WO1999033470A1 - ANTI-$i(HELICOBACTER PYLORI) - Google Patents

Abstract

An anti-Helicobacter pylori containing a prostanoic acid derivative or a medicinally acceptable salt thereof as the active ingredient. The prostanoic acid derivative or medicinally acceptable salt thereof exhibits a selective sterilizing effect against helicobacters and can safely prevent or remedy medical and veterinary diseases related to infections with helicobacters.

Description

 Description Anti-Helicobacter agent Technical field

 The present invention contemplates a drug for preventing or treating a medically or silently related disease associated with Helicobacter genus bacterial infection, and a method for preventing or treating the disease. The present invention relates to a medicament for preventing or treating a disease associated with Helicobacter pylori infection, particularly peptic ulcer, and a method for preventing or treating the same in humans. . Background art

 Helicobacter pylori is a gram-negative bacillus (La nc et :, 1, 1273–1275, 1983) isolated from gastric mucosa of gastric ulcer patients in 1983 by Australia's Marsha 11 and Warren, and has recently become chronic. It has been attracting attention as a causative factor in human upper gastrointestinal diseases such as gastritis, gastric and duodenal ulcers, gastric cancer and lymphoma.

 At the NIH Consensus Conference held in the United States in February 1994, a unified view on “peptic ulcer disease and Helicobacter pylori infection” was published (NIH Cons ensus, He1i cob acter py l or iinp ep ticulcerdiseases, JA MA, 272, 65--69, 1994), `` Helicobacter pylori infection is confirmed as an antisecretory drug, regardless of whether it is the first time or recurrence. Antimicrobial-added eradication therapy is required. "

At present, various combinations of drugs, mainly antibiotics, are being tried to eradicate Helicobacter pylori. In Europe and the United States, the combination therapy of bismuth, metronidazole and antimicrobial agents, and the combination therapy of acid secretion inhibitor proton pump inhibitor and amoxicillin are mainly used. Recently, a combination therapy with prounitol, sofalcone and amoxicillin has also been used. Despite this, no eradication rates have been obtained with any of these therapies. In addition, the administration of antibiotics not only raises concerns about diarrhea and other side effects, but has also begun to point out the risk of emergence of resistant bacteria if eradication fails. Helicobacter pylori. In addition to Helicobacter, Helicobacter bacteria have been found in many animal species. Helicopter from the dog's intestinal tract-Helicobacter cisterc anis, Helicobacter mustera from the stomach of Ferret, Helicobacter b. Ferris from the stomach of dogs and cats. (Helic ob ac terfe 1 is), Helicobacter heirmani (Helic obac ter heilmanni), Helicobacter hepatics from the liver and intestine of mice. s), helicopter * kita ** bilis (Helic ob ac terbi 1 is), helicopter muridalum (He 1 ic ob ac ter mu ridar um), etc. have been found in the intestinal tract of rats. It is known to have pathogenic properties such as gastritis, enteritis and hepatic armpit. In addition, helicobacter ferris not only infects humans and induces gastritis, but also infects animal species that are carcinogenic, such as by infecting mice. It has also been reported to cause lesions.

Prostaglandins (PGs) are a group of naturally occurring substances with a wide variety of biological activities and have a common prostanoic acid skeleton. Naturally occurring PGs are classified into PGAs, PGBs, PGCs, PGDs, PGEs, PGFs, PGGs, PGHs, PGIs, PGJs due to their five-membered structural characteristics. It is further classified into subclasses such as 1, 2, and 3 depending on the degree of unsaturation and oxidation state. Many synthetic analogs of these PGs are also known. Among these, a stable PG I ₂ derivative having a skeleton obtained by converting the structure of the exo-enol-ether portion, which is a characteristic structure of PGI ₂ , to interm-phenylene is disclosed in Japanese Patent Publication No. 1-53672, It is described in the announcement of 2-1 2226 and the publication of Tokuhei 2-57548, which also disclose that they are effective as a therapeutic agent for digestive disorders. However, it was completely unknown that these prostanic acid derivatives have antibacterial activity against Helicobacter genus bacteria such as Helicobacter pylori. According to the above NIH recommendation, in the treatment of upper gastrointestinal tract diseases, especially digestive disorders, a new therapeutic agent that selectively exerts an antibacterial action on Helicobacter virilis and does not induce resistant bacteria One of the issues is to develop it.

 In order to solve this problem, an object of the present invention is to provide a clinically useful anti-helicopter agent and a method for preventing or treating the same. Disclosure of the invention

 The present invention relates to an anti-Helicobacter agent comprising a prostanoic acid derivative or a pharmaceutically acceptable salt thereof as an active ingredient, and a prophylactic or therapeutic method using the same. BEST MODE FOR CARRYING OUT THE INVENTION

 The brostanoic acid derivative of the present invention is any of PGAs, PGBs, PGCs, PGDs, PGEs, PGFs, PGGs, PGHs, PGIs, and PGJs having a prostanoic acid skeleton. It may also be a derivative of any of the subclasses such as 1, 2, and 3, which are classified according to the degree of unsaturation and the state of oxidation. The brostanoic acid derivative of the present invention includes not only natural but also any synthetic derivative.

Further, the carbon number of the basic skeleton of brostanoic acid is generally 20, but the carbon number of the prostanoic acid derivative of the present invention is not particularly limited. Preferably pro Stan acid derivative used in the present invention may be a PG 1 ₂ derivatives or any salt thereof, but further good Mashiku the following general formula (I)

[式中、 R¹は、

Where R ¹ is

(A) One C〇OR ² , where R ² is

 1) hydrogen or pharmacologically acceptable cations,

 2) straight chain alkyl having 1 to 12 carbons or partial alkyl having 3 to 14 carbons,

3) -ZR ³

Wherein Z is a valence bond, or a linear or branched alkylene represented by C _t H ₂₁ ,

t represents an integer of 1 to 6, R ³ is a substituted consequent opening alkyl cycloalkyl, or R ⁴ of 1-3 carbon atoms substituted with 3-12 of 3 to 12 carbon atoms, R ⁴ is hydrogen Or alkyl having 1 to 5 carbon atoms,

Where n is an integer from 1 to 5,

5) -Z-Ar ¹

Where Z is the same as defined above, A r ¹ is phenyl, α-naphthyl, β-naphthyl), 2-pyridyl, 3-pyridyl, 4-pyridyl, α-furyl, β-furyl, α-phenyl, ) 8-Chenyl or substituted phenyl (wherein the substituent is at least one of chlorine, bromine, fluorine, iodine, trifluoromethyl, alkyl having 1 to 4 carbon atoms, nitro, cyano, methoxy, phenyl, phenoxy, ρ-acetamidobenzamide,-CH = N-ΝΗ-C (2 0)-NH ₂ , -NH-C (= Ph) Ph,-NH-1 C (= 0)-CH ₃ or — NH- C (= 0) as an -NH _2),

6) -CtH ₂ tCOOR ⁴

Where C _t H _2t and R ⁴ are the same as defined above,

7)-C _t H _2t N (R ⁴ ) 2

Where C _t H _2t and R are the same as defined above,

8) -CH (R ⁵ )-C (= 〇)-R ⁶

Where R ⁵ is hydrogen or benzoyl, R ^s is phenyl, P-bromophenyl, p-chlorophenyl, p-biphenyl, p-nitrophenyl, p-penzamide phenyl, 2-naphthyl,

9) One C. H _2. — W—R ⁷ Where W is —CH = CH—, 1 CH2 CR ⁷ —, or —C3 C 1, and R ⁷ is hydrogen or straight or branched alkyl having 1 to 30 carbon atoms or aralkyl

, P is an integer from 1 to 5, or

10) -CH (CH ₂ 〇R ⁸ ) 2

Where R ⁸ is alkyl or acyl having 1 to 30 carbon atoms,

(B)-CH ₂ 〇H

(C)-C (= 0) N (R ⁹ ) 2

Where R ⁹ is hydrogen, linear alkyl having 1 to 12 carbons, branched alkyl having 3 to 12 carbons, cycloalkyl having 3 to 12 carbons, cycloalkylalkylene having 4 to 13 carbons, phenyl, Substitution! : Nil (wherein the substituent is as defined in the above (A) 5)), aralkyl having 7 to 12 carbon atoms or one S02R ¹ . And R ¹ . Represents alkyl having 1 to 10 carbons, cycloalkyl having 3 to 12 carbons, phenyl, substituted phenyl (where substituted grave is the same as in the case of (A) 5) above), and aralkyl having 7 to 12 carbons, Two R ^{9 s} may be the same or different, but one is — SOzR ¹ . Other R ⁹ shall not be -S 0 ₂ R ¹ °, or

 (D) -CH2OTHP (THP is a tetrahydrovinyl group), and A is

1)-(CH ₂ ) _m-

2) -CH = CH-CH _2-

3)-CH ₂ -CH = CH-

 5)-CH = CH-

6) One—CH ₂ — or

 7) — C3 C1

Here, m represents an integer of 1 to 3, Y is hydrogen, alkyl having 1 to 4 carbon atoms, chlorine, bromine, fluorine, formyl, methoxy, or nitro, and B is one X-C ( ^{R: 1) (R 12)} oR 13 wherein R ¹¹ is hydrogen or alkyl having 1 to 4 carbon atoms, R 1 ³ is hydrogen, Ashiru 1 to 14 carbon atoms, 6 to 15 carbon atoms Aroiru, tetrahydro Vilanyl, tetrahydrofuranyl, 1-ethoxyshethyl or t-butyl, and X is

 2) —CH = CH-or

 3) — C3 C1

R ¹² is

 1) linear alkyl having 1 to 12 carbons, branched alkyl having 3 to 14 carbons, or

2) -Z-Ar ²

Where Z is the same as defined above, Ar ² is phenyl, α-naphthyl, β-naphthyl), or at least one of chlorine, bromine, fluorine, iodine, trifluoromethyl, and carbon atoms having 1 to 4 carbon atoms. Alkyl, nitro, cyano, methoxy, phenyl or phenyl substituted phenyl; or

Here, C _t H _2t is the same as defined above, and R ″ is a straight-chain alkyl having 1 to 6 carbons, a branched alkyl having 3 to 6 carbons, phenyl, at least one chlorine, bromine, fluorine, iodine, and trifur. Substituted with 1 to 4 carbon atoms such as orthomethyl, alkyl having 1 to 4 carbon atoms, nitro, cyano, methoxy, phenyl or phenoxy-substituted phenyl, cyclopentyl, cyclohexyl, or linear alkyl having 1 to 4 carbon atoms Represents cyclopentyl or cyclohexyl,

4) -ZR ³

Where Z and R ³ are the same as defined above,

Where C _t H _2t is the same as defined above, R ^1S and R ¹⁶ represent hydrogen, methyl, ethyl, propyl or butyl, or

6)-C _u H _2u -C three C- R ¹⁷

Here, u is an integer of 1 to 7, C _u H ₂ u represents a linear or branched alkylene, R ¹⁷ represents a linear alkyl having 1 to 6 carbons,

E is hydrogen, or —OR ^18, where R ¹⁸ is a C 1-12 acyl, a C 7-15 aroyl or R ² (where R ² is the same as defined above), and the general formula is d Body, 1 body or 1 d body]

4, 8-interm-phenylene brostaglandin I ₂ derivative represented by Its pharmaceutically acceptable salts are used. 'The prostanoic acid derivative of the present invention can be produced by a known method. For example, the compound represented by the general formula (I) or a salt thereof is disclosed in Japanese Patent Publication No. 5-3672, Japanese Patent Publication No. 2-2122, Japanese Patent Publication No. 2-5 758 Can be produced by the method described in

 Specific examples of the prostanoic acid derivative represented by the above general formula (I) include, for example, the following derivatives.

[Table 1] Specific examples of broth rust conductors

 Compound number R1 Ar B E

 1 -CH20H-(CH2) 2- -CH = CH-CH (OH> C (CH2) 2-OPh -OH-CH20H -CH = CH- -CH = CH-CH (OH)-(CH2) 4- CH3-OH

3 -CH20H -C≡C- -CH = CH-CH (OH) -C (CH2) 2 -OPh -OH

Pharmaceutically acceptable salts of the above-mentioned exemplified compounds include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, methylamine salt, dimethylamine salt and trimethylamine. Salts, amine salts such as methylpiperidine salt, ethanolamine salt, diethanolamine salt, triethanolamine salt and lysine salt, ammonium salt, and basic amino acid salt.

 The brostanic acid derivative according to the present invention can be administered orally or parenterally for prevention or treatment. For oral administration, solid preparations such as tablets, granules, capsules and powders, or liquid preparations such as syrups and elixirs can be used. In addition, parenteral administration preparations such as injection preparations, rectal preparations, skin external preparations, inhalants and the like can also be used.

The prostanoic acid derivative in the present invention can be administered by adding excipients, stabilizers, and the like that are commonly used in the formulation of drugs. Such additives include, for example, animal oils, vegetable oils, paraffin, gum arabic, or sugars such as flour, lactose, saccharose, fructose, dextrin, mannitol, etc. Inorganic salts such as calcium carbonate, calcium sulfate, etc .; organic acid salts such as sodium citrate, sodium lactate, magnesium stearate; water-soluble such as methylcellulose, gelatin, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, hydroxyethyl cellulose For example, alcohols such as anionic polymers, ethanol, glycerin, propylene glycol, and sorbitol, surfactants such as sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, and glycerin fatty acid ester are used.

 INDUSTRIAL APPLICABILITY The brostanic acid derivative of the present invention is effective for the prevention and treatment of medical or veterinary diseases associated with infection with Helicobacter bacteria, and in humans, Helicobacter pylori. It is effective, but not limited to, in the prevention and treatment of infection-related diseases, especially peptic ulcers.

 The dosage of the brostanic acid derivative of the present invention varies depending on the age, body weight, disease state, dosage form, etc. of the patient, but usually 1 to 1000 mg per adult is administered once or several times a day. can do.

 【Example】

 Hereinafter, the present invention will be described in more detail with reference to examples.

Example 1

Measurement of antibacterial activity of brostanic acid derivatives against Helicobacter pylori: Plain containing 7% oma blood coated with Helicobacter pylori (ATCC43504, ATCC43526, and TK1402) on a heart-infection agar medium A blank disc (Pecton and Dickinson) was placed. After soaked the test compound 10 1 dissolved in dimethyl sulfoxide to disk, 5% 〇 _2, 10% C_〇 _2, microaerophilic under 85% N _2, and培菱4 days at 37 ° C . After completion of the culture, the diameter of the growth inhibition circle formed around the disc was measured, and the diameter was determined in accordance with the calculation formula of Hu1tmark et al. (The EMBO Journal, 2, 571-576, 1983). The bactericidal concentration (LC) of the test compound was calculated. From these results, it was confirmed that the prostanoic acid derivative had an antibacterial activity against Helicobacter pylori (Table 2). [Table 2 – Antibacterial activity of brostane against Nocobacter. Bicoli (bacterial concentration LC)

 Helicopter.

 Compound number Unit

 ATCC43504 ATCC43526 T 1402 Dimethyl sulfoxide NO ND ND

1 u M 162 ± 26 153 Sat 107 Sat 9

2 uM 6 ± 19 162 ± 19 180 ± 35

3 M 311 ± 46 324 ± 47 242 ± 64 D-noc doomed (detected) Example 2

Measurement of antibacterial activity of prostanoic acid derivatives against Helicobacter bacteria:

Plank discs (Becton & Dickinson Co., Ltd.) on a Brain Heart Infusion Agar Medium containing 7% umbrella blood coated with Helicobacter Mustella (ATCC43772) and Helicobacter B. muldarum (ATCC49282) ). After impregnated with test compound 10 y 1 dissolved in dimethyl sulfoxide to disk, 5% 0 _2, 10% C_〇 _2, of 85% N ₂ Features aerobic under were cultured for 4 days at 37 ° C . After completion of the culture, the diameter of the growth inhibition circle formed around the disc was measured, and the concentration of each test compound was determined according to the calculation formula of Hu1tmark et al. (The EMBO Journal, 2, 571-576, 1983). The bactericidal concentration (LC) was calculated. From these results, it was confirmed that the prostanoic acid derivative has antibacterial activity against Helicobacter bacteria (Table 3).

Helicopter-1.Mustella helicopter.Muridalm Compound number Unit

 ATCC43772 ATCC49282 Dimethyl sulfo-oxide D ND

 1, u M 181 68.6

ND = noc dacc xJ ((^ T issued) Defeat 3

Measurement of antibacterial activity of brostanic acid derivatives against bacteria other than Helicobacter: Escherichia coli (ATCC 43827), Staphylococcus aureus (two clinical isolates of 081119-016 and 081120-073), and Lactobacillus (ATCC 4356, ATCC 12315) , ATCC 35020). As a medium, a medium for a drug-sensitive disc (manufactured by Niken Seika Co., Ltd.) was used for Escherichia coli, a Tributy agar medium for Staphylococcus aureus, and a Lactobacillus MR S agar medium for lactobacilli. A disc was placed on each medium coated with the bacteria, and the test compound dissolved in dimethylsulfoxide was impregnated with 101, and then cultured at 37 ° C in 100% air for 1 to 2 days. After completion of the culture, the diameter of the growth arresting circle formed around the disc was measured, and the diameter was determined according to the calculation formula of Hu1tmark et al. (The EMBO Journal, 2, 571—576, 1983). The bactericidal concentration (LC) of each test compound was calculated. From these results, it was confirmed that the prostanoic acid derivative did not act on bacteria other than the genus Helicobacter, and that the antibacterial activity of the prostanoic acid derivative was selectively expressed in bacteria belonging to the genus Helicobacter (Table 4). ).

[Table 4〗 Antibacterial activity against bacteria other than brostan ¾ 锈 conductor helicopter ¾ (bactericidal concentration LC)

 Bacteria Staphylococcus aureus Lactobacillus

 Compound number Unit

 ATCC43827 081119-016 081120-073 ATCC4356 ATCC12315 ATCC35020 Dimethyl sulfo oxide ND ND ND D ND ND

1 ND ND ND ND ND ND

2 Αί ND ND D ND ND ND

3 uU ND ND ND ND D ND

ND = noc deteatd (detected)

Industrial applicability

 It has been clarified that the brostanic acid derivative of the present invention or a pharmaceutically acceptable salt thereof exhibits a selective eradication effect against Helicobacter genus bacteria. Therefore, the use of the compound of the present invention makes it possible to safely prevent or treat medical or medical diseases related to infection with Helicobacter bacteria, such as peptic ulcers.

Claims

The scope of the claims  1. An anti-Helicobacter agent containing a brostanic acid derivative or a pharmaceutically acceptable salt thereof as an active ingredient. 2. The anti-helicopter agent according to claim 1, wherein the brostanic acid derivative is a prostag I ₂ derivative. 3. The prostaglandin ₁₂ derivative has the following general formula (I)

Where R ¹ is (A) One C〇〇R ² , where R ² is  1) hydrogen or pharmacologically acceptable cations,  2) 1 ~ 12 carbons! : Chain alkyl or branched alkyl having 3 to 14 carbon atoms, 3) -ZR ³ Here, Z is a valence bond or a linear or branched alkylene represented by C _t H _2t , t is an integer of 1 to 6, R ³ is cycloalkyl having 3 to 12 carbon atoms or R 4 Is a substituted cycloalkyl having 3 to 12 carbon atoms, which is substituted by 1 to 3 of the following formulas, wherein R ⁴ is hydrogen or an alkyl having 1 to 5 carbon atoms, 4) ― (CH ₂ CH ₂ 〇) _n CHs  Where n is an integer from 1 to 5, 5) -Z-Ar ¹ Where Z is the same as defined above, A is phenyl, α-naphthyl, β-naphthyl), 2-pyridyl, 3-pyridyl, 4-pyridyl, α-furyl, / S-furyl, α-thyl Phenyl, monophenyl or substituted phenyl (wherein the substituent is at least one of chlorine, bromine, fluorine, iodine, trifluoromethyl, alkyl having 1 to 4 carbon atoms, nitro, cyano, methoxy, phenyl, phenoxy, ρ-acetamide penzamide,-CH = N-NH-C (= 0)-NH ₂ , -NH-C (= 0)-Ph, -NH 1 C (= 〇) 1 CH ₃ or 1 NH- C (= 〇) - those which are NH _2), 6) -C _t H ₂ tCOOR ⁴ Where C _t H _2t and R ⁴ are the same as defined above, 7)-C _t H _2t N (R ⁴ ) 2 Where C _t H _2t and R ⁴ are the same as defined above, 8) -CH (R ⁵ )-C (= 0) -R ⁶ Where R ⁵ is hydrogen or benzoyl, R ⁶ is phenyl, p-bromophenyl, p-chlorophenyl, P-biphenyl, p-nitrophenyl, p-penzamidophenyl, 2-naphthyl,

Where W is — CH = CH —, — CH = CR ⁷ —, or — C3 C 1, and R ⁷ is hydrogen or C 1-30! : A chain or branched alkyl or aralkyl, p is an integer of 1 to 5, or 10) -CH (CH ₂ 〇R ⁸ ) 2 Where R ⁸ is alkyl or acyl having 1 to 30 carbon atoms, (B) -CH ₂ OH (C)-C (= 〇) N (R ⁹ ) 2 Where R ⁹ is hydrogen, linear alkyl having 1 to 12 carbons, branched alkyl having 3 to 12 carbons, cycloalkyl having 3 to 12 carbons, cycloalkylalkylene having 4 to 13 carbons, phenyl, Substituted n: nil (wherein the substituent is as defined in (A) 5) above), aralkyl having 7 to 12 carbon atoms or —S02R ¹ . Wherein R ^1Q is alkyl having 1 to 10 carbons, cycloalkyl having 3 to 12 carbons, phenyl, substituted phenyl (where the substituent is the same as in the case of the above (A) 5), and carbon atoms of 7 to 12 Two R ⁹ may be the same or different, but one is — S02R ¹ . In other words, the other R ⁹ is — S〇 ₂ R ¹ . Not, or (D) — CH ₂ 〇THP (THP is tetrahydroviranyl group), and A is 1)-(CH ₂ ) _m- 2) - CH two CH - CH ₂ - 3) -CH ₂ -CH = CH-

 5)-CH = CH- 6) — 0— CH ₂ — or  7) — C3 C— and Where m represents an integer of 1 to 3, Y is hydrogen, alkyl having 1 to 4 carbon atoms, chlorine, bromine, fluorinated, formyl, methoxy, or nitro, and B is — XC (R ¹¹ ) (R ¹² ) 〇R ¹³ where R ¹¹ Is hydrogen or alkyl having 1 to 4 carbons, and R ¹³ is hydrogen, acyl having 1 to 14 carbons, aroyl having 6 to 15 carbons, tetrahydroviranyl, tetrahydrofuranyl, 1-ethoxyxyl or t-butyl. And X is 1)-CH ₂ -CH _2- 2) — CH = CH-or  3) One C3 C1 R ¹² is  1) linear alkyl having 1 to 12 carbons, branched alkyl having 3 to 14 carbons, or 2)-Z-Ar ² Where Z is the same as defined above, Ar ² is phenyl, α-naphthyl, β-naphthyl), or at least one chlorine, bromine, fluorine, iodine, trifluoromethyl, alkyl having 1 to 4 carbon atoms , Nitro, cyano, methoxy, phenyl or phenyl substituted phenyl, or

Where C _t H _2t is the same as defined above, R ¹⁴ is straight-chain alkyl having 1 to 6 carbons, branched alkyl having 3 to 6 carbons, phenyl, at least one chlorine, bromine, fluorine, iodine, and trifur O-methyl, alkyl having 1 to 4 carbon atoms, nitro, cyano, methoxy, phenyl or phenoxy-substituted phenyl, cyclopentyl, cyclohexyl Represents cyclopentyl or cyclohexyl substituted with 1 to 4 straight-chain alkyl having 1 to 4 carbon atoms, or 4) -ZR ³ Where Z and R ³ are the same as defined above, 5) -CtH _2t -CH = C (R ^1S ) R ¹⁶ Here, C _t H _2t is the same as defined above, and R ^1S and R ^1S represent hydrogen, methyl, ethyl, propyl, or butyl, or 6)-C _u H _2u -C3 C- R ¹⁷ Here, U is an integer of 1 to 7, C _u H ₂ u represents a straight-chain or branched alkylene, R ¹⁷ represents a straight-chain alkyl having 1 to 6 carbon atoms, E is hydrogen, or -OR ¹⁸ where R "represents a C 1-12 acyl, a C 7-15 aroyl or R ² (where R ² is as defined above), and the general formula is d-form, 1-form or d 1 anti Helicobacter one agent according to claim 1-2, wherein 4, 8 is an inter -m- off We two alkylene prostaglandin I ₂ derivative represented by the representative of the body. 4. A method for preventing or treating a disease associated with bacterial infection of the genus Helicobacter, which comprises administering an effective amount of a prostanoic acid derivative. 5. The method according to claim 4, wherein the prostanoic acid derivative is a prostaglandin ₁₂ derivative. 6. The prostaglandin ₁₂ derivative has the following general formula (I)

Where R ¹ is (A) One CO〇R ² , where R ² is  1) hydrogen or pharmacologically acceptable cations,  2) straight chain alkyl having 1 to 12 carbons or partial alkyl having 3 to 14 carbons, 3) -ZR ³ Wherein Z is Ri straight or branched吱alkylene der represented by a valence bond, or H _2t, t is an integer of 1 to 6, R ³ is cycloalkyl or R ⁴ having 3 to 12 carbon atoms 1 is a substituted cycloalkyl of to the number of 3-12 carbon atoms substituted with 1-3, R ⁴ is alkyl of hydrogen or carbon atoms 1 to 5

Where n is an integer from 1 to 5, 5) -Z-Ar ¹ Where Z is the same as defined above, Ar ¹ is phenyl, "—naphthyl, β-naphthyl), 2-pyridyl, 3-pyridyl, 4-pyridyl, hyfuryl, β-furyl, α-phenyl, —Chenyl or substituted phenyl (where the substituent is at least one of chlorine, bromine, fluorinated, iodine, trifluoromethyl, alkyl having 1 to 4 carbon atoms, nitro, cyano, methoxy, phenyl, phenoxy, ρ - § Seto amide Penn ami de, - CH = N - NH- C (= 0) - NH 2, -NH-C (= 〇) - Ph, -NH one C (= 0) - CH ₃ or one NH — C (= 〇) which is NH ₂ ), 6) -CtH _2t COOR ⁴ Where C _t H _2t and R ⁴ are the same as defined above,

Where C _t H _2t and R ⁴ are the same as defined above, 8) -CH (R ⁵ )-C (= 〇) -R ⁶ Where R ⁵ is hydrogen or benzoyl, R ⁶ is phenyl, p-bromophenyl, p-chlorophenyl, p-biphenyl, p-ditrophenyl, P-benzamidephenyl, 2-naphthyl, 9)-C. H _2P -W- R ⁷ Where W is one CH = CH-, — CH = CR ⁷ —, or — C3 C — and R ⁷ is Hydrogen or carbon number 1 ~ 30! : Chain or alkyl or aralkyl , P is an integer from 1 to 5, or 10) -CH (CH ₂ 〇R ⁸ ) 2 Where R ⁸ is alkyl or acyl having 1 to 30 carbon atoms, (B)-CH ₂ 〇H (C)-C (= 〇) N (R ⁹ ) 2 Where R ⁹ is hydrogen, linear alkyl having 1 to 12 carbons, alkyl having 3 to 12 carbons, cycloalkyl having 3 to 12 carbons, cycloalkylalkylene having 4 to 13 carbons, phenyl, Substituted phenyl (where the substituent is as defined in (A) 5) above), aralkyl having 7 to 12 carbon atoms or —S02R ¹ . And R ¹ . Is alkyl having 1 to 10 carbons, cycloalkyl having 3 to 12 carbons, phenyl, and phenyl: nnil (wherein the substituent is the same as in the case of (A) 5) above), and aralkyl having 7 to 12 carbons And two R ⁹ may be the same or different, but when one represents —S0 ₂ R ^{1 ()} , the other R ⁹ shall not be one S 0 ₂ R ¹ °. Or (D) One CH ₂ 〇THP (THP is a tetrahydroviranyl group), and A is 1)-(CH ₂ ) _m- 2)-CH = CH-CH _2- 3) -CH ₂ -CH = CH-

 5)-CH2 CH- 6) One 0—CH ₂ — or  7) — C3 C1  Where m is an integer from 1 to 3, Y is hydrogen, alkyl having 1 to 4 carbon atoms, chlorine, bromine, fluorine, formyl, methoxy, or nitro; and B is one X—C (R ¹¹ ) (R ¹² ) OR ¹³ where R ¹¹ Is hydrogen or alkyl having 1 to 4 carbons, R ¹³ is hydrogen, acyl having 1 to 14 carbons, aloizore having 6 to 15 carbons, tetrahydroviranyl, tetrahydrofuranyl, 1-ethoxyl or t-butyl. And X is 1) -CH ₂ -CH _2- 2) — CH = CH-or  3) — C3 C— and R ¹² is  1) straight chain alkyl having 1 to 12 carbons, partially alkyl having 3 to 14 carbons, or 2) -Z-Ar ² Wherein Z is the same as defined above, Ar ² is phenyl, α-naphthyl, β-naphthyl), or at least one chlorine, bromine, fluorine, iodine, trifluoromethyl, alkyl having 1 to 4 carbon atoms , Nitro, cyano, methoxy, phenyl or phenyl substituted phenyl, or

Where C _t H _2t is the same as defined above, R ¹⁴ is straight-chain alkyl having 1 to 6 carbons, branched alkyl having 3 to 6 carbons, phenyl, at least one chlorine, bromine, fluorine, iodine, and triflu Substituted with 1 to 4 carbon atoms such as orthomethyl, alkyl having 1 to 4 carbon atoms, nitro, cyano, methoxy, phenyl or phenoxy-substituted phenyl, cyclopentyl, cyclohexyl, or linear alkyl having 1 to 4 carbon atoms. Represents cyclopentyl or cyclohexyl, or 4) -ZR ³ Where Z and R ³ are the same as defined above, 5)-C _t H _2t -CH = C (R ^1S ) R ¹⁶ Wherein C _t H _2t is the same as defined above, R ¹⁵ and R ¹⁶ represent hydrogen, methyl, ethyl, propyl, or butyl, or 6)-C _u H _2u -C3 C- R ¹⁷ Here, u is an integer of 1 to 7, C u H _{2 u} represents a straight-chain or branched alkylene, R ¹⁷ represents a straight-chain alkyl having 1 to 6 carbon atoms, E represents hydrogen or one OR ¹⁸ Here, R ¹⁸ represents an acyl having 1 to 12 carbons, an aroyl having 7 to 15 carbons or R ² (where R ² is the same as defined above), and the general formula is d-form, 1-form or d 1-form 4, preventing or treating method according to claim 4 or 5, wherein the 8-inter m- phenylene broth tag run Gin I ₂ derivatives represented by the representative.