Medical devices having homogeneous charge density and methods for making same

Abstract

The present invention relates to ionic silicone hydrogel polymers comprising at least one pharmaceutical or nutriceutical component and displaying improved lysozyme uptake, low contact angle and reduced water soluble polymeric ammonium salt uptake.

We claim: 
     
         1 . An anionic, silicone hydrogel contact lens comprising in or on said silicone hydrogel at least one statistical copolymer comprising units derived from at least 10 weight % of at least one non-ionic hydrophilic monomer and at least one anionic monomer and wherein said contact lens comprises at least one pharmaceutical or nutraceutical component and has a contact angle of about 70° or less, at least about 50 μg/lens lysozyme uptake, and less than about 10% uptake of at least one polycationic component when contacted with 3 mL of an ophthalmic solution comprising said 0.001 wt % polycationic component, 0.56% citrate dihydrate and 0.021% citric acid monohydrate (wt/wt). 
     
     
         2 . The contact lens of  claim 1  wherein said statistical copolymer is non-reactive and is associated with or entangled in said silicone hydrogel contact lens. 
     
     
         3 . The contact lens of  claim 2  wherein said statistical copolymer comprises about 20 to about 80 mol % units from said anionic monomer. 
     
     
         4 . The contact lens of  claim 2  wherein said statistical copolymer comprises about 20 to about 60 mol % units from said anionic monomer. 
     
     
         5 . The contact lens of  claim 3  wherein said statistical copolymer comprises about 80 to about 20 mol % units from said non-ionic hydrophilic monomer. 
     
     
         6 . The contact lens of  claim 3  wherein said statistical copolymer comprises about 80 to about 40 mol % units from said non-ionic hydrophilic monomer. 
     
     
         7 . The contact lens of  claim 2  wherein said statistical copolymer is associated with at least part of said silicone hydrogel contact lens. 
     
     
         8 . The contact lens of  claim 18  wherein said statistical copolymer is present in or on said contact lens in a concentration sufficient to provide a concentration of units from said anionic monomer of about 0.1 to about 5 mol %. 
     
     
         9 . The contact lens of  claim 18  wherein said statistical copolymer is present in or on said contact lens in a concentration sufficient to provide a concentration of units from said anionic monomer of about 0.2 to about 4 mol %. 
     
     
         10 . The contact lens of  claim 2  wherein said statistical copolymer is formed by RAFT polymerization, free radical polymerization, or step growth polymerization 
     
     
         11 . The contact lenses of  claim 2  wherein said non-reactive statistical copolymer further comprises a hydrophobic block on at least one terminus. 
     
     
         12 . The contact lens of  claim 11  wherein said hydrophobic block comprises polydialkylsiloxane, polydiarylsiloxane and mixtures thereof. 
     
     
         13 . The contact lens of  claim 12  wherein said alkyl is selected from C 1 -C 4  alkyl. 
     
     
         14 . The composition of  claim 12  wherein said hydrophobic block comprises polydimethylsiloxane or polydiethylsiloxane. 
     
     
         15 . The contact lens of  claim 12  wherein said hydrophobic block comprises between about 6 and about 200 siloxy units. 
     
     
         16 . The contact lens of  claim 12  wherein said hydrophobic block comprises between about 6 and about 200 siloxy units. 
     
     
         17 . The contact lens of  claim 2  wherein said units from said non-ionic hydrophilic monomer and said anionic monomer when polymerized have a degree of polymerization of at least about 300. 
     
     
         18 . The contact lens of  claim 1  wherein said silicone hydrogel is said statistical copolymer. 
     
     
         19 . The contact lens of  claim 1 ,  2  or  18  wherein said anionic monomer and said non-ionic hydrophilic monomer have the same reactive functionality. 
     
     
         20 . The contact lenses of  claim 19  wherein said anionic monomer and said non-ionic hydrophilic monomer are selected from (meth)acrylamides. 
     
     
         21 . The contact lenses of  claim 19  wherein said anionic monomer and said non-ionic hydrophilic monomer are selected from (meth)acrylates. 
     
     
         22 . The contact lenses of  claim 19  wherein said anionic monomer and said non-ionic hydrophilic monomer are selected from vinyls. 
     
     
         23 . The contact lens of  claim 1  wherein said lysozyme uptake is at least about 70 μg/lens. 
     
     
         24 . The contact lens of  claim 1  wherein said lysozyme uptake is at least about 100 μg/lens. 
     
     
         25 . The contact lens of  claim 1  wherein said polycationic component is selected from the group consisting of cationic water soluble polymeric ammonium salts, polyquaternium containing compounds, water soluble polymeric tetraalkyl phosphonium salts and mixtures thereof. 
     
     
         26 . The contact lens of  claim 1  wherein said polycationic component is selected from the group consisting of biguanides, bisbiguanides, polycationic polymers having quartenary ammonium centers and combinations thereof. 
     
     
         27 . The contact lens of  claim 1  wherein said polycationic component is selected from the group consisting of polyhexamethylene biguanide PQ-1, PQ-42, and mixtures thereof. 
     
     
         28 . The contact lens of  claim 1  further comprising a water content of between about 20% and about 70%. 
     
     
         29 . The contact lens of  claim 1  further comprising a water content of between about 25% and about 65%. 
     
     
         30 . The contact lens of  claim 20  wherein said anionic monomer is selected from the group consisting of 3-acrylamidopropionic acid, 4-acrylamidobutanoic acid, 5-acrylamidopentanoic acid, sodium-2-(acrylamido)-2-methylpropane sulphonate, 2-acrylamido-2-methylpropane sulfonic acid and combinations thereof. 
     
     
         31 . The contact lens of  claim 21  wherein said anionic monomer is selected from the group consisting of (meth)acrylic acid, acrylic acid, 3-sulphopropyl (meth)acrylate potassium salt, 3-sulphopropyl (meth)acrylate sodium salt, sulphoethyl methacrylate, and mixtures thereof. 
     
     
         32 . The contact lens of  claim 21  wherein said anionic monomer comprises (meth)acrylic acid. 
     
     
         33 . The contact lens of  claim 21  wherein said anionic monomer is selected from the group consisting of N-vinyloxycarbonyl-α-alanine, N-vinyloxycarbonyl-β-alanine, 2-vinyl-4,4-dimethyl-2-oxazolin-5-one, vinyl sulphonate sodium salt, vinyl sulphonate salt, and mixtures thereof. 
     
     
         34 . A silicone hydrogel formed from a reactive mixture comprising
 major polymerizable components comprising at least one reactive silicone-containing component, at least one reactive ionic monomer, optional reactive hydrophilic components and crosslinker; and   minor polymerizable components selected from the group consisting of visibility tint and dyes, UV absorbers, photochromic compounds, pharmaceutical compounds, nutriceutical compounds, and mixtures thereof;   wherein said major polymerizable components comprise a single reactive functionality.   
     
     
         35 . The silicone hydrogel of  claim 34  wherein said single reactive functionality is selected from the group consisting of acrylate, methacrylate, acrylamide, methacrylamide, vinyl and styryl. 
     
     
         36 . The silicone hydrogel of  claim 34  wherein said single reactive functionality is selected from the group consisting of acrylamide, methacrylamide and vinyl. 
     
     
         37 . A silicone hydrogel contact lens comprising between about 50 ppm and about 1 wt % of at least one uncrosslinked statistical copolymer comprising at least about 10 weight % of at least one non-ionic hydrophilic monomer and at least about 20 mol % of at least one anionic repeating unit distributed randomly throughout said polymer. 
     
     
         38 . The contact lens of  claim 37  wherein said copolymer is present in an amount between about 20 ppm and 2000 ppm. 
     
     
         39 . The contact lens of  claim 37  wherein said copolymer is present in an amount between about 50 ppm and 1500 ppm. 
     
     
         40 . The silicone hydrogel of  claim 34  wherein said single reactive functionality is methacrylamide and said reactive ionic monomer comprises at least one acrylamido sulphonic acid or acrylamido sulphonic acid salt. 
     
     
         41 . The silicone hydrogel of  claim 40  wherein said acrylamido sulphonic acid comprises an alkylene group comprising 2 to 4 carbon atoms. 
     
     
         42 . The silicone hydrogel of  claim 40  wherein said acrylamido sulphonic acid comprises 2-acrylamido-2-methylpropane sulfonic acid salt. 
     
     
         43 . The contact lens of  claim 1  wherein said at least one pharmaceutical pharmaceutical or nutraceutical component is cationic. 
     
     
         44 . The contact lens of  claim 1  wherein said at least one pharmaceutical pharmaceutical or neutraceutical component is selected from the group consisting of atropine, pirenzepine, doxycycline, brimonidine, brinzolamide, dorzolamide, betaxolol, apraclonidine, ccr2 antagonist, olopatadine, alcaftadine, betaxolol, bupivacaine, carbachol, carteolol, chlortetracycline, cyclopentolate, dibutoline, dipivefrin, ephedrine, erythromycin, gentamycin, gramicidin, homatropine ketotifen, levobunolol, levocabastine, lidocaine, lignocaine, lomefloxacin, mepivacaine, naphazoline, neomycin, ofloxacin, oxybuprocaine, pheniramine, physostigmine, pilocarpine, polymyxin B, proparacaine, pyrilamine, tetracaine, tetracycline, tetrahydrozoline, timolol, tropicamide, vidarabine, pharmaceutically acceptable salts thereof and combinations thereof and the like. 
     
     
         45 . The contact lens of  claim 1  wherein said at least one pharmaceutical pharmaceutical or neutraceutical component is selected from the group consisting of atropine, pirenzepine, doxycycline, brimonidine, brinzolamide, dorzolamide, betaxolol, apraclonidine, ccr2 antagonist, olopatadine, alcaftadine, betaxolol, bupivacaine, carbachol, carteolol, chlortetracycline, cyclopentolate, dibutoline, dipivefrin, erythromycin, gentamycin, gramicidin, homatropine ketotifen, levobunolol, levocabastine, lidocaine, lignocaine, lomefloxacin, mepivacaine, naphazoline, ofloxacin, pheniramine, physostigmine, pilocarpine, polymyxin B, proparacaine, pyrilamine, tetracaine, tetrahydrozoline, timolol, tropicamide pharmaceutically acceptable salts thereof and combinations thereof and the like. 
     
     
         46 . The contact lens of  claim 1  wherein said at least one pharmaceutical pharmaceutical or nutraceutical component is selected from the group consisting of atropine, ketotifen, olopatadine, alcaftadine, levocabastine, pirenzepine, doxycycline, brimonidine, brinzolamide, dorzolamide, betaxolol, apraclonidine, ccr2 antagonist, olopatadine pharmaceutically acceptable salts thereof and combinations thereof and the like. 
     
     
         47 . The contact lens of  claim 1 ,  44 ,  45  or  46 , wherein said at least one pharmaceutical or nutraceutical component in a symptom mitigating effective amount. 
     
     
         48 . The contact lens of  claim 47  wherein said symptom mitigating effective amount is between about 5 μg and about less than 200 μg. 
     
     
         49 . The contact lens of  claim 47  wherein said symptom mitigating effective amount is between about 9 μg and about 100 μg. 
     
     
         50 . The contact lens of  claim 47  wherein said symptom mitigating effective amount alleviates symptoms for between about 5 minutes, and about 12 hours from insertion of said contact lens on a human's eye. 
     
     
         51 . The contact lens of  claim 47  wherein said contact lens comprises a modulus which increases less than about 30% after three autoclave cycles.