Methods and Compositions for Treating Meibomian Gland Dysfunction

Abstract

The invention provides methods, compositions, and kits containing a minocycline topical suspension, for treating meibomian gland dysfunction and related disorders.

1 . A method of treating meibomian gland dysfunction, comprising topically administering to the eyelid margin of a patient in need thereof once or twice per day a dose of a minocycline topical suspension to treat the meibomian gland dysfunction, wherein the dose provides from about 0.1 mg to about 1.4 mg of minocycline, and the minocycline topical suspension comprises:
 a) minocycline in a suspended form within the topical suspension;   b) a liquid medium that dissolves less than 5% (w/w) of the minocycline at room temperature after two hours, wherein the liquid medium contains mineral oil; and   c) a polymeric hydrocarbon gelling agent;   wherein particles of minocycline in the topical suspension have a D90 particle size less than 8 microns, and the topical suspension comprises from about 0.1% (w/w) to about 2% (w/w) minocycline.   
     
     
         2 . The method of  claim 1 , wherein the dose of minocycline topical suspension provides from about 0.1 mg to about 0.2 mg of minocycline. 
     
     
         3 . The method of  claim 1 , wherein the dose of minocycline topical suspension provides about 0.15 mg of minocycline. 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the dose of minocycline topical suspension provides from about 0.45 mg to about 0.55 mg of minocycline. 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the topical suspension comprises from about 0.3% (w/w) to about 1% (w/w) minocycline. 
     
     
         8 . The method of  claim 1 , wherein the topical suspension comprises from about 0.2% (w/w) to about 0.4% (w/w) minocycline. 
     
     
         9 . The method of  claim 1 , wherein the topical suspension comprises about 0.3% (w/w) minocycline. 
     
     
         10 . The method of  claim 1 , wherein the topical suspension comprises 0.3% (w/w) minocycline. 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the topical suspension comprises about 1% (w/w) minocycline. 
     
     
         13 . The method of  claim 1 , wherein an amount of from about 35 μL to about 65 μL of the minocycline topical suspension is topically administered to the eyelid margin of the patient. 
     
     
         14 - 19 . (canceled) 
     
     
         20 . The method of  claim 1 , wherein the dose of minocycline topical suspension is administered twice per day. 
     
     
         21 . The method of  claim 10 , wherein the dose of minocycline topical suspension is administered twice per day, wherein the first dose of minocycline topical suspension is administered in the morning and the second dose of minocycline topical suspension is administered in the evening. 
     
     
         22 - 31 . (canceled) 
     
     
         32 . The method of  claim 1 , wherein the patient has an inflamed meibomian gland. 
     
     
         33 - 38 . (canceled) 
     
     
         39 . A method of treating meibomian gland dysfunction in a patient having a tear film matrix metalloproteinase-9 (MMP-9) concentration greater than about 40 ng/mL, comprising topically administering to the eye of said patient in need thereof a therapeutically effective amount of minocycline to treat the meibomian gland dysfunction. 
     
     
         40 . The method of  claim 1 , wherein the method produces a reduction in vascular engorgement score of at least 1. 
     
     
         41 . The method of  claim 1 , wherein after a duration of at least three months where the patient has received a dose of minocycline topical suspension each day, the patient has a vascular engorgement score of no greater than 1.5. 
     
     
         42 . (canceled) 
     
     
         43 . The method of  claim 1 , wherein the method produces a reduction in Eye Discomfort Visual Analog Score of at least 20 percent. 
     
     
         44 . The method of  claim 1 , wherein after a duration of at least three months where the patient has received a dose of minocycline topical suspension each day, the patient has an Eye Discomfort Visual Analog Score of no greater than 50. 
     
     
         45 - 56 . (canceled) 
     
     
         57 . The method of  claim 1 , wherein the polymeric hydrocarbon gelling agent comprises an ethylene-propylene-styrene copolymer having a weight-average molecular weight in the range of from about 150,000 g/mol to about 250,000 g/mol. 
     
     
         58 - 61 . (canceled) 
     
     
         62 . The method of  claim 1 , wherein the polymeric hydrocarbon gelling agent comprises a butylene-ethylene-styrene copolymer having a weight-average molecular weight in the range of from about 50,000 g/mol to about 150,000 g/mol. 
     
     
         63 - 69 . (canceled) 
     
     
         70 . The method of  claim 1 , wherein the polymeric hydrocarbon gelling agent comprises at least about 80% (w/w) mineral oil. 
     
     
         71 . (canceled) 
     
     
         72 . The method of  claim 1 , wherein the minocycline topical suspension comprises from about 60% (w/w) to about 80% (w/w) of the polymeric hydrocarbon gelling agent. 
     
     
         73 . (canceled) 
     
     
         74 . (canceled) 
     
     
         75 . (canceled) 
     
     
         76 . The method of  claim 72 , wherein the minocycline topical suspension comprises from about 20% (w/w) to about 40% (w/w) of the liquid medium that dissolves less than 5% (w/w) of the minocycline at room temperature after two hours, wherein the liquid medium contains mineral oil. 
     
     
         77 - 80 . (canceled) 
     
     
         81 . The method of  claim 76 , wherein the liquid medium that dissolves less than 5% (w/w) of the minocycline at room temperature after two hours comprises at least 99% (w/w) mineral oil. 
     
     
         82 - 90 . (canceled)