JP2005514441A5 - - Google Patents
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- Publication number
- JP2005514441A5 JP2005514441A5 JP2003559507A JP2003559507A JP2005514441A5 JP 2005514441 A5 JP2005514441 A5 JP 2005514441A5 JP 2003559507 A JP2003559507 A JP 2003559507A JP 2003559507 A JP2003559507 A JP 2003559507A JP 2005514441 A5 JP2005514441 A5 JP 2005514441A5
- Authority
- JP
- Japan
- Prior art keywords
- phenylphenylmethyl
- oxopropyl
- carboxy
- amino
- pharmaceutically acceptable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 239000011780 sodium chloride Substances 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 5
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 239000004072 C09CA03 - Valsartan Substances 0.000 claims description 3
- SJSNUMAYCRRIOM-QFIPXVFZSA-N Valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 claims description 3
- 125000004494 ethyl ester group Chemical group 0.000 claims description 3
- 229960004699 valsartan Drugs 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims 6
- 230000002401 inhibitory effect Effects 0.000 claims 6
- 239000008194 pharmaceutical composition Substances 0.000 claims 5
- -1 3- carboxy-1-oxopropyl Chemical group 0.000 claims 4
- UEBQNXUHSKFIIR-FQEVSTJZSA-N C(C)OC([C@](CCN)(C)CC1=CC=C(C=C1)C1=CC=CC=C1)=O Chemical compound C(C)OC([C@](CCN)(C)CC1=CC=C(C=C1)C1=CC=CC=C1)=O UEBQNXUHSKFIIR-FQEVSTJZSA-N 0.000 claims 1
- ZBSFEPOXERUZFE-SFHVURJKSA-N C1(=CC=CC=C1)C1=CC=C(C=C1)C[C@@](C(=O)O)(CCN)C Chemical compound C1(=CC=CC=C1)C1=CC=C(C=C1)C[C@@](C(=O)O)(CCN)C ZBSFEPOXERUZFE-SFHVURJKSA-N 0.000 claims 1
- 206010007554 Cardiac failure Diseases 0.000 claims 1
- 206010019280 Heart failure Diseases 0.000 claims 1
- 239000000400 angiotensin II type 1 receptor blocker Substances 0.000 claims 1
- 230000003042 antagnostic Effects 0.000 claims 1
- 239000005557 antagonist Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 241000700159 Rattus Species 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 230000001631 hypertensive Effects 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- XAIFNLJOYACUNR-IBGZPJMESA-N CC(C)[C@@H](C(O)=O)N(Cc(cc1)ccc1-c(cccc1)c1-c1nnn[nH]1)C(C)=O Chemical compound CC(C)[C@@H](C(O)=O)N(Cc(cc1)ccc1-c(cccc1)c1-c1nnn[nH]1)C(C)=O XAIFNLJOYACUNR-IBGZPJMESA-N 0.000 description 1
- VPGRYOFKCNULNK-ACXQXYJUSA-N Deoxycorticosterone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)COC(=O)C)[C@@]1(C)CC2 VPGRYOFKCNULNK-ACXQXYJUSA-N 0.000 description 1
- 229960004486 Desoxycorticosterone acetate Drugs 0.000 description 1
- 210000003734 Kidney Anatomy 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003276 anti-hypertensive Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000000271 cardiovascular Effects 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 229940079593 drugs Drugs 0.000 description 1
- 230000003902 lesions Effects 0.000 description 1
- 210000000056 organs Anatomy 0.000 description 1
- 230000002085 persistent Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 201000011528 vascular disease Diseases 0.000 description 1
Description
長期かつ未制御の高血圧性血管疾病は、心臓および腎臓のような標的器官において様々な病変を最終的に引き起こす。持続性高血圧は、脳卒中の頻度増加も引き起こし得る。それゆえ、組み合わせ処置の利点をさらに認識するために、血圧降下の評価項目以外に、降圧治療の有効性を評価する、さらなる心血管の評価項目の検査が非常に必要である。
代表的な試験は、例えば、以下の方法を適用して、バルサルタンとＮ−（３−カルボキシ−１−オキソプロピル）−（４Ｓ）−ｐ−フェニルフェニルメチル）−４−アミノ−２Ｒ−メチルブタン酸 エチル エステルの組合せで行われ得る：
薬物の有効性は、正常塩量の食事または塩を添加した食事（ラットの固形飼料中４〜８％の塩、または飲料水として１％ＮａＣｌ）のいずれかで維持された、酢酸デオキシコルチコステロン−塩ラット（ＤＤＣＡ塩）および自然発生高血圧発症ラット（ＳＨＲ）を含む様々な動物モデルで調べられる。
薬物の有効性は、正常塩量の食事または塩を添加した食事（ラットの固形飼料中４〜８％の塩、または飲料水として１％ＮａＣｌ）のいずれかで維持された、酢酸デオキシコルチコステロン−塩ラット（ＤＤＣＡ塩）および自然発生高血圧発症ラット（ＳＨＲ）を含む様々な動物モデルで調べられる。
該組成物において、成分（ｉ）および（ｉｉ）が得られて、一緒に、交互、または１つの組み合わされた単位用量剤形または２つの別々の単位用量剤形で別々に投与され得る。単位用量剤形は、固定した組合せでもあり得る。
Claims (6)
- （ｉ）ＡＴ１−拮抗剤バルサルタンまたはその薬学的に許容される塩、および
（ｉｉ）ＮＥＰ阻害剤であるＮ−（３−カルボキシ−１−オキソプロピル）−（４Ｓ）−（ｐ−フェニルフェニルメチル）−４−アミノ−２Ｒ−メチルブタン酸またはそのエチルエステルもしくはそれらの薬学的に許容される塩、および薬学的に許容される担体を含む、医薬組成物。 - ＮＥＰ阻害剤が、Ｎ−（３−カルボキシ−１−オキソプロピル）−（４Ｓ）−（ｐ−フェニルフェニルメチル）−４−アミノ−２Ｒ−メチルブタン酸エチルエステルである、請求項１に記載の医薬組成物。
- ＮＥＰ阻害剤が、Ｎ−（３−カルボキシ−１−オキソプロピル）−（４Ｓ）−（ｐ−フェニルフェニルメチル）−４−アミノ−２Ｒ−メチルブタン酸である、請求項１に記載の医薬組成物。
- 高血圧または心不全の処置または予防のために使用する、（ｉ）ＡＴ１−拮抗剤バルサルタンまたはその薬学的に許容される塩、および（ｉｉ）ＮＥＰ阻害剤であるＮ−（３−カルボキシ−１−オキソプロピル）−（４Ｓ）−（ｐ−フェニルフェニルメチル）−４−アミノ−２Ｒ−メチルブタン酸またはそのエチルエステルもしくはそれらの薬学的に許容される塩、および薬学的に許容される担体を含む医薬組成物。
- ＮＥＰ阻害剤が、Ｎ−（３−カルボキシ−１−オキソプロピル）−（４Ｓ）−（ｐ−フェニルフェニルメチル）−４−アミノ−２Ｒ−メチルブタン酸エチルエステルである、請求項４に記載の医薬組成物。
- ＮＥＰ阻害剤が、Ｎ−（３−カルボキシ−１−オキソプロピル）−（４Ｓ）−（ｐ−フェニルフェニルメチル）−４−アミノ−２Ｒ−メチルブタン酸である、請求項４に記載の医薬組成物。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34966002P | 2002-01-17 | 2002-01-17 | |
| US60/349,660 | 2002-01-17 | ||
| PCT/EP2003/000415 WO2003059345A1 (en) | 2002-01-17 | 2003-01-16 | Pharmaceutical compositions comprising valsartan and nep inhibitors |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011116928A Division JP2011207898A (ja) | 2002-01-17 | 2011-05-25 | バルサルタンおよびｎｅｐ阻害剤を含む医薬組成物 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2005514441A JP2005514441A (ja) | 2005-05-19 |
| JP2005514441A5 true JP2005514441A5 (ja) | 2011-08-04 |
| JP4820056B2 JP4820056B2 (ja) | 2011-11-24 |
Family
ID=23373410
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003559507A Expired - Lifetime JP4820056B2 (ja) | 2002-01-17 | 2003-01-16 | バルサルタンおよびｎｅｐ阻害剤を含む医薬組成物 |
| JP2011116928A Withdrawn JP2011207898A (ja) | 2002-01-17 | 2011-05-25 | バルサルタンおよびｎｅｐ阻害剤を含む医薬組成物 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011116928A Withdrawn JP2011207898A (ja) | 2002-01-17 | 2011-05-25 | バルサルタンおよびｎｅｐ阻害剤を含む医薬組成物 |
Country Status (29)
| Country | Link |
|---|---|
| EP (1) | EP1467728B1 (ja) |
| JP (2) | JP4820056B2 (ja) |
| KR (2) | KR100984939B1 (ja) |
| CN (2) | CN1615134A (ja) |
| AT (1) | ATE370732T1 (ja) |
| AU (1) | AU2003206738C1 (ja) |
| BE (1) | BE2016C025I2 (ja) |
| BR (2) | BR122018015003B8 (ja) |
| CA (1) | CA2472399C (ja) |
| CO (1) | CO5600999A2 (ja) |
| CY (2) | CY1106959T1 (ja) |
| DE (1) | DE60315795T2 (ja) |
| DK (1) | DK1467728T3 (ja) |
| EC (1) | ECSP045190A (ja) |
| ES (1) | ES2290429T3 (ja) |
| FR (1) | FR16C0019I2 (ja) |
| HU (1) | HUS1600024I1 (ja) |
| IL (2) | IL162661A0 (ja) |
| LU (1) | LU93074I2 (ja) |
| MX (1) | MXPA04006917A (ja) |
| NL (1) | NL300811I2 (ja) |
| NO (2) | NO333191B1 (ja) |
| NZ (1) | NZ533968A (ja) |
| PL (1) | PL212318B1 (ja) |
| PT (1) | PT1467728E (ja) |
| RU (1) | RU2334513C3 (ja) |
| SI (1) | SI1467728T1 (ja) |
| WO (1) | WO2003059345A1 (ja) |
| ZA (1) | ZA200405117B (ja) |
Families Citing this family (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008503546A (ja) * | 2004-06-23 | 2008-02-07 | ゾルファイ ファーマスーティカルズ ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｎｅｐ阻害剤、内因性エンドセリン産生系阻害剤およびａｔ１受容体アンタゴニスト阻害剤を含有する医薬組成物 |
| US20080102120A1 (en) * | 2004-12-24 | 2008-05-01 | Miha Vrbinc | Solid Pharmaceutical Composition Comprising Valsartan |
| MY146830A (en) * | 2005-02-11 | 2012-09-28 | Novartis Ag | Combination of organic compounds |
| WO2007045663A2 (en) * | 2005-10-19 | 2007-04-26 | Novartis Ag | Combination of an ati receptor antagonist and a np inhibitor fro treating ia hypertension and heartfailure |
| WO2007051007A2 (en) * | 2005-10-28 | 2007-05-03 | Novartis Ag | Combination of antihypertensives with cholesterol-lowering agent |
| AR057882A1 (es) | 2005-11-09 | 2007-12-26 | Novartis Ag | Compuestos de accion doble de bloqueadores del receptor de angiotensina e inhibidores de endopeptidasa neutra |
| WO2007106708A2 (en) * | 2006-03-10 | 2007-09-20 | Novartis Ag | Combinations of the angiotensin ii antagonist valsartan and the nep inhibitor daglutril |
| CZ300801B6 (cs) * | 2006-06-07 | 2009-08-12 | Helvetia Pharma A.S. | Kompozice s valsartanem v pevných lékových formách |
| BRPI0806700A8 (pt) | 2007-01-12 | 2019-01-22 | Novartis Ag | processo |
| GB0708507D0 (en) | 2007-05-02 | 2007-06-13 | Queen Mary & Westfield College | Substituted phosphonates and their use |
| EP3067043B1 (en) * | 2007-11-06 | 2022-11-30 | Novartis AG | Pharmaceutical compositions based on superstructures of angiotensin receptor antagonist/blocker (arb) and neutral endopeptidase (nep) inhibitor |
| CN101774941A (zh) * | 2009-01-13 | 2010-07-14 | 浙江九洲药业股份有限公司 | 2-酰基氨基-3-联苯基丙酸的制备及拆分方法 |
| AR076706A1 (es) | 2009-05-28 | 2011-06-29 | Novartis Ag | Derivados aminobutiricos sustituidos como inhibidores de neprilisina |
| MX2011012628A (es) | 2009-05-28 | 2011-12-14 | Novartis Ag | Derivados amino-propionicos sustituidos como inhibidores de neprilisina. |
| JO2967B1 (en) | 2009-11-20 | 2016-03-15 | نوفارتس ايه جي | Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors |
| AU2011295170B2 (en) | 2010-08-23 | 2014-12-18 | Novartis Ag | Process for the preparation of intermediates for the manufacture of NEP inhibitors |
| US8673974B2 (en) | 2010-11-16 | 2014-03-18 | Novartis Ag | Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors |
| AU2013304949C1 (en) * | 2012-08-24 | 2020-12-24 | Novartis Ag | NEP inhibitors for treating diseases characterized by atrial enlargement or remodeling |
| KR20150119107A (ko) | 2013-02-14 | 2015-10-23 | 노파르티스 아게 | 개선된 생체내 효능을 갖는 nep 억제제로서의 치환된 비스페닐 부탄산 유도체 |
| KR20150119109A (ko) | 2013-02-14 | 2015-10-23 | 노파르티스 아게 | Nep (중성 엔도펩티다제) 억제제로서의 치환된 비스페닐 부타노익 포스폰산 유도체 |
| CN104230865B (zh) * | 2013-06-13 | 2018-01-09 | 上海翰森生物医药科技有限公司 | 联芳基取代的4‑氨基丁酸衍生物及其制备方法和用途 |
| JP2016530282A (ja) | 2013-08-26 | 2016-09-29 | ノバルティス アーゲー | 新規使用 |
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| KR20210120560A (ko) | 2020-03-27 | 2021-10-07 | 주식회사 유영제약 | 고함량의 주성분을 포함하는 정제 및 그 제조방법 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU1256692A (en) * | 1991-02-06 | 1992-09-07 | Schering Corporation | Combination of an angiotensin II antagonist or renin inhibitor with a neutral endopeptidase inhibitor |
| US5217996A (en) * | 1992-01-22 | 1993-06-08 | Ciba-Geigy Corporation | Biaryl substituted 4-amino-butyric acid amides |
| CA2168066A1 (en) * | 1995-02-08 | 1996-08-09 | James R. Powell | Treatment of hypertension and congestive heart failure |
| CA2405496A1 (en) * | 2000-04-03 | 2001-10-11 | Richard A. Reeves | Vasopeptidase inhibitors to treat isolated systolic hypertension |
| HUP0301390A3 (en) * | 2000-06-22 | 2005-04-28 | Novartis Ag | Oral pharmaceutical composition containing valsartan |
| DK1313714T3 (da) * | 2000-07-19 | 2008-12-15 | Novartis Ag | Valsartansalte |
| US6777443B2 (en) * | 2001-05-15 | 2004-08-17 | Novartis Ag | Dipeptide derivatives |
-
2003
- 2003-01-16 IL IL16266103A patent/IL162661A0/xx unknown
- 2003-01-16 CN CNA038022680A patent/CN1615134A/zh active Pending
- 2003-01-16 WO PCT/EP2003/000415 patent/WO2003059345A1/en active Application Filing
- 2003-01-16 AU AU2003206738A patent/AU2003206738C1/en active Active
- 2003-01-16 DK DK03704413T patent/DK1467728T3/da active
- 2003-01-16 NZ NZ533968A patent/NZ533968A/en not_active IP Right Cessation
- 2003-01-16 KR KR1020047011124A patent/KR100984939B1/ko active IP Right Review Request
- 2003-01-16 MX MXPA04006917A patent/MXPA04006917A/es active IP Right Grant
- 2003-01-16 EP EP03704413A patent/EP1467728B1/en not_active Expired - Lifetime
- 2003-01-16 SI SI200331029T patent/SI1467728T1/sl unknown
- 2003-01-16 CA CA2472399A patent/CA2472399C/en not_active Expired - Lifetime
- 2003-01-16 CN CN201110029600.7A patent/CN102091330B/zh not_active Expired - Lifetime
- 2003-01-16 KR KR1020107010521A patent/KR20100057704A/ko not_active Application Discontinuation
- 2003-01-16 PL PL369773A patent/PL212318B1/pl unknown
- 2003-01-16 DE DE60315795T patent/DE60315795T2/de not_active Expired - Lifetime
- 2003-01-16 AT AT03704413T patent/ATE370732T1/de active
- 2003-01-16 JP JP2003559507A patent/JP4820056B2/ja not_active Expired - Lifetime
- 2003-01-16 BR BR122018015003A patent/BR122018015003B8/pt not_active IP Right Cessation
- 2003-01-16 ES ES03704413T patent/ES2290429T3/es not_active Expired - Lifetime
- 2003-01-16 PT PT03704413T patent/PT1467728E/pt unknown
- 2003-01-16 BR BRPI0306907A patent/BRPI0306907B8/pt active IP Right Grant
- 2003-01-16 RU RU2004125178A patent/RU2334513C3/ru active
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2004
- 2004-06-21 IL IL162661A patent/IL162661A/en active Protection Beyond IP Right Term
- 2004-06-28 ZA ZA2004/05117A patent/ZA200405117B/en unknown
- 2004-07-14 EC EC2004005190A patent/ECSP045190A/es unknown
- 2004-08-06 CO CO04076723A patent/CO5600999A2/es active IP Right Grant
- 2004-08-13 NO NO20043380A patent/NO333191B1/no not_active IP Right Cessation
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2007
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2011
- 2011-05-25 JP JP2011116928A patent/JP2011207898A/ja not_active Withdrawn
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2016
- 2016-05-17 FR FR16C0019C patent/FR16C0019I2/fr active Active
- 2016-05-18 BE BE2016C025C patent/BE2016C025I2/nl unknown
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