7-{(3S,4S)-3-[(cyclopropylamino)methyl]-4-fluoropyrrolidine-1-yl}-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid crystal

Patent metadata

Field	Value
Publication number	US-RE47785-E
Application number	US-201815969342-A
Country	US
Kind code	E1
Filing date	May 2, 2018
Priority date	Nov 10, 2011
Publication date	Dec 31, 2019
Grant date	Dec 31, 2019

Abstract

Disclosed is a technique for improving the water solubility and storage stability of 7-{(3S,4S)-3-[(cyclopropylamino)methyl]-4-fluoropyrrolidine-1-yl}-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (compound (1)) that is safe and not only has a strong antibacterial action but also is effective for resistant bacteria for which conventional antibacterial agent are less effective. Crystals of the hydrochloride salt of the compound (1), crystals of the hydrochloride salt hydrate of the compound (1), and crystals of the methanesulfonate salt of the compound (1) are provided. In these crystals, decomposition due to influences of light is suppressed as compared to that in crystals of the compound (1) in free, and their storage stability is high. These crystals have higher solubility in water than the crystals of the compound (1) in free.

First claim

The invention claimed is:

1. A crystalline hydrochloride salt of a compound 7-{(3S,4S)-3-[(cyclopropylamino)methyl]-4-fluoropyrrolidine-1-yl}-6fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid.

2. The crystalline hydrochloride salt according to claim 1 , wherein the hydrochloride salt includes an anhydrous of the hydrochloride salt of the compound and/or a hydrate of the hydrochloride salt of the compound.

3. The crystalline hydrochloride salt according to claim 1 , wherein the crystalline hydrochloride salt includes comprises an anhydrous crystal of the hydrochloride salt of the compound.

4. The crystalline hydrochloride salt according to claim 1 , wherein the hydrochloride salt includes comprises a hydrate crystal of the hydrochloride salt of the compound.

5. A pharmaceutical comprising the crystalline hydrochloride salt according to claim 1 .

6. An antibacterial agent comprising the crystalline hydrochloride salt according to claim 1 or prepared by incorporating the crystalline hydrochloride salt according to claim 1 as an active pharmaceutical ingredient.

7. The antibacterial agent according to claim 6 , wherein the antibacterial agent is an oral dosage formulation.

8. The antibacterial agent according to claim 6 , wherein the antibacterial agent is an injection.

9. A method for producing the crystalline hydrochloride salt according to claim 1 , comprising:
adding hydrochloric acid to a 2-propanol solution of 7-{(3S,4S)-3-[(cyclopropylamino)methyl]-4-fluoropyrrolidine-1-yl}-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid.

10. A crystalline hydrochloride salt of a compound 7-{(3S,4S)-3-[(cyclopropylamino)methyl]-4-fluoropyrrolidine-1-yl}-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid obtained by adding hydrochloric acid to a 2-propanol solution of the compound.

11. The crystalline compound of claim 1, wherein, in differential thermal analysis (DTA), an exothermic peak appears only in the vicinity of 210° C., and in thermogravimetric (TG) analysis, no weight loss occurs below 100° C.

12. A crystalline hydrochloride salt of a compound 7-{(3S,4S)-3-[(cyclopropylamino)methyl]-4-fluoropyrrolidine-1-yl}-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid comprising crystals having powder x-ray pattern peaks at diffraction angles 2θ of 10.8°±0.2°, 12.9°±0.2°, and 24.7°±0.2° or 9.4°±0.2° and 17.7±0.2°, or mixtures thereof.

Assignees

• Kyorin Seiyaku Kk

Inventors

• Araya Ichiro
• Goto Akinori
• Minagawa Wataru
• Funada Keiko
• Nagao Muneki

Classifications

• A61P31/04

  Antibacterial agents · CPC title

• C07D401/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• A61K31/4709

  Non-condensed quinolines and containing further heterocyclic rings · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title