Methods of treatment for cholestatic and fibrotic diseases

Abstract

The present invention relates to a synergistic combination of active ingredients for use in the treatment of fibrotic diseases.

1 . A method of treating a fibrotic disorder comprising administering a therapeutically effective amount of a pharmaceutical composition to a subject in need thereof, wherein the pharmaceutical composition consists essentially of (i) Nitazoxanide (NTZ), Tizoxanide (TZ) or Tizoxanide glucuronide (TZG), or a pharmaceutically acceptable salt of NTZ, TZ or TZG; and
 (ii) at least one statin selected in the group consisting of pitavastatin, fluvastatin, simvastatin, atorvastatin, lovastatin, and pravastatin.   
     
     
         2 . The method of  claim 1 , wherein the fibrotic disorder is selected in the group consisting of liver, gut, kidney, skin, epidermis, endodermis, muscle, tendon, cartilage, heart, pancreas, lung, uterus, nervous system, testis, penis, ovary, adrenal gland, artery, vein, colon, intestine, biliary tract, soft tissue, bone marrow, joint eye, and stomach fibrosis. 
     
     
         3 . The method according to  claim 2 , wherein the fibrotic disorder is a liver fibrosis. 
     
     
         4 . The method according to  claim 3 , wherein the liver fibrosis is selected from the group consisting of non-alcoholic steatohepatitis (NASH), alcohol-induced liver fibrosis, drug-induced liver fibrosis, and liver cirrhosis. 
     
     
         5 . The method according to  claim 3 , the method consisting essentially of administrating simultaneously, sequentially or separately a therapeutically effective amount of:
 (i) Nitazoxanide (NTZ) and   (ii) at least one statin selected in the group consisting of pitavastatin, fluvastatin, simvastatin, atorvastatin, lovastatin, and pravastatin;   to a subject in need thereof.   
     
     
         6 . A method of treating a fibrotic disorder comprising administering to a subject in need thereof a kit comprising:
 (i) a composition comprising Nitazoxanide (NTZ), Tizoxanide (TZ) or Tizoxanide glucuronide (TZG), or a pharmaceutically acceptable salt of NTZ, TZ or TZG; and   (ii) a composition comprising at least one statin, wherein the at least one statin is selected in the group consisting of pitavastatin, fluvastatin, simvastatin, atorvastatin, lovastatin, and pravastatin,   
       wherein the compositions are administered simultaneously, sequentially or separately administration to said subject. 
     
     
         7 . The method according to  claim 6 , wherein the fibrotic disorder is selected in the group consisting of liver, gut, kidney, skin, epidermis, endodermis, muscle, tendon, cartilage, heart, pancreas, lung, uterus, nervous system, testis, penis, ovary, adrenal gland, artery, vein, colon, intestine, biliary tract, soft tissue, bone marrow, joint eye, and stomach fibrosis. 
     
     
         8 . The method according to  claim 7 , wherein the fibrotic disorder is a liver fibrosis. 
     
     
         9 . The method according to  claim 8 , wherein the liver fibrosis is selected from the group consisting of non-alcoholic steatohepatitis (NASH), alcohol-induced liver fibrosis, drug-induced liver fibrosis, and liver cirrhosis.