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-eythro-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 the treatment of a hepatitis B virus infection in a human comprising administering an effective amount of β-L-2′-deoxythymidine, or a pharmaceutically acceptable salt thereof in a pharmaceutically acceptable carrier that provides controlled release of the β-L-2′-deoxythymidine.
2. The method of claim 1 , wherein the β-L-2′-deoxythymidine is at least 95% in its designated enantiomeric form.
3. The method of claim 1 , wherein the carrier is in the form of an implant.
4. The method of claim 1 , wherein the carrier is a microencapsulated delivery system.
5. The method of claim 1 , wherein the carrier comprises a biocompatible biodegradable polymer.
6. The method of claim 5 , wherein the biodegradable polymer comprises an ethylene vinyl acetate polymer.
7. The method of claim 5 , wherein the biodegradable polymer comprises a polyanhydride polymer.
8. The method of claim 5 , wherein the biodegradable polymer comprises a polyglycolic acid polymer.
9. The method of claim 5 , wherein the biodegradable polymer comprises a polyorthoester polymer.
10. The method of claim 5 , wherein the biodegradable polymer comprises a polyacetic acid polymer.
11. The method of claim 5 , wherein the biodegradable polymer comprises collagen.
12. A method for the treatment of a hepatitis B virus infection in a human comprising administering an effective amount of β-L-2′-deoxycytidine, or a pharmaceutically acceptable salt thereof in a pharmaceutically acceptable carrier that provides controlled release of the β-L-2′-deoxycytidine.
13. The method of claim 12 , wherein the β-L-2′-deoxycytidine is at least 95% in its designated enantiomeric form.
14. The method of claim 12 , wherein the carrier is in the form of an implant.
15. The method of claim 12 , wherein the carrier is a microencapsulated delivery system.
16. The method of claim 12 , wherein the carrier comprises a biocompatible biodegradable polymer.
17. The method of claim 16 , wherein the biodegradable polymer comprises an ethylene vinyl acetate polymer.
18. The method of claim 16 , wherein the biodegradable polymer comprises a polyanhydride polymer.
19. The method of claim 16 , wherein the biodegradable polymer comprises a polyglycolic acid polymer.
20. The method of claim 16 , wherein the biodegradable polymer comprises a polyorthoester polymer.
21. The method of claim 16 , wherein the biodegradable polymer comprises a polyacetic acid polymer.
22. The method of claim 16 , wherein the biodegradable polymer comprises collagen.
23. The method of claim 1 wherein the β-L-2′-deoxythymidine is administered in combination or alternation with an effective amount of a compound selected from the group consisting of β-L-2-hydroxymethyl-5-(cytosin-1-yl)-1,3-oxathiolane (3TC), cis-2-hydroxymethyl-5-(5-fluorocytosin-1 -yl)-1,3-oxathiolane (FTC), β-L-2′-fluoro-5-methyl-arabinofuranolyl-uridine (L-FMAU), β-D-2,6-diaminopurine diaxolane (DAPD), famciclovir, penciclovir, 2-amino-1,9-dihydro-9-[4-hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl]-6H-purin-6-one (entecavir, BMS-200475), 9-[2-(phosphono-methoxy)ethyl]adenine (PMEA, adefovir, dipivoxil); lobucavir, ganiciclovir and ribavirin.
24. The method of claim 12 wherein the β-L-2′-deoxycytidine is administered in combination or alternation with an effective amount of a compound selected from the group consisting of β-L-2-hydroxymethyl-5 -(cytosin-1-yl)-1,3-oxathiolane (3TC), cis-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane (FTC), β-L-2′-fluoro-5-methyl-arabinofuranolyl-uridine (L-FMAU), β-D-2,6-diaminopurine diaxolane (DAPD), famciclovir, penciclovir, 2-amino-1,9-dihydro-9-[4-hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl]-6H-purin-6-one (entecavir, BMS-200475), 9-[2-(phosphono-methoxy)ethyl]adenine (PMEA, adefovir, dipivoxil); lobucavir, ganiciclovir and ribavirin.