Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-11-09
2001-02-06
Reamer, James H. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
Reexamination Certificate
active
06184230
ABSTRACT:
TECHNICAL FIELD
This invention relates to a medicament, particularly an anti-
Helicobacter pylori
pharmaceutical composition. In particular, it relates to an anti-
Helicobacter pylori
agent which is useful for the treatment and prevention of various diseases caused by the infection with
Helicobacter pylori.
BACKGROUND ART
Helicobacter pylori
is a pathogenic bacterium discovered in 1983, which is regarded as the cause of diseases at the upper digestive organs, such as peptic ulcers (e.g., gastric and duodenal ulcers), inflammations (e.g., gastritis) and gastric cancer, and of MALT (mucosa-associated lymphoid tissue) lymphoma or as a background pathogenic factor of chronic heart diseases. Studies on the treatment of
Helicobacter pylori
infection are active now, and a large number of therapeutic methods have been reported, including those for removing the bacterium or those for preventing relapse, as described below. The examples include a single agent administration method using bismuth, an antibiotic, a proton pump inhibitor (PPI), an antitumor agent, or the like and a multiple agent combination method (two agent combination or three agent combination) which uses a combination of these agents, etc. (“Internal Medicine”, Special Edition, vol. 78, no. 1 (1996), published by Nankodo). However, these therapeutic methods have many problems to be solved, such as high frequency of administration times, requirement of administration in a dose larger than the usual dose in some cases, onset of diarrhea or constipation caused by the drug administration and generation of resistant strains.
The compound related to the present invention as a substance useful as an anti-
Helicobacter pylori
pharmaceutical composition, is disclosed in JP-A-7-189 (the term “JP-A” as used herein means an “unexamined published Japanese patent application”) as a substance YL-02729S, and its use is particularly antibacterial activity upon methicillin-resistant
Staphylococcus aureus
. Said patent application does not suggest or report about antibacterial activity of the substance YL-02729S upon
Helicobacter pylori.
DISCLOSURE OF THE INVENTION
The inventors of the present invention have carried out extensive studies on the aforementioned substance YL-02729S and, as a result, found that it has an excellent anti-
Helicobacter pylori
activity and also that said substance has high selectivity and does not exert influences upon other bacteria.
The following describes the present invention in detail.
The present invention relates to an anti-
Helicobacter pylori
pharmaceutical composition containing a 1-hydroxy-3-methyl-quinolone derivative represented by the following formula (I)
or a pharmaceutically acceptable salt thereof as an active ingredient, preferably an anti-
Helicobacter pylori
pharmaceutical composition containing 1-hydroxy-2-(2-trans-nonenyl)-3-methyl-4(1H)-quinolone or a pharmaceutically acceptable salt thereof as an active ingredient, and to the use of a 1-hydroxy-3-methyl-quinolone derivative represented by the following formula (I)
or a pharmaceutically acceptable salt thereof for the production of an anti-
Helicobacter pylori
agent.
The present invention also relates to the use of an anti-
Helicobacter pylori
pharmaceutical composition containing a 1-hydroxy-3-methyl-quinolone derivative represented by the formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient for the prevention or treatment of
Helicobacter pylori
infection, to a method for the administration of the substance of formula (I) and other agent, preferably an antibiotic, an acid-related agent or an H2 blocker, simultaneously or at an interval and to the use thereof for the prevention of relapse of diseases caused by
Helicobacter pylori
infection. Also included in the present invention is a prodrug of the substance of formula (I) obtained by a usual means.
Since the active ingredient (I) of the anti-
Helicobacter pylori
pharmaceutical composition of the present invention has double bonds, cis isomer and trans isomer, as well as tautomers exist therein. Existence of the tautomers is disclosed in JP-A-7-189 as follows.
Examples of the pharmaceutically acceptable salt include acid addition salts with inorganic acids or organic acids, of which pharmaceutically acceptable salts are desirable. Illustrative examples of such salts include acid addition salts with mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid and phosphoric acid, with organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, methanesulfonic acid and ethanesulfonic acid or with acidic amino acids such as aspartic acid and glutamic acid. Hydrates and various solvates of the active ingredient are also included in the present invention. Also, said active ingredient exists in polymorphic forms in some cases, and all of such crystal forms are included in the present invention.
The production method disclosed in JP-A-7-189 can be cited as a typical method for the production of the active ingredient of the anti-
Helicobacter pylori
pharmaceutical composition of the present invention. Regarding a fermentation method for the production of said active ingredient, it is desirable to employ a method in which a bacterium belonging to the genus Arthrobacter, such as Arthrobacter sp. YL-02729S which has been deposited in National Institute of Bioscience and Human Technology under an international deposition No. FERM BP-6326, is cultured, and the compound of interest is isolated and purified from said culture in the usual way.
INDUSTRIAL APPLICABILITY
Since the invention compound shows antibacterial action upon
Helicobacter pylori
, the present invention is effective for the treatment or prevention of bacterial infection with
Helicobacter pylori
in human and with related bacteria belonging to the genus Helicobacter in animals. Also, the anti-
Helicobacter pylori
pharmaceutical composition of the present invention is useful for the prevention (including prevention of relapse) or treatment of diseases of the upper digestive organs, such as peptic ulcers (e.g., gastric and duodenal ulcers), inflammations (e.g., acute or chronic gastritis or duodenitis) and gastric cancer, as well as MALT (mucosa-associated lymphoid tissue) lymphoma or chronic heart diseases.
Preparation method and administration method of the anti-
Helicobacter pylori
pharmaceutical composition of the present invention are described in the following in detail.
The pharmaceutical composition containing one or more of the substance represented by the aforementioned formula (I) and pharmaceutically acceptable salts thereof as an active ingredients is administered orally or parenterally by preparing it into dosage forms such as tablets, powders, fine granules, granules, capsules, pills, solutions, injections, suppositories, ointments or adhesive preparations using generally used carriers, fillers and other additives for pharmaceutical preparation use.
Clinical dose of the present invention for human is optionally decided by taking into consideration symptoms, body weight, age, sex and other conditions of each patient to be treated.
The dose is generally from 0.1 to 500 mg in the case of oral administration, or from 0.01 to 100 mg in the case of parenteral administration, per day per adult, and the daily dose is divided into 1 to several doses per day. Since the dose varies depending on various conditions, a smaller amount than the above range may be sufficient in some cases. In this connection, the anti-
Helicobacter pylori
pharmaceutical composition of the present invention can be used in combination with other drugs such as antibacterial agents which will be described later, simultaneously or at an interval.
The solid composition of the present invention for use in oral administration is used in the form, for example, of tablets, powders or granules. In such a solid composition, one or more of the act
Komiya Masayuki
Rantiatmodjo Ratna Murni
Tanaka Kouichi
Watanabe Masato
Reamer James H.
Sughrue Mion Zinn Macpeak & Seas, PLLC
Yamanouchi Pharmaceutical Co. Ltd.
LandOfFree
Anti-helicobacter pylori pharmaceutical composition does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Anti-helicobacter pylori pharmaceutical composition, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Anti-helicobacter pylori pharmaceutical composition will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2565955