CN1146418C - 血管紧张肽转化酶抑制剂和钙通道拮抗剂的定量结合物及其制备方法和在心血管疾病的治疗中的用途 - Google Patents
血管紧张肽转化酶抑制剂和钙通道拮抗剂的定量结合物及其制备方法和在心血管疾病的治疗中的用途 Download PDFInfo
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- CN1146418C CN1146418C CNB981098371A CN98109837A CN1146418C CN 1146418 C CN1146418 C CN 1146418C CN B981098371 A CNB981098371 A CN B981098371A CN 98109837 A CN98109837 A CN 98109837A CN 1146418 C CN1146418 C CN 1146418C
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- nitrendipine
- enalapril
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- A—HUMAN NECESSITIES
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- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/55—Protease inhibitors
- A61K38/556—Angiotensin converting enzyme inhibitors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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Abstract
Description
依那普利的含量% | 降解产物 | ||
二鲸蜡哌嗪 | 依那普利酸 | ||
开始时,室温 | 103.1 | 0.04 | 0.04 |
3个月,室温 | 103.7 | 0.00 | 0.08 |
3个月,40℃ | 102.3 | 0.04 | 0.12 |
3个月,40℃,+75%RH | 102.6 | 0.04 | 0.12 |
3个月,50℃ | 102.3 | 0.19 | 0.41 |
尼群地平含量% | 降解产物吡啶衍生物 | |
开始时,室温 | 100.8 | 0.00 |
3个月,室温 | 99.0 | 0.05 |
3个月,40℃ | 102.2 | 0.02 |
3个月,40 ℃,+75%RH | 99.7 | 0.04 |
3个月,50 ℃ | 100.1 | 0.05 |
依那普利的含量% | 降解产物 | ||
二鲸蜡哌嗪 | 依那普利酸 | ||
开始时,室温 | 102.1 | 0.00 | 0.04 |
3个月,室温 | 101.7 | 0.00 | 0.08 |
3个月,40℃ | 100.9 | 0.06 | 0.15 |
3个月,40℃,+75%RH | 101.2 | 0.08 | 0.17 |
3个月,50℃ | 100.4 | 0.26 | 0.41 |
尼群地平含量% | 降解产物吡啶衍生物 | |
开始时,室温 | 99.1 | 0.00 |
3个月,室温 | 98.1 | 0.01 |
3个月,40℃ | 99.0 | 0.01 |
3个月,40℃,+75%RH | 98.8 | //0.02 |
3个月,50℃ | 97.2 | 0.06 |
实施例1 | 实施例2 | |||
时间(分) | 溶解的依那普利% | C.V.% | 溶解的依那普利% | C.V.% |
0.0 | 0.00 | 0.00 | 0.00 | 0.00 |
5.0 | 24.96 | 8.79 | 26.26 | 4.31 |
10.0 | 48.18 | 6.48 | 51.71 | 4.57 |
15.0 | 70.46 | 6.27 | 76.71 | 5.56 |
30.0 | 104.55 | 0.42 | 101.00 | 1.27 |
60.0 | 103.76 | 0.52 | 101.58 | 0.72 |
实施例1 | 实施例2 | |||
时间(分) | 溶解的尼群地平% | C.V.% | 溶解的尼群地平% | C.V.% |
0.0 | 0.00 | 0.00 | 0.00 | 0.00 |
5.0 | 23.10 | 9.82 | 25.95 | 5.57 |
10.0 | 45.35 | 7.47 | 49.55 | 4.41 |
15.0 | 66.98 | 6.53 | 71.70 | 4.04 |
30.0 | 97.90 | 0.36 | 93.51 | 1.07 |
60.0 | 98.76 | 0.47 | 95.18 | 0.01 |
压力 | n | 给药后时间 | ||||||||||
0 | 5 | 15 | 30 | 45 | 60 | 120 | 240 | 360 | 540 | |||
马来酸依那普利1mg/kg口服 | 收缩 | 9 | 168(6) | 165(5) | 144(2) | 139(3) | 139(6) | 134(1) | 141(3) | 146(1) | 148(4) | 165(6) |
尼群地平3mg/kg口服 | 收缩 | 7 | 172(6) | 119(2) | 117(6) | 112(4) | 115(3) | 119(6) | 141(5) | 163(2) | 169(1) | 160(5) |
马来酸依那普利(1mg/kg,口服)和尼群地平(3mg/kg口服)的结合物 | 收缩 | 9 | 165(6) | 134(2) | 112(5) | 107(6) | 109(3) | 112(5) | 124(4) | 137(1) | 144(5) | 163(3) |
马来酸依那普利(0.5mg/kg,口服)和尼群地平(1.5mg/kg,口服)的结合物 | 收缩 | 8 | 170(6) | 124(4) | 109(3) | 112(2) | 114(3) | 116(6) | 128(6) | 138(5) | 141(4) | 148(4) |
依那普利1mg.kg口服 | 舒张 | 9 | 138(5) | 138(3) | 123(1) | 116(4) | 117(1) | 109(1) | 116(5) | 116(3) | 117(2) | 126(4) |
尼群地平3mg/kg口服 | 舒张 | 7 | 136(5) | 105(1) | 83(4) | 84(2) | 88(5) | 92(1) | 113(4) | 128(3) | 132(2) | 131(5) |
马来酸依那普利(1mg/kg,口服)和尼群地平(3mg/kg,口服)的结合物 | 舒张 | 9 | 141(5) | 121(1) | 94(3) | 87(2) | 92(1) | 94(4) | 104(2) | 117(1) | 116(3) | 123(5) |
马来酸依那普利(0.5mg/kg,口服)和尼群地平(1.5mg/kg,口服)的结合物 | 舒张 | 8 | 137(5) | 104(2) | 88(1) | 92(5) | 92(4) | 95(1) | 107(3) | 114(4) | 118(5) | 119(2) |
治疗mg/kg/天 | 基值 | 1周 | 4周 | 13周 | 26周 | |
0h 4h 8h | 0h 4h 8h | 0h 4h 8h | 0h 4h 8h | |||
对照 | SisDimsMean | 124(16,2)80(12,7)95(13,7) | 120 123 130(23,7) (18,5) (10,3)78 82 83(14,7) (13,2) (8,4)92 95 99(17,4) (14,6) (8,5) | 119 118 123(20,8) (17,5) (14,5)76 75 75(128,) (11,2) (10,5)90 90 91(15,3) (12,6) (11,4) | 123 120 119(19,4 ) (18,4) (16,8)78 78 76(12,9) (16,7) (13,3)93 92 91(14,7) (16,8) (13,9) | 127 125 133(20,3) (14,5) (18,4)84 79 84(14,5) (9,5) (11,3)98 95 100(16,2) (10,8) (13,6) |
马来酸依那普利和尼群地平(1∶!)1和1 | 120(15,6)81(8,2)94(10,1) | 113 104 119(16,5) (9,9) (13,5)74 66 75(9,4) (9,8) (6,0)87 79 90(11,5) (9,1) (8,2) | 112 103 112(12,5) (13,6) (11,0)76 63 66(6,8) (6,0) (10,3)88 76 82(8,1) (8,2) (10,3) | 112 103 109(15,3) (16,0) (20,9)73 65 72(8,0) (7,6) (15,3)86 78 84(9,9) (10,0) (16,7) | 113 107 113(16,9) (18,9) (17,1)73 68 71(7,0) (7,5) (9,9)87 81 85(10,0) (11,1) (11,3) | |
马来酸依那普利和尼群地平(1∶!)3和3 | 126(13,7)83(8,5)97(9,5) | 132 96 121(18,9) (14,0) (14,1)83 55 73(9,6) (6,5) (8,0)99 68 89(11,9) (8,0) (9,2) | 118 98 113(12,5) (14,1) (20,4)72 58 70(7,0) (10,0) (9,6)87 72 84(8,7) (11,0) (12,7) | 116 93 108(13,0) (11,0) (13,1)73 61 68(7,6) (7,8) (11,3)87 72 81(9,3) (8,6) (11,1) | 123 99 111(19,8) (14,3) (17,1)80 58 69(10,7) (11,3) (11,5)94 72 83(13,4) (11,9) (13,0) | |
马来酸依那普利和尼群地平(1∶!)6和6 | 125(15,2)81(10,8)96(11,2) | 127 93 113(13,5) (12,1) (8,3)83 55 67(10,3) (6,2) (6,2)98 69 86(10,8) (6,0) (107) | 113 92 103(12,1) (6,9) (13,9)75 51 60(10,1) (8,3) (11,1)87 65 74(10,3) (6,5) (11,9) | 116 85 100(12,5) (11,1) (12,3)74 53 57(8,6) (6,6) (8,6)88 64 71(9,6) (7,1) (9,2) | 117 92 100(15,6) (11,8) (11,6)78 55 61(11,5) (6,6) (9,3)91 68 74(12,5) (7,1) (9,7) |
Claims (13)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ES9701017 | 1997-05-13 | ||
ES009701017A ES2125198B1 (es) | 1997-05-13 | 1997-05-13 | Asociacion a dosis fija de un inhibidor de la enzima convertidora de angiotensina y de un antagonista de los canales de calcio, procedimiento para su preparacion y su utilizacion para el tratamiento de enfermees cardiovasculares. |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1212869A CN1212869A (zh) | 1999-04-07 |
CN1146418C true CN1146418C (zh) | 2004-04-21 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CNB981098371A Expired - Lifetime CN1146418C (zh) | 1997-05-13 | 1998-05-12 | 血管紧张肽转化酶抑制剂和钙通道拮抗剂的定量结合物及其制备方法和在心血管疾病的治疗中的用途 |
Country Status (23)
Country | Link |
---|---|
EP (1) | EP0884054B9 (zh) |
JP (1) | JP3576806B2 (zh) |
CN (1) | CN1146418C (zh) |
AR (1) | AR011730A1 (zh) |
AT (1) | ATE236653T1 (zh) |
AU (1) | AU735404B2 (zh) |
BR (1) | BR9805597A (zh) |
CA (1) | CA2234899C (zh) |
CZ (1) | CZ292616B6 (zh) |
DE (1) | DE69813083T2 (zh) |
DK (1) | DK0884054T3 (zh) |
ES (2) | ES2125198B1 (zh) |
HU (1) | HUP9801075A3 (zh) |
IL (1) | IL124253A (zh) |
NO (1) | NO315545B1 (zh) |
NZ (1) | NZ330447A (zh) |
PL (1) | PL192117B1 (zh) |
PT (1) | PT884054E (zh) |
RU (1) | RU2182002C2 (zh) |
SK (1) | SK284337B6 (zh) |
TR (1) | TR199800847A2 (zh) |
TW (1) | TW562679B (zh) |
ZA (1) | ZA983806B (zh) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HU226950B1 (en) * | 1999-11-03 | 2010-03-29 | Richter Gedeon Nyrt | The magnesium salt of enalapril and antihypertensive pharmaceutical composition containing it |
ES2287110T3 (es) * | 2000-04-11 | 2007-12-16 | Sankyo Company, Limited | Composicion farmaceutica estabilizada que contiene un bloqueador de calcio consistente en azelnidipina. |
ATE374641T1 (de) * | 2001-01-26 | 2007-10-15 | Schering Corp | Kombinationen vom ppar-aktivator fenofibrat mit dem hemmer der sterol-absorption ezetimibe zur behandlung von kardiovaskulären indikationen |
EA008196B1 (ru) * | 2002-12-16 | 2007-04-27 | Киссеи Фармасьютикал Ко., Лтд. | Твердая лекарственная форма для перорального применения |
RU2618471C2 (ru) * | 2012-12-03 | 2017-05-03 | Закрытое Акционерное Общество "Вертекс" | Пероральная фармацевтическая композиция диуретика и ингибитора АПФ в микронизированной форме, лекарственное средство и его применение |
CN109350733A (zh) * | 2018-06-08 | 2019-02-19 | 山东理工职业学院 | 一种马来酸依那普利片剂的制备方法 |
CN109985013B (zh) * | 2019-05-10 | 2021-08-10 | 河北君圣药业有限公司 | 一种尼群地平分散片及其制备方法 |
CN115501224A (zh) * | 2022-10-09 | 2022-12-23 | 南昌大学第一附属医院 | 马来酸依那普利叶酸片联合通心络在制备治疗高血压合并颈动脉硬化药物的应用 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
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DE3437917A1 (de) * | 1984-10-17 | 1986-04-17 | Bayer Ag, 5090 Leverkusen | Kombination von dihydropyridinen mit ace-hemmern sowie ihre verwendung in arzneimitteln |
USH734H (en) * | 1988-03-07 | 1990-02-06 | E. R. Squibb & Sons, Inc. | Method for inhibiting onset of or treating migraine headaches employing an ACE inhibitor |
JPH01275529A (ja) * | 1988-03-21 | 1989-11-06 | E R Squibb & Sons Inc | 晩発性運動障害の抑制治療剤 |
CA2007525A1 (en) * | 1989-01-30 | 1990-07-30 | Zola P. Horovitz | Method for facilating dieting employing an ace inhibitor |
US5160744A (en) * | 1991-06-27 | 1992-11-03 | Alza Corporation | Verapmil therapy |
US5246944A (en) * | 1991-08-13 | 1993-09-21 | Merck & Co., Inc. | Quinoline angiotensin ii antagonists incorporating a substituted benzyl element |
YU48602B (sh) * | 1991-11-25 | 1998-12-23 | Krka Tovarna Zdravil P.O. | Postupak za dobijanje stabilne formulacije soli enalaprila |
SI9300504A (en) * | 1993-09-28 | 1995-04-30 | Krka | Process for preparation solid dispersions and deposits of calcium antagonist dihidropyrimidine derivates and pharmaceutical compositions comprising the same |
US5573780A (en) * | 1995-08-04 | 1996-11-12 | Apotex Usa Inc. | Stable solid formulation of enalapril salt and process for preparation thereof |
-
1997
- 1997-05-13 ES ES009701017A patent/ES2125198B1/es not_active Expired - Fee Related
-
1998
- 1998-04-28 IL IL12425398A patent/IL124253A/xx not_active IP Right Cessation
- 1998-05-05 CZ CZ19981381A patent/CZ292616B6/cs not_active IP Right Cessation
- 1998-05-06 ZA ZA983806A patent/ZA983806B/xx unknown
- 1998-05-08 NO NO19982112A patent/NO315545B1/no not_active IP Right Cessation
- 1998-05-11 TW TW087107210A patent/TW562679B/zh not_active IP Right Cessation
- 1998-05-11 AR ARP980102163A patent/AR011730A1/es active IP Right Grant
- 1998-05-11 SK SK616-98A patent/SK284337B6/sk not_active IP Right Cessation
- 1998-05-12 DE DE69813083T patent/DE69813083T2/de not_active Expired - Lifetime
- 1998-05-12 RU RU98109345/14A patent/RU2182002C2/ru active
- 1998-05-12 AT AT98500119T patent/ATE236653T1/de active
- 1998-05-12 CN CNB981098371A patent/CN1146418C/zh not_active Expired - Lifetime
- 1998-05-12 PL PL326246A patent/PL192117B1/pl unknown
- 1998-05-12 CA CA002234899A patent/CA2234899C/en not_active Expired - Lifetime
- 1998-05-12 DK DK98500119T patent/DK0884054T3/da active
- 1998-05-12 HU HU9801075A patent/HUP9801075A3/hu unknown
- 1998-05-12 EP EP98500119A patent/EP0884054B9/en not_active Revoked
- 1998-05-12 PT PT98500119T patent/PT884054E/pt unknown
- 1998-05-12 ES ES98500119T patent/ES2197443T3/es not_active Expired - Lifetime
- 1998-05-13 AU AU65973/98A patent/AU735404B2/en not_active Expired
- 1998-05-13 NZ NZ330447A patent/NZ330447A/xx not_active IP Right Cessation
- 1998-05-13 BR BR9805597-6A patent/BR9805597A/pt active Search and Examination
- 1998-05-13 JP JP13059098A patent/JP3576806B2/ja not_active Expired - Lifetime
- 1998-05-13 TR TR1998/00847A patent/TR199800847A2/xx unknown
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Effective date of registration: 20110324 Address after: Barcelona Patentee after: FERRER INTERNACIONAL, S.A. Address before: Little Switzerland Lange Patentee before: Procter & Gamble Pharmaceutical Co.,Ltd. |
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Granted publication date: 20040421 |