Ophthalmic formulations providing durable ocular lubrication

Abstract

This disclosure is directed to an ophthalmic formulation for dry eye and other ocular indications that provides long-lasting benefits. The formulations described herein provide durable relief and last two to ten longer on the eye than currently marketed products. The disclosure also provides methods of alleviating the symptoms of dry eye, methods for delivering ophthalmic pharmaceuticals, and methods of manufacture of the long-lasting ophthalmic formulations.

1 .- 50 . (canceled) 
     
     
         51 . A method for alleviating the symptoms of dry eye, the method comprising the step of:
 contacting an eye with an ophthalmic solution, the ophthalmic solution comprising
 a wax dispersion comprising natural beeswax, an anionic polar surfactant and water; and 
 an oil-in-water emulsion comprising an oil and water, 
 wherein: 
 (i) the oil is a mixture of a lighter molecular weight and a heavier molecular weight oil and is present in a concentration of about 1.0 to about 6.25 weight percent; 
 (ii) the anionic polar surfactant is a mixture of a Polysorbate 80 in a concentration of about 0.35 to about 0.45 weight percent and an anionic polar dimyristoylphosphatidylglyerol in a concentration of about 0.35 to about 0.45 weight percent; and 
 (iii) the natural beeswax is present in a concentration of about 0.20 to about 1.25 weight percent; and 
 wherein the ophthalmic solution: 
 (i) forms a meta stable emulsion which separates into an oil phase and a water phase on contact with an eye; 
 (ii) provides a dwell time on the eye of at least two hours; and 
   (iii) is formulated as a free flowing liquid at room temperature.   
     
     
         52 . The method of  claim 51 , wherein on contact with an eye, the ophthalmic solution interacts with:
 a lipid layer;   an aqueous layer;   a mucin layer;   an interface between the lipid layer and the aqueous layer; and   an interface between the aqueous layer and the mucin layer of the eye and or the corneal cells.   
     
     
         53 . The method of  claim 51 , wherein the natural beeswax is  Cera alba  or  Cera flava.    
     
     
         54 . The method of  claim 51 , wherein the lighter molecular weight oil and heavier molecular weight oil are each a mineral oil. 
     
     
         55 . The method of  claim 51 , wherein the ophthalmic solution has an osmolality of from about 230 to about 260 mOsmol/kg. 
     
     
         56 . The method of  claim 51 , wherein the ophthalmic solution is packaged in a sterile multi-use or sterile single use container. 
     
     
         57 . The method of  claim 51 , wherein the ophthalmic solution is packaged in a multi-dose non-preserved (MDNP) container. 
     
     
         58 . The method of  claim 51 , wherein the ophthalmic solution further comprises hyaluronic acid. 
     
     
         59 . A method for rebuilding tear film in a subject in need thereof, the method comprising the step of:
 contacting an eye with an ophthalmic solution, the ophthalmic solution comprising
 a wax dispersion comprising natural beeswax, an anionic polar surfactant and water; and 
 an oil-in-water emulsion comprising an oil and water, 
 wherein: 
 (i) the oil is a mixture of a lighter molecular weight and a heavier molecular weight oil and is present in a concentration of about 1.0 to about 6.25 weight percent; 
 (ii) the anionic polar surfactant is a mixture of a Polysorbate 80 in a concentration of about 0.35 to about 0.45 weight percent and an anionic polar dimyristoylphosphatidylglyerol in a concentration of about 0.35 to about 0.45 weight percent; and 
 (iii) the natural beeswax is present in a concentration of about 0.20 to about 1.25 weight percent; and 
 wherein on contact with an eye, the ophthalmic solution rebuilds the tear film. 
   
     
     
         60 . The method of  claim 59 , wherein the ophthalmic solution:
 (i) forms a meta stable emulsion which separates into an oil phase and a water phase on contact with an eye;   (ii) provides a dwell time on the eye of at least two hours; and   (iii) is formulated as a free flowing liquid at room temperature.   
     
     
         61 . The method of  claim 59 , wherein on contact with an eye, the ophthalmic solution interacts with:
 a lipid layer;   an aqueous layer;   a mucin layer;   an interface between the lipid layer and the aqueous layer; and   an interface between the aqueous layer and the mucin layer of the eye and or the corneal cells.   
     
     
         62 . The method of  claim 59 , wherein the natural beeswax is  Cera alba  or  Cera flava.    
     
     
         63 . The method of  claim 59 , wherein the lighter molecular weight oil and heavier molecular weight oil are each a mineral oil. 
     
     
         64 . The method of  claim 59 , wherein the ophthalmic solution has an osmolality of from about 230 to about 260 mOsmol/kg. 
     
     
         65 . The method of  claim 59 , wherein the ophthalmic solution further comprises hyaluronic acid. 
     
     
         66 . A method for durable lubrication of an eye, the method comprising the step of:
 contacting an eye with an ophthalmic solution, the ophthalmic solution comprising
 a wax dispersion comprising natural beeswax, an anionic polar surfactant and water; and 
 an oil-in-water emulsion comprising an oil and water, 
 wherein: 
 (i) the oil is a mixture of a lighter molecular weight and a heavier molecular weight oil and is present in a concentration of about 1.0 to about 6.25 weight percent; 
 (ii) the anionic polar surfactant is a mixture of a Polysorbate 80 in a concentration of about 0.35 to about 0.45 weight percent and an anionic polar dimyristoylphosphatidylglyerol in a concentration of about 0.35 to about 0.45 weight percent; and 
 (iii) the natural beeswax is present in a concentration of about 0.20 to about 1.25 weight percent; and 
   wherein on contact with an eye, the ophthalmic solution provides durable eye lubrication for at least two hours.   
     
     
         67 . The method of  claim 66 , wherein on contact with an eye, the ophthalmic solution provides durable eye lubrication for greater than three hours. 
     
     
         68 . The method of  claim 66 , wherein the lighter molecular weight oil and heavier molecular weight oil are each a mineral oil. 
     
     
         69 . The method of  claim 66 , wherein the ophthalmic solution has an osmolality of from about 230 to about 260 mOsmol/kg. 
     
     
         70 . The method of  claim 66 , wherein the ophthalmic solution further comprises hyaluronic acid.