Biocompatible polymers and co-polymers, and uses thereof

Abstract

The invention relates to highly biocompatible or biophilic un-cross-linked or cross-linked polymers comprising one or more side-chain active acrylic amino acids of formula I. The invention further concerns various highly biocompatible, cross-linked co-polymers comprising one or more monomers of formula I, and one or more other polymerizable monomers. Uses of such polymers and co-polymers for the production of contact lenses, intraocular lenses, implants, wound healing slabs, additives for food and cosmetics, conductive plastics, spinnable fibers, and the like are disclosed.

1 . A biocompatible co-polymer comprising one or more polymerizable principal monomers, the principal monomers containing at least one ethylenically unsaturated bond, one or more co-principal monomers of the formula 
       
         
           
           
               
               
           
         
       
       wherein X is —NH(CH 2 ) 4 —, —O—C 6 H 4 —CH 2 —, —OCH 2 —, —O—CH(CH 3 )—, —S—CH 2 —, or —O— proline, and R is H or CH 3 ,
 a cross-linking agent having a plurality of polymerizable ethylenically unsaturated groups and a free radical initiator. 
 
     
     
         2 . The co-polymer of  claim 1  wherein co-principal monomers and principal monomers are present at weight ratios between about 1:9 and 1:4. 
     
     
         3 . The co-polymer of  claim 1  wherein at least one of the principal monomers is a hydrophilic monomer that is a hydroxyalkyl ester or amide, either N-substituted or unsubstituted, of an alpha-, beta-unsaturated carboxylic acid, a N-vinyl lactam or a 2-acrylamido-2-methylpropane sulfonic acid. 
     
     
         4 . The co-polymer of  claim 1  wherein at least one of the principal monomers is a hydrophobic monomer that is an alkyl, cycloalkyl or aryl acrylate or methacrylate, a mono- or disubstituted itaconate, a styrene or styrene derivative, an acrylonitrile, a vinyl ester, a vinyl ether, an allyl ester, or a fluorine or silicon-containing acrylate or methacrylate. 
     
     
         5 . The co-polymer of  claim 1  wherein the principal monomers are combinations of two monomers capable of forming a hydrogel, the combinations of monomers selected from the group consisting of hydroxyethylmethacrylate and methyl methacrylate, vinyl pyrrolidone and hydroxyethylmethacrylate, vinyl pyrrolidone and methyl methacrylate, glyceral methacrylate and methyl methacrylate, hydroxyethylmethacrylate or diacetone acyl amide and hydroxyalkyl methacrylates, hydroxyethylmethacrylate or diacetone acyl amide and acrylates with the alkyl groups having from 2 to 6 carbon atoms, hydroxyethylmethacrylate or diacetone acyl amide and vinyl hydroxy acetate, hydroxyethylmethacrylate or diacetone acyl amide and vinyl hydroxy propionate, hydroxyethylmethacrylate or diacetone acyl amide and vinyl hydroxy butyrate, hydroxyethylmethacrylate or diacetone acyl amide and N-vinyl lactams namely N-vinyl pyrrolidone, N-vinyl caprolactam and N-vinyl piperidone, hydroxyethylmethacrylate or diacetone acyl amide and N,N dialkyl amino ethyl methacrylates and acrylates with the alkyl groups having from 0 to 2 carbon atoms, hydroxyethylmethacrylate or diacetone acyl amide and hydroxyalkyl vinyl ethers with the alkyl groups having 2 to 4 carbon atoms, hydroxyethylmethacrylate or diacetone acyl amide and 1-vinyloxy 2-hydroxyethylene, hydroxyethylmethacrylate or diacetone acyl amide and 1-vinyloxy 5-hydroxy 3-oxapentane, hydroxyethylmethacrylate or diacetone acyl amide and 1-vinyloxy 8-hydroxy 3,6-dioxaoctane, hydroxyethylmethacrylate or diacetone acyl amide and 1-vinyloxy 14-hydroxy 3,6,9,12 tetraoxatetradectane, hydroxyethylmethacrylate or diacetone acyl amide and N-vinyl morpholine; hydroxyethylmethacrylate or diacetone acyl amide and N,N dialkyl acrylamide with the alkyl groups having from 0 to 2 carbons atoms hydroxyethylmethacrylate or diacetone acyl amide and alkyl vinyl ketone with the alkyl group having 1 to 2 carbon atoms, hydroxyethylmethacrylate or diacetone acyl amide and N-vinyl succinimide or N-vinyl glutarimide, hydroxyethylmethacrylate or diacetone acyl amide and N-vinyl imidazole, and hydroxyethylmethacrylate or diacetone acyl amide and N-vinyl 3-morpholinone. 
     
     
         6 . The co-polymer of  claim 1  wherein at least one of the principal monomers is a compound of the formula 
       
         
           
           
               
               
           
         
       
       wherein:
 X is H or CH. 3 ; m is 0-10; Y is nothing, 0, S, or NR wherein R is H, CH 3 , C n H 2n+1  (n=1-10) iso-OC 3 H 7 , C 6 H 5 , or CH 2 C 6  H 5 ; Ar is any aromatic ring, such as benzene, which can be unsubstituted or substituted with H, CH 3 , C 2 H 5 , n-C 3 H 7 , iso-C 3 H 7 , OCH 3 , C 6 H 11 , Cl, Br, C 6 H 5  or CH 2 C 6 H 5 . 
 
     
     
         7 . The co-polymer of  claim 6  wherein the at least one principal monomer is selected from the group consisting of 2-ethylphenoxy acrylate, 2-ethylphenoxy methacrylate, 2-ethylthiophenyl acrylate, 2-ethylthiophenyl methacrylate, 2-ethylaminophenyl acrylate, 2-ethylaminophenyl methacrylate, phenyl acrylate, phenyl methacrylate, benzyl acrylate, benzyl methacrylate, 2-phenylethyl acrylate, 2-phenylethyl methacrylate, 3-phenylpropyl acrylate, 3-phenylpropyl methacrylate, 3-propylphenoxy acrylate, 3-propylphenoxy methacrylate, 4-butylphenoxy acrylate, 4-butylphenoxy methacrylate, 4-phenylbutyl acrylate, 4-phenylbutyl methacrylate, 4-methylphenyl acrylate, 4-methylphenyl methacrylate, 4-methylbenzyl acrylate, 4-methylbenzyl methacrylate, 2-2-methylphenylethyl acrylate, 2-2-methylphenylethyl methacrylate, 2-3-methylphenylethyl acrylate, 2-3-methylphenylethyl methacrylate, 2-4-methylphenylethyl acrylate, 2-4-methylphenylethyl methacrylate, 2-(4-propylphenyl)ethyl acrylate, 2-(4-propylphenyl)ethyl methacrylate, 2-(4-(1-methylethyl)phenyl)ethyl acrylate, 2-(4-(1-methylethyl)phenyl)ethyl methacrylate, 2-(4-methoxyphenyl)ethyl acrylate, 2-(4-methoxyphenyl)ethyl methacrylate, 2-(4-cyclohexylphenyl)ethyl acrylate, 2-(4-cyclohexylphenyl)ethyl methacrylate, 2-(2-chlorophenyl)ethyl acrylate, 2-(2-chlorophenyl)ethyl methacrylate, 2-(3-chlorophenyl)ethyl acrylate, 2-(3-chlorophenyl)ethyl methacrylate, 2-(4-chlorophenyl)ethyl acrylate, 2-(4-chlorophenyl)ethyl methacrylate, 2-(4-bromophenyl)ethyl acrylate, 2-(4-bromophenyl)ethyl methacrylate, 2-(3-phenylphenyl)ethyl acrylate, 2-(3-phenylphenyl)ethyl methacrylate, 2-(4-phenylphenyl)ethyl methacrylate, 2-(4-phenylphenyl)ethyl methacrylate, 2-(4-benzylphenyl)ethyl acrylate, and 2-(4-benzylphenyl)ethyl methacrylate. 
     
     
         8 . The co-polymer of  claim 6  wherein the principal monomers are 2-phenylethylacrylate and 2-phenylethyl-methacrylate. 
     
     
         9 . The co-polymer of  claim 1  wherein a first principal monomer is a compound of the formula 
       
         
           
           
               
               
           
         
       
       wherein:
 X is H or CH. 3 ; m is 0-10; Y is nothing, 0, S, or NR wherein R is H, CH 3 , C 6 H 2n+1  (n=1-10) iso-OC 3 H 7 , C 6 H 5 , or CH 2 C 6  H 5 ; Ar is any aromatic ring, such as benzene, which can be unsubstituted or substituted with H, CH 3 , C 2 H 5 , n-C 3 H 7 , iso-C 3 H 7 , OCH 3 , C 6 H 11 , Cl, Br, C 6 H 5  or CH 2 C 6  H 5 ; 
 
       and wherein a second principal monomer is a hydrophilic monomer. 
     
     
         10 . The co-polymer of  claim 9  wherein the second principal monomer is selected from the group consisting of 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, 2-N-ethylacrylate pyrrolidone, 2-hydroxy-3-phenoxypropyl acrylate, 2,3-dihydroxypropyl acrylate, 2,3-dihydroxypropyl methacrylate, 2-N-vinyl pyrrolidone, polyethylene oxide:200 monomethyl ether monomethacrylate, polyethylene oxide:200 monomethacrylate, and polyethylene oxide:1000 dimethacrylate. 
     
     
         11 . The co-polymer of  claim 1  wherein the cross-linking agent having a plurality of polymerizable ethylenically unsaturated groups is selected from the group consisting of ethylene glycol diacrylate or dimethacrylate, diethylene glycol diacrylate or dimethacrylate, triethylene glycol diacrylate or dimethacrylate, tetraethylene glycol diacrylate or dimethacrylate, polyethylene glycol diacrylate or dimethacrylate, trimethylolpropane triacrylate or trimethacrylate, bisphenol A diacrylate or dimethacrylate, ethoxylated bisphenol A diacrylate or dimethacrylate, pentaerythritol tri- and tetra-acrylate or methacrylate, tetramethylene diacrylate or dimethacrylate, methylene bisacrylamide or methacrylamide, dimethylene bisacrylamide or methacrylamide, N,N′-dihydroxyethylene bisacrylamide or methacrylamide, hexamethylene bisacrylamide or methacrylamide, decamethylene bisacrylamide or methacrylamide, divinyl benzene, vinyl methacrylate, allyl methacrylate, 1,3-bis(4-methacryloyl oxyalkyl)tetra disiloxane and similar polyorgano-siloxanes, resonance-free di(alkylene tertiary amine) cyclic compounds and di- or polyvinyl ethers of di- or polyvalent alcohols. 
     
     
         12 . The co-polymer of  claim 1  wherein the cross-linking agent having a plurality of polymerizable ethylenically unsaturated groups is present in an amount from 0.1 wt % to 20 wt % of total monomers.