Ophthalmic compositions comprising povidone-iodine

Abstract

A topical ophthalmic composition comprised of povidone-iodine 0.01% to 10.0% combined with a steroid or non-steroidal anti-inflammatory drug. This solution is useful in the treatment of active infections of at least one tissue of the eye (e.g., conjunctiva and cornea) from bacterial, mycobacterial, viral, fungal, or amoebic causes, as well as treatment to prevent such infections in appropriate clinical settings (e.g. corneal abrasion, postoperative prophylaxis, post-LASIK/LASEK prophylaxis). Additionally the solution is effective in the prevention of infection and inflammation in the post-operative ophthalmic patient.

1 .- 44 . (canceled) 
     
     
         45 . A composition comprising a mixture of
 a) povidone-iodine at a concentration of between 0.01% and 10% by weight, and   b) a steroid, wherein the steroid is selected from the group consisting of prednisolone, prednisone, and salts and esters thereof, and wherein, after a period of one month after mixing the steroid and povidone-iodine to form the composition, the steroid concentration is at least 90% by weight of the steroid starting concentration.   
     
     
         46 . The composition of  claim 45 , wherein the povidone-iodine is at a concentration of between 0.1% and 2.5% by weight. 
     
     
         47 . The composition of  claim 45 , wherein the povidone-iodine is at a concentration of between 0.5% and 2% by weight. 
     
     
         48 . The composition of  claim 45 , wherein the total concentration of the povidone-iodine and the steroid is between 0.1% and 4.5% by weight in the composition. 
     
     
         49 . The composition of  claim 45 , wherein the steroid is at a concentration of between 0.01% and 10% by weight. 
     
     
         50 . The composition of  claim 45 , wherein the steroid is at a concentration of between 0.05% and 2% by weight. 
     
     
         51 . The composition of  claim 45 , wherein the composition further comprises an antimicrobial preservative. 
     
     
         52 . The composition of  claim 51 , wherein the antimicrobial preservative is selected from the group consisting of benzalkonium chloride, thimerosal, chlorobutanol, methyl paraben, propylparaben, phenyl ethyl alcohol, EDTA, sorbic acid, polyquarternium 1, and a combination thereof. 
     
     
         53 . The composition of  claim 51 , wherein the antimicrobial preservative is at a concentration of about 0.001% to 1.0% by weight in the composition. 
     
     
         54 . The composition of  claim 45 , wherein the composition further comprises a co-solvent/surfactant. 
     
     
         55 . The composition of  claim 54 , wherein the co-solvent/surfactant is selected from the group consisting of polysorbate 20, polysorbate 60, polysorbate 80, Pluronic F-68, Pluronic F-84, Pluronic P-103, cyclodextrin, tyloxapol, and a combination thereof. 
     
     
         56 . The composition of  claim 54 , wherein the co-solvent/surfactant is at a concentration of about 0.01% to 2% by weight in the composition. 
     
     
         57 . The composition of  claim 45 , wherein the composition further comprises a viscosity increasing agent. 
     
     
         58 . The composition of  claim 57 , wherein the viscosity increasing agent is selected from the group consisting of polyvinyl alcohol, polyvinylpyrrolidone, methyl cellulose, hydroxy propyl methylcellulose, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxy propyl cellulose, and a combination thereof. 
     
     
         59 . The composition of  claim 57 , wherein the viscosity increasing agent is at a concentration of about 0.01% to 2% by weight in the composition. 
     
     
         60 . The composition of  claim 45 , wherein the composition is in a form selected from the group consisting of a solution, suspension, emulsion, ointment, cream, gel, and controlled-release/sustained-release vehicle. 
     
     
         61 . The composition of  claim 45 , comprising: 0.5 to 2% (w/w) povidone-iodine; 0.05 to 2% (w/w) steroid; 0.005% to 0.02% (w/w) EDTA; 0.01 to 0.5% (w/w) sodium chloride; 0.02 to 0.1% (w/w) tyloxapol; 0.5% to 2% (w/w) sodium sulfate; and 0.1 to 0.5% (w/w) hydroxyethylcellulose. 
     
     
         62 . The composition of  claim 45 , comprising: 1.0% (w/w) povidone-iodine; 0.1% (w/w) steroid; 0.01% (w/w) EDTA; 0.3% (w/w) sodium chloride salt; 0.05% (w/w) tyloxapol; 1.2% (w/w) sodium sulfate; and 0.25% (w/w) hydroxyethylcellulose. 
     
     
         63 . The composition of  claim 45 , wherein the composition retains 90% by weight of its povidone-iodine and 90% by weight of its steroid after a period of 3 months in a lighted environment. 
     
     
         64 . The composition of  claim 45 , wherein the composition retains 90% by weight of its povidone-iodine and 90% by weight of its steroid after a period of 1 year in a lighted environment. 
     
     
         65 . The composition of  claim 45 , wherein the composition is an aqueous solution. 
     
     
         66 . A composition comprising a mixture of
 a) povidone-iodine at a starting concentration of between 0.01% and 10% by weight, and   b) a steroid, wherein the steroid is selected from the group consisting of prednisolone, prednisone, and salts and esters thereof, and wherein, after a period of one month after mixing the steroid and povidone-iodine to form the composition, the povidone-iodine concentration is at least 90% by weight of the starting concentration of povidone-iodine.   
     
     
         67 . The composition of  claim 66 , wherein the povidone-iodine is at a starting concentration of between 0.1% and 2.5% by weight. 
     
     
         68 . The composition of  claim 66 , wherein the povidone-iodine is at a starting concentration of between 0.5% and 2% by weight. 
     
     
         69 . The composition of  claim 66 , wherein the total concentration of the povidone-iodine and the steroid is between 0.1% and 4.5% by weight in the composition. 
     
     
         70 . The composition of  claim 66 , wherein the steroid is at a concentration of between 0.01% and 10% by weight. 
     
     
         71 . The composition of  claim 66 , wherein the steroid is at a concentration of between 0.05% and 2% by weight. 
     
     
         72 . The composition of  claim 66 , wherein the composition further comprises an antimicrobial preservative. 
     
     
         73 . The composition of  claim 72 , wherein the antimicrobial preservative is selected from the group consisting of benzalkonium chloride, thimerosal, chlorobutanol, methyl paraben, propylparaben, phenyl ethyl alcohol, EDTA, sorbic acid, polyquarternium 1, and a combination thereof. 
     
     
         74 . The composition of  claim 72 , wherein the antimicrobial preservative is at a concentration of about 0.001% to 1.0% by weight in the composition. 
     
     
         75 . The composition of  claim 66 , wherein the composition further comprises a co-solvent/surfactant. 
     
     
         76 . The composition of  claim 75 , wherein the co-solvent/surfactant is selected from the group consisting of polysorbate 20, polysorbate 60, polysorbate 80, Pluronic F-68, Pluronic F-84, Pluronic P-103, cyclodextrin, tyloxapol, and a combination thereof. 
     
     
         77 . The composition of  claim 75 , wherein the co-solvent/surfactant is at a concentration of about 0.01% to 2% by weight in the composition. 
     
     
         78 . The composition of  claim 66 , wherein the composition further comprises a viscosity increasing agent. 
     
     
         79 . The composition of  claim 78 , wherein the viscosity increasing agent is selected from the group consisting of polyvinyl alcohol, polyvinylpyrrolidone, methyl cellulose, hydroxy propyl methylcellulose, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxy propyl cellulose, and a combination thereof. 
     
     
         80 . The composition of  claim 78 , wherein the viscosity increasing agent is at a concentration of about 0.01% to 2% by weight in the composition. 
     
     
         81 . The composition of  claim 66 , wherein the composition is in a form selected from the group consisting of a solution, suspension, emulsion, ointment, cream, gel, and controlled-release/sustained-release vehicle. 
     
     
         82 . The composition of  claim 66 , comprising: 0.5 to 2% (w/w) povidone-iodine; 0.05 to 2% (w/w) steroid; 0.005% to 0.02% (w/w) EDTA; 0.01 to 0.5% (w/w) sodium chloride; 0.02 to 0.1% (w/w) tyloxapol; 0.5% to 2% (w/w) sodium sulfate; and 0.1 to 0.5% (w/w) hydroxyethylcellulose. 
     
     
         83 . The composition of  claim 66 , comprising: 1.0% (w/w) povidone-iodine; 0.1% (w/w) steroid; 0.01% (w/w) EDTA; 0.3% (w/w) sodium chloride salt; 0.05% (w/w) tyloxapol; 1.2% (w/w) sodium sulfate; and 0.25% (w/w) hydroxyethylcellulose. 
     
     
         84 . The composition of  claim 66 , wherein the composition retains 90% by weight of its polyvinylpyrrolidinone-iodine and 90% by weight of its steroid after a period of 3 months in a lighted environment. 
     
     
         85 . The composition of  claim 66 , wherein the composition retains 90% by weight of its polyvinylpyrrolidinone-iodine and 90% by weight of its steroid after a period of 1 year in a lighted environment. 
     
     
         86 . The composition of  claim 66 , wherein the composition is an aqueous solution.