Prophylactic and therapeutic use of oltipraz as an antifibrotic and anticirrhotic agent in the liver and pharmaceutical composition containing oltipraz

#1. Field of the Invention

#The present invention relates to a prophylactic and therapeutic use of 5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz) as an antifibrotic and anticirrhotic agent in the liver and to a pharmaceutical composition comprising oltipraz as an active ingredient.

#2. Description of the Related Art

#FIG. 1a is a photograph of liver tissue of a normal animal (H&E staining).

#FIG. 1b is a photograph of liver tissue from the group to which oltipraz was administered (H&E staining).

#FIG. 1c is a photograph of liver tissue from the group to which DMN was administered (H&E staining).

#The present inventors have made an unprecedented discovery in which oltipraz has been found to have an unexpectedly surprising effect of treating and preventing hepatic fibrosis and cirrhosis by inhibiting TGF-β production.

#As shown above, it is known that oltipraz protects against hepatotoxicity and inhibits the carcinogenic process. However, no other reference had ever disclosed or reported the effect of oltipraz in the treatment and prevention of hepatic fibrosis and cirrhosis as is taught by the current invention.

#Fibrosis, a preliminary stage of cirrhosis, occurs when severe damage is done to the liver and is due to by a variety of factors. Cirrhosis is partially related to carcinogenesis and notably increases the risk of liver cancer in its victims. However, the pathological mechanism of cirrhosis is clearly distinguishable from liver cancer. That is, hepatic fibrosis occurs when there is chronic and severe damage to hepatic tissue. The causative factors for liver damage include viruses, parasites, alcohol consumption, chemicals, and medicines. Hepatic fibrosis occurs through the overproduction of the extracellular matrix (e.g., type I, III and IV collagen) caused by the activation of non-parenchymal cells in hepatic tissue, such as Kupffer cells, stellate cells, etc. More specifically, fibrosis occurs due to the activation and subsequent transformation of stellate cells into myofibroblasts. The activated stellate cells then produce excess extracellular matrices. Furthermore, fibrosis and cirrhosis are clearly distinguishable as pathological phenomena apart from viral hepatitis and liver cancer. Thus, their respective treatments and preventions are also distinguishable. However, currently, there is no clinically viable drug for hepatic cirrhosis.