JP2011098965A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2011098965A5 JP2011098965A5 JP2010250815A JP2010250815A JP2011098965A5 JP 2011098965 A5 JP2011098965 A5 JP 2011098965A5 JP 2010250815 A JP2010250815 A JP 2010250815A JP 2010250815 A JP2010250815 A JP 2010250815A JP 2011098965 A5 JP2011098965 A5 JP 2011098965A5
- Authority
- JP
- Japan
- Prior art keywords
- weight percent
- composition
- pharmaceutically acceptable
- spherical particles
- iii
- 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
Links
- 239000000203 mixture Substances 0.000 claims description 36
- 239000012798 spherical particle Substances 0.000 claims description 18
- 238000009498 subcoating Methods 0.000 claims description 10
- 239000011248 coating agent Substances 0.000 claims description 7
- 238000000576 coating method Methods 0.000 claims description 7
- JWNPDZNEKVCWMY-VQHVLOKHSA-N neratinib Chemical compound C=12C=C(NC(=O)\C=C\CN(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 JWNPDZNEKVCWMY-VQHVLOKHSA-N 0.000 claims description 7
- -1 4- (3-Chloro-4- (pyridin-2-ylmethoxy) phenylamino) -3-cyano-7-ethoxyquinolin-6-yl Chemical group 0.000 claims description 6
- 239000002702 enteric coating Substances 0.000 claims description 6
- 238000009505 enteric coating Methods 0.000 claims description 6
- 229920000642 polymer Polymers 0.000 claims description 6
- 229950008882 polysorbate Drugs 0.000 claims description 6
- 229920000136 polysorbate Polymers 0.000 claims description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 6
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 229920003174 cellulose-based polymer Polymers 0.000 claims description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 3
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 3
- 229950008835 neratinib Drugs 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 239000000080 wetting agent Substances 0.000 claims description 3
- RANOMAHFIQOQIG-UHFFFAOYSA-N 2-aminoquinoline-3-carbonitrile Chemical class C1=CC=C2C=C(C#N)C(N)=NC2=C1 RANOMAHFIQOQIG-UHFFFAOYSA-N 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 239000005551 L01XE03 - Erlotinib Substances 0.000 claims description 2
- 239000002147 L01XE04 - Sunitinib Substances 0.000 claims description 2
- 239000002136 L01XE07 - Lapatinib Substances 0.000 claims description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 229960001433 erlotinib Drugs 0.000 claims description 2
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 claims description 2
- LBWFXVZLPYTWQI-IPOVEDGCSA-N n-[2-(diethylamino)ethyl]-5-[(z)-(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C LBWFXVZLPYTWQI-IPOVEDGCSA-N 0.000 claims description 2
- 229940034785 sutent Drugs 0.000 claims description 2
- 229940094060 tykerb Drugs 0.000 claims description 2
- 238000000034 method Methods 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000032837 Ring chromosome 16 syndrome Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 229920005601 base polymer Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25938709P | 2009-11-09 | 2009-11-09 | |
| US61/259,387 | 2009-11-09 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015013685A Division JP5982020B2 (ja) | 2009-11-09 | 2015-01-27 | 嘔吐および下痢などの状態を解消または軽減するためのコーティングされた薬物球状体およびその用途 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2011098965A JP2011098965A (ja) | 2011-05-19 |
| JP2011098965A5 true JP2011098965A5 (enExample) | 2013-12-19 |
| JP5866116B2 JP5866116B2 (ja) | 2016-02-17 |
Family
ID=43828063
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010250815A Active JP5866116B2 (ja) | 2009-11-09 | 2010-11-09 | 嘔吐および下痢などの状態を解消または軽減するためのコーティングされた薬物球状体およびその用途 |
| JP2015013685A Active JP5982020B2 (ja) | 2009-11-09 | 2015-01-27 | 嘔吐および下痢などの状態を解消または軽減するためのコーティングされた薬物球状体およびその用途 |
| JP2016025515A Pending JP2016094478A (ja) | 2009-11-09 | 2016-02-15 | 嘔吐および下痢などの状態を解消または軽減するためのコーティングされた薬物球状体およびその用途 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015013685A Active JP5982020B2 (ja) | 2009-11-09 | 2015-01-27 | 嘔吐および下痢などの状態を解消または軽減するためのコーティングされた薬物球状体およびその用途 |
| JP2016025515A Pending JP2016094478A (ja) | 2009-11-09 | 2016-02-15 | 嘔吐および下痢などの状態を解消または軽減するためのコーティングされた薬物球状体およびその用途 |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US8524281B2 (enExample) |
| EP (1) | EP2498751B1 (enExample) |
| JP (3) | JP5866116B2 (enExample) |
| CN (4) | CN102724962B (enExample) |
| AR (1) | AR078951A1 (enExample) |
| AU (1) | AU2010315362B2 (enExample) |
| CA (1) | CA2780332C (enExample) |
| ES (1) | ES2729677T3 (enExample) |
| NZ (1) | NZ599762A (enExample) |
| TW (1) | TWI429437B (enExample) |
| WO (1) | WO2011056741A2 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108421044A (zh) | 2005-02-03 | 2018-08-21 | 综合医院公司 | 治疗吉非替尼耐药性癌症的方法 |
| BRPI0618042A2 (pt) | 2005-11-04 | 2011-08-16 | Wyeth Corp | usos de uma rapamicina e de uma herceptina, produto, pacote farmacêutico, e, composição farmacêutica |
| US8022216B2 (en) | 2007-10-17 | 2011-09-20 | Wyeth Llc | Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof |
| CN102641270A (zh) | 2008-06-17 | 2012-08-22 | 惠氏有限责任公司 | 含有hki-272和长春瑞滨的抗肿瘤组合 |
| US8669273B2 (en) | 2008-08-04 | 2014-03-11 | Wyeth Llc | Antineoplastic combinations of 4-anilino-3-cyanoquinolines and capecitabine |
| IL264349B2 (en) | 2009-04-06 | 2024-01-01 | Wyeth Llc | Regimen comprising neratinib for the treatment of cancer |
| NZ599762A (en) | 2009-11-09 | 2014-07-25 | Wyeth Llc | Coated drug spheroids and uses thereof for eliminating or reducing conditions such as emesis and diarrhea |
| CN102675287A (zh) * | 2011-03-11 | 2012-09-19 | 江苏恒瑞医药股份有限公司 | (e)-n-[4-[[3-氯-4-(2-吡啶基甲氧基)苯基]氨基]-3-氰基-7-乙氧基-6-喹啉基]-3-[(2r)-1-甲基吡咯烷-2-基]丙-2-烯酰胺的可药用的盐、其制备方法及其在医药上的应用 |
| US9301957B2 (en) * | 2011-11-14 | 2016-04-05 | Novartis Ag | Immediate release 4-methyl-3-4[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-N-[5-(4-methyl-1H-imidazol-1-YL)-3-(trifluoromethyl)phenyl] benzamide formulation |
| WO2025213381A1 (en) * | 2024-04-10 | 2025-10-16 | Hangzhou Jitai Pharmaceutical Technology Co., Ltd | Neratinib-cyclodextrin composition and method for preparing same |
Family Cites Families (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS54119021A (en) * | 1978-03-06 | 1979-09-14 | Nippon Kayaku Co Ltd | Carcinostatic agent |
| JPH0436237A (ja) * | 1990-06-01 | 1992-02-06 | Taiho Yakuhin Kogyo Kk | 抗腫瘍性複合製剤 |
| US6002008A (en) | 1997-04-03 | 1999-12-14 | American Cyanamid Company | Substituted 3-cyano quinolines |
| US6288082B1 (en) | 1998-09-29 | 2001-09-11 | American Cyanamid Company | Substituted 3-cyanoquinolines |
| US6297258B1 (en) | 1998-09-29 | 2001-10-02 | American Cyanamid Company | Substituted 3-cyanoquinolines |
| US6384051B1 (en) | 2000-03-13 | 2002-05-07 | American Cyanamid Company | Method of treating or inhibiting colonic polyps |
| IL161921A0 (en) | 2001-11-27 | 2005-11-20 | Wyeth Corp | 3-Cyanoquinolines as inhibitors of egf-r and her2 kinases |
| US20040122048A1 (en) * | 2002-10-11 | 2004-06-24 | Wyeth Holdings Corporation | Stabilized pharmaceutical composition containing basic excipients |
| CL2004000016A1 (es) | 2003-01-21 | 2005-04-15 | Wyeth Corp | Compuesto derivado de cloruro de 4-amino-2-butenoilo o una sal farmaceuticamente aceptable del mismo; procedimiento para preparar dicho compuesto, util como intermediario en la sintesis de compuestos inhibidores de proteina quinasa tirosina. |
| US20050025825A1 (en) * | 2003-07-31 | 2005-02-03 | Xanodyne Pharmacal, Inc. | Tranexamic acid formulations with reduced adverse effects |
| AU2004266572A1 (en) | 2003-08-01 | 2005-03-03 | Wyeth Holdings Corporation | Use of combination of an epidermal growth factor receptor kinase inhibitor and cytotoxic agents for treatment and inhibition of cancer |
| US7399865B2 (en) | 2003-09-15 | 2008-07-15 | Wyeth | Protein tyrosine kinase enzyme inhibitors |
| TWI372066B (en) * | 2003-10-01 | 2012-09-11 | Wyeth Corp | Pantoprazole multiparticulate formulations |
| US20050142192A1 (en) | 2003-10-15 | 2005-06-30 | Wyeth | Oral administration of [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)alkyl] phosphonic acid and derivatives |
| EP3611273A1 (en) | 2004-03-31 | 2020-02-19 | The General Hospital Corporation | Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments |
| JP5159303B2 (ja) * | 2005-03-03 | 2013-03-06 | 武田薬品工業株式会社 | 放出制御組成物 |
| DE602006012972D1 (de) | 2005-04-28 | 2010-04-29 | Wyeth Corp | Mikronisierte tanaproget zusammensetzungen und verfahren zu ihrer herstellung |
| CN101180269A (zh) * | 2005-05-25 | 2008-05-14 | 惠氏公司 | 制备3-氰基-喹啉的方法和由其制得的中间体 |
| AR054833A1 (es) * | 2005-07-15 | 2007-07-18 | Wyeth Corp | Formas de dosificacion de liberacion retardada oral altamemte biodisponibles de succinato de o-desmetilvenlafaxina |
| BRPI0618042A2 (pt) | 2005-11-04 | 2011-08-16 | Wyeth Corp | usos de uma rapamicina e de uma herceptina, produto, pacote farmacêutico, e, composição farmacêutica |
| CN101300029A (zh) * | 2005-11-04 | 2008-11-05 | 惠氏公司 | mTOR抑制剂、赫赛汀和/或HKI-272的抗肿瘤组合 |
| PL1948180T3 (pl) * | 2005-11-11 | 2013-09-30 | Boehringer Ingelheim Int | Terapia skojarzona raka polegająca na podawaniu inhibitorów EGFR/HER2 |
| CN101340895A (zh) * | 2005-12-22 | 2009-01-07 | 惠氏公司 | 包含替加环素的口服制剂 |
| TW200806282A (en) * | 2006-05-05 | 2008-02-01 | Wyeth Corp | Solid dosage formulations |
| KR20090104862A (ko) | 2007-01-12 | 2009-10-06 | 와이어쓰 | 정제내 정제 조성물 |
| US8022216B2 (en) | 2007-10-17 | 2011-09-20 | Wyeth Llc | Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof |
| WO2009061349A1 (en) | 2007-11-05 | 2009-05-14 | Puretech Ventures | Methods, kits, and compositions for administering pharmaceutical compounds |
| CN101185633A (zh) * | 2007-12-14 | 2008-05-28 | 山东蓝金生物工程有限公司 | 一种治疗实体肿瘤的尼拉替尼缓释植入剂 |
| CA2711558C (en) * | 2008-01-04 | 2016-12-13 | Intellikine, Inc. | Phosphatidyl inositol-3 kinase inhibiting compounds |
| US20090246198A1 (en) * | 2008-03-31 | 2009-10-01 | Takeda Pharmaceutical Company Limited | Mapk/erk kinase inhibitors and methods of use thereof |
| TWI519322B (zh) * | 2008-04-15 | 2016-02-01 | 愛戴爾製藥股份有限公司 | 包含弱鹼性藥物及控制釋放劑型之組合物 |
| CN102641270A (zh) | 2008-06-17 | 2012-08-22 | 惠氏有限责任公司 | 含有hki-272和长春瑞滨的抗肿瘤组合 |
| US8669273B2 (en) | 2008-08-04 | 2014-03-11 | Wyeth Llc | Antineoplastic combinations of 4-anilino-3-cyanoquinolines and capecitabine |
| WO2010048477A2 (en) | 2008-10-24 | 2010-04-29 | Wyeth Llc | Improved process for preparation of coupled products from 4-amino-3-cyanoquinolines using stabilized intermediates |
| IL264349B2 (en) | 2009-04-06 | 2024-01-01 | Wyeth Llc | Regimen comprising neratinib for the treatment of cancer |
| RU2011152105A (ru) | 2009-07-02 | 2013-08-10 | УАЙТ ЭлЭлСи | Составы таблеток 3-цианохинолина и их применение |
| US20120135952A1 (en) | 2009-07-17 | 2012-05-31 | Hanall Biopharma Co., Ltd. | Butyric acid salt of n,n-dimethyl imidocarbon imidic diamide, method of preparing same, and pharmaceutical compositions and combinations containing same |
| WO2011008053A2 (ko) | 2009-07-17 | 2011-01-20 | 한올바이오파마주식회사 | Ｎ,ｎ-디메틸 이미도디카르본이미딕 디아미드의 프로피온산염, 이의 제조방법, 이를 포함하는 약제학적 조성물 및 이를 포함하는 복합제제 |
| KR20110021691A (ko) | 2009-08-25 | 2011-03-04 | 한올바이오파마주식회사 | 메트포르민 메탄설폰산염, 그의 제조방법, 그를 포함하는 약학 조성물 및 그를 포함하는 복합제제 |
| KR101211227B1 (ko) | 2009-08-25 | 2012-12-11 | 한올바이오파마주식회사 | 메트포르민 아스코르브산염, 그의 제조방법, 그를 포함하는 약학 조성물 및 그를 포함하는 복합제제 |
| KR101190953B1 (ko) | 2009-08-25 | 2012-10-12 | 한올바이오파마주식회사 | 메트포르민 타우린염, 그의 제조방법, 그를 포함하는 약학 조성물 및 그를 포함하는 복합제제 |
| NZ599762A (en) | 2009-11-09 | 2014-07-25 | Wyeth Llc | Coated drug spheroids and uses thereof for eliminating or reducing conditions such as emesis and diarrhea |
| FI4066821T3 (fi) | 2009-11-09 | 2025-05-13 | Wyeth Llc | Neratinibimaleaatin tablettiformulaatioita |
| EP3575413A1 (en) | 2009-12-11 | 2019-12-04 | Wyeth LLC | Phosphatidylinositol-3-kinase pathway biomarkers |
| CA2787048C (en) | 2010-01-13 | 2021-06-22 | Wyeth Llc | A cut-point in pten protein expression that accurately identifies tumors and is predictive of drug response to a pan-erbb inhibitor |
-
2010
- 2010-11-01 NZ NZ59976210A patent/NZ599762A/en unknown
- 2010-11-01 ES ES10787212T patent/ES2729677T3/es active Active
- 2010-11-01 CN CN201080060547.0A patent/CN102724962B/zh active Active
- 2010-11-01 AU AU2010315362A patent/AU2010315362B2/en active Active
- 2010-11-01 CN CN201710247590.1A patent/CN107308130B/zh active Active
- 2010-11-01 CA CA2780332A patent/CA2780332C/en active Active
- 2010-11-01 CN CN201610509189.6A patent/CN106074445B/zh active Active
- 2010-11-01 CN CN201710247663.7A patent/CN107441058A/zh active Pending
- 2010-11-01 WO PCT/US2010/054934 patent/WO2011056741A2/en not_active Ceased
- 2010-11-01 EP EP10787212.9A patent/EP2498751B1/en active Active
- 2010-11-05 US US12/940,797 patent/US8524281B2/en active Active
- 2010-11-09 JP JP2010250815A patent/JP5866116B2/ja active Active
- 2010-11-09 TW TW99138517A patent/TWI429437B/zh active
- 2010-11-09 AR ARP100104154 patent/AR078951A1/es not_active Application Discontinuation
-
2013
- 2013-08-29 US US14/014,254 patent/US9211264B2/en active Active
-
2015
- 2015-01-27 JP JP2015013685A patent/JP5982020B2/ja active Active
-
2016
- 2016-02-15 JP JP2016025515A patent/JP2016094478A/ja active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NZ599762A (en) | Coated drug spheroids and uses thereof for eliminating or reducing conditions such as emesis and diarrhea | |
| RU2370495C2 (ru) | Дополнительные гетероциклические соединения и их применение в качестве антагонистов метаботропного глутаматного рецептора | |
| MX2022002952A (es) | Formulaciones de liberacion modificada de 2-[3-[4-amino-3-(2-fluor o-4-fenoxi-fenil)pirazolo[3,4-d]pirimidin-1-il]piperidina-1-carbo nil]-4-metil-4-[4-(oxetan-3-il)piperazin-1-il]pent-2-enenitrilo. | |
| RU2008148547A (ru) | Фармацевтические композиции, включающие дулоксетина гидрохлорид с замедленным высвобождением | |
| CN105106203B (zh) | 富马酸沃诺拉赞的药物组合物及其制备方法 | |
| CN102933573B (zh) | 包含酰胺衍生物或其可药用盐的药物组合物 | |
| JP2007511510A (ja) | 持続放出性ベンラファキシン製剤 | |
| TW200635618A (en) | Solid dosage form comprising proton pump inhibitor and suspension made thereof | |
| CN1301534A (zh) | 稳定的缓释口服给药组合物 | |
| US9770437B2 (en) | Compositions of eltrombopag | |
| NO20081325L (no) | Nye doseringsformuleringer | |
| IE880901L (en) | A crivastine containing composition | |
| NO330144B1 (no) | Gastrobeskyttede omeprazolmikrogranuler, fremgangsmate for a oppna slike og farmasoytiske preparater | |
| WO2008067399A3 (en) | Controlled-release multi-layer formulation of piperazine-piperidine antagonists and agonists of the 5-th1a receptor having enhanced intestinal dissolution | |
| JPWO2017018473A1 (ja) | 錠剤 | |
| RU2011152105A (ru) | Составы таблеток 3-цианохинолина и их применение | |
| RU2014129508A (ru) | Новая комбинация | |
| RU2007148195A (ru) | Пероральные дозированные формы о-десметилвенлафаксин сукцината повышенной биодоступности с отсроченным высвобождением | |
| WO2012150412A1 (fr) | Nouvelle association entre le 4-{3-[cis-hexahydrocyclopenta[c]pyrrol-2(1h)-yl]propoxy}benzamide et un inhibiteur de l'acetylcholinesterase et les compositions pharmaceutiques qui la contiennent | |
| TW201707702A (zh) | 一種含有喹啉衍生物或其鹽的醫藥組成物 | |
| CA2471566A1 (en) | Combination of mtp inhibitors or apob-secretion inhibitors with fibrates for use as pharmaceuticals | |
| EA200600675A1 (ru) | Гранулы, содержащие гидрохлорид венлафаксина | |
| RU2401110C2 (ru) | Препарат в форме пеллет с замедленным высвобождением для вертиго | |
| MXPA05008711A (es) | Uso de r-10-hidroxi-10,11-dihidro-carbamazepina en dolor neuropatico. | |
| AT393625B (de) | Verfahren zur herstellung eines neuen therapeutischen praeparates enthaltend co-dergocrine und einen calciumantagonisten |