Phosphonocephem compound

• US 7,419,973 B2
• Filed: 02/23/2005
• Issued: 09/02/2008
• Est. Priority Date: 08/10/2000
• Status: Expired due to Term

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Pharmaceutical Company Limited
• Inventors: Ishikawa, Tomoyasu, Iizawa, Yuji, Hashiguchi, Shohei
• Primary Examiner(s): Berch; Mark L
• Application Number:
  US11/063,715
• Publication Number:
  US 20050176697A1
• Time in Patent Office: 1,287 Days
• Field of Search: None
• US Class Current: 514/203
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07F 9/65613 containing the ring system (X = CH2, O, S, NH) optionally with an additional double bond and/or substituents, e.g. cephalosporins and analogs

Abstract

A cephem compound (particularly its crystal) represented by the formula [I], wherein X is CH₃COOH, CH₃CH₂COOH or CH₃CN, 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.

Claims

1. A pharmaceutical composition comprising a pH adjuster and a compound of formula (I):

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 CH₃COOH.

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 CH₃COOH 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.