Phosphonocephem compound
View Patent ↗A cephem compound (particularly its crystal) represented by the formula [I], wherein X is CH 3 COOH, CH 3 CH 2 COOH or CH 3 CN, and n is 0 to 5, is useful as an antibacterial agent (particularly anti-MRSA agent) and shows superior quality such as high solid stability, possible long-term stable preservation and the like.
1. A pharmaceutical composition comprising a pH adjuster and a compound of formula (I):
wherein X is CH 3 COOH or CH 3 CH 2 COOH and n is 0-5.
2. The composition of claim 1 wherein the compound of formula (I) is in the form of a crystal.
3. The composition of claim 1 wherein n is 1.
4. The composition of claim 1 wherein X is CH 3 COOH.
5. The composition of claim 4 wherein the compound of formula (I) has peaks near diffraction angles of 16.32, 19.06, 19.90, 20.98 and 23.24° in powder X-ray diffraction (CuKα).
6. The composition of claim 4 wherein the compound of formula (I) has peaks near diffraction angles of 11.82, 17.16, 17.80, 19.32, 20.00, 21.20, 21.78, 22.94, 24.10 and 27.02° in powder X-ray diffraction (CuKα).
7. The composition of claim 1 , wherein X is CH 3 COOH and n is 1.
8. The composition of claim 1 wherein the pH adjuster is a basic amino acid or a carbonate of an alkaline metal or alkaline earth metal.
9. The composition of claim 1 wherein the pH adjuster is L-arginine.
10. The composition of claim 1 wherein the pH adjuster is present in an amount sufficient to make the pH of a solution of the composition in the range of pH 4 to pH 10.
11. The composition of claim 1 wherein the pH adjuster is present in an amount sufficient to make the pH of a solution of the composition in the range of pH 4.5 to pH 8.5.
12. The composition of claim 1 wherein the pH adjuster is present in an amount sufficient to make the pH of a solution of the composition in the range of pH 5.0 to pH 8.0.
13. The composition of claim 1 wherein the pH adjuster is present in an amount sufficient to make the pH of a solution of the composition in the range of pH 5.0 to pH 7.5.
14. The composition of claim 9 wherein the L-arginine is present in an amount ranging from 0.1 to 5.0 equivalents relative to the amount of the compound of formula (I).
15. The composition of claim 9 wherein the L-arginine is present in an amount ranging from 2.0 to 3.5 equivalents relative to the amount of the compound of formula (I).
16. The composition of claim 9 wherein the L-arginine is present in an amount ranging from 2.5 to 3.2 equivalents relative to the amount of the compound of formula (I).
17. The composition of claim 1 further comprising a solubilizing agent selected from the group consisting of sodium sulfite, sodium hydrosulfite, sodium hydrogen sulfite, sodium pyrosulfite and L-cysteine.
18. The composition of claim 17 wherein the solubilizing agent is present in an amount ranging from 0.001 to 2.0 equivalents relative to the amount of the compound of formula (I).
19. The composition of claim 17 wherein the solubilizing agent is present in an amount ranging from 0.01 to 0.5 equivalents relative to the amount of the compound of formula (I).
20. The composition of claim 17 wherein the solubilizing agent is present in an amount ranging from 0.05 to 0.2 equivalents relative to the amount of the compound of formula (I).
21. The composition of claim 1 , further comprising a solvent.
22. The composition of claim 21 , wherein the solvent is water, physiological saline or a 5% glucose solution.
23. The composition of claim 7 , wherein the pH adjuster is L-arginine.