β-L-2′-deoxy-nucleosides for the treatment of hepatitis B
View Patent ↗This invention is directed to a method for treating a host infected with hepatitis B comprising administering an effective amount of an anti-HBV biologically active 2′-deoxy-β-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2′-deoxy-β-L-erythro-pentofuranonucleoside has the formula: wherein R is selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate, or a phosphate derivative; and BASE is a purine or pyrimidine base which may be optionally substituted. The 2′-deoxy-β-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof may be administered either alone or in combination with another 2′-deoxy-β-L-erythro-pentofuranonucleoside or in combination with another anti-hepatitis B agent.
1. A method for inhibiting replication of human hepatitis B virus in cells in a human host in need thereof and infected with a hepatitis B virus comprising contacting the cells with an effective amount of β-L-thymidine of the formula:
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the cells are contacted with an effective amount of β-L-thymidine of the formula:
3. The method of claim 1 , wherein the cells are contacted with an effective amount of a pharmaceutically acceptable salt of β-L-thymidine of the formula:
4. A method for the treatment of a hepatitis B virus infection in an infected human host in need thereof and comprising administering to the human host an amount of β-L-thymidine of the formula:
or a pharmaceutically acceptable salt thereof, with a dosage effective to treat the hepatitis B virus infection by oral administration.
5. The method of claim 4 , wherein an effective amount of β-L-thymidine of the formula:
is administered.
6. The method of claim 4 , wherein an effective amount of a pharmaceutically acceptable salt of β-L-thymidine of the formula:
is administered.
7. The method of claim 4 , comprising administering orally a unit dosage form of β-L-thymidine or a pharmaceutically acceptable salt thereof.
8. The method of claim 7 , wherein the unit dosage form comprises about 50-1000 mg of β-L-thymidine or a pharmaceutically acceptable salt thereof.
9. The method of claim 7 , wherein the unit dosage form is a tablet.
10. The method of claim 9 , wherein the unit dosage form further comprises microcrystalline cellulose, gum tragacanth, gelatin, starch, lactose, alginic acid, Primogel, corn starch, magnesium stearate, Sterotes, colloidal silicon dioxide, sucrose, saccharin, peppermint, methyl salicylate, or orange flavoring.
11. The method of claim 4 , wherein β-L-thymidine or a pharmaceutically acceptable salt thereof is administered at the dosage of about 1 to 20 mg/kg of body weight per day.
12. The method of claim 4 , further comprising wherein β-L-thymidine or a pharmaceutically acceptable salt thereof is at least 95% in its designated enantiomeric form.
13. The method of claim 4 , wherein the hepatitis B virus infection is a chronic persistent hepatitis B virus infection.
14. The method of claim 4 , wherein the hepatitis B virus infection is a chronic infection.
15. The method of claim 4 , wherein the amount of β-L-thymidine or a pharmaceutically acceptable salt thereof is effective to inhibit viral replication in vivo.
16. The method of claim 4 , wherein the human host in need thereof is anti-HBV antibody positive or HBV-positive.
17. The method of claim 4 , wherein the human host in need thereof has chronic liver inflammation caused by hepatitis B virus.
18. The method of claim 4 , wherein the human host in need thereof has cirrhosis, acute hepatitis, fulminant hepatitis, chronic persistent hepatitis, or fatigue.