WO1994000417A1 - Zinc tranexamate compound - Google Patents
Zinc tranexamate compound Download PDFInfo
- Publication number
- WO1994000417A1 WO1994000417A1 PCT/JP1993/000852 JP9300852W WO9400417A1 WO 1994000417 A1 WO1994000417 A1 WO 1994000417A1 JP 9300852 W JP9300852 W JP 9300852W WO 9400417 A1 WO9400417 A1 WO 9400417A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compound
- zinc
- organic acid
- acid
- acid salt
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/46—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino or carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Definitions
- the present invention relates to a novel zinc tranexamate compound, a pharmaceutically acceptable organic acid salt thereof, a method for producing the same, and an anti-inflammatory and anti-ulcer agent containing the same as an active ingredient.
- Tranexamic acid inhibits the binding of brassminogen and brassin to fibrin, reduces their fibrinolytic activity and suppresses bleeding. It is said that these mechanisms suppress blood vessel weakness and have antiallergic and anti-inflammatory effects. Specifically, it is said to be effective for hyperemia, redness, swelling, and pain in actors such as tonsillitis, pharyngolaryngitis, stomatitis, and oral mucosa. There are also good reports on the synthesis and pharmacological activity of zinc tranexamate compounds.
- the present inventors have synthesized a large number of zinc compounds in order to develop excellent anti-ulcer and anti-gastritis agents, and studied their therapeutic effects.As a result, they have shown that zinc tranexamate has a remarkable effect. The present inventors have found and further studied and completed the present invention.
- the present invention provides a compound of the formula (I)
- the present invention relates to a novel zinc tranexamate compound represented by the formula: and a pharmaceutically acceptable organic acid salt thereof, a production method thereof, and an anti-inflammatory and anti-ulcer agent containing the same as an active ingredient.
- a zinc compound As the alcohol agent, it is preferable to use, for example, an alkali metal alcoholate such as sodium methylate, sodium ethylate, potassium methylate, potassium methoxide or potassium l-butoxide.
- an alkali metal alcoholate such as sodium methylate, sodium ethylate, potassium methylate, potassium methoxide or potassium l-butoxide.
- a zinc salt soluble in a reaction solvent such as zinc acetate, zinc chlorobromide or zinc iodide is usually used, but other zinc compounds may be used.
- the reaction is preferably performed in an anhydrous solvent, and is usually performed in a suitable solvent such as methanol or ethanol at room temperature or under heating for several minutes to several hours. After the reaction, the precipitated compound of the formula (I) can be purified by a conventional method.
- the present invention includes pharmaceutically acceptable organic acid salts of compound (I), such as acetic acid, glycolic acid, lactic acid, malonic acid, succinic acid, malic acid, tartaric acid, maleic acid, and fumaric acid.
- organic acid salts of compound (I) such as acetic acid, glycolic acid, lactic acid, malonic acid, succinic acid, malic acid, tartaric acid, maleic acid, and fumaric acid.
- examples include salts of aliphatic carboxylic acids such as acids, amino acids such as aspartic acid and glutamic acid, and aromatic carboxylic acids such as benzoic acid and phthalic acid.
- the organic acid salt of compound (I) can be obtained, for example, by adding compound (I) to an organic acid dissolved in methanol or another anhydrous solvent and reacting the same.
- the compound of the formula (I) of the present invention and an organic acid salt thereof have excellent anti-stomatitis, anti-gastric and duodenal ulcer and anti-gastric and duodenal inflammation, and have low toxicity.
- the compound of the formula (I) and an organic acid salt thereof can be used in various forms such as tablets, capsules, granules and powders by itself or mixed with an appropriate pharmacologically acceptable excipient, carrier or diluent. Can be used orally or parenterally.
- the organic acid salt of compound (I) is soluble in water, it can be used in a wide range of applications such as injections, infusions, syrups, eye drops, dental agents and external solutions such as nasal drops and inhalants. .
- test compound was suspended in 0.5% carboxymethylcellulose water and administered in a volume of 200 ml body weight of 1 mlZ. Controls received the same volume of vehicle alone.
- Ethyl hydrochloride (ethanol containing 0.15 mol hydrochloric acid in 60% ethanol) was orally administered in a volume of 200 ml body weight of 1 mlZ.
- the animals were killed with ether, the stomach and duodenum were removed, and the contents were removed from the duodenum.
- 8 ml of a 2% formalin solution was injected into the stomach from the duodenum.
- the pylorus was further immersed in the same solution for 10 minutes and lightly fixed (hereinafter abbreviated as formalin treatment).
- the stomach is incised along the greater curvature, and the length (mm) of each injury (erosion) occurring in the glandular stomach is measured under a dissecting microscope (10 magnification), and the damage per animal was calculated.
- the test compound was orally administered 1 hour before administration of hydrochloric acid / ethanol. Table 1 shows the results. ⁇ table 1 ⁇
- Rats were placed in a Tokyo University medicinal stress box, immersed in the aquarium at step 2 to the level of the xiphoid process, and subjected to stress. Eight hours later, it was raised from the water tank and killed with ether. After removal of the stomach and formalin treatment, the length (mm) of the damage occurring in the glandular stomach was measured, and the total damage per animal was calculated. The test compound was orally administered immediately before the stress load. Table 2 shows the results.
- the zinc tranexamate monohydrate of the compound of the present invention showed an excellent inhibitory effect in the anti-ulcer test as compared with the control compounds tranexamic acid and cetraxate hydrochloride.
- Cetraxate hydrochloride is the most effective and widely used gastric mucosal protective factor potentiator currently on the market.It contains tranexamic acid in the molecule but is still 600 to 80 mg per day. Is the amount used.
- cetraxate hydrochloride since the compound of the present invention has an action clearly superior to that of cetraxate hydrochloride, a sufficient effect can be expected at a dose of 300 mg to 40 mg per day, and it is tasteless and odorless. It has the advantage of being easy to take.
- the organic acid salt of the compound of the present invention is soluble in water, it can be used for a wide range of uses such as injections and external solutions.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/356,282 US5506264A (en) | 1992-06-23 | 1993-06-21 | Zinc tranexamate compounds |
DE69313640T DE69313640T2 (de) | 1992-06-23 | 1993-06-21 | Zink-tranexamat derivat |
EP93913570A EP0647616B1 (en) | 1992-06-23 | 1993-06-21 | Zinc tranexamate compound |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP4189831A JPH0725724B2 (ja) | 1992-06-23 | 1992-06-23 | トラネキサム酸亜鉛化合物 |
JP4/189831 | 1992-06-23 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1994000417A1 true WO1994000417A1 (en) | 1994-01-06 |
Family
ID=16247945
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP1993/000852 WO1994000417A1 (en) | 1992-06-23 | 1993-06-21 | Zinc tranexamate compound |
Country Status (5)
Country | Link |
---|---|
US (1) | US5506264A (ja) |
EP (1) | EP0647616B1 (ja) |
JP (1) | JPH0725724B2 (ja) |
DE (1) | DE69313640T2 (ja) |
WO (1) | WO1994000417A1 (ja) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001247458A (ja) * | 2000-03-08 | 2001-09-11 | Hamari Chemicals Ltd | トラネキサム酸亜鉛化合物を含む糖尿病治療剤 |
US20050025825A1 (en) * | 2003-07-31 | 2005-02-03 | Xanodyne Pharmacal, Inc. | Tranexamic acid formulations with reduced adverse effects |
US20090214644A1 (en) * | 2003-07-31 | 2009-08-27 | Xanodyne Pharmaceuticals, Inc. | Tranexamic acid formulations with reduced adverse effects |
US8022106B2 (en) * | 2004-03-04 | 2011-09-20 | Ferring B.V. | Tranexamic acid formulations |
US7947739B2 (en) | 2004-03-04 | 2011-05-24 | Ferring B.V. | Tranexamic acid formulations |
US20090215898A1 (en) * | 2004-03-04 | 2009-08-27 | Xanodyne Pharmaceuticals, Inc. | Tranexamic acid formulations |
US20050245614A1 (en) * | 2004-03-04 | 2005-11-03 | Xanodyne Pharmaceuticals, Inc. | Tranexamic acid formulations |
US20050244495A1 (en) * | 2004-03-04 | 2005-11-03 | Xanodyne Pharmaceuticals, Inc. | Tranexamic acid formulations |
WO2006023000A1 (en) * | 2004-07-30 | 2006-03-02 | Xanodyne Pharmaceuticals, Inc. | Tranexamic acid formulations |
US20100280117A1 (en) * | 2009-04-30 | 2010-11-04 | Xanodyne Pharmaceuticals, Inc. | Menorrhagia Instrument and Method for the Treatment of Menstrual Bleeding Disorders |
US8597683B2 (en) | 2010-11-30 | 2013-12-03 | Watson Pharmaceuticals, Inc. | Modified release tranexamic acid formulation |
US20140220136A1 (en) * | 2013-02-05 | 2014-08-07 | Bordoloi Biotech, Llc | System and method for delivering protease inhibitors |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS60163813A (ja) * | 1984-02-04 | 1985-08-26 | Morishita Jintan Kk | 抗プラスミン薬 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5759847A (en) * | 1980-09-29 | 1982-04-10 | Hisamitsu Pharmaceut Co Inc | 4-aminomethylcyclohexanecarboxylic acid derivative |
EP0079872B1 (en) * | 1981-11-17 | 1985-03-20 | KabiVitrum AB | Antifibrinolytically active compounds |
-
1992
- 1992-06-23 JP JP4189831A patent/JPH0725724B2/ja not_active Expired - Fee Related
-
1993
- 1993-06-21 DE DE69313640T patent/DE69313640T2/de not_active Expired - Fee Related
- 1993-06-21 US US08/356,282 patent/US5506264A/en not_active Expired - Lifetime
- 1993-06-21 EP EP93913570A patent/EP0647616B1/en not_active Expired - Lifetime
- 1993-06-21 WO PCT/JP1993/000852 patent/WO1994000417A1/ja active IP Right Grant
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS60163813A (ja) * | 1984-02-04 | 1985-08-26 | Morishita Jintan Kk | 抗プラスミン薬 |
Also Published As
Publication number | Publication date |
---|---|
JPH0649006A (ja) | 1994-02-22 |
JPH0725724B2 (ja) | 1995-03-22 |
EP0647616B1 (en) | 1997-09-03 |
DE69313640T2 (de) | 1998-01-08 |
EP0647616A4 (en) | 1995-08-16 |
US5506264A (en) | 1996-04-09 |
EP0647616A1 (en) | 1995-04-12 |
DE69313640D1 (de) | 1997-10-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0668851B1 (en) | A novel arylpropionic derivative, a process for the preparation and the use thereof as an analgesic agent | |
AU2016358448B2 (en) | Salts of tetracyclines | |
WO1994000417A1 (en) | Zinc tranexamate compound | |
WO2009038204A1 (ja) | 新規長鎖脂肪酸誘導体化合物及びそれら化合物を有効成分とするgタンパク質共役型レセプター作動剤 | |
ES2215769T3 (es) | Forma cristalina de acido (s)-2-etoxi-3-(4-(2-(4-metanosulfoniloxifenil)etoxi)fenil)propanoico. | |
WO2005023766A1 (en) | Salt of atorvastatin with metformin | |
JPH0148254B2 (ja) | ||
JP3891503B2 (ja) | 製薬学的に活性なβ−アミノ酸類の許容性の改善 | |
JP3356304B2 (ja) | 抗炎、抗潰瘍剤 | |
JP2569060B2 (ja) | グルタミルシスティン誘導体、その製造法およびそれを有効成分とする組織グルタチオンレベル向上剤 | |
TWI285204B (en) | Polymorphs of a crystalline azabicyclo[2,2.2]octan-3-amine citrate and their pharmaceutical compositions | |
JPH0692948A (ja) | 新規なアセタミド誘導体及びその用途 | |
JP2589245B2 (ja) | N−(3−アルキル(またはアルケニル)−4−ヒドロキシベンゾイル)グリシン亜鉛錯体 | |
JPS6310701B2 (ja) | ||
JPS641470B2 (ja) | ||
JPH07228528A (ja) | 水溶性トラネキサム酸亜鉛化合物 | |
WO2008056377A2 (en) | Polymorphic forms of rimonabant | |
JP2811136B2 (ja) | シメチジン亜鉛錯体 | |
JPS6354338A (ja) | 4−フエニル−4−オキソ−2−ブテン酸の新誘導体、その製造法、薬剤としての使用及びそれを含有する組成物 | |
JP3129370B2 (ja) | 食欲抑制剤 | |
JPH072696B2 (ja) | 新規なフェニル酢酸誘導体とその調製方法 | |
JP2001181251A (ja) | アスピリン誘導体、その製造方法、並びにこれを有効成分として含有する抗炎症剤 | |
JPH06256185A (ja) | ビタミンe誘導体およびそれを有効成分とする抗潰瘍剤 | |
JPH0931096A (ja) | シクロペンタン−β−アミノ酸トリペプチド類 | |
JPH07238019A (ja) | 水溶性タウリン亜鉛化合物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): CA KR US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 08356282 Country of ref document: US |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1993913570 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1993913570 Country of ref document: EP |
|
NENP | Non-entry into the national phase |
Ref country code: CA |
|
WWG | Wipo information: grant in national office |
Ref document number: 1993913570 Country of ref document: EP |