CN1152685C - 内皮素受体拮抗剂在制备治疗肥胖的药物方面的用途 - Google Patents
内皮素受体拮抗剂在制备治疗肥胖的药物方面的用途 Download PDFInfo
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Abstract
利用内皮素受体拮抗剂生产控制肥胖及由肥胖引起的一些疾病的药物。
Description
本发明涉及控制肥胖及由肥胖引起的一些疾病的方法。
肽激素内皮素是已知具有很强的血管收缩作用的药物。因此，内皮素受体拮抗剂主要在心血管病理方面进行检验。
本发明涉及内皮素受体拮抗剂用于生产控制肥胖及由肥胖引起的一些疾病的药物的方法。
能够用作内皮素受体拮抗剂的包括内皮素A受体拮抗剂以及内皮素A和B受体拮抗剂的混合物。
特别适合的内皮素受体拮抗剂是：
1.TBC-11251(医药化学杂志.，40，No.11，1690-97，1997)，
2.BMS-193884(EP 558,258)
3.BMS-207940(药物开发，(13.06.97))，
4.BQ-123(试验药的实验评价，1997，6，No.5，475-487)，
5.SB-209670(试验药的实验评价，1997，6，No.5，475-487)，
6.SB-217242(试验药的实验评价，1997，6，No.5，475-487)，
7.SB-209598(药物科学发展方向.，17，177-81，1996)，
8.TAK-044(试验药的实验评价，1997，6，No.5，475-487)，
9.Bosentan(药物科学发展方向.，18，408-12，1997)，
10.PD-156707(医药化学杂志，40，No.7，1063-74，1997)，
11.L-749329(生物有机医药化学通讯.，7，No.3，275-280，1997)，
12.L-754142(试验药的实验评价，1997，6，No.5，475-4 87)，
13.ABT-627(医药化学杂志.，40，No.20，3217-27，1997)，
14.A-127772(医药化学杂志，39，No，5，1039-1048，1996)，
15.A-206377(第213届美国化学协会全国会议旧金山，加利福尼亚，USA，4月1 3-17日，1997，Poster，MEDI 193)，
16.A-182086(医药化学杂志.，40，No.20，3217-27，1997)，
17.EMD-93246(第211届美国化学协会全国会议新奥尔良，USA，1996，Poster，MEDI 143)，
18.EMD-122801(生物有机医药化学通讯.，8，No.1，17-22，1998)，
19.ZD-1611(药物科学发展方向.，18，408-12，1997)，
20.AC-610612(药物研究与开发焦点新闻(18.05.98))，
21.T-0201(日本药学会第70届年会，Chiba，Japan，22-25 March 1997，Lecture，0-133)，
22.J-104132(药物研究与开发焦点新闻(15.12.97))尤其是下列化合物：
所谓肥胖，是指当体重至少超过正常体重的20％。肥胖的原因是吃得太多或者不能正常地利用食物，例如，家族性的血胆固醇含量太高。由于肥胖引起的，或与肥胖有关的疾病，特别值得提出的是高血压，2型糖尿病、高脂血病、慢性肾衰竭、动脉硬化，可能还包括痛风。
到目前为止，虽然困难很大，但动物实验已能制造肥胖的病理模型(喂以极高剂量的胆固醇)。最近已培养出缺乏阿朴脂蛋白E基因的小鼠，用于试验抗肥胖的物质。
用阿朴脂蛋白E造模的老鼠，研究了内皮素受体拮抗剂物质23的效果。对照组的大鼠，如预料的那样，由于喂以高脂饲料，体重大大增加。这与肝的增大及肝的脂肪退化有关。在平行实验组内，动物以物质23治疗(50mg/kg/d)。该组动物的体重和肝重的增加完全被抑制。且肝的组织学变化不明显。
内皮素A和内皮素A/B受体拮抗剂必须终生给药，其剂量是每人每天50至500mg。
内皮素A和内皮素A/B受体拮抗剂一般通过口服给药，例如，采用糖衣或无糖衣的片剂、硬的或软的胶囊、溶液、乳状液或悬浮液。但是，亦可采用直肠给药，例如栓剂，亦可采用肠胃外给药，例如注射液形式。
为了生产糖衣或无糖衣的片剂和硬壳明胶胶囊，按照本发明，有效化合物可以同药物上惰性的、有机或无机赋形剂结合加工。在制备糖衣或无糖衣片剂以及硬胶囊中，能用作赋形剂的有乳糖、玉米淀粉或类似物，滑石粉、硬脂酸或其盐类。适合用于软胶囊的赋形剂是菜油、蜡、油脂、半固体或液体的多元醇。
适合于生产溶液和糖浆的赋形剂是，例如，水、多元醇、蔗糖、软化糖、葡萄糖及类似物。适合用于注射液的赋形剂是水、醇、多元醇、甘油、菜油。适合用于栓剂的赋形剂是天然油或凝固油、蜡、脂、半液状或液状多元醇及其类似物。
药物制剂进一步还可能包括：防腐剂、助溶剂、稳定剂、湿润剂、乳化剂、甜味剂、色素、香味剂、改变渗透压的盐、缓冲剂、涂渍剂和/或抗氧剂。
以下各例说明本发明。
例1
含下列组成的涂渍包衣片剂的生产：
化合物23 300.0mg
无水乳糖 30.0mg
微晶纤维素 30.0mg
聚乙烯吡咯烷酮 20.0mg
硬脂酸镁 5.0mg
聚乙二醇6000 0.8mg
黄色氧化铁 1.2mg
二氧化钛 0.3mg
滑石粉 0.7mg
将化合物23、乳糖、纤维素和聚乙烯吡咯烷酮放到一起、湿法制粒，再干燥。过筛后的颗粒同硬脂酸镁混合，混合物被压成椭园形片芯，每个重390.0mg。再把片芯涂上包衣，最后涂渍包衣的片剂重量达到400mg。
例2
涂渍包衣的片剂的制备方法同例1，但是包含300mg化合物26代替300mg化合物23。
例3
生产含有下列组成的硬壳胶囊：
化合物23 250.0mg
结晶乳糖 18.0mg
聚乙烯吡咯烷酮 15.0mg
微晶纤维素 17.5mg
羧甲基淀粉钠 10.0mg
滑石粉 0.7mg
硬脂酸镁 3.0mg
首先将前面5个成分湿法制粒并干燥。该颗粒再同羧甲基淀粉钠、滑石粉和硬脂酸镁混合，将混合物填充到0号硬胶囊中。
Claims (2)
1.下式23-26的内皮素受体拮抗剂在制备用于控制肥胖以及由肥胖引起的疾病的药物方面的用途，
2.按照权利要求1的用途，其中由肥胖引起的疾病是高血压、II型糖尿病、高脂血症、慢性肾衰竭和动脉硬化。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19754082.1 | 1997-12-05 | ||
| DE19754082A DE19754082A1 (de) | 1997-12-05 | 1997-12-05 | Methode zur Bekämpfung der Fettleibigkeit |
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| CN1301162A CN1301162A (zh) | 2001-06-27 |
| CN1152685C true CN1152685C (zh) | 2004-06-09 |
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| CNB988118327A Expired - Fee Related CN1152685C (zh) | 1997-12-05 | 1998-11-21 | 内皮素受体拮抗剂在制备治疗肥胖的药物方面的用途 |
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| US (1) | US6197780B1 (zh) |
| EP (1) | EP1035851B1 (zh) |
| JP (1) | JP2002512173A (zh) |
| KR (1) | KR20010032779A (zh) |
| CN (1) | CN1152685C (zh) |
| AT (1) | ATE204172T1 (zh) |
| AU (1) | AU751053B2 (zh) |
| BR (1) | BR9815335A (zh) |
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| HK (1) | HK1037141A1 (zh) |
| HU (1) | HUP0100171A3 (zh) |
| NO (2) | NO324694B1 (zh) |
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| DE19533023B4 (de) * | 1994-10-14 | 2007-05-16 | Basf Ag | Neue Carbonsäurederivate, ihre Herstellung und Verwendung |
| EP1130027A1 (de) * | 2000-02-29 | 2001-09-05 | Aventis Pharma Deutschland GmbH | Memno-Peptide, Verfahren zu ihrer Herstellung und Verwendung derselben |
| US20050175667A1 (en) * | 2004-02-10 | 2005-08-11 | Wenda Carlyle | Use of endothelin antagonists to prevent restenosis |
| JP2010536880A (ja) | 2007-08-22 | 2010-12-02 | ギリード・コロラド・インコーポレーテッド | 糖尿病の合併症のための療法 |
| SI3329919T1 (sl) | 2011-11-11 | 2020-02-28 | Gilead Apollo, Llc | Inhibitorji ACC in njihove uporabe |
| WO2016099233A2 (ru) * | 2014-10-20 | 2016-06-23 | Товарищество С Ограниченной Ответственностью "Фармацевтическая Компания "Ромат" | Фармацевтическая композиция для лечения туберкулеза |
| AR106472A1 (es) | 2015-10-26 | 2018-01-17 | Gilead Apollo Llc | Inhibidores de acc y usos de los mismos |
| EA201890910A1 (ru) | 2015-11-25 | 2018-11-30 | Джилид Аполло, Ллс | ФУНГИЦИДНЫЕ КОМПОЗИЦИИ, СОДЕРЖАЩИЕ ПРОИЗВОДНЫЕ 2,4-ДИОКСО-1,4-ДИГИДРОТИЕНО[2,3-d]ПИРИМИДИНА |
| AU2016361428A1 (en) | 2015-11-25 | 2018-05-24 | Gilead Apollo, Llc | Triazole ACC inhibitors and uses thereof |
| MX2018006288A (es) | 2015-11-25 | 2018-09-07 | Gilead Apollo Llc | Inhibidores de acc tipo ester y usos de los mismos. |
| CN108349995B (zh) | 2015-11-25 | 2021-08-03 | 吉利德阿波罗公司 | 吡唑acc抑制剂及其用途 |
| TWI788281B (zh) | 2016-03-02 | 2023-01-01 | 美商基利阿波羅有限責任公司 | 噻吩并嘧啶二酮acc抑制劑之固體型式及其製造方法 |
| CN110461328A (zh) | 2017-03-28 | 2019-11-15 | 吉利德科学公司 | 治疗肝疾病的治疗组合 |
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| KR950704314A (ko) | 1992-12-01 | 1995-11-17 | 가와노 다케히코 | 1,8-나프티리딘-2-온 유도체 및 그 사용 방법(1,8-naphthyridin-2-one derivative and use thereof) |
| WO1997008169A1 (en) * | 1995-08-24 | 1997-03-06 | Warner-Lambert Company | Furanone endothelin antagonists |
| JP3116347B2 (ja) * | 1996-11-13 | 2000-12-11 | 田辺製薬株式会社 | 医薬組成物 |
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- 1998-11-21 CZ CZ20002006A patent/CZ300442B6/cs not_active IP Right Cessation
- 1998-11-21 AT AT98965685T patent/ATE204172T1/de active
- 1998-11-21 JP JP2000523980A patent/JP2002512173A/ja active Pending
- 1998-11-21 HU HU0100171A patent/HUP0100171A3/hu unknown
- 1998-11-21 KR KR1020007006075A patent/KR20010032779A/ko not_active Application Discontinuation
- 1998-11-21 CN CNB988118327A patent/CN1152685C/zh not_active Expired - Fee Related
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Also Published As
| Publication number | Publication date |
|---|---|
| ES2162493T3 (es) | 2001-12-16 |
| CZ20002006A3 (cs) | 2000-11-15 |
| HK1037141A1 (en) | 2002-02-01 |
| WO1999029308A2 (de) | 1999-06-17 |
| EP1035851A2 (de) | 2000-09-20 |
| AU2153599A (en) | 1999-06-28 |
| NO324694B1 (no) | 2007-12-03 |
| BR9815335A (pt) | 2000-10-17 |
| CN1301162A (zh) | 2001-06-27 |
| CA2311423A1 (en) | 1999-06-17 |
| NO20002777D0 (no) | 2000-05-30 |
| HUP0100171A3 (en) | 2003-10-28 |
| ATE204172T1 (de) | 2001-09-15 |
| KR20010032779A (ko) | 2001-04-25 |
| AU751053B2 (en) | 2002-08-08 |
| EP1035851B1 (de) | 2001-08-16 |
| NO20002777L (no) | 2000-06-02 |
| RU2003138080A (ru) | 2005-06-10 |
| DE59801230D1 (de) | 2001-09-20 |
| JP2002512173A (ja) | 2002-04-23 |
| WO1999029308A3 (de) | 1999-09-30 |
| CZ300442B6 (cs) | 2009-05-20 |
| RU2292891C2 (ru) | 2007-02-10 |
| CA2311423C (en) | 2008-01-29 |
| DE19754082A1 (de) | 1999-06-10 |
| HUP0100171A2 (hu) | 2003-02-28 |
| NO20074419L (no) | 2000-06-02 |
| US6197780B1 (en) | 2001-03-06 |
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