WO2003039437A2 - Oral verabreichbare pharmazeutische zubereitung umfassend liposo mal verkapseltes taxol - Google Patents
Oral verabreichbare pharmazeutische zubereitung umfassend liposo mal verkapseltes taxol Download PDFInfo
- Publication number
- WO2003039437A2 WO2003039437A2 PCT/DE2002/004120 DE0204120W WO03039437A2 WO 2003039437 A2 WO2003039437 A2 WO 2003039437A2 DE 0204120 W DE0204120 W DE 0204120W WO 03039437 A2 WO03039437 A2 WO 03039437A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pharmaceutical preparation
- preparation according
- taxol
- peg
- lipid component
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
- A61K38/13—Cyclosporins
-
- 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—Liposomes
-
- 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—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Definitions
- Orally administrable pharmaceutical preparation comprising liposomally encapsulated taxol
- the invention relates to pharmaceutical preparations which are suitable for the oral use of liposomally encapsulated taxol, its derivatives and taxanes. Areas of application of the invention are medicine and the pharmaceutical industry.
- Taxol (chemical: Paclitaxel) is a natural substance found in the bark of various yew species (Taxazeen), which is derived from these barks and also by chemical synthesis [J. Amer. Chem. Soc, 1110: 5917-5919 (1988)]. Taxol requires the aggregation of the microtubules from tubulin dimers and stabilizes the microtubules by inhibiting their depolymerization. Furthermore, there is an abnormal arrangement and bundling of microtubules during the entire cell cycle, which leads to the formation of multiple microtubular dividing stars during mitosis and thus to the inhibition of the normal dynamic reorganization of the microtubular network.
- Taxol Since the vital cell function in the interphase and during mitosis is thereby decisively influenced, Taxol shows a clear antineoplastic activity against various tumors, u. a. against implanted B16 melanoma, P388 leukemia and against human breast tumors.
- the applicability of Taxol is severely limited due to its low water solubility.
- Solubilizers such as cremophor (polyethoxylated castor oil) and alcohol improve the solubility, but lead to considerable side effects when used, e.g. to anaphylactoid reactions. Nerd thinning with physiological saline for application has the disadvantage that taxol in physiological saline does not have sufficient stability (maximum 24 hours).
- a dose-limiting side effect is myelosuppression, primarily neutropenia [Semin. Oncol. 19: 646-662 (1992)]. Due to their amphiphilic character, liposomes offer the possibility to include or incorporate both water- and lipid-soluble substances.
- Taxol as an almost water-insoluble substance can be dissolved with high efficiency in the lipid phase of liposomes of suitable composition, which can be used to treat different types of tumors and localizations.
- taxol in free and liposomal form was tested for anti-tumor activity on two human glioblastomas in the nude model (12.5 mg kg / 4 days). Both forms led to a significant reduction in tumor growth [In-Nivo 6 (l): 23-7 (1992)].
- WO 93/18751 describes the encapsulation of taxol in liposomes and the use of the products obtained for the treatment of cancer. A combination of this treatment with hyperthermia is preferred.
- the Taxol liposomes produced show improved stability. From DE 44 30 593 C2, a high-pressure homogenization process for the production of liposomally encapsulated taxol is known, the liposomes having a high taxol content and high stability.
- Taxol is excellent as a cytostatic, but its use is limited to parenteral preparations. An effectiveness of Taxol when administered orally has not been established internationally. Oral application forms for liposomally encapsulated taxol are also not yet known.
- Taxol was administered in an oral dosage form as a bolus of 50 mg and the effectiveness of the agent was determined on the basis of the tumor mass (ovarian carcinoma (human) on the ⁇ ude mouse).
- B and C show the effectiveness after oral application of unencapsulated taxol (B) and unencapsulated taxol in combination with cyclosporin A, with the tumor mass hardly reducing.
- the efficacy can be deduced after oral administration of liposomally encapsulated taxol, the tumor mass being significantly reduced.
- the preferred dosage for liposomally encapsulated taxol is 1 x 50 mg / kg body weight daily.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Dispersion Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Epoxy Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2002350386A AU2002350386A1 (en) | 2001-11-08 | 2002-11-06 | Orally administered pharmaceutical preparation comprising liposomically encapsulated paclitaxel |
JP2003541531A JP2005511578A (ja) | 2001-11-08 | 2002-11-06 | リポソームに封入されたタキソールを含む経口投与用の医薬製剤 |
US10/495,039 US20050019386A1 (en) | 2001-11-08 | 2002-11-06 | Orally administered pharmaceutical preparation comprising liposomically encapsulated paclitaxel |
EP02785050A EP1443904A2 (de) | 2001-11-08 | 2002-11-06 | Oral verabreichbare pharmazeutische zubereitung umfassend liposomal verkapseltes taxol |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10154464.2 | 2001-11-08 | ||
DE10154464A DE10154464B4 (de) | 2001-11-08 | 2001-11-08 | Oral verabreichbare pharmazeutische Zubereitung umfassend liposomal verkapseltes Taxol |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2003039437A2 true WO2003039437A2 (de) | 2003-05-15 |
WO2003039437A3 WO2003039437A3 (de) | 2003-07-10 |
Family
ID=7704785
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/DE2002/004120 WO2003039437A2 (de) | 2001-11-08 | 2002-11-06 | Oral verabreichbare pharmazeutische zubereitung umfassend liposo mal verkapseltes taxol |
Country Status (6)
Country | Link |
---|---|
US (1) | US20050019386A1 (de) |
EP (1) | EP1443904A2 (de) |
JP (1) | JP2005511578A (de) |
AU (1) | AU2002350386A1 (de) |
DE (1) | DE10154464B4 (de) |
WO (1) | WO2003039437A2 (de) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6750246B1 (en) | 2000-02-03 | 2004-06-15 | Bristol-Myers Squibb Company | C-4 carbonate taxanes |
WO2006095798A1 (ja) | 2005-03-09 | 2006-09-14 | Sunstar Inc. | フィトステロールを含んだリポソームを含有する抗癌用経口組成物、該リポソームによる癌の予防又は治療 |
WO2008140203A1 (en) * | 2007-05-15 | 2008-11-20 | Korea Research Institute Of Chemical Technology | Phospholipid nanospheres for solubilization of diterpenoid alkaloid and preparation |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005002546A1 (en) * | 2003-06-27 | 2005-01-13 | Smithkline Beecham Corporation | Stabilized topotecan liposomal composition and methods |
MX2008014953A (es) * | 2006-05-26 | 2009-03-05 | Bayer Healthcare Llc | Combinaciones de medicamentos con diarilureas sustituidas para el tratamiento de cancer. |
US20090088393A1 (en) * | 2007-09-28 | 2009-04-02 | Zomanex, Llc | Methods and formulations for converting intravenous and injectable drugs into oral dosage forms |
EA022182B1 (ru) * | 2012-12-24 | 2015-11-30 | Общество С Ограниченной Ответственностью "Технология Лекарств" | Способ получения липосомальной формы доцетаксела |
JP6386676B2 (ja) * | 2015-10-02 | 2018-09-05 | 株式会社リケン | 焼結バルブシート |
CN113384705A (zh) * | 2021-06-28 | 2021-09-14 | 西南大学 | 泊洛沙姆修饰的脂质体的制备及在口服药物递送中的应用 |
KR20240047637A (ko) * | 2022-10-05 | 2024-04-12 | 한국과학기술연구원 | 탁산을 포함하는 경구 투여용 약학 조성물 및 이의 제조방법 |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994026253A1 (en) * | 1993-05-19 | 1994-11-24 | The Liposome Company, Inc. | Liposome having a multicomponent bilayer which contains a bioactive agent as an integral component of the bilayer |
US5415869A (en) * | 1993-11-12 | 1995-05-16 | The Research Foundation Of State University Of New York | Taxol formulation |
WO1997003651A1 (en) * | 1995-07-20 | 1997-02-06 | Danbiosyst Uk Limited | Lipid vehicle drug delivery composition containing vitamin e |
US5827831A (en) * | 1989-06-28 | 1998-10-27 | Nexstar Pharmaceuticals, Inc. | Lipid nucleotide analog prodrugs for oral administration |
US6090407A (en) * | 1997-09-23 | 2000-07-18 | Research Development Foundation | Small particle liposome aerosols for delivery of anti-cancer drugs |
US6153217A (en) * | 1999-01-22 | 2000-11-28 | Biodelivery Sciences, Inc. | Nanocochleate formulations, process of preparation and method of delivery of pharmaceutical agents |
WO2001012229A1 (en) * | 1999-08-17 | 2001-02-22 | Ivax-Cr A.S. | Pharmaceutical compositions for oral and topical administration |
WO2002020020A1 (en) * | 2000-09-08 | 2002-03-14 | Pharmacia Italia S.P.A. | Exemestane as chemopreventing agent |
WO2002053138A2 (en) * | 2001-01-02 | 2002-07-11 | Elisabeth Shanahan-Prendergast | Treatment for inhibiting neoplastic lesions using incensole and/or furanogermacrens |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5616688A (en) * | 1981-09-08 | 1997-04-01 | The Rockefeller University | Macrophage-derived inflammatory mediator (MIP-1α and MIP-1β) |
WO1993018751A1 (en) * | 1992-03-23 | 1993-09-30 | Georgetown University | Liposome encapsulated taxol and a method of using the same |
DE4430593C2 (de) * | 1994-08-20 | 1999-01-14 | Max Delbrueck Centrum | Verfahren zur Herstellung von Liposomal verkapseltem Taxol |
US5580899A (en) * | 1995-01-09 | 1996-12-03 | The Liposome Company, Inc. | Hydrophobic taxane derivatives |
US6106858A (en) * | 1997-09-08 | 2000-08-22 | Skyepharma, Inc. | Modulation of drug loading in multivescular liposomes |
US6146659A (en) * | 1998-07-01 | 2000-11-14 | Neopharm, Inc. | Method of administering liposomal encapsulated taxane |
US7217735B1 (en) * | 1999-04-09 | 2007-05-15 | Au Jessie L-S | Methods and compositions for enhancing delivery of therapeutic agents to tissues |
US6656504B1 (en) * | 1999-09-09 | 2003-12-02 | Elan Pharma International Ltd. | Nanoparticulate compositions comprising amorphous cyclosporine and methods of making and using such compositions |
-
2001
- 2001-11-08 DE DE10154464A patent/DE10154464B4/de not_active Expired - Fee Related
-
2002
- 2002-11-06 AU AU2002350386A patent/AU2002350386A1/en not_active Abandoned
- 2002-11-06 US US10/495,039 patent/US20050019386A1/en not_active Abandoned
- 2002-11-06 WO PCT/DE2002/004120 patent/WO2003039437A2/de active Application Filing
- 2002-11-06 EP EP02785050A patent/EP1443904A2/de not_active Withdrawn
- 2002-11-06 JP JP2003541531A patent/JP2005511578A/ja active Pending
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5827831A (en) * | 1989-06-28 | 1998-10-27 | Nexstar Pharmaceuticals, Inc. | Lipid nucleotide analog prodrugs for oral administration |
WO1994026253A1 (en) * | 1993-05-19 | 1994-11-24 | The Liposome Company, Inc. | Liposome having a multicomponent bilayer which contains a bioactive agent as an integral component of the bilayer |
US5415869A (en) * | 1993-11-12 | 1995-05-16 | The Research Foundation Of State University Of New York | Taxol formulation |
WO1997003651A1 (en) * | 1995-07-20 | 1997-02-06 | Danbiosyst Uk Limited | Lipid vehicle drug delivery composition containing vitamin e |
US6090407A (en) * | 1997-09-23 | 2000-07-18 | Research Development Foundation | Small particle liposome aerosols for delivery of anti-cancer drugs |
US6153217A (en) * | 1999-01-22 | 2000-11-28 | Biodelivery Sciences, Inc. | Nanocochleate formulations, process of preparation and method of delivery of pharmaceutical agents |
WO2001012229A1 (en) * | 1999-08-17 | 2001-02-22 | Ivax-Cr A.S. | Pharmaceutical compositions for oral and topical administration |
WO2002020020A1 (en) * | 2000-09-08 | 2002-03-14 | Pharmacia Italia S.P.A. | Exemestane as chemopreventing agent |
WO2002053138A2 (en) * | 2001-01-02 | 2002-07-11 | Elisabeth Shanahan-Prendergast | Treatment for inhibiting neoplastic lesions using incensole and/or furanogermacrens |
Non-Patent Citations (1)
Title |
---|
VAN ASPEREN J ET AL: "Enhanced oral absorption and decreased elimination of paclitaxel in mice cotreated with cyclosporin A." CLINICAL CANCER RESEARCH: AN OFFICIAL JOURNAL OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH. UNITED STATES OCT 1998, Bd. 4, Nr. 10, Oktober 1998 (1998-10), Seiten 2293-2297, XP001097687 ISSN: 1078-0432 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6750246B1 (en) | 2000-02-03 | 2004-06-15 | Bristol-Myers Squibb Company | C-4 carbonate taxanes |
WO2006095798A1 (ja) | 2005-03-09 | 2006-09-14 | Sunstar Inc. | フィトステロールを含んだリポソームを含有する抗癌用経口組成物、該リポソームによる癌の予防又は治療 |
EP1857112A1 (de) * | 2005-03-09 | 2007-11-21 | Sunstar Inc. | Mittel gegen krebs zur oralen anwendung mit liposom-haltigen phytosterolen und prävention oder behandlung von krebs mit dem liposom |
EP1857112A4 (de) * | 2005-03-09 | 2009-07-01 | Sunstar Inc | Mittel gegen krebs zur oralen anwendung mit liposom-haltigen phytosterolen und prävention oder behandlung von krebs mit dem liposom |
WO2008140203A1 (en) * | 2007-05-15 | 2008-11-20 | Korea Research Institute Of Chemical Technology | Phospholipid nanospheres for solubilization of diterpenoid alkaloid and preparation |
Also Published As
Publication number | Publication date |
---|---|
DE10154464A1 (de) | 2003-05-22 |
WO2003039437A3 (de) | 2003-07-10 |
US20050019386A1 (en) | 2005-01-27 |
JP2005511578A (ja) | 2005-04-28 |
EP1443904A2 (de) | 2004-08-11 |
DE10154464B4 (de) | 2005-10-20 |
AU2002350386A1 (en) | 2003-05-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DE4447770C2 (de) | Verfahren zur Herstellung von liposomal verkapseltem Taxol | |
DE60115045T2 (de) | Verbesserte liposomale camptothecine und deren verwendungen | |
DE60216139T3 (de) | Arylharnstoff-verbindungen in kombination mit anderen zytostatisch oder zytotoxisch wirksamen stoffen zur behandlungen menschlicher krebserkrankungen | |
US5147859A (en) | Complexes of glycerrhetinic acid with phospholipids and pharmaceutical and cosmetic compositions containing them | |
DE69531701T2 (de) | Sphingosome mit verbesserter arzneistoffabgage | |
DE69735949T2 (de) | Zusammensetzung geeignet zur behandlung der pferdelahmheit | |
US7122553B2 (en) | Liposomal formulation of irinotecan | |
DE1792410A1 (de) | Pharmakologische Komposition und Verfahren zu ihrer Herstellung | |
JP2012162577A (ja) | がん治療のための細胞増殖抑制剤及び電子受容体を含有する医薬製剤 | |
WO2003039437A2 (de) | Oral verabreichbare pharmazeutische zubereitung umfassend liposo mal verkapseltes taxol | |
EP1135193B1 (de) | Mittel zur tumortherapie auf liposomenbasis, die tamoxifen enthalten | |
DE60025494T2 (de) | Epothilon zusammensetzungen | |
DE4408011C1 (de) | Pharmazeutisches Mittel zur Tumortherapie | |
KR102068265B1 (ko) | 양파 추출물 및 리포좀을 포함하는 조성물 | |
WO2004012744A1 (de) | Anwendung von alkylphosphocholinen in kombination mit antitumormedikamenten | |
EP0470437A1 (de) | Wässriges Liposomensystem | |
DE19650778A1 (de) | Verwendung von Dopaminrezeptor-Antagonisten in der palliativen Tumortherapie | |
JP2003512313A (ja) | 6,9−ビス−[(2−アミノエチル)−アミノ]ベンゾ[g]イソキノリン−5,10−ジオンジマレエートのリポソーム製剤 | |
EP0611303B1 (de) | Carboplatin oder Lobaplatin ENTHALTENDE ZUBEREITUNGEN ZUR ANTITUMORTHERAPIE UND/ODER STIMULIERUNG DES HÄMATOPOETISCHEN SYSTEMS | |
DE60115429T2 (de) | Antikrebs-Kombinationen aus DMXAA und Paclitaxel oder Docetaxel | |
EP1534283B1 (de) | Liposomale formulierungen von phenylalanin-derivaten | |
JPH04169531A (ja) | 脂溶性白金錯体を含有するリポソーム製剤 | |
DE69928805T2 (de) | Liposomale Formulierungen von Busulfan | |
WO2009089845A1 (de) | Mittel zur intraartikulären injektion | |
Capasso | SVILUPPO, CARATTERIZZAZIONE E VALUTAZIONEDI CARRIER COLLOIDALI O MICROPARTICELLARIPER LA VEICOLAZIONE DI FARMACI |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LU MC NL PT SE SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2003541531 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2002785050 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 2002785050 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 10495039 Country of ref document: US |