Methods for stabilizing oxidatively unstable compositions

Abstract

Ophthalmic compositions and methods of preparing such compositions are disclosed.

1 . (canceled) 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 56  wherein the polymer is soluble in the ophthalmic composition and is present in an amount between about 2.5 μmoles/liter to about 5000 μmoles/liter. 
     
     
         5 . The method of  claim 56  wherein the polymer is soluble in the ophthalmic composition and is present in an amount between about 20 μmoles/liter to about 1000 μmoles/liter. 
     
     
         6 . The method of  claim 56  wherein the polymer is soluble in the ophthalmic composition and is present in an amount between about 100 μmoles/liter to about 600 μmoles/liter. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 56  wherein the stabilizing agent is diethylenetriaminepentaacetic acid or salts there of and the polymer is present in the ophthalmic composition in an amount between about 100 μmoles/liter to about 1000 μmoles/liter 
     
     
         9 . The method of  claim 56  wherein the oxidatively unstable pharmaceutical ingredient is selected from the group consisting of acrivastine, antazoline, astemizole, azatadine, azelastine, buclizine, bupivacaine, cetirizine, clemastine, cyclizine, cyproheptadine, ebastine, emedastine, eucatropine, fexofenadine, homatropine, hydroxyzine, ketotifen, levocabastine, levoceterizine, lomefloxacin, meclizine, mepivacaine, mequitazine, methdilazine, methapyrilene, mianserin, norastemizole, norebastine, ofloxacin, oxymetazoline, pheniramine, physostigmine, picumast, promethazine, scopolamine, terfenadine, tetrahydozoline, thiethylperazine, timolol, trimeprazine, triprolidine, pharmaceutically acceptable salts and mixtures thereof. 
     
     
         10 . The method of  claim 56  wherein the oxidatively unstable pharmaceutical ingredient is selected from the group consisting of acrivatine, antazoline, astemizole, azatadine, azelastine, clemastine, cyproheptadine, ebastine, emedastine, eucatropine, fexofenadine, homatropine, hydroxyzine, ketotifen, levocabastine, levoceterizine, meclizine, mequitazine, methdialazine, methapyrilene, norastemizole, norebastine, oxymetazoline, physootigmine, picumast, promethazine, scopolamine, terfenadine, tetrahyerozoline, fimilol, trimeprazine, triprolidine, and pharmaceutically acceptable salts thereof. 
     
     
         11 . The method of  claim 56  wherein the oxidatively unstable pharmaceutical ingredient is selected from the group consisting of phenarimine, ketotifen, ketotifen fumarate, nor ketotifen fumarate olopatadine and mixtures thereof. 
     
     
         12 . The method of  claim 56  wherein the oxidatively unstable pharmaceutical ingredient is selected from the group consisting of ketotifen, its pharmaceutically acceptable salts, and mixtures thereof. 
     
     
         13 . The method of  claim 56  wherein the oxidatively unstable pharmaceutical ingredient is selected from the group consisting of vitamins A, D, E, lutein, zeaxanthin, lipoic acid, flavonoids, ophthalmically compatible fatty acids, such as omega 3 and omega 6 fatty acids and combinations thereof. 
     
     
         14 . The method of  claim 56  wherein the stabilizing agent is diethylenetriaminepentaacetic acid or salts there of, and the oxidatively unstable pharmaceutical ingredient is selected from the group consisting of ketotifen, its pharmaceutically acceptable salts, and mixtures thereof. 
     
     
         15 . The method of  claim 56  wherein the stabilizing agent is the calcium salt diethylenetriaminepentaacetic acid, and the oxidatively unstable pharmaceutical ingredient is selected from the group consisting of ketotifen, pharmaceutically acceptable salts of ketotifen and mixtures thereof. 
     
     
         16 . The method of  claim 56  wherein the ophthalmic composition has a pH of about 6.6 to about 7.2. 
     
     
         17 . The method of  claim 56  wherein the ophthalmic composition has a pH of about 6.8 to about 7.2. 
     
     
         18 - 55 . (canceled) 
     
     
         56 . A method of stabilizing an ophthalmic composition comprising an oxidatively unstable pharmaceutical ingredient wherein said method comprises
 (a) functionalizing said stabilizing agent with a polymerizable group,   (b) polymerizing an effective amount of the product of step (a) with at least one type of polymerizable monomer, and   (c) contacting the ophthalmic composition comprising an oxidatively unstable pharmaceutical ingredient with the polymer of step (b).   
     
     
         57 . The method of  claim 56  wherein the stabilizing agent is selected from the group consisting of silica, chitin derivative such as chitosan, cellulose its derivatives, and N,N,N′,N′,N″,N″-hexa(2-pyridyl)-1,3,5-tris(aminomethyl)benzene, diethylenetriaminepentaacetic acid, and salts of diethylenetriaminepentaacetic acid. 
     
     
         58 . The method of  claim 56  wherein the stabilizing agent is selected from the group consisting of diethylenetriaminepentaacetic acid, and salts of diethylenetriaminepentaacetic acid. 
     
     
         59 . A method of stabilizing an ophthalmic composition comprising an oxidatively unstable excipient wherein said method comprises
 (a) functionalizing said stabilizing agent with a polymerizable group,   (b) polymerizing an effective amount of the product of step (a) with at least one type of polymerizable monomer, and   (c) contacting the ophthalmic composition comprising an oxidatively unstable excipient with the polymer of step (b).   
     
     
         60 . The method of  claim 59  wherein the stabilizing agent is selected from the group consisting of silica, chitin derivative such as chitosan, cellulose its derivatives, and N,N,N′,N′,N″,N″-hexa(2-pyridyl)-1,3,5-tris(aminomethyl)benzene, diethylenetriaminepentaacetic acid, and salts of diethylenetriaminepentaacetic acid, and acid. 
     
     
         61 . The method of  claim 59  wherein the stabilizing agent is selected from the group consisting of diethylenetriaminepentaacetic acid, and salts of diethylenetriaminepentaacetic acid. 
     
     
         62 - 67 . (canceled)