A novel composition for nonalcoholic fatty liver disease (nafld)

Abstract

The present invention provides a compound of Formula (I) or pharmaceutical acceptable thereof, wherein ‘R’ is herein described. In addition, the invention relates to composition comprising effective therapeutic amount of compound of formula (I) and methods of using the compounds for treating or prevention disorder such as nonalcoholic fatty liver disease (NAFLD) including fatty liver (steatosis), nonalcoholic steatohepatitis (NASH), and cirrhosis (advanced scarring of the liver).

1 . A pharmaceutical composition comprising
 (a) a pharmaceutically active substance of Formula (I);   
       
         
           
           
               
               
           
         
         wherein ‘R’ is selected from hydroxy, hydroxyalkyl, acyl, alkoxy, alkylthio, thioalkyl, aryloxy, arylthio and M +  represents suitable metal cations selected from Na+, K+, Ca+2, Mg+2 
         (b) suitable additives 
         (c) a suitable stabilizer; 
         (d) optionally one or more pharmaceutically acceptable excipients for the treatment of nonalcoholic fatty liver disease (NAFLD). 
       
     
     
         2 . The pharmaceutical composition as claimed in  claim 1  used for the reduction and removal of lipid accumulated in the liver cells (hepatocytes). 
     
     
         3 . The pharmaceutical composition of  claim 1  for the prevention and/or reducing/ameliorating the conditions associated with non-alcoholic fatty liver disease (NAFLD) including fatty liver (steatosis), non-alcoholic steatohepatitis (NASH), and cirrhosis (advanced scarring of the liver). 
     
     
         4 . The pharmaceutical composition of  claim 3  wherein the disease condition is fatty liver (steatosis). 
     
     
         5 . The pharmaceutical composition of  claim 3  wherein the disease condition is non-alcoholic steatohepatitis (NASH). 
     
     
         6 . The pharmaceutical composition of  claim 3  wherein the disease condition cirrhosis. 
     
     
         7 . The pharmaceutical composition as claimed in  claim 1  wherein the suitable stabilizer is selected from antioxidants or chelating agents. 
     
     
         8 . The pharmaceutical composition as claimed in  claim 7  wherein the suitable antioxidants are selected from citric acid, alpha tocopherol, sodium sulphite, sodium metabisulphite, butylated hydroxy anisole (BHA), BHT (2,6-di-tert-butyl-4-methylphenol), monothioglycerol, Vitamin C (ascorbic acid). 
     
     
         9 . The pharmaceutical composition as claimed in  claim 7  wherein the suitable chelating agents are selected from Disodium EDTA, citric acid and or its salts, maleic acid, chlorambutol, chlorhexidine. 
     
     
         10 . The pharmaceutical composition as claimed in  claim 1  wherein pharmaceutically active substance of Formula (I) is used in the range of 0.5 mg to 5 g. 
     
     
         11 . The pharmaceutical composition as claimed in  claim 1  wherein the suitable excipients are selected from solubilizers, diluents, fillers, disintegrants, binder, lubricants, glidants, wetting agents and solvents. 
     
     
         12 . The pharmaceutical composition as claimed in  claim 1  wherein the suitable additives are selected from sodium benzoate, sodium hydroxide, sodium sulfite and sodium carbonate. 
     
     
         13 . The pharmaceutical composition as claimed in  claim 1  wherein the suitable binders are selected from acacia alginic acid, tragacanth, carboxymethylcellulose sodium, poly (vinylpyrrolidone), compressible sugar (e.g., NuTab), ethylcellulose, gelatin, liquid glucose, methyl cellulose, povidone and pregelatinized starch, combinations thereof; poly(ethylene glycol), guar gum, polysaccharide, bentonites, sugars, invert sugars, poloxamers (PLURONIC F68, PLURONIC F127), collagen, albumin, celluloses in nonaqueous solvents, and the like or their suitable combinations; poly(propylene glycol), polyoxyethylene-polypropylene copolymer, polyethylene ester, polyethylene sorbitan ester, poly(ethylene oxide), microcrystalline cellulose, poly(vinylpyrrolidone). 
     
     
         14 . The pharmaceutical composition as claimed in  claim 1  wherein the suitable glidants selected from glicolloidal silica, calcium silicate, magnesium silicate, silicon hydrogel, corn starch and talc. 
     
     
         15 . The pharmaceutical composition as claimed in  claim 1  wherein the suitable glidants selected from calcium stearate, magnesium stearate, mineral oil, stearic acid, zinc stearate. 
     
     
         16 . The pharmaceutical composition as claimed in  claim 1  wherein the suitable lubricants are selected from calcium stearate, magnesium stearate, mineral oil, stearic acid and zinc stearate. 
     
     
         17 . The pharmaceutical composition as claimed in  claim 1  wherein the suitable disintegrant are selected from starches such as corn starch, potato starch, pre-gelatinized and modified starches, sweeteners, clays, microcrystalline cellulose, carsium, alginates, sodium starch glycolate, gums, guar, locust bean, karaya, pectin, tragacanth. 
     
     
         18 . The pharmaceutical composition as claimed in  claim 1  wherein the suitable wetting agent are selected from poloxamers, gelatin, casein, Glycerol mono-oleate, lecithin (phosphatides), gum acacia, cholesterol, tragacanth, stearic acid, benzalkonium chloride, calcium stearate, glycerol monostearate, cetostearyl alcohol, sodium lauryl sulphate, sodium dodecyl sulfate, salts of bile acids, cetomacrogol emulsifying wax, sorbitan esters, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyethylene glycols, polyoxyethylene stearates, colloidal silicon dioxide, phosphates, sodium dodecylsulfate, carboxymethylcellulose calcium, carboxy methylcellulose, sodium methyl cellulose, hydroxyethyl cellulose, hydroxylpropyl cellulose, hydroxy propyl methyl cellulose phthalate, noncrystalline cellulose, magnesium aluminum silicate, triethanolamine, polyvinyl alcohol, and poly vinyl pyrrolidone. 
     
     
         19 . The composition as claimed in  claim 1  is formulated in tablet or capsule forms. 
     
     
         20 . The composition as claimed in  claim 1  wherein the pH is maintained in the range of 6 to 10. 
     
     
         21 . The compound as claimed in  claim 1  wherein R is —SMe and M +  is Mg +2 . 
     
     
         22 . The compound of  claim 1  is magnesium salt of compound of formula (I) wherein R is —SMe. 
     
     
         23 . A method of treating and/or ameliorating nonalcoholic fatty liver disease (NAFLD) by treating a patient the composition as claimed in  claim 1 . 
     
     
         24 . The method as claimed in  claim 23 , wherein the disease condition includes fatty liver (steatosis), non-alcoholic steatohepatitis (NASH), and cirrhosis of the liver. 
     
     
         25 . The method as claimed in  claim 23  wherein the composition comprises compound of formula (I) wherein M is —SMe and M +  is Mg +2 . 
     
     
         26 . Use of the composition of  claim 1  for the treatment of non-alcoholic fatty liver disease (NAFLD).