Method for sterilization of hydrogel contact lenses

Abstract

The present invention provides an aqueous solution for sterilizing and storing ophthalmic devices, preferably a contact lens, made of a hydrogel material, preferably a poly(oxyalkylene)-containing hydrogel material. The solution comprises one or more organic buffer agents, such as a Good buffer or a bis-aminopolyols; an organic tonicity-adjusting agent with multiple hydroxyl groups in an amount sufficient to provide an osmolarity of from about 200 to about 450 mosm/l, wherein the aqueous solution has a pH of from about 5.5 to about 8.5, provided that the aqueous solution include phosphate buffer at a concentration of about 15 mM or less and about 5000 ppm sodium chloride. The present invention also provides a method for sterilizing and storing an ophthalmic device using an aqueous solution of the invention.

1 . An aqueous solution for sterilizing and storing an ophthalmic device, wherein the ophthalmic device is made of a poly(oxyalkylene)-containing polymeric material, the solution comprising:
 an α-oxo-multi-acid or salt thereof in an amount sufficient to have a reduced susceptibility to oxidative degradation of the poly(oxyalkylene)-containing polymeric material;   one or more buffer agents selected from group consisting of TRIS (tris(hydroxymethyl)aminomethane), bis-aminopolyols, triethanolamine, ACES (N-(2-hydroxyethyl)-2-aminoethanesulfonic acid), BES (N,N-Bis(2-hydroxyethyl)-2-aminoethanesulfonic acid), HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), MES (2-(N-morpholino)ethanesulfonic acid), MOPS 3-[N-morpholino]-propanesulfonic acid, PIPES (piperazine-N,N′-bis(2-ethanesulfonic acid), TES (N-[Tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid), and salts thereof;   an organic tonicity-adjusting agent in an amount sufficient to provide an osmolarity of from about 200 to about 450 milli-osmole in 1000 ml (unit: mosm/l), wherein the organic tonicity-adjusting agent is selected from the group consisting of glycerol, sorbitol, xylitol, mannitol, propylene glycol, polyethylene glycol (PEG) with a molecular weight of about 400 Da or less, and mixtures thereof,   wherein the aqueous solution has a pH of from about 5.5 to about 8.5, provided that the aqueous solution include phosphate buffer at a concentration of about 15 mM or less and about 5000 ppm sodium chloride.   
     
     
         2 . The solution of  claim 1 , wherein the one or more buffer agents are selected from the group consisting of TRIS, bis-aminopolyols, and salts thereof, wherein the bis-aminopolyols have formula (I) 
       
         
           
           
               
               
           
         
       
       wherein a, b, c, d, e, f, g, and h are independently an integer from 1 to 6; and R and R′ are independently selected from the group consisting of —H, —CH 3 , —(CH 2 ) 2-6 —H, and —(CH 2 ) 1-6 —OH. 
     
     
         3 . The solution of  claim 2 , wherein the one or more buffer agents are TRIS and salt thereof. 
     
     
         4 . The solution of  claim 2 , wherein the one or more buffer agents are 1,3-bis(tris[hydroxymethyl]methylamino)propane and salt thereof. 
     
     
         5 . The solution of  claim 2 , wherein the x-oxo-multi-acid is citric acid or malic acid. 
     
     
         6 . The solution of  claim 2 , wherein the ophthalmic device is a hydrogel contact lens which is composed of a poly(oxyalkylene)-containing polyurea material. 
     
     
         7 . The solution of  claim 2 , wherein the solution contains less than about 1000 ppm chloride ion. 
     
     
         8 . The solution of  claim 2 , wherein the solution contains about 10 mM or less of phosphate buffer. 
     
     
         9 . The solution of  claim 2 , wherein the solution imparts a reduced autoclave-induced haziness to the ophthalmic device, wherein the reduced autoclave-induced haziness is characterized by having less than about 10% autoclave-induced reduction in light transmissibility at 500 nm. 
     
     
         10 . The solution of  claim 2 , wherein the solution imparts a reduced autoclave-induced haziness to the ophthalmic device, wherein the reduced autoclave-induced haziness is characterized by having less than about 5% autoclave-induced reduction in light transmissibility at 500 nm. 
     
     
         11 . The solution of  claim 2 , wherein the solution has a surface tension of about 50 mN/m or smaller. 
     
     
         12 . A method for sterilizing and storing ophthalmic devices, comprising the steps of:
 placing an ophthalmic device in an aqueous solution in a container;   autoclaving the sealed container with the ophthalmic device; and   sealing the container,   wherein the ophthalmic device is made of a poly(oxyalkylene)-containing polymeric material,   wherein the aqueous solution comprises   an α-oxo-multi-acid or salt thereof in an amount sufficient to have a reduced susceptibility to oxidation degradation of the poly(oxyalkylene)-containing polymeric material,   one or more buffer agents selected from group consisting of TRIS, bis-aminopolyols, triethanolamine, ACES, BES, HEPES, MES, MOPS, PIPES, TES, and salts thereof, and   an organic tonicity-adjusting agent in an amount sufficient to provide an osmolarity of from about 200 to about 450 milli-osmole in 1000 ml (unit: mosm/l),   wherein the organic tonicity-adjusting agent is selected from the group consisting of glycerol, sorbitol, xylitol, mannitol, propylene glycol, polyethylene glycol (PEG) with a molecular weight of about 400 Da or less, and mixtures thereof,   wherein the aqueous solution has a pH of from about 5.5 to about 8.5, provided that the aqueous solution include phosphate buffer at a concentration of about 15 mM or less and about 5000 ppm sodium chloride.   
     
     
         13 . The method of  claim 12 , wherein the one or more buffer agents are selected from the group consisting of TRIS, bis-aminopolyols, and salts thereof, wherein the bis-aminopolyols have formula (I) 
       
         
           
           
               
               
           
         
       
       wherein a, b, c, d, e, f, g, and h are independently an integer from 1 to 6; and R and R′ are independently selected from the group consisting of —H, —CH 3 , —(CH 2 ) 2-6 —H, and —(CH 2 ) 1-6 —OH. 
     
     
         14 . The solution of  claim 13 , wherein the one or more buffer agents are TRIS and salt thereof. 
     
     
         15 . The solution of  claim 13 , wherein the one or more buffer agents are 1,3-bis(tris[hydroxymethyl]methylamino)propane and salt thereof. 
     
     
         16 . The solution of  claim 13 , wherein the (x-oxo-multi-acid is citric acid or malic acid. 
     
     
         17 . The solution of  claim 13 , wherein the ophthalmic device is a hydrogel contact lens which is composed of a poly(oxyalkylene)-containing polyurea material. 
     
     
         18 . The solution of  claim 13 , wherein the solution contains less than about 1000 ppm chloride ion. 
     
     
         19 . The solution of  claim 13 , wherein the solution contains about 10 mM or less of phosphate buffer. 
     
     
         20 . The solution of  claim 13 , wherein the solution imparts a reduced autoclave-induced haziness of the ophthalmic device, wherein the reduced autoclave-induced haziness is characterized by having less than about 10% autoclave-induced reduction in light transmissibility at 500 nm. 
     
     
         21 . The solution of  claim 13 , wherein the solution has a surface tension of about 50 dyne/cm or smaller. 
     
     
         22 . An ophthalmic product, comprising a sealed container which has been subjected to sterilization by autoclave, wherein the sealed container includes an aqueous solution and an ophthalmic device immersed in the aqueous solution, wherein the ophthalmic device is composed of a hydrogel material, wherein the aqueous solution includes an organic tonicity-adjusting agent in an amount sufficient to provide an osmolarity of from about 200 to about 450 milli-osmole in 1000 ml (unit: mosm/l) and one or more buffer agents selected from group consisting of tris-(hydroxymethyl)aminomethane) (TRIS), bis-aminopolyols, triethanolamine, N-(2-hydroxyethyl)-2-aminoethanesulfonic acid (ACES), N,N-Bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (BES), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), 2-(N-morpholino)ethanesulfonic acid (MES), 3-[N-morpholino]-propanesulfonic acid (MOPS), piperazine-N,N′-bis(2-ethanesulfonic acid) (PIPES), N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid (TES), and salts thereof, wherein the organic tonicity-adjusting agent is selected from the group consisting of glycerol, sorbitol, xylitol, mannitol, propylene glycol, polyethylene glycol (PEG) with a molecular weight of about 400 Da or less, and mixtures thereof, wherein the aqueous solution has a pH of from about 5.5 to about 8.5, wherein the aqueous solution include phosphate buffer at a concentration of about 15 mM or less and about 5000 ppm sodium chloride so that the solution imparts a reduced autoclave-induced haziness to the ophthalmic device, wherein the reduced autoclave-induced haziness is characterized by having less than about 5% autoclave-induced reduction in light transmissibility at 500 nm.