Antimicrobial medical devices

• US 8,425,926 B2
• Filed: 07/14/2004
• Issued: 04/23/2013
• Est. Priority Date: 07/16/2003
• Status: Active Grant

• Current Assignee: Alcon Incorporated
• Original Assignee: Novartis Ag
• Inventors: Qiu, Yongxing, Lally, John Martin
• Primary Examiner(s): Long, Scott
• Assistant Examiner(s): Alawadi, Sarah
• Application Number:
  US10/891,407
• Publication Number:
  US 20050013842A1
• Time in Patent Office: 3,205 Days
• Field of Search: None
• US Class Current: 424/423
• CPC Class Codes: A01N 59/16 Heavy metals; Compounds thereof
• CPC Class Codes: A61L 12/088 Heavy metals
• 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 2300/442 Colorants, dyes
• CPC Class Codes: A61L 2300/624 Nanocapsules
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: B29D 11/00038 Production of contact lenses
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: G02B 1/043 Contact lenses

Abstract

The present invention provides methods for making an antimicrobial medical device, preferably an antimicrobial ophthalmic device, more preferably an antimicrobial extended-wear contact lens, which contains silver nano-particles distributed uniformly therein. The antimicrobial medical device can exhibit antimicrobial activity over an extended period of time.

Claims

1. A method for making an antimicrobial medical device, comprising the steps of:

obtaining a polymerizable fluid composition comprising a siloxane-containing macromer and a vinylic monomer capable of reducing silver cations;

adding a desired amount of a soluble silver salt into the fluid composition to form a polymerizable dispersion comprising silver nanoparticles and said silver nanoparticles having a stability of at least about 60 minutes, wherein the silver nanoparticles are formed by reducing the silver cations in the soluble silver salt with the vinylic monomer;

introducing an amount of the polymerizable dispersion in a mold for making a medical device; and

polymerizing the polymerizable dispersion in the mold to form the antimicrobial medical device containing silver nanoparticles.

2. The method of claim 1, wherein the medical device is an ophthalmic device.

3. The method of claim 2, wherein the polymerizable fluid composition is selected from the group consisting of formulations of lotrafilcon A, lotrafilcon B, etafilcon A, genfilcon A, lenefilcon A, polymacon, acquafilcon A, and balafilcon.

4. The method of claim 2, wherein the siloxane-containing macromer is selected from the group consisting of Macromer A, Macromer B, Macromer C, and Macromer D,

wherein Macromer A is a polysiloxane macromer having a number-average molecular weight of 2000 to 10,000 and the the segment of the formula:

CP—

PAO-DU-ALK—

PDMS-ALK-DU-PAO—

CP

where PDMS is a divalent poly(disubstituted siloxane), ALK is an alkylene or alkylenoxy group having at least 3 carbon atoms, DU is a diurethane-containing group, PAO is a divalent polyoxyalkylene, and CP is selected from acrylates and methacrylates,

wherein Macromer B is a polysiloxane-comprising perfluoroalkyl ether and has the formula;

P₁—

(Y)_m-(L-X₁)p-Q-(X₁-L)_p-(Y)_m—

P₁

where each P₁, independently of the others, is a free-radical-polymerizable group;

each Y, independently of the others, is —

CONHCOO—

, —

CONHCONH—

, —

OCONHCO—

, —

NHCONHCO—

, —

NHCO—

, —

CONH—

, —

NHCONH—

, —

COO—

, —

OCO—

, —

NHCOO—

or —

OCONH—

;

m and p, independently of one another, are 0 or 1;

each L, independently of the others, is a divalent radical of an organic compound having up to 20 carbon atoms;

each X₁, independently of the others, is —

NHCO—

, —

CONH—

, —

NHCONH—

, —

COO—

, —

OCO—

, —

NHCOO—

or —

OCONH—

; and

Q is a bivalent polymer fragment consisting of the segments;

(a) -(E)_k-Z—

CF₂—

(OCF₂)_x—

(OCF₂CF₂)_y—

OCF₂—

Z-(E)_k-,

where x+y is a number in the range of from 10 to 30;

each Z, independently of the others, is a divalent radical having up to 12 carbon atoms or Z is a bond;

each E, independently of the others, is —

(OCH₂CH₂)_q—

, where q has a value of from 0 to 2, and where the link —

Z-E- represents the sequence —

Z—

(OCH₂CH₂)_q—

; and

k is 0 or 1;

(b)

5. The method of claim 1, wherein the polymerizable fluid composition comprises a siloxane-containing monomer and/or a hydrophilic vinylic monomer.

6. The method of claim 5, wherein the polymerizable fluid composition comprises:

(a) about 20 to 40 weight percent of a siloxane-containing macromer, (b) about 5 to 30 weight percent of a siloxane-containing monomer, and (c) about 10 to 35 weight percent of a hydrophilic vinylic monomer.

7. The method of claim 1, wherein the vinylic monomer capable of reducing silver cations is selected from the group consisting of acrylamide, methacrylamide, di(lower alkyl)acrylamides, di(lower alkyl)methacrylamides, (lower allyl)acrylamides, (lower allyl)methacrylamides, hydroxyl-substituted (lower alkyl)acrylamides, hydroxyl-substituted (lower alkyl)methacrylamides, and N-vinyl lactams.

8. The method of claim 7, wherein the vinylic monomer is N,N-dimethylacrylamide (DMA) or N-vinyl-2-pyrrolidone (NVP).

9. The method of claim 1, wherein the polymerizable fluid composition further comprises a biocompatible reducing agent.

10. The method of claim 1, wherein the polymerizable fluid composition further comprises a stabilizer for stabilizing silver nano-particles.

11. The method of claim 10, wherein the stabilizer is a polyacrylic acid (PAA), a poly(ethyleneimine) (PEI), a poly(vinylpyrrolidone) (PVP), a copolymer of acrylic acid (AA) with a vinylic monomer, acrylic acid, or polyionic material having carboxyl, amino and/or sulfur-containing groups.

12. The method of claim 1, wherein a stabilizer is added into the polymerizable fluid composition together with the soluble silver salt, wherein the stabilizer is a polyacrylic acid (PAA), a poly(ethyleneimine) (PEI), a poly(vinylpyrrolidone) (PVP), a copolymer of acrylic acid (AA) with a vinylic monomer, acrylic acid, or polyionic material having carboxyl, amino and/or sulfur-containing groups.

13. The method of claim 1, wherein a biocompatible reducing agent is added into the mixture while mixing thoroughly the mixture so as to facilitate the formation of the polymerizable dispersion containing silver nano-particles.

14. The method claim 1, wherein the polymerizable fluid composition further comprises a pigment or a dye.

15. The method of claim 14, wherein the pigment is phthalocyanine blue, cobalt blue, Toner cyan BG, Permajet blue B2G, phthalocyanine green, chromium sesquioxide, an iron oxide, or carbazole violet, wherein the dye is a reactive blue dye.

16. The method of claim 9, wherein the biocompatible reducing agent is selected from the group consisting of ascorbic acid, biocompatible salts thereof, and salts of citrate.

17. The method of claim 13, wherein the biocompatible reducing agent is selected from the group consisting of ascorbic acid, biocompatible salts thereof, and biocompatible salts of citrate.