CN1705479B - 2-[n,n-二(羧甲基)氨基]-3-氰基-4-羧甲基-噻吩-5-甲酸二锶盐在制备治疗胃十二指肠疼痛的药物中的用途 - Google Patents

2-[n,n-二(羧甲基)氨基]-3-氰基-4-羧甲基-噻吩-5-甲酸二锶盐在制备治疗胃十二指肠疼痛的药物中的用途 Download PDF

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CN1705479B
CN1705479B CN2003801018229A CN200380101822A CN1705479B CN 1705479 B CN1705479 B CN 1705479B CN 2003801018229 A CN2003801018229 A CN 2003801018229A CN 200380101822 A CN200380101822 A CN 200380101822A CN 1705479 B CN1705479 B CN 1705479B
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carboxymethyl
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Y·楚泽罗斯
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Laboratoires Servier SAS
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    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • 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
    • 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]

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Abstract

本发明涉及2-[N，N-二(羧甲基)氨基]-3-氰基-4-羧甲基-噻吩-5-甲酸二锶盐在制备治疗胃十二指肠疼痛的药物中的用途。

Description

2-[N，N-二(羧甲基)氨基]-3-氰基-4-羧甲基-噻吩-5-甲酸二锶盐在制备治疗胃十二指肠疼痛的药物中的用途
本发明涉及2-[N，N-二(羧甲基)氨基]-3-氰基-4-羧甲基-噻吩-5-甲酸二锶盐在制备治疗胃十二指肠疼痛的药物中的用途。
在欧洲专利说明书0 415 850中描述了2-[N，N-二(羧甲基)氨基]-3-氰基-4-羧甲基-噻吩-5-甲酸二锶盐。该化合物具有抗骨质疏松的性质，使得它可用于治疗如骨质疏松的骨疾病。该化合物也用于治疗皮肤和血管老化、肝功能失调和牙齿疾病。
此外，在欧洲专利说明书0 813 869中述及2-[N，N-二(羧甲基)氨基]-3-氰基-4-羧甲基-噻吩-5-甲酸二锶盐具有抗关节炎的性质，从而可以将它用于治疗关节病。
本申请人发现，式(I)的2-[N，N-二(羧甲基)氨基]-3-氰基-4-羧甲基-噻吩-5-甲酸二锶盐及其水合物具有胃保护性质，因此它们可用于制备治疗胃十二指肠疼痛的药物：
Figure G2003801018229D00011
在临床研究中已表明，式(I)化合物(也称作雷奈酸锶(strontiumranelate))能够使胃痛获得显著的改善。
令人更加惊奇地是，采用不同的锶盐(氯化锶)进行的体内研究结果表明，氯化锶迅速引起所治疗的动物的表面出现出血性损伤。
据此，本领域的技术人员肯定无法想到不同的锶盐(在该情况下为雷奈酸锶)却得到完全相反的结果。
这些令人惊奇的结果使得申请人考虑将锶盐及其水合物用于制备治疗胃十二指肠疼痛、尤其是胃炎和十二指肠炎以及任何急性或慢性胃粘膜炎症的药物组合物。
胃炎和十二指肠炎的某些症状为消化粘膜的刺激状态，伴有与每日进食相关的腹部疼痛。不同种类的食物或酒精饮料可加重炎症。这些炎症也可是溃疡的先兆。因此，需要给予各种治疗以保护粘膜或减少胃酸分泌。
药物组合物可以为各种形式，适于通过口服、胃肠外、经皮、鼻、直肠或经舌的途径给药，优选注射剂、片剂、舌下片剂、舌下或直肠给药剂型(glossettes)、明胶胶囊、胶囊、锭剂、栓剂、霜剂、软膏、皮肤凝胶剂等形式。
除了雷奈酸锶或者在适当时为其水合物外，本发明的药物组合物还包括一种或多种选自稀释剂、润滑剂、粘合剂、崩解剂、吸附剂、着色剂、甜味剂等的赋形剂或载体。
如下所提及的实例是非限定性的：
◆稀释剂：乳糖、葡萄糖、蔗糖、甘露醇、山梨醇、纤维素、甘油。
◆润滑剂：硅胶、滑石粉、硬脂酸及其镁盐和钙盐、聚乙二醇。
◆粘合剂：硅酸铝、硅酸镁、淀粉、明胶、黄芪胶、甲基纤维素、羧甲基纤维素钠和聚乙烯吡咯烷酮。
◆崩解剂：琼脂、褐藻酸及其钠盐、泡腾混合物。
根据患者性别、年龄和体重、给药途径、疾病性质以及相关的治疗，所用的剂量可以有所不同，范围为每24小时给予雷奈酸锶25mg至6g，例如每24小时给予化合物100mg至4g。
雷奈酸锶的日剂量优选为每天2g。
临床研究
该研究采用1649名患者进行。其中719名患者采用雷奈酸锶进行治疗，723名患者采用安慰剂治疗。治疗期间为1101±321天。雷奈酸锶的剂量为每天2g。
治疗结束后观察到：用雷奈酸锶进行治疗的患者组较安慰剂治疗的患者组胃痛明显减少(至少30％)。

Claims (1)

1.2-[N，N-二(羧甲基)氨基]-3-氰基-4-羧甲基-噻吩-5-甲酸的二锶盐或其水合物在制备用于治疗胃炎患者的胃十二指肠疼痛的药物中的用途。
CN2003801018229A 2002-11-05 2003-11-04 2-[n,n-二(羧甲基)氨基]-3-氰基-4-羧甲基-噻吩-5-甲酸二锶盐在制备治疗胃十二指肠疼痛的药物中的用途 Expired - Fee Related CN1705479B (zh)

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FR02/13805 2002-11-05
FR0213805A FR2846558B1 (fr) 2002-11-05 2002-11-05 Utilisation du sel distrontique de l'acide 2-n,n-di(carboxymethyl)amino-3-cyano-4-carboxymethyl- thiophene-5-carboxylique pour l'obtention de medicaments destines au traitement des douleurs gastro-duodenales
PCT/FR2003/003279 WO2004043455A1 (fr) 2002-11-05 2003-11-04 Utilisation du sel distrontique de l'acide 2-[n,n-di(carboxymethyl)amino]-3-cyano-4-carboxymethyl-thiophene-5-carboxylique pour l'obtention de medicaments destines au traitement des douleurs gastro-duodenales

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EP1534305B9 (en) 2003-05-07 2007-03-07 Osteologix A/S Treating cartilage / bone conditions with water-soluble strontium salts
WO2005123098A2 (en) * 2004-06-17 2005-12-29 Osteologix A/S Preventing gastrointestinal side-effects with strontium salts
US20070292535A1 (en) * 2006-06-19 2007-12-20 Tabbiner Philip S Strontium compositions and methods of treating arthritic and or osteoporitic conditions
US20070292529A1 (en) * 2006-06-19 2007-12-20 Tabbiner Philip S Strontium compositions and methods of treating osteoporotic conditions
EP2530068A1 (en) 2011-05-31 2012-12-05 Lacer, S.A. New strontium salts, synthesis and use thereof in the treatment of osteoporosis

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US5866168A (en) * 1995-10-26 1999-02-02 Societe L'oreal S.A. Dermatological/pharmaceutical compositions comprising lanthanide, manganese, tin, zinc, yttrium, cobalt, barium and/or strontium salts as substance P antagonists
US6146636A (en) * 1997-09-22 2000-11-14 Societe L'oreal S.A. Substance P antagonists comprising rosaceae plant extracts

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FR2651497B1 (fr) * 1989-09-01 1991-10-25 Adir Nouveaux sels de metaux bivalents de l'acide n, n-di (carboxymethyl)amino-2 cyano-3 carboxymethyl-4 carboxy-5 thiophene, leur procede de preparation et les compositions pharmaceutiques les renfermant.
FR2749759B1 (fr) * 1996-06-17 1999-11-26 Adir Utilisation de sels de strontium pour l'obtention de compositions pharmaceutiques destinees au traitement de l'arthrose
US6489356B2 (en) * 2000-09-05 2002-12-03 Edward Leung Method for treating pain in humans

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Publication number Priority date Publication date Assignee Title
US5866168A (en) * 1995-10-26 1999-02-02 Societe L'oreal S.A. Dermatological/pharmaceutical compositions comprising lanthanide, manganese, tin, zinc, yttrium, cobalt, barium and/or strontium salts as substance P antagonists
US6146636A (en) * 1997-09-22 2000-11-14 Societe L'oreal S.A. Substance P antagonists comprising rosaceae plant extracts

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BR0315917A (pt) 2005-09-20
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ZA200503082B (en) 2006-07-26
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CN1705479A (zh) 2005-12-07
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