JPH0930970A - Antimicrobial agent - Google Patents
Antimicrobial agentInfo
- Publication number
- JPH0930970A JPH0930970A JP7204072A JP20407295A JPH0930970A JP H0930970 A JPH0930970 A JP H0930970A JP 7204072 A JP7204072 A JP 7204072A JP 20407295 A JP20407295 A JP 20407295A JP H0930970 A JPH0930970 A JP H0930970A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- active ingredient
- helicobacter pylori
- present
- agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000004599 antimicrobial Substances 0.000 title abstract 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 22
- 239000004480 active ingredient Substances 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- 239000003242 anti bacterial agent Substances 0.000 claims description 8
- 229940037467 helicobacter pylori Drugs 0.000 abstract description 17
- 239000007924 injection Substances 0.000 abstract description 5
- 238000002347 injection Methods 0.000 abstract description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 4
- 208000000718 duodenal ulcer Diseases 0.000 abstract description 4
- 206010017758 gastric cancer Diseases 0.000 abstract description 4
- 239000000203 mixture Substances 0.000 abstract description 4
- 201000011549 stomach cancer Diseases 0.000 abstract description 4
- 208000007107 Stomach Ulcer Diseases 0.000 abstract description 3
- 201000005917 gastric ulcer Diseases 0.000 abstract description 3
- 239000008187 granular material Substances 0.000 abstract description 3
- 239000003826 tablet Substances 0.000 abstract description 3
- 239000011230 binding agent Substances 0.000 abstract description 2
- 239000002775 capsule Substances 0.000 abstract description 2
- 238000009472 formulation Methods 0.000 abstract description 2
- 239000000314 lubricant Substances 0.000 abstract description 2
- 239000003002 pH adjusting agent Substances 0.000 abstract description 2
- 239000006215 rectal suppository Substances 0.000 abstract description 2
- 229940100618 rectal suppository Drugs 0.000 abstract description 2
- 239000007787 solid Substances 0.000 abstract description 2
- 239000000243 solution Substances 0.000 abstract description 2
- 239000003381 stabilizer Substances 0.000 abstract description 2
- 239000004615 ingredient Substances 0.000 abstract 1
- 241000590002 Helicobacter pylori Species 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 230000000844 anti-bacterial effect Effects 0.000 description 7
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 208000008469 Peptic Ulcer Diseases 0.000 description 3
- 230000008029 eradication Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 208000011906 peptic ulcer disease Diseases 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 206010019375 Helicobacter infections Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229960003022 amoxicillin Drugs 0.000 description 2
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229940126409 proton pump inhibitor Drugs 0.000 description 2
- 239000000612 proton pump inhibitor Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 125000002817 1-piperidinomethyl group Chemical group [H]C([H])([*])N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010054949 Metaplasia Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000007478 blood agar base Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 1
- 229960001596 famotidine Drugs 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000015689 metaplastic ossification Effects 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- -1 organic acid salts Chemical class 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
- 229960000620 ranitidine Drugs 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、抗菌剤に関する。
更に詳しくは、抗ヘリコバクター作用を有する抗菌剤に
関する。TECHNICAL FIELD The present invention relates to an antibacterial agent.
More specifically, it relates to an antibacterial agent having an anti-Helicobacter action.
【０００２】[0002]
【従来の技術】従来胃内には塩酸が存在するため、細菌
の生育には適さない環境が作り上げられており、胃内に
は細菌が生息しないと考えられてきた。しかし、最近人
の胃粘膜よりヘリコバクターピロリ（Helicobacter pyl
ori）と命名された菌が分離された（Goodwin,C,S.et a
l. Int.J.Syst.Bact.39:397-405,1989)。さらに、この
ヘリコバクターピロリは胃炎の原因の８０％以上に関わ
っていると述べられ消化性潰瘍、ことに十二指潰瘍の再
発の最もおおきな原因の１つであることも明かになって
きている。また、ヘリコバクターピロリ感染が持続する
と胃粘膜萎縮ひいては腸上皮化生を生じ、胃ガン、こと
に分化型胃ガンの発生と密接な関わりを有することが明
かになりつつある。2. Description of the Related Art Conventionally, since hydrochloric acid exists in the stomach, an environment not suitable for the growth of bacteria has been created, and it has been considered that bacteria do not inhabit the stomach. However, recently helicobacter pylori (Helicobacter pylori)
ori) was isolated (Goodwin, C, S. et a
Int. J. Syst. Bact. 39: 397-405, 1989). Furthermore, it has been revealed that Helicobacter pylori is involved in more than 80% of the causes of gastritis, and it is becoming clear that it is one of the largest causes of recurrence of peptic ulcer, especially duodenal ulcer. Moreover, it is becoming clear that persistent Helicobacter pylori infection causes atrophy of gastric mucosa and in turn metaplasia of intestinal epithelium, and is closely related to the development of gastric cancer, particularly differentiated gastric cancer.
【０００３】ヘリコバクターピロリの除菌方法はいまだ
完璧なものは発見されていないが、ビスマス製剤、メト
ロニダゾール、アモキシシリンまたはテトラサイクリン
の３者併用が最も有効とされている。また、プロトンポ
ンプ阻害薬に抗ヘリコバクターピロリ作用が観察され、
プロトンポンプ阻害薬とアモキシシリンの併用療法も検
討が行われている（Iwahi,T.et al. Antimicrob. Agent
s. Chemother 35:490-496, 1991)。ヘリコバクターピロ
リの除菌に成功した例では、十二指腸潰瘍と胃潰瘍の再
発率が明らかにヘリコバクターピロリ陽性群より低かっ
たとの報告もある(Hentschel, E. et al. N. Engl. J.
Med. 328:308-312,1993、 Graham, D.Y. et al. Ann. I
ntern. Med.116: 705-708, 1992)。Although a perfect eradication method for Helicobacter pylori has not been found yet, the combination of bismuth preparation, metronidazole, amoxicillin or tetracycline is considered to be most effective. In addition, anti-Helicobacter pylori action was observed for proton pump inhibitors,
Combination therapy with a proton pump inhibitor and amoxicillin is also under consideration (Iwahi, T. et al. Antimicrob. Agent
S. Chemother 35: 490-496, 1991). It has also been reported that the recurrence rate of duodenal ulcer and gastric ulcer was clearly lower in Helicobacter pylori-positive patients than in the Helicobacter pylori-positive group (Hentschel, E. et al. N. Engl. J.
Med. 328: 308-312,1993, Graham, DY et al. Ann. I
ntern. Med. 116: 705-708, 1992).
【０００４】[0004]
【発明が解決しようとする課題】上記のようにヘリコバ
クターピロリの除菌はこれまでどの治療法によっても不
可能であった消化性潰瘍の再発を防止する根本治療法と
して有用である。またヘリコバクターピロリ感染は、慢
性の感染症としての性格も有しており、感染時期の違い
や菌種の違い、宿主側のヘリコバクターピロリに対する
免疫反応の違いなどにより多様化している。As described above, eradication of Helicobacter pylori is useful as a fundamental treatment method for preventing recurrence of peptic ulcer, which has been impossible by any of the above treatment methods. In addition, Helicobacter pylori infection also has a character as a chronic infectious disease, and is diversified due to differences in the time of infection and bacterial species, and differences in the immune reaction against Helicobacter pylori on the host side.
【０００５】[0005]
【課題を解決するための手段】本発明者らは、上記課題
に鑑み、ヘリコバクターピロリの除菌に有効な化合物を
種々検討した結果、ある種のアミノアルキルピリジルオ
キシ誘導体がヘリコバクターピロリに対する抗菌作用を
有することを見いだし、本発明を完成した。すなわち、
本発明は式[Means for Solving the Problems] In view of the above problems, the present inventors have conducted various studies on compounds effective for eradication of Helicobacter pylori, and as a result, certain aminoalkylpyridyloxy derivatives have an antibacterial action against Helicobacter pylori. The present invention has been completed and the present invention has been completed. That is,
The present invention uses the formula
【化２】 で表される化合物または医薬上許容し得る塩を有効成分
とする抗菌剤である。Embedded image It is an antibacterial agent containing a compound represented by or a pharmaceutically acceptable salt as an active ingredient.
【０００６】本発明の有効成分である式（Ｉ）で表され
る１−アミノ−２−［４−〈４−（１−ピペリジノメチ
ル）ピリジル−２−オキシ〉−シス−２−ブテニルアミ
ノ］−１−シクロブテン−３，４−ジオン化合物（以
下、本発明化合物と称する）は特開昭６１−８５３６５
号公報の実施例１に開示された公知の化合物である。こ
の化合物は、同公報において、ヒスタミンＨ2受容体拮
抗作用を有し、動物に対し胃酸分泌抑制効果、さらに防
御作用として粘膜保護作用や粘液分泌促進作用を有する
ことが明らかにされている。しかし同公報には、本発明
化合物が抗菌剤として、特にヘリコバクターピロリに対
する抗菌作用を有することについては、全く記載がな
く、かつ示唆もされていない。1-amino-2- [4- <4- (1-piperidinomethyl) pyridyl-2-oxy> -cis-2-butenylamino] -1 represented by the formula (I) which is an active ingredient of the present invention. -Cyclobutene-3,4-dione compound (hereinafter referred to as the compound of the present invention) is disclosed in JP-A-61-85365.
It is a known compound disclosed in Example 1 of the publication. It is clarified in this publication that this compound has a histamine H 2 receptor antagonistic action, an inhibitory effect on gastric acid secretion in animals, and a protective effect on mucous membranes and a mucus secretion promoting effect. However, the publication does not describe or suggest that the compound of the present invention has an antibacterial activity as an antibacterial agent, particularly against Helicobacter pylori.
【０００７】本発明の医薬上許容しうる塩とは、塩酸
塩、硫酸塩などの鉱酸の塩、マレイン酸塩、マロン酸
塩、蓚酸塩、酒石酸塩などの有機酸塩である。特開昭３
−２５１５７１号公報には、本発明化合物の塩酸塩が開
示されている。同公報は、この塩酸塩についての有用
性、すなわち塩酸塩が周囲の湿潤の状態にも安定した組
成を示すことを開示している。しかし同公報には、本発
明化合物が抗菌剤として、特にヘリコバクターピロリに
対する抗菌作用を有することについては、全く記載がな
く、かつ示唆もしていない。この塩酸塩は、本発明抗菌
剤の有効成分として特に有用である。The pharmaceutically acceptable salts of the present invention are salts of mineral acids such as hydrochlorides and sulfates, and organic acid salts such as maleates, malonates, oxalates and tartrates. JP-A-3
-251571 discloses the hydrochloride salt of the compound of the present invention. The publication discloses the utility of this hydrochloride salt, ie that the hydrochloride salt shows a stable composition even in the surrounding wet state. However, in this publication, there is no description or suggestion that the compound of the present invention has an antibacterial action against Helicobacter pylori, especially as an antibacterial agent. This hydrochloride is particularly useful as an active ingredient of the antibacterial agent of the present invention.
【０００８】本発明化合物の投与量は症状により異なる
が通常成人に対する１回投与量は、１ｍｇ〜１００ｍ
ｇ、好ましくは５ｍｇ〜８０ｍｇである。投与形態は経
口、注射、直腸坐剤のいずれでもよく、注射剤を調製す
る場合は上記主薬にｐＨ調製剤、緩衝剤、安定化剤、賦
形剤などを添加してもよい。経口用固形剤を調製する場
合は、主薬に賦形剤、さらに必要に応じて結合剤、崩壊
剤、滑沢剤、着色剤、矯味剤、矯臭剤などを加えたのち
常法により錠剤、被覆錠剤、顆粒剤、散剤、カプセル剤
などを作ることができる。Although the dose of the compound of the present invention varies depending on the symptoms, a single dose for an adult is usually 1 mg to 100 m.
g, preferably 5 mg to 80 mg. The dosage form may be oral, injection, or rectal suppository. When preparing an injection, a pH adjusting agent, a buffer, a stabilizer, an excipient, etc. may be added to the above-mentioned main drug. When preparing a solid preparation for oral use, an excipient, and if necessary, a binder, a disintegrating agent, a lubricant, a coloring agent, a flavoring agent, a flavoring agent, etc. are added, and then tablets and coatings are carried out by a conventional method. Tablets, granules, powders, capsules and the like can be made.
【０００９】[0009]
【発明の効果】本発明によれば、抗ヘリコバクターピロ
リ作用を有する抗菌剤が提供される。本発明によれば、
ヘリコバクターピロリの除菌により、消化性潰瘍、例え
ば十二指腸潰瘍、胃潰瘍の再発予防に有効であり、ひい
ては胃ガンの予防にも有用である。According to the present invention, an antibacterial agent having an anti-Helicobacter pylori action is provided. According to the present invention,
By eradicating Helicobacter pylori, it is effective in preventing recurrence of peptic ulcer such as duodenal ulcer and gastric ulcer, and is also useful in preventing gastric cancer.
【００１０】[0010]
【実施例】以下、実施例および試験例を挙げ本発明を具
体的に説明する。 実施例１ （液剤処方） 本発明化合物 ５重量部 塩化ナトリウム １０重量部 水 ８５重量部 日本薬局方製剤総則注射剤の項に準じて製造した。EXAMPLES The present invention will be specifically described below with reference to examples and test examples. Example 1 (Liquid formulation) Compound of the present invention 5 parts by weight Sodium chloride 10 parts by weight Water 85 parts by weight It was manufactured according to the item of General Rules for Injectable Preparations of the Japanese Pharmacopoeia.
【００１１】実施例２ （錠剤処方） 本発明化合物 １０重量部 乳糖 ３９重量部 デンプン ４０重量部 ヒドロキシプロピルセルロース １０重量部 ステアリン酸マグネシウム １重量部 日本薬局方製剤総則注射剤の項に準じて製造した。Example 2 (Tablet formulation) Compound of the present invention 10 parts by weight Lactose 39 parts by weight Starch 40 parts by weight Hydroxypropyl cellulose 10 parts by weight Magnesium stearate 1 part by weight Manufactured in accordance with the Japanese Pharmacopoeia General Rules Injection. .
【００１２】実施例３ （顆粒剤処方） 本発明化合物 １０重量部 マンニトール ５４．４重量部 デンプン ３０重量部 ヒドロキシプロピルセルロース ５重量部 ステアリン酸マグネシウム ０．５重量部 日本薬局方製剤総則注射剤の項に準じて製造した。Example 3 (Granule formulation) Compound of the present invention 10 parts by weight Mannitol 54.4 parts by weight Starch 30 parts by weight Hydroxypropyl cellulose 5 parts by weight Magnesium stearate 0.5 parts by weight It was manufactured according to.
【００１３】試験例１ （検体）本発明化合物をジメチルスルホキシド（ＤＭＳ
Ｏ）に溶解し、ＤＭＳＯで２培希釈系列を作成した。抗
菌力測定の際、溶液と培地とは１：９９割合で混合し
た。使用された本発明化合物の化学名および構造式を次
に示す。（Z)-３−アミノ−４−［４−［４−（ピペリ
ジノメチル）−２−ピリジルオキシ］−２−ブテニルア
ミノ］−３−シクロブテン−１，２−ジオン モノ塩酸
塩。Test Example 1 (Sample) The compound of the present invention was prepared from dimethyl sulfoxide (DMS).
O) and dissolved in DMSO to make a 2-culture dilution series. When measuring the antibacterial activity, the solution and the medium were mixed at a ratio of 1:99. The chemical names and structural formulas of the compounds of the present invention used are shown below. (Z) -3-Amino-4- [4- [4- (4-piperidinomethyl) -2-pyridyloxy] -2-butenylamino] -3-cyclobutene-1,2-dione monohydrochloride.
【化３】 Embedded image
【００１４】（試験方法）抗菌力測定は日本化学療法学
会標準法に準じ、寒天平板希釈法を用いて測定した。感
受性測定用培地として、Blood Agar Base No2 (OXOID社
製)に馬脱繊血（日本生物材料センター社製）を５％と
なるように添加したものを用いた。１０6cfu/mlの菌を
培地に接種、１０％炭酸ガスの条件下で、３５℃、７２
時間培養した。抗菌力は菌の発育が肉眼的に認められな
い最小の薬剤濃度（ＭＩＣ：最小発育阻止濃度、μｇ／
ｍｌ）で示した。(Test method) The antibacterial activity was measured by the agar plate dilution method according to the standard method of the Japanese Society of Chemotherapy. As a susceptibility measurement medium, Blood Agar Base No2 (manufactured by OXOID) supplemented with horse defibrinated blood (manufactured by Japan Biomaterials Center) at 5% was used. Inoculate the medium with 10 6 cfu / ml of the bacterium, and under the condition of 10% carbon dioxide gas, at 35 ° C, 72
Cultured for hours. Antibacterial activity is the minimum drug concentration (MIC: minimum inhibitory concentration, μg /
ml).
【００１５】（結果）結果を表１に示す。 表１ H.pylori H.pylori H.pylori 被検薬 ATCC43504 ATCC43579 ATCC43629 本発明化合物 ５０ ２５ ２５ ファモチジン ＞８００ ８００ ＞８００ シメチジン ＞８００ ＞８００ ＞８００ ラニチジン ＞８００ ＞８００ ＞８００ ＊：同時比較でないため、参考値として表に示した。 表１から明かなごとく、本発明の有効成分である式
（Ｉ）で表される化合物のヘリコバクターピロリに対す
る抗菌力（ＭＩＣ）は２５〜５０μｇ／ｍｌを示した。(Results) The results are shown in Table 1. Table 1 H.pylori H.pylori H.pylori Test compound ATCC43504 ATCC43579 ATCC43629 Compound of the present invention 50 25 25 Famotidine> 800 800> 800 Cimetidine>800>800> 800 Ranitidine>800>800> 800 *: Not a simultaneous comparison. It is shown in the table as a reference value. As is clear from Table 1, the antibacterial activity (MIC) of the compound represented by formula (I), which is the active ingredient of the present invention, against Helicobacter pylori was 25 to 50 μg / ml.
Claims (1)
成分とする抗菌剤。(1) Formula (1) An antibacterial agent comprising a compound represented by: or a pharmaceutically acceptable salt thereof as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7204072A JPH0930970A (en) | 1995-07-19 | 1995-07-19 | Antimicrobial agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7204072A JPH0930970A (en) | 1995-07-19 | 1995-07-19 | Antimicrobial agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0930970A true JPH0930970A (en) | 1997-02-04 |
Family
ID=16484309
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7204072A Pending JPH0930970A (en) | 1995-07-19 | 1995-07-19 | Antimicrobial agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0930970A (en) |
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| US7504384B2 (en) | 2000-01-10 | 2009-03-17 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of infection |
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| US8304395B2 (en) | 2000-01-10 | 2012-11-06 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Lipid conjugates in the treatment of disease |
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-
1995
- 1995-07-19 JP JP7204072A patent/JPH0930970A/en active Pending
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| US8304395B2 (en) | 2000-01-10 | 2012-11-06 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Lipid conjugates in the treatment of disease |
| US8076312B2 (en) | 2000-01-10 | 2011-12-13 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd | Use of lipid conjugates in the treatment of disease |
| US7504384B2 (en) | 2000-01-10 | 2009-03-17 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of infection |
| US7608598B2 (en) | 2000-01-10 | 2009-10-27 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of conjunctivitis |
| US7772196B2 (en) | 2000-01-10 | 2010-08-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of diseases |
| US7811999B2 (en) | 2000-01-10 | 2010-10-12 | Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. | Use of lipid conjugates in the treatment of diseases |
| US7393938B2 (en) | 2000-01-10 | 2008-07-01 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of diseases |
| US9040078B2 (en) | 2000-01-10 | 2015-05-26 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of diseases of the nervous system |
| US8916539B2 (en) | 2000-01-10 | 2014-12-23 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of disease |
| US8501701B2 (en) | 2000-01-10 | 2013-08-06 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Use of lipid conjugates in the treatment of disease |
| AU2011201154B2 (en) * | 2004-03-02 | 2012-11-29 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of disease |
| WO2005084307A3 (en) * | 2004-03-02 | 2007-01-18 | Yissum Res Dev Co | Use of lipid conjugates in the treatment of disease |
| US8865681B2 (en) | 2004-03-02 | 2014-10-21 | Yissum Research Development Company of the Hebrew Unitersity of Jerusalem | Use of lipid conjugates in the treatment of diseases or disorders of the eye |
| AU2005218545B2 (en) * | 2004-03-02 | 2010-12-16 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Use of lipid conjugates in the treatment of disease |
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