AU2007240158A1 - Antimicrobial contact lenses and methods for their production - Google Patents

Description

-1-

AUSTRALIA

PATENTS ACT 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT

ORIGINAL

Name of Applicant: Actual Inventors: Johnson Johnson Vision Care, Inc.

Diana Zanini and Alli Azaam and James D. Ford and Robert B.

Steffen and Douglas G. Vanderlaan and James R. Petisce Address for Service is: SHELSTON IP Margaret Street SYDNEY NSW 2000 CCN: 3710000352 Telephone No: Facsimile No.

(02) 9777 1111 (02) 9241 4666 Attorney Code: SW Invention Title: ANTIMICROBIAL CONTACT LENSES AND METHODS FOR THEIR PRODUCTION Details of Original Application No. 2002239725 dated 21 Dec 2001 The following statement is a full description of this invention, including the best method of performing it known to me/us:- File: 39396AUP02 501387412 1.DOC5844 ANTIMICROBIAL CONTACT LENSES AND METHODS FOR THEIR

PRODUCTION

The present application is a divisional application of Australian Application No. 2002239725, which is incorporated in its entirety herein by Sreference.

0RELATED

INVENTIONS

This patent application claims priority from a provisional patent oo application, U.S. Ser. No. 60/257,030, that was filed on December 21, 2000.

SFIELD OF THE INVENTION This invention relates to contact lenses having antimicrobial properties as Swell as methods of their production, use, and storage.

BACKGROUND OF THE INVENTION Contact lenses have been used commercially to improve vision since the 1950s. The first contact lenses were made of hard materials. Although these lenses are currently used, they are not suitable for all patients due to their poor initial comfort and their relatively low permeability to oxygen. Later developments in the field gave rise to soft contact lenses, based upon hydrogels, which are extremely popular today. Many users find soft lenses are more comfortable, and increased comfort levels allow soft contact lens users to wear their lenses for far longer hours than users of hard contact lenses.

Despite this advantage, the extended use of the lenses can encourage the buildup of bacteria or other microbes, particularly, Pseudomonas aeruginosa, on the surfaces of soft contact lenses. The build-up of bacteria or other microbes is not unique to soft contact lens wearers and may occur during the use of hard contact lenses as well.

Therefore, there is a need to produce contact lenses that inhibit the growth of bacteria or other microbes and/or the adhesion of bacterial or other microbes on the surface of contact lenses. Further there is a need to produce contact lenses which do not promote the adhesion and/or growth of bacteria or other microbes on the surface of the contact lenses. Also there is a need to produce contact lenses that inhibit adverse responses related to the growth of bacteria or other microbes.

Others have recognized the need to produce soft contact lenses that C inhibit the growth of bacteria. In US Patent No. 5,213,801, the production of an Santibacterial contact lens is disclosed, where an antibacterial metal ceramic material within a soft contact lens is incorporated into a contact lens. This

INO

procedure contains a number of steps and may not be suitable for producing all types of lenses in a production environment. The steps include making a silver 00 In ceramic material that is fine enough to be used in a contact lens and then forming the lens with the powdered ceramic. However, lenses containing these Stypes of materials often lack the clarity required by contact lens users.

Although these methods and lenses are known, other contact lenses that inhibit the growth and/or adhesion of bacteria or other microbes and are of sufficient optical clarity, as well as methods of making those lenses are still needed. It is this need, which this invention seeks to meet.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 Lenses N G Movement and Silver Concentration Figure 2 Lens Q Movement and Silver Concentration DETAILED DESCRIPTION OF THE INVENTION This invention includes an antimicrobial lens comprising, consisting essentially of, or consisting of, silver and a polymer comprising a monomer of Formula I, 11, III or IV

R

1 R 11 R. R12) Oha ka I II R 21 YR 3 1 0a)= tIN N, (ICH 2 r)w$ 22; -N R 32 III

IV

CI wherein R' is hydrogen orC C 16 alkyl; 1-10 R' is -OR 3 -N -S-(0H 2 )d-R 3 ,or -(0H 2 )d-R wherein d isO0-8; R 3 is substituted C 1 ~alkyl 00 where the alkyl substituents are selected from one or more members of the group consisting of carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, C 1 ,alkyldisulfide,

C,

1 ,alkylsulfide, phenyldisulfide, urea, Cj 14 alkylurea, phenylurea, thiourea,

C

1 6 alkylthiourea, phenylthiourea, substituted

C,

1 ,alkyldisulfide, substituted phenyldisulfide, substituted

C

14 ,alkylurea, substituted phenylurea, substituted

C,

16 alkylthiourea, and substituted phenylthiourea wherein the C 1 6 alkyldisulfide, phenyldisulfide, Cl 1 ,alkylurea, Cl-6alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 14 ,alkyl, haloC 14 6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; -(CR 4

R

5 )q-(CH R3)mS 3

H

wherein R 4 R6, and R 6 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and

C

1 .6alkyl, q is 1-6, and m is 0-6;

-(CH

2 )n-S-S-(CH 2 ),NH-.C(O)CR 7CH 2 wherein R' is hydrogen or Cl 1 ,alkyl, n is 1-6, and x is 1-6; c1 wherein

R

9 and R" 0 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and

C

1 ,,aikyl, t isl1-6, and u is 0-6; 00 phenyl; benzyl; pyridinyl; pyrimidinyl; pyrazinyl; benzimidazolyl; benzoth iazolyl; benzotriazoyl; naphthaloyl; quinolinyl; indoiyl; thiadiazolyl; triazolyl; 4-methylpiperidin-1 -yi; 4-methylpiperazin-1 -yl; substituted phenyl; substituted benzyl; substituted pyridinyl; substituted pyrimidinyl; substituted pyrazinyl; substituted benzimidazolyl; substituted benzothiazolyl; substituted benzotriazolyl; substituted naphthaloyl; substituted quinolinyl; substituted indolyl; ri substituted thiadiazolyl; substituted triazolyl; substituted 4-mnethylpiperidin-1 -yI; or substituted 4-methyipiperazin-1-yl, wherein the substituents are selected from one or more 00 members of the group consisting of C 1 6 alkyI, haloC 1 -,al kyl, halogen, sulfonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amidine, N-(2-aminopyrimidine)sulfonyl, N-(aminopyridine)sulfonyl, N-(aminopyrazine)sulfonyl,

N-(

2 -aminopyrimidine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carbonyl, N-(2-aminopyrimidine)phosphonyl, N-(2-aminopyridine)phosphonyl, N-(aminopyrazine)phosphonyl, N-(aminobenzimidazolyl)sulfonyl, N-(aminobenzothiazolyI)sulfonyl, N-(aminobenzotriazolyl)sulfonyl, N-(aminoindolyl)sulfonyl, N-(aminothiazoyl)sufonyl, N-(aminotriazolyl)sulfonyl, N-(amino-4-methylpiperidinyl)sulfonyl, N-(amino-4-methylpiperaziny)sulfonyl, N-(aminobenzimidazolyl)carbonyl, N-(aminobenzothiazolyl)carbonyl, N-(aminobenzotriazolyl)carbonyl, N-(aminoindolyl)carbonyl, N-(aminothiazolyl)carbonyl, N-(aminotriazolyl)carbonyl, N-(a min o-4-methyl pipe ridi nyl)carbonyl, N-(a min o-4-.methy pipe razinyl)ca rbon yl N-(2-aminobenzimidazolyl )phosphonyl, N-(2-aminobenzothiazolyl)phosphonyl, N-(2-aminobenzotriazolyl)phosphonyl, N-(2-aminoindolyl)phosphonyl, N-(2-aminothiazolyl)phosphonyl, N-(2-aminotriazolyl)phosphonyl, N-(amino-4-methylpiperidinyl) phosphonyl, N-(a mi no-4-m ethyl piperazi nyl) phosphonyl, acetamide, nitrile, thiol, C 16 alkyldisulflde, C,.,alkylsulfide, phenyl disulfide, urea, C 16 alkylurea, phenylurea, thiourea, C,-,alkylthiourea, phenylthiourea, substituted C1.

6 alkyldisulfide, substituted phenyldisulfide, substituted Cl 1 ,alkylurea, substituted Cl 1 ,alkylthiourea, substituted phenylurea, and substituted phenylthiourea wherein the C, 1 ,alkyldisulfide, phenyldisulfide,

C

1 6 alkylurea, Cl-6alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C,.

6 alkyI, haloC 1 6 alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; a is

R"

1 is hydrogen or C 1 8 alkyl; R is hydroxyl, sulfonic acid, phosphonic acid, carboxylic acid, acetamide, th loG 1 6 alkylcarbonyl, C 14 ,alkyldisulfide, Cl-6alkylsulfide, phenyl disulfide, urea, Cl-6alkylurea, phenylurea, thiourea,

C

1 -6alkylthiourea, phenylthiourea, -OR" 3

-NH-R

1 3

-S-(CH

2 )d-R' 3

-(CH

2 )d-R 13

-C(O)NH--(CH

2 )d-R 13 -(0HA)-R 13 substituted

C

1 .6alkyldisulfide, substituted phenyldisulfide, substituted C,-6alkylurea, substituted p henylu rea, substituted phenyith iourea or substituted Cl-6alkylthiourea wherein the substituents are selected from the group consisting of C,,alkyl, haloC 1 6 alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; where Cl d is 0-8;

R'

3 is thioC 16 alkylcarbonyl; substituted

C

16 ,alkyl where the alkyl substituents are selected from one or 00 more members of the group consisting of hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, C 1 -6alkyldisulfide, N ~C 1 .,alkylsulfide, phenyidisulfide, urea, C,,alkylurea, phenylurea, thiourea, Cl- 4 alkylthiourea, phenylthiourea, substituted C, 1 ,alkyldisulfide, substituted phenyldisulfide, substituted C 1 8 alkylurea, substituted phenylurea, substituted Cl 6 alkylthiourea and substituted phenylthiourea wherein the Cl~alkyldisulfide, phenyldisulfide,

C,

14 alkylurea, C 1 ,alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of Cl 1 ,alkyl, haloC,.6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; -(CR 14 R')q-(CHR' 6 3

H

where R 1 4

R'

5 and R' are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and

C

1 ~alkyl, q isl1-6, and mn is 0-6; 7C2 where R 17 is hydrogen or Cj.,alkyl, n is 1-6, and x isl1-6; -(CR 18

R

19 )t-(CHR 2 0

)(OH)

2 where R1 8

R'

9 and R" 0 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and C,-,alkyl, t is 1-6, and u isO0-6; phenyl; 00 benzyl; pyridinyl; pyrimidinyl; pyrazinyl; benzimidazolyl; benzoth iazolyl; benzotriazolyl; naphthaloyl; quinolinyl; indolyl; thiad iazolyl; triazolyl; 4-methylpiperidin-1 -yl; 4-methylpiperazin-I -yl; substituted phenyl; substituted benzyl; substituted pyridinyl; substituted pyrimidinyl; substituted pyrazinyl; substituted benzimidazolyl; substituted benzothiazolyl; substituted benzotriazolyl; substituted naphthaloyl; substituted quinolinyl; substituted indolyl; substituted thiadiazolyl; C1 substituted triazolyl; susiue -ehlpprdn1y;o substituted 4-methylpiperdin-1 -y;o susiutd4mthNieDzn1y wherein the substituents are selected from one or more members of the group consisting of C 1 -6aikyl, 00 haloC 16 ,alkyl, halogen, sulfonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amidine, N-(2-aminopyrimidine)sulfonyl, N-(aminopyridine)sulfonyl, N-(aminopyrazine)sulfonyl, N-(2-aminopyrimidine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carbony, N-(2-aminopyrimidine)phosphonyl, N-(2-aminopyridine)phosphonyl, N-(aminopyrazine)phosphonyl, N-(aminobenzimidazolyl)sulfonyl, N-(aminobenzothiazoyl)sulfonyl, N-(aminobenzotriazolyl)sulfonyl, N-(aminoindolyl)sulfonyl, N-(aminothiazolyl)sulfonyl, N-(aminotriazolyl)sulfonyl, N-(amino-4-methylpiperidinyl)sulfonyl, N-(amino-4-methylpiperazinyl)sulfonyl, N-(aminobenzimidazolyl)carbonyl, N-(aminobenzothiazolyl)carbonyl, N-(aminobenzotriazolyl)carbonyl, N-(aminoindolyl)carbonyl, N-(aminothiazolyl)carbonyl, N-(aminotriazolyl )carbonyl, N-(amino-4-methylpipeidinyl )carbonyl, N-(amino-4-methylpiperazinyl)carbonyl, N-(2-aminobenzimidazolyl)phosphonyl, N-(2-aminobenzothiazolyl)phosphonyl, N-(2-aminobenzotriazolyl )phosphonyl, N-(2-aminoindolyl)phosphonyl, N 2 a i o h a oyUh s h n l N-(2-aminothiazolyl)phosphonyl, INDaintaollposhnl N-(amino-4-methylpiperid inyl) phosphonyl, N-(amino-4-methylpiperazinyl) phosphonyl, acetamide, nitrile, thiol, C,.,alkyldisulfide, 0 1 8 alkylsulfide, phenyl disulfide, urea, 0 16 alkylurea, phenylurea, thiourea,

C,

1 ealkylthiourea, phenylthiourea, substituted Cl~alkyldisulfide, substituted phenydisulfide, substituted

C

1 .alkylurea, substituted C, 1 .alkylth iourea, substituted phenylu rea, and substituted phenylthiourea wherein the C 16 alkyldisulfide, phenyldisulfide,

C

1 ,alkylurea, C 1 -,alkythiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of Cl 1 ,alkyl, haloC 1 6 alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; b is p is R 21 is hydrogen; R22 is hydroxyl, sulfonic acid, phosphonic acid, carboxylic acid, thiOCI.

6 alkylcarbonyl, thioC,.6alkylaminocarbonyl, Cl 14 alkyldisulfide, phenyldisulfide,

-C(O)NH(CH

2 16 -S0 3 H, -C(O)NH(CH 2 1 -6-P(O)(OH) 2

-OR

23 -NH-R -C (O)NH-(CH 2 )d-R 23

-S-(CH

2 )d-R 23

-(CH

2 )d-R 3 urea, Cl- 6 alkylurea, phenylurea, thiourea, C 1 .,alkylthiourea, phenylthiourea, substituted Cl-6aikyldisulfide, substituted phenyldisulfide, substituted

C

14 6alkylurea, substituted, C 1 .6alkylthiourea substituted phenylurea or substituted phenylthiourea wherein the substituents are selected from the group consisting of C 1 -,alkyl, haloC 1 6 alky), halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrite, where d is 0-8; R 2 3 is thioC,.

6 aikylcarbonyl,

C

1 6 alkyl, substituted Cl 1 6alkyl where the alkyl substituents are selected from one or more members of the group consisting of C1-6alkyl, halo

C

16 alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, C 1 -,alkyldisulfide,

G

1 -6alkylsulfide, phenyldisulfide, urea, C,,alkylurea, phenyiurea, thiourea, C,-,aikylthiourea, phenylthiourea, substituted Cl,,alkyldisulfide, substituted phenyidisulfide, substituted

C

1 -6alkylurea, substituted phenylurea, substituted Cl-6alkylthiourea, and substituted phenylthiourea wherein the Cl 14 alkyldisuifide, phenyldisulfide,

C

1 -,alkylurea, Cl 1 ,alkylthiourea, phenyturea, and phenylthiourea substituents are selected from the group consisting of C,.,alkyJ, haloC 1 -6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrite;

-(CR

2 4

R?

5 )q(CHR 2 6

),,SQ

3

H

where R 24

R

2 and R' 6 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and

C

1 .alkyl, q is 1-6, and m is 0-6 -(CH2)n-S-S-(CH 2 )vKNH.-C(O)CR 27

CH

2 where R" 7 is hydrogen or C, 1 ,alky(, n is 1-6, and x is 1-6; -(CR 28 R 29 )t-(CHR 3 0 2 IND where R 28 R 2 1, and R 3 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and 00 C -6alkyi, t is 1-6, and u is 0-6; N- phenyl; benzyl; pyrid inyl; pyrimid inyl; pyrazinyl; benzimidazolyl; benzothiazolyl; benzotriazolyl; naphthaloyl; quinolinyl; indolyl; thiadiazolyl: triazolyl; 4-methylpiperidin-1 -yI; 4-methylpiperazin-1 -yl; substituted phenyl; substituted benzyl; substituted pyridinyl; substituted pyrimidinyl; substituted pyrazinyl; substituted benzimidazolyl; substituted benzothiazoly; substituted benzotriazolyl; substituted naphthaioyl; N substituted quinolinyl; susiuedidlU substituted tidiolyl; susiutdtNdiDll substituted triazolyl; substituted 4-methylpiperidin-1 -yl; or substituted 4-methylpiperazin-1 -yl, wherein the substituents are selected from one or more c-i members of the group consisting of C 1 -6alkyl, haloC 1 6 alkyl, halogen, sulfonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amidine, N-(2-aminopyrimidine)sulfonyl, N-(aminopyridine)sulfonyl, N-(aminopyrazine)sulfonyl, N-(2-aminopyrimidine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carbonyl, N-(2-aminopyrimidine)phosphonyl, N-(2-aminopyridine)phosphonyl, N-(aminopyrazine)phosphonyl, N-(aminobenzimidazolyl)sulfonyl, N-(aminobenzothiazolyl)sulfonyl, N-(aminobenzotriazolyl)sulfonyl, N-(aminoindolyl)sulfonyl, N-(a min oth iazolyl)sulIfonyl, N-(aminotriazolyl)sulfonyl, N-(amino-4-methytpiperidinyl)sulfonyl, N-(amino-4-methylpiperazinyl)sulfonyl, N-(aminobenzimidazolyl)carbonyl, N-(aminobenzothiazolyl)carbonyl, N-(aminobenzotriazolyl)carbonyl, N-(aminoindolyl)carbonyl, N-(aminothiazolyl)carbonyl, N-(aminotriazolyl)carbonyl, N-(amino-4-methyl piperidinyl)carbonyl, N-(amino-4-methylpiperazinyl)carbonyl, C1 N-(2-aminobenzimidazolyl)phosphonyl, 'N-(-aminouenzothiazolyI)phosphonyl, N-(2-a minobenzotriazolyl)phos phony, N-(2-aminoindolyl)phosphonyl, N-(2-aminothiazolyl )phosphonyl, 00 N-(2-aminotriazoyl)phosphonyl, N-(amino-4-methylpiperidinyI) phosphonyl, N-(amino-4-methylpiperazinyl) phosphonyl, acetamide, nitrile, thiol, C,-,aikyldisulfde,

C,

1 ,alkylsulfide, phenyl disulfide, urea, Cl-6alkylurea, phenylurea, thiourea,

C

1 6 atkylthiourea, phenylthiourea, substituted C,.,aikyldisulfide, substituted phenyldisulfide, substituted

C

16 alkylurea, substituted C 1 -,alkylthiourea, substituted phenylurea, and substituted phenylthiourea wherein the C 1 ,atkyldisulfide, phenyldisutfide, Cl 1 ,,alkylurea, Cl 1 ,alkythiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 1 -,alkyl, haloC 1 6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amnine, amnidine, acetamide, and nitrite; w is 0-1; Y is oxygen or sulfur;

R

3 1 is hydrogen or C, 14 alkyl; R 32 is hydroxyl, sulfonic acid, phosphonic acid, carboxylic acid, thioC 1 6 alkylcarbonyl, thioC, 1 .alkylaminocarbonyl,

-C(O)NH-(CH

2 )d -R 33 -0-R 33 -NH-R -S-(CH 2 )d -R 33

-(CH

2 R, Cl.,alkyldisulfide, phenyldisulfide, urea, C 1 -,alkylurea, phenylurea, thiourea, Cl-6alkylthiourea, phenylthiourea, C 1 6alkylamine, phenylamine, substituted

C

1 -6atkyldisulfide, substituted phenyidisulfide, substituted phenyiurea, substituted

C

1 .,alkyamine, substituted phenylammne, substituted phenylthiourea, substituted C 1 6 alkylurea or substituted N

C

16 alkylthiourea wherein the substitutents are selected from the group consisting of C 1 -,alky(, haloC 14 6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile where d is 0-8; 00 R' is th'oC 16 alkylcarbonyl, Cl.,alkyl, substituted C 1 6 alkyl where the alkyl substituents are selected from one or more members of the group consisting of C,,alkyl, halo C,.

6 ,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, Cl 1 ,,alkyldisulflde, Ci.ealkylsulflde, phenyldisulfide, urea, C,.

6 alkylurea, phenylurea, thiourea,

C

1 -6aikylthiourea, phenylthiourea, substituted Cl 1 ,alkyldisulfide, substituted phenyldisulfide, substituted C, 14 alkylurea, substituted phenylurea, substituted C,,alkylthiou rea or substituted phenylthiourea wherein the C 1 6 alkyldisulfide, phenyldisulfide,

C

1 -,alkylurea, C 14 alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 1 .,alkyl, haloC,,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; -(CR 34 R 3 5)q(CHR 3 6 )SO 3

H

where R 31, and R 3 Mare independently selected from the group consisting of hydrogen, halogen, hydroxyl, and Cl 1 ,alkyl, q is 1-6, and mnis 0-6;

-(CH

2 2 H-C(O)0R 37

CH

2 where R" 7 is hydrogen or C, 1 .alkyI, n isl1-6, and x is 1-6; 0039 4)_ -(CR 3 8

R

3 )-(CHR 0 o)(OH )2 where R3 9 and R" 0 are independently selected from N the group consisting of hydrogen, halogen, hydroxyl, and C1, 6 alkyl, t is 1-6, and u is 0-6; phenyl; benzyl; pyridinyl; pyrimidinyl; pyrazinyl; benzimidazolyl; benzothiazolyl; benzotriazoyl; naphthaloyl; quinolinyl; indolyl; thiadiazolyl; triazolyl; 4-methylpiperidin-1 -yl; 4-methylpiperazin-1 -yl; substituted phenyl; substituted benzyl; substituted pyridinyl; substituted pyrimidinyl; substituted pyrazinyl; substituted benzimidazolyl; susiue eztizlU IND substituted benzothiazolyi; substituted naphthaloyl; 00 substituted quinolinyl; substituted indolyl; substituted thiadiazolyl; substituted triazolyl; substituted 4-methylpiperidin-1-yi; or substituted 4-methylpiperazin-1 -yI, wherein the substituents are selected from one or more members of the group consisting of C,.6alkyI, haloC 1 ~aikyl, halogen, sulfonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amidine, N-(2-aminopyrimid ine)sulfonyl, N-(aminopyridine)sulfonyl, N-(aminopyrazine)suifonyl, N-(2-aminopyrimidine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carbonyl, N-(2-aminopyrimidine)phosphonyl, N-(2-aminopyricine)phosphonyl, N-(aminopyrazine)phosphonyl, N-(aminobenzimidazolyl)sulfonyl, N-(aminobenzothiazolyl)sulfonyl, N-(aminobenzotriazolyl)sulfonyl, N-(aminoindolyl)sulfonyl, N-(aminothiazolyl)suffonyl, N-(aminotriazolyl)sulfonyl, N-(amino.4-methylpiperidiny )sulfonyl, N-(amino-4-methylpiperazinyl)sulfonyl, N-(aminobenzimidazolyl)carbonyl, N-(aminobenzothiazolyl)carbonyl, N-(aminobenzotriazolyl)carbonyl, N-(aminoindolyl)carbonyl, N-(amninothiazolyl)carbony(, U N-(aminotriazolyi)carbonyl, N-(amino-4-methylpiperidinyl)carbonyl, N-(ammno-4-methypiperazinyl)carbonyl,

N-(

2 -aminobenzimidazolyl)phosphonyl, 00

N-(

2 -aminobenzothiazolyl)phosphonyl,

N-(

2 -aminobenzotriazolyl)phosphonyl, N-(2-aminoindolyl)phosphonyl, N-(2-aminothiazolyl)phosphonyl, N-2aifotriazoylphosphonyl, N-(amino-4-methylpiperidinyl) phosphonyl, N-(amino-4-methylpiperazinyl) phosphonyl, acetamide, nitrile, thil, C, 1 ,alkyldisulflde, Cl,alkylsulfide, phenyl disulfide, urea, Cl.,alkylurea, phenylurea, thiourea, Cl.

6 alkylthiourea, phenylthiourea, substituted Cl.0alkyldisulfide, substituted phenyldisulfide, substituted

C

1 ,alkylurea, substituted Cl.0alkylthiourea, substituted phenylurea, and substituted phenylthiourea wherein the Cl.6aikyldisulfide, phenyldisulfide,

C,.

6 alkylurea,

C,

14 alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C, 14 alkyl, haloC,.,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; R 4 1 is hydrogen, Cl 1 ,alkyI, phenyl,

C

16 alkylcarbonyl, phenylcarbonyl, substituted

C

16 ,alkyl, substituted phenyl, substituted Cl.

6 alkylcarbonyl or substituted phenylcarbonyl, wherein the substituents are selected from the group consisting of

C

14 6alkyl, haloC 16 ,alkyl, halogen, hydroxyl, carboxylic acid, Ssulfonic acid, phosphonic acid, amine, amidine, acetamide, and N nitrile.

l As used herein, the term "lens" refers to opthalmic devices that reside in 0 5 or on the eye. These devices can provide optical correction or may be cosmetic.

The term lens includes but is not limited to soft contact lenses, hard contact 00 lenses, intraocular lenses, overlay lenses, ocular inserts, and optical inserts.

Soft contact lenses are made from silicone elastomers or hydrogels, which include but are not limited to silicone hydrogels and fluorohydrogels. These hydrogels contain hydrophobic and/or hydrophilic monomers that are covalently bound to one another in the cured lens. As used herein the term "polymers" means copolymers, homopolymers, or mixtures thereof. The monomers of Formula I, II, Ill or IV, or their homopolymers, are added to the monomer mix of contact lenses, prior to polymerization in an amount based on the weight percent of the initial monomer mix, including a suitable diluent if said diluent is used in the preparation of the polymer. The weight percentage of the monomers of the invention can vary with the lens formulation. The maximum percentage of monomers of Formula I, II, 111 or IV is the percentage that does not compromise the physical properties of the resulting contact lens, such as, but not limited to modulus, of the resulting lens. The minimum percentage of monomers of Formula I, II, III or IV is an amount that allows the incorporation of a sufficient amount of silver into a lens. Preferably, about 0.01 to about 20.0 weight percent of monomers of Formula I, II, 111 or IV are added, to a contact lens formulation, more preferably, about 0.01 to about 1.5 weight percent, even more preferably, about 0.01 to about 0.4 weight percent, most preferably, about 0.2 weight percent.

Monomers of Formula I, II, III or IV are added to the soft contact lens formulations described in U.S. Pat. No. 5,710,302, WO 9421698, EP 406161,

JP

2000016905, U.S. Pat. No. 5,998,498, US Pat. App. No. 09/532,943 and U.S.

Pat. No. 6,087,415. In addition, monomers of Formula I, II, III or IV may be added to the formulations of commercial soft contact lenses. Examples of commercially available soft contact lenses formulations include but are not N limited to, the formulations of etafilcon A, genfilcon A, lenefilcon A, polymacon, acquafilcon A, balafilcon A, and lotrafilcon A. The preferable contact lens formulations are etafilcon A, balafilcon A, and silicone hydrogels, as prepared in U.S. Pat. No. 5,760,100; U.S. Pat. No. 5,776,999; U.S. Pat. No.5,849,811;

U.S.

Pat. No. 5,789,461; U.S. Pat. No. 5,998,498, US Pat. App. No. 09/532,943, a OO continuation-in-part of U.S. Pat. App. No. 09/532,943, filed on August 30, 2000, Sand U.S. Pat. No. 6,087,415. These patents are hereby incorporated by reference for the hydrogel compositions contained therein. Lenses prepared o from the aforementioned formulations and the monomers of Formula II, II, Ill or IV may be coated with a number of agents that are used to coat lenses. For example, the procedures, compositions, and methods of U.S. Pat. Nos.

3,854,982; 3,916,033; 4,920,184; and 5,002,794; 5,712,327; and 6,087,415 as well as WO 0127662, may be used and these patents are hereby incorporated by reference for those procedures, compositions, and methods. In addition to the cited coating patents, there are other methods of treating a lens once it is formed. The lenses of this invention may be treated by these methods and the following publications which illustrate these methods are hereby incorporated by reference in their entirety, U. S. Pat. No.5,453,467; U.S. Pat. No. 5,422,402;

WO

9300391; U.S. Pat. No.4,973,493; and U.S. No. Pat 5,350,800.

Hard contact lenses are made from polymers that include but are not limited to polymers of poly(methyl)methacrylate, silicon acrylates, fluoroacrylates, fluoroethers, polyacetylenes, and polyimides, where the preparation of representative examples may be found in JP 200010055; JP 6123860; and U.S.

Pat. No. 4,330,383. Intraocular lenses of the invention can be formed using known materials. For example, the lenses may be made from a rigid material including, without limitation, polymethyl methacrylate, polystyrene, polycarbonate, or the like, and combinations thereof. Additionally, flexible materials may be used including, without limitation, hydrogels, silicone materials, acrylic materials, fluorocarbon materials and the like, or combinations thereof.

Typical intraocular lenses are described in WO 0026698; WO 0022460; WO 9929750; WO 9927978; WO 0022459; and JP 2000107277. The O polymerizable monomers of Formula I, 11, III or IV may be added to hard contact lens formulations and intraocular lens formulations in the same manner and at O the same percentage as described above for soft contact lenses. All of the references mentioned in this application are hereby incorporated by reference in their entirety.

00 I As used herein, the term "silver" refers to silver metal that is incorporated into a lens. While not wanting to be bound as to the oxidation state of the silver N(Ag or Ag 2 that is incorporated into the lens, silver may be added to the lens by washing the cured and hydrated lens in a silver solution such as silver Snitrate in deionized water Other sources of silver include but are not limited to silver acetate, silver citrate, silver iodide, silver lactate, silver picrate, and silver sulfate. The concentration of silver in these solutions can vary from the concentration required to add a known quantity of silver to a lens to a saturated silver solution. In order to calculate the concentration of the silver solution needed, the following calculation is used: the concentration of silver solution is equal to the desired amount of silver per lens, multiplied by the dry weight of the lens divided by the total volume of treating solution.

silver solution concentration (pg/mL) [desired silver in lens (pg/g) x average dry lensweight total volume of treating solution (mL) For example, if one requires a lens containing 40 pg/g of silver, the dry weight of the lens is 0.02 g, and the vessel used to treat said lens has a volume of 3mL, the required silver concentration would be 0.27 pg/mL.

Silver solutions containing anywhere from about 0.10 pg/mL to 0.3 grams/mL have been used to prepare the lenses of the invention. Aside from deionized water, other liquid mediums can be used such as water, aqueous buffered solutions and organic solutions such as polyethers or alcohols.

Typically, the lens is washed in the silver solution for about 60 minutes, though the time may vary from about 1 minute to about 2 hours and at temperatures ranging from about 50C to about 1 30 0 C. After the silver treatment the lenses are washed with several portions of water to obtain a lens where silver is 0 incorporated into the polymer. The amount of silver that is incorporated into the Slenses ranges from about 20 ppm to about 100,000 ppm, where any lens containing at least about 20 ppm has antimicrobial properties. The preferred I amount of silver that is incorporated into the lens is about 20 ppm to about 4,000 ppm, more preferably, 20 ppm to about 1,500 ppm, even more preferably about ppm to about 600 ppm, and most preferably about 30 ppm to about 75 ppm.

00 The term "antimicrobial" refers to a lens that exhibit one or more of the Sfollowing properties the inhibition of the adhesion of bacteria or other microbes Sto the lenses, the inhibition of the growth of bacteria or other microbes on the lenses, and the killing of bacteria or other microbes on the surface of the lenses N or in a radius extending from the lenses (hereinafter adhesion of bacteria or other microbes to the lenses, the growth of bacteria or other microbes to the lenses and the presence of bacterial or other microbes on the surface of lenses is collectively referred to as "microbial production"). The lenses of the invention inhibit the microbial production by at least 25%. Preferably, the lenses of the invention exhibit at least a 1-log reduction 90% inhibition) of viable bacteria or other microbes, more preferably a 2-log reduction 99% inhibition) of viable bacteria or other microbes. Such bacteria or other microbes include but are not limited to those organisms found in the eye, particularly Pseudomonas aeruginosa, Acanthamoeba species, Staphyloccus. aureus, E. coli, Staphyloccus epidermidis, and Serratia marcesens. Preferably, said antimicrobial lens is a clear lens, that has clarity comparable to currently available commercial lenses such as but not limited to, etafilcon A, genfilcon A, lenefilcon A, polymacon, acquafilcon A, balafilcon A, and lotrafilcon A.

The term "phosphonyl" refers to a radical having the following structure 0

HO

With respect to the monomers of Formula I, there are some monomers that are preferred. The preferred monomers of Formula I include monomers where

R

1 is hydrogen or C13alkyl; Ris NH-R 3 d isO0 R R 3 is substituted Phenyl, -(CR 4 R 5 )q-(CHR 6

)MSO

3 H, -(CR 8

R

9 2 or -(CH 2 )n-S-S.(CH 2 )NH-C(O)CRCH2; IND 5 R' is hydrogen or C 1 -3alkyl; 0 5 i yrgno 1 akl is hydrogen or 0 1 3 alkyl; 00 R' ishdrgn-r3;3lkl qmisl1-3; R' is hydrogen or C,-,alkyl; R' is hydrogen or C 1 ,alkyl; R' is hydrogen or C,.

3 alkyl;

R"

0 is hydrogen or 0 1 3 alkyl; t is 1-3; u is 1-3; n is 2-4; and x is 2-4.

The more preferred monomers of Formula I include monomer where R' is hydrogen or methyl1; R 2 is NH-R 3 R' is -(CR 4

R

5 )q(CHR 8 )m-SO 3 H, -(CR 8

R

9 )1,(CHR 10 2 or

-(CH

2 2 )CHR R 7

CH

2 R 4 is hydrogen or methyl; R,9 is hydrogen or methyl; qisl1-2; m is 1-2; R 6 is hydrogen or methyl; R 7 is hydrogen; R' is hydrogen or methyl; R' is hydrogen or methyl;

R

1 0 is hydrogen or methyl; t is 1; u is 1-2; n is 2-3; and x is 2-3.

The most preferred monomers of Formula I include the following monomers 0 S 0 CH 3

H

N~ J N KSOH

H

and With respect to the monomers of Formula 11, there are some monomers that are preferred. The preferred monomers of Formula 11 include monomers where a is 1-2;

R"

1 is hydrogen or C 1 -3alkyl; R 12 is sulfonic acid, carboxylic acid, phosphonic acid, C, 14 alkyldisulfide,

C

1 .6alkylsulfide, phenyldisulfide, substiuted phenyldisulfide or NH-R 1 3 R 13 is thioC 14 6alkylcarbonyl.I The most preferred monomers of Formula 11 include the following monomers O j S NH

N

S

0 -a 2, 2 S3 and C0 2

H

With respect to the monomers of Formula 111, there are some monomers that are preferred. The preferred monomers of Formula III include monomers 00 5 where p is 1-3; b is 1-2;

R

2 is hyd rogen; R22 is sulfonic acid, phosphonic'acid, carboxylic acid, thioC -,alkylcarbonyl' thioC,,alkylaminocarbonyl, Cl.,alkyldisuffide, C,,alkylsulfide, phenyldisulfide, substiuted phenyldisulfide,

H

3 0S-(CH 2 1 .6NHC(O) or (HO )2(O)P-(CH 2 1 .eNHC(O).

The most preferred monomers of Formula IIl include the following monomers 0 2 ,H 2 an d H0 3 S

H

With respect to the monomers of Formula IV, there are some monomers that are preferred. The preferred monomers of Formula IV include monomers where w isO0-1; R 31 is hydrogen; r-

R

32 is amine, C 1 .alkylamine, phenylamine, substituted phenylamine, N thioC,,alkylcarbonyl;

R

41 is hydrogen

ID

0 5 The most preferred monomers of Formula IV include the following monomers 00 o (S A N O H0 2 C

N

0

H

S2 H

HO

3 S Nf N Nf I s H ,and For monomers of all formula, the preferred points of attachment are as follows pyridinyl is 4, for pyrimidinyl is 2, for benzimidazolyl is 2, for benzothiazole is 2, for benzotriazolyl is 5, for quinolinyl is 2, for indolyl is 4 or for thiadiazole is 3, or 5, and for triazolyl is 3 or 5, where positions containing hydrogen may be substituted with the named substituents.

Further, the invention includes an antimicrobial lens comprising, consisting essentially of, or consisting of, silver and a polymer comprising a binding monomer where said cured lens can reversibly bind silver. The terms antimicrobial, lens, and silver all have their aforementioned meanings and preferred ranges. The term "binding monomer" means any polymerizable monomer that can reversibly bind silver. The term "cured lens" refers to contact lens monomer formulations polymerized with binding monomers. The potential ability of a cured lens to reversibly bind silver can be estimated by examining the stability constant of the selected binding monomers. These estimates can be determined by known methods. (See R.I. Tilley, Aust J. Chem. 1990, 43,1573).

The log of the stability constants, of the cured lense of the invention are about 0.6 to about 15.0; that is, logp n where i3 stability constant for a cured lens that binds n molecules of silver preferably, about 2 to about 7.3, and more preferably about 3.6 to 6.9.

r- The advantages of the antimicrobial lenses of the invention are many.

SFor example, other antimicrobial lenses that incorporate silver usually contain silver coordinated to some inorganic particulate matter (see US Pat. No.

Q 5,213,801, discussing the use of silver ceramics). Often that particulate matter is I 5 visible to the naked or magnified eye, and it can affect the visual acuity of the user. However, the lenses of the invention do not have this problem. The 0o monomers of Formula I, II, III or IV and other binding monomers are generally soluble with all of the other components of the antimicrobial lenses. Therefore when the lenses are produced they do not have substantial particulate matter due to their antimicrobial components. The antimicrobial lenses of the invention O have comparable clarity to commercial lenses such as etafilicon A, genfilcon A, lenefilcon A, polymacon, acquafilcon A, balafilcon A, and lotrafilcon A.

Further, the invention includes a method of producing an antimicrobial lens comprising, silver and a polymer comprising a monomer of Formula I, II, III or IV

R

1

R

11 RT 2

R

12

III

R

21 R 31 b-N 32 N' R 2 b R R 4 1 III

IV

wherein R' R 4 1 Y, a, q, m, n, p, d, b, t, u, w, and x are as described above wherein the method comprises, consists essentially of, or consists of the steps of preparing a lens comprising a monomer of Formula I, II, III or IV and treating said lens with a silver solution.

8 The terms lens, antimicrobial, lens, silver, R 1

R

41 Y, a, q, m, n, p, d, b, t, u, w, N and x, all have their aforementioned meanings and preferred ranges. The term, U

C

"silver solution" refers to any liquid medium containing silver. The liquid medium Sincludes but is not limited to water, deionized water, aqueous buffered solutions, alcohols, polyols, and glycols, where the preferred medium is deionized water.

The silver of the solution is typically a silver salt such as silver nitrate, silver 00 n acetate, silver citrate, silver iodide, silver lactate, silver picrate, and silver sulfate.

The concentration of silver in these solutions can vary from the concentration required to add a known quantity of silver to a lens to a saturated silver solution.

In order to calculate the concentration of the silver solution needed, the following calculation is used: the concentration of silver solution is equal to the desired amount of silver per lens, multiplied by the dry weight of the lens divided by the total volume of treating solution.

silver solution concentration (pg/mL) [desired silver in lens (pg/g) x average dry lens weight total volume of treating solution (mL) For example, if one requires a lens containing 40 pg/g of silver, the dry weight of the lens is 0.02g, and the vessel used to treat said lens has a volume of 3mL, the required silver concentration would be 0.27 pg/mL.

Silver solutions containing anywhere from about 0.10 pg/mL to 0.3 grams/mL have been used to prepare the lenses of the invention. Aside from deionized water, other liquid mediums can be used such as water, aqueous buffered solutions and organic solutions such as polyethers, or alcohols.

Typically, the lens is washed in the silver solution for about 60 minutes, though the time may vary from about 1 minute to about 2 hours and at temperatures ranging from about 5 0 C to about 130 0 C. After the silver treatment the lenses are washed with several portions of water to obtain a lens where silver is incorporated into the polymer.

Still further, the invention includes a lens case comprising, consisting essentially of, or consisting of silver and a polymer of a monomer of Formula I, II, III or IV O R1 R 0 R K (U 0 a 2R 12

II

21 R31

R

21 y 00 -N 32 N I II IV Swherein R' R 41 Y, a, q, m, n, p, d, b, t, u, w, and x are as described above The terms lens, silver, R' R 41 Y, a, q, m, n, p, d, b, t, u, w, and x, all have their aforementioned meanings and preferred ranges. The term lens case refers to a container that is adapted to define a space in which to hold a lens when that lens is not in use. This term includes packaging for lenses, where packaging includes any unit in which a lens is stored after curing. Examples of this packaging include but are not limited to single use blister packs, multiple use storage cases and the like.

One such container is illustrated in Figure 3 of U.S. Pat. 5,515,117 which is hereby incorporated by reference in its entirety. The polymers of Formula I, II, III or IV can be incorporated in the lens container 22, the cover 24, or the lens basket 26, where they are preferably incorporated into the lens container or the lens basket.

Aside from the polymers of Formula I, II, III or IV the container components may be made of a transparent, thermo-plastic polymeric material, such as polymethylmethacrylate, polyolefins, such as poly-ethylene, polypropylene, their copolymers and the like; polyesters, polyurethanes; acrylic polymers, such as polyacrylates and polymethacrylates; polycarbonates and the like and is made, or any combination thereof, molded, using conventional techniques as a single unit.

Silver may be incorporated into the lens container in the same manner that it is incorporated into the antimicrobial lenses of the invention. More QI specifically, the polymers of Formula I, 11, 111 or IV are combined with the ID formulation of the other components, molded, cured, and subsequently treated with a silver solution. Preferably, polymers of Formula 1, II, II or IV are present 00 in any or all of the lens case components at about 0.01 to about 10.0 weight percent (based on the initial monomer mix), more preferably about 0.01 to about percent. Storing lenses in such an environment inhibits the growth of bacteria on said lenses and adverse effects that are caused by the proliferation of bacterial. Another example of such a lens case is the lens case can be found in U.S. Pat. No. 6,029,808 which is hereby incorporated by reference for the blister pack housing for a contact lens disclosed therein.

Yet still further, the invention includes a method of reducing the adverse effects associated with microbial production in the eye of a mammal, comprising, consisting essentially of, or consisting of providing an antimicrobial lens wherein said lens comprises silver and a polymer of a monomer of Formula I, 11, Ill or IV

R

1 R 1 1 0 R ^R 12 p 31 (R O R, N22 (CH 2 w 111

IV

wherein R 1

R

41 Y, a, q, m, n, p, d, b, t, u, w, and x are as described above The terms lens, antimicrobial, lens, silver, R 1

R

41 a, q, m, n, p, d, b, t, u, w and x, all have their aforementioned meanings and preferred ranges. The phrase "adverse effects associated with microbial production" includes but is not Slimited to, ocular inflammation, contact lens related peripheral ulcers, contact U lens associated red eye, infiltrative keratitis, and microbial keratitis.

Providing a lens that fits a wide range of patients has been a quest of eye IDcare practitioners and lens manufactures for a number of years. In order to produce such a lens, many variables, such as lens material, design, surface 0 treatments, and additional components such as ophthalmic drugs, tints, dyes and pigments can come into play. For example it has been shown that if one adds too much of an additional component, such as an antimicrobial agent, a lens that will become adhered to the eye is produced. However, if one is attempting to produce an antimicrobial lens, a balance should be struck between producing a lens that contains enough antimicrobial agent to produce the desired effect without producing a lens that adheres to the eye.

One way to assess if a lens fit is acceptable the lens is not adhered) is to assess the tightness of the fit of a lens. (Young, G. et al., Influence of Soft Contact Lens Design on Clinical Performance, Optometry and Vision Science, Vol 70, No., 5 pp. 394-403) Tightness of a lens may be assessed using an in vivo push up test. In that test, a lens is placed on a patient's eye. Subsequently, an eye care practitioner presses his or her finger digitally upward against the lower lid of the patient's eye and observes whether the lens moves on the patient's eye Lenses that do not move under these circumstances are not considered to be a good fit for the patient's eye, for lenses that are too tight will not move when the patient blinks and may become uncomfortable. Therefore one of the objects of this invention is to produce an antimicrobial lens that does not adhere to the patient's eye.

To meet this objective, the invention includes an antimicrobial lens comprising, consisting essentially of, or consisting of silver, wherein said lens has sufficient movement on the eye of a patient. The terms lens, antimicrobial, lens, silver, R 1

R

41 Y, a, q, m, n, p, d, b, t, u, w, and x, all have their aforementioned meanings and preferred ranges. The phrase "movement on the eye of a patient" refers to whether a lens, when placed on the eye of a patient moves under the push-up test described above. This test is described in further detail in Contact Lens Practice, Chapman Hall, 1994, edited by M. Ruben and M. Guillon, pgs. 589-99. Under this test lenses are given an -2 rating if they do not move on the eye of a patient in the digital push-up test. Therefore lenses Sthat score greater than a on the digital push-up test are lenses that move on a patient's eye. In a statistically significant patient population, lenses that may 00 be suitable for one patient may not be suitable for another. Therefore, lenses having sufficient movement are lenses that move on at least about 50 to about 100% of a given patient population. Preferably, said lenses move on about 75 to N about 100%, of patients, more preferably, about 80 to about 100%, most preferably about 90 to about 100%.

The lenses of the invention are one method of making lenses that contain silver and have sufficient movement on the eye of a patient; however, they are not only lenses containing silver that may have sufficient movement. Other methods of incorporating into contact lenses may be used, provided that those methods produce lenses having sufficient movement on the eye of a patient.

In order to illustrate the invention the following examples are included.

These examples do not limit the invention. They are meant only to suggest a method of practicing the invention. Those knowledgeable in contact lenses as well as other specialties may find other methods of practicing the invention.

However, those methods are deemed to be within the scope of this invention.

EXAMPLES

The following abbreviations were used in the examples APDS acrylamidophenylsulfide AMPSA 2-acrylamido-2-methyl-1 -propanesulfonic acid; CYST N,N'-(bisacryloyl)cystamine; PVP= polyvinylpyrrolidinone; MAA methacrylic acid; PAA poly(acrylic acid) ATU allylthiourea; VIM vinyl imidazole; MABP methacrylamido bipyrimidine; MAHB 4 -methacryloxy-2-hydroxybenzophenone; PSPM N-[p-(N-pyrimidin-2-sulfamoyl)phenyl~methacr.ylamide Cell/prot (Acryl amidomethyl)celulose acetate propionate IND 3M3P 3 -methyl-3-propanol D30 =3,7-dimethyl-3-octanol 00 TM t-amyl alcohol BAGE glycerin esterified with boric acid DI= deionized water; PBS phosphate-buffered saline, pH 7.4 ±0.2; io TPBS Phosphate-buffered saline with 0.05% Tween Tm 80, pH 7.4 ±0.2; TSA sterile tryptic soy agar; TSB sterile tryptic soy broth; IPA isopropyl alcohol, 60% v/v Dl; IPA isopropyl alcohol, 70% v/v Dl; 10% IPA isopropyl alcohol, 10% v/v Dl; VVD modified vortex device; TBACB tetrabutyl ammonium-m-chlorobenzoate TMI dimethyl meta-isopropenyl benzyl isocyanate MMA methyl methacrylate HEMVA hydroxyethyl methacrylate Bloc-HEMA 2-(trimethylsiloxy) ethyl methacrylate TRIS tris(trimethylsiloxy)-3-methaci-yloxypropylsilane mPDMS mono-methacryloxypropyl terminated polydimethylsiloxane

MW=

800-1000 DMA N,N-dimethylacrylamide Blue HEMVA the reaction product of reactive blue number 4 and HEMA as described in Example 4 of U.S. Patent 5,944,853 DAROCUR 1173 =2-h yd roxy-2-methyl- 1 -ph enyl-pro pan- 1 -one EGDMA =ethyleneglycol dimethacrylate TMVPTMA trimethyloyl propane trimethacrylate TEGDMA tetra ethyleneg lycol dimethacrylate 0 Norbloc 2-(2'-hydroxy-5-methacrylyloxyethylphenyl)-2H-benzotriazole CGI 1850 1:1 blend of 1-hydroxycyclohexyl phenyl ketone and bis (2,6- Q dimethyoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide THF tetrahydrofuran 0 5 HAM hydroxyalkylmethacrylate, as described in US. Patent No. 5,98,498 w/w weight/total weight 00 I w/v weight/total volume Sv/v =volume/total volume pHEMA poly(hydroxyethyl) methacrylate coating as described in Example 14 0l0 of U.S. Serial No. 09/921,192, "Methods for Coating Articles by Mold Transfer" The contact lenses of the invention were evaluated using the following biological assay, where Test B is the preferred method for determining inhibition of microbial production under the present invention.

Test A Inhibition of Bacterial Growth/Adhesion A culture of Pseudomonas aeruginosa, ATCC# 15442 (ATCC, Rockville, MD) was grown overnight in a nutrient medium. The bacterial inoculum was prepared to result in a final concentration of approximately 1 x 108 colony forming units/mL. Three contact lenses were rinsed with phosphate buffered saline (PBS) pH 7.4 Each rinsed contact lens was combined with two (2) mL of bacterial inoculum into a sterile glass vial, which was rotated in a shakerincubator (100 rpm) for two hrs. at 37 20C. Each lens was rinsed with PBS to remove loosely bound cells, placed into 10 mL of PBS containing 0.05% w/v TweenTM 80 and vortexed at 2000 rpm for three minutes. The resulting supernatant was enumerated for viable bacteria, and the results, reported of the detected viable bacteria attached to three lenses were averaged.

Test B Inhibition of Bacterial Growth/Adhesion A culture of Pseudomonas aeruginosa, ATCC# 15442 (ATCC, Rockville, MD) was grown overnight in a nutrient medium. The bacterial inoculum was Sprepared to result in a final concentration of approximately 1 x 106 colony Sforming units/mL. Three contact lenses were rinsed with phosphate buffered saline (PBS) pH 7.4 Each rinsed contact lens was combined with two (2) SmL of bacterial inoculum into a sterile glass vial, which was rotated in a shakerincubator (100 rpm) for 24 hr. at 35 2°C. Each lens was rinsed with PBS to 0 remove loosely bound cells, placed into 10 mL of PBS containing 0.05% w/v TweenTM 80 and vortexed at 2000 rpm for three minutes. The resulting supernatant was enumerated for viable bacteria, and the results, reported of the detected viable bacteria attached to three lenses were averaged.

The formulations that were used to prepare the lenses of the invention were prepared as follows.

Macromer 2 Preparation To a dry container housed in a dry box under nitrogen at ambient temperature was added 30.0 g (0.277 mol) of bis(dimethylamino)methylsilane, a solution of 13.75 mL of a 1M solution of TBACB (386.0 g TBACB in 1000 mL dry THF), 61.39 g (0.578 mol) of p-xylene, 154.28 g (1.541 mol) methyl methacrylate (1.4 equivalents relative to initiator), 1892.13 (9.352 mol) 2-(trimethylsiloxy)ethyl methacrylate (8.5 equivalents relative to initiator) and 4399.78 g (61.01 mol) of THF. To a dry, three-necked, round-bottomed flask equipped with a thermocouple and condenser, all connected to a nitrogen source, was charged the above mixture prepared in the dry box.

The reaction mixture was cooled to 15 °C while stirring and purging with nitrogen. After the solution reached 15 191.75 g (1.100 mol) of 1trimethylsiloxy-1-methoxy-2-methylpropene (1 equivalent) was injected into the reaction vessel. The reaction was allowed to exotherm to approximately 62 °C and then 30 mL of a 0.40 M solution of 154.4 g TBACB in 11 mL of dry THF was metered in throughout the remainder of the reaction. After the temperature of reaction reached 30 °C and the metering began, a solution of 467.56 g (2.311 O mol) 2-(trimethylsiloxy)ethyl methacrylate (2.1 equivalents relative to the Sinitiator), 3636.6. g (3.463 mol) n-butyl monomethacryloxypropyl- Spolydimethylsiloxane (3.2 equivalents relative to the initiator), 3673.84 g (8.689 o mol), TRIS (7.9 equivalents relative to the initiator) and 20.0 g bis(dimethylamino)methylsilane was added.

00 (O The mixture was allowed to exotherm to approximately 38-42 °C and then Sallowed to cool to 30 At that time, a solution of 10.0 g (0.076 mol) N bis(dimethylamino)methylsilane, 154.26 g (1.541 mol) methyl methacrylate (1.4 0 10 equivalents relative to the initiator) and 1892.13 g (9.352 mol) 2l trimethylsiloxy)ethyl methacrylate (8.5 equivalents relative to the initiator) was added and the mixture again allowed to exotherm to approximately 40 The reaction temperature dropped to approximately 30 °C and 2 gallons of THF were added to decrease the viscosity. A solution of 439.69 g water, 740.6 g methanol and 8.8 g (0.068 mol) dichloroacetic acid was added and the mixture refluxed for hours to de-block the protecting groups on the HEMA. Volatiles were then removed and toluene added to aid in removal of the water until a vapor temperature of 110 °C was reached.

The reaction flask was maintained at approximately 110 °C and a solution of 443 g (2.201 mol) TMI and 5.7 g (0.010 mol) dibutyltin dilaurate were added.

The mixture was reacted until the isocyanate peak was gone by IR. The toluene was evaporated under reduced pressure to yield an off-white, anhydrous, waxy reactive monomer. The macromer was placed into acetone at a weight basis of approximately 2:1 acetone to macromer. After 24 hrs, water was added to precipitate out the macromer and the macromer was filtered and dried using a vacuum oven between 45 and 60 °C for 20-30 hrs.

Macromer 1 Preparation The procedure for Macromer 2 used except that 19.1 mole parts HEMA, mole parts MAA, 2.8 mole parts MMA; 7.9 mole parts TRIS, 3.3, mole parts mPDMS, and 2.0 mole parts TMI were used.

1 Macromer 3 Preparation a The procedure for Macromer 2 was used except that 19.1 mole parts HEMA, 7.9 mole parts TRIS, 3.3 mole parts mPDMS, and 2.0 mole parts TMI were 00 used.

In Marcromer 4 Preparation The procedure for Macromer 2 was used except that dibutyltin dilaurate was replaced with triethylamine.

Base Monomer Formations and Lens Preparation Formulations A-R, listed in Table 1, are representative base monomer mixes (all amounts are calculated as weight percent of the total weight of the combination). The polymerizable monomers of the invention are added to these mixtures as indicated in Table 2 and contact lenses are prepared according to the following method.

Contact lenses are prepared by adding the indicated amount of the polymerizable monomer to about 10 g of the base monomer mix in the presence of 1 5%wt acetic acid (when Marcromer 4 is used, no acetic acid is added) and a diluent suitable for compatiblizing the components, as indicated in Table 1. This mixture issonicated at 25-37°C until all components are dissolved (30-120 minutes) and was subsequently loaded into an eight cavity lens mold of the type described in U.S. Pat. No. 4,640,489 and cured for 1200 sec at temperatures of, but not limited to, 25 to 90°C, preferably between 45 to 75*C. Polymerization occurred under a nitrogen purge and was either photoinitiated with 5 mW cm 2 of UV light generated with an Andover Corp. 420PS10-25 AM39565-02 light filter, or photoinitiated with visible light generated with a Philips TL 20W/03T fluorescent bulb. The time of curing varied from 7 minutes to 60 minutes. After curing, the molds are opened, and the lenses are either released in a 1:1 blend of water and ethanol, then leached in ethanol to remove any residual monomers and diluent, or Nreleased in a 60% IPA/water, then leached in IPA/DI to remove any residual j monomers and diluent. Finally the lenses were equilibrated in either physiological Sborate-buffered saline or de-ionized water.

O

IND

00 o

O"-

2007240158 06 Dec 2007 Table 1 Formulation A B C D E F G H I J K M N O P Q R Macromer 1 2 3 3 2 2 2 2 2 2 2 2 2 2 2 2 2 [Macromer] 30.00 25.00 60.00 20.00 17.98 17.98 18.00 19.98 17.98 17.98 19.98 40.00 18.00 18.00 18.00 TRIS 0.00 18.00 0.00 40.00 21.00 21.00 14.00 8.00 20.00 25.00 20.00 20.00 14.00 14.00 14.00 DMA 27.00 28.00 36.00 36.00 25.50 25.50 26.00 26.00 22.00 9.00 23.00 35.00 26.00 26.00 26.00 mPDMS 39.00 18.00 0.00 0.00 21.00 21.00 28.00 28.50 25.50 30.00 28.50 28.00 28.00 28.00 Norbloc 2.00 2.00 3.00 3.00 2.00 2.00 2.00 2.00 2.00 2.00 2.00 3.00 2. 200 2 .00 CG11850 2.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 2.00 1.00 1.00 1.00 TEGDMA 0.00 0.00 0.00 0.00 1.50 1.50 1.00 1.50 1.5 0. 1.50 0.25 0.50 HEMA 0.00 0.00 0.00 0.00 5.00 5.00 5.00 5.00 5.00 7.00 5.00 5.00 5.00 5.00 96.8 98.6 Blue HEMA 0.00 0.00 0.00 0.00 0.02 0.02 0.02 0.02 0.02 0.02 0.02 PVP 0.00 8.00 0.00 0.00 5.00 5.00 5.00 8.00 5.00 7.50 9.00 5.00 Darocur 0.3 0.30 1173 EGDMA 0.8 0.8 TMPTMA 0.1 0.1 MAA Diluent 41 20 20 None 20 50.00 20.00 37.50 20.00 40.00 50.00 20 20. 20.00 20.00 20.00 52.00 52.00 Diluent 3M3P 3M3P 3M3P NA D30 TAA D30 3M3P TAA 3M3P 3M3P D30 D30 D30 D30 BAGE BAGE

CD

Example 1 SPreparation of Antimicrobial Contact Lenses Usina PSPM Contact lenses prepared from PSPM (2365 ppm or 0.24 weight per 00 cent) and base monomer mix (Table 1,10.0 were treated with a 10% w/v solution of AgNO 3 in deionized water for about 60 minutes (30 lenses in 60 mL of 10 wt.% AgNO 3 in deionized water). The treated lenses were removed from the silver solution and placed into distilled water (300 mL). The lenses were either rolled or stirred in distilled water for at least about 20 minutes. This water washing procedure was repeated three more times. The resulting lenses were stored in saline solution and tested to determine their antimicrobial potential. The results of the bacterial adhesion assay are presented in Table 2.

In addition, the lenses were analyzed by inductively coupled argon plasma atomic emission spectroscopy (ICP-AES) of a hydrogenfluoride (HF) digest of a dry lens or using instrumental neutron activation analysis, to determine the amount of silver that was incorporated in the lenses. This data is presented in Table 2.

Example 2 Preparation of Antimicrobial Contact Lenses Using Polymerizable Monomers other than PSPM The procedure of Example 1 was repeated replacing the amount of polymerizable ligand and the base monomer mix as indicated by Table 2.

Table 2 lists, the Base Monomer Mix (from Table the polymerizable monomer of Formula I; the concentration of the polymerizable monomer of Formula 1 in ppm; the amount of silver incorporated into the lens; the inhibition from the bacterial assay, using lenses made from formulation Q without any added polymerizable monomer as the control; the inhibition from the bacterial assay using lenses made from formulation G as the control.

(Lenses were tested by inductively coupled plasma atomic emission spectroscopy). The antimicrobial activity of formulation Q lenses and formulation G lenses are statistically the same (95% confidence In the Base Monomer Mix column, the "Ag" suffix indicates that the lenses were treated with 10% AgNO, as described in Example 1.

Base Monomer no Monomer MixFormula I Q-Ag PSPM G PSPM G PSPM G-Ag PSPM G-Ag PSPM G ATU G-Ag

ATU

G ATU G-Ag ATU G VIM G-Ag VIM R-Ag MAA R-Ag MAA R-Ag MAA G MAA G MAA G MAA G-Ag MAA G-Ag MAA G-Ag MAA G-Ag MAA G MAHB G MAHB Table 2 [Formula I] [Ag], of Inhibition InhibitionTrial ppm 2365 2365 2365 2365 2365 438 438 2800 2800 1124 1124 9,000 18,000 36,000 18,000 27,000 36,000 5,000 18,000 27,000 36,000 3610 16,000 ppm

N/A

265

N/A

N/A

2700

N/A

15 550 1100

N/A

N/A

N/A

1800 r

Q

96.68 75.83 60.64 99.64 97.74 20.00 45.00 0.00 0.00 40.00 32.65 0.00 36.85 94.89 60.53 36.84 1.62 46.17 91.34 93.00 91.50 26.32 27.32

G

N/A

52.99 42.55 99.30 96.71

N/A

N/A

N/A

N/A

N/A

N/A

0.00 38.38 95.01 46.43 14.29 0.00 47.48

N/A

N/A

N/A

N/A

N/A

0-Ag 0-Ag 0-Ag

G

0-Ag 0-Ag 0-Ag

G

0-Ag

G

G

G

G

G

G

G

G

G

0

G

G

G-Ag G-Ag G-Ag 0-Ag G-Ag 0-Ag 0-Ag 0-Ag G-Ag

MAHB

MAHB

MAHB*

MABP

MABP

MABP

MABP

MABP*

C EL L/p rot GELL/prot

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

AMPSA

3610 16,000 16,000 2512 89,000 2512 89,000 89,000 10,000 10,000 500 1000 1500 2000 2000 2000 2924 3000 3000 3000 4000 5000 500 1000 1500 2000 2000 2000 2924 3000 3000 1.9

N/A

310

N/A

1.9 61 3.4 <*3 54.

296

N/A

378 383 140

N/A

48 58.70 13.48 8.36 45.22 0.00 53.08 12.13 70.03 38.30 40.73 43.17 16.07 18.94 18.44 29.03 10.71 5.13 49.28 60.12 13.42 0.00 10.38 67.00 59.78 95.97 93.52 98.93 95.02 97.42 93.40 99.13

N/A

35.15 0.00 21.82 14.34 33.03 34.14 54.38 58.99 60.61 0.00 0.00 0.00 0.00 0.00 0.00 28.50 22.81 30.35 0.00 0.00 0.00 17.69 0.00 89.94 90.13 98.13 87.58 98.02 89.96 98.49 G-Ag AMPSA 3000 150 98.95 98.52 3 SG-Ag AMPSA 4000 N/A 92.02 87.85 G-Ag AMPSA 5000 N/A 92.25 88.20 SN AMPSA 3000 65.00 56.20 N-Ag AMPSA 3000 N/A 98.51 98.14 0 G CYST 2000 64.43 47.39 G CYST 3000 61.76 43.45 G CYST 3600 0.00 0.00 G CYST 4000 55.57 34.30 1 G CYST 4000 38.34 0.00 2 G CYST 4000 8.37 0.00 3 G CYST 4000 30.90 9.57 4 G CYST 5000 0.00 0.00 G-Ag CYST 2000 324 90.10 85.35 G-Ag CYST 3000 436 90.33 85.70 G-Ag CYST 3600 N/A 92.76 94.54 G-Ag CYST 4000 692 93.81 90.84 1 G-Ag CYST 4000 725 95.49 88.09 2 G-Ag CYST 4000 750 92.64 81.65 3 G-Ag CYST 4000 732 97.22 96.36 4 G-Ag CYST 5000 900 85.62 78.73 N CYST 4000 36.61 20.67 1 N CYST 4000 52.82 38.26 2 N-Ag CYST 4000 744 94.24 92.79 1 N-Ag CYST 4000 640 99.20 98.96 2 N-Ag CYST 4000 719 98.43 97.95 3 O CYST 4000 67.04 56.87 O-Ag CYST 4000 778 97.00 96.07 P CYST 4000 46.51 30.00 P-A CYST 4000 760 98.30 97.77 N/A indicates data not available O indicates that the lenses were prepared by the method of Example 3 indicateds that the lenses were not analyzed for silver content Example 3 Preparation of Antimicrobial Contact Lenses Using Polymerizable Monomers other than PSPM and Treated with a Base Before Silver Treatment SContact lenses prepared from a polymerizable monomer (as denoted by San asterix in Table 2; in addition, Table 2 also lists the concentration used) Sand base monomer mix were treated with either 10% w/v solution of Na 2

CO

3 in deionized water, 10% w/v solution of NaHCO, in deionized water, 10% w/v CN solution of NaOH in deionized water, or 1 M NaOMe in methanol for about minutes to about 20 hours (30 lenses in 30 mL of any basic solution). The treated lenses were then removed from the basic solution and placed into deionized water (30 mL). The lenses were either rolled or stirred for a minimum of 10 minutes. This water washing procedure was repeated at least twice. The base treated lenses were then treated with a 10% w/v solution of AgNO 3 in deionized water for about 60 minutes (30 lenses in 60 mL of 10 wt.% AgN03 in deionized water). The base/silver treated lenses were removed from the silver solution and placed into distilled water (300 mL). The lenses were either rolled or stirred in deionized water for at least twenty minutes. This water washing procedure was repeated three more times. The resulting lenses were stored in saline solution and tested to determine their antimicrobial potential.

Table 2 lists, the Base Monomer Mix (from Table the polymerizable monomer of Formula I; the concentration of the polymerizable monomer of Formula 1 in ppm; the amount of silver incorporated into the lens; the inhibition from the bacterial assay, using lenses made from formulation Q without any added polymerizable monomer as the control; the inhibition from the bacterial assay using lenses made from formulation G as the control. The antimicrobial activity of formulation Q lenses and formulation G lenses are statistically the same (95% confidence In the Base Monomer Mix column, the "Ag" suffix indicates that the lenses were treated with 10% AgNO 3 as described in Example 1.

SExample 4 Preparation of Antimicrobial Contact Lenses Containing CYST CYST (0.2 weight percent based on weight of the monomer mix) was 00 n polymerized in monomer mix G and cured using the methods outlined in Base O Monomer Formulations and Lens Preparation.

SA mixture of sodium borate (3.70 g) and boric acid (18.52 g) was placed in a 2 L volumetric flask and diluted to volume with deionized water to give SBorate Buffered Packing Solution. Silver nitrate (0.1042 g) was weighed into a 100 mL volumetric flask and de-ionized water was added to volume to give Silver Stock Solution. The Silver Stock Solution was further diluted with the Borate Buffered Solution to give a working solution concentration of 0.33 ug Ag/mL. The cured lenses were transferred into vials containing 3 mL of the working solution. The vials were sealed and autoclaved for 2 hours 121°C.

The treated lenses were removed from the vials and washed with several portions of de-ionized water and subsequently re-packaged in Sodium Chloride Packing Solution (3 mL in vials of 0.85% sodium chloride, 0.9% boric acid, 0.18% sodium borate, 0.01% EDTA adjusted to pH of The resulting lenses were analyzed for silver content by Instrumental Neutron Activation Analysis (INAA). Lenses produced by this method were characterized by a silver concentration of 46 ug/g.

Example Movement of Lenses Lenses were prepared using the method of Examples 1 2, and 4. The amount of polymerizable ligands and the base monomer are listed. To determine the amount of silver present in each lens type, samples were sent Galbraith Laboratories, Inc. (Knoxville, TN) for silver analysis by inductively coupled plasma atomic emission. The first ten lens types in Table 3

O

1^

IN

0 o

(N

0

Q

Os were tested on ten (10) subjects per type of lens using the push up assay (Contact Lens Practice, Chapman Hall, 1994, edited by M. Ruben and M.

Guillon, pgs. 589-99). The last six entries in Table 3 were tested on twentythree (23) subjects per type of lens using the push-up assay. All lenses were 5 evaluated 30 minutes after placing the lenses on patients' eyes. The percentage of lenses having acceptable movement qualities was calculated as follows. Any lens having a score of greater than -2 on the push up test was an acceptable lens. In a each patient study, the number of acceptable lenses was divided by the total number lenses. Lenses having a percentage of movement equal to or greater than 50% are the preferred lenses. In addition, prior to insertions in a patient's eyes the efficacy of the lenses N and G were tested using microbial tests, A and B respectively. The activity of the lenses in these assays is listed in Table 3 as a the log reduction of the assay. Figure 1 shows the percentage lenses having acceptable movement vs the amount of silver in each lens.

Base Monomer Mix N-Ag N-Ag 1 N-Ag N-Ag N-Ag N-Ag N-Ag 2 G-Ag G-Ag G-Ag G-Ag G-Ag Monomer of Formula I

CYST

CYST

CYST

CYST

CYST

CYST

CYST

CYST

CYST

CYST

CYST

CYST

Table 3 [Formula I] ppm 4000 4000 4000 4000 4000 4000 4000 2000 2000 2000 2000 2000 [Ag] ppm 764 760 823 261 661 212 790 60 56 164 50 41 Log Reduction Assays 1.80 1.60 1.10 1.23 1.48 0.84 1.17 1.41 1.45 1.24 2.17 2.24 O G-Ag CYST 2000 42 2.18 0 G-Ag CYST 2000 49 2.01 G-Ag CYST 2000 43 1.91 G-Ag CYST 2000 49 1.00 G-Ag APDS 2000 313 1.57 1 lenses coated with PAA 00 In 2 lenses coated with pHEMA t"- Example 6 Movement of Lenses Lenses were prepared using the method of Examples 1 and 2. The amount of polymerizable ligands and the base monomer are listed. To determine the amount of silver present in each lens type, samples were sent Galbraith Laboratories, Inc. (Knoxville, TN) for silver analysis by inductively coupled plasma atomic emission spectroscopy before the lenses were inserted into the eyes of patients. The lens types listed in Table 4 were tested on ten (10) subjects per type of lens using the push up assay (Contact Lens Practice, Chapman Hall, 1994, edited by M. Ruben and M. Guillon, pgs.

589-99). The lenses were evaluated 30 minutes after placing the lenses on patients' eyes and the percentage of acceptable movement was calculated as described in Example 5. In addition, the lenses were analyzed for pre-wear antimicrobial efficacy using Test B. The activity of the lenses in these assays is listed in Table 4 as a the log reduction of the assay. Figure 2 shows the percentage lenses having acceptable movement vs the amount of silver in each lens.

Table 4 Base Monomer of [Formula I] [Ag] Log Reduction Monomer Mix Formula I ppm ppm Assays O Q-Ag CYST 2000

N/A

0 Q-Ag CYST 1000 851 N/A Q-Ag CYST 500 332 N/A Q-Aq CYST 250 58 1.94 indicates not analyze for silver concentration 00 Example 7 Movement of Lenses In addition to the testing procedures of Example 5, the lenses of SExample 4 were tested after 10 hours, 1 week, 2 weeks and 4 weeks of daily wear use. The percentage of acceptable movement of the lenses was 100%.

CN The lenses were removed from patients' eyes after 10 hours, 1 week, 2 weeks and 4 weeks of use and subsequently analyzed to determine the amount of silver remaining in the lenses. Prior to use, the lenses contained 46 ppm of silver (STD Forty percent of the silver was lost between 10 hours and one week of daily wear. After one week of daily wear, no further loss of silver was observed.

Example 8 Silver Spike Solution and Lenses CYST (0.4 weight percent based on weight of the monomer mix) was polymerized in monomer mix N and cured using the methods outlined in Base Monomer Formulations and Lens Preparation.

Silver nitrate (0.0787 g) was weighed into a 25 mL volumetric flask and Borate Buffered Packing Solution was added to volume to give Solution C 2000 pg/mL). Solution C was further diluted with the Borate Buffered Solution to give the Silver Spike Solution 20 pg/mL). The cured lenses were transferred to vials containing Borate Buffered Packing Solution (3 mL, made by the method of Example 11) and 50pL of Silver Spike Solution was added using an eppendorf pipet. The vials were sealed and autoclaved for 3 consecutive cycles of 30 minutes each 121 C. The resulting lenses were analyzed for silver content by Instrumental Neutron Activation Analysis (INAA).

The average silver content of the lenses was 45.4 pg/g.

o Example 9 a Silver Spike Solution and Lenses SCYST (0.2 weight percent based on the weight of the monomer mix) was polymerized in monomer mix G and cured using the methods outlined in Base Monomer Formulations and Lens Preparation. A number of lenses were 00 placed in a jacketed beaker, (60 containing 800 mL of sodium borohydride 0 solution (200 pg/mL). The lenses were agitated using a magnetic stirrer for C min and subsequently rinsed several times with de-ionized water at 60 "C.

Subsequently, the lenses were placed in vials containing Borate SBuffered Packing Solution (3 mL, made by the method of Example 11) and 501L of Silver Spike Solution (Example 8) was added using an eppendorf pipet. The vials were sealed and autoclaved for 3 consecutive cycles of minutes each 121°C. The resulting lenses were analyzed for silver content by INAA. The average silver content of the lenses was 44.1 pg/g.

Example Silver Spike Solution and Lenses CYST (02 weight percent based on the weight of the monomer mix) was polymerized in monomer mix G and cured using the methods outlined in Base Monomer Formulations and Lens Preparation. A number of lenses were placed in a jacketed beaker, (60 containing 800 mL of sodium borohydride solution (200 pg/mL). The lenses were agitated using a magnetic stirrer for min and subsequently rinsed several times with de-ionized water at 60 °C.

Subsequently, the lenses were placed in vials containing Sodium Chloride Packing Solution (3 mL, of 0.85% sodium chloride, 0.9% boric acid, 0.18% sodium borate, 0.01% EDTA adjusted to pH of 7.3) and 50pL of Silver Spike Solution was added using an eppendorf pipet. The vials were sealed and autoclaved for 3 consecutive cycles of 30 minutes each 121"C. The resulting lenses were analyzed for silver content by INAA. The average silver content of the lenses was 44.2 pg/g.

0Example 11 Preparation of Antimicrobial Contact Lenses Containing CYST CYST (0.2 weight percent based on the weight of the monomer mix) was polymerized in monomer mix G and cured using the methods outlined in Base Monomer Formulations and Lens Preparation.

00 In A mixture of sodium borate (1.85 g) and boric acid (9.26 g) was placed O in a 1L volumetric flask and diluted to volume with deionized water to give SBorate Buffered Packing Solution. Silver nitrate (0.0162 g) was weighed into a O io 50 mL volumetric flask and de-ionized water was added to volume to give C-i Silver Stock Solution. The Silver Stock Solution was further diluted with the Borate Buffered Solution to give Solution A (1.0 pg/mL) and Solution B pg/mL). The cured lenses were transferred into vials containing 3 mL of either Solution A or Solution B. The vials were sealed and autoclaved for 3 consecutive cycles of 30 minutes each 121°C. The resulting lenses were analyzed for silver content by inductively coupled plasma atomic emission spectroscopy. Lenses made using Solution A had an average silver content of 151 pg/g. Lenses made using Solution B had an average silver content of Pg/g.

Claims (50)

1. 4-methylpiperidin-1 -yI; 4-methylpiperazin-1 -yI; substituted phenyl; substituted benzyl; 00 sbtttdprdnl substituted pyrimdinyl; substituted pyrimiinyl; substituted pyraziny);oyl substituted benzimidazolyl; substituted benzothiazolyl; substituted naphthaloyl; substituted quinolinyl; substituted indolyl; substituted thiadiazolyl; substituted triazolyl; substituted 4-methylpiperidin-1 -yi; or substituted 4-methylpiperazin-1 -yl, wherein the substituents are selected from one or more members of the group consisting of Cl 1 ,alkyl, haloC,,,alkyI, halogen, sulfonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amidine, N-(2-aminopyrimidine)sulfonyI, N-(aminopyridine)sulfol, N-(aminopyrazine)sulfonyl, N-(2-aminopyrimidine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carboflyl, N-(2-aminopyrimidine)phosphonyl, N-(2-aminopyridine)phosphoflyt, N-(aminopyrazine)phosphofl, N-(aminobenzimidazolyl )sulfonyl, N-(aminobenzothiazolyl)sulfonyl, N-(aminobenzotriazoly)sulfonyl, N-(aminoindolyl)suifonyl, N-(aminothiazolyl)sulfonyl, N-(aminotriazoiyl)sulfonyl, N-(amino-4-methylpiperidinyl)sulfonyl, N-(amino-4-methylpiperazinyl)sulfonyl, 00 N-(a min obenzi mid azolyl)ca rbonyi, N-(aminobenzothiazolyl)carbonyl, N-(aminobenzotriazolyl)carbonyl, N-(aminoindoiyl)carbonyl, N-(aminothiazoiyl)carbonyl, N-(aminotriazoiyl)carbonyl, N-(amino-4-methylpiperidinyl)carbonyl, N-(amino-4-methylpiperazinyl)carbonyl, N-(2-aminobenzimidazolyl)phosphonyl, N-(2-aminobenzothiazolyl)phosphonyl, N-(2-aminobenzotriazolyl)phosphony, N-(2-aminoindolyl)phosphonyl, N-(2-aminothiazolyl)phosphonyl, N-(2-aminotriazolyl)phosphonyl, N-(amino-4-methylpiperidinyl) phosphonyl, N-(a min o-4-methylp iperazinyl) phosphonyl, acetamide, nitrile, thiol, C 1 6 alkyldisulfide, C,. 8 alkylsulfide, phenyl disulfide, urea, C 1 -,alkylurea, phenylurea, thiourea, Cl 1 ,alkylthiou rea, phenylthiourea, substituted C, 14 alkyldisulflde, substituted phenyldisulfide, substituted C 1 -6alkylurea, substituted C, 1 ,alkylthiou rea, substituted phenylurea, and substituted phenylthiourea wherein the C 1 -,alkyldisulfide, phenyldisulfide, Cl~alkylu rea, C 1 ~alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C,6alkyl, haloC 16 -alkyI, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic (Ni acid, amine, amidine, acetamide, and nitrile; a is R" 1 is hydrogen or Cl-6alky; R 12 is hydroxyl, sulfonic acid, phosphonic acid, carboxylic acid, acetamide, thioC 14 ,alkylcarbonyl, Cl,,alkyldisulfide, Cl 14 alkylsulfide, 00 phenyl disulfide, urea, Cl-6alkylurea, phenylurea, thiourea, 1 6 alkylthiourea, phenylthiourea, -OR" 3 -N H-R' 3 -S-(CH 2 )d-R' 3 -(CH 2 )d-R' 3 -C(O)NH--(0H 2 )d-R' 3 -(0H 2 )d-R 13 substituted C 14 ,alkyldisulfide, substituted phenyldisulfide, substituted C, 14 alkylurea, substituted phenylurea, substituted phenylthiourea or substituted C,.,alkylthiourea wherein the substituents are selected from the group consisting of Cl. 6 alkyl, haloC 1 -,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; where d is 0-8; R 13 is thioC,.,alkylcarbonyl; substituted C,.6alkyl where the alkyl substituents are selected from one or more members of the group consisting of hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, C, 1 6alkyldisulflde, C 1 6 alkylsuifide, phenyldisulfide, urea, Cl 1 ,alkylurea, phenylurea, thiourea, C 1 ~alkylthiourea, phenylthiourea, substituted C, 1 6alkyld isu Ifide, substituted phenyldisulfide, substituted C~alkylurea, substituted phenylurea, substituted C, 1 ,alkylthiourea and substituted phenylthiourea wherein the C, 14 alkyldisulflde, phenyldisulfide, Cl. 6 alkylurea, C.alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 1 -6alkyl, haloC, 4 6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amnidine, acetamide, and nitrite; -(CR 1 4 R 5 )q-~(CHR' 6 ),**SOH where R" 4 R" 6 and R" 6 are independently selected from the group consisting of hydrogen, halogen, 00 hydroxyl, and C,-6alkyl, q is 1-6, and m is 0-6; -(C 2 2 )XNH-C(O)CR 7 CH 2 where R 1 7 is hydrogen or Cl,alkyl, n is 1-6, and x is 1-6; -(CR' 8 R' 9 20 )(OH) 2 where R' 8 R 1 9 and R 20 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and Cl,alkyI, t is 1-6, and u is 0-6; phenyl; benzyl; pyridinyl; pyrimidinyl; pyrazinyl; benzimidazolyl; benzothiazolyl; benzotriazolyl; naphthaloyl; quinolinyl; indolyl; thiadiazolyl; triazolyl; 4-methylpiperidin-1 -yI; 4-methylpiperazin-1 -yI; IND substituted phenyl; substituted benzyl; 00 substituted pyridinyl; substituted pyrimidinyl; substituted pyrazinyl; C1 substituted benzimidazolyl; substituted benzothiazolyl; substituted benzotriazolyl; substituted naphthaloyl; substituted quinolinyl; substituted indolyl; substituted thiadiazolyl; substituted triazolyl; substituted 4-methylpiperidin-1 -yl; or substituted 4-methylpiperazin- l-yl wherein the substituents are selected from one or more members of the group consisting of Cl 1 ,alkyl, haloC 1 .,alkyl, halogen, sulfonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amidine, N:-(2-ami nopyri mid ine)sulfonyl, N-(aminopyridine)sulfonyl, N-(aminopyrazine)sulfonyl, N-(2-aminopyrimidine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carbony!, N-(2-aminopyrimidine)phosphonyl, N-(2-aminopyridine)phosphonyl, N-(aminopyrazine)phosphonyl, N-(aminobenzimidazolyl)sulfonyl, N-(aminobenzothiazoiyl)sulfonyl, N-(aminobenzotriazolyl)sulfonyl, N-(aminoindolyl)sulfonyl, N-(aminothiazolyl)sulfonyl, N min otriazolyl)su lfonyl, N-(amino-4-methylpiperidinyl)sulfonyl, N-(amino-4-methylpiperazinyl)sulfonyl, N-(aminobenzimidazolyl )carbonyl, N-(aminobenzothiazolyl)carbonyl, N N-(aminoindolyl)carbonyl, N-(aminothiazolyl)carbonyl, N-(aminotriazolyl)carbonyl, N-(amino-4-methylpiperidinyl)carbonyl, N-(amino-4-methylpiperazinyl)carbonyl, N-(2-am inobenzi mid azolyl)ph osph onyl, N-(2-aminobenzothiazolyl)phosphony, N-(2-aminobenzotriazolyl)phosphonyl, N-(2-amnoindolyl)phosphonyl, N-(2-aminothiazolyl)phosphonyl, N-(2-aminotriazolyl)phosphonyl, N-(amino-4-methylpiperidinyl) phosphonyl, N-(amino-4-methylpiperazinyl) phosphonyl, acetamide, nitrile, thiol, C,.6alkyldisulfide, Cl 1 ,alkylsulfide, phenyl disulfide, urea, C, 14 alkylurea, phenylurea, thiourea, C 1 -6alkylthiourea, phenylthiourea, substituted Cl 1 ,alkyldisulfide, substituted phenyldisulfide, substituted C 1 _,alkylurea, substituted C 1 .6alkylthiourea, substituted phenylurea, and substituted phenylthiourea wherein the Cl-6alkyldisulfide, phenyldisulfide, C 1 _,alkylurea, C,. 6 alkythiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 1 _6alkyl, haloC,-,aIkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; b is p is is hydrogen; R" 2 is hydroxyl, sulfonic acid, phosphonic acid, carboxylic acid, thioC,,,alkylcarbonyl, thioC 1 .,alkylaminocarbonyl, C 14 ,alkyldisulfide, phenyldisulfide, -C(O)NH(CH 2 1 ,6-SO 3 H, -C(O)N H(CH 2 14
2. 6-P(O)(OH) 2 -OR 23 -NH-R C(O)NH-(CH 2 )d-R 3 -S-(CH 2 )d-R 23 -(CH 2 )d-R 2 3 urea, C, 1 6alkylurea, phenylurea, thiourea, C 1 6 alkylthiourea, phenylthiourea, substituted C 16 ,alkyldisulfide, substituted phenyldisulfide, substituted Cl 1 ,alkylurea, substituted, C 1 6 alkylthiourea substituted phenylurea or substituted phenylthiourea wherein the substituents are selected from the group consisting of C 16 alkyI, haloC 1 -,alkyI, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile, where d is 0-8; R 2 1 is thioC 1 -,alkylcarbonyl, C 14 ,alkyl, substituted C 18 alkyl where the alkyl substituents are selected from one or more members of the group consisting of C 14 ,alkyl, halo C 1 ~alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, Cl 14 alkyldisulfide, C 1 .,alkylsulffde, phenyldisulfide, urea, C 14 ,alkylurea, phenylurea, thiourea, C, 16 alkylthiourea, phenylthiourea, substituted C 1 -6alkyldisulfjde, substituted phenyldisulfide, substituted Cl 1 ,alkylurea, substituted phenylures, substituted C 1 -6alkylth iourea, and substituted phenylthiourea wherein the Cl-aalkyldisulfide, phenyldisulfide, N1 Cl 1 ,alkylurea, Ci 1 ,alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C, 14 alkyl, haloC 1 -6alkyI, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; 00 24 R 2 1)q(CHR 26 ),SQ 3 H where R 24 R 25 and R 2 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and C, 1 .alkyl, q is 1-6, and m is 0-6 -(CH 2 )n-S-S-(CH 2 )),NH-C(o)CR 27 CH 2 where R 2 1 is hydrogen or C,,,alkyl, n is 1-6, and x is 1-6; -(CR 28 R 29 )t-(CHR 3 0 2 where R 2 8 R 2 9 and R' are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and Cl 1 ,alkyl, t is 1-6, and u is 0-6; phenyl; benzyl; pyridinyl; pyrimidinyl; pyrazinyl; benzimidazolyl; benzothiazolyl; benzotriazolyl; naphthaloyl; quinolinyl; indolyl; thiadiazolyl; IND triazolyl; 4-methylpiperazin-1 -yl; 0 s u bst h itute d p h en -yl; substituted penyl; C1 substituted pyinyl; substituted pyriidinyl; substituted pyraziinyl; substituted benazimiaoyl; substituted benzothiazolyl; substituted benzotriazoyl; substituted naphthaloyl; substituted quinolinyl; substituted indolyl; substituted thiadiazolyl; substituted triazolyl; substituted 4-methylpiperidin-1 -yl; or substituted 4-methylpiperazin-1 -yI, wherein the substituents are selected from one or more members of the group consisting of C 16 alkyl, haloC 14 ,alkyl, halogen, sutfonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amnidine, N-(2-aminopyrimidine)sulfonyl, N-(aminopyridine)sulfonyl, N-(aminopyrazine)sulfonyl, N-(2-aminopyrimidine)carbonyl, N-(aminopyridine)carbonyi, N-(aminopyrazine)carbonyl, N-(2-aminopyrimidine)phosphonyl, N-(2-aminopyridine)phosphonyl, N-(aminopyrazine)phosphonyl, o N-(aminobenzimidazolyl)sulfonyl, N-(aminobenzothiazolyl)sulfonyl, IND N-(aminobenzotriazolyl)sulfonyl, N-(aminoindolyl)sulfonyl, N-(aminothiazolyl)sufonyl, 00 N-(a min otriazolyl)su Ifon yl, N-(amino-4-methylpiperidinyl)sulfonyl, N-(amino-4-methylpiperazinyl)sulfonyl, C1 N-(aminobenzimidazolyl)carbonyl, N-(aminobenzothiazolyi)carbonyl, C1 N-(aminobenzotriazolyl)carbonyl, N-(aminoindolyi)carbonyl, N-(aminothiazolyl)carbonyl, N-(aminotriazolyl)carbonyl, N-(amino-4-methyipiperidinyl)carbonyl, N-(a mi no-4-methyl pipe razinyl)ca rbonyl, N-(2-aminobenzimidazolyl)phosphonyl, N-(2-aminobenzothiazolyl)phosphonyl, N-(2-aminobenzotriazolyl)phosphonyl, N-(2-aminoindolyl)phosphonyt, N-(2-aminothiazolyl)phosphonyl, N-(2-aminotriazolyl)phosphonyl, N-(a min o-4-methyl pipe rid inyl) phosphonyl, N-(amino-4-methylpiperazinyl) phosphonyl, acetamide, nitrile, thiol, C 1 -6alkyldisulfide, C 14 6alkylsulfide, phenyl disulfide, urea, C 1 -6alkylurea, phenylurea, thiourea, Cl 1 ,alkylthiourea, phenylthiourea, substituted C, 1 ,alkyldisulfide, substituted phenyldisulfide, substituted C 1 .6alkyurea, substituted C, 1 .alkylthiourea, substituted phenylurea. and substituted phenylthiourea wherein the Cl 1 ,alkyldisulfide, phenyldisulfide, 0 1 6 alkylurea, C, 1 ,alkylthiourea, phenylurea,.and phenylthiourea substituents are selected from the group consisting of 0 16 ,alkyl, haloC,.ealkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic IND acid, amine, amidine, acetamide, and nitrile; w is0-1; 00 Y is oxygen or sulfur; R" is hydrogen or C, 1 ,alkyl; R 32 is hydroxyl, sulfonic acid, phosphonic acid, carboxylic acid, rithioC 1 6 alkylcarbonyl, th ioC,.,alkylaminocarbonyl, -C(O)N H-(CH 2 )d -R 3 -0-R 33 -NH-R 3 -S-(CH 2 )d-R -(CH 2 )d-R 33 C, 14 alkyldisulfide, phenyldisulfide, urea, Cl.ralkylurea, phenylurea, thiourea, Ci 1 ealkylthiourea, phenylthiourea, C 14 ,alkylamine, phenylamnine, substituted Cl-6alkyldisulfide, substituted phenyldisulfide, substituted phenylurea, substituted C 1 .,alkylamine, substituted phenylamine, substituted phenylthiourea, substituted C, 1 6alkylurea or substituted C 16 alkylthiourea wherein the substitutents are selected from the group consisting of C,,alkyl, haloC,.,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile where d isO-8; R 33 is thioC 1 .,alkylcarbonyl, C,.6alkyl, substituted Cl..alkyI where the alkyl substituents are selected from one or more members of the group consisting of C,-,alkyl, halo C 14 ,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, Cl-6alkyldisulfide, C, 1 6alkylsulfide, phenyldisulfide, urea, C 1 -6alkylurea, phenylurea, thiourea, Cl 1 ,alkylthiourea, phenylthiourea, substituted C 1 -6alkyldisulfide, substituted phenyldisulfide, substituted C 14 ,alkylurea, substituted phenylurea, substituted C,,alkylthiou rea or substituted 1-10 phenylthiourea wherein the C 1 .,alkyldisulfide, phenyldisulfide, 00 ~C,,alkylurea, C,.,alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C,. 6 a~kyl, haioC,,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and N nitrile; -(CR 34 R 35 )q-(CHR 3 )So 3 H where R34, R 3 and R-3 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and C 1 -6alkyl, q is 1-6, and m isO0-6; -(CH 2 2 H-C(O )CR 37 CH 2 where R 3 1 is hydrogen or C 1 -,alkyl, n is 1-6, and x is 1-6; -(CR 3 8 R39)t(CHR 40 2 where R 3 R3 9 and R 4 0 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and C 14 6alkyI, t is 1-6, and u is 0-6; phenyl; benzyl; pyridinyl; pyrimidinyl; pyrazinyl; o benzimidazolyl; benzoth lazolyl; IND benzotriazolyl; naphthaloyl; 00 quinolinyl; indolyl; thiadiazolyl; triazolyl; 4 -methylpiperidin-1 -y; 4 -methylpiperazin-1 -yl; substituted phenyl; substituted benzyl; substituted pyridinyl; substituted pyrimidinyl; substituted pyrazinyl; substituted benzimidazolyl; substituted benzothiazolyi; substituted benzotriazolyl; substituted naphthaloyl; substituted quinolinyl; substituted indolyl; substituted thiadiazolyl; substituted triazolyl; substituted 4-methylpiperidin-1-yl; or substituted 4-methyl piperazin-1I-yl, wherein the substituents are selected from one or more members of the group consisting of Cl 1 ,alkyl, haloC 18 6alkyl, halogen, sulfonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amidine, N-( 2 -aminopyrimidine)suffonyl, N-(aminopyridine)sulfonyl, N-(aminopyrazine)sulfonyl, U N-(2-aminopyrimidine)carbonyl, N-(aminopyiidine)carbonyl, N-(aminopyrazine)carbonyl, IND N-(2-aminopyrimidine)phosphonyl, 2 a i o y id n h s h n l 00 N-(2aminopyrzine)phosphonyl, 00 N-(amenimkazoy 1 ,phsu 1 ony, N-(aminobenzothiazolyl)sulfonyl, N-(aminobenzotriazolyl)sufonyl, N-(aminoindolyl)sulfonyl, N-(amiriothiazolyl)sulfonyl, N-(aminotriazotyl)sulfonyl, N-(amino-4-methylpiperidinyl)sulfonyl, N-(amino-4-methylpiperazinyl)sulfonyl, N-(aminobenzimidazolyl)carbonyl, N-(aminobenzothiazoiyt)carbonyl, N-(aminobenzotriazolyl)carbonyl, N-(aminoindolyI)carbonyl, N-(aminothiazolyl)carbonyl, N-(aminotriazolyl)carbonyt, N-(amino-4-methylpiperidinyl)carbonyl, N-(amino-4-methylpiperazinyl)carbonyl, N-(2-aminobenzimidazolyl)phosphonyl, N-(2-aminobenzothiazolyl)phosphonyl, N-(2-aminobenzotriazolyl)phosphonyl, N-(2-aminoindoiyl)phosphonyl, N-(2-aminothiazolyl)phosphonyl, N-(2-aminotriazolyl)phosphonyl, N-(amin'o-4-methylpiperidinyl) phosphonyl, N-(amino-4-methylpiperazinyl) phosphonyl, acetamide, nitrile, thiol, C 1 .,alkyldisulfide, Cl.,aikyisulfide, phenyl disulfide, urea, C 14 ,aIkylurea, phenylurea, thiourea, C 1 0 alkylthiourea, phenylthiourea, substituted Cl-6alkyldisulfide, substituted phenyldisulfide, substituted C 14 6alkylurea, substituted C 14 ,alkylthiourea, substituted phenylurea, and substituted phenylthiourea wherein the C 1 -,alkyldisulfide, phenyldisuifide, Cl-,alkylurea, C 16 alkylthiourea, phenylurea, and 00 phenylthiourea substituents are selected from the group consisting of Cl.,alkyI, haloC 1 -,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic N acid, amine, amidine, acetamide, and nitrile; is hydrogen, C, 1 ,alkyl, phenyl, C 1 .alkylcarbonyl, phenylcarbonyl, (Ni substituted C 1 -6alkyl, substituted phenyl, substituted ClalkylcarbonyI or substituted phenylcarbonyl, wherein the substituents are selected from the group consisting of Cl-6alkyl, haloC 1 6 alkyi, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic: acid, amine, amidine, acetamide, and nitrile. 2. The antimicrobial lens of claim 1 comprising a polymer comprising a monomer of Formula 1. 3. The antimicrobial lens of claim 2 wherein, R' is hydrogen or C 1 -3alkyl; R 2 is NH-R 3 d isO0 R 3 is substituted phenyl, -(CR 4 R 5 )q-(CHR 6 ),mSO 3 H, -(CR 8 R 9 )t-(CHR 1 2 or -(CH 2 2 H-C(O)CR 7 CH 2 R' is hydrogen or C,- 3 alkyl; R' is hydrogen or Cl 3 alkyl; R 6 is hydrogen or Cl. 3 alkyI; q is 1-3; O m is 1-3; o R 7 is hydrogen or C 1 ,alkyl; Q R 8 is hydrogen or C 1 ,alkyl; IN R 9 is hydrogen or C1-alkyl; R 1 0 is hydrogen or C. 3 alkyl; 00 t is 1-3; uis 1-3; n is 2-4; and x is 2-4. C4. The antimicrobial lens of claim 2 wherein the lens is a soft contact lens. The antimicrobial lens of claim 2 wherein the monomer of Formula I is present at about 0.01 to about 1.5 weight percent. 6. The antimicrobial lens of claim 2 wherein the monomer of Formula I is present at about 0.01 to about 0.8 weight percent.
3. 7. The antimicrobial lens of claim 2 wherein the monomer of Formula I is present at about 0.01 to about 0.3 weight percent.
4. 8. The antimicrobial lens of claim 2 wherein the monomer of Formula I is present at about 0.01 to about 0.2 weight percent.
5. 9. The antimicrobial lens of claim 2 wherein the monomer of Formula I is present at about 0.01 to about 0.09 weight percent. The antimicrobial lens of claim 2 wherein the lens is a silicone hydrogel.
6. 11. The antimicrobial lens of claim 2 wherein, the lens is etafilcon A, balafilcon, A, acquafilcon A, lenefilcon A, or lotrafilcon A. S12. The antimicrobial lens of claim 2 wherein, R 1 is hydrogen or methyl; R 2 is NH-R 3 R 3 is -(CR 4 R 5 )q-(CHR)m-SO 3 H, -(CR 8 R 9 )-(CHR'O),-P(o)(OH)2or 00 -(CH 2 2 )xNH-C(O)CHR 7 CH,; R 4 is hydrogen or methyl; OR 5 is hydrogen or methyl; q is 1-2; m is 1-2; R 6 is hydrogen or methyl; R 7 is hydrogen; R 8 is hydrogen or methyl; R 9 is hydrogen or methyl; R 1 0 is hydrogen or methyl; t is 1; u is 1-2; n is 2-3; and x is 2-3.
7. 13. The antimicrobial lens of claim 2 wherein the monomer of Formula I is selected from the group consisting of H Y 2 2 CH 3 CH3 S02-NH N S03H A NN H and H C- O O 0 14. The antimicrobial lens of claim 2 wherein silver is present at about Q ppm to about 1,200 ppm. IND O
8. 15. The antimicrobial lens of claim 2 wherein silver is present at about oO ppm to about 600 ppm. In
9. 16. The antimicrobial lens of claim 2 wherein silver is present at about ppm to about 150 ppm. c
10. 17. The antimicrobial lens of claim 2 wherein silver is present at about ppm to about 75 ppm.
11. 18. The antimicrobial lens of claim 2 wherein the lens is a silicone hydrogel and the monomer of Formula I is H 2
12. 19. The antimicrobial lens of claim 18 wherein silver is present at about ppm to about 150 ppm and the monomer of Formula I is present at about 0.01 to about 1.5 weight percent. The antimicrobial lens of claim 2 wherein the lens is etafilcon A, balafilcon, A, acquafilcon A, lenefilcon, or lotrafilcon A and the monomer of Formula I is H 2
13. 21. The antimicrobial lens of claim 20 wherein silver is present at about ppm to about 150 ppm and the monomer of Formula I is present at U about 0.01 to about 1.5 weight percent. S22. The antimicrobial lens of claim 21 wherein the lens is etafilcon A. 00 23. The antimicrobial lens of claim 21 wherein the lens is acquafilcon A. In
14. 24. The lens of claim 23 wherein silver is present at about 20 ppm to about 75 ppm. 010 The antimicrobial lens of claim 1 comprising a polymer comprising a monomer of Formula II.
15. 26. The antimicrobial lens of claim 25 wherein, a is 1-2, R 1 is hydrogen or C. 3 alkyl, R 12 is sulfonic acid, carboxylic acid, phosphonic acid, C,alkyldisulfide, C,.alkylsulfide, phenyldisulfide, substiuted phenyldisulfide or NH-R 1 3 R 13 is thioC 1 6alkylcarbonyl.
16. 27. The antimicrobial lens of claim 25 wherein the monomer of Formula II is selected from the group consisting of NH S 2 2 C0 2 H SO 3 H and 71
17. 28. The antimicrobial lens of claim 25 wherein the lens is a soft contact lens. 0O
18. 29. The antimicrobial lens of claim 25 wherein the monomer of Formula II is 0o present at about 0.01 to about 1.5 weight percent. The antimicrobial lens of claim 25 wherein the monomer of Formula 1I is present at about 0.01 to about 0.8 weight percent.
19. 31. The antimicrobial lens of claim 25 wherein the monomer of Formula II is present at about 0.01 to about 0.3 weight percent.
20. 32. The antimicrobial lens of claim 25 wherein the lens is etafilcon A, balafilcon, A, acquafilcon A, lenefilcon A, or lotrafilcon A.
21. 33. The antimicrobial lens of claim 25 wherein silver is present at about ppm to about 150 ppm and the monomer of Formula II is present at about 0.01 to about 1.5 weight percent.
22. 34. The antimicrobial lens of claim 33 wherein the lens is etafilcon A or acquafilcon A. The antimicrobial lens of claim 1 comprising a polymer comprising a monomer of Formula III.
23. 36. The antimicrobial lens of claim 35 wherein, p is 1-3; bis 1-2; R 21 is hydrogen; N R 2 is sulfonic acid, phosphonic acid, carboxylic acid, U thioC,6alkylcarbonyl, thioC,,.alkylaminocarbonyl, C 1 ,alkyldisulfide, C, 1 .alkylsulfide, phenyldisulfide, substiuted phenyldisulfide, SH 3 OS-(CH 2 1 6 NHC(O) or (HO) 2 (0)P-(CH 2 16 NHC(O)-. 00
24. 37. The antimicrobial lens of claim 35 wherein the monomer of Formula III is selected from the group consisting of O 2, 2 AIIand 0 K NN Ho3s_/ N HO 3 S
25. 38. The antimicrobial lens of claim 35 wherein the lens is a soft contact lens.
26. 39. The antimicrobial lens of claim 35 wherein the monomer of Formula III is present at about 0.01 to about 1.5 weight percent. The antimicrobial lens of claim 35 wherein the monomer of Formula III is present at about 0.01 to about 0.8 weight percent.
27. 41. The antimicrobial lens of claim 35 wherein the monomer of Formula III is present at about 0.01 to about 0.3 weight percent.
28. 42. The antimicrobial lens of claim 35 wherein, the lens is etafilcon A, balafilcon, A, acquafilcon A, lenefilcon A, or lotrafilcon A.
29. 43. The antimicrobial lens of claim 35 wherein silver is present at about Q ppm to about 150 ppm and the monomer of Formula II is present at ND about 0.01 to about 1.5 weight percent. O O 44. The antimicrobial lens of claim 43 wherein the lens is etafilcon A or acquafilcon A. The antimicrobial lens of claim 1 comprising a polymer comprising a monomer of Formula IV.
30. 46. The antimicrobial lens of claim 45 wherein, w is 0-1; R 31 is hydrogen; R 32 is amine, Cl 3 alkylamine, phenylamine, substituted phenylamine; thioC.aalkylcarbonyl; R 41 is hydrogen.
31. 47. The antimicrobial lens of claim 45 wherein the monomer of Formula IV is selected from the group consisting of 0 S N N 2 H HO3S---V N N I S H ,and
32. 48. The antimicrobial lens of claim 45 wherein the lens is a soft contact lens. O 0 49. The antimicrobial lens of claim 45 wherein the monomer of Formula IV is O present at about 0.01 to about 1.5 weight percent. N0 50. The antimicrobial lens of claim 45 wherein the monomer of Formula IV is present at about 0.01 to about 0.8 weight percent. 00
33. 51. The antimicrobial lens of claim 45 wherein the monomer of Formula IV is present at about 0.01 to about 0.3 weight percent. Slo 52. The antimicrobial lens of claim 45 wherein the lens is etafilcon A, c balafilcon, A, acquafilcon A, lenefilcon A, or lotrafilcon A.
34. 53. The antimicrobial lens of claim 45 wherein silver is present at about ppm to about 150 ppm and the monomer of Formula IV is present at about 0.01 to about 1.5 weight percent.
35. 54. The antimicrobial lens of claim 53 wherein the lens is etafilcon A or acquafilcon A.
36. 55. A method of producing an antimicrobial lens comprising, silver and a polymer comprising a monomer of Formula I, II, III or IV R1 R 11 R 2 R 12 R31 R 2 1 Y N 32Y N, (CH 2 rw III IV III IV wherein R' is hydrogen or Cl 1 ,alky(; R 2 is -OR 3 -NH-R 3 -S-(CH 2 I)d-R 3 ,or -(CH 2 )d-R 3 wherein d is 0-8; R 3 is substituted C,. 6 afkyl where the alkyl substituents are selected from one or more members of the group consisting of carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, Cl 1 ,alkyldisulfide, Cl.,aikylsulfide, phenyldisulfide, urea, C,. 6 alkylurea, phenylurea, thiourea, C, 1 ,alkylthiourea, phenylthiourea, substituted C, 14 alkyldisulfide, substituted phenyldisulfide, substituted C 14 ,alkylurea, substituted phenylurea, substituted C,,,alkylthiourea, and substituted phenylthiourea wherein the Cl 14 alkyldisulfide, phenyldisulfide, C,,alkylurea, C, 14 alkylthiourea, phenylurea, and phenylthiourea substituents; are selected from the group consisting of C 14 6alkyI, haloC 1 -6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrite; -(CR 4 R 5 )q-(CH Rr)mSO 3 H wherein R 4 R 5 and R' are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and C,.6alkyl, q is 1-6, and m is 0-6; -(CH 2 )n-S-S-(CH 2 )xNH-C(O)CR 7 CH 2 wherein R 7 is hydrogen or Cl 1 ,alkyI, n is 1-6, and x is 1-6; -(CRBR 9 R 10 )2 U wherein and R' 0 are independently selected from the group consisting of hydrogen, halogen, IND hydroxyl, and C 16 alkyl, t is 1-6, and 00 u is 0-6; phenyl; benzyl; pyridinyl; pyrimidinyl; pyrazinyl; benzimidazolyl; benzothiazolyl; benzotriazolyl; naphthaloyl; quinolinyl; indolyl; thiadiazolyl; triazolyl; 4-methylpiperidin-1 -yl; 4-methylpiperazin-1 -yl; substituted phenyl; substituted benzyl; substituted pyridinyl; substituted pyrimidinyl; substituted pyrazinyl; substituted benzimidazolyl; substituted benzothiazolyl; substituted benzotriazolyl; substituted naphthaloyl; substituted quinolinyl; substituted indolyl; su siutdtidizil substituted thiiazolyl; IND ~substituted 4-methyl pipe ridin- 1 -yI; or substituted 4-methyl piperazin-1 -yl, 00 wherein the substituents are selected from one or more members of the group consisting of C 1 6 alkyl, haloC 1 6 alkyl, halogen, sulfonic acid, phosphonic acid, (Ni hydroxyl, carboxylic acid, amine, amidine, N-(2-aminopyrimid ine)sulfonyl, (Ni N-(aminopyridine)su Ifonyl, N-(aminopyrazine)sulfonyl, N-(2-aminopyrimid ine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carbonyl, N-(2-aminopyrimidine)phosphonyl, N-(2-aminopyridine)phosphonyl, N-(aminopyrazine)phosphonyl, N-(aminobenzimidazolyl)sulfonyl, N-(aminobenzothiazolyl)sulfonyl, N-(aminobenzotriazolyt)su Ifonyl, N-(aminoindolyl)sulfonyl, N-(aminothiazolyl)sulfonyl, N-(a min otriazolyl)sulIfonyl, N-(a min o-4-methyl p iperid inyl)s u fonyl, N-(amino-4-methylpiperazinyl)sulfonyl, N-(aminobenzimidazolyl)carbonyl, N-(aminobenzothiazolyl)carbonyl, N-(aminobenzotriazolyl)carbonyl, N-(aminoindolyl)carbonyl, N-(aminothiazolyl)carbonyl, N-(a min otriazolyl)ca rbonyl, N-(a min o-4-methyl pi perid inyl)ca rbo nyl, N-(a min o-4-methyl p ipe razi nyl)ca rbo nyl, N-(2-aminobenzimidazolyl )phosphonyl, N-(2-aminobenzothiazolyl)phosphonyl, o N-(2-aminobenzotriazolyl)phosphonyl, N-(2-aminoindolyl)phosphonyl, IND N-(2-aminothiazolyl)phosphonyl, N-(2-aminotriazolyl)phosphonyl, 00 N-(amino-4-methylpiperidinyl) phosphonyl, N-(amino-4-methylpiperazinyl) phosphonyl, acetamide, nitrile, thiol, Cl.6alkyldisulfide, Cl 1 ,alkylsulfide, phenyl C1 disulfide, urea, C,-,alkylurea, phenylurea, thiourea, C 1 6 alkylthiourea, phenylthiourea, substituted C1 C, 16 alkyldisulfide, substituted phenyldisulfide, substituted C 1 -6alkylurea, substituted C 1 .6alkylthiourea, substituted phenylurea, and substituted phenylthiou rea wherein the C,.6alkyldisulfide, phenyldisulfide, C 1 .,alkylurea, C,.,alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of Cl-6alkyl, haloC,.,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; a R 1 is hydrogen or C, 1 6alkyl; R 12 is hydroxyl, sulfonic acid, phosphonic acid, carboxylic acid, acetamide, thioCj,, 0 alkylcarbonyl, C 14 alkyldlisulflde, Cl 1 ,alkylsulfide, phenyl disulfide, urea, C 1 ~alkylurea, phenylurea, thiourea, Cl-6alkylthiourea, phenylthiourea, -OR" 3 -S-(CH 2 )d-R' 3 -(CH 2 )d-R 13 -C(O)NH--(GH 2 )d-R 13 -(CHA)-R 13 substituted C, 4 6alkyldisulfide, substituted phenyldisulfide, substituted C,-6alkylurea, substituted phenylurea, substituted phenylth iou rea or substituted Cl 1 ,alkylthiourea wherein the substituents are selected from the group consisting of Cl-6alkyl, haloC 1 .,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; where d isO0-8; R" is thioC 1 6 alkylcarbonyl; are selected from one or 00 more members of the group consisting of hydroxyl, tr~ carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, C 1 -,alkyldisulfide, Cl~alkylsulfide, phenyidisuifide, urea, Cl 1 ,alkylurea, phenylurea, thiourea, 0 1 6 alkylthiourea, phenylthiourea, C1 substituted C 16 alkyld isulfide, substituted phenyidisulfide, substituted C 16 alkylurea, substituted phenylu rea, substituted C 16 ,alkylth iourea and substituted phenylthiourea wherein the C 1 -,alkyldisulfide, phenyldisuffide, Cl 1 ,alkylurea, C 1 .6alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C,,alkyl, haloC,,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; -(CR 14 R 1 5 )q(CHR' 6 )m,-SO 3 H where R 14 R 1 5 and R" 6 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and C 1 .6alkyl, q is 1-6, and m is 0-6; -(CH 2 2 ),,NH-C(O)CR 17 CH 2 1 where R 1 7 is hydrogen or C 16 alkyl, n is 1-6, and x is 1-6; -(CR 18 Rlg)t-(CHR 2 0 2 where R" 8 R' 9 and R" 0 are independently selected (N from the group consisting of hydrogen, halogen, hydroxyl, and C 1 -,alkyl, t is 1-6, and u is, 0-6; phenyl; 00 benzyl; pyridiny); pyrimidinyl: pyrazinyl; benzimidazolyl; benzothiazolyl; benzotriazolyi; naphthaloyl; quinolinyl; indolyl; thiad lazolyl; triazolyl; 4-methylpiperidin-1 -yl; 4-methylpiperazin-1 -yl; substituted phenyl; substituted benzyl; substituted pyridinyl; substituted pyrimidinyl; substituted pyrazinyl; substituted benzimidazolyi; substituted benzothiazolyl; substituted benzotriazolyl; substituted naphthaloyl; substituted quinolinyl; substituted indoly); substituted thiadiazolyl; substituted triazolyl; s u s i u e e h l p p r d n 1 y o substituted 4-methyl pipe rdin-1 -ylo susiueINDtyppeai- y wherein the substituents are selected from one or more members of the group consisting of C,- 6 alkyl, haloC 1 -,alkyI, halogen, sulfonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amidirie, N-(2-aminopyrimidine)sulfonyl, N-(aminopyridine)sulfonyl, N-(aminopyrazine)sulfonyl, N-(2-aminopyrimidine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carbonyl, N-(2-aminopyrimidine)phosphonyl, N-(2-aminopyridine)phosphonyl, N-(aminopyrazine)phosphonyl, N-(aminobenzimidazolyl)sulfonyl, N-(a minobenzothiazolyl)sulfonyl, N-(aminobenzotriazolyl)suifonyl, N-(aminoindolyl)sulfonyl, N-(aminothiazolyl)sulfonyl, N-(aminotriazolyl)sulfonyl, N-(amino-4-methylpiperidinyl)sulfonyl, N-(amino-4-methylpiperazinyl)sulfonyl, N-(aminobenzimidazolyl)carbonyl, N-(aminobenzothiazolyl)carbonyl, N-(a minobenzotriazolyl)carbonyl, N-(aminoindolyl)carbonyl, N-(aminothiazolyl)carbonyl, N-(aminotriazolyl)carbonyl, N-(amino-4-methylpiperidinyl)carbonyl, N-(amino-4-methylpiperazinyl)carbonyl, N min obenzi mid azo lyl)ph osphonyl, N-(2-aminobenzothiazolyl)phosphonyl, N-(2-a minobenzotriazolyl)phosphonyl, N-(2-aminoindoyl )phosphonyl, N 2 a i o h a oyUh s h n l N-(2-aminothiazolyl)phosphonyl, INDaiotizllphshnl s N-(amino-4-methylpiperidinyl) phosphonyl, N-(a min o-4-meth yl pipe razinyl) phosphonyl, acetamide, 00 nitrite, thiol, C,-,alkyldisulflde, C,.6alkylsulfide, phenyl disulfide, urea, C, 1 6alkylurea, phenylurea, thiourea, C 1 alkylthiourea, phenylthiourea, substituted C 1 6 a1 kyldisulfide, substituted phenyidisulfide, substituted C,.,alkylurea, substituted Cl 1 ,alkylthiourea, substituted phenylu rea, and substituted phenylthiourea wherein the Cl 1 ,alkyldisulflde, phenyldisulfide, Cl. 6 alkylurea, C, 1 6alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C, 14 alkyl, haloC 14 ,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; b is p R 2 1 is hydrogen; R' is hydroxyl, sulfonic acid, phosphonic acid, carboxylic acid, thioC,.6alkylcarbonyl, thioC 1 .,alkylaminocarbonyl, C 1 -6alkyldisulfide, phenyldisulfide, -C(O)NH(CH 2 1 -SO 3 H, -C(O)NH(CH 2 1 2 -OR 23 -NH-R 2 C(O)NH-(CH 2 )d-R 2 -S-(CH 2 )d-R 23 -(CH 2 )d-R 2 3 urea, C 1 -6alkylurea, phenylurea, thiourea, Cl-6alkylthiourea, phenylthiourea, substituted C,,alkyldisulfide, substituted phenyldisulfide, substituted C 16 ,alkylurea, substituted, C 1 -6alkylthiourea substituted phenylurea or substituted phenylthiourea wherein the substituents are selected from the group consisting of C 16 alkyl, haloCl- 6 alkyI, halogen, hydroxyl, IN 0 carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile, where d is 0-8; R" 3 is thioC 1 -,alkylcarbonyl, C, 1 6alkyl, substituted C 16 ,alkyl where the alkyl substituents are selected from one or more members of the group consisting of C 16 alkyl, halo C 1 -6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrite, thiol, C 16 alkyldisulfide, Cl-6alkylsulfide, phenyldisulfide, urea, Cl.,alkylurea, phenylurea, thiourea, C 1 ,alkylthiourea, phenylthiourea, substituted C 14 salkyldisulfide, substituted phenyldisulfide, substituted C 1 .6alkylurea, substituted phenylurea, substituted Cl 1 ,alkylthiourea, and substituted phenylthiourea wherein the Cl 14 alkyldisulfide, phenyldisulfide, C 14 ,alkylurea, C 1 6 alkylthiourea, phenylurea, and phenylthiourea substituents; are selected from the group consisting of C, 14 alkyl, haloC 1 -6alkyI, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitriie; -(CR 24 R 25 )q(CH R 26 )m,,SO 3 H where R' 4 R 2 1, and R" 6 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and C 1 ,alkyl, q is 1-6, and m is 0-6 -(CH 2 2 H-C(O)CR 27 CH 2 where R 27 is hydrogen or C 1 -6alkyl, n is 1-6, and x is 1-6; -(CR 2 8 R 29 )-(CHR 3 0 )(OH) 2 where R 2 1, R 2 1, and R 3 0 are independently selected from the group consisting of hydrogen, halogen, 00 hydroxyl, and Cl 1 ,alkyI, t is 1-6, and u is 0-6; phenyl; benzyl; pyrid inyl; pyrimidinyl; pyrazinyl; benzimidazolyl; benzothiazolyt; benzotriazolyl; naphthaloyl; qu inolinyl; indolyl; thiadiazolyl; triazolyl; 4-methylpiperidin-1 -yi; 4-methylpiperazin-1 -yI; substituted phenyl; substituted benzyl; substituted pyridinyl; substituted pyrimidinyl; substituted pyrazinyl; substituted benzimidazolyl; substituted benzothiazolyl; substituted benzotriazolyl; N substituted naphthaloyl; susiue unlnU substituted inotiyl; susittdNnoDl substituted thiadiazolyl; substituted triazolyl; susiue0-mtypprdi- y;o substituted 4-methylpiperazin-1 -yl, o wherein the substituents are selected from one or more members of the group consisting of C 1 .,alkyI, haloC 1 .,alkyl, halogen, suifonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amidine, N-(2-aminopyri mid ine)sulIfonyl, N-(aminopyridine)sulfonyl, N-(aminopyrazine)sulfonyl, N-(2-aminopyrimidine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carbonyl, N-(2-aminopyrimidine)phosphonyl, N-(2-aminopyridine)phosphonyl, N-(aminopyrazine)phosphonyl, N-(aminobenzimidazoyl)sulfonyl, N-(aminobenzothiazolyl)sulfonyl, N-(aminobenzotriazolyl)sulfonyl, N -(amino indolyl)su Ifonyl, N-(aminothiazolyl)sulfonyl, N-(aminotriazolyl)sulfonyl, N-(amino-4-methylpiperidinyl)sulfonyl, N-(a mino-4-methyl pipe razinyl)su Ifon yl, N-(aminobenzimidazolyl)carbonyl, N-(aminobenzothiazolyt)carbonyl, N-.(ami nobenzotriazolyl)carbonyl, N-(aminoindolyl)carbonyl, N-(aminothiazolyl)carbonyl, N-(aminotriazolyl)carbonyl, N-(amino-4-methylpiperidinyl)carbonyl, N-(amino-4-methylpiperazinyl)carbonyl, N-(2-aminobenzimidazolyl)phosphonyl, N-(2-aminobenzothiazolyl)phosphonyl, N-(2-aminobenzotriazolyl)phosphonyl, N-(2-aminoindolyl)phosphonyl, 00 N-(2 *ami noth iazolyl) phos phony[, N-(2-aminotriazolyl)phosphonyl, N-(amino-4-methylpiperidinyi) phosphonyl, N-(amino-4-methylpiperazinyi) phosphonyf,*acetamide, nitrile, thiol, C 1 -,alkyldisulfide, C, 1 ,alkylsulfide, phenyl disulfide, urea, C,,alkylurea, phenylurea, thiourea, C, 1 ,alkylthiourea, phenylthiourea, substituted Cl 1 6 al kyld isul[fide, substituted phenyldisu Ifide, substituted C, 14 alkylurea, substituted C 1 -,alkylthiourea, substituted phenylurea, and substituted phenylthiourea wherein the C 1 -,alkyldisulfide, phenyldisulfide, C, 1 6alkylurea, Cl.,alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 1 -,alkyI, haloC 14 ,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamnide, and nitrile; W isO0-1; Y is oxygen or sulfur; R" 1 is hydrogen or C 1 .,alkyl; R 1 2 is hydroxyl, sulfonic acid, phosphonic acid, carboxylic acid, thioC 14 ,alkylcarbonyl, thioC 1 -6alkylaminocarbonyl, -C(O)N H-(CH 2 )d -R 3 3 -NH-R33 S-(CH 2 )d -R 33 -(CH 2 )d -R 3 3 C 14 alkyldisulfide, phenyldisul fide, urea, C 16 alkylurea, phenylurea, thiourea, C,-,alkythiourea, phenylthiourea, Cl 1 ,alkylamine, phenylamine, substituted C,. 0 alkyldisulfide, substituted. phenyldisuffide, substituted phenylurea, substituted Cl 6 aikylamine, substituted phenylamine, substituted phenylthiourea, substituted C,-,alkylurea or substituted C 1 .6alkylthiourea wherein the substitutents; are selected from the group consisting of C 1 ,alkyl, ha~oC 1 -6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile where 00 d is 0-8; R 1 3 is thioC 1 -,alkylcarbonyl, C, 1 6alkyl, substituted C 1 -,alkyl where the alkyl substituents are selected from one or more members of the group consisting of C, 1 ,alkyl, halo C 1 ~alkyI, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, Cl 1 ,alkyldisulfide, Cl~alkylsulfide, phenyldisulfide, urea, C 16 ,alkylurea, phenylurea, thiourea, C 1 -,alkylthiourea, phenylthiourea, substituted C 16 ,alkyldisulfide, substituted phenyldisulfide, substituted C 14 6alkylurea, substituted phenytu rea, substituted C 1 -6al kylthiou rea or substituted phenylthiourea wherein the C 1 -,alkyldisulfide, phenyldisulfide, C 1 -,alkylurea, C 14 ,alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 1 -6alkyl, haloC 1 .,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; -(GR34R 35 )q-(CH R 36 )mS 3 H where R34, R 3 5 and R 3 Mare independently selected from the group consisting of hydrogen, halogen, hydroxyl, and Cl 1 ,alkyl, q is 1-6, and m is 0-6; 2 2 )XNH-C(O)CR 37 CH 2 where R" 7 is hydrogen or C 1 -6alkyl, 00 n is 1-6, and x is 1-6; RwR 3 9 )t-(CH R 40 H) 2 where R 38 R31, and R" 0 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and C,,alkyl, is 1-6, and u is 0-6; phenyl; benzyl; pyridinyl; pyrimidinyl; pyrazinyl; benzimidazolyl; benzothiazolyl; benzotriazolyl; naphthaloyl; quinolinyl; indolyl; thiadiazolyl; triazolyl; 4-methylpiperidin-1 -yl; 4-methylpiperazin- I -yl; substituted phenyl; substituted benzyl; substituted pyridinyl; N substituted pyrimidinyl; substituted pyrazinyl; substituted benzimidazolyl; substituted benzothiazolyl; substituted benzotriazolyl; 00 substituted naphthaloyl; substituted quinolinyl; substituted indolyl; substituted thiadiazoly]; substituted triazolyl; substituted 4-methylpiperidin-1 -yl; or substituted 4-methylpiperazin-1 -yi, wherein the substituents are selected from one or more members of the group consisting of C 1 -,alkyl, haloCl- 6 alkyl, halogen, sulfonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amidine, N-(2-aminopyrimidine)sulfonyl, N-(aminopyridine)sulfonyl, N-(aminopyrazine)sulfonyl, N-(2-aminopyrimidine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carbonyl, N-(2-aminopyrimid ine)phosphonyl, N-(2-aminopyridine)phosphonyl, N-(aminopyrazine)phosphonyl, N-(a mi nobenzi mid azoyl)s ulfonyl, N-(aminobenzothiazolyl)sulfonyl, N-(aminobenzotriazoyl )sulfonyl, N-(aminoindolyl)sulfonyl, N-(aminothiazoiyl)sulfonyl, N-(aminctriazolyl)sulfonyl, N-(amino-.4-methylpiperidinyl)sulfonyl, N-(amino-4-methylpiperazinyl)sulfonyl, N-(ami nobenzi mid azolyl)ca rbonyl, N-(aminobenzothiazolyl)carbonyl, N-(aminobenzotriazolyl)carbonyl, N-(aminoindolyl)carbonyl, N-(aminothiazolyl)carbonyl, N-(aminotriazolyl)carbonyl, N-(amino-4-methylpiperidinyl)carboriyl, 00 N-(amino-4-methylpiperazinyl)carbonyl, N min obe nzi mid azolyl)phos phonyl, N-(2-aminobenzothiazolyl)phosphonyl, N-(2-aminobenzotriazoiyl)phosphonyl, N-(2-aminoindolyl)phosphonyl, N-(2-aminothiazolyl)phosphonyl, N-(2-aminotriazolyl)phosphonyl, N-(amino-4-methylpiperidinyl) phosphonyl, N-(amino-4-methylpiperazinyl) phosphonyl, acetamide, nitrile, thiol, C,-,alkyldisulfide, Cl 1 ,alkylsulfide, phenyl disulfide, urea, C,,alk ylurea, phenylurea, thiourea, CI-6alkylthiourea, phenylthiourea, substituted CI- 8 alkyldisulfide, substituted phenyldisulfide, substituted Cl-6alkylurea, substituted C 14 ,alkylthiourea, substituted phenylurea, and substituted phenylthiourea wherein the C 14 6alkyldisulfide, phenyldisulfide, Cl 1 ,alkylurea, Cl 1 .alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 1 0 6alkyI, haloC 14 6alkyI, halogen, hydroxyl, carboxylic acid, suifonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; W' 1 is hydrogen, C, 1 6alkyl, phenyl, Cl 1 ,alkylcarbonyl, phenylcarbonyl, substituted C 1 -6alkyl, substituted phenyl, substituted C 1 -,alkylcarbonyl or substituted phenylcarbonyl, wherein o the substituents are selected from the group consisting of C, 4 alkyl, haloC, 1 alkyl, halogen, hydroxyl, carboxylic acid, Ssulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile. where the method comprises the steps of oO I0 preparing a lens comprising a monomer of Formula I, II, III or IV and S(b) treating said lens with a silver solution.
37. 56. The method of claim 55 wherein the silver solution is aqueous silver nitrate having a concentration of about 0.1 pg/mL to about .3 g/mL.
38. 57. The method of claim 55 wherein, treating comprises soaking the lens comprising a polymer of a monomer of Formula I, II, III or IV with a silver solution.
39. 58. The method of claim 55 wherein, the lens comprising a polymer of a monomer of Formula I, II, III or IV is soaking for about 2 minutes to about 2 hours.
40. 59. The method of claim 55 wherein, treating comprises storing the lens comprising a polymer of a monomer of Formula I, II, III or IV with a silver solution for about 20 minutes to about 5 years. An antimicrobial lens comprising silver and a polymer comprising a binding monomer wherein said antimicrobial lens can reversibly bind silver.
41. 61. The antimicrobial lens of claim 60 wherein the binding monomer has a stability constant of about 2 to about 7.3.
42. 62. A lens case comprising siliver and a polymer comprising a monomer of Formula 1, 11, 111 or IV RI R 1 2 0a II 0 R 32 AN .(HW 141 R IV wherein R' is hydrogen or Cl 14 alkyI; Ris -OR -NH-R 3 -S-(CH 2 )d-R',or -(CH 2 )d-R wherein d is 0-8; R 3 is substituted Cl,alkyl where the alkyl substituents are selected from one or more members of the group consisting of carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, Cl 14 alkyldisuifide, Cealkylsulflde, phenyld isulfide, urea, 0 1 6 alkylurea, phenylurea, th iourea, Cl 1 ,alkylthiourea,,phenylthiourea, substituted C, _al kyld isul[fide, substituted phenyldisulfide, substituted C 16 alkylurea, substituted phenylurea, substituted G 16 alkylthiourea, and substituted phenylthiourea wherein the Cl. 6 alkyldisulfide, phenyldisulfide, C,- 6 alkylurea, Cl-,alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the N group consisting of C 1 ~alkyl, haloC,-,,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; -(CR R 5 9)q(CHR 6 )m,,SOH wherein and R 6 are independently selected from 00 the group consisting of hydrogen, halogen, hydroxyl, and C 16 alkyl, q is 1-6, and m is 0-6; -(CH 2 )n-S-S-(CH 2 H-C(O)CR 7CH 2 wherein R' is hydrogen or C 1 -6alkyl, n is 1-6, and x is 1-6; -(CR 8 R 9 0 2 wherein and R" 0 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and C 1 -6alkyl, t is 1-6, and u is 0-6;, phenyl; benzyl; pyridinyl; pyrimidinyl; pyrazinyl: benzimidazolyl: benzothiazolyl; benzotriazolyl; naphthaloyl; quinolinyl; indolyl; th iad iazolyl; c-i triazolyl; 0 4-methylpiperidin-1 -yl; 4-methylpiperazin-1 -yl; substituted phenyl; substituted benzyl; 00 substituted pyrid inyl; substituted pyrimidinyl; substituted pyrazinyl; 1 0s b ti u e b n i id z l l substituted benzimidazolyl; substituted benzothiazolyr; substituted naphthaloyl; substituted quinolinyl; substituted indolyl; substituted thiadiazolyl; substituted triazolyl; substituted 4-methylpiperidin-1 -yl; or substituted 4-methyl pipe razi n-1 -yl, wherein the substituents are selected from one or more members of the group consisting of Cl 14 alkyl, haloC 14 ,alkyl, halogen, sulfonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amidine, N-(2-aminopyrimid ine)sulfonyl, 215 N-(aminopyridine)sulfonyl, N-(aminopyrazine)sulfonyl, N-(2-aminopyrimidine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carbonyl, N-(2-aminopyrimidine)phosphonyl, N-(2-aminopyridine)phosphonyl, N-(aminopyrazine)phosphonyl, N-(aminobenzimidazolyl)sulfony, N-(aminobenzothiazolyl)sulfony, o N-(aminobenzotriazolyl)sulfonyl, N-(aminoindolyl)sulforiyl, N-(aminothiazolyl)sulfonyl, N-(aminotriazolyl)sulfonyl, N-(amino-4-methyl piperidinyl)sulfonyl, 00 N-(amino-4-methyipiperazinyl)sufonyl, N-(aminobenzimidazolyl)carbonyl, N-(aminobenzothiazolyl)carbonyl, N-(aminobenzotriazoyl)carbonyl, N-(aminoindolyl)carbonyl, N-(aminothiazolyl)carbonyl, N-(aminotriazoly[)carbonyl, N-(amino-4-methylpiperidinyl)carbonyl, N-(amino-4-methylpiperazinyi)carbonyl, N-(2-a mino be nzi mid azolyl) phosph onyl, N-(2-aminobenzothiazolyl)phosphonyl, N-(2-aminobenzotriazolyl)phosphonyl, N-(2-aminoindolyl)phosphonyl, N-(2-aminothiazolyl)phosphonyl, N-(2-aminotriazolyl)phosphonyl, N-(amino-4-methylpipeicinyl) phosphonyl, N-(amino-4-methylpiperazinyl) phosphonyl, acetamide, nitrile, thiol, C 1 -6alkyldisuffide, Cl 4 alkylsulfide, phenyl disulfide, urea, C,,alkylurea, phenylurea, thiourea, C, 14 alkylthiou rea, phenylthiou rea, substituted C, 1 ,alkyldisulfide, substituted phenyldisulfide, substituted Cl,alkylurea, substituted Cl~alkylthiourea, substituted phenylurea, and substituted phenylthiourea wherein the Cj 14 alkyldisulfide, phenyldisulfide, Cl-6alkylurea, C 1 6 alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 1 ~alkyl, haloC 1 .,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic U acid, amine, amidine, acetamide, and nitrile; a is R" 1 is hydrogen or C 1 -,alkyl; R 12 is hydroxyl, sulfonic acid, phosphonic acid, carboxylic acid, 00 ~acetamide, thioC,. 6 aikylcarbonyl, Cl-6alkyldisulfide, Cl-6alkylsulflde, phenyl disulfide, urea, Cl 1 ,alkylurea, phenylurea, thiourea, Cl 1 ,alkylthiourea, phenylthiourea, -OR" 3 -NH-R' 3 -S-(CH 2 )d-R 13 -(CH 2 )d-R 13 -C(O)NH-(CH 2 )d-R -(CH 2 )d-R 13 substituted Cl-,alkyldisulfide, substituted phenyldisulfide, substituted C 14 ,alkylu rea, substituted phenylurea, substituted phenylthiourea or substituted 0 1 6 alkylthiourea wherein the substituents are selected from the group consisting of C 1 _6alkyl, haloC 1 .6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; where d is 0-8; R 13 is thioC 1 -6alkylcarbonyl; substituted Cl 14 alkyl where the alkyl substituents are selected from one or more members of the group consisting of hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, Cl 1 ,alkyldisulfide, Ci 1 ,alkylsulfide, phenyldisulfide, urea, C 1 _6alkylurea, phenylurea, thiourea, C, 1 ,alkylthiourea, phenylthiourea, substituted C 1 -6alkyld isulfide, substituted phenyldisulfide, substituted Cl-6alkylurea, substituted phenylurea, substituted C 1 -,alkylthiourea and substituted phenylthiourea wherein the Cl-6alkyldisulfide, phenyldisulfide, C 1 6 alkylurea, Cl.6alkylthiourea, phenyiurea, and phenylthiourea substituents are selected from the group consisting of Cl 10 alkyi, haloC, 1 6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; IND 14R 5 )q-(CH R' 6 )mS0 3 H where R 1 4 and R 1 6 are independently selected 00 from the group consisting of hydrogen, halogen, hydroxyl, and Cl.,alkyl, q is 1-6, and C~1 m is 0-6; -(CH 2 )I-S-S-(CH 2 ),NH-C(O)CR 17 CH 2 CIwhere R 17 is hydrogen or C, 14 alkyl, n is 1-6, and x is 1-6; -(CR 1 8 R 19 )t-(CHR 2 0 2 where R 1 8 R 1 9 and R 2 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and Cl 14 alkyl, t is 1-6, and u is 0-6; phenyl; benzyl; pyridinyl; pyrimidinyl; pyrazinyl; benzimidazolyl: benzothiazolyl; benzotriazolyl; naphthaloyl; quinolinyl; indolyl; thiadiazolyl; triazolyl; o 4-methylpiperidin-1 -yl; 4-methylpiperazin-1 -yI; IND substituted phenyl; substituted benzyl; 00 substituted pyridinyl; s u s i ue0 0r m d n l substituted pyrimiinyl; substituted pyrazinyal; l 0 10 substituted benzimidazolyl; substituted benzothiazofyl; substituted naphthaloyl; substituted quinolinyl; substituted indolyl; substituted thiadiazolyl; substituted triazolyl; substituted 4-methylpiperidin-1 -yi; or substituted 4-methylpiperazin- 1-yl wherein the substituents are selected from one or more members of the group consisting of C, 14 alkyl, haloC 14 alkyI, halogen, sulfonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amidine, N-(2-aminopyrimidine)sulfonyl, N-(aminopyridine)sulfonyl, N-(aminopyrazine)sulfonyl, N-(2-aminopyrimidine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carbonyl, N-(2-aminopyrimid ine)phosphonyl, N-(2-aminopyridine)phosphonyl, N-(aminopyrazine)phosphonyl, N-(aminobenzimidazolyl)sufonyl, N-(aminobenzothiazolyl)sulfonyl, N-(aminobenzotriazolyl)sufonyl, N-(aminoindolyl)sulfonyl, N-(aminothiazolyl)sulfony, N-(aminotriazolyl)su Ifonyi, IND N-(amino-4-methylpiperidinyl)sulfonyl, N-(amino-4-methylpiperazinyl)sulfonyl, N-(aminobenzimidazolyl)carbonyl, 00 tfl N-(aminobenzothiazolyl)carbonyl, N-(aminobenzotriazolyl)carbonyl, N-(aminoindolyl)carbonyl, N-(aminothiazolyl)carbonyl, 0 10 N-(aminotriazolyl)carbonyl, N N-(amino-4-methylpiperazinyl)carbonyl, N-(2aminob-ezyimidaziy)hosponyl, N-(2-aminobenzothiazoly)phosphonyl, N-(2-aminobenzotriazolyl)phosphonyl, ~N-(2-aminoinoaolyl)phosphonyl, N-(2-aminotiaolyl)phosphonyl, N-(2-aminotriazolyl )phosphonyl, N-(2aminot-methylphperinyl hshn, ~~N-(amino-4-methylpiperazinyl) phosphonyl, aeaie nitrile, thiol, Cl 14 alkyldisulfide, C,,alkylsulflde, phenyl disulfide, urea, C 1 -,alkylurea, phenylurea, thiourea, C 1 .,alkylthiourea, phenylthiourea, substituted Cl 1 6alkyldisulfide, substituted phenyldisulfide, substituted C 1 -,alkylurea, substituted C 14 ,alkylthiourea, substituted phenylurea, and substituted phenylthiourea wherein the C 1 -,alkyldisulfide, phenyldisulfide, Cl-6alkylurea, C 1 ,alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 1 -,alkyl, haloC,,alkyI, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; b is p is R" 1 is hydrogen; R" 2 is hydroxyl, suifonic acid, phosphonic acid, carboxylic acid, thioC, 1 ,alkylcarbonyI, thioC 16 alkylaminocarbonyl, Cl. 6 alkyldisulfide, phenyldisulfide, -C(O)NH(CH 2 1 -SO 3 H, -C(O)N H(CH 2 1 2 -OR 23 -NH-R -C (O)NH-(CH 2 )d-R23' -S-(CH 2 )d-R23, -(CH 2 )d-R 3 urea, C 1 6 ,alkylurea, phenylurea, thiourea, C 1 lalkylthiourea, phenylthiourea, substituted C,. 6 alkyidisulfide, substituted phenyldisuifide, substituted C 1 .,alkyiu rea, substituted, Cl, alkylthiou rea substituted phenylu rea or substituted phenylthiourea wherein the substituents are selected from the group consisting of C,.,alkyl, haioC,-6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrite, where d is 0-8; R 23 is thioC,.6alkyicarbonyl, C 1 8 alkyi, substituted C 1 .6alkyl where the alkyl substituents are selected from one or more members of the group consisting of Cl 14 alkyI, halo C,,afkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, C 1 -6alkyldisulfide, Cl,,alkylsulfide, phenyidisuifide, urea, C 1 _,alkylurea, phenyiurea, thiourea, C, 14 alkylthiourea, phenylthiourea, substituted Cl 1 ,alkyldisulfide, substituted phenyldisulfide, substituted Cl.,alkylurea, substituted phenylurea, substituted Cl-6alkylthiourea, and substituted phenylth iou rea wherein the Cl-6alkyldisulfide, phenyldisulfide, C,,aikylurea, C, 1 6alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the IND group consisting of C 14 6alkyl, haloCj 1 ,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic 00 acid, amine, amidine, acetamide, and nitrile; -(CR 2 4 R 25 )q(CHR 2 0)MSO 3 H where R 2 1, R 2 1, and R 2 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and Cl 1 ,alkyl, CI q is 1-6, and m is 0-6 -(CH 2 )1,-S-S-(CH 2 H-C(O)0R 2 7 CH 2 where R 27 is hydrogen or C 1 ,alkyl, n isl1-6, and x is 1-6; -(CR 2 B R29),-(CHR 30 2 where R 28 R 2 1, and R 30 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and Cl 14 alkyl, t is 1-6, and u is 0-6; phenyl; benzyl; pyridinyl; pyrimidinyl; pyrazinyl; benzimidazolyl; benzothiazolyl; benzotriazolyl; naphthaloyl; quinolinyi; indolyl; thiadiazolyl; IND triazolyl; 4-methylpiperidin-1 -yI; 00 4-methylpiperazin-1 -yI; In substituted phenyl; substituted benzyl; ri substituted pyridinyl; substituted pyrimidinyl; N substituted pyrazinyl; substituted benzimidazolyl; substituted benzothiazolyl; substituted benzotriazolyl; substituted naphthaloyl; substituted quinolinyl; substituted indolyl; substituted thiadiazolyl; substituted triazolyl; substituted 4-methylpiperidin-1 -yI; or substituted 4-methylpi perazin-1 -yl, wherein the substituents are selected from one or more members of the group consisting of C 1 -,alkyl, haloC, 14 alkyl, halogen, sulfonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amidine, N-(2-aminopyrimidine)sulfonyl, N-(aminopyridine)sulfonyl, N-(aminopyrazine)sulfonyl, N-(2-aminopyrimidine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carbonyl, N-(2-aminopyrimidine)phosphonyl, N-(2-aminopyridine)phosphonyl, 103 N-(aminopyrazine)phosphonyl, o N-(aminobenzimidazolyl)sulfonyl, N-(amiriobenzothiazolyl)sulfonyl, IND N-(aminobenzotriazolyl)sulfonyl, N-(aminoindolyisulfonyi, N-(aminothiazolyl)sulfonyl, 00 N-(aminotriazolyl)sulfonyl, InN-(ami no-4-methyl pipe rid inyl)suIfo nyl, N-(amino-4-methylpiperazinyl)sulfonyl, c-i N-(aminobenzimidazolyl)carbonyl, N-(aminobenzothiazolyl)carbonyl, ci N-(aminobenzotriazolyl)carbonyl, N-(aminoindolyl)carbonyl, N-(aminothiazolyl)carbonyl, N-(aminotriazolyl)carbonyl, N-(amino-4-methylpiperidinyl)carbonyl, N-(amino-4-methylpiperazinyl)carbonyl, N-(2-a min obenzimid azolyt)phosphonyl, N-(2-aminobenzothiazolyl)phosphony N-(2-aminobenzotriazolyl)phosphonyl, N-(2-aminoindolyl)phosphonyl, N-(2-aminothiazolyl)phosphonyl, N-(2-aminotriazolyl)phosphonyl, N-(amino-4-methylpiperidinyl) phosphonyl, N-(amino-4-methylpiperazinyl) phosphonyl, acetamide, nitTile, thiol, C 10 ,alkyldisulfide, Cl 1 ,alkylsulfide, phenyl disulfide, urea, C 14 ,alkylurea, phenylurea, thiourea, C 1 -,alkylthiourea, phenylthiourea, substituted Cl. 6 alkyldisulfide, substituted p henyid isul[fide, substituted Cl-6alkylu rea, substituted Cl-6alkylthiourea, substituted phenylurea, and substituted phenylthiourea wherein the Cl-6alkyldisulfide, phenyldisulfide, Cl 1 ,aikylurea, C,-,alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C, 1 6alkyl, haloC,-,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; W isO0-1; 00 Y is oxygen or sulfur; R 3 1 is hydrogen or Cl.,alkyl; R 32 is hydroxyl, sulfonic acid, phosphonic acid, carboxylic acid, NthioC 1 .,alkylcarbonyl, thioC,-6alkylaminocarbonyl, -C(O)N H-(CH 2 )d -R 3 3 010 -0-R33, -NH-R 3 -S-(CH 2 )d -R 33 -(CH 2 )d -R 3 3 Cl-6alkyldisulfide, N1 phenyldisulfide, urea, C, 14 alkylurea, phenylurea, thiourea, Cl-6alkylthiourea, phenylthiourea, Cl 1 ,alkylamine, phenylamine, substituted Cl 1 ,alkyldisulfide, substituted phenyldisulfide, substituted phenylurea, substituted C 1 -,alkylamine, substituted phenylamine, substituted phenylthiourea, substituted Cl 14 alkylu rea or substituted C 14 6alkylthiourea wherein the substitutents are selected from the group consisting of Cl 14 alkyl, haloC,.6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile where d is 0-8; R-"is thioC,. 6 alkylcarbonyl, Cl.,alkyl, substituted C 14 ,alkyI where the alkyl substituents, are selected from one or more members of the group consisting of Cl 1 ,alkyl, halo C,,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, Cl. 6 alkyldisulfide, C 1 -,alkylsulfide, phenyldisulfide, urea, C 16 ,alkylurea, phenylurea, thiourea, C,. 6 alkylthiourea, phenylthiourea, substituted C 16 ,alkyldisulfide, substituted phenyldisulfide, substituted C 10 alkylurea, substituted phenylurea, substituted C 1 -6alkylth iou rea or substituted IND phenylthiourea wherein the Cl-6alkyldisulfide, phenyldisulfide, 00 C 1 -6alkylurea, Cl- 6 alkylthiourea, phenylurea, and In phenylthiourea substituents are selected from the group consisting of Cl 1 ,alkyl, haloC 1 .,alkyI, N- halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and c-I nitrite; -(GR34R 35 36 )m'_SO 3 H where R" 5 and R" 6 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and C,.6alkyl, q is 1-6, and m isQ0-6; -(CH 2 2 ).,NH-C(O)CR 37 CH 2 where R 37 is hydrogen or C, 14 alkyl, n is 1-6, and x is 1-6; -(CR 38 R 3 9 H R 40 )2 where R" 8 R3', and R 4 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and Cl.,alkyl, t is 1-6, and u is 0-6; phenyl; benzyl; pyridinyl; pyrimidinyl; pyrazinyl; o benzimidazolyl; benzothiazolyl; IND benzotriazolyl; naphthaloyl; 00 quinolinyl; indolyl; thiadiazolyl; triazolyl; 4-methylpiperidin-1 -yl; Cl 4-methylpiperazin-1 -yl; substituted phenyl; substituted benzyf; substituted pyridinyl; substituted pyrimidinyl; substituted pyrazinyl; substituted benzimidazolyl; substituted benzothiazolyl; substituted benzotriazoyt; substituted naphthaloyl; substituted quinolinyl; substituted indolyl; substituted thiadiazolyl; substituted triazolyl; substituted 4-methylpiperidin-1-yl; or substituted 4-m ethyl piperazin- 1 -yI, wherein the substituents are selected from one or more members of the group consisting of C 1 -6alkyl, haloC 1 -,alkyl, halogen, sulfonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amidine, N-(2-aminopyd mid ine)sulfo nyl, 107 N-(aminopyridine)sulfonyl, N-(arninopyrazine)sulfonyl, U N-(2-aminopyrimidine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carbonyl, IND N-(2-amiriopyrimidine)phosphony, N-(2-a m ino pyrid ine)phos phony[, 00 N-(aminopyrazine)phosphonyl, N-(aminobenzimidazolyl)sulfonyl, N-(aminobenzothiazolyl )sulfonyl, N-(aminobenzotriazolyl)sulfonyl, N-(aminoindolyl)sulfonyl, N-(aminothiazolylsulfonyI, N-(aminotriazolyl)sulfonyl, N-(a mino-4-methyl pipe rid in yl)s u fonyl, N-(amino-4-methyl piperazinyl)sulfonyi, N-(aminobenzimidazolyl)carbonyl, N*-(aminobenzothiazolyl)carbonyl, N-(aminobenzotriazolyl)carbonyl, N-(aminoindolyl)carbonyl, N-(aminothiazolyl)carbonyl, N-(aminotriazolyt)carbonyl, N-(a mino-4-methylpiperidinyI)carbonyl, N-(amino-4-methyl piperazinyl)carbonyl, N-(2-aminobenzimidazolyl)phosphonyl, N-(2-aminobenzothiazolyl)phosphonyl, N-(2-aminobenzotriazolyl)phosphonyl, N-(2-aminoindolyl)phosphonyl, N-(2-aminothiazolyl)phosphonyl, N-(2-aminotriazolyl)phosphonyl, N-(amino-4-methylpiperidinyl) phosphonyl, N-(amino-4-methylpiperazinyl) phosphonyl, acetamide, nitrile, thiol, Cl 1 ,alkyld isulfide, C,,alkyisulfide, phenyl disulfide, urea, C 16 a1 kylurea, phenylurea, thiourea, C,.6alkylthicurea, phenylthiourea, substituted C,.alkyldisulfide, substituted phenyldisulfide, substituted C 1 -6alkylurea, substituted Cl 14 alkylthiourea, substituted phenylurea, and substituted phenylthiourea IND wherein the Cl.6alkyldisulfide, phenyldisulfide, C 1 .,aikylurea, C 1 .akylthiourea, phenylurea, and 00 phenylthiourea substituents are selected from the group consisting of C 1 -6alkyl, haloC 1 -,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic C1 acid, amine, amidine, acetamide, and nitrile; R 41 is hydrogen, C 1 -6alkyl, phenyl, C 1 -6alkylcarbonyl, phenylcarbonyl, (Ni substituted Cl 1 ,alkyl, substituted phenyl, substituted C 16 alkylcarbonyl or substituted phenylcarbonyl, wherein the substituents are selected from the group consisting of C 1 -,alkyl, haloC 1 -,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile.
43. 63. A method of reducing the adverse effects associated with microbial production in the eye of a mammal comprising providing an antimicrobial lens, wherein said lens comprises, silver and a polymer comprising a monomer of the Formula 1, 11, 111 or IV II (R22) ~N R 32 N 109 wherein R' is hydrogen or Cl. 6 alkyl; R 2 is -OR 3 -NH-R 3 -S-(CH 2 )d-R 3 or -(CH 2 )d-R 3 wherein di is 0-8; R 3 is substituted C 1 _6alkyl where the alkyl substituents are selected from one or more members of the group consisting of carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, C,. 8 ,alkyldisulfide, Cl-6alkylsulfide, phenyldisulfide, urea, G 1 -,alkylurea, phenylurea, thiourea, Cl 1 ,alkylthiourea, phenylthiourea, substituted Cl,alkyldisulfide, substituted phenyldisulf'ide, substituted C,6alkylurea, substituted phenylurea, substituted Cl-6alkylthiourea, and substituted phenylthiourea wherein the Cl 1 ,alkyldisulfide, phenyldisulfide, C 1 _,alkylurea, C,. 6 alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 14 alkyl, haloC,,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; -(0R 4 R 5 )j-(CHR")mSO 3 H wherein R 4 and R" are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and C 1 ,alkyl, q is 1-6, and m is 0-6; -(CH 2 )n-S-S-(CH 2 ).NH-C(O )CR 7 CH 2 wherein R 7 is hydrogen or C 1 -6alkyl, 110 n is 1-6, and x is 1-6; -(CRBR 9 )t-(CH R 1 2 IND wherein and R'O are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and C,.akl t is 1-6, and u is 0-6; phenyl; benzyl; ri pyridinyl; pyrimidinyl; pyrazi nyl; benzimidazolyl; benzothiazolyl; benzotriazolyl; naphthaloyl; quinolinyl; indolyl; thiadiazolyl; triazolyl; 4-methylpiperidin-1 -yl; 4-methylpiperazin-1 -yl; substituted phenyl; substituted benzyl; substituted pyridinyl; substituted pyrimidinyl; substituted pyrazinyl; substituted benzimidazolyl; substituted benzothiazolyl; substituted benzotriazolyl; substituted naphthaloyl; substituted quinolinyl; substituted indolyl; IND substituted thiadiazolyl; substituted triazolyl; 00 substituted 4-methylpiperidii-1 -yI; or substituted 4-methylpiperazini-1 -yl, wherein the substituents are selected from one or more CI members of the group consisting of C 1 .,alkyl, haloC 16 ,alkyl, halogen, sulfonic acid, phosphonic acid, C1 hydroxyl, carboxylic acid, amine, amnidine, N-(2-aminopyrimid ine)sulfonyl, N-(aminopyridine)sulfonyl, N-(aminopyrazine)sulfonyl, N-(2-aminopyrimidine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carbonyl, N-(2-aminopyrimidine)phosphonyl, N-(2-aminopyridine)phosphonyl, N-(aminopyrazine)phosphonyl, N-(aminobenzimidazoly)sulfonyl, N-(aminobenzothiazolyl)sulfonyl, N-(aminobenzotriazolyl)sulfonyl, N-(aminoindolyl)sulfonyl, N-(aminothiazolyl)sulfonyl, N-(aminotriazolyl)sutfonyl, N-(a mino-4-methyl pipe rid inyl)sulfon yl, N-(amino-4-methylpiperazinyl)sulfonyl, N-(aminobenzimidazolyl)carbonyl, N-(aminobenzothiazoyl)carbonyl, N-(a min obe nzotriazolyl)ca rbonyl, N-(aminoindolyl)carbonyl, N-(aminothiazoiyl)carbonyl, N-(aminotriazolyl)carbonyl, N-(amino-4-methylpiperidinyl)carbonyl, N-(amino-4-methyipiperazinyl )carbonyl, N-(2-aminobenzimidazolyl)phosphonyl, N-(2-aminobenzothiazolyl)phosphonyl, IND min obenzotriazo lyl)phosph onyl, N-(2-aminoindolyl)phosphonyl, 00 N-(2-aminothiazolyl)phosphony(, N-(2-aminotriazolyl)phosphonyl, 5N-(amino-4-methyl pipe rid inyl) phosphonyl, N-(amino-4-methylpiperazinyl) phosphonyl, acetamide, C)o1 nitrile, thiol, Cl-6alkyldisulfide, Cl 1 ,alkylsulfide, phenyl c-i disulfide, urea, Cl-6alkylurea, phenylurea, thiourea, Cl.,alkylthiourea, phenylthiourea, substituted Cl-6alkyldisulfide, substituted phenyldisuifide, substituted C 14 ,alkylurea, substituted C 14 ,alkylthiourea, substituted phenylurea, and substituted phenylthiourea wherein the Cl-6alkyldisulfide, phenyldisulfide, Cl-6alkylurea, Cl 1 ,alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 1 -6alkyI, haloCl-6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; a is R 1 1 is hydrogen or Cj 1 ,alkyl; R 12 is hydroxyl, sulfonic acid, phosphonic: acid, carboxylic acid, acetamide, thioC,,alkylcarbonyl, C 14 6alkyldisulfide, C 16 alkylsulfide, phenyl disulfide, urea, C 14 6alkylurea, phenylurea, thiourea, Cl~alkylthiourea, phen~,lthiourea, -OR 13 -NH-R1 3 -S-(0H 2 )d-R 13 -(CH 2 )d-R 13 -C(O)NH--(CH 2 )d-R -(CH 2 )d-R 13 substituted C, 1 6alkyldisulfide, substituted phenyldisulfide, substituted C 1 -,alkylurea, substituted phenylurea, substituted phenylthiourea or substituted C 1 .6alkylthiourea wherein the substituents are selected from the group consisting of C 1 ,,alkyl, haloC,.6alkyI, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; where d is 0-8; R 13 is thioC 1 6 alkylcarbonyl; substituted C 16 alkyl 00 where the alkyl substituents are selected from one or more members of the group consisting of hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, C 1 -,alkyldisulfide, Cl.,alkylsulfide, phenyldisulfide, urea, C 1 -6alkylurea, phenylurea, thiou rea, Cl 1 ,alkylthiourea, phenylthiourea, substituted Cl 1 ,alkyldisulfide, substituted phenyldisutfide, substituted C 1 -,alkylurea, substituted phenylurea, substituted C 1 -6alkylthiourea and substituted phenylthiourea wherein the C 1 -6alkyldisulfide, phenyldisulfide, C 1 .,alkylurea, C 1 6 alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 1 .6alkyl, haloC 14 6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; -(CR 14 R1 6 )q(CHR 16 ),SO 3 H where R 14 R 15 and are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and C,,alkyl, q is 1-6, and m is 0-6; -(CH 2 )n-S-S-(CH 2 )XNH-C(O)CR 17 CH 2 where R 17 is hydrogen or C 1 -,alkyI, n is 1-6, and x is 1-6; CKI -(CR 18 R 19 )i-(CHR 20 2 where R" 8 R" 9 and R" 0 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and Cl-,alkyI, t is 1-6, and 00 u is 0-6; phenyl; benzyl; pyridinyl; pyrimidinyl; pyrazinyl; benzimidazolyl; benzothiazolyl; benzotriazolyl; naphthaloyl; quinolinyl; indolyl; thiadiazolyl; triazolyl; 4-methylpiperid in-i -yl; 4-methylpiperazin-1 -yl; substituted phenyl; substituted benzyl; substituted pyridinyl; substituted pyrimidinyl; substituted pyrazinyl; substituted benzimidazolyl; substituted benzothiazolyl; substituted benzotriazoly; substituted naphthaloyl; substituted quinolinyl; susittd noil substituted tidiolyl; INDsubstituted thiiazolyl; ~~~substituted triazolylieii-1y;o substituted 4-methylpiperdin-1-yi;o susiue04mtyppeai- y wherein the substituents are selected fo n rmr members of the group consisting of Cl 1 ,alkyl, haloC 16 ,alkyI, halogen, suifonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amidine, N N-(2-aminopyrimidine)sulfonyl, N-(aminopyridine)sulfonyl, N-(aminopyrazine)sulfonyl, N-(2-aminopyrimidine)carbonyl, N-(aminopyridirne)carbonyl, N-(aminopyrazine)carbonyl, N-(2-aminopyrimidine)phosphonyl, N-(2-aminopyridine)phosphonyl, N-(aminopyrazine)phosphonyl, N-(aminobenzimidazoiyI)sufony, N-(aminobenzothiazolyl)sulfonyl, N-(aminobenzotriazolyl)sulfonyl, N-(aminoindolyi)sulfonyl, N-(aminothiazolyl)sulfonyl, N-(aminotriazolyl)sulfonyl, N-(amino-4-methylpiperidinyl)sulfonyl, N-(amino-4-methylpiperazinyl)sulfonyl, N-(aminobenzimidazolyl)carbonyl, N-(aminobenzothiazolyl)carbonyl, N-(aminobenzotriazolyl )carbonyl, N-(aminoindolyl)carbonyl, N-(aminothiazolyl)carbonyl, N-(aminotriazolyl)carbonyl, N-(amino-4-methylpiperid inyl)carbonyl, N-(amino-4-methyipiperazinyl)carbonyl, 116 N-(2-aminobenzimidazolyl)phosphonyl, N-(2-aminobenzothiazolyl)phosphonyl, N-(2-aminobenzotriazolyl)phos phony), IND N-(2-aminoindolyl)phosphonyl, N-(2-aminothiazolyl)phosphonyl, 00 N-(2-aminotriazolyl)phosphonyl, N-(amino-4-methylpiperidinyl) phosphonyl, m ino-4-meth yipipe razi nyl) phosphonyl, acetamide, nitrile, thiol, Cl.alkyldisulfide, Cl 1 ,alkylsulfide, phenyl disulfide, urea, Cl 1 ,alkylurea, phenylurea, thiourea, Cl 1 ,alkylthiourea, phenyithiourea, substituted CI-6alkyldisulfide, substituted phenyldisulfide, substituted 0 1 .,alkylurea, substituted Cl. 6 ,alkylthiourea, substituted phenylurea, and substituted phenylthiourea wherein the Cl 1 ,alkyldisulfide, phenylclisulfide, C 14 ,alkylurea, C 1 -,alkylthiou rea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 14 ,alkyl, haloC,.6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; b is p is R 2 1 is hydrogen; R' is hydroxyl, sulfonic acid, phosphonic acid, carboxylic acid,/ thioC 1 6 alkyicarbonyl, thioC 1 -,alkylaminocarbonyl, Cl. 6 alkyldisulfide, phenyldisulfide, -C(O)NH(CH 2 16 -SO 3 H, 2 -OR 23 -NH-R 2 -C (O)NH-(CH 2 )d-R 23 -S-(CH)d-R 2 3 -(CH 2 )d-R 2 urea, Cl 1 ,alkylurea, phenylurea, thiourea, Cl 1 ,alkylthiourea, phenylthiourea, substituted Cl 1 ,alkytdisulfide, substituted phenyldisulfide, substituted C,-alkylurea, substituted, C 1 -6alkylthiou rea substituted phenylurea or substituted phenylthiourea wherein the substituents are selected from the group consisting of C,. 6 alkyl, haloC, 18 alkyl, halogen, hydroxyl, carboxylic acid, suifonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile, where d is 0-8; R" 3 is thioC 1 alkylcarbonyl, C,,al kyl, substituted C 1 .,alkyl where the alkyl substituents are selected from one or more members of the group consisting of C 1 -6alkyl, halo C,6alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrite, thiol, C,.,alkyldisulfide, C, 1 ,alkylsulflde, phenyldisulfide, urea, C,,alkylurea, phenylurea, thiourea, C 18 alkylthiourea, phenylthiourea, substituted C, 1 6alkyldisulfide, substituted phenyldisulfide, substituted C 14 6alkylurea, substituted phenylurea, substituted C 1 -,alkylthiourea, and substituted phenylthiourea wherein the C 14 ,alkyldisulfide, phenyldisulfide, C, 1 ,alkylurea, C,.6alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 1 ~alkyl, haloC,,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; -(CR 24 R 25 )q(CH R 26 )mSOH where R 2 1, R 2 1, and R 2 6 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and C 16 alkyl, q is 1-6, and M is 0-6 -(CH 2 2 H-C(O)CR 27 CH 2 1 where R 2 1 is hydrogen or C,a(kyl, n is 1-6, and x is 1-6; -(CR 28 R 29 )-(CHR 3 0 2 where R 2 1, R 2 1, and R 30 are independently selected 00 from the group consisting of hydrogen, halogen, hydroxyl, and C 1 -,alkyl, t is 1-6, and uis 0-6; phenyl; benzyl; pyridinyi; pyrimidinyl; pyrazinyl;, benzimidazolyl; benzothiazolyl; benzotriazolyl; naphthaloyi; quinolinyl; indolyl; thiadiazolyl; triazolyl; 4-methylpiperdin-1 -yI; 4-methylpiperazin-1 -yl; substituted phenyl; substituted benzyl; substituted pyridinyl; substituted pyrimidinyL; substituted pyrazinyl; substituted benzimidazolyl; 119 substituted benzothiazolyl; N substituted benzotriazolyl; substituted naphthaloyl; substituted quinolinyl; substituted indolyl; substituted thiadiazolyl; 00 substituted triazolyl; substituted 4-methylpiperidin-1 -yl; or substituted 4-methylpiperazin- 1-yl, wherein the substituents are selected from one or more members of the group consisting of CI. 6 alkyI, haloCl- 6 alkyl, halogen, sulfonic acid, phosphonic acid, hydroxyl, carboxylic acid, amine, amidine, N-(2-aminopyrimid ine)sulfonyl, N-(aminopyridine)sulfonyl, N-(aminopyrazine)sufonyl, N-(2-aminopyrimidine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carbonyl, N-(2-aminopyrimidine)phosphonyl, N-(2-aminopyridine)phosphonyt, N-(aminopyrazine)phosphonyl, N-(aminobenzimidazolyl)sulfonyl, N-(a min obenzoth iazolyl)sulfonyl, N-(aminobenzotriazolyl)sulfonyl, N-(aminoindolyl)sulfonyl, N-(aminothiazolyl)sulfonyl, N-(aminotriazolyl)sulfonyl, N-(amino-4-methylpiperidinyl)sulfonyl, N-(amino-4-methylpiperazinyl)sulfonyl, N-(aminobenzimidazolyl)carbonyl, N-(aminobenzothiazolyl)carbonyl,. N-(a min obenzotriazolyl)ca rbonyl, N-(aminoindolyl)carbonyl, N-(aminothiazolyl)carbonyl, 120 N-(aminotriazolyl)carbonyl, N-(amino-4-methylpiperidinyl)carbonyl, N mi no-4-m ethyl pi perazi nyl)carbonyl, N-(2-aminobenzimidazolyl )phosphonyl, N-(2-aminobenzothiazolyl)phosphonyl, N-(2-aminobenzotriazolyl)phosphonyl, 00 N-(2-aminoindolyl)phosphonyl, N-(2-aminothiazolyl)phosphonyl, N-(2-aminotriazolyl)phosphonyl, N-(amino-4-methylpiperidinyl) phosphonyl, N-(amino-4-methylpiperazinyl) phosphonyl, acetamide, nitrile, thiol, C 1 .,alkyldisulfide, C 1 -,alkylsulfide, phenyl disulfide, urea, C 1 6 alkylurea, phenylurea, thiourea, C 16 ,alkylthiou rea, phenylthiou rea, substituted C 14 ,alkytdisulfide, substituted phenyldisulfide, substituted C 1 -,alkylurea, substituted C 14 6alkylthiourea, substituted phenylurea, and substituted phenylthiourea wherein the Cl,,alkyldisulfide, phenyldisulfide, Cl 1 6 alkylurea, C 1 -,alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 1 -6alkyl, haloC 14 alkyl, halogen, hyd roxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; w isO0-1; Y is oxygen or sulfur; R 31 is hydrogen or C 1 ,,alkyl; R" 2 is hydroxyl, sulfonic acid, phosphonic acid, carboxylic acid, thioC,.,alkylcarbonyl, thioC,,alkylaminocarbonyl, -C(O)NH-(0H 2 )d -R 3 -0-R 33 -NH-R -S-(CH 2 )d -R33, -(CH 2 )d -R 33 Cl-6alkyldisulfide, phenyld isulfide, urea, C,,.alkylurea, phenylurea, thiourea, C 1 6 alkylthiourea, phenylthiourea, C 1 -6alkylamine, phenylarnine, substituted C 16 ,alkyldisulfide, substituted phenyldisulfide, substituted o phenylurea, substituted Cl-6alkylamine, substituted phenylamine, substituted phenylthiourea, substituted C, 1 6alkylurea or substituted C 14 ,alkylthiourea wherein the substitutents are selected from the group consisting of Cl 1 ,alkyl, haloC 1 -6alkyl, halogen, hydroxyl, carboxylic acid, 00 sulfonic acid, phosphonic acid, amine, amidine, acetamnide, and nitrile where d is 0-8; c-iR 3 3 isthioC 1 6 alkylcarbonyl, Ni substituted C, 1 ,alkyl where the alkyl substituents are selected from one or more members of the group consisting of C, 1 ,alkyl, halo C 1 -,alkyl, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, nitrile, thiol, Cl 1 ,alkyldisulfide, Cl-6alkylsulfide, phenyldisulfide, urea, C 1 -,alkylurea, phenylurea, thiourea, C,,alkylthiou rea, phenylthiourea, substituted C,,alkyldisulfide, substituted phenyldisulfide, substituted Cl-6alkylurea, substituted phenylurea, substituted C 14 ,alkylthiou rea or substituted phenyithiourea wherein the Cl.,alkyldisulflde, phenyldisulfide, C,,alkylurea, C, 1 ,alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 1 -6alkyl, haloC 16 ,alkyi, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrile; -(CR 34 R 35 )q-(CH R 36 )m"SO 3 H 122 where R" 5 and R 3 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and C, 1 ,alkyl, q is 1-6, and m isO-6; -(CH 2 2 ),NH-C(o )CR 37 CH 2 00 ~where R 37 is hydrogen or Cl 1 alkyl, n is 1-6, and x is 1-6; -(CR 38 R 39 )(CHR 40 )p(o )(OH) 2 where R" 8 R3', and R" 0 are independently selected from the group consisting of hydrogen, halogen, hydroxyl, and C 1 ~alkyI, t is 1-6, and u isO-6; phenyl; benzyl; pyridinyl; pyrimidinyl; pyrazinyl; benzimidazolyl; benzoth iazolyl; benzotriazolyl; naphthaloyl; quinolinyl; iridolyl; thiadiazolyi; triazolyl; 4-methylpiperidin-1 -yl; 4-methylpiperazin-1 -yi; substituted phenyl; substituted benzyl; N substituted pyridinyl; substituted pyrimidinyl; substituted pyrazinyl; INusiutdbDimdzll substituted benzothiazolyl; 00siuedbnohizll 00 substituted benzotriazolyl; substituted naphthaloyl; substituted quinolinyl; substituted indolyl; substituted thiadiazolyl; substituted triazolyl; substituted 4-methylpiperidin-1 -yi; or substituted 4-methylpiperazin-1 -yI, wherein the substituents are selected from one or more members of the group consisting of C 1 -,alkyl, haloC, 1 ,alkyl, halogen, sulfonic acid, phosphonic acid,. hydroxyl, carboxylic acid, amine, amidine, N-(2-aminopyrimidine)sulfonyl, N-(aminopyridine)sulfonyl, N-(aminopyrazine)sulfonyl, N-(2-a minopyri mid ine)carbonyl, N-(aminopyridine)carbonyl, N-(aminopyrazine)carbonyl, N-(2-aminopyrimidine)phosphonyl, N-(2-aminopyridine)phosphonyl, N-(aminopyrazine)phosphonyl, N-(aminobenzimidazolyl)sulfonyl, N-(aminobenzothiazoyl)sulfonyl, N-(aminobenzotriazolyl)sulfonyl, N-(aminoindolyl)sulfonyl, N-(aminothiazolyl)sulfonyl, N-(aminotriazolyl)sulfonyl, N-(amino-4..methylpiperidinyi)sulfonyi, 124 N-(amino-4-methylpiperazinyl)sulfonyl, N-(aminobenzimidazolyl)carbonyl, N-aioeztiaoyUabnl N-(aminobenzothiazolyl)carbonyl, INDiobnorazllcabnt N-(aminoindolyl)carbonyi, N-(aminothiazolyl)carbonyl, N-(aminotriazolyl)carbonyl, 00 N(mn--ehlieiiy~abnl N-(amino-4-methylpiperidinyl)carbonyl, N-(2amino4-ethyiprazoyl)carbponyl, N-(2-a minobenzimidazolyl )phosphonyl, N-(2-aminobenzothiazolyl)phosphonyl, N-(2-aminobnzoaolyl)phosphonyl, N-(2-aminotidolyl)phosphonyl, N-(2-aminotiazolyl)phosphonyl, ~~N-(2aminotriazolylphphnyl, hshnl 15N-(amirio-4-methylpiperdinyl) phosphonyl, aeaie nitrile, thiol, C, 14 alkyldisulfide, C 1 -6alkylsulfide, phenyl disulfide, urea, Cl,alkyiurea, phenylurea, thiourea, C,.6alkylthiourea, phenylthiourea, substituted Cl-6alkyldisulfide, substituted phenyldisulfide, substituted C 1 -,alkylurea, substituted C 1 -6alkylthiourea, substituted phenylurea, and substituted phenylthiourea wherein the C -,alkyld isu [fide, phenyidisutfide, C, 1 6alkylurea, C 14 ,alkylthiourea, phenylurea, and phenylthiourea substituents are selected from the group consisting of C 1 -,alkyl, haloC, 1 ,alkyI, halogen, hydroxyl, carboxylic acid, sulfonic acid, phosphonic acid, amine, amidine, acetamide, and nitrite; R" 1 is hydrogen, C, 16 alkyl, phenyl, C 1 ,alkylcarbonyl, phenylcarbonyl, substituted Cl-BalkyI, substituted phenyl, substituted Cl 1 ,alkylcarbonyl or substituted phenylcarbonyl, wherein the substituents are selected from the group consisting of C 1 .alkyl, haloC, 1 alkyl, halogen, hydroxyl, carboxylic acid, Ssulfonic acid, phosphonic acid, amine, amidine, acetamide, 0 5 and nitrile. oO I 64. An antimicrobial lens comprising silver, wherein said lens has sufficient movement on the eye of a patient. t"-
44. 65. The lens of claim 64 having about 50 to about 100 percent movement.
45. 66. The lens of claim 64 having about 75 to about 100 percent movement.
46. 67. The lens of claim 64 having about 90 to about 100 percent movement.
47. 68. An antimicrobial lens comprising silver, wherein said lens inhibits microbial production by at least
48. 69. The lens of claim 68 wherein said les inhibits microbial production by at least about 50% to at least about 99%. The lens of claim 68 wherein said les inhibits microbial production by at least about 80% to at least about 99%.
49. 71. An antimicrobial lens comprising silver, wherein said lens has sufficient movement on the eye of a patient and said lens inhibits microbial production by at least
50. 72. The lens of claim 71 having about 50% to about 100% movement and said lens inhibits microbial production by 75% to about 100%.