Viral hepatitis treatment

Abstract

The present disclosure relates to methods for treating viral hepatitis, compounds useful in the treatment of viral hepatitis, and pharmaceutical compositions comprising such compounds. In one embodiment, pharmaceutical compositions comprising nitazoxanide, tizoxanide, or derivatives and/or mixtures thereof are provided, as well as methods of treating hepatitis C using such compositions.

What is claimed is: 
     
       1. A method of treating hepatitis C in a patient suffering from hepatitis C, the method comprising administering to the patient a compound selected from nitazoxanide and tizoxanide or a mixture thereof, in an amount effective to reduce serum hepatitis C virus RNA in the serum of the patient to undetectable levels after administering the compound to the patient for a first period of time between about 3 days and about 24 weeks, wherein the amount is from 100 mg to 2000 mg per day. 
     
     
       2. The method of  claim 1 , wherein the compound is administered in the form of a composition further comprising a pharmaceutically acceptable carrier. 
     
     
       3. The method of  claim 2 , wherein the composition comprises a mixture of nitazoxanide and tizoxanide. 
     
     
       4. The method of  claim 2 , wherein the composition further comprises one or more additional biologically active agents selected from the group consisting of an interferon, an anti-diabetic agent, ribavirin and 2-methyl cytidine. 
     
     
       5. The method of  claim 1  or  3 , further comprising, after the first period of time, administering the compound or composition and an interferon to the patient for a second period of time of between about 1 week and about 48 weeks. 
     
     
       6. The method of  claim 1 , wherein the compound is administered to the patient for a period of between about 3 days and about 2 years. 
     
     
       7. The method of  claim 1  or  3 , wherein the method further comprises administering one or more additional active agents selected from the group consisting of an interferon, an anti-diabetic agent, ribavirin and 2-methyl cytidine. 
     
     
       8. The method of  claim 7 , wherein the one or more additional active agents comprises an interferon. 
     
     
       9. The method of  claim 8 , wherein the interferon is formulated separately from the compound. 
     
     
       10. The method of  claim 8 , wherein the interferon is interferon α-2a, interferon α-2b, or a polyethylene glycol conjugate of interferon α-2a or interferon α-2b. 
     
     
       11. The method of  claim 8 , wherein the interferon is administered to the patient for a period of about 1 week to about 48 weeks. 
     
     
       12. The method of  claim 11 , wherein the interferon is administered to the patient for a period of about 1 week to about 4-12 weeks. 
     
     
       13. The method of  claim 8 , wherein the interferon is administered to the patient between 1 and 3 times each week. 
     
     
       14. The method of  claim 8 , wherein administration of the interferon is initiated after the first period of time. 
     
     
       15. The method of  claim 8 , wherein the first period of time is between about 1 week and about 4 weeks. 
     
     
       16. The method of  claim 1 , wherein the compound is administered to the patient one to three times each day during the period of treatment. 
     
     
       17. The method of  claim 7 , wherein the one or more additional active agents comprises an anti-diabetes agent. 
     
     
       18. The method of  claim 17 , wherein the anti-diabetes agent is formulated separately from the compound. 
     
     
       19. The method of  claim 4 , wherein the composition comprises an anti-diabetes agent. 
     
     
       20. The method of  claim 4 , wherein the composition comprises an interferon. 
     
     
       21. The method of  claim 4 , wherein the composition comprises an interferon and an anti-diabetes agent. 
     
     
       22. A method of treating a patient suffering from hepatitis C, the method comprising (a) pretreating the patient for a predetermined period of time with an amount of nitazoxanide, tizoxanide or a mixture thereof, said amount being in the range of 100 mg to 2000 mg per day, and (b) after the predetermined period of time, administering to the patient an amount of an interferon, wherein the method is effective to reduce serum hepatitis C virus RNA in the serum of the patient to undetectable levels. 
     
     
       23. The method of  claim 22 , wherein the predetermined period of time is between about 3 days and about 3 months. 
     
     
       24. The method of  claim 23 , wherein the predetermined period of time is between about 1 week and about 4 weeks. 
     
     
       25. The method of  claim 22 , wherein interferon is selected from interferon α-2a, interferon α-2b, and a polyethylene glycol conjugate of interferon α-2a or interferon α-2b. 
     
     
       26. The method of  claim 25 , wherein step (b) further comprises administering a compound selected from nitazoxanide, tizoxanide or a mixture thereof. 
     
     
       27. A method of treating liver fibrosis comprising administering to a subject in need thereof an effective amount of a compound selected from nitazoxanide, tizoxanide and a mixture thereof. 
     
     
       28. The method of claim 27, wherein the compound is administered in the form of a composition further comprising a pharmaceutically acceptable carrier. 
     
     
       29. The method of claim 28, wherein the composition comprises a mixture of nitazoxanide and tizoxanide. 
     
     
       30. The method of claim 27, wherein the fibrosis is caused by hepatitis. 
     
     
       31. The method of claim 30, wherein the hepatitis is hepatitis C. 
     
     
       32. The method of claim 27, wherein the effective amount is from about 100 mg to about 2000 mg per day. 
     
     
       33. The method of claim 27, wherein the effective amount is from 250 mg to 1000 mg per day. 
     
     
       34. The method of claim 27, wherein the effective amount achieves and maintains in the subject a blood level of tizoxanide between 0.1 μg/ml and 10 μg/ml. 
     
     
       35. The method of claim 27, wherein the compound is administered orally in an oral dosage form. 
     
     
       36. The method of claim 35, wherein the oral dosage form is a tablet, a capsule, a caplet or a particulate. 
     
     
       37. The method of claim 35, wherein the oral dosage form provides a sustained release of the compound over an extended period of time. 
     
     
       38. The method of claim 35, wherein the subject is a human. 
     
     
       39. The method of claim 27, wherein the fibrosis comprises fibrous portal expansion. 
     
     
       40. The method of claim 27, wherein the fibrosis is bridging fibrosis. 
     
     
       41. The method of claim 27, wherein said administering slows down progression of the fibrosis.