Claims
- 1. An article of manufacture for human pharmaceutical use comprising:
(a) an oral dosage form comprising a PDE5 inhibitor having an IC50 for the inhibition of PDE5 less than 10 nM, and sufficient bioavailability to be effective in about 1 to about 10 mg unit oral dosages; (b) a package insert providing that the PDE5 inhibitor is useful to treat sexual dysfunction in a patient in need thereof by utilizing a chronic dosing regimen; and (c) a container.
- 2. An article of manufacture for human pharmaceutical use comprising:
(a) an oral dosage form comprising a PDE5 inhibitor having an IC50 less than 10 nM, and a sufficient bioavailability to be effective in about 1 to about 10 mg unit oral dosages; (b) a package insert providing that the PDE5 inhibitor is useful to treat sexual dysfunction in a patient in need thereof by utilizing a chronic dosing regimen, wherein the chronic dosing regimen improves vascular conditioning; and (c) a container.
- 3. An article of manufacture for human pharmaceutical use comprising:
(a) an oral dosage form comprising a PDE5 inhibitor having an IC50 less than 10 nM, and a sufficient bioavailability to be effective in about 1 to about 10 mg unit oral dosages; (b) a package insert providing that the PDE5 inhibitor is useful to treat sexual dysfunction in a patient in need thereof by utilizing a chronic dosing regimen, wherein the chronic dosing regimen improves vascular conditioning compared to an acute or on-demand dosing of sildenafil; and (c) a container.
- 4. An article of manufacture for human pharmaceutical use comprising:
(a) an oral dosage form comprising a PDE5 inhibitor having an IC50 less than 10 nM, and a sufficient bioavailability to be effective in about 1 to about 10 mg unit oral dosages; (b) a package insert providing that the PDE5 inhibitor is useful to treat sexual dysfunction in a patient in need thereof by utilizng a chronic dosing regimen, wherein the chronic dosing regimen improves vascular conditioning compared to an acute or on-demand dosing of vardenafil; and (c) a container.
- 5. The article of manufacture of claims 1 through 4, wherein the PDE5 inhibitor further has
(i) at least a 100 fold differential in IC50 values for the inhibition of PDE5 versus PDE6, and (ii) at least 1000 fold differential in IC50 values for the inhibition of PDE5 versus PDE1c.
- 6. The article of claims 1 through 4 wherein the oral dosage form comprises about 1 mg, about 2 mg, about 5 mg, or about 10 mg, of the PDE5 inhibitor.
- 7. The article of claims 1 through 4 wherein the chronic dosing regimen is a daily dosing regimen.
- 8. The article of claims 1 through 4 wherein the chronic dosing regimen comprises administration of about 1 mg/day to about 10 mg/day of the PDE5 inhibitor.
- 9. The article of claims 1 through 4 wherein the package insert provides a maximum dosage of the PDE5 inhibitor of about 10 mg per day.
- 10. The article of claims 1 through 4 wherein the PDE5 inhibitor is selected from the group consisting of
(6R,12aR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)pyrazino[2′,1′:6,1]pyrido[3,4-b]indole-1,4-dione; (3S,6R,12aR)-2,3,6,7,12,12a-hexahydro-2,3-dimethyl-6-(3,4-methylenedioxyphenyl)pyrazino[2′,1′:6,1]-pyrido[3,4-b]indole-1,4-dione; 5-(2-ethoxy-5-morpholinoacetylphenyl)-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one; 5-(5-morpholinoacetyl-2-n-propoxyphenyl)-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one; 5-[2-allyloxy-5-(4-methyl-1-piperazinylsulphonyl)-phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo-[4,3-d]pyrimidin-7-one; 5-{2-ethoxy-5-[4-(2-propyl)-piperazinylsulphonyl]-phenyl}-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo-[4,3-d]pyrimidin-7-one; 5-{2-ethoxy-5-[4-(2-hydroxyethyl)-1-piperazinylsulphonyl)phenyl}-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one; 5-{5-[4-(2-hydroxyethyl)-1-piperazinylsulphonyl]-2-n-propoxyphenyl}-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one; 5-[2-ethoxy-5-(4-methyl-1-piperazinylcarbonyl)-phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo-[4,3-d]pyrimidin-7-one; and 5-[2-ethoxy-5-(1-methyl-2-imidazolyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one.
- 11. The article of claim 10 wherein the chronic dosing regimen comprises administration of about 1 mg/day to about 10 mg/day of the PDE5 inhibitor.
- 12. The article of claims 1 through 4 wherein the PDE5 inhibitor is selected from the group consisting of sildenafil and vardenafil.
- 13. The article of claims 1 through 4, wherein the PDE5 inhibitor has the structure
- 14. A method of treating sexual dysfunction comprising using an article of manufacture of claims 1 through 4.
- 15. A method of treating sexual dysfunction comprising a chronic administration to an individual in need thereof of one or more oral dosage form of a PDE5 inhibitor in an amount of about 1 mg/day to about 10 mg/day for at least three days.
- 16. The method of claim 15 wherein the chronic administration of a PDE5 inhibitor is a daily administration.
- 17. A method of improving a relaxant response in corpus cavernosum smooth muscle comprising a chronic administration of a PDE5 inhibitor selected from (6R,12aR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)pyrazino[2′,1′:6,1]-pyrido[3,4-b]indole-1,4-dione for at least three days.
- 18. The method of claim 17 comprising the chronic administration of about 1 mg/day to about 10 mg/day of the PDE5 inhibitor.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. application Ser. No. 09/558,911, filed Apr. 26, 2000, which claims the benefit of provisional patent application Serial No. 60/132,036, filed Apr. 30, 1999.
Provisional Applications (1)
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Number |
Date |
Country |
|
60132036 |
Apr 1999 |
US |
Divisions (1)
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Number |
Date |
Country |
Parent |
09834442 |
Apr 2001 |
US |
Child |
10341664 |
Jan 2003 |
US |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
09558911 |
Apr 2000 |
US |
Child |
09834442 |
Apr 2001 |
US |