Antimicrobial medical devices

• US 20050013842A1
• Filed: 07/14/2004
• Published: 01/20/2005
• Est. Priority Date: 07/16/2003
• Status: Active Grant

• Current Assignee: Alcon Incorporated
• Original Assignee: Novartis Ag
• Inventors: Lally, John Martin, Qiu, Yongxing
• Granted Patent: US 8,425,926 B2
• Time in Patent Office: Days
• 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;

forming a polymerizable dispersion comprising silver nanoparticles and having a stability of at least about 60 minutes, wherein the silver nanoparticles are formed by adding a desired amount of a soluble silver salt into the fluid composition;

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;

—

(E)_k-Z-CF₂—

(OCF₂)_x—

(OCF₂CF₂)_y—

OCF₂-Z-(E)_k-,  

 

(a)

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)

wheren is an integer from 5 to 100;

Alk is alkylene having up to 20 carbon atoms;

80-100% of the radicals R₁, R₂, R₃ and R₄, independently of one another, are alkyl and 0-20% of the radicals R₁, R₂, R₃ and R₄, independently of one another, are alkenyl, aryl or cyanoalkyl; and

(c) X₂—

R—

X₂, where R is a divalent organic radical having up to 20 carbon atoms, and each X₂, independently of the others, is —

NHCO—

, —

CONH—

, —

NHCONH—

, —

COO—

, —

OCO—

, —

NHCOO—

or OCONH—

;

with the provisos that there must be at least one of each segment (a), (b), and (c) in Q, that each segment (a) or (b) has a segment (c) attached to it, and that each segment (c) has a segment (a) or (b) attached to it;

wherein Macromer C has an average molecular weight of from about 300 to about 30,000 and comprises at least one segment of the formula (I), (IV), (V), (VI) or (VII);

in which (a) is a polysiloxane segment;

(b) is a polyol segment which contains at least 4 carbon atoms;

Z is a segment (c) or a group X₁;

(c) is defined as X₂—

R—

X₂, wherein R is a bivalent radical of an organic compound having up to 20 carbon atoms and each X₂ independently of the other is a bivalent radical which contains at least one carbonyl group;

X₁ is defined as X₂;

x is 0, 1 or 2;

q has an average numerical value of 1-20; and

(d) is a radical of the formula (II);

X₃-L-(Y)_k-P₁  

 

(II)

in which P₁ is alkenyl, alkenylaryl or alkenylarylenealkyl having up to 20 carbon atoms;

Y and X₃ independently of one another are a bivalent radical which contains at least one carbonyl group;

k is 0 or 1; and

L is a bond or a divalent radical having up to 20 carbon atoms of an organic compound,

wherein the polysiloxane segment (a) is derived from a compound of the formula (III);

in which n is an integer from 5 to 500;

99.8-25% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are alkyl and 0.2-75% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are partly fluorinated alkyl, aminoalkyl, alkenyl, aryl, cyanoalkyl, alk-NH-alk-NH₂ or alk-(OCH₂)_m—

(OCH₂)p-OR₇, R₇ is hydrogen or lower alkyl, alk is alkylene, and m and p independently of one another are an integer from 0 to 10, one molecule containing at least one primary amino or hydroxyl group, wherein the alkylenoxy groups —

(OCH₂CH₂)_m and —

(OCH₂)_p in formula (III) are either distributed randomly in a ligand alk-(OCH₂CH₂)_m—

(OCH₂)_p—

OR₇ or are distributed as blocks in a chain,

wherein the polysiloxane segment (a) in formula (I) is linked a total of 1-50 times, via a group Z with the segment (b) or another segment (a), Z in an a-Z-a sequence always being a segment (c),

wherein the segments (b) in Macromer C according to the formula (VI) are linked in total (per molecule) with up to 20 with up to 6 polymerizable segments (d),

wherein the average number of segments (d) per molecule of the formula (VII) is in the range from 2 to 5, and very preferably is in the range from 3 to 4,

wherein macromer D has the formula;

ACRYLATE-LINK-O—

ALK—

PDAS—

ALK—

O—

ALK-LINK-ACRYLATE

in which the ACRYLATE is selected from acrylates and methacrylates;

LINK is selected from urethanes and dirurethane linkages;

ALK—

O—

ALK is R₁—

O—

R₂ or R₃—

O—

R₄, R₁, R₂, R₃, and R₄, independently of one another, are lower alkylene; and

PDAS is a poly(dialkylsiloxane) having a segment of the formula;

in which n is an integer from about 5 to about 500; and

R₅, R₆, R₇, and R₈ are, independently of one another, are lower alkyl.

5. The method of claim 1, wherein the polymerizable fluid composition comprises a siloxane-containing monomer and/or a hydrophilic 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 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. A method for making an antimicrobial medical device, comprising the steps of:

obtaining a polymerizable fluid composition comprising a siloxane-containing macromer and a soluble silver salt;

forming a polymerizable dispersion comprising silver nanoparticles and having a stability of at least about 60 minutes, wherein the silver nanoparticles are formed by adding into the fluid composition at least one biocompatible reducing agent;

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.

15. The method of claim 14, wherein the medical device is an ophthalmic device.

16. The method of claim 15, wherein the polymerizable fluid composition is obtained by dissolving a desired amount of the silver salt in a formulation selected from the group consisting of formulations of lotrafilcon A, lotrafilcon B, etafilcon A, genfilcon A, lenefilcon A, polymacon, acquafilcon A, and balafilcon.

17. The method of claim 15, 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;

-(E)_k-Z-CF₂—

(OCF₂)_x—

(OCF₂CF₂)_y—

OCF₂-Z-(E)_k-,  

 

(a)

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;

wheren is an integer from 5 to 100;

Alk is alkylene having up to 20 carbon atoms;

80-100% of the radicals R₁, R₂, R₃ and R₄, independently of one another, are alkyl and 0-20% of the radicals R₁, R₂, R₃ and R₄, independently of one another, are alkenyl, aryl or cyanoalkyl; and

(c) X₂—

R—

X₂, where R is a divalent organic radical having up to 20 carbon atoms, and each X₂, independently of the others, is —

NHCO—

, —

CONH—

, —

NHCONH—

, —

COO—

, —

OCO—

, —

NHCOO—

or OCONH—

;

with the provisos that there must be at least one of each segment (a), (b), and (c) in Q, that each segment (a) or (b) has a segment (c) attached to it, and that each segment (c) has a segment (a) or (b) attached to it;

wherein Macromer C has an average molecular weight of from about 300 to about 30,000 and comprises at least one segment of the formula (I), (IV), (V), (VI) or (VII);

in which (a) is a polysiloxane segment;

(b) is a polyol segment which contains at least 4 carbon atoms;

Z is a segment (c) or a group X₁;

(c) is defined as X₂—

R—

X₂, wherein R is a bivalent radical of an organic compound having up to 20 carbon atoms and each X₂ independently of the other is a bivalent radical which contains at least one carbonyl group;

X₁ is defined as X₂;

x is 0, 1 or 2;

q has an average numerical value of 1-20; and

(d) is a radical of the formula (II);

X₃-L-(Y)_k-P₁  

 

(II)

in which P₁ is alkenyl, alkenylaryl or alkenylarylenealkyl having up to 20 carbon atoms;

Y and X₃ independently of one another are a bivalent radical which contains at least one carbonyl group;

k is 0 or 1; and

L is a bond or a divalent radical having up to 20 carbon atoms of an organic compound,

wherein the polysiloxane segment (a) is derived from a compound of the formula (III);

in which n is an integer from 5 to 500;

99.8-25% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are alkyl and 0.2-75% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are partly fluorinated alkyl, aminoalkyl, alkenyl, aryl, cyanoalkyl, alk-NH-alk-NH₂ or alk-(OCH₂)_m—

(OCH₂)p-OR₇, R₇ is hydrogen or lower alkyl, alk is alkylene, and m and p independently of one another are an integer from 0 to 10, one molecule containing at least one primary amino or hydroxyl group, wherein the alkylenoxy groups —

(OCH₂CH₂)_m and —

(OCH₂)_p in formula (III) are either distributed randomly in a ligand alk-(OCH₂CH₂)_m—

(OCH₂)_p—

OR₇ or are distributed as blocks in a chain,

wherein the polysiloxane segment (a) in formula (I) is linked a total of 1-50 times, via a group Z with the segment (b) or another segment (a), Z in an a-Z-a sequence always being a segment (c),

wherein the segments (b) in Macromer C according to the formula (VI) are linked in total (per molecule) with up to 20 with up to 6 polymerizable segments (d),

wherein the average number of segments (d) per molecule of the formula (VII) is in the range from 2 to 5, and very preferably is in the range from 3 to 4,

wherein macromer D has the formula;

ACRYLATE-LINK-ALK—

O—

ALK—

PDAS—

ALK—

O—

ALK-LINK-ACRYLATE

in which the ACRYLATE is selected from acrylates and methacrylates;

LINK is selected from urethanes and dirurethane linkages;

ALK—

O—

ALK is R₁—

O—

R₂ or R₃—

O—

R₄, R₁, R₂, R₃, and R₄, independently of one another, are lower alkylene; and

PDAS is a poly(dialkylsiloxane) having a segment of the formula;

in which n is an integer from about 5 to about 500; and

R₅, R₆, R₇, and R₈ are, independently of one another, are lower alkyl.

18. The method of claim 14, wherein the polymerizable fluid composition comprises a siloxane-containing monomer and/or a hydrophilic monomer.

19. The method of claim 18, 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 monomer.

20. The method of claim 19, wherein the siloxane-containing monomer is selected from the group consisting of methacryloxyalkylsiloxanes, tristrimethylsilyloxysilylpropyl methacrylate (TRIS), 3-methacryloxy propylpentamethyldisiloxane and bis(methacryloxypropyl)tetramethyldisiloxane, and mixtures thereof, wherein the hydrophilic monomer is selected from the group consisting of N,N-dimethylacrylamide (DMA), 2-hydroxyethylmethacrylate (HEMA), hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate (HPMA), trimethylammonium 2-hydroxy propylmethacrylate hydrochloride, dimethylaminoethyl methacrylate (DMAEMA), dimethylaminoethylmethacrylamide, acrylamide, methacrylamide, allyl alcohol, vinylpyridine, glycerol methacrylate, N-(1,1dimethyl-3-oxobutyl)acrylamide, N-vinyl-2-pyrrolidone (NVP), acrylic acid, methacrylic acid and mixtures thereof.

21. The method of claim 14, wherein the polymerizable fluid composition further comprises a stabilizer for stabilizing silver nano-particles.

22. The method of claim 21, 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, acylic acid, or polyionic material having carboxyl, amino and/or sulfur-containing groups.

23. The method of claim 14, wherein a stabilizer is added into the polymerizable fluid composition together with the biocompatible reducing agent, 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, acylic acid, or polyionic material having carboxyl, amino, and/or sulfur-containing groups.

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

obtaining a stabilized-silver nano-particle solution or lyophilized stabilized-silver nano-particles;

directly dispersing a desired amount of the stabilized-silver nano-particle solution or the lyophilized stabilized-silver nano-particles in a polymerizable fluid composition comprising a siloxane-containing macromer to form a polymerizable dispersion having a stability of at least about 60 minutes;

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.

25. The method of claim 24, wherein the medical device is an ophthalmic device.

26. The method of claim 24, wherein the stabilized-silver nano-particles are obtained by reducing silver ions or silver salts in a solution in the presence of a stabilizer by means of a reducing agent or of heating or UV irradiation.

27. The method of claim 26, 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, acylic acid, or polyionic material having carboxyl, amino, and/or sulfur-containing groups.

28. The method of claim 25, 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.

29. The method of claim 25, 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;

-(E)_k-Z-CF₂—

(OCF₂)_x—

(OCF₂CF₂)_y—

OCF₂-Z-(E)_k-,  

 

(a)

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)

wheren is an integer from 5 to 100;

Alk is alkylene having up to 20 carbon atoms;

80-100% of the radicals R₁, R₂, R₃ and R₄, independently of one another, are alkyl and 0-20% of the radicals R₁, R₂, R₃ and R₄, independently of one another, are alkenyl, aryl or cyanoalkyl; and

(c) X₂—

R—

X₂, where R is a divalent organic radical having up to 20 carbon atoms, and each X₂, independently of the others, is —

NHCO—

, —

CONH—

, —

NHCONH—

, —

COO—

, —

OCO—

, —

NHCOO—

or OCONH—

;

with the provisos that there must be at least one of each segment (a), (b), and (c) in Q, that each segment (a) or (b) has a segment (c) attached to it, and that each segment (c) has a segment (a) or (b) attached to it;

wherein Macromer C has an average molecular weight of from about 300 to about 30,000 and comprises at least one segment of the formula (I), (IV), (V), (VI) or (VII);

in which (a) is a polysiloxane segment;

(b) is a polyol segment which contains at least 4 carbon atoms;

Z is a segment (c) or a group X₁;

(c) is defined as X₂—

R—

X₂, wherein R is a bivalent radical of an organic compound having up to 20 carbon atoms and each X₂ independently of the other is a bivalent radical which contains at least one carbonyl group;

X₁ is defined as X₂;

x is 0, 1 or 2;

q has an average numerical value of 1-20;

and (d) is a radical of the formula (II);

X₃-L-(Y)_k-P₁  

 

(II)

in which P₁ is alkenyl, alkenylaryl or alkenylarylenealkyl having up to 20 carbon atoms;

Y and X₃ independently of one another are a bivalent radical which contains at least one carbonyl group;

k is 0 or 1; and

L is a bond or a divalent radical having up to 20 carbon atoms of an organic compound,

wherein the polysiloxane segment (a) is derived from a compound of the formula (III);

in which n is an integer from 5 to 500;

99.8-25% of the radicals R₁, R₂, R₃, R₄, R₅ and

R₆ independently of one another are alkyl and 0.2-75% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are partly fluorinated alkyl, aminoalkyl, alkenyl, aryl, cyanoalkyl, alk-NH-alk-NH₂ or alk-(OCH₂)_m—

(OCH₂)p-OR₇, R₇ is hydrogen or lower alkyl, alk is alkylene, and m and p independently of one another are an integer from 0 to 10, one molecule containing at least one primary amino or hydroxyl group, wherein the alkylenoxy groups —

(OCH₂CH₂)_m and —

(OCH₂)_p in formula (III) are either distributed randomly in a ligand alk-(OCH₂CH₂)_m—

(OCH₂)_p—

OR₇ or are distributed as blocks in a chain,

wherein the polysiloxane segment (a) in formula (I) is linked a total of 1-50 times, via a group Z with the segment (b) or another segment (a), Z in an a-Z-a sequence always being a segment (c),

wherein the segments (b) in Macromer C according to the formula (VI) are linked in total (per molecule) with up to 20 with up to 6 polymerizable segments (d),

wherein the average number of segments (d) per molecule of the formula (VII) is in the range from 2 to 5, and very preferably is in the range from 3 to 4,

wherein macromer D has the formula;

ACRYLATE-LINK-ALK—

O—

ALK—

PDAS—

ALK—

O—

ALK-LINK-ACRYLATE

in which the ACRYLATE is selected from acrylates and methacrylates;

LINK is selected from urethanes and dirurethane linkages;

ALK—

O—

ALK is R₁—

O—

R₂ or R₃—

O—

R₄, R₁, R₂, R₃, and R₄, independently of one another, are lower alkylene; and

PDAS is a poly(dialkylsiloxane) having a segment of the formula;

in which n is an integer from about 5 to about 500; and

R₅, R₆, R₇, and R₆ are, independently of one another, are lower alkyl.

30. The method of claim 25, wherein the polymerizable fluid composition comprises a siloxane-containing monomer and/or a hydrophilic monomer.

31. The method of claim 30, 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 monomer.

32. The method of claim 31, wherein the siloxane-containing monomer is selected from the group consisting of methacryloxyalkylsiloxanes, tristrimethylsilyloxysilylpropyl methacrylate (TRIS), 3-methacryloxy propylpentamethyldisiloxane and bis(methacryloxypropyl)tetramethyldisiloxane, and mixtures thereof, wherein the hydrophilic monomer is selected from the group consisting of N,N-dimethylacrylamide (DMA), 2-hydroxyethylmethacrylate (HEMA), hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate (HPMA), trimethylammonium 2-hydroxy propylmethacrylate hydrochloride, dimethylaminoethyl methacrylate (DMAEMA), dimethylaminoethylmethacrylamide, acrylamide, methacrylamide, allyl alcohol, vinylpyridine, glycerol methacrylate, N-(1,1dimethyl-3-oxobutyl)acrylamide, N-vinyl-2-pyrrolidone (NVP), acrylic acid, methacrylic acid and mixtures thereof.

33. An antimicrobial ophthalmic device, comprising:

a polymer matrix, silver-nanoparticles distributed therein and at least one dye and/or pigment distributed therein in a substantially uniform amnner, wherein the polymer matrix includes a polysiloxane unit, has a high oxygen permeability characterized by a D_k greater than 60 barrers and a high ion permeability characterized by an ionoflux diffusion coefficient of great than 6.0×

10<sup>−

4</sup> mm²/min, and comprises a water content of at least 15 weight percent when fully hydrated, wherein the antimicrobial medical device exhibit at least a 5-fold reduction (≧

80% inhibition) of viable microorganisms, and wherein the dye and/or pigment, in combination with the color of the silver nano-particle, provides a desired color.

34. The antimicrobial ophthalmic device of claim 33, wherein the polymer matrix is a polymerization product of a polymerizable composition including a siloxane-containing macromer, a siloxane-containing monomer, and a hydrophilic monomer.

35. The antimicrobial ophthalmic device of claim 34, 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;

-(E)_k-Z-CF₂—

(OCF₂)_x—

(OCF₂CF₂)_y—

OCF₂-Z-(E)_k-,  

 

(a)

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)

wheren is an integer from 5 to 100;

Alk is alkylene having up to 20 carbon atoms, 80-100% of the radicals R₁, R₂, R₃ and R₄, independently of one another, are alkyl and 0-20% of the radicals R₁, R₂, R₃ and R₄, independently of one another, are alkenyl, aryl or cyanoalkyl; and

(c) X₂—

R—

X₂, where R is a divalent organic radical having up to 20 carbon atoms, and each X₂, independently of the others, is —

NHCO—

, —

CONH—

, —

NHCONH—

, —

COO—

, —

OCO—

, —

NHCOO—

or OCONH—

;

with the provisos that there must be at least one of each segment (a), (b), and (c) in Q, that each segment (a) or (b) has a segment (c) attached to it, and that each segment (c) has a segment (a) or (b) attached to it;

wherein Macromer C has an average molecular weight of from about 300 to about 30,000 and comprises at least one segment of the formula (I), (IV), (V), (VI) or (VII);

in which (a) is a polysiloxane segment;

(b) is a polyol segment which contains at least 4 carbon atoms;

Z is a segment (c) or a group X₁;

(c) is defined as X₂—

R—

X₂, wherein R is a bivalent radical of an organic compound having up to 20 carbon atoms and each X₂ independently of the other is a bivalent radical which contains at least one carbonyl group;

X₁ is defined as X₂;

x is 0, 1 or 2;

q has an average numerical value of 1-20; and

(d) is a radical of the formula (II);

X₃-L-(Y)_k—

P₁  

 

(II)

in which P₁ is alkenyl, alkenylaryl or alkenylarylenealkyl having up to 20 carbon atoms;

Y and X₃ independently of one another are a bivalent radical which contains at least one carbonyl group;

k is 0 or 1; and

L is a bond or a divalent radical having up to 20 carbon atoms of an organic compound,

wherein the polysiloxane segment (a) is derived from a compound of the formula (III);

in which n is an integer from 5 to 500;

99.8-25% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are alkyl and 0.2-75% of the radicals R₁, R₂, R₃, R₄, R₅ and R₆ independently of one another are partly fluorinated alkyl, aminoalkyl, alkenyl, aryl, cyanoalkyl, alk-NH-alk-NH₂ or alk-(OCH₂)_m—

(OCH₂)p-OR₇, R₇ is hydrogen or lower alkyl, alk is alkylene, and m and p independently of one another are an integer from 0 to 10, one molecule containing at least one primary amino or hydroxyl group, wherein the alkylenoxy groups —

(OCH₂CH₂)_m and —

(OCH₂)_p in formula (III) are either distributed randomly in a ligand alk-(OCH₂CH₂)_m—

(OCH₂)_p—

OR₇ or are distributed as blocks in a chain,

wherein the polysiloxane segment (a) in formula (I) is linked a total of 1-50 times, via a group Z with the segment (b) or another segment (a), Z in an a-Z-a sequence always being a segment (c),

wherein the segments (b) in Macromer C according to the formula (VI) are linked in total (per molecule) with up to 20 with up to 6 polymerizable segments (d),

wherein the average number of segments (d) per molecule of the formula (VII) is in the range from 2 to 5, and very preferably is in the range from 3 to 4,

wherein macromer D has the formula;

ACRYLATE-LINK-ALK—

O—

ALK—

PDAS—

ALK—

O—

ALK-LINK-ACRYLATE

in which the ACRYLATE is selected from acrylates and methacrylates;

LINK is selected from urethanes and dirurethane linkages;

ALK—

O—

ALK is R₁—

O—

R₂ or R₃—

O—

R₄, R₁, R₂, R₃, and R₄, independently of one another, are lower alkylene; and

PDAS is a poly(dialkylsiloxane) having a segment of the formula;

in which n is an integer from about 5 to about 500; and

R₅, R₆, R₇, and R₈ are, independently of one another, are lower alkyl.

36. The ophthalmic device of claim 34, wherein the concentration of the siloxane-containing macromer is about 20 to 40 weight percent, wherein the concentration of the siloxane-containing monomer is about 5 to 30 weight percent, and wherein the concentration of the hydrophilic monomer is about 10 to 35 weight percent.

37. The ophthalmic device of claim 36, wherein the siloxane-containing monomer is selected from the group consisting of methacryloxyalkylsiloxanes, tristrimethylsilyloxysilylpropyl methacrylate (TRIS), 3-methacryloxy propylpentamethyldisiloxane and bis(methacryloxypropyl)tetramethyldisiloxane, and mixtures thereof, wherein the hydrophilic monomer is selected from the group consisting of N,N-dimethylacrylamide (DMA), 2-hydroxyethylmethacrylate (HEMA), hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate (HPMA), trimethylammonium 2-hydroxy propylmethacrylate hydrochloride, dimethylaminoethyl methacrylate (DMAEMA), dimethylaminoethylmethacrylamide, acrylamide, methacrylamide, allyl alcohol, vinylpyridine, glycerol methacrylate, N-(1,1dimethyl-3-oxobutyl)acrylamide, N-vinyl-2-pyrrolidone (NVP), acrylic acid, methacrylic acid and mixtures thereof.

38. The ophthalmic device of claim 34, wherein the polymerizable composition comprises a vinylic monomer capable of reducing silver cations, wherein the vinylic monomer 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.

39. The ophthalmic device of claim 38, wherein the vinylic monomer is N,N-dimethylacrylamide (DMA) or N-vinyl-2-pyrrolidone (NVP).

40. The ophthalmic device of claim 34, wherein the polymerizable composition comprises a stabilizer for stabilizing silver nano-particles.

41. The ophthalmic device of claim 40, 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, acylic acid, or polyionic material having carboxyl, amino, and/or sulfur-containing groups.

42. The ophthalmic device of claim 34, wherein the polymerizable composition comprises a pigment or a dye.

43. The ophthalmic device of claim 42, 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 blue HEMA.