Method for treating meibomian gland disease

Abstract

A method for treating a patient having meibomian gland disease, ocular irritation associated with delayed tear clearance, or recurrent corneal epithelial erosion, is disclosed. Preferably, the method concerns treatment of a patient with topical tetracycline, a derivative or analogue of tetracycline, or a chemically modified tetracycline (CMT). Oral administration of a CMT is also disclosed as part of the method for treating meibomian gland disease, ocular irritation associated with delayed tear clearance, or recurrent corneal epithelial erosion.

1 - 22 . (canceled) 
     
     
         23 . A pharmaceutical composition formulated for topical administration to an eye comprising a non-antimicrobial amount of a tetracycline as an active ingredient in an amount effective to treat meibomian gland disease when administered topically to the eye, and a pharmaceutically acceptable aqueous solution. 
     
     
         24 . The composition of  claim 23 , wherein said active ingredient has a final concentration of between about 0.001% to about 1.0%. 
     
     
         25 . The composition of  claim 23 , wherein said active ingredient has a final concentration of about 0.025%. 
     
     
         26 . The composition of  claim 23 , wherein said active ingredient is doxycycline. 
     
     
         27 . The composition of  claim 23 , wherein said composition comprises one or more members of the group consisting of a balanced salt solution, a gel and a sustained-release preparation. 
     
     
         28 . The composition of  claim 23 , wherein said tetracycline is a non-antimicrobial tetracycline. 
     
     
         29 . The composition of  claim 28 , wherein said tetracycline is a tetracycline that lacks a dimethylamino side chain at position 4. 
     
     
         30 . The composition of  claim 28 , wherein said tetracycline is selected from the group consisting of 4-dedimethylaminotetracycline, 4-dedimethylamino-5-oxytetracycline, 4-dedimethylamino-7-chlorotetracycline, 4-hydroxy-4-dedimethylaminotetracycline, 4-dedimethylamino-12a-deoxytetracycline, 4-dedimethylamino-11-hydroxy-12a-deoxytetracycline, 4-dedimethylamino-7-dimethylaminotetracycline, 6-dimethyl-6-deoxy-4-dedimethylaminotetracycline, 6-o-deoxy-5-hydroxy4-dedimethylaminotetracycline, 11a-chlortetracycline, 12a-deoxytetracycline and 2-nitrilo analogs of tetracycline. 
     
     
         31 . The composition of  claim 23 , wherein said active ingredient is oxytetracycline. 
     
     
         32 . The composition of  claim 23 , wherein said active ingredient is minocycline. 
     
     
         33 . The composition of  claim 23 , wherein said composition is formulated for topical administration to one or more of an eye, an ocular surface, a preocular tear film, an eyelid skin, and a lid margin. 
     
     
         34 . The composition of  claim 23 , wherein said composition increases tear clearance in the eye of the patient, decreases ocular surface inflammation, decreases meibomian gland inflammation, neutralizes inflammatory and matrix degrading factors, decreases the level of an inflammatory cytokine in aqueous tears, or increases production of interleukin-1 receptor antagonist by corneal epithelium. 
     
     
         35 . The composition of  claim 34 , wherein said cytokine is interleukin-1-alpha. 
     
     
         36 . The composition of  claim 23 , wherein said composition inhibits one or more members of the group consisting of: matrix metalloproteinase activity in tear fluid, synthesis and activation of interleukin-1β, conversion of precursor interleukin-1β to mature interleukin-1β, reactive oxygen species in tear fluid and ocular surface epithelium. 
     
     
         37 . The composition of  claim 36 , wherein said matrix metalloproteinase comprises matrix metalloproteinase-9. 
     
     
         38 . A pharmaceutical composition formulated for topical administration to an eye comprising a non-antimicrobial amount of a tetracycline as an active ingredient in an amount effective to treat meibomian gland disease when administered topically to the eye, and a pharmaceutically acceptable aqueous solution, wherein said active ingredient has a final concentration of about 0.025%, and wherein said composition is formulated as one or more members of the group consisting of a balanced salt solution, a gel and a sustained release preparation. 
     
     
         39 . A method of treating a patient having ocular rosacea, said method comprising topically administering an effective, non-antimicrobial amount of tetracycline to an eye of said patient having ocular rosacea. 
     
     
         40 . The method of  claim 39 , wherein the tetracycline is administered at a concentration of between about 0.02% and about 3%. 
     
     
         41 . The method of  claim 39 , wherein said tetracycline is doxycycline. 
     
     
         42 . The method of  claim 39 , wherein said tetracycline is oxytetracycline. 
     
     
         43 . The method of  claim 39 , wherein said tetracycline is minocycline. 
     
     
         44 . The method of  claim 39 , wherein said tetracycline is a non-antimicrobial tetracycline. 
     
     
         45 . The method of  claim 44 , wherein said tetracycline is a tetracycline that lacks a dimethylamino side chain at position 4. 
     
     
         46 . The method of  claim 44 , wherein said tetracycline is selected from the group consisting of 4-dedimethylaminotetracycline, 4-dedimethylamino-5-oxytetracycline, 4-dedimethylamino-7-chlorotetracycline, 4-hydroxy-4-dedimethylaminotetracycline, 4-dedimethylamino-12a-deoxytetracycline, 4-dedimethylamino-11-hydroxy-12a-deoxytetracycline, 4-dedimethylamino-7-dimethylaminotetracycline, 6-dimethyl-6-deoxy-4-dedimethylaminotetracycline, 6-o-deoxy-5-hydroxy4-dedimethylaminotetracycline, 11a-chlortetracycline, 12a-deoxytetracycline and 2-nitrilo analogs of tetracycline. 
     
     
         47 . The method of  claim 39 , wherein said amount increases tear clearance in the eye of the patient, decreases ocular surface inflammation, decreases meibomian gland inflammation, neutralizes inflammatory and matrix degrading factors, decreases the level of an inflammatory cytokine in aqueous tears, or increases production of interleukin-1 receptor antagonist by corneal epithelium. 
     
     
         48 . The method of  claim 47 , wherein said cytokine is interleukin-1-alpha. 
     
     
         49 . The method of  claim 39 , wherein said treatment comprises inhibiting a member selected from the group consisting of: matrix metalloproteinase activity in tear fluid, synthesis and activation of interleukin-1β, conversion of precursor interleukin-1β to mature interleukin-1β, reactive oxygen species in tear fluid and ocular surface epithelium. 
     
     
         50 . The method of  claim 49 , wherein said matrix metalloproteinase comprises matrix metalloproteinase-9.