Desethylhydroxychloroquine for the treatment of diseases associated with inflammation

Abstract

Compositions and methods are provided for inhibiting or treating the early and established stages of inflammatory diseases by administration of an effective dose of the desethylhydroxychloroquine (DHCQ). A benefit of the methods is the ability to deliver a dose of agent that is effective in treating inflammation while sparing the individual from retinal toxicity.

1 . A pharmaceutical composition comprising:
 a unit dose of 25 to 3000 ma desethylhydroxychloroquine or salt and/or ester thereof effective in treating inflammation with decreased retinal toxicity in combination with an effective dose of one or more statins; and a pharmaceutically acceptable excipient.   
     
     
         2 - 39 . (canceled) 
     
     
         40 . The composition of  claim 1 , wherein the statin is selected from the group consisting of atorvastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. 
     
     
         41 . The composition of  claim 40 , wherein the statin is present at a dose of from 1 to 250 mg. 
     
     
         42 . The composition of  claim 41 , wherein the statin is present as a concentration of from 5 to 60 mg. 
     
     
         43 . The composition of  claim 1 , wherein the dose of desethylhydroxychloroquine is about 100-600 mg. 
     
     
         44 . A method of treating an inflammatory disease comprising:
 administering to an individual in need thereof a pharmaceutical composition comprising a unit dose of 25 to 3000 mg desethylhydroxychloroquine, or a salt and/or ester thereof effective in treating inflammation with decreased retinal toxicity in combination with an effective dose of one or more statins; and a pharmaceutically acceptable excipient.   
     
     
         45 . The method of  claim 44 , wherein a daily amount of desethylhydroxychloroquine administered to the individual for the first 1 to 16 weeks is higher than the daily amount of desethylhydroxychloroquine administered subsequently. 
     
     
         46 . The method of  claim 44 , wherein the statin is selected from the group consisting of atorvastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. 
     
     
         47 . The method of  claim 46 , wherein the statin is present at a dose of from 1 to 250 mg. 
     
     
         47 . The method of  claim 47 , wherein the statin is present as a concentration of from 5 to 60 mg. 
     
     
         48 . The method of  claim 44 , wherein the dose of desethylhydroxychloroquine is about 100-600 mg. 
     
     
         49 . The method of  claim 44 , wherein the inflammatory disease is a degenerative disease selected from the group consisting of osteoarthritis, Alzheimer's disease, and macular degeneration. 
     
     
         50 . The method of  claim 44 , wherein the inflammatory disease is a metabolic disease selected from the group consisting of type II diabetes, atherosclerosis and non-alcoholic steatohepatitis. 
     
     
         51 . The method of  claim 44 , wherein after 10 years of said administration, the individual is substantially without symptoms of retinal toxicity. 
     
     
         52 . The method of  claim 44 , wherein there is reduced screening for retinal toxicity. 
     
     
         53 . The method of  claim 52 , wherein screening starts after 10 years of said administration. 
     
     
         54 . The method of  claim 44 , wherein there is no screening for retinal toxicity.