Use of 7-[(3s,4s)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition for the treatment of pulmonary abscesses

Abstract

This invention relates to a more effective and safer treatment for respiratory infections. The therapeutic agent for aspiration pneumonia, pulmonary suppuration, or pulmonary abscess of the present invention contains 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or its pharmaceutically permissible salt as the active ingredient.

Description

Treatment agents for aspiration pneumonia, lung suppuration, or lung abscess This invention relates to a treatment agent for aspiration pneumonia, pulmonary suppuration, or pulmonary abscess. Since the development of norfloxacin, the world has been developing quinolone carboxylic acid-based antibacterial agents known as neoquinolones. Currently, a large number of neoquinolone antibacterial agents are widely used as drugs for the treatment of infectious diseases. On the other hand, the applicant disclosed a quinolinone carboxylic acid derivative represented by general formula (1) (Patent Document 1). [Chemistry 1] In equation (1), R 1 R represents an alkyl group having 1 to 6 carbon atoms that can be substituted by one or two or more halogen atoms, a cycloalkyl group having 3 to 6 carbon atoms that can be substituted by one or two or more halogen atoms, or an aryl or heteroaryl group that can be substituted by one or two or more substituents selected from the same or different halogen atoms and amine groups. 2 R represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a pharmaceutically acceptable cation. 3 R represents a hydrogen atom, a halogen atom, a hydroxyl group, an amino group, or an alkyl group having 1 to 3 carbon atoms. 4 R represents a hydrogen atom or a halogen atom. 5 R represents a fluorine atom. 6 It represents a hydrogen atom or a fluorine atom, A represents a nitrogen atom or =CX (X represents a hydrogen atom, a halogen atom, an amino group, a cyano group, an alkyl group with 1 to 3 carbon atoms that can be substituted by one or more halogen atoms, or an alkoxy group with 1 to 3 carbon atoms). Furthermore, Patent Document 1 discloses 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid as one of the aforementioned quinoline carboxylic acid derivatives. Patent Document 2 discloses its hydrochloride salt. Furthermore, aspiration pneumonia is one example of respiratory infections. Aspiration pneumonia accounts for a large proportion of pneumonia cases in the elderly and is a serious disease characterized by its refractory and recurrent nature, as well as a high mortality rate (Non-Patent Literature 1). Common pathogens causing aspiration pneumonia include anaerobic bacteria, Staphylococcus aureus, and enteric bacteria (Non-Patent Literature 1). To date, no effective treatment method for aspiration pneumonia has been established. Currently available quinolone preparations include levofloxacin, ciprofloxacin, pazufloxacin, moxifloxacin, sitafloxacin, and garafloxacin. For aspiration pneumonia, which is a more severe form, injectable preparations are often used in the initial treatment. However, among the aforementioned quinolone preparations, injectable levofloxacin, ciprofloxacin, and pazufloxacin have insufficient antibacterial activity against anaerobic bacteria and are not recommended for patients suspected of having aspiration pneumonia (Non-Patent Literature 2). If administered orally, sitafloxacin, moxifloxacin, and galafloxacin may be effective against anaerobic bacterial infections (Non-Patent Literature 3 to 5), but there are no reports of papers with strong evidence regarding aspiration pneumonia, and they have not been established as effective treatments to date. As an example of a respiratory infection, similar to aspiration pneumonia, primarily caused by anaerobic bacteria, lung abscess (Non-Patent Literature 6) can be cited. Regarding moxifloxacin or pazufloxacin, although there are reports of therapeutic effects (Non-Patent Literature 3-4 and Non-Patent Literature 7), they have not yet been established as effective treatment methods. [Prior Art Literature] [Non-Patent Literature] [Non-Patent Literature 1] Journal of the Japanese Society of Internal Medicine, No. 99, No. 11, November 10, 2010, pp. 2746-2751. [Non-Patent Literature 2] Japanese Society of Respiratory Medicine, Medical and Nursing Related Pneumonia Diagnosis and Treatment Guidelines, p. 23. [Non-Patent Literature 3] Infection (Munich, Germany) (2008), 36(1), 23-30. [Non-Patent Literature 4] Expert Review of Respiratory Medicine (2007), 1(1), 111-119. [Non-Patent Literature 5] Japanese Society of Respiratory Medicine, Adult Pneumonia Diagnosis and Treatment Guidelines 2017, p. 24. [Non-Patent Literature 6] Journal of the Japanese Society of Respiratory Medicine, 49(9): 623-628, 2011. [Non-Patent Literature 7] Nippon Kagaku Ryoho Gakkai Zasshi (1999), 47 (Suppl. 1), 196-203. [Patent Literature] [Patent Document 1] International Publication No. 2005 / 026147 [Patent Document 2] International Publication No. 2013 / 069297 (The problem the invention aims to solve) The purpose of this invention is to provide a novel therapeutic agent for respiratory organ infections. (Technical means to solve the problem) The inventors have researched a highly effective and safe treatment for respiratory infections. Through diligent research, the inventors discovered that 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid is extremely effective as a treatment for aspiration pneumonia, pulmonary suppuration, or pulmonary abscess, thus completing this invention. The main points of this invention are as follows. [1] A therapeutic agent for aspiration pneumonia, pulmonary suppuration or pulmonary abscess, comprising 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically permissible salt thereof as an active ingredient. [2] A therapeutic agent for aspiration pneumonia, comprising 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically permissible salt thereof as an active ingredient. [3] A therapeutic agent for pulmonary suppuration or pulmonary abscess, comprising 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically permissible salt thereof as an active ingredient. [4] In the therapeutic agent described in [1], the pathogens causing the aspiration pneumonia, pulmonary suppuration, or pulmonary abscess are selected from one or more species of bacteria belonging to the genus *Prevotella*, the genus *Peptostreptococcus*, the genus *Micromonas*, the genus *Peptobacter*, the genus *Fingoldii*, and the genus *Clostridium*. [5] The therapeutic agent described in [2] contains one or more bacteria selected from the group consisting of bacteria belonging to the genus *Prevotella*, bacteria belonging to the genus *Peptostreptococcus*, bacteria belonging to the genus *Micromonas*, bacteria belonging to the genus *Peptobacterium*, bacteria belonging to the genus *Fingoldii*, and bacteria belonging to the genus *Clostridium*. [6] The therapeutic agent described in [3] contains one or more bacteria selected from the group consisting of bacteria belonging to the genus *Prevotella*, bacteria belonging to the genus *Peptostreptococcus*, bacteria belonging to the genus *Micromonas*, bacteria belonging to the genus *Peptobacterium*, bacteria belonging to the genus *Fingoldii*, and bacteria belonging to the genus *Clostridium*. [7] The therapeutic agent described in [1] contains one or more of the following bacteria as selected from the group consisting of Bacteroides, Prevotella, Pyrrolizum, Clostridium, Ciliophora, Peptostreptococcus, Micromonas, Vanillinella, Tylosporium, Streptococcus pharyngiomatosis, and Actinomyces. [8] The therapeutic agent described in [2] contains one or more of the following bacteria as selected from the group consisting of Bacteroides, Prevotella, Micromonas, Vanillinella, and Actinomyces.[9] The therapeutic agent described in [3] contains one or more of the following pathogens of the above-mentioned pulmonary suppuration or pulmonary abscess: bacteria belonging to the genus Bacteroides, bacteria belonging to the genus Prevotella, bacteria belonging to the genus Pyrrolizum, bacteria belonging to the genus Clostridium, bacteria belonging to the genus Ciliophora, bacteria belonging to the genus Peptostreptococcus, bacteria belonging to the genus Micromonas, bacteria belonging to the genus Vanilloidococcus, bacteria belonging to the genus Tylenol, and streptococci of pharyngitis.

[10] The therapeutic agent described in [1] wherein the daily dose of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or its pharmaceutically permissible salt is converted into the daily dose of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid is 300 mg on the first day and 150 mg thereafter.

[11] The therapeutic agent described in [2] wherein the daily dose of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or its pharmaceutically permissible salt is converted into the daily dose of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid is 300 mg on the first day and 150 mg thereafter.

[12] The therapeutic agent described in [3] wherein the daily dose of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or its pharmaceutically permissible salt is converted to 300 mg on the first day and 150 mg thereafter. (Compared to the efficacy of prior art). According to the present invention, a therapeutic agent comprising administering 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically permissible salt thereof to a patient for aspiration pneumonia, pulmonary suppuration or pulmonary abscess is provided. The following describes in detail one embodiment of the present invention. This embodiment of the therapeutic agent relates to a treatment for respiratory diseases, particularly a treatment for respiratory infections. More specifically, this embodiment of the therapeutic agent relates to a treatment comprising administering 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or a pharmaceutically permissible salt thereof to a patient, including a human, for aspiration pneumonia, pulmonary suppuration, or pulmonary abscess. Respiratory organ infection refers to an infection occurring in any part of the respiratory system. Furthermore, the term "respiratory system" is a general term for organs related to respiration, referring to the organs from the nasal vestibule through the nasal cavity, pharynx, larynx, trachea, bronchi, bronchioles to the alveoli. In this instruction manual, "aspiration pneumonia" refers to a respiratory condition including swelling or infection of the lungs or large respiratory tract, considered to be caused by inhalation of harmful substances. Patients with aspiration pneumonia will experience symptoms such as cough or difficulty breathing. In this instruction manual, a patient with aspiration pneumonia is someone who meets the following criteria: • A clear, acutely appearing infiltrative shadow is found on chest X-ray or computed tomography (CT) images. • Confirmed obvious aspiration, confirmed recurrent choking, confirmed functional impairment in swallowing function evaluation tests, or a complication of a disease with the possibility of swallowing dysfunction, or a history of such a condition. • Demonstrates characteristic symptoms and inflammatory manifestations of aspiration pneumonia. Furthermore, the characteristic symptoms and inflammatory manifestations of so-called aspiration pneumonia include cough, purulent sputum, moist rales, dyspnea, fever, positive C-reactive protein (CRP), increased white blood cell count, and hypoxemia. The term "pulmonary suppuration" in this instruction manual, also known as lung abscess, refers to a necrotizing lung infection caused by the inhalation of bacteria from the mouth or throat into the lungs. Patients with pulmonary suppuration may experience symptoms such as fatigue, loss of appetite, night sweats, fever, weight loss, and cough with sputum. In this instruction manual, "patient with pulmonary suppuration" refers to someone who meets the following criteria: • A mass-like shadow or a shadow with internal cavities (nodular shadow, tumor shadow) is found on a chest X-ray or CT scan (regardless of whether an air-fluid level is formed due to pus accumulation). • Characteristic symptoms and inflammatory manifestations of pulmonary suppuration or lung abscess are present. Furthermore, the characteristic symptoms and inflammatory manifestations of pulmonary suppuration or lung abscess include cough, purulent sputum, moist rales, dyspnea, fever, positive CRP, increased white blood cell count, and hypoxemia. To effectively treat diseases such as aspiration pneumonia, pulmonary suppuration, or lung abscess, it is important to find compounds that are safe and effective against anaerobic pathogens. The applicant has discovered that 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid and its pharmaceutically permissible salts are effective against anaerobic pathogens, unlike other quinolinone compounds. For example, injectable formulations of quinolinone compounds such as levofloxacin, ciprofloxacin, or pazufloxacin are considered unsuitable as treatments for aspiration pneumonia (Non-Patent Literature 2). However, the applicant discovered that 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid and its pharmaceutically permissible salts are effective against anaerobic pathogens, thereby being effective in the treatment of aspiration pneumonia. Furthermore, 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or its pharmaceutically permissible salts, for example, can be manufactured according to the methods described in Patent Document 1 or 2. Examples of partial anaerobic bacteria that can cause aspiration pneumonia, pulmonary suppuration, or pulmonary abscess include: bacteria belonging to the genus *Bacteroides*, bacteria belonging to the genus *Prevotella*, bacteria belonging to the genus *Porphyromonas*, bacteria belonging to the genus *Fusobacterium*, bacteria belonging to the genus *Leptotrichia*, and bacteria belonging to the genus *Peptostreccus*. Bacteria belonging to the genus *Streptococcus*, the genus *Parvimonas*, the genus *Veillonella*, the genus *Tissierella*, the genus *Peptoniphilus*, the genus *Finegoldia*, the *Streptococcus Anginosus* group (a general anaerobic bacterium included in the genus *Streptococcus*), and the genus *Actinomyces*. 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid exhibits high antibacterial activity against the above-mentioned anaerobic bacteria, and shows high therapeutic efficacy against aspiration pneumonia, lung suppuration, or lung abscess. Examples of pathogens that can cause aspiration pneumonia include: bacteria belonging to the genus *Prevotella*, bacteria belonging to the genus *Peptostreptococcus*, bacteria belonging to the genus *Parvimonas*, bacteria belonging to the genus *Peptoniphilus*, bacteria belonging to the genus *Finegoldia*, bacteria belonging to the genus *Fusobacterium*, bacteria belonging to the genus *Bacteroides*, and bacteria included in the genus *Streptococcus*. Regarding the treatment of aspiration pneumonia, especially when the pathogens causing aspiration pneumonia belong to the genus Bacteroides, Prevotella, Micromonas, Vanilloidococcus, or Actinomyces, 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid exhibit higher therapeutic efficacy. Examples of pathogens causing lung suppuration or lung abscess include: bacteria belonging to the genus *Prevotella*, bacteria belonging to the genus *Peptostreptococcus*, bacteria belonging to the genus *Parvimonas*, bacteria belonging to the genus *Peptoniphilus*, bacteria belonging to the genus *Finegoldia*, bacteria belonging to the genus *Fusobacterium*, bacteria belonging to the genus *Bacteroides*, and bacteria included in the genus *Streptococcus*. Regarding the treatment of pulmonary suppuration or lung abscess, especially when the pathogens causing pulmonary suppuration or lung abscess are bacteria belonging to the genus *Prevotella*, *Pyrrolizum*, *Clostridium*, *Ciliophora*, *Peptostreptococcus*, *Micromonas*, *Vanillococcus*, *Taylorus*, or *Streptococcus pharyngis*, 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid exhibit higher therapeutic efficacy. Examples of bacteria belonging to the genus *Prevotella* include: *P. denticola*, *P. loescheii*, *P. melaninogenica*, *P. intermedia*, *P. nigrescens*, *P. pallens*, *P. buccae*, *P. oris*, *P. buccalis*, *P. oralis*, *P. bivia*, *P. disiens*, *P. pleuritidis*, *P. bergensis*, *P. timonensis*, or *P. nanceiencis*. From the perspective of the therapeutic effect of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid, it is preferable to cite *P. melaninogenica*, *P. intermedia*, or *P. buccae* as the pathogens of aspiration pneumonia, and *P. melaninogenica*, *P. intermedia*, or *P. oralis* as the pathogens of lung abscess or pulmonary suppuration. Examples of bacteria belonging to the genus *Peptostreptococcus* include, for example, *P. anaerobius* (anaerobic peptostreptococcus) or *P. stomatis* (stomatitis peptostreptococcus). Examples of bacteria belonging to the genus *Micromonas* include *P. micra*. From the perspective of the therapeutic effect of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid], it is preferable to list *P. micra* as the causative agent of aspiration pneumonia, pulmonary suppuration, or pulmonary abscess. Examples of bacteria belonging to the genus *Peptoniphilus* include *Peptoniphilus asaccharolyticus*, *Peptoniphilus ivorii*, *Peptoniphilus lacrimalis*, and *Peptoniphilus harei*. From the perspective of the therapeutic effect of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid, it is better to cite the case of Peptoniphilus asaccharolyticus as the causative agent of aspiration pneumonia, pulmonary suppuration, or pulmonary abscess. As a bacterium belonging to the genus *Fingoldia*, *Finegoldia magna* can be cited as an example. From the viewpoint of the therapeutic effect of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid, it is more appropriate to cite *Finegoldia magna* as a pathogen causing aspiration pneumonia, lung abscess, or lung abscess. Examples of bacteria belonging to the genus *Clostridium* include: *F. necrophorum*, *F. nucleatum*, *F. mortiferum*, and *F. varium*. From the perspective of the therapeutic effect of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid, it would be more appropriate to list *F. nucleatum* or *F. necrophorum* as the causative agents of pulmonary suppuration or lung abscess. Examples of bacteria belonging to the genus *Bacteroides* include: *Bacteroides fragilis*, *Bacteroides thetaiotaomicron*, *Bacteroides vulgatus*, *Bacteroides ovatus*, *Bacteroides uniformis*, *Bacteroides eggerthii*, *Bacteroides nordii*, *Bacteroides salyersae*, and *Bacteroides massiliensis*. From the perspective of the therapeutic effect of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid, it is preferable to list *Bacteroides fragilis* as the causative agent of pulmonary abscess or lung suppuration. Examples of bacteria belonging to the genus *Pyrrolomonas* include: *P. gingivalis*, *P. endodontalis*, *P. asaccharolytica*, *P. levii*, and *P. uenonis*. From the perspective of the therapeutic effect of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid], it would be more appropriate to list *P. gingivalis* or *P. endodontalis* as the pathogens of pulmonary abscesses or pulmonary suppuration. Examples of bacteria belonging to the genus *Lysimachia* include: *L. buccalis* (oral lichen), *L. hofstadii* (Hospital lichen), *L. hongkongensis* (Hong Kong lichen), *L. shahii* (Shahii lichen), *L. goodfellowii* (Goodfellowii lichen), *L. trevisanii* (Trevii lichen), or *L. wadei* (Wadei lichen). From the perspective of the therapeutic effect of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid], it is preferable to list *L. buccalis* as the causative agent of pulmonary suppuration or lung abscess. Examples of bacteria belonging to the genus *V. parvula*, *V. atypica*, or *V. montpelliensis* can be listed as follows: Examples of bacteria belonging to the genus *Tylospora* include *T. creatinini*, *T. creatinophila*, and *T. praeacuta*. From the perspective of the therapeutic effect of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid, it is preferable to list *T. creatinini* as the causative agent of pulmonary abscess or lung suppuration. Examples of bacteria belonging to the streptococcal group of pharyngitis include *Streptococcus intermedius* and *Streptococcus constellatus*. From the perspective of the therapeutic effect of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid, it would be more appropriate to list *S. intermedius* or *S. constellatus* as the causative agents of pulmonary abscess or pulmonary suppuration. Examples of bacteria belonging to the genus *Actinomyces* include: *A. europaeus*, *A. georgiae*, *A. gerencseriae*, *A. graevenitzii*, *A. israelii*, *A. meyeri*, *A. naeslundii*, *A. neuii*, *A. odontolyticus*, *A. radicidentis*, *A. radingae*, *A. turicensis*, *A. urogenitalis*, *A. viscocus*, or *Actinomyces* sp. (genus *Actinomyces*). From the perspective of the therapeutic effect of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid, it is better to cite the case of A. odontolyticus as the pathogen of aspiration pneumonia. The term "pathogenic bacteria" in this instruction manual also includes bacteria that have acquired drug resistance. Drug resistance refers to the phenomenon where an organism develops resistance to a drug, rendering the drug ineffective or less effective. Examples of drug resistance include: penicillin resistance, cephalosporin resistance, carbapenem resistance, aminoglycoside resistance, macrocyclic lactone resistance, lincomycin resistance, trimethoprim-sulfamethoxazole resistance, tetracycline resistance, metronidazole resistance, glycopeptide resistance, acetazolidinone resistance, dapoxetine resistance, or quinolone resistance. Among the aforementioned pharmaceutical ingredients, pharmaceutically permissible additives contained together with 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid may include, for example, excipients, lubricants, binders, disintegrants, stabilizers, flavoring and odor-correcting agents, and diluents. There are no particular limitations on such additives as long as they can be used in the manufacture of pharmaceutical preparations; for example, those listed in the "Dictionary of Pharmaceutical Additives" published by the Japan Pharmaceutical Additives Association and Pharmaceutical Daily (2007) may be appropriately used. The therapeutic agent of this embodiment can be administered to humans or other subjects using forms and routes of administration known in conventional pharmaceutical science, and can be administered orally or non-orally in the form of preparations such as powders, tablets, capsules, granules, powders, syrups, injections, ophthalmic solutions, aqueous nasal drops, aqueous ear drops, and inhalation solutions. That is, the therapeutic agent of this embodiment can be manufactured by mixing the active ingredient with physiologically permissible carriers, excipients, binders, diluents, etc., and in dosage forms such as those exemplified above. In the therapeutic agent of this embodiment, in terms of reducing side effects, easy administration, compact formulation, and preventing the emergence of drug-resistant bacteria, the minimum daily dosage of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or its pharmaceutically permissible salt is preferably 10 mg or more, 20 mg or more, 50 mg or more, 100 mg or more, 125 mg or more, or 150 mg or more. Furthermore, the maximum daily dosage is preferably 300 mg or less, 250 mg or less, 200 mg or less, or 175 mg or less. The daily dosage of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or its pharmaceutically permissible salt may be, for example, 10 mg or more and 300 mg or less, more preferably 20 mg or more and 250 mg or less, further preferably 50 mg or more and 200 mg or less, further preferably 100 mg or more and 200 mg or less, further preferably 125 mg or more and 175 mg or less, and most preferably 150 mg. Furthermore, the above-mentioned daily dosage is converted to free volume values ​​when using pharmaceutically permissible salts of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid. The daily dosage can be administered once or divided into 2-3 doses, preferably once daily. Additionally, if the effect is insufficient, twice the daily dosage may be used. Furthermore, to quickly achieve the target blood concentration, a loading dosing is preferable. Loading dosing refers to a dosing design used in the initial stages of dosing to achieve the target blood concentration earlier by increasing the daily dosage or the number of daily doses. The initial stage of dosing refers to days 1 to 3 of the dosing program, preferably days 1 to 2, and even more preferably day 1. Also, the increment in daily dosage is preferably twice the usual daily dosage. When administering a loading dose, it is preferable to use twice the daily dose on the first day of administration. More preferably, the daily dose of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or its pharmaceutically permissible salt, converted to free form, is 300 mg on the first day of administration and 150 mg thereafter. The preferred dosage of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid hydrochloride is 300 mg on the first day of administration and 150 mg thereafter. Here, the dosage refers to the value obtained by converting 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid hydrochloride to its free form. The pharmaceutically permissible salts of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid may be used. Examples of pharmaceutically permissible salts include: salts with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid; salts with organic acids such as maleic acid, fumaric acid, succinic acid, malic acid, malonic acid, methanesulfonic acid, toluenesulfonic acid, benzenesulfonic acid, lactic acid, oxalic acid, acetic acid, trifluoroacetic acid, and tartaric acid; or salts with metals such as sodium, potassium, magnesium, calcium, aluminum, cesium, chromium, cobalt, copper, iron, zinc, platinum, and silver. Among these, hydrochloride salts are particularly preferred. Furthermore, the term "free form" refers to 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid, which is not in any form as a salt, co-crystallized form, or hydrate. Its molecular formula is C1. 21 H 2 4F 3N 3O 4. A compound with a molecular weight of 439.44. The therapeutic agent of this embodiment may also be composed solely of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or its pharmaceutically permissible salt as the active ingredient. Alternatively, the therapeutic agent of this embodiment may also be composed of a pharmaceutical composition containing 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or its pharmaceutically permissible salt, and other compounds acting as the active ingredient and / or pharmaceutically permissible additives. The pharmaceutical composition may contain one or more compounds as other compounds that function as the active ingredient and / or pharmaceutically permissible additives. The pharmaceutical composition is prepared, for example, by mixing 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or its pharmaceutically permissible salt with one or more of the other compounds and additives that function as the active ingredient. Based on the above embodiments, a technique relating to a therapeutic agent with high therapeutic efficacy and safety for aspiration pneumonia, lung abscess, or lung abscess can be provided. By using the appropriate components described in this specification, even with a smaller dosage, side effects can be reduced, the frequency of drug-resistant bacteria can be decreased, and sufficient therapeutic effect can be obtained. (Example) The following examples illustrate the invention in further detail, but the scope of the invention is not limited to these examples. A 150 mg injection of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid (hereinafter also referred to as Clinical Trial Drug A) was manufactured according to the method disclosed in International Publication No. 2016 / 195014. Furthermore, the "150 mg" in the so-called 150 mg injection refers to the weight of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid hydrochloride in its free volume equivalent. When manufacturing the injection, 162.5 mg of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid hydrochloride (free volume equivalent: 150 mg) is used. (Trial Example 1) Aspiration Pneumonia: Thirteen subjects suspected of having aspiration pneumonia who met the following criteria were given clinical trial drug A via intravenous infusion for 7 to 14 days. • Acute, clear infiltrative shadows were observed on chest X-ray or CT images taken within 48 hours prior to the start of administration. • Obvious aspiration, choking, or swallowing dysfunction, a disease with a possibility of swallowing dysfunction, or a history of such dysfunction. • Characteristic symptoms and inflammatory manifestations of aspiration pneumonia were observed. Two vials (300 mg / day) of clinical trial drug A were administered on day 1, and one vial (150 mg / day) was administered on day 2, thereafter maintaining the same dosage (150 mg / day). For injections, each vial was administered via intravenous infusion over approximately one hour. (Trial Example 2) Pulmonary Suppuration or Pulmonary Abscess: Eleven subjects suspected of having pulmonary suppuration or pulmonary abscess who met the following criteria were given clinical trial drug A via intravenous infusion for 7 to 14 days. • Patients aged 16 years or older with a mass-like shadow or shadow with internal cavity (nodular shadow, tumor shadow) on chest X-ray or CT images taken within 48 hours prior to the start of administration. Furthermore, regardless of the presence or absence of air-fluid levels due to pus accumulation. • Presenting characteristic symptoms and inflammatory manifestations of pulmonary suppuration or pulmonary abscess. Two vials (300 mg / day) of clinical trial drug A were administered on day 1, and one vial (150 mg / day) was administered on day 2, thereafter maintaining the same dosage (150 mg / day). For the injection, each vial was administered via intravenous infusion over approximately one hour. The clinical efficacy of Trial Examples 1 and 2 was determined based on the clinical efficacy criteria for pneumonia in the "Clinical Evaluation Method for Novel Antibacterial Drugs in Respiratory Infections (Second Edition), Journal of the Japanese Society for Chemotherapy. 2012; 60 (1): 30-45.9". The following criteria were set for evaluation. Furthermore, the primary evaluation item was the efficacy rate of clinical trial drug A at the end or discontinuation of administration. In this instruction manual, "end of administration" refers to the evaluation date following the completion date of administration of clinical trial drug A. "Termination" refers to the evaluation date implemented within 3 days from the final administration date or termination date of clinical trial drug A. Furthermore, "end of administration or termination" is expressed as End of Treatment (EOT). CRP, short for C-reactive protein, is an acute-phase reactant produced rapidly in response to various inflammations. In bacterial infections such as pneumonia, it rises within hours and rapidly decreases as the inflammation subsides, thus serving as an indicator for observing treatment efficacy. • Early Efficacy Evaluation and End of Treatment (EOT) Early efficacy evaluation is conducted 3 days after administration, according to Table 1, using three levels: "early treatment effect," "no early treatment effect," and "undetermined." The definition of "early therapeutic effect" is defined as cases where significant improvement is observed after 3 days of administration (regardless of whether administration is terminated or continued after 4 days). Furthermore, for cases where CRP levels or chest X-rays do not improve after 3 days compared to before administration, even if CRP or chest X-ray results remain unchanged or worsen, improvement in clinical symptoms and body temperature is considered an indication of "early therapeutic effect." If CRP or chest X-ray results remain unchanged or worsen, and clinical symptoms and body temperature remain unchanged or do not improve, it is considered an indication of "no early therapeutic effect." Taking full account of the safety of the subjects, the responsible physician of the clinical trial may appropriately decide to discontinue the clinical trial and replace it with other antibiotics. Moreover, samples for microbiological evaluation are collected before initiating appropriate alternative antibiotic treatment. Furthermore, if the termination date is the start date of administration (day 0) or the second day of administration (day 1), no early efficacy evaluation is required. If the termination date is the third day of administration (day 2) or later, the results of the examination at the time of termination will be used for evaluation. At the end of treatment (EOT), the clinical effect at the end of administration or at the time of termination will be evaluated according to Table 1, using three levels: "effective," "ineffective," and "indeterminate." If the termination occurs after the day following the end of administration, the clinical effect at the end of administration will be evaluated; the clinical effect at the time of termination does not need to be evaluated. Also, if the treatment is terminated or if the clinical trial drug is switched to an alternative antibiotic after the trial drug administration ends, it will be deemed "ineffective." However, if the treatment is deemed "effective" at the end of treatment (EOT) according to the criteria in Table 1, this is not limited to the case of switching to an alternative antibiotic. Furthermore, in the case of switching to an alternative antibiotic, the prescribed examinations, examinations, and determinations at the end of treatment should, in principle, be performed before the change. [Table 1] Table 1. Criteria for Early Efficacy Evaluation and Treatment End Criteria The early efficacy evaluation and results at the end of treatment for Experiments 1 and 2 are shown in Tables 2 and 3. [Table 2] [Table 3] Furthermore, the effectiveness rate is calculated using the following formula: Effectiveness Rate = (Number of subjects judged as "valid" ÷ Number of subjects judged as "valid" or "invalid") × 100% Tables 2 and 3 show that 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or its pharmaceutically permissible salts exhibit high therapeutic efficacy for aspiration pneumonia, pulmonary abscess, or lung abscess. In particular, the efficacy rate at the end of treatment was significantly higher, at 100% for aspiration pneumonia and 91% for pulmonary abscess or lung abscess. The microbiological effects of different pathogens in Experiments 1 and 2 are shown in Tables 4 and 5. [Table 4] [Table 5] Tables 4 and 5 show that 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid, or its pharmaceutically permissible salts, exhibit high antibacterial efficacy against pathogens causing aspiration pneumonia, lung suppuration, or lung abscess. (Industrial Applicability) According to this embodiment, a treatment agent for aspiration pneumonia, pulmonary suppuration, or pulmonary abscess can be provided, and it is industrially useful.

Claims

1. Use of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or its pharmaceutically permissible salt for the preparation of a therapeutic pharmaceutical composition for lung abscess. The daily dose of 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid or its pharmaceutically permissible salt, converted to 7-[(3S,4S)-3-{(cyclopropylamino)methyl}-4-fluoropyrrolidin-1-yl]-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-sideoxy-1,4-dihydroquinoline-3-carboxylic acid, is 300 mg on the first day and 150 mg thereafter. The above-mentioned therapeutic pharmaceutical composition is administered intravenously via injection.

2. The use of, as claimed in claim 1, for the preparation of a pharmaceutical composition for the treatment of lung abscess, wherein, The pathogens causing the aforementioned lung abscesses are selected from one or more species of bacteria belonging to the genus *Peptostreptococcus*, the genus *Peptobacterium*, the genus *Fingoldii*, the genus *Tylomycin*, the genus *Streptococcus pharynx*, and the genus *Actinomyces*.

3. As in claim 1, the use for preparing a pharmaceutical composition for the treatment of lung abscess, wherein, The pathogens causing the aforementioned lung abscess belong to the genus *Peptostreptococcus*.