EP1443904A2 - Preparation pharmaceutique d'administration orale contenant du paclitaxel encapsule dans des liposomes - Google Patents

Preparation pharmaceutique d'administration orale contenant du paclitaxel encapsule dans des liposomes

Info

Publication number
EP1443904A2
EP1443904A2 EP02785050A EP02785050A EP1443904A2 EP 1443904 A2 EP1443904 A2 EP 1443904A2 EP 02785050 A EP02785050 A EP 02785050A EP 02785050 A EP02785050 A EP 02785050A EP 1443904 A2 EP1443904 A2 EP 1443904A2
Authority
EP
European Patent Office
Prior art keywords
pharmaceutical preparation
preparation according
taxol
peg
lipid component
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.)
Withdrawn
Application number
EP02785050A
Other languages
German (de)
English (en)
Inventor
Regina Reszka
Iduna Fichtner
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Max Delbrueck Centrum fuer Molekulare in der Helmholtz Gemeinschaft
Original Assignee
Max Delbrueck Centrum fuer Molekulare in der Helmholtz Gemeinschaft
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Max Delbrueck Centrum fuer Molekulare in der Helmholtz Gemeinschaft filed Critical Max Delbrueck Centrum fuer Molekulare in der Helmholtz Gemeinschaft
Publication of EP1443904A2 publication Critical patent/EP1443904A2/fr
Withdrawn legal-status Critical Current

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)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Dispersion Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (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

L'invention concerne des préparations pharmaceutiques qui conviennent à l'utilisation par voie orale de paclitaxel encapsulé dans des liposomes, ses dérivés et le taxane. De préférence, ils contiennent également au moins un immuno-modulateur, de préférence, de la cyclosporine, et/ou au moins la cytokine, de préférence, la cytokine PEG.
EP02785050A 2001-11-08 2002-11-06 Preparation pharmaceutique d'administration orale contenant du paclitaxel encapsule dans des liposomes Withdrawn EP1443904A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10154464 2001-11-08
DE10154464A DE10154464B4 (de) 2001-11-08 2001-11-08 Oral verabreichbare pharmazeutische Zubereitung umfassend liposomal verkapseltes Taxol
PCT/DE2002/004120 WO2003039437A2 (fr) 2001-11-08 2002-11-06 Preparation pharmaceutique d'administration orale contenant du paclitaxel encapsule dans des liposomes

Publications (1)

Publication Number Publication Date
EP1443904A2 true EP1443904A2 (fr) 2004-08-11

Family

ID=7704785

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02785050A Withdrawn EP1443904A2 (fr) 2001-11-08 2002-11-06 Preparation pharmaceutique d'administration orale contenant du paclitaxel encapsule dans des liposomes

Country Status (6)

Country Link
US (1) US20050019386A1 (fr)
EP (1) EP1443904A2 (fr)
JP (1) JP2005511578A (fr)
AU (1) AU2002350386A1 (fr)
DE (1) DE10154464B4 (fr)
WO (1) WO2003039437A2 (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6750246B1 (en) 2000-02-03 2004-06-15 Bristol-Myers Squibb Company C-4 carbonate taxanes
WO2005002546A1 (fr) * 2003-06-27 2005-01-13 Smithkline Beecham Corporation Compositions liposomales stabilisee de topotecane et procedes
US20080102111A1 (en) * 2005-03-09 2008-05-01 Hiromichi Imanaka Anticancer Composition for Oral Use Comprising Liposome Containing Phytosterols and Prevention or Treatment for Cancer Using the Liposome
MX2008014953A (es) * 2006-05-26 2009-03-05 Bayer Healthcare Llc Combinaciones de medicamentos con diarilureas sustituidas para el tratamiento de cancer.
KR20080101056A (ko) * 2007-05-15 2008-11-21 한국화학연구원 지질나노입자를 포함하는 디테르페노이드 알칼로이드계약물 용액 및 이의 제조방법
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

Family Cites Families (17)

* Cited by examiner, † Cited by third party
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)
US5411947A (en) * 1989-06-28 1995-05-02 Vestar, Inc. Method of converting a drug to an orally available form by covalently bonding a lipid to the drug
WO1993018751A1 (fr) * 1992-03-23 1993-09-30 Georgetown University Taxol encapsule dans des liposomes et son procede d'utilisation
WO1994026253A1 (fr) * 1993-05-19 1994-11-24 The Liposome Company, Inc. Liposome ayant une couche a composants multiples qui contient un agent bioactif en tant que composants integres dans la bicouche
US5415869A (en) * 1993-11-12 1995-05-16 The Research Foundation Of State University Of New York Taxol formulation
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
GB9514878D0 (en) * 1995-07-20 1995-09-20 Danbiosyst Uk Vitamin E as a solubilizer for drugs contained in lipid vehicles
US6106858A (en) * 1997-09-08 2000-08-22 Skyepharma, Inc. Modulation of drug loading in multivescular liposomes
US6090407A (en) * 1997-09-23 2000-07-18 Research Development Foundation Small particle liposome aerosols for delivery of anti-cancer drugs
US6146659A (en) * 1998-07-01 2000-11-14 Neopharm, Inc. Method of administering liposomal encapsulated taxane
US6153217A (en) * 1999-01-22 2000-11-28 Biodelivery Sciences, Inc. Nanocochleate formulations, process of preparation and method of delivery of pharmaceutical agents
US7217735B1 (en) * 1999-04-09 2007-05-15 Au Jessie L-S Methods and compositions for enhancing delivery of therapeutic agents to tissues
GB2355656B (en) * 1999-08-17 2004-04-07 Galena As Pharmaceutical compositions for oral and topical administration
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
AU2001289865B2 (en) * 2000-09-08 2007-03-01 Pharmacia Italia S.P.A. Exemestane as chemopreventing agent
US20040092583A1 (en) * 2001-01-02 2004-05-13 Elizabeth Shanahan-Prendergast Treatment for inhibiting neoplastic lesions

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO03039437A2 *

Also Published As

Publication number Publication date
DE10154464A1 (de) 2003-05-22
WO2003039437A2 (fr) 2003-05-15
WO2003039437A3 (fr) 2003-07-10
US20050019386A1 (en) 2005-01-27
JP2005511578A (ja) 2005-04-28
DE10154464B4 (de) 2005-10-20
AU2002350386A1 (en) 2003-05-19

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