WO1993025558A1 - Compose complexe acide 2-aminoethanesulfonique/zinc - Google Patents

Compose complexe acide 2-aminoethanesulfonique/zinc Download PDF

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Publication number
WO1993025558A1
WO1993025558A1 PCT/JP1993/000813 JP9300813W WO9325558A1 WO 1993025558 A1 WO1993025558 A1 WO 1993025558A1 JP 9300813 W JP9300813 W JP 9300813W WO 9325558 A1 WO9325558 A1 WO 9325558A1
Authority
WO
WIPO (PCT)
Prior art keywords
zinc
compound
complex compound
formula
aminoethanesulfonic acid
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.)
Ceased
Application number
PCT/JP1993/000813
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
Hajime Fujimura
Takahiro Yabuuchi
Teruo Tanaka
Yoichi Nagamura
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Research Institute for Production Development
Original Assignee
Research Institute for Production Development
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Research Institute for Production Development filed Critical Research Institute for Production Development
Priority to EP93913534A priority Critical patent/EP0646586B1/en
Priority to US08/356,305 priority patent/US5489609A/en
Priority to DE69314794T priority patent/DE69314794T2/de
Publication of WO1993025558A1 publication Critical patent/WO1993025558A1/ja
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/01—Sulfonic acids
    • C07C309/02—Sulfonic acids having sulfo groups bound to acyclic carbon atoms
    • C07C309/03—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C309/13—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton
    • C07C309/14—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton containing amino groups bound to the carbon skeleton
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/28—Compounds containing heavy metals
    • A61K31/315—Zinc compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics

Definitions

  • the present invention relates to a novel zinc 2-aminoethanesulfonate complex compound, a method for producing the same, and an anti-hepatitis agent, a liver function improving agent and an anti-ulcer agent containing the compound as an active ingredient.
  • the present inventors have synthesized a large number of compounds and tested their activity in order to develop excellent pharmaceuticals from 2-aminoenesulfone and derivatives.
  • an alkali agent and a zinc compound are reacted with 21-aminoethanesulfonic acid, a bis (2-aminoethanesulfonic acid) bis (2-aminoethanesulfonic acid alkali metal salt) represented by the following formula (A) is obtained. It has been found that zinc can be synthesized (Japanese Patent Application No. Hei 4-212464).
  • the compound of the formula (A) has an anti-hepatitis effect, a liver function improving effect and an anti-ulcer effect which are superior to 2-aminoethanesulfonic acid, but its zinc content is lower in the case of sodium salt and potassium salt. They are relatively low, 10.776% and 10.21%, respectively. Therefore, the present inventors conducted further research in order to obtain a zinc 2-aminoenesulfonate compound having a higher zinc content, and found that bis (2-aminoethanesulfonate) having a zinc content of 20.85% was obtained. Zinc was synthesized.
  • the present invention relates to the formula [I].
  • CH 2 - NH 2 ⁇ H, NCH represented by 2- Aminoe evening Nsuruhon zinc complex compound and anti-hepatitis agent containing them as active ingredient to the preparation line, related to liver function improving and anti-ulcer agents .
  • the compound of the formula (I) can be produced by reacting a zinc compound (0.5 mol) with an alkali metal salt of 2-aminoenedisulfonic acid (1 mol).
  • the metal salt of 2-aminoethanesulfonic acid can be prepared by reacting 2-aminoethanesulfonic acid (1 mol) with an alkali agent (1 mol). The resulting metal salt may be isolated and reacted with the zinc compound, but may be reacted with the zinc compound without isolation.
  • an alkali metal alcohol such as sodium methylate, sodium ethylate, potassium methoxide, potassium methoxide or potassium thiobutoxide.
  • zinc compound zinc bromide and zinc iodide are preferable, but other zinc compounds may be used.
  • the reaction between the zinc compound and the metal salt of 2-aminoenesulfonic acid is usually carried out in a suitable solvent such as methanol or ethanol at room temperature or under heating for several hours. It can be purified by conventional means.
  • the compound of the formula (I) of the present invention has excellent anti-hepatitis, hepatic function-improving and anti-ulcer effects, and has low toxicity, and is therefore used as an anti-hepatitis agent, hepatic function-improving agent and anti-ulcer agent.
  • This compound is mixed with appropriate excipients, carriers, diluents, etc. which are per se or pharmacologically acceptable.
  • TTZ Zinc bis (2-aminoethanesulfonic acid)
  • the obtained blood was centrifuged at 3000 rpm for 15 minutes, and the activities of aspartate transaminase (AST) and alanine transaminase (ALT) in the serum were measured by the Lippi method. Table 1 shows the results.
  • the TTZ of the compound of the present invention showed a significant inhibitory effect at the same level as that of FTZ, but the same amount of the control comparators, 2-amino sulfonic acid, glucanthione and glycyrrhizin, were also present. It did not show an inhibitory effect.
  • Rat isolated hepatocytes were prepared by the Segren's collagenase flow method, and a hepatocyte suspension was prepared so that the isolated cells had a concentration of 2 ⁇ 10 6 / m 1.
  • a 25% carbon tetrachloride i "rib oil solution was placed in an Erlenmeyer flask containing 2 ml of the flask, and the flask was filled with about 0.1%.
  • TTZ of the compound of the present invention showed the same level of inhibitory action as FTZ, and clearly showed a better inhibitory action than 2-aminoenosulfonic acid alone.
  • TTZ of the compound of the present invention has a clear protective effect against lethal toxicity of acetoaldehyde at a lower dose than FTZ, and this effect was even stronger than that of 2-aminoenedisulfonic acid.
  • test compound was suspended in 0.5% carboxymethylcellulose sodium aqueous solution, and 1 OmlZkg was orally administered 30 minutes before administration of hydrochloric acid and ethanol.
  • the control group received only the vehicle (0.5% carboxymethylcellulose sodium water). Table 4 shows the above results.
  • the novel zinc 2-aminoenosulfonate complex compound of the present invention has an effect in anti-hepatitis tests superior to known 2-aminoenosulfonic acid, glucanthione and glycyrrhizin.
  • Acetaldehyde a metabolite It has the effect of enhancing the detoxifying function of various compounds in the liver, which exerts a strong protective effect against lethal toxicity of the compound.
  • the anti-ulcer test showed a clear inhibitory effect.
  • high safety was confirmed in toxicity tests. Therefore, the present invention can provide a new drug having both an anti-hepatitis effect, a liver function improving effect and an anti-ulcer effect.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/JP1993/000813 1992-06-18 1993-06-14 Compose complexe acide 2-aminoethanesulfonique/zinc Ceased WO1993025558A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP93913534A EP0646586B1 (en) 1992-06-18 1993-06-14 2-aminoethanesulfonic acid/zinc complex compound
US08/356,305 US5489609A (en) 1992-06-18 1993-06-14 2-aminoethanesulfonic acid zinc complex compound
DE69314794T DE69314794T2 (de) 1992-06-18 1993-06-14 Komplex von 2-aminäthansulfonsäure und zink

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP4186090A JPH0725771B2 (ja) 1992-06-18 1992-06-18 ２−アミノエタンスルホン酸亜鉛錯化合物
JP4/186090 1992-06-18

Publications (1)

Publication Number Publication Date
WO1993025558A1 true WO1993025558A1 (fr) 1993-12-23

Family

ID=16182196

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1993/000813 Ceased WO1993025558A1 (fr) 1992-06-18 1993-06-14 Compose complexe acide 2-aminoethanesulfonique/zinc

Country Status (5)

Country Link
US (1) US5489609A (enExample)
EP (1) EP0646586B1 (enExample)
JP (1) JPH0725771B2 (enExample)
DE (1) DE69314794T2 (enExample)
WO (1) WO1993025558A1 (enExample)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5475028A (en) * 1992-01-14 1995-12-12 Zaidan Hojin Seisan Kaihatsu Kagaku Kenkyusho 2-aminoethanesulfonic acid zinc complex

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3837769B2 (ja) * 1995-06-12 2006-10-25 大塚製薬株式会社 抗ウイルス剤
US11505703B2 (en) 2017-11-30 2022-11-22 Dow Toray Co., Ltd. Curable silicone rubber composition

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0206692A2 (en) * 1985-06-14 1986-12-30 Ed. Geistlich Söhne Ag Für Chemische Industrie Topically administrable pharmaceutical compositions

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5292605A (en) * 1976-01-26 1977-08-04 Canon Kk Thermoodeveloping photoosensitive material for electrostatic printing master
FR2457281A1 (fr) * 1979-05-23 1980-12-19 Meram Lab Nouveaux derives de l'acide 3-aminopropanesulfonique ayant une activite membranaire renforcee
JPH0670070B2 (ja) * 1992-01-14 1994-09-07 財団法人生産開発科学研究所 ２−アミノエタンスルホン酸亜鉛錯体

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0206692A2 (en) * 1985-06-14 1986-12-30 Ed. Geistlich Söhne Ag Für Chemische Industrie Topically administrable pharmaceutical compositions

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5475028A (en) * 1992-01-14 1995-12-12 Zaidan Hojin Seisan Kaihatsu Kagaku Kenkyusho 2-aminoethanesulfonic acid zinc complex

Also Published As

Publication number Publication date
EP0646586A4 (enExample) 1995-05-10
EP0646586A1 (en) 1995-04-05
EP0646586B1 (en) 1997-10-22
US5489609A (en) 1996-02-06
JPH0649077A (ja) 1994-02-22
DE69314794T2 (de) 1998-02-26
JPH0725771B2 (ja) 1995-03-22
DE69314794D1 (de) 1997-11-27

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