CN101176788A - Ace抑制剂/利尿剂/叶酸联用的药物组合物及其用途 - Google Patents
Ace抑制剂/利尿剂/叶酸联用的药物组合物及其用途 Download PDFInfo
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- CN101176788A CN101176788A CNA2007101657788A CN200710165778A CN101176788A CN 101176788 A CN101176788 A CN 101176788A CN A2007101657788 A CNA2007101657788 A CN A2007101657788A CN 200710165778 A CN200710165778 A CN 200710165778A CN 101176788 A CN101176788 A CN 101176788A
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- folic acid
- hydrochlorothiazide
- hypertension
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Abstract
Description
合用类型 | 合用剂量配比,mg* |
ACE抑制剂和利尿剂 | 苯那普利/氢***(5/6.25,10/12.5,20/12.5,20/25) |
卡托普利/氢***(25/15,25/25,50/15,50/25) | |
依那普利/氢***(5/12.5,10/25) | |
赖诺普利/氢***(10/12.5,20/12.5,20/25) | |
莫昔普利/氢***(7.5/12.5,15/25) | |
喹那普利/氢***(10/12.5,20/12.5,20/25) | |
咪达普利/氢***(5/12.5,10/12.5,10/25) | |
群多普利/氢***(1/12.5,2/12.5,2/25) | |
培哚普利/氢***(4/12.5,8/12.5,8/25) | |
西拉普利/氢***(2.5/12.5,5/12.5,5/25) | |
福辛普利/氢***(10/12.5,20/12.5,20/25) | |
雷米普利/氢***(2.5/12.5,5/12.5,5/25) | |
*可得到多种固定剂量的复方药物。每种药物的剂量均为mg |
组别 | 剂量(mg/kg) | 动物数 | 脑卒中发生数(发生率) | 首次发作时间(天,以试验开始时间计算) | 病理组织学观察发生数(发生率) |
正常组 | - | 29 | 0(0%) | 1(3.4%) | |
模型组 | - | 28 | 12(42.9%) | 37、56、 60、73、80、94、94、107、115、123、135、135(92±32) | 24(85.7%)** |
赖诺普利+氢*** | 1+1.25 | 27 | 6(22.2%) | 74、74、88、126、126(97.6±26.5) | 10(37.0%)▲▲ |
赖诺普利+氢***+叶酸 | 1+1.25+0.04 | 29 | 4(13.8%)▲ | 98、130、138(122±21) | 6(20.7%)▲▲ |
组别 | 剂量(mg/kg) | 动物数 | 中膜厚度(μm) | 管腔内径(μm) | 中膜厚度/管腔内径(%) |
正常组 | - | 29 | 12.3±3.1 | 103.9±17.0 | 12.4±3.0 |
模型组 | - | 28 | 50.4±8.2** | 90.7±10.7** | 56.6±7.9** |
赖诺普利+氢*** | 1+1.25 | 27 | 36.8±5.6▲▲ | 100.5±12.5▲▲ | 36.8±9.3▲▲ |
赖诺普利+氢***+叶酸 | 1+1.25+0.04 | 29 | 32.6±4.7▲▲ | 112.3±16.5▲▲ | 27.9±6.5▲▲★★ |
组别 | 剂量(mg/kg) | 脑卒中发生数/实际观察数 | 病理组织学观察脑卒中发生数/实际观察数 |
对照组模型组**依那普利/氢***依那普利/氢***+叶酸 | --1+1.251+1.25+0.08 | 0/3014/29**9/305/30▲▲ | 1/3022/27**15/30▲7/29▲▲★ |
组别 | 剂量(mg/kg) | 动物数 | 中膜厚度(μm) | 管腔内径(μm) | 中膜厚度/管腔内径(%) |
对照组模型组依那普利/氢***依那普利/氢***+叶酸 | --1+1.251+1.25+0.08 | 28252627 | 19.3±4.055.4±8.5**42.8±7.1▲▲35.6±6.3▲▲★★ | 104.3±18.576.5±9.7**84.3±13.2▲▲85.1±14.6▲▲ | 18.8±4.173.1±11.1**51.6±7.3▲▲41.5±6.8▲▲★★ |
组别 | 剂量(mg/kg) | 数量(n) | 降压幅度(mmHg) | NO(mmol/L) | ET(pg/ml) |
正常组 | - | 18 | -5.3±4.6 | 84.2±18.5 | 124.6±23.9 |
高血压 | - | 16 | -20.1±8.1** | 44.3±10.2** | 190.5±41.8** |
培哚普利/氢***+叶酸 | 0.4+1.25+0.04 | 16 | 28.3±7.4▲▲ | 70.6±13.6▲▲★ | 138.44±22.6▲▲★ |
培哚普利/氢***+叶酸 | 0.4+1.25+0.08 | 17 | 34.0±10.4▲▲ | 68.6±10.3▲▲★ | 140.6±18.1▲▲★ |
培哚普利/氢*** | 0.4+1.25 | 17 | 26.6±6.5▲▲ | 58.5±8.5▲▲ | 160.2±20.8▲ |
叶酸 | 0.08 | 16 | -12.4±4.9▲ | 54.7±9.2▲ | 168.3±38.9 |
组别 | 剂量(mg/kg) | 数量(n) | 24hα1-微球蛋白(μg/d) | 尿蛋白(mg/d) | Ccr(ml/min) | BUN(mmol/L) |
正常组 | - | 18 | 3.2±2.4 | 2.3±0.8 | 0.35±0.10 | 7.14±1.32 |
高血压 | - | 16 | 25.7±6.1** | 9.3±3.1** | 0.12±0.03** | 10.20±3.05** |
培哚普利/氢***+叶酸 | 0.4+1.25+0.04 | 16 | 15.0±2.6▲▲★ | 5.6±1.1▲▲★ | 0.22±0.04▲▲★ | 8.25±2.12 |
培哚普利/氢***+叶酸 | 0.4+1.25+0.08 | 17 | 14.8±3.2▲▲★ | 5.3±1.4▲▲★★ | 0.24±0.04▲▲★★ | 8.10±1.62 |
培哚普利/氢*** | 0.4+1.25 | 17 | 18.5±4.1▲▲ | 6.9±1.6▲▲ | 0.19±0.03▲▲ | 7.97±1.60 |
叶酸 | 0.08 | 16 | 21.8±3.9 | 7.8±1.8 | 0.30±0.04 | 8.67±1.96 |
组别 | 剂量(mg/kg) | 数量(n) | 左心室重量(mg) | 室重指数(mg/g) | 心肌胶原含量(mg/g) |
正常组 | - | 18 | 670.7±88.9 | 1.63±0.35 | 1.03±0.33 |
高血压 | - | 16 | 936.4±136.7** | 2.55±0.42** | 1.96±0.43** |
培哚普利/氢***+叶酸 | 0.4+1.25+0.04 | 16 | 748.8±106.4▲▲ | 1.92±0.34▲▲ | 1.38±0.24▲▲★ |
培哚普利/氢***+叶酸 | 0.4+1.25+0.08 | 17 | 736.3±126.6▲▲ | 1.85±0.32▲▲ | 1.42±0.18▲▲★ |
培哚普利/氢*** | 0.4 | 17 | 799.1±159.1▲▲ | 2.11±0.39▲▲ | 1.62±0.22▲▲ |
叶酸 | 0.08 | 16 | 885.2±218.6 | 2.30±0.45 | 1.88±0.41 |
组别 | 剂量(mg/kg) | 数量(n) | LVSP(mmHg) | LVEDP(mmHg) | +dp/dtmax(mmHg/s×103) | -dp/dtmax(mmHg/s×103) |
正常组 | - | 16 | 129±13 | -2±8 | 12.4±2.5 | 8.7±1.2 |
高血压 | - | 16 | 188±30** | 29±14** | 7.3±2.1** | 5.0±1.5** |
培哚普利/氢***+叶酸 | 0.4+1.25+0.04 | 14 | 142±17▲▲ | -0±6▲▲★★ | 11.5±2.4▲▲★ | 7.3±1.4▲▲ |
培哚普利/氢***+叶酸 | 0.4+1.25+0.08 | 15 | 137±19▲▲ | 2±5▲▲★★ | 11.5±2.1▲▲★ | 7.7±1.3▲▲★ |
培哚普利/氢*** | 0.4+1.25 | 15 | 152±23▲▲ | 10±3▲▲ | 9.5±1.9▲▲ | 6.6±1.1▲▲ |
叶酸 | 0.08 | 16 | 177±26 | 20±9 | 8.8±2.2 | 5.6±1.6 |
组别 | 剂量(mg/kg) | 数量(n) | 降压幅度(mmHg) | NO(mmol/L) | ET(pg/ml) |
正常组 | - | 17 | -3.9±4.1 | 50.6±10.2 | 174.6±40.3 |
高血压 | - | 15 | -16.9±4.8** | 20.6±4.3** | 302.4±51.6** |
咪达普利/吲达帕胺+叶酸 | 1+0.25+0.04 | 18 | 30.0±6.2▲▲ | 34.4±6.5▲▲★★ | 185.9±34.7▲▲★★ |
咪达普利/吲达帕胺+叶酸 | 1+0.25+0.08 | 16 | 32.5±8.2▲▲★ | 32.8±4.6▲▲★ | 193.2±40.9▲▲★ |
咪达普利/吲达帕胺 | 1+0.25 | 17 | 25.6±5.8▲▲ | 27.8±5.1▲▲ | 232.1±30.6▲▲ |
叶酸 | 0.08 | 16 | -10.8±4.6▲ | 25.0±4.9▲ | 268.7±54.8 |
组别 | 剂量(mg/kg) | 动物数 | 尿蛋白(mg) | 24hα1-微球蛋白(μg) | Ccr(ml/min) | BUN(mmol/L) |
正常组 | - | 17 | 1.4±2.1 | 10.1±3.1 | 0.654±0.102 | 5.20±0.84 |
高血压 | - | 15 | 10.5±3.9** | 48.8±13.2** | 0.314±0.058** | 7.53±1.58** |
咪达普利/吲达帕胺+叶酸 | 1+0.25+0.04 | 18 | 5.4±1.8▲▲★ | 29.9±6.2▲▲★ | 0.426±0.052▲▲ | 6.67±0.89 |
咪达普利/吲达帕胺+叶酸 | 1+0.25+0.08 | 16 | 5.3±1.5▲▲★ | 28.3±5.3▲▲★★ | 0.462±0.032▲▲★★ | 6.07±0.64▲▲ |
咪达普利/吲达帕胺 | 1+0.25 | 17 | 7.3±2.4▲ | 36.6±8.7▲▲ | 0.386±0.049▲▲ | 6.72±0.76▲ |
叶酸 | 0.08 | 16 | 9.2±3.4 | 40.2±9.1 | 0.366±0.051 | 7.35±1.02 |
组别 | 剂量(mg/kg) | 动物数 | 左心室重量(mg) | 室重指数(mg/g) | 心肌胶原含量(mg/g) |
正常组 | - | 17 | 820.3±156.2 | 2.12±0.32 | 3.18±0.47 |
高血压 | - | 15 | 1102.4±215.1** | 3.73±0.44** | 6.39±1.26** |
咪达普利/吲达帕胺+叶酸 | 1+0.25+0.04 | 18 | 842.6±156.2▲▲ | 3.03±0.32▲▲ | 4.75±0.38▲▲★ |
咪达普利/吲达帕胺+叶酸 | 1+0.25+0.08 | 16 | 828.5±127.9▲▲ | 2.86±0.38▲▲ | 4.59±0.45▲▲★ |
咪达普利/吲达帕胺 | 1+0.25 | 17 | 867.8±145.6▲▲ | 3.12±0.43▲▲ | 5.26±0.73▲▲ |
叶酸 | 0.08 | 16 | 965.8±167.4 | 3.33±0.46 | 6.07±1.18 |
组别 | 剂量(mg/kg) | 动物数 | CVF(%) | PVCA(%) |
WKY组 | - | 17 | 1.11±0.24 | 0.84±0.17 |
高血压组 | - | 15 | 3.48±0.60** | 2.68±0.47** |
咪达普利+引达帕胺+叶酸 | 1+0.25+0.04 | 18 | 2.44±0.36▲▲★★ | 1.89±0.30▲▲ |
咪达普利+吲达帕胺+叶酸 | 1+0.25+0.08 | 16 | 2.53±0.42▲▲★ | 1.83±0.24▲▲★ |
咪达普利+吲达帕胺 | 1+0.25 | 17 | 2.94±0.38▲▲ | 2.17±0.36▲▲ |
叶酸 | 0.08 | 16 | 3.24±0.36 | 2.50±0.48 |
组别 | 剂量(mg/kg) | 动物数 | 中膜厚度(μm) | 血管内径(μm) | 中膜厚度/内径(%) |
正常组 | - | 17 | 35.2±7.6 | 278.6±46.8 | 13.0±3.2 |
高血压 | - | 15 | 54.5±10.5** | 188.3±28.6** | 30.6±6.1** |
咪达普利/吲达帕胺+叶酸 | 1+0.25+0.04 | 18 | 40.2±6.5▲▲ | 243.8±32.4▲▲ | 16.2±3.3▲▲★★ |
咪达普利/吲达帕胺+叶酸 | 1+0.25+0.08 | 16 | 37.7±6.1▲▲★ | 257.4±26.9▲▲ | 14.8±2.9▲▲★★ |
咪达普利/吲达帕胺 | 1+0.25 | 17 | 44.6±8.3▲▲ | 220.6±33.9▲▲ | 20.6±3.9▲▲ |
叶酸 | 0.08 | 16 | 50.6±10.3 | 205.4±27.2 | 25.4±5.2 |
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CN103338758A (zh) * | 2010-12-03 | 2013-10-02 | 拉乌夫·雷基克 | 叶酸-雷米普利组合:具细胞保护性、神经保护性及视网膜保护性的眼科组合物 |
CN103386130A (zh) * | 2013-06-27 | 2013-11-13 | 深圳奥萨医药有限公司 | Ace抑制剂/噻嗪类利尿剂/5-甲基四氢叶酸药物组合物及用途 |
WO2022104621A1 (zh) * | 2020-11-19 | 2022-05-27 | 北京睿创康泰医药研究院有限公司 | 固定剂量的sglt-2抑制剂与血管紧张素转化酶抑制剂的组合物及用途 |
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CN1679943A (zh) * | 2002-07-31 | 2005-10-12 | 安徽省生物医学研究所 | 一种改善acei类降压药药效的复方药 |
CN1245160C (zh) * | 2003-09-15 | 2006-03-15 | 启东盖天力药业有限公司 | 含吲哒帕胺和血管紧张素转换酶抑制剂的复方降压制剂 |
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Publication number | Priority date | Publication date | Assignee | Title |
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CN103338758A (zh) * | 2010-12-03 | 2013-10-02 | 拉乌夫·雷基克 | 叶酸-雷米普利组合:具细胞保护性、神经保护性及视网膜保护性的眼科组合物 |
CN103386130A (zh) * | 2013-06-27 | 2013-11-13 | 深圳奥萨医药有限公司 | Ace抑制剂/噻嗪类利尿剂/5-甲基四氢叶酸药物组合物及用途 |
WO2022104621A1 (zh) * | 2020-11-19 | 2022-05-27 | 北京睿创康泰医药研究院有限公司 | 固定剂量的sglt-2抑制剂与血管紧张素转化酶抑制剂的组合物及用途 |
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