JP2012515210A - ベンダムスチン遊離塩基の新規の形態 - Google Patents
ベンダムスチン遊離塩基の新規の形態 Download PDFInfo
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- JP2012515210A JP2012515210A JP2011546322A JP2011546322A JP2012515210A JP 2012515210 A JP2012515210 A JP 2012515210A JP 2011546322 A JP2011546322 A JP 2011546322A JP 2011546322 A JP2011546322 A JP 2011546322A JP 2012515210 A JP2012515210 A JP 2012515210A
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- free base
- bendamustine free
- bendamustine
- diffraction pattern
- ray powder
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/16—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
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- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
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| PCT/US2010/020992 WO2010083276A1 (en) | 2009-01-15 | 2010-01-14 | Novel forms of bendamustine free base |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016512529A (ja) * | 2013-03-12 | 2016-04-28 | セファロン、インク． | ナノ粒子及びナノ粒子製剤 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9376394B2 (en) * | 2009-12-23 | 2016-06-28 | Dr. Reddy's Laboratories Ltd. | Preparation of bendamustine and its salts |
| EP3895694A1 (en) | 2010-01-28 | 2021-10-20 | Eagle Pharmaceuticals, Inc. | Formulations of bendamustine |
| WO2012176214A2 (en) * | 2011-06-20 | 2012-12-27 | Hetero Research Foundation | Process for bendamustine hydrochloride |
| RS58744B1 (sr) | 2012-03-20 | 2019-06-28 | Eagle Pharmaceuticals Inc | Tečna kompozicija za upotrebu u postupku lečenja stanja koja reaguju na bendamustin kod pacijenata kojima su potrebne smanjene zapremine za davanje |
| DK2827862T3 (da) | 2012-03-20 | 2024-02-12 | Eagle Pharmaceuticals Inc | Formuleringer af bendamustin |
| US20230241218A1 (en) * | 2012-07-10 | 2023-08-03 | Eagle Pharmaceuticals, Inc. | Formulations of bendamustine |
| EP2988655B1 (en) | 2013-04-26 | 2023-04-12 | Genentech, Inc. | Contour integration perimetry vision test |
| US20240148696A1 (en) | 2022-10-25 | 2024-05-09 | Softkemo Pharma Inc. | Lyophilized bendamustine-cyclodextrin composition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DD159877A1 (de) * | 1981-06-12 | 1983-04-13 | Wolfgang Krueger | Verfahren zur herstellung von 4-[1-methyl-5-bis(2-chloraethyl)amino-benzimidazolyl-2]-buttersaeure |
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| DD159289A1 (de) | 1981-06-01 | 1983-03-02 | Uwe Olthoff | Verfahren zur herstellung stabiler injektionsloesungen von n-lostverbindungen |
| US5204335A (en) * | 1986-10-31 | 1993-04-20 | Asta Pharma Aktiengesellschaft | Ifosfamide lyophilisate and process for its preparation |
| US5227373A (en) * | 1991-10-23 | 1993-07-13 | Bristol-Myers Squibb Co. | Lyophilized ifosfamide compositions |
| DK0752248T3 (da) * | 1992-11-13 | 2000-11-13 | Idec Pharma Corp | Terapeutisk anvendelse af kimæriske og radioaktivt mærkede antistoffer mod humant B-lymfocytbegrænset differentieringsantig |
| US5595721A (en) * | 1993-09-16 | 1997-01-21 | Coulter Pharmaceutical, Inc. | Radioimmunotherapy of lymphoma using anti-CD20 |
| PT725642E (pt) * | 1993-10-27 | 2000-05-31 | Upjohn Co | Prostaglandina e 1 estabilizada |
| US5561121A (en) | 1993-11-09 | 1996-10-01 | American Cyanamid Company | Stable lyophilized thiotepa composition |
| US5955504A (en) | 1995-03-13 | 1999-09-21 | Loma Linda University Medical Center | Colorectal chemoprotective composition and method of preventing colorectal cancer |
| DE19529057B4 (de) * | 1995-08-08 | 2007-12-13 | Baxter Healthcare S.A. | Ifosfamid-Lyophilisat-Zubereitungen |
| US6077850A (en) * | 1997-04-21 | 2000-06-20 | G.D. Searle & Co. | Substituted benzopyran analogs for the treatment of inflammation |
| US20040072889A1 (en) * | 1997-04-21 | 2004-04-15 | Pharmacia Corporation | Method of using a COX-2 inhibitor and an alkylating-type antineoplastic agent as a combination therapy in the treatment of neoplasia |
| US6034256A (en) * | 1997-04-21 | 2000-03-07 | G.D. Searle & Co. | Substituted benzopyran derivatives for the treatment of inflammation |
| ATE315392T1 (de) * | 1998-07-09 | 2006-02-15 | Francis A Nardella | Zusammensetzungen zur behandlung chronischer lymphatischer leukämie |
| US5972912A (en) * | 1998-12-17 | 1999-10-26 | S.P. Pharmaceuticals | Method for lyophilizing ifosfamide |
| US6569402B1 (en) * | 1998-12-18 | 2003-05-27 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals |
| US6380210B1 (en) * | 1999-04-02 | 2002-04-30 | Neurogen Corporation | Heteroaryl fused aminoalkyl-imidazole derivatives: selective modulators of GABAa receptors |
| US6545034B1 (en) * | 1999-07-23 | 2003-04-08 | The Regents Of The University Of California | Use of etodolac for the treatment of chronic lymphocytic leukemia |
| DE10016077A1 (de) | 2000-03-31 | 2001-12-13 | Cellcontrol Biomedical Lab Gmb | Verfahren und Vorrichtung zum automatischen Nachweisen einer Wirkung eines zellbeeinflussenden Mittels auf lebende Zellen |
| US20040152672A1 (en) * | 2000-08-09 | 2004-08-05 | Carson Dennis A. | Indole compounds useful for the treatment of cancer |
| KR20040025880A (ko) * | 2000-12-11 | 2004-03-26 | 다케다 야쿠힌 고교 가부시키가이샤 | 수용해성이 개선된 의약 조성물 |
| EP1350793A1 (en) * | 2000-12-11 | 2003-10-08 | Takeda Chemical Industries, Ltd. | Medicinal compositions having improved absorbability |
| EP1435877B1 (de) * | 2001-10-15 | 2009-04-15 | Hemoteq AG | Beschichtung von stents zur verhinderung von restenose |
| US6613927B1 (en) | 2002-02-08 | 2003-09-02 | American Pharmaceutical Partners, Inc. | Sterile lyophilized ifosfamide and associated methods |
| DE10306724A1 (de) | 2002-02-28 | 2003-09-18 | G O T Therapeutics Gmbh | Vesikuläre Verkapselung von Bendamustin |
| ATE389183T1 (de) | 2002-03-22 | 2008-03-15 | Univ Muenchen L Maximilians | Zytokapazität-verfahren |
| EP1495124A2 (en) | 2002-04-17 | 2005-01-12 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Smac-peptides as therapeutics against cancer and autoimmune diseases |
| EP1354952A1 (en) | 2002-04-17 | 2003-10-22 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Smac-peptides as therapeutics against cancer and autoimmune diseases |
| MXPA04011111A (es) | 2002-05-09 | 2005-07-14 | Hemoteq Gmbh | Productos medicos que comprenden un revestimiento hemocompatible, produccion y uso de los mismos. |
| WO2004012769A1 (en) * | 2002-08-02 | 2004-02-12 | The Regents Of The University Of California | Therapeutic inhibitionof protein kinases in cancer cells |
| DE10304403A1 (de) | 2003-01-28 | 2004-08-05 | Röhm GmbH & Co. KG | Verfahren zur Herstellung einer oralen Arzneiform mit unmittelbarem Zerfall und Wirkstofffreisetzung |
| EP1444989A1 (en) | 2003-02-07 | 2004-08-11 | Giorgio Dr. Stassi | Sensitizing cells for apoptosis by selectively blocking cytokines |
| EP1594900A2 (en) * | 2003-02-14 | 2005-11-16 | Salmedix, Inc. | Compositions and methods for the detection and treatment of methylthioadenosine phosphorylase deficient cancers |
| CN1829514A (zh) * | 2003-07-25 | 2006-09-06 | 惠氏公司 | Cci－779冻干制剂 |
| US8436190B2 (en) * | 2005-01-14 | 2013-05-07 | Cephalon, Inc. | Bendamustine pharmaceutical compositions |
| CN102177140B (zh) * | 2008-10-08 | 2016-01-27 | 赛福伦公司 | 用于制备苯达莫司汀的方法 |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DD159877A1 (de) * | 1981-06-12 | 1983-04-13 | Wolfgang Krueger | Verfahren zur herstellung von 4-[1-methyl-5-bis(2-chloraethyl)amino-benzimidazolyl-2]-buttersaeure |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016512529A (ja) * | 2013-03-12 | 2016-04-28 | セファロン、インク． | ナノ粒子及びナノ粒子製剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20110110293A (ko) | 2011-10-06 |
| MX2011007557A (es) | 2011-08-12 |
| BRPI1004922A2 (pt) | 2019-09-24 |
| NZ594010A (en) | 2013-08-30 |
| ZA201105099B (en) | 2012-03-28 |
| EA020767B1 (ru) | 2015-01-30 |
| EA201170934A1 (ru) | 2011-12-30 |
| CA2749101A1 (en) | 2010-07-22 |
| CN102281877A (zh) | 2011-12-14 |
| CN103554030A (zh) | 2014-02-05 |
| AU2016204902A1 (en) | 2016-08-04 |
| SG172810A1 (en) | 2011-08-29 |
| EP2387400A1 (en) | 2011-11-23 |
| UA109109C2 (uk) | 2015-07-27 |
| IL213725A0 (en) | 2011-07-31 |
| US8076366B2 (en) | 2011-12-13 |
| CN102281877B (zh) | 2014-07-23 |
| WO2010083276A1 (en) | 2010-07-22 |
| AU2010204765A1 (en) | 2011-07-28 |
| US20100210701A1 (en) | 2010-08-19 |
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