Agent for treatment of liver diseases containing pyrazolopyrimidinone derivative
Inventors
Choi, Seul Min • Ahn, Byong Ok • Yoo, Moohi
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-8796286-B2
Publication Date
2014-08-05
Expiration Date
Abstract
The present invention relates to the pharmaceutical composition for prevention and treatment of liver diseases containing pyrazolopyrimidine derivative as an active ingredient. According to the present invention, pyrazolopyrimidine derivative has an excellent effect on inhibiting collagen synthesis in hepatic stellate cells and acts directly on the portal vein. Particularly, it may increase the diameter and the amount of blood flow of the portal vein, and finally decrease the pressure thereof. Therefore, pyrazolopyrimidine derivative can be used advantageously for prevention and treatment of hepatic fibrosis, liver cirrhosis caused by hepatic fibrosis, portal hypertension and various complications caused by portal hypertension. In addition, pyrazolopyrimidine derivative according to the present invention can reduce dosing frequency because of its long half-life, and therefore, has an advantage to improve the drug compliance of patients suffering from chronical liver diseases.
Core Innovation
The invention relates to pharmaceutical use of a pyrazolopyrimidinone having Formula I, characterized as a PDE5 inhibitor, for liver diseases. The disclosed approach addresses hepatic fibrosis and conditions associated with hepatic portal hypertension by administering an effective amount of the pyrazolopyrimidinone of Formula I to a mammal in need thereof.
A key aspect is inhibition of collagen synthesis in hepatic stellate cells, which is presented as a mechanism for preventing and/or treating hepatic fibrosis. The disclosed outcomes extend to fibrosis-driven liver cirrhosis and hepatic fibrosis-related portal hypertension.
Another aspect is direct action on the portal vein, presented as increasing portal vein diameter and blood flow while decreasing portal pressure. The described therapeutic effect is linked to prevention and/or treatment of hepatic fibrosis, portal hypertension, and complications of portal hypertension.
Claims Coverage
The independent claims provided cover four distinct methods of using a pyrazolopyrimidinone having Formula I, including reducing hepatic fibrosis, inhibiting collagen synthesis, inhibiting hepatic portal hypertension, and treating complications caused by hepatic portal hypertension. The inventive features are centered on administration of an effective amount of the Formula I pyrazolopyrimidinone to a mammal in need thereof, with treatment scope differentiated by the stated disease/physiological target.
Reducing hepatic fibrosis by administering Formula I pyrazolopyrimidinone
A method of reducing hepatic fibrosis in a mammal comprising administering an effective amount of a pyrazolopyrimidinone having Formula I to a mammal in need thereof.
Inhibiting collagen synthesis by administering Formula I pyrazolopyrimidinone
A method of inhibiting collagen synthesis in a mammal comprising administering an effective amount of a pyrazolopyrimidinone having Formula I to a mammal in need thereof.
Inhibiting hepatic portal hypertension by administering Formula I pyrazolopyrimidinone
A method for inhibiting hepatic portal hypertension in a mammal comprising administering an effective amount of a pyrazolopyrimidinone having Formula I to a mammal in need thereof.
Treating hepatic portal hypertension complications by administering Formula I pyrazolopyrimidinone
A method for treating a complication caused by hepatic portal hypertension in a mammal comprising administering an effective amount of a pyrazolopyrimidinone having Formula I to a mammal in need thereof, wherein the complication is selected from the group consisting of esophageal varices, splenic enlargement, hypersplenism, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy and hepatopulmonary syndrome.
Across the independent claims, the core inventive concept is administration of an effective amount of a pyrazolopyrimidinone having Formula I to achieve specified therapeutic effects: reducing hepatic fibrosis, inhibiting collagen synthesis, inhibiting hepatic portal hypertension, and treating selected complications caused by hepatic portal hypertension.
Stated Advantages
Prevention/treatment of hepatic fibrosis.
Prevention/treatment of fibrosis-driven cirrhosis.
Prevention/treatment of portal hypertension.
Reduction of portal pressure while markedly increasing portal flow.
Improved human pharmacokinetics, including a longer half-life than sildenafil and vardenafil, supporting reduced dosing frequency and improved compliance.
Documented Applications
Prevention/treatment of hepatic fibrosis.
Prevention/treatment of fibrosis-driven cirrhosis.
Prevention/treatment of hepatic portal hypertension.
Treatment of complications of portal hypertension, including esophageal varices, splenic enlargement, hypersplenism, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatopulmonary syndrome, and hepatic encephalopathy.
Comparative use in relation to sildenafil and vardenafil, including potency comparison and human pharmacokinetics comparison.
Interested in licensing this patent?