Modified release compositions of epalrestat or a derivative thereof and methods for using the same

Abstract

Modified release pharmaceutical compositions of epalrestat are provided. Methods of manufacturing the tablets and treating various diseases and conditions, including diabetes and diabetic complications, by administering the modified release compositions to patients in need thereof are also provided.

1 .- 32 . (canceled) 
     
     
         33 . A modified release pharmaceutical composition, comprising epalrestat or a pharmaceutically acceptable derivative thereof; and one or more water-swellable polymers; wherein the sustained release pharmaceutical composition is administered to a patient once or twice a day to provide a continuous therapeutic effect throughout the day. 
     
     
         34 . The modified release pharmaceutical composition of  claim 33 , which
 (i) when administered to a patient on a regular dosing schedule, provides a relatively flat plasma concentration profile of epalrestat at steady state, wherein there are no substantial peaks or troughs in the relatively flat plasma concentration profile, and the minimum plasma concentration of epalrestat in the relatively flat plasma concentration profile is sufficient to provide a therapeutic effect to the patient; or   (ii) when administered to a patient on a regular dosing schedule, provides a relatively flat plasma concentration profile of epalrestat at steady state such that a mean Cmin/Cmax epalrestat ratio during dosing interval is about 0.55 to about 1.0, and the Cmin is sufficient to provide a therapeutic effect; or   (iii) provides to a patient a therapeutic effect for about 12 to about 24 hours and a relatively flat plasma concentration profile of epalrestat at steady state such that the minimum plasma concentration of epalrestat during the dosing interval is about 55% of the maximum plasma concentration during the dosing interval.   
     
     
         35 . The modified release pharmaceutical composition of  claim 33 , wherein the water-swellable polymer is a cellulose ether polymer. 
     
     
         36 . The modified release pharmaceutical composition of  claim 35 , wherein the cellulose ether polymer is hypromellose, hydroxypropyl ethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, methyl cellulose or a combination thereof. 
     
     
         37 . The modified release pharmaceutical composition of  claim 33 , wherein the water-swellable polymer is a non-cellulose based water-swellable polymer. 
     
     
         38 . The modified release pharmaceutical composition of  claim 37 , wherein the non-cellulose based water-swellable polymer to anionic derivatives of agar; anionic derivatives of guar gum; anionic derivatives of locust bean gum; anionic derivatives of xanthan gum; anionic derivatives of alginin (such as alginates); anionic derivatives of polysaccharides of mannose and galactose, or chi to san; anionic derivatives of modified starch; or a combination thereof. 
     
     
         39 . The modified release pharmaceutical composition of  claim 33 , further comprising a release rate adjusting agent. 
     
     
         40 . The modified release pharmaceutical composition of  claim 39 , wherein the release rate adjusting agent is saccharide-based. 
     
     
         41 . The modified release pharmaceutical composition of  claim 40 , wherein the saccharide-based release rate adjusting agent is a polyol compound selected from arabitol, xylitol, ribitol, mannitol, sorbitol, dulcitol, fucitol, iditol, isomalt, maltitol, and lactitiol. 
     
     
         42 . The modified release pharmaceutical composition of  claim 33 , wherein epalrestat or a pharmaceutically acceptable derivative thereof is choline hydrogen diepalrestat. 
     
     
         43 . The modified release pharmaceutical composition of  claim 33 , for use in treating diabetes or a diabetic complication in a subject in need thereof. 
     
     
         44 . The use of  claim 43 , wherein the diabetic complication is selected from the group consisting of diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic retinopathy, diabetic gastroparesis, cataracts, foot ulcers, diabetic macroangiopathy, diabetic microangiopathy, high blood glucose, high HbAlc levels, and combinations thereof. 
     
     
         45 . The modified release pharmaceutical composition of  claim 33 , for use in inhibiting aldose reductase or affording cardioprotection in a subject in need thereof. 
     
     
         46 . The modified release pharmaceutical composition of  claim 45 , wherein the subject has been diagnosed with, or at risk for, coronary heart disease, cardiac dysfunction, or myocardial stunning. 
     
     
         47 . The modified release pharmaceutical composition of  claim 33 , for use in treating cardiac tissue ischemia in a subject in need thereof.