CA2753641C - Bendamustine cyclopolysaccharide compositions - Google Patents
Bendamustine cyclopolysaccharide compositions Download PDFInfo
- Publication number
- CA2753641C CA2753641C CA2753641A CA2753641A CA2753641C CA 2753641 C CA2753641 C CA 2753641C CA 2753641 A CA2753641 A CA 2753641A CA 2753641 A CA2753641 A CA 2753641A CA 2753641 C CA2753641 C CA 2753641C
- Authority
- CA
- Canada
- Prior art keywords
- bendamustine
- composition
- cyclopolysaccharide
- sbecd
- cyclodextrin
- 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.)
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Classifications
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- 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
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US20854109P | 2009-02-25 | 2009-02-25 | |
| US61/208,541 | 2009-02-25 | ||
| US26994409P | 2009-07-01 | 2009-07-01 | |
| US61/269,944 | 2009-07-01 | ||
| US27136409P | 2009-07-20 | 2009-07-20 | |
| US61/271,364 | 2009-07-20 | ||
| US27929309P | 2009-10-19 | 2009-10-19 | |
| US61/279,293 | 2009-10-19 | ||
| US12/711,979 US8436032B2 (en) | 2009-02-25 | 2010-02-24 | Bendamustine cyclopolysaccharide compositions |
| PCT/IB2010/000502 WO2010097700A1 (en) | 2009-02-25 | 2010-02-24 | Bendamustine cyclopolysaccharide compositions |
| US12/711,979 | 2010-02-24 |
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| CA2753641A1 CA2753641A1 (en) | 2010-09-02 |
| CA2753641C true CA2753641C (en) | 2014-09-16 |
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| CA2753641A Active CA2753641C (en) | 2009-02-25 | 2010-02-24 | Bendamustine cyclopolysaccharide compositions |
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| Country | Link |
|---|---|
| US (2) | US8436032B2 (OSRAM) |
| EP (2) | EP2792369B1 (OSRAM) |
| JP (1) | JP5654498B2 (OSRAM) |
| KR (1) | KR101798951B1 (OSRAM) |
| CN (2) | CN102935080A (OSRAM) |
| AU (1) | AU2010217297A1 (OSRAM) |
| CA (1) | CA2753641C (OSRAM) |
| ES (2) | ES2525257T3 (OSRAM) |
| HU (1) | HUE038234T2 (OSRAM) |
| NO (1) | NO2792369T3 (OSRAM) |
| RU (2) | RU2734236C2 (OSRAM) |
| WO (1) | WO2010097700A1 (OSRAM) |
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| CA2753641C (en) | 2009-02-25 | 2014-09-16 | Supratek Pharma, Inc. | Bendamustine cyclopolysaccharide compositions |
| HUE054836T2 (hu) | 2010-01-28 | 2021-10-28 | Eagle Pharmaceuticals Inc | Bendamusztin kiszerelései |
| WO2011103150A2 (en) * | 2010-02-18 | 2011-08-25 | Cephalon, Inc. | Lyophilized preparations of bendamustine |
| US20110207764A1 (en) * | 2010-02-23 | 2011-08-25 | Valery Alakhov | Cyclopolysaccharide compositions |
| US8383663B2 (en) | 2010-07-19 | 2013-02-26 | Supratek Pharma Inc. | Bendamustine anionic-catioinic cyclopolysaccharide compositions |
| EP2758052B9 (en) * | 2011-09-18 | 2019-03-27 | Euro-Celtique S.A. | Pharmaceutical composition comprising an HDAC inhibitor and a cyclopolysaccharide |
| AR092790A1 (es) | 2012-02-01 | 2015-05-06 | Euro Celtique Sa | Derivados bencimidazolicos del acido hidroxamico |
| JP6224064B2 (ja) | 2012-03-20 | 2017-11-01 | イーグル・ファーマシューティカルズ・インコーポレーテッド | 低減された投与容量を必要とする患者におけるベンダムスチン応答性症状の治療方法 |
| HRP20240056T1 (hr) * | 2012-03-20 | 2024-03-29 | Eagle Pharmaceuticals, Inc. | Formulacije bendamustina |
| US20230241218A1 (en) * | 2012-07-10 | 2023-08-03 | Eagle Pharmaceuticals, Inc. | Formulations of bendamustine |
| JP2016501876A (ja) * | 2012-11-30 | 2016-01-21 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | ステロイドの抗痙攣活性 |
| CN109953954A (zh) * | 2013-08-27 | 2019-07-02 | V·沃道里斯 | 苯达莫司汀医药组合物 |
| GB201409488D0 (en) | 2014-05-28 | 2014-07-09 | Euro Celtique Sa | Pharmaceutical composition |
| GB201409471D0 (en) | 2014-05-28 | 2014-07-09 | Euro Celtique Sa | Pharmaceutical composition |
| GB201409485D0 (en) | 2014-05-28 | 2014-07-09 | Euro Celtique Sa | Pharmaceutical composition |
| CA3040155C (en) | 2016-10-11 | 2024-01-16 | Euro-Celtique S.A. | Compound for use in the treatment of hodgkin lymphoma |
| GB201709406D0 (en) | 2017-06-13 | 2017-07-26 | Euro-Cletique S A | Compounds for treating TNBC |
| GB201709403D0 (en) | 2017-06-13 | 2017-07-26 | Euro Celtique Sa | Compounds for treating sarcoma |
| GB201709402D0 (en) | 2017-06-13 | 2017-07-26 | Euro Celtique Sa | Compounds for treating t-pll |
| GB201709405D0 (en) | 2017-06-13 | 2017-07-26 | Euro Celtique Sa | Compounds for treating ovarian cancer |
| AU2018346395A1 (en) | 2017-10-05 | 2020-04-30 | Mecox Curemed Co., Ltd. | Oral bendamustine formulations |
| US11730815B2 (en) * | 2018-11-26 | 2023-08-22 | Good Health, Llc | Stable liquid pharmaceutical compositions comprising bendamustine |
| JP2022522928A (ja) | 2018-12-18 | 2022-04-21 | ムンディファーマ・インターナショナル・コーポレーション・リミテッド | 多発性骨髄腫を治療するための化合物 |
| EP4134068A4 (en) * | 2020-04-09 | 2024-02-07 | Bika Biotechnology (Guangzhou) Co., Ltd. | Bendamustine composition and use thereof |
| CN111557904A (zh) * | 2020-04-09 | 2020-08-21 | 比卡生物科技（广州）有限公司 | 苯达莫司汀组合物及其用途 |
| US20240148696A1 (en) | 2022-10-25 | 2024-05-09 | Softkemo Pharma Inc. | Lyophilized bendamustine-cyclodextrin composition |
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| DD159289A1 (de) | 1981-06-01 | 1983-03-02 | Uwe Olthoff | Verfahren zur herstellung stabiler injektionsloesungen von n-lostverbindungen |
| US6407079B1 (en) * | 1985-07-03 | 2002-06-18 | Janssen Pharmaceutica N.V. | Pharmaceutical compositions containing drugs which are instable or sparingly soluble in water and methods for their preparation |
| US5068226A (en) * | 1987-12-07 | 1991-11-26 | Cyclex, Inc. | Pharmaceutical preparations containing cyclodextrins and their use in iontophoretic therapies |
| US5602112A (en) * | 1992-06-19 | 1997-02-11 | Supergen, Inc. | Pharmaceutical formulation |
| DE59607089D1 (de) * | 1995-03-10 | 2001-07-19 | Roche Diagnostics Gmbh | Polypeptid-enthaltende pharmazeutische darreichungsformen in form von mikropartikeln und verfahren zu deren herstellung |
| JP4979843B2 (ja) * | 1995-03-10 | 2012-07-18 | ロッシュ ディアグノスティクス ゲゼルシャフト ミット ベシュレンクテル ハフツング | 微粒子の形のポリペプチド含有投薬形 |
| US6624141B1 (en) * | 1999-03-17 | 2003-09-23 | The Regents Of The University Of Michigan | Protamine fragment compositions and methods of use |
| DE10204792A1 (de) * | 2002-02-06 | 2003-08-14 | Merck Patent Gmbh | Lyophilisierte Zubereitung enthaltend Immuncytokine |
| RU2321597C2 (ru) * | 2002-04-19 | 2008-04-10 | Новартис Аг | Биоматериал, способ его приготовления и его применение, медицинское средство, имплантат и вкладыш |
| WO2004060310A2 (en) * | 2002-12-31 | 2004-07-22 | Altus Pharmaceuticals Inc. | Human growth hormone crystals and methods for preparing them |
| CN1976679B (zh) * | 2003-12-31 | 2011-08-31 | 锡德克斯药物公司 | 含有磺基烷基醚环糊精以及皮质甾类的吸入制剂 |
| EP1740184A1 (en) * | 2004-03-30 | 2007-01-10 | Pfizer Products Incorporated | Combinations of signal transduction inhibitors |
| WO2005120551A1 (en) * | 2004-06-07 | 2005-12-22 | Nastech Pharmaceutical Company Inc. | Intranasal formulations of interferon beta free of stabilizers that are proteins or polypeptides |
| ATE509617T1 (de) * | 2004-08-03 | 2011-06-15 | Royal College Surgeons Ireland | Phenytoinformulierungen und ihre verwendungen in der wundheilung |
| JP2008519032A (ja) * | 2004-11-03 | 2008-06-05 | キュラジェン コーポレイション | Ｆｇｆ−２０の調合物、生成方法および使用 |
| CA2585659A1 (en) * | 2004-11-05 | 2006-06-22 | Cephalon, Inc. | Cancer treatments |
| US20060128653A1 (en) * | 2004-12-10 | 2006-06-15 | Chunlin Tang | Pharmaceutical formulation of decitabine |
| US8436190B2 (en) | 2005-01-14 | 2013-05-07 | Cephalon, Inc. | Bendamustine pharmaceutical compositions |
| UA94036C2 (ru) * | 2005-01-14 | 2011-04-11 | Сефалон, Инк. | Фармацевтическая композиция бендамустина, предназначенная для лиофилизации |
| BRPI0607299A2 (pt) | 2005-01-28 | 2009-08-25 | Univ Brigham Young | ativação de glicolipìdio bacteriano de células nkt restritas a cd1d |
| US8158152B2 (en) * | 2005-11-18 | 2012-04-17 | Scidose Llc | Lyophilization process and products obtained thereby |
| CN1846685A (zh) | 2006-01-25 | 2006-10-18 | 济南帅华医药科技有限公司 | 含苯达莫司汀和其增效剂的缓释注射剂 |
| EP2079450A2 (en) | 2006-11-08 | 2009-07-22 | Novavax, INC. | Method of preparing solid dosage forms of multi-phasic pharmaceutical compositions |
| US8425459B2 (en) * | 2006-11-20 | 2013-04-23 | Lutonix, Inc. | Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent |
| EP2131849B1 (en) | 2007-03-02 | 2011-10-26 | The University Of Wollongong | Compositions and methods for delivery of anti-cancer agents |
| CN101219113A (zh) | 2008-01-28 | 2008-07-16 | 济南帅华医药科技有限公司 | 含苯达莫司汀的复方抗癌缓释注射剂 |
| CA2753641C (en) | 2009-02-25 | 2014-09-16 | Supratek Pharma, Inc. | Bendamustine cyclopolysaccharide compositions |
| CN101606934B (zh) * | 2009-07-27 | 2011-09-28 | 江苏奥赛康药业有限公司 | 盐酸苯达莫司汀组合物 |
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2010
- 2010-02-24 CA CA2753641A patent/CA2753641C/en active Active
- 2010-02-24 US US12/711,979 patent/US8436032B2/en active Active
- 2010-02-24 HU HUE14177306A patent/HUE038234T2/hu unknown
- 2010-02-24 AU AU2010217297A patent/AU2010217297A1/en not_active Abandoned
- 2010-02-24 ES ES10745872.1T patent/ES2525257T3/es active Active
- 2010-02-24 EP EP14177306.9A patent/EP2792369B1/en active Active
- 2010-02-24 RU RU2016124871A patent/RU2734236C2/ru not_active Application Discontinuation
- 2010-02-24 CN CN2012104076231A patent/CN102935080A/zh active Pending
- 2010-02-24 ES ES14177306.9T patent/ES2675620T3/es active Active
- 2010-02-24 KR KR1020117022330A patent/KR101798951B1/ko active Active
- 2010-02-24 EP EP10745872.1A patent/EP2400987B1/en active Active
- 2010-02-24 NO NO14177306A patent/NO2792369T3/no unknown
- 2010-02-24 RU RU2011138844/15A patent/RU2591804C2/ru not_active Application Discontinuation
- 2010-02-24 CN CN2010800183017A patent/CN102421451B/zh active Active
- 2010-02-24 WO PCT/IB2010/000502 patent/WO2010097700A1/en not_active Ceased
- 2010-02-24 JP JP2011550669A patent/JP5654498B2/ja active Active
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- 2013-03-11 US US13/793,442 patent/US8703964B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| RU2011138844A (ru) | 2013-04-10 |
| AU2010217297A1 (en) | 2011-10-20 |
| US20100216858A1 (en) | 2010-08-26 |
| US8436032B2 (en) | 2013-05-07 |
| CN102421451B (zh) | 2013-11-06 |
| EP2400987A4 (en) | 2012-08-22 |
| JP5654498B2 (ja) | 2015-01-14 |
| ES2675620T3 (es) | 2018-07-11 |
| KR101798951B1 (ko) | 2017-11-20 |
| RU2016124871A (ru) | 2018-12-04 |
| RU2734236C2 (ru) | 2020-10-13 |
| US20130190372A1 (en) | 2013-07-25 |
| HUE038234T2 (hu) | 2018-10-29 |
| CA2753641A1 (en) | 2010-09-02 |
| JP2012519657A (ja) | 2012-08-30 |
| EP2792369B1 (en) | 2018-04-18 |
| EP2792369A1 (en) | 2014-10-22 |
| CN102421451A (zh) | 2012-04-18 |
| ES2525257T3 (es) | 2014-12-19 |
| EP2400987A1 (en) | 2012-01-04 |
| RU2016124871A3 (OSRAM) | 2019-11-11 |
| RU2591804C2 (ru) | 2016-07-20 |
| EP2400987B1 (en) | 2014-09-03 |
| NO2792369T3 (OSRAM) | 2018-09-15 |
| KR20120015294A (ko) | 2012-02-21 |
| WO2010097700A1 (en) | 2010-09-02 |
| CN102935080A (zh) | 2013-02-20 |
| US8703964B2 (en) | 2014-04-22 |
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