Claims
- 1. A pharmaceutical composition for oral administration which is a solution comprising(a) (2S,3S,5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-onyl)-3-methylbutanoyl)amino-1,6-diphenylhexane, (b) a pharmaceutically acceptable organic solvent which comprises a pharmaceutically acceptable long chain fatty acid selected from the group consisting of saturated, mono-unsaturated and di-unsaturated C12 to C18 carboxylic acids which are liquids at room temperature or a mixture of the pharmaceutically acceptable long chain fatty acid and a pharmaceutically acceptable alcohol, and, optionally, (c) a pharmaceutically acceptable surfactant.
- 2. The composition of claim 1 comprising(a) (2S,3S,5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-onyl)-3-methyl butanoyl)amino-1,6-diphenylhexane in the amount of from about 1% to about 50% by weight of the total solution, (b) a pharmaceutically acceptable organic solvent which comprises (i) a pharmaceutically acceptable long chain fatty acid selected from the group consisting of saturated, mono-unsaturated and di-unsaturated C12 to C18 carboxylic acids which are liquids at room temperature in the amount of from about 20% to about 99% by weight of the total solution or (ii) a mixture of (1) the pharmaceutically acceptable long chain fatty acid in the amount of from about 20% to about 99% by weight of the total solution and (2) a pharmaceutically acceptable alcohol in the amount of from about 0% to about 15% by weight of the total solution and (c) a pharmaceutically acceptable surfactant in the amount of from about 0% to about 40% by weight of the total solution.
- 3. The composition of claim 1 wherein the solution is encapsulated in a hard gelatin capsule or a soft elastic gelatin capsule.
- 4. The composition of claim 1 wherein the solvent comprises (1) a pharmaceutically acceptable long chain fatty acid selected from the group consisting of saturated, mono-unsaturated and di-unsaturated C12 to C18 carboxylic acids which are liquids at room temperature in the amount of from about 40% to about 70% by weight of the total solution and (2) ethanol or propylene glycol in the amount of from about 1% to about 15% by weight of the total solution or a mixture of ethanol and propylene glycol in the amount of from about 1% to about 15% by weight of the total solution.
- 5. The composition of claim 1 wherein the solvent comprises (1) a pharmaceutically acceptable long chain fatty acid selected from the group consisting of saturated, mono-unsaturated and di-unsaturated C12 to C18 carboxylic acids which are liquids at room temperature in the amount of from about 40% to about 70% by weight of the total solution and (2) ethanol in the amount of from about 10% to about 12% by weight of the total solution or propylene glycol in the amount of from about 5% to about 10% by weight of the total solution or a mixture of ethanol and propylene glycol in the amount of from about 5% to about 15% by weight of the total solution.
- 6. The composition of claim 1 wherein the solvent comprises (1) oleic acid in the amount of from about 40% to about 70% by weight of the total solution and (2) ethanol in the amount of from about 10% to about 12% by weight of the total solution or propylene glycol in the amount of from about 5% to about 10% by weight of the total solution or a mixture of ethanol and propylene glycol in the amount of from about 10% to about 15% by weight of the total solution.
- 7. The composition of claim 1 comprising(a) (2S,3S,5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-onyl)-3-methyl butanoyl)amino-1,6-diphenylhexane in the amount of from about 1% to about 50% by weight of the total solution, (b) a pharmaceutically acceptable organic solvent which comprises (i) a pharmaceutically acceptable long chain fatty acid selected from the group consisting of saturated, mono-unsaturated and di-unsaturated C12 to C18 carboxylic acids which are liquids at room temperature in the amount of from about 20% to about 99% by weight of the total solution or (ii) a mixture of (1) the pharmaceutically acceptable long chain fatty acid in the amount of from about 20% to about 99% by weight of the total solution and (2) a pharmaceutically acceptable alcohol in the amount of from about 0% to about 15% by weight of the total solution and (c) a pharmaceutically acceptable surfactant in the amount of from about 0% to about 40% by weight of the total solution.
- 8. The composition of claim 7 comprising(a) (2S,3S,5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-onyl)-3-methylbutanoyl)amino-1,6-diphenylhexane in the amount of from about 5% to about 35% by weight of the total solution, (b) a pharmaceutically acceptable organic solvent which comprises (i) a pharmaceutically acceptable long chain fatty acid selected from the group consisting of saturated, mono-unsaturated and di-unsaturated C12 to C18 carboxylic acids which are liquids at room temperature in the amount of from about 30% to about 70% by weight of the total solution or (ii) a mixture of (1) the pharmaceutically acceptable long chain fatty acid in the amount of from about 30% to about 70% by weight of the total solution and (2) a pharmaceutically acceptable alcohol in the amount of from about 6% to about 12% by weight of the total solution and (c) a pharmaceutically acceptable surfactant in the amount of from about 2% to about 20% by weight of the total solution.
- 9. The composition of claim 7 comprising(a) (2S, 3S, 5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-onyl)-3-methyl butanoyl)amino-1,6-diphenylhexane in the amount of from about 1% to about 50% by weight of the total solution, (b) a pharmaceutically acceptable organic solvent which comprises (i) oleic acid in the amount of from about 20% to about 99% by weight of the total solution or (ii) a mixture of (1) oleic acid in the amount of from about 20% to about 99% by weight of the total solution and (2) ethanol in the amount of from about 0% to about 12% by weight of the total solution or propylene glycol in the amount of from about 0% to about 10% by weight of the total solution or a mixture thereof in the amount of from about 0% to about 15% by weight of the total solution and (c) polyoxyl 35 castor oil in the amount of from about 0% to about 20% by weight of the total solution.
- 10. The composition of claim 9 comprising(a) (2S, 3S, 5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-onyl)-3-methyl butanoyl)amino-1,6-diphenylhexane in the amount of from about 5% to about 35% by weight of the total solution, (b) a pharmaceutically acceptable organic solvent which comprises (i) oleic acid in the amount of from about 30% to about 70% by weight of the total solution or (ii) a mixture of (1) oleic acid in the amount of from about 30% to about 70% by weight of the total solution and (2) ethanol in the amount of from about 10% to about 12% by weight of the total solution or propylene glycol in the amount of from about 5% to about 10% by weight of the total solution or a mixture thereof in the amount of about 10% by weight of the total solution and (c) polyoxyl 35 castor oil in the amount of from about 5% to about 10% by weight of the total solution.
- 11. The composition of claim 7 comprising(a) (2S, 3S, 5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-(2S-(1-tetrahydro-pyrimid-2-onyl)-3-methyl butanoyl)amino-1,6-diphenylhexane in the amount of about 30% by weight of the total solution, (b) a pharmaceutically acceptable organic solvent which comprise a mixture of (1) oleic acid in the amount of about 50% by weight of the total solution and (2) ethanol in the amount of about 10% by weight of the total solution and (c) polyoxyl 35 castor oil in the amount of about 10% by weight of the total solution.
Parent Case Info
This application is a division of U.S. Ser. No. 09/347,077, filed Jul. 2, 1999, which is a division of U.S. Ser. No. 09/966,495, filed Nov. 7, 1997 which claims the benefit of U.S. Provisional Application for Patent No. 60/031,463, filed Nov. 21, 1996.
US Referenced Citations (11)
Number |
Name |
Date |
Kind |
4997851 |
Isaacs et al. |
Mar 1991 |
A |
5196438 |
Martin et al. |
Mar 1993 |
A |
5413999 |
Vacca et al. |
May 1995 |
A |
5484801 |
Al-Razzak et al. |
Jan 1996 |
A |
5484926 |
Dressman et al. |
Jan 1996 |
A |
5541206 |
Kempf et al. |
Jul 1996 |
A |
5559158 |
Al-Razzak et al. |
Sep 1996 |
A |
5643878 |
Bold et al. |
Jul 1997 |
A |
5725878 |
Al-Razzak et al. |
Mar 1998 |
A |
5914332 |
Sham et al. |
Jun 1999 |
A |
5948436 |
Al-Razzak et al. |
Sep 1999 |
A |
Foreign Referenced Citations (30)
Number |
Date |
Country |
490667 |
Jun 1992 |
EP |
532466 |
Mar 1993 |
EP |
541168 |
May 1993 |
EP |
560268 |
Sep 1993 |
EP |
580402 |
Jan 1994 |
EP |
9208701 |
May 1992 |
WO |
WO 9208701 |
May 1992 |
WO |
WO 9307128 |
Apr 1993 |
WO |
9307128 |
Apr 1993 |
WO |
9323368 |
Nov 1993 |
WO |
WO 9323368 |
Nov 1993 |
WO |
WO 9405639 |
Mar 1994 |
WO |
9405639 |
Mar 1994 |
WO |
9506061 |
Mar 1995 |
WO |
WO 9506061 |
Mar 1995 |
WO |
9509614 |
Apr 1995 |
WO |
9509614 |
Apr 1995 |
WO |
9509843 |
Apr 1995 |
WO |
9520384 |
Aug 1995 |
WO |
9520384 |
Aug 1995 |
WO |
WO 9530670 |
Nov 1995 |
WO |
9530670 |
Nov 1995 |
WO |
WO 9603113 |
Feb 1996 |
WO |
9603113 |
Feb 1996 |
WO |
9701349 |
Jan 1997 |
WO |
9701349 |
Jan 1997 |
WO |
9720554 |
Jun 1997 |
WO |
9720554 |
Jun 1997 |
WO |
WO 9721685 |
Jun 1997 |
WO |
9721685 |
Jun 1997 |
WO |
Non-Patent Literature Citations (7)
Entry |
Gulnik et al, Biochemistry, vol. 34, pp. 9282-9287, Jul. 1995.* |
Mazur et al, 83CA:1409r, Jul. 1995.* |
Kempf, et al., Proc. Natl. Acad Sci. USA 92 2484 (1995). |
Mazur, et al., Chem Abstr. 83: 1409r (1975). |
Kempf, et al., Proc. Natl. Acad. Sci. USA vol. 92 p. 2484 (1995). |
Mazur, et al., Chem. Abstr. vol. 83, p. 1409r (1975). |
Mimoto, et al., Chem Pharm. Bull. 40 (8) 2251-2253 (1992). |
Provisional Applications (1)
|
Number |
Date |
Country |
|
60/031463 |
Nov 1996 |
US |