Ophthalmic compositions of rifamycins and uses thereof

Abstract

Provided herein are ophthalmic pharmaceutical formulations comprising a rifamycin compound. Also provided herein are methods of treating ocular diseases or disorders by administering such ophthalmic formulations. This invention relates generally to pharmaceutical compositions or formulations suitable for administration to an eye. In some aspects, this invention relates to ophthalmic pharmaceutical compositions or formulations comprising one or more rifamycin compounds selected from the group consisting of rifampicin, rifabutin, rifapentine. In one aspect, the invention relates to methods of treating an ocular disease, disorder or condition comprising administering to a patient in need thereof an ophthalmic composition comprising an effective amount of a rifamycin compound selected from the group consisting of rifampicin, rifabutin, rifapentine, and rifaximin.

1 . A method of treating an ocular disease, disorder or condition comprising administering to a patient in need thereof an ophthalmic composition comprising an effective amount of a rifamycin compound selected from the group consisting of rifampicin, rifabutin, rifapentine and rifaximin, or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The method of  claim 1 , wherein the ocular disease, disorder or condition is selected from age related macular degeneration (AMD), ocular neovascularization, retinal ganglion cell injury and brain damage. 
     
     
         3 . A method of treating age-related macular degeneration (AMD) comprising administering to a patient in need thereof an ophthalmic composition comprising a therapeutically effective amount of a rifamycin compound selected from the group consisting of rifampicin, rifabutin, rifapentine and rifaximin, or a pharmaceutically acceptable salt thereof. 
     
     
         4 . A method of treating ocular neovascularization comprising administering to a patient in need thereof an ophthalmic composition comprising a therapeutically effective amount of a rifamycin compound selected from the group consisting of rifampicin, rifabutin, rifapentine and rifaximin, or a pharmaceutically acceptable salt thereof. 
     
     
         5 . The method of  claim 4 , wherein the ocular neovascularization comprises retinal neovascularization. 
     
     
         6 . A method of protecting optic nerve cells comprising administering to a patient in need thereof an ophthalmic composition comprising a therapeutically effective amount of a rifamycin compound selected from the group consisting of rifampicin, rifabutin, rifapentine and rifaximin, or a pharmaceutically acceptable salt thereof. 
     
     
         7 . The method of  claim 6 , wherein the optic nerve cells are retinal ganglion cells. 
     
     
         8 . A method of inhibiting brain damage comprising administering to a patient in need thereof an ophthalmic composition comprising a therapeutically effective amount of a rifamycin compound selected from the group consisting of rifampicin, rifabutin, rifapentine and rifaximin, or a pharmaceutically acceptable salt thereof. 
     
     
         9 . An ophthalmic composition comprising an effective amount of rifamycin compound selected from the group consisting of rifampicin, rifabutin, rifapentine and rifaximin, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         10 . The ophthalmic composition of  claim 9 , wherein the pharmaceutically acceptable carrier comprises a tonicity adjusting agent. 
     
     
         11 . The ophthalmic composition of  claim 10 , wherein the tonicity adjusting agent is saline, dextrose, glycerin, aqueous potassium chloride, buffer salts, propylene glycol, or mannitol. 
     
     
         12 . The ophthalmic composition of  claim 10  in the form of a topical eye drop. 
     
     
         13 . The ophthalmic composition of any one of the  claims 10 - 12  for use in the manufacture of a medicament for treatment of an ocular disease, disorder or condition. 
     
     
         14 . The ophthalmic composition of  claim 13 , wherein the ocular disease, disorder or condition is selected from age related macular degeneration (AMD), ocular neovascularization, retinal ganglion cell injury and brain damage. 
     
     
         15 . A formulation for treatment of an ocular disease, disorder or condition, comprising an effective amount of rifamycin compound selected from the group consisting of rifampicin, rifabutin, rifapentine and rifaximin, and at least one pharmaceutically acceptable carrier material. 
     
     
         16 . The formulation of  claim 15 , wherein the carrier material comprises an ocular/ophthalmic carrier. 
     
     
         17 . The formulation of  claim 15 , further comprising one or more of a surfactant, an anti-bacterial agent, a pH buffering agent, an antioxidant agent, a preservative agent, or a combination thereof. 
     
     
         18 . A method of inhibiting ocular neovascularization in a retina of a patient in need thereof, comprising administering topically a pharmaceutically acceptable composition comprising up to about 1% (g/100 mL of the composition, or weight/volume, or (w/v)), or about 0.1% to about 1%, or about 0.25% to about 1%, or about 0.5% to about 1%, or about 0.1% to about 0.5%, or about 0.25% to about 0.5%, or about 0.25%, or about 0.5% of rifampicin and at least one pharmaceutically acceptable excipient to an eye of the patient containing the retina. 
     
     
         19 . A pharmaceutically acceptable topical eye drop composition comprising up to about 1% (g/100 mL of the composition weight/volume or (w/v)), or about 0.1% to about 1%, or about 0.25% to about 1%, or about 0.5% to about 1%, or about 0.1% to about 0.5%, or about 0.25% to about 0.5%, or about 0.25%, or about 0.5% of rifampicin and at least one pharmaceutically acceptable excipient. 
     
     
         20 . A pharmaceutically acceptable composition for subcutaneous injection comprising up to about 1% (g/100 mL of the composition weight/volume or (w/v)), or about 0.1% to about 1%, or about 0.25% to about 1%, or about 0.5% to about 1%, or about 0.1% to about 0.5%, or about 0.25% to about 0.5%, or about 0.25%, or about 0.5% of rifampicin and at least one pharmaceutically acceptable excipient. 
     
     
         21 . A method of reducing retina thickness in a patient in need thereof comprising administering to the patient an ophthalmic composition comprising an effective amount of a rifamycin compound selected from the group consisting of rifampicin, rifabutin, rifapentine and rifaximin, or a pharmaceutically acceptable salt thereof. 
     
     
         22 . The method of  claim 21 , wherein the patient is suffering from age related macular degeneration (AMD), ocular neovascularization, retinal ganglion cell injury, or brain damage. 
     
     
         23 . The method of  claim 21 , wherein the ocular neovascularization comprises retinal neovascularization. 
     
     
         24 . The method of  claim 21 , wherein the ophthalmic composition is a topical eye drop. 
     
     
         25 . The method of  claim 21 , wherein ophthalmic composition comprising an effective amount of the rifamycin compound selected from the group consisting of rifampicin, rifabutin, rifapentine and rifaximin, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         26 . The method of  claim 25 , wherein the pharmaceutically acceptable carrier comprises a tonicity adjusting agent. 
     
     
         27 . The method of  claim 25 , wherein the tonicity adjusting agent is saline, dextrose, glycerin, aqueous potassium chloride, buffer salts, propylene glycol, or mannitol.