ZA200106677B - Spontaneously dispersible n-benzoyl staurosporine compositions. - Google Patents
Spontaneously dispersible n-benzoyl staurosporine compositions. Download PDFInfo
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- ZA200106677B ZA200106677B ZA200106677A ZA200106677A ZA200106677B ZA 200106677 B ZA200106677 B ZA 200106677B ZA 200106677 A ZA200106677 A ZA 200106677A ZA 200106677 A ZA200106677 A ZA 200106677A ZA 200106677 B ZA200106677 B ZA 200106677B
- Authority
- ZA
- South Africa
- Prior art keywords
- composition
- surfactant
- benzoylstaurosporine
- pharmaceutical composition
- bioavailability
- Prior art date
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Classifications
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- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
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- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
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- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
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Landscapes
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- Biophysics (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
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- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Vascular Medicine (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
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| GBGB9903547.9A GB9903547D0 (en) | 1999-02-16 | 1999-02-16 | Organic compounds |
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| ZA200106677B true ZA200106677B (en) | 2003-01-14 |
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| ZA200106677A ZA200106677B (en) | 1999-02-16 | 2001-02-14 | Spontaneously dispersible n-benzoyl staurosporine compositions. |
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| EP (1) | EP1152750B1 (fr) |
| JP (2) | JP5057610B2 (fr) |
| KR (2) | KR100880859B1 (fr) |
| CN (1) | CN100367930C (fr) |
| AR (2) | AR022589A1 (fr) |
| AT (1) | ATE430554T1 (fr) |
| AU (1) | AU765776B2 (fr) |
| BR (1) | BRPI0008228B8 (fr) |
| CA (1) | CA2362277C (fr) |
| CL (1) | CL2009001682A1 (fr) |
| CZ (1) | CZ303979B6 (fr) |
| DE (1) | DE60042151D1 (fr) |
| DK (1) | DK1152750T3 (fr) |
| EC (1) | ECSP083351A (fr) |
| ES (1) | ES2326783T3 (fr) |
| GB (1) | GB9903547D0 (fr) |
| HK (1) | HK1045807B (fr) |
| HU (1) | HUP0105364A3 (fr) |
| ID (1) | ID30504A (fr) |
| IL (3) | IL144512A0 (fr) |
| MY (1) | MY128362A (fr) |
| NO (1) | NO331232B1 (fr) |
| NZ (1) | NZ513529A (fr) |
| PE (1) | PE20001499A1 (fr) |
| PL (1) | PL198330B1 (fr) |
| PT (1) | PT1152750E (fr) |
| RU (1) | RU2266121C2 (fr) |
| SI (1) | SI1152750T1 (fr) |
| SK (1) | SK286967B6 (fr) |
| TR (1) | TR200102385T2 (fr) |
| TW (1) | TWI240636B (fr) |
| WO (1) | WO2000048571A1 (fr) |
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| US6200968B1 (en) * | 1998-08-06 | 2001-03-13 | Cephalon, Inc. | Particle-forming compositions containing fused pyrrolocarbazoles |
| US7795246B2 (en) | 1998-08-06 | 2010-09-14 | Cephalon, Inc. | Particle-forming compositions containing fused pyrrolocarbazoles |
| DK1372611T3 (da) * | 2001-03-26 | 2006-09-18 | Novartis Ag | Farmaceutisk sammensætning omfattende staurosporin med ringe vandoplöselighed, et overfladeaktivt stof og en vandoplöselig polymer |
| BR0209647A (pt) | 2001-05-16 | 2004-07-27 | Novartis Ag | Combinação que compreende n-{5-[4-(4-metil-piperazino-metil)-benzoilamido]-2-metil fenil}-4-(3-piridil)-2-pirimidina-amina e um agente quimioterapêutico |
| TWI302836B (en) | 2001-10-30 | 2008-11-11 | Novartis Ag | Staurosporine derivatives as inhibitors of flt3 receptor tyrosine kinase activity |
| GB0206215D0 (en) | 2002-03-15 | 2002-05-01 | Novartis Ag | Organic compounds |
| CN101897662B (zh) * | 2002-07-23 | 2013-05-22 | 诺瓦提斯公司 | 包含药物、软膏基质和增溶剂/分散剂的眼用软膏剂组合物 |
| US7842791B2 (en) | 2002-12-19 | 2010-11-30 | Nancy Jean Britten | Dispersible pharmaceutical compositions |
| TWI324604B (en) * | 2003-06-18 | 2010-05-11 | Novartis Ag | New use of staurosporine derivatives |
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| GT200500310A (es) * | 2004-11-19 | 2006-06-19 | Compuestos organicos | |
| CA2660086C (fr) | 2006-08-16 | 2014-09-16 | Novartis Ag | Methode de fabrication de dispersions solides de composes therapeutiquesde cristallinite elevee |
| FR2918566B1 (fr) | 2007-07-11 | 2009-10-09 | Pierre Fabre Medicament Sa | Composition pharmaceutique stable d'un sel hydrosoluble de vinflunine. |
| WO2009067221A2 (fr) * | 2007-11-20 | 2009-05-28 | Cephalon, Inc. | Microémulsion contenant un composé indolocarbazole et formes pharmaceutiques la contenant |
| EP2229936B1 (fr) * | 2009-03-09 | 2015-05-06 | PharmaSol GmbH | Formules de testostérone de taille nano pour une meilleure biodisponibilité |
| WO2011000811A2 (fr) * | 2009-06-30 | 2011-01-06 | Novartis Ag | Composés organiques |
| CA2785251A1 (fr) * | 2009-12-22 | 2011-06-30 | Leo Pharma A/S | Composition cutanee comprenant un analogue de la vitamine d et un melange de solvant et de tensioactifs |
| JO3337B1 (ar) * | 2010-12-13 | 2019-03-13 | Debiopharm Sa | تركيبات صيدلية تشمل أليسبوريفير |
| US9387446B2 (en) | 2011-09-22 | 2016-07-12 | Ariel-University Research And Development Company Ltd. | Emulsions and methods of making emulsions |
| CN114712308A (zh) | 2015-12-09 | 2022-07-08 | 磷肌酸有限公司 | 药物制剂 |
| KR20190032265A (ko) * | 2015-12-09 | 2019-03-27 | 포스파제닉스 리미티드 | 약제학적 제형 |
| CN110662733A (zh) | 2016-12-21 | 2020-01-07 | 埃维科生物技术有限公司 | 方法 |
| WO2021097256A1 (fr) | 2019-11-14 | 2021-05-20 | Cohbar, Inc. | Peptides antagonistes de cxcr4 |
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| US4963367A (en) | 1984-04-27 | 1990-10-16 | Medaphore, Inc. | Drug delivery compositions and methods |
| US4735939A (en) | 1987-02-27 | 1988-04-05 | The Dow Chemical Company | Insecticidal activity of staurosporine |
| US5093330A (en) * | 1987-06-15 | 1992-03-03 | Ciba-Geigy Corporation | Staurosporine derivatives substituted at methylamino nitrogen |
| DE3824034C1 (fr) * | 1988-07-15 | 1989-09-14 | Gustav 7290 Freudenstadt De Memminger | |
| KR0148748B1 (ko) * | 1988-09-16 | 1998-08-17 | 장 크라메르, 한스 루돌프 하우스 | 사이클로스포린을 함유하는 약학조성물 |
| CA2108266C (fr) | 1991-04-19 | 2003-06-03 | Albert J. Owen | Formulations de microemulsions convertibles |
| GB9113872D0 (en) | 1991-06-27 | 1991-08-14 | Sandoz Ag | Improvements in or relating to organic compounds |
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| US5981568A (en) * | 1993-01-28 | 1999-11-09 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
| CH686761A5 (de) * | 1993-05-27 | 1996-06-28 | Sandoz Ag | Galenische Formulierungen. |
| US5639474A (en) | 1993-07-01 | 1997-06-17 | Hanmi Pharm. Ind., Ltd. | Cyclosporin soft capsule composition |
| DE69434626D1 (de) | 1993-11-17 | 2006-04-20 | Athena Neurosciences Inc | Transparente flüssigkeit zur verabreichung von verkapselten medikamenten |
| GB9325395D0 (en) | 1993-12-11 | 1994-02-16 | Ciba Geigy Ag | Compositions |
| WO1995022331A1 (fr) | 1994-02-18 | 1995-08-24 | Cephalon, Inc. | Solutions aqueuses d'indolocarbazole |
| EP0763041A1 (fr) * | 1994-06-01 | 1997-03-19 | Novartis AG | Derives d'indolocarbazole destines a sensibiliser a des agents antitumoraux des cellules a resistance multiple aux antitumoraux |
| GB2308545B (en) | 1994-10-26 | 1999-06-02 | Novartis Ag | Pharmaceutical microemulsion preconcentrates |
| IL129547A (en) | 1994-10-26 | 2001-01-11 | Novartis Ag | Pharmaceutical compositions comprising a macrolide and an acid |
| EP0711556A1 (fr) * | 1994-11-09 | 1996-05-15 | Ciba-Geigy Ag | Solutions intraveineuses contenant des dérivés de staurosporine |
| EP0733372A3 (fr) * | 1995-03-21 | 1998-05-20 | Ciba-Geigy Ag | Base pharmaceutique pour la formulation de nanosuspensions |
| WO1998013032A1 (fr) | 1996-09-27 | 1998-04-02 | Trega Biosciences, Inc. | Compositions d'agents therapeutiques convenant pour l'administration orale |
| DE19641672A1 (de) | 1996-10-10 | 1998-04-16 | Beiersdorf Ag | Kosmetische oder dermatologische Zubereitungen auf der Basis von ethylenoxidfreien und propylenoxidfreien Emulgatoren zur Herstellung von Mikroemulsionsgelen |
| US5827522A (en) | 1996-10-30 | 1998-10-27 | Troy Corporation | Microemulsion and method |
| NZ314060A (en) | 1997-01-13 | 1997-08-22 | Bernard Charles Sherman | Pharmaceutical microemulsion preconcentrate comprising cyclosporin dissolved in a solvent system comprising hydrophobic solvent(s) and surfactant(s) |
| BR9807528A (pt) * | 1997-01-30 | 2000-03-14 | Novartis Ag | Composições farmacêuticas isentas de óleo contendo ciclosporina a |
| ES2174462T3 (es) | 1997-07-29 | 2002-11-01 | Upjohn Co | Formulacion autoestimulante para compuestos lipofilos. |
| SI0999826T1 (en) | 1997-07-29 | 2004-12-31 | Pharmacia & Upjohn Company | Self-emulsifying formulation for lipophilic compounds |
| US6346511B1 (en) | 1997-09-08 | 2002-02-12 | Panacea Biotec Limited | Pharmaceutical composition comprising cyclosporin |
| US6979456B1 (en) * | 1998-04-01 | 2005-12-27 | Jagotec Ag | Anticancer compositions |
| GB9814527D0 (en) * | 1998-07-03 | 1998-09-02 | Cyclacel Ltd | Delivery system |
| AR013276A1 (es) | 1998-07-31 | 2000-12-13 | Panacea Biotec Ltd | Composicion de ciclosporina transparente |
| US6248363B1 (en) * | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
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1999
- 1999-02-16 GB GBGB9903547.9A patent/GB9903547D0/en not_active Ceased
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2000
- 2000-02-14 BR BRPI0008228A patent/BRPI0008228B8/pt not_active IP Right Cessation
- 2000-02-14 SI SI200031035T patent/SI1152750T1/sl unknown
- 2000-02-14 EP EP00909165A patent/EP1152750B1/fr not_active Expired - Lifetime
- 2000-02-14 ID IDW00200101649A patent/ID30504A/id unknown
- 2000-02-14 TR TR2001/02385T patent/TR200102385T2/xx unknown
- 2000-02-14 DK DK00909165T patent/DK1152750T3/da active
- 2000-02-14 CZ CZ20012931A patent/CZ303979B6/cs not_active IP Right Cessation
- 2000-02-14 DE DE60042151T patent/DE60042151D1/de not_active Expired - Lifetime
- 2000-02-14 WO PCT/EP2000/001196 patent/WO2000048571A1/fr active Application Filing
- 2000-02-14 NZ NZ513529A patent/NZ513529A/en not_active IP Right Cessation
- 2000-02-14 AR ARP000100627A patent/AR022589A1/es not_active Application Discontinuation
- 2000-02-14 HU HU0105364A patent/HUP0105364A3/hu unknown
- 2000-02-14 PL PL350556A patent/PL198330B1/pl unknown
- 2000-02-14 JP JP2000599363A patent/JP5057610B2/ja not_active Expired - Fee Related
- 2000-02-14 CN CNB008038244A patent/CN100367930C/zh not_active Expired - Lifetime
- 2000-02-14 ES ES00909165T patent/ES2326783T3/es not_active Expired - Lifetime
- 2000-02-14 AT AT00909165T patent/ATE430554T1/de active
- 2000-02-14 KR KR1020017009391A patent/KR100880859B1/ko active Protection Beyond IP Right Term
- 2000-02-14 PT PT00909165T patent/PT1152750E/pt unknown
- 2000-02-14 RU RU2001124597/15A patent/RU2266121C2/ru active
- 2000-02-14 SK SK1172-2001A patent/SK286967B6/sk not_active IP Right Cessation
- 2000-02-14 KR KR1020087015449A patent/KR20080064914A/ko not_active Application Discontinuation
- 2000-02-14 CA CA2362277A patent/CA2362277C/fr not_active Expired - Lifetime
- 2000-02-14 AU AU31542/00A patent/AU765776B2/en active Active
- 2000-02-14 IL IL14451200A patent/IL144512A0/xx active IP Right Grant
- 2000-02-14 PE PE2000000113A patent/PE20001499A1/es not_active Application Discontinuation
- 2000-02-15 MY MYPI20000530A patent/MY128362A/en unknown
- 2000-03-13 TW TW089104503A patent/TWI240636B/zh not_active IP Right Cessation
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2001
- 2001-02-14 ZA ZA200106677A patent/ZA200106677B/en unknown
- 2001-07-23 IL IL144512A patent/IL144512A/en not_active IP Right Cessation
- 2001-08-15 NO NO20013964A patent/NO331232B1/no not_active IP Right Cessation
- 2001-08-15 US US09/930,335 patent/US20020061873A1/en not_active Abandoned
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2002
- 2002-09-13 HK HK02106758.7A patent/HK1045807B/zh not_active IP Right Cessation
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2007
- 2007-09-21 US US11/859,077 patent/US8575147B2/en not_active Expired - Fee Related
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2008
- 2008-07-04 EC EC2008003351A patent/ECSP083351A/es unknown
- 2008-07-07 IL IL192666A patent/IL192666A0/en unknown
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2009
- 2009-07-31 CL CL2009001682A patent/CL2009001682A1/es unknown
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2011
- 2011-08-05 AR ARP110102851A patent/AR082579A2/es not_active Application Discontinuation
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2012
- 2012-01-05 JP JP2012000816A patent/JP2012111763A/ja active Pending
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2013
- 2013-10-15 US US14/053,661 patent/US8722664B2/en not_active Expired - Fee Related
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