Patent EA-000626-B1 (EA)
Title: Synergistic combinations of zidovudine, 1592u89 and 3tc or ftc
Inventor: BARRY DAVID WALTER
IPC: A61P31/12
Filed: 1996-03-28
Abstract: 1. A combination comprising (1S,4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-l-methanol and (2R,cis)-4-amino-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one or a physiologically functional derivative thereof, or (2R,cis)-4-amino-5-fluoro-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(l H)-pyrimidin-2-one or a physiologically functional derivative thereof. 2. A combination comprising (1S,4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-l-methanol and (2R,cis)-4-amino-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one or (2R,cis)-4-amino-5-fluoro-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(l H)-pyrimidin-2-one. 3. A combination comprising (1S,4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-l-methanol and (2R,cis)-4-amino-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one or a physiologically functional derivative thereof or (2R,cis)-4-amino-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(l H)-pyrimidin-2-one or a physiologically functional derivative thereof and further comprising zidovudine or a physiologically functional derivative thereof. 4. A combination comprising (1S,4R)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-l-methanol and (2R,cis)-4-amino-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1 H)-pyrimidin-2-one or a physiologically functional derivative thereof, (2R,cis)-4-amino-5-fluoro-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(l H)-pyrimidin-2-one or a physiologically functional derivative thereof and further comprising zidovudine or a physiologically functional derivative thereof. 5. A combination according to Claim 3 wherein the ratio of (1S,4R)-cis-4-[2-amino-6(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol:zidovudine: (2R,cis)-4-amino-1 -(2-hydroxymethyl-l,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one is in the ratio of 1 to 20:1 to 20:1 to 10 by weight. 6. A combination according to Claim 4 wherein the ratio of (1S,4R)-cis-4-[2-amino-6(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol:zidovudine:(2R,cis)-4-amino-5-fluoro-1 -(2-hydroxymethyl-l, 3-oxathiolan-5-yl)-(lH)-pyrimidin-2-one or is in the ratio of 1 to 20: 1 to 20: 1 to 10 by weight. 7. A pharmaceutical formulation comprising a combination according to Claims 1 to 6 in association with one or more pharmaceutically acceptable carriers therefor in unit dosage. 8. A method for the treatment or prevention of the symptoms or effects of an HIV infection in an infected animal which comprises treating said animal with a therapeutically effective amount of a combination as defined in any Claim from 1 to 4. 9. A method according to Claim 10 wherein the combination is administered simultaneously. 10. A method according to Claim 10 wherein the combination is administered sequentially. 11. A method according to Claim 10 wherein the combination is administered as a single combined formulation. 12. A method according to any of Claims 10 to 13 in which said animal is a human. 13. Use of (lS,4R)-cis-4-[2-amino-6(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol in the manufacture of a medicament for the treatment or prevention of the symptoms or effects of an HIV infection administration either simultaneously or sequentially with a) zidovudine and (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one, for the treatment and/or prophylaxis of an HIV infection; or b) zidovudine and (2R,cis)-4-amino-5-fluoro-1-(2-hydroxymethyl-1.3-oxathiolan-5-yl)-(lH)-pyrimidin-2-one. 14. Use of (1S,4R)-cis-4-[2-amino-6(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol, zidovudine and (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one, zidovudine and (2R,cis)-4-amino-5-fluoro-1-(2-hydroxymethyl-1.3-oxathiolan-5-yl)-(lH)-pyrimidin-2-one. 15. Use as claimed in any Claim 13 or 14 for the treatment and for prophylaxis of an HIV infection resistant to nucleoside or non-nucleoside inhibitors in the treatment of AIDS or in the treatment of AIDS related conditions or AIDS dementia complex.