CA2379660A1 - Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs - Google Patents
Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs Download PDFInfo
- Publication number
- CA2379660A1 CA2379660A1 CA002379660A CA2379660A CA2379660A1 CA 2379660 A1 CA2379660 A1 CA 2379660A1 CA 002379660 A CA002379660 A CA 002379660A CA 2379660 A CA2379660 A CA 2379660A CA 2379660 A1 CA2379660 A1 CA 2379660A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- compound
- camptothecin
- liposomal
- cpt
- 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.)
- Abandoned
Links
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Classifications
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/365,632 US6096336A (en) | 1996-01-30 | 1999-08-03 | Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs |
| US09/365,632 | 1999-08-03 | ||
| US09/499,684 US6352996B1 (en) | 1999-08-03 | 2000-02-08 | Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs |
| US09/499,684 | 2000-02-08 | ||
| PCT/US2000/020136 WO2001008663A2 (en) | 1999-08-03 | 2000-07-25 | Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2379660A1 true CA2379660A1 (en) | 2001-02-08 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002379660A Abandoned CA2379660A1 (en) | 1999-08-03 | 2000-07-25 | Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs |
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| Country | Link |
|---|---|
| US (1) | US6352996B1 (enExample) |
| EP (1) | EP1200068A2 (enExample) |
| JP (1) | JP2003528808A (enExample) |
| AU (1) | AU6492600A (enExample) |
| CA (1) | CA2379660A1 (enExample) |
| WO (1) | WO2001008663A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102161680A (zh) * | 2011-02-24 | 2011-08-24 | 湖南方盛华美医药科技有限公司 | 磷酰胺酯喜树碱衍生物以及其制备方法、药物组合物和用途 |
Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6420378B1 (en) * | 1999-10-15 | 2002-07-16 | Supergen, Inc. | Inhibition of abnormal cell proliferation with camptothecin and combinations including the same |
| US20040009229A1 (en) * | 2000-01-05 | 2004-01-15 | Unger Evan Charles | Stabilized nanoparticle formulations of camptotheca derivatives |
| AU2001270413A1 (en) * | 2000-06-30 | 2002-01-14 | Inex Pharmaceuticals Corporation | Improved liposomal camptothecins and uses thereof |
| US20030059375A1 (en) * | 2001-08-20 | 2003-03-27 | Transave, Inc. | Method for treating lung cancers |
| PT1432402E (pt) * | 2001-10-03 | 2007-02-28 | Celator Pharmaceuticals Inc | Composições para administração de combinações de fármacos |
| CA2383259A1 (en) | 2002-04-23 | 2003-10-23 | Celator Technologies Inc. | Synergistic compositions |
| US7850990B2 (en) | 2001-10-03 | 2010-12-14 | Celator Pharmaceuticals, Inc. | Compositions for delivery of drug combinations |
| CA2477982A1 (en) * | 2002-03-05 | 2003-09-18 | Transave, Inc. | Methods for entrapment of bioactive agent in a liposome or lipid complex |
| JP2006502233A (ja) * | 2002-08-02 | 2006-01-19 | トランセーブ，インク． | 白金凝集物およびその製造方法 |
| US9186322B2 (en) * | 2002-08-02 | 2015-11-17 | Insmed Incorporated | Platinum aggregates and process for producing the same |
| US7879351B2 (en) * | 2002-10-29 | 2011-02-01 | Transave, Inc. | High delivery rates for lipid based drug formulations, and methods of treatment thereof |
| ES2539591T3 (es) * | 2002-10-29 | 2015-07-02 | Insmed Incorporated | Liberación sostenida de antiinfectantes |
| US7718189B2 (en) | 2002-10-29 | 2010-05-18 | Transave, Inc. | Sustained release of antiinfectives |
| US7670604B2 (en) | 2002-12-13 | 2010-03-02 | Aurelium Biopharma, Inc. | Vimentin directed diagnostics and therapeutics for multidrug resistant neoplastic disease |
| AU2003302986A1 (en) * | 2002-12-13 | 2004-07-09 | Aurelium Biopharma Inc. | Nucleophosmin directed diagnostics and therapeutics for multidrug resistant neoplastic disease |
| WO2005062058A1 (en) * | 2002-12-13 | 2005-07-07 | Aurelium Biopharma Inc. | Vimentin directed diagnostics and therapeutics for multidrug resistant neoplastic disease |
| US7226748B2 (en) * | 2003-01-03 | 2007-06-05 | Aurelium Biopharma, Inc. | HSC70 directed diagnostics and therapeutics for multidrug resistant neoplastic disease |
| WO2004080819A2 (en) * | 2003-03-14 | 2004-09-23 | Aurelium Biopharma Inc. | Triosephosphate isomerase directed diagnostics and therapeutics for multidrug resistant neoplastic disease |
| US20040204435A1 (en) * | 2003-04-09 | 2004-10-14 | Joachim Liehr | Alternating treatment with topoisomerase I and topoisomerase II inhibitors |
| US20050249822A1 (en) * | 2004-03-18 | 2005-11-10 | Transave, Inc. | Administration of cisplatin by inhalation |
| EP1755623A4 (en) * | 2004-05-21 | 2007-10-17 | Transave Inc | TREATMENT OF LUNG DISEASES AND BEFORE A PULMONARY DISEASE |
| EP1752150B1 (en) | 2004-06-01 | 2016-08-31 | Kabushiki Kaisha Yakult Honsha | Irinotecan preparation |
| ITRM20040288A1 (it) * | 2004-06-11 | 2004-09-11 | Sigma Tau Ind Farmaceuti | Uso della 7-t-butossiimminometilcamptotecina per la preparazione di un medicamento per il trattamento delle neoplasie dell'utero. |
| WO2006052767A2 (en) * | 2004-11-05 | 2006-05-18 | Inex Pharmaceuticals Corporation | Compositions and methods for stabilizing liposomal camptothecin formulations |
| US20060246124A1 (en) * | 2004-11-08 | 2006-11-02 | Pilkiewicz Frank G | Methods of treating cancer with lipid-based platinum compound formulations administered intraperitoneally |
| US20060135546A1 (en) * | 2004-12-16 | 2006-06-22 | Jagadevappa Basavaraja | Methods for the purification of 20(S)- camptothecin |
| US20060283742A1 (en) * | 2005-06-16 | 2006-12-21 | Canel Lightning Co. Ltd. | Multi-lamp display packaging for lamps with collapsible lampshades |
| US9107824B2 (en) | 2005-11-08 | 2015-08-18 | Insmed Incorporated | Methods of treating cancer with high potency lipid-based platinum compound formulations administered intraperitoneally |
| US20070190180A1 (en) * | 2005-11-08 | 2007-08-16 | Pilkiewicz Frank G | Methods of treating cancer with high potency lipid-based platinum compound formulations administered intravenously |
| WO2007056264A2 (en) * | 2005-11-08 | 2007-05-18 | Transave, Inc. | Methods of treating cancer with high potency lipid-based platinum compound formulations administered intraperitoneally |
| WO2007056236A2 (en) * | 2005-11-08 | 2007-05-18 | Transave, Inc. | Methods of treating cancer with lipid-based platinum compound formulations administered intravenously |
| WO2007064658A2 (en) * | 2005-11-30 | 2007-06-07 | Transave, Inc. | Safe and effective methods of administering therapeutic agents |
| ES2275443B1 (es) * | 2005-11-30 | 2008-06-01 | Italfarmaco, S.A. | Procedimiento de preparacion de liposomas. |
| ES2798263T3 (es) | 2005-12-08 | 2020-12-10 | Insmed Inc | Composiciones a base de lípidos de antiinfecciosos para tratar infecciones pulmonares |
| WO2007106549A2 (en) * | 2006-03-15 | 2007-09-20 | Alza Corporation | Method for treating brain cancer |
| KR20090036585A (ko) * | 2006-08-11 | 2009-04-14 | 더 크리스터스 스텔린 파운데이션 포 캔서 리서치 | 캄프토테신의 에스테르의 제조 방법 |
| US20100196455A1 (en) * | 2007-05-04 | 2010-08-05 | Transave, Inc. | Compositions of Multicationic Drugs for Reducing Interactions with Polyanionic Biomolecules and Methods of Use Thereof |
| US9333214B2 (en) | 2007-05-07 | 2016-05-10 | Insmed Incorporated | Method for treating pulmonary disorders with liposomal amikacin formulations |
| US9119783B2 (en) | 2007-05-07 | 2015-09-01 | Insmed Incorporated | Method of treating pulmonary disorders with liposomal amikacin formulations |
| US9114081B2 (en) | 2007-05-07 | 2015-08-25 | Insmed Incorporated | Methods of treating pulmonary disorders with liposomal amikacin formulations |
| US7572803B2 (en) * | 2007-10-25 | 2009-08-11 | The Christus Stehlin Foundation For Cancer Research | Hydrated crystalline esters of camptothecin |
| US8067432B2 (en) * | 2008-03-31 | 2011-11-29 | University Of Kentucky Research Foundation | Liposomal, ring-opened camptothecins with prolonged, site-specific delivery of active drug to solid tumors |
| WO2013177226A1 (en) | 2012-05-21 | 2013-11-28 | Insmed Incorporated | Systems for treating pulmonary infections |
| RU2682249C2 (ru) * | 2012-05-31 | 2019-03-18 | Терумо Кабусики Кайся | рН-ЧУВСТВИТЕЛЬНЫЙ НОСИТЕЛЬ И СПОСОБ ЕГО ПОЛУЧЕНИЯ, И рН-ЧУВСТВИТЕЛЬНОЕ ЛЕКАРСТВЕННОЕ СРЕДСТВО, И рН-ЧУВСТВИТЕЛЬНАЯ ЛЕКАРСТВЕННАЯ КОМПОЗИЦИЯ, ГДЕ КАЖДОЕ ИЗ НИХ СОДЕРЖИТ НОСИТЕЛЬ, И СПОСОБ КУЛЬТИВИРОВАНИЯ С ИХ ПРИМЕНЕНИЕМ |
| WO2014039533A2 (en) | 2012-09-04 | 2014-03-13 | Eleison Pharmaceuticals, Llc | Preventing pulmonary recurrence of cancer with lipid-complexed cisplatin |
| EP2733821A1 (en) | 2012-11-14 | 2014-05-21 | GE Energy Power Conversion Technology Ltd | A rotating electrical machine having a segmented stator |
| WO2014081887A1 (en) | 2012-11-20 | 2014-05-30 | Spectrum Pharmaceuticals | Improved method for the preparation of liposome encapsulated vincristine for therapeutic use |
| MX2015006681A (es) | 2012-11-29 | 2016-04-06 | Insmed Inc | Formulaciones de vancomicina estabilizadas. |
| ES2755941T3 (es) | 2014-05-15 | 2020-04-24 | Insmed Inc | Métodos para tratar infecciones pulmonares micobacterianas no tuberculosas |
| TWI678213B (zh) | 2015-07-22 | 2019-12-01 | 美商史倍壯製藥公司 | 用於長春新鹼硫酸鹽脂質體注射之即可使用的調配物 |
| EP3426301A4 (en) * | 2016-03-08 | 2019-11-06 | Los Gatos Pharmaceuticals, Inc. | VERBUNDNANOPARTICLES AND USES THEREOF |
| WO2019191627A1 (en) | 2018-03-30 | 2019-10-03 | Insmed Incorporated | Methods for continuous manufacture of liposomal drug products |
| WO2021172359A1 (ja) * | 2020-02-25 | 2021-09-02 | 大日本住友製薬株式会社 | Ｃｄｋ９阻害剤プロドラッグ及びそれを内封するリポソーム |
| TW202323251A (zh) * | 2021-08-23 | 2023-06-16 | 日商住友製藥股份有限公司 | 自我分解型cdk9抑制劑前藥及內封其之脂質體 |
Family Cites Families (67)
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| US3894029A (en) | 1971-08-26 | 1975-07-08 | Basf Ag | Production of camptothecin and camptothecin-like compounds |
| US4399282A (en) | 1979-07-10 | 1983-08-16 | Kabushiki Kaisha Yakult Honsha | Camptothecin derivatives |
| JPS56108787A (en) | 1980-01-31 | 1981-08-28 | Sato Yakugaku Kenkyusho:Kk | Camptothecin coline salt and its preparation |
| US4473692A (en) | 1981-09-04 | 1984-09-25 | Kabushiki Kaisha Yakult Honsha | Camptothecin derivatives and process for preparing same |
| JPS6019790A (ja) | 1983-07-14 | 1985-01-31 | Yakult Honsha Co Ltd | 新規なカンプトテシン誘導体 |
| CA1237671A (en) | 1983-08-01 | 1988-06-07 | Michael W. Fountain | Enhancement of pharmaceutical activity |
| US4663161A (en) | 1985-04-22 | 1987-05-05 | Mannino Raphael J | Liposome methods and compositions |
| US5059421A (en) | 1985-07-26 | 1991-10-22 | The Liposome Company, Inc. | Preparation of targeted liposome systems of a defined size distribution |
| US4801459A (en) | 1986-08-05 | 1989-01-31 | Liburdy Robert P | Technique for drug and chemical delivery |
| US5106742A (en) | 1987-03-31 | 1992-04-21 | Wall Monroe E | Camptothecin analogs as potent inhibitors of topoisomerase I |
| US4894456A (en) | 1987-03-31 | 1990-01-16 | Research Triangle Institute | Synthesis of camptothecin and analogs thereof |
| US5053512A (en) | 1987-04-14 | 1991-10-01 | Research Triangle Institute | Total synthesis of 20(S) and 20(R)-camptothecin and compthothecin derivatives |
| US5227380A (en) | 1987-03-31 | 1993-07-13 | Research Triangle Institute | Pharmaceutical compositions and methods employing camptothecins |
| US5180722A (en) | 1987-04-14 | 1993-01-19 | Research Triangle Institute | 10,11-methylenedioxy-20(RS)-camptothecin and 10,11-methylenedioxy-20(S)-camptothecin analogs |
| CA1332413C (en) | 1987-06-25 | 1994-10-11 | Kabushiki Kaisha Yakult Honsha | Camptothecin derivatives and process for preparing same |
| JPS6461482A (en) | 1987-08-31 | 1989-03-08 | Yakult Honsha Kk | Dehydrocamptothecin and production thereof |
| US4943579A (en) | 1987-10-06 | 1990-07-24 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Water soluble prodrugs of camptothecin |
| US5043165A (en) | 1988-12-14 | 1991-08-27 | Liposome Technology, Inc. | Novel liposome composition for sustained release of steroidal drugs |
| US5077057A (en) | 1989-04-05 | 1991-12-31 | The Regents Of The University Of California | Preparation of liposome and lipid complex compositions |
| US5549910A (en) | 1989-03-31 | 1996-08-27 | The Regents Of The University Of California | Preparation of liposome and lipid complex compositions |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5552154A (en) | 1989-11-06 | 1996-09-03 | The Stehlin Foundation For Cancer Research | Method for treating cancer with water-insoluble s-camptothecin of the closed lactone ring form and derivatives thereof |
| US5225404A (en) | 1989-11-06 | 1993-07-06 | New York University | Methods of treating colon tumors with tumor-inhibiting camptothecin compounds |
| ATE186461T1 (de) | 1990-09-28 | 1999-11-15 | Smithkline Beecham Corp | Verfahren zur herstellung wasserlöslicher camptothecinanaloge, sowie die verbindungen 10- hydroxy-11-c(1-6)-alkoxycamptothecin |
| US5122383A (en) | 1991-05-17 | 1992-06-16 | Theratech, Inc. | Sorbitan esters as skin permeation enhancers |
| US5126351A (en) | 1991-01-24 | 1992-06-30 | Glaxo Inc. | Antitumor compounds |
| KR930702984A (ko) | 1991-02-21 | 1993-11-29 | 스튜어트 알. 슈터 | 비-소세포 폐암의 치료 |
| CA2097163C (en) | 1992-06-01 | 2002-07-30 | Marianna Foldvari | Topical patch for liposomal drug delivery system |
| US5391745A (en) | 1992-07-23 | 1995-02-21 | Sloan-Kettering Institute For Cancer Research | Methods of preparation of camptothecin analogs |
| US5552156A (en) | 1992-10-23 | 1996-09-03 | Ohio State University | Liposomal and micellular stabilization of camptothecin drugs |
| FR2697752B1 (fr) | 1992-11-10 | 1995-04-14 | Rhone Poulenc Rorer Sa | Compositions antitumorales contenant des dérivés du taxane. |
| EP0602361B1 (de) | 1992-11-17 | 1997-01-22 | C. Rob. Hammerstein GmbH | Rückenlehnengelenk für einen Fahrzeugsitz |
| US5631237A (en) | 1992-12-22 | 1997-05-20 | Dzau; Victor J. | Method for producing in vivo delivery of therapeutic agents via liposomes |
| US5352789A (en) | 1993-02-25 | 1994-10-04 | The Stehlin Foundation For Cancer Research | Methods for purifying camptothecin compounds |
| US5527913A (en) | 1993-02-25 | 1996-06-18 | The Stehlin Foundation For Cancer Research | Methods for purifying camptothecin compounds |
| US5613958A (en) | 1993-05-12 | 1997-03-25 | Pp Holdings Inc. | Transdermal delivery systems for the modulated administration of drugs |
| US5880131A (en) | 1993-10-20 | 1999-03-09 | Enzon, Inc. | High molecular weight polymer-based prodrugs |
| US5840900A (en) | 1993-10-20 | 1998-11-24 | Enzon, Inc. | High molecular weight polymer-based prodrugs |
| AU683957B2 (en) | 1993-11-05 | 1997-11-27 | Amgen, Inc. | Liposome preparation and material encapsulation method |
| GB9402934D0 (en) | 1994-02-16 | 1994-04-06 | Erba Carlo Spa | Camptothecin derivatives and process for their preparation |
| GB9410388D0 (en) | 1994-05-24 | 1994-07-13 | Erba Carlo Spa | Method for the preparation of 9-amino camptothecin |
| US5786344A (en) | 1994-07-05 | 1998-07-28 | Arch Development Corporation | Camptothecin drug combinations and methods with reduced side effects |
| US5646159A (en) | 1994-07-20 | 1997-07-08 | Research Triangle Institute | Water-soluble esters of camptothecin compounds |
| US5505958A (en) | 1994-10-31 | 1996-04-09 | Algos Pharmaceutical Corporation | Transdermal drug delivery device and method for its manufacture |
| KR960029336A (ko) * | 1995-01-09 | 1996-08-17 | 김충환 | 캄토테신 유도체, 그의 제조 방법 및 이를 함유하는 항암제 |
| US5660855A (en) | 1995-02-10 | 1997-08-26 | California Institute Of Technology | Lipid constructs for targeting to vascular smooth muscle tissue |
| US5736156A (en) | 1995-03-22 | 1998-04-07 | The Ohio State University | Liposomal anf micellular stabilization of camptothecin drugs |
| US5780052A (en) | 1995-04-24 | 1998-07-14 | Northeastern University | Compositions and methods useful for inhibiting cell death and for delivering an agent into a cell |
| US5834012A (en) | 1995-05-03 | 1998-11-10 | Roman Perez-Soler | Lipid complexed topoisomerase I inhibitors |
| GB9510716D0 (en) | 1995-05-26 | 1995-07-19 | Pharmacia Spa | Substituted camptothecin derivatives and process for their preparation |
| US5726181A (en) | 1995-06-05 | 1998-03-10 | Bionumerik Pharmaceuticals, Inc. | Formulations and compositions of poorly water soluble camptothecin derivatives |
| US6214836B1 (en) * | 1995-06-06 | 2001-04-10 | Dr. Reddy's Research Foundation | Water soluble analogues of 20(S)-camptothecin |
| US5785991A (en) | 1995-06-07 | 1998-07-28 | Alza Corporation | Skin permeation enhancer compositions comprising glycerol monolaurate and lauryl acetate |
| US5643599A (en) | 1995-06-07 | 1997-07-01 | President And Fellows Of Harvard College | Intracellular delivery of macromolecules |
| WO1997001728A1 (en) * | 1995-06-29 | 1997-01-16 | Siemens Components, Inc. | Localized illumination using tir technology |
| SG50747A1 (en) | 1995-08-02 | 1998-07-20 | Tanabe Seiyaku Co | Comptothecin derivatives |
| CA2192725C (en) | 1995-12-28 | 2004-04-20 | Kenji Tsujihara | Camptothecin derivatives |
| US5731316A (en) * | 1996-01-30 | 1998-03-24 | The Stehlin Foundation For Cancer Research | Derivatives of camptothecin and methods of treating cancer using these derivatives |
| US6096336A (en) | 1996-01-30 | 2000-08-01 | The Stehlin Foundation For Cancer Research | Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs |
| US5874105A (en) | 1996-01-31 | 1999-02-23 | Collaborative Laboratories, Inc. | Lipid vesicles formed with alkylammonium fatty acid salts |
| ES2214634T3 (es) | 1996-08-19 | 2004-09-16 | Bionumerik Pharmaceuticals, Inc. | Derivados muy lipofilos de la camptotecina. |
| AU4424797A (en) | 1996-09-18 | 1998-04-14 | Dragoco Inc. | Liposome encapsulated active agent dry powder composition |
| US5827533A (en) | 1997-02-06 | 1998-10-27 | Duke University | Liposomes containing active agents aggregated with lipid surfactants |
| US5922877A (en) | 1997-08-05 | 1999-07-13 | The Stehlin Foundation For Cancer Research | Methods of preparing and purifying 9-nitro-20-camptothecin |
| US6090407A (en) | 1997-09-23 | 2000-07-18 | Research Development Foundation | Small particle liposome aerosols for delivery of anti-cancer drugs |
| US6111107A (en) | 1997-11-20 | 2000-08-29 | Enzon, Inc. | High yield method for stereoselective acylation of tertiary alcohols |
| ATE216998T1 (de) * | 1999-03-09 | 2002-05-15 | Sigma Tau Ind Farmaceuti | Camptothecin-derivate mit antitumor-wirkung |
-
2000
- 2000-02-08 US US09/499,684 patent/US6352996B1/en not_active Expired - Lifetime
- 2000-07-25 CA CA002379660A patent/CA2379660A1/en not_active Abandoned
- 2000-07-25 JP JP2001513393A patent/JP2003528808A/ja active Pending
- 2000-07-25 EP EP00952177A patent/EP1200068A2/en not_active Withdrawn
- 2000-07-25 AU AU64926/00A patent/AU6492600A/en not_active Abandoned
- 2000-07-25 WO PCT/US2000/020136 patent/WO2001008663A2/en not_active Ceased
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102161680A (zh) * | 2011-02-24 | 2011-08-24 | 湖南方盛华美医药科技有限公司 | 磷酰胺酯喜树碱衍生物以及其制备方法、药物组合物和用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2001008663A3 (en) | 2001-07-26 |
| EP1200068A2 (en) | 2002-05-02 |
| WO2001008663A2 (en) | 2001-02-08 |
| US6352996B1 (en) | 2002-03-05 |
| AU6492600A (en) | 2001-02-19 |
| JP2003528808A (ja) | 2003-09-30 |
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| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued |