top of the antimicrobial metal-containing LbL coating.

42. A method for producing a contact lens having an antimicrobial metal-containing LbL coating thereon, comprising the steps of:

(a) forming a mold for making the contact lens, wherein the mold comprises a first mold portion defining a first optical surface and a second mold portion defining a second optical surface, wherein said first mold portion and said second mold portion are configured to receive each other such that a contact lens-forming cavity is formed between said first optical surface and said second optical surface;

(b) applying a transferable antimicrobial LbL coating, using a layer-by-layer polyelectrolyte deposition technique, onto at least one of said optical surface, wherein the transferable antimicrobial LbL coating comprises at least one layer of a first charged material and at least one layer of a second charged material having charges opposite of the charges of the first charged material, wherein at least one of the first and second charged material is selected from the group consisting of charged antimicrobial metal nano-particles, charged antimicrobial metal-containing nanoparticles, silver-polyelectrolyte complexes formed between silver ions and a polycationic material having amino groups, silver-polyelectrolyte complexes formed between silver ions and a polyionic material having sulfur-containing groups, and combinations thereof;

(c) positioning said first mold portion and said second mold portion such that said mold portions receive each other and said optical surfaces define said contact lens forming cavity;

(d) dispensing a polymerizable composition into said contact lens-forming cavity; and

(e) curing said polymerizable composition within said contact lens-forming cavity such that the contact lens is formed, whereby said transferable antimicrobial LbL coating detaches from said at least one optical surface of said mold portion and reattaches to said formed contact lens such that said contact lens becomes coated with the antimicrobial metal-containing LbL coating.

43. A method of claim 42, wherein the method further comprises a step of reducing silver ions in the transferable antimicrobial LbL coating or in the silver-containing antimicrobial LbL coating to form silver nano-particles.

44. A method of claim 43, wherein said reducing occurs by means of a reducing agent, UV irradiation, or heating.

45. A method of claim 42, further comprising the step of covalently attaching at least one antimicrobial agent to the antimicrobial LbL coating through the reactive sites of the antimicrobial LbL coating on the contact lens, wherein said at least one antimicrobial agent is selected from the group consisting of a polyquat which exhibits antimicrobial activity, furanones, antimicrobial peptides, isoxazolinones, and organic selenium compounds.