EP2155189A2 - Direkte auflösung von docetaxel in einer lösung in polysorbat 80 - Google Patents

Direkte auflösung von docetaxel in einer lösung in polysorbat 80

Info

Publication number
EP2155189A2
EP2155189A2 EP08805654A EP08805654A EP2155189A2 EP 2155189 A2 EP2155189 A2 EP 2155189A2 EP 08805654 A EP08805654 A EP 08805654A EP 08805654 A EP08805654 A EP 08805654A EP 2155189 A2 EP2155189 A2 EP 2155189A2
Authority
EP
European Patent Office
Prior art keywords
docetaxel
polysorbate
solvent
solution
acetonitrile
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Withdrawn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
EP08805654A
Other languages
English (en)
French (fr)
Inventor
Jean-René Authelin
Eric Didier
Elie Fouque
Mostafa Nakach
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.)
Aventis Pharma SA
Original Assignee
Rhone Poulenc Rorer SA
Aventis Pharma SA
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=39048780&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP2155189(A2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Rhone Poulenc Rorer SA, Aventis Pharma SA filed Critical Rhone Poulenc Rorer SA
Publication of EP2155189A2 publication Critical patent/EP2155189A2/de
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
    • C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems

Definitions

  • the present invention relates to a novel process for preparing a solution of docetaxel " in polysorbate 80.
  • It relates, according to a first means of implementing the invention, more particularly the solubilization of docetaxel in an organic solvent, its mixture with polysorbate 80 and the evaporation of the solvent.
  • the ethanol used in the final formulation of the commercial composition containing docetaxel is not the only solvent usable in the context of the present invention.
  • solvents capable of solubilizing docetaxel and miscible in all proportions with polysorbate are usable. It is thus possible to use solvents having a boiling point of between 40 and 153 ° C. at atmospheric pressure, among these solvents, mention may be made of chloroalkanes and in particular dichloromethane, chloroform, amides such as dimethylformamide, dimethylacetamide, esters such ethyl acetate, ketones such as acetone, methyl isobutyl ketone, nitriles such as acetonitrile.
  • the preferred solvents are selected from acetone, acetonitrile, methylene chloride, dimethylformamide.
  • the docetaxel used as raw material in the context of the present invention may be an amorphous docetaxel or a crystallized docetaxel in any form such as an acetonate, an alcoholate, a hydrate or a crystal with acetonitrile.
  • the process according to the invention is not limited to the dissolution of docetaxel in solid form in a solvent followed by the addition of polysorbate and distillation of the solvent but may also consist in using the docetaxel solution obtained at the outlet of a purification column.
  • This solution may be a solution of docetaxel in a single solvent such as ethyl acetate, acetone, methylene chloride, or tetrahydrofuran, but may also be a solution in a mixture of the solvents mentioned above.
  • This column is usually made of a silica column but any other material for purification is usable.
  • a silica and in particular a silica sold under the trade name Lichrospher.
  • a Lichrospher silica with a particle diameter of 12 ⁇ m is most preferably used.
  • the docetaxel solution to be purified is preferably a solution of docetaxel in ethyl acetate or a mixture of ethyl acecate with a hydrocarbon such as cyclohexane, hexanes or toluene.
  • the solution from the purification column if the docetaxel content has the required purity, can be mixed directly with the polysorbate and the solvent (s) evaporated (s) without intermediate step of crystallization of docetaxel in any solvate form. This presents a considerable advantage from the economic point of view.
  • docetaxel trihydrate 4.3320 g of docetaxel trihydrate are dissolved in 37.9 g of absolute ethanol, 108.0 g of polysorbate 80 are added dropwise, and a large foam appears. It is distilled under a pressure of 50 mbar with a bath temperature of 40 ° C. After 4 hours and 10 minutes of distillation, 33.9 g of distillate and 167.8 g (to be verified) of docetaxel solution in polysorbate are obtained. containing less than 0.01% ethanol and 0.28% impurities.
  • the method consists in the deprotection (detaching) of the docetaxel diprotected in prosition 7 and 10 to give docetaxel which is isolated by crystallization in a toluene / acetonitrile mixture.
  • 90OmL of ethyl acetate, 7.8 mg of 4-methoxyphenol and 78 g of docetaxel di were charged. protected by a trichlroethoxycarbonyl group.
  • the reaction medium is stirred and then distilled under reduced pressure 12OmL of ethyl acetate. Back at 23 ° C, 37g of zinc is charged. 74 g of acetic acid are then poured while maintaining the temperature at 25 ⁇ 2 ° C.
  • docetaxel trihydrate 4.33 g of docetaxel trihydrate are dissolved in 165.4 g of dichloromethane, 108.0 g of polysorbate 80 are added dropwise. It is distilled under a pressure of 84 mbar with a bath temperature of 38 ° C. After 5 hours 5 minutes of distillation, 101.2 g of docetaxel solute are obtained in the polysorbate containing 0.11% of dichloromethane and 0.35% of impurities.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (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)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Processes Of Treating Macromolecular Substances (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Plural Heterocyclic Compounds (AREA)
EP08805654A 2007-06-08 2008-06-06 Direkte auflösung von docetaxel in einer lösung in polysorbat 80 Withdrawn EP2155189A2 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0704095A FR2917088B1 (fr) 2007-06-08 2007-06-08 Dissolution directe du docetaxel dans un solvant dans le polysorbate 80
PCT/FR2008/000766 WO2009004188A2 (fr) 2007-06-08 2008-06-06 Dissolution directe du docetaxel dans un solvant dans le poly sorbate 80

Publications (1)

Publication Number Publication Date
EP2155189A2 true EP2155189A2 (de) 2010-02-24

Family

ID=39048780

Family Applications (1)

Application Number Title Priority Date Filing Date
EP08805654A Withdrawn EP2155189A2 (de) 2007-06-08 2008-06-06 Direkte auflösung von docetaxel in einer lösung in polysorbat 80

Country Status (32)

Country Link
US (1) US20100197776A1 (de)
EP (1) EP2155189A2 (de)
JP (1) JP2010529094A (de)
KR (1) KR20100022033A (de)
CN (2) CN102908309A (de)
AR (1) AR066889A1 (de)
AU (1) AU2008270141A1 (de)
BR (1) BRPI0812438A2 (de)
CA (1) CA2689466A1 (de)
CL (1) CL2008001650A1 (de)
CO (1) CO6260063A2 (de)
CR (1) CR11144A (de)
DO (1) DOP2009000249A (de)
EA (1) EA200971137A1 (de)
EC (1) ECSP099789A (de)
FR (1) FR2917088B1 (de)
GT (1) GT200900306A (de)
HN (1) HN2009003363A (de)
IL (1) IL202517A0 (de)
MA (1) MA31671B1 (de)
MX (1) MX2009013216A (de)
MY (1) MY151417A (de)
NI (1) NI200900209A (de)
NZ (1) NZ581634A (de)
PA (1) PA8783101A1 (de)
SV (1) SV2009003428A (de)
TN (1) TN2009000396A1 (de)
TW (1) TW200916095A (de)
UA (1) UA99828C2 (de)
UY (1) UY31129A1 (de)
WO (1) WO2009004188A2 (de)
ZA (1) ZA200908662B (de)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011139899A2 (en) 2010-05-03 2011-11-10 Teikoku Pharma Usa, Inc. Non-aqueous taxane pro-emulsion formulations and methods of making and using the same
JO3685B1 (ar) 2012-10-01 2020-08-27 Teikoku Pharma Usa Inc صيغ التشتيت الجسيمي للتاكسين غير المائي وطرق استخدامها

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2678833B1 (fr) * 1991-07-08 1995-04-07 Rhone Poulenc Rorer Sa Nouvelles compositions pharmaceutiques a base de derives de la classe des taxanes.
US6040330A (en) * 1999-01-08 2000-03-21 Bionumerik Pharmaceuticals, Inc. Pharmaceutical formulations of taxanes
GB9920548D0 (en) * 1999-08-31 1999-11-03 Rhone Poulenc Rorer Sa Treatment of hepatocellular carcinoma
US20020041898A1 (en) * 2000-01-05 2002-04-11 Unger Evan C. Novel targeted delivery systems for bioactive agents
US6838569B2 (en) * 2002-12-16 2005-01-04 Dabur India Limited Process for preparation of paclitaxel trihydrate and docetaxel trihydrate
JPWO2006057429A1 (ja) * 2004-11-24 2008-06-05 ナノキャリア株式会社 ブロックコポリマーのモーフォロジーの変化方法
BRPI0600194A (pt) * 2006-01-30 2007-10-23 Quiral Quimica Do Brasil S A composições farmacêuticas contendo docetaxel e um inibidor de degradação e processo de obtenção das mesmas

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2009004188A2 *

Also Published As

Publication number Publication date
CL2008001650A1 (es) 2009-10-23
AU2008270141A1 (en) 2009-01-08
CN101677986A (zh) 2010-03-24
CO6260063A2 (es) 2011-03-22
UA99828C2 (ru) 2012-10-10
MY151417A (en) 2014-05-30
CA2689466A1 (fr) 2009-01-08
MA31671B1 (fr) 2010-09-01
UY31129A1 (es) 2009-01-30
WO2009004188A2 (fr) 2009-01-08
US20100197776A1 (en) 2010-08-05
BRPI0812438A2 (pt) 2014-12-02
PA8783101A1 (es) 2009-01-23
NZ581634A (en) 2012-05-25
ZA200908662B (en) 2011-04-28
NI200900209A (es) 2010-10-04
IL202517A0 (en) 2010-06-30
GT200900306A (es) 2011-06-17
CR11144A (es) 2010-03-23
TN2009000396A1 (fr) 2010-12-31
DOP2009000249A (es) 2009-11-30
EA200971137A1 (ru) 2010-04-30
FR2917088A1 (fr) 2008-12-12
AR066889A1 (es) 2009-09-16
WO2009004188A3 (fr) 2009-03-26
JP2010529094A (ja) 2010-08-26
CN102908309A (zh) 2013-02-06
SV2009003428A (es) 2010-02-05
FR2917088B1 (fr) 2009-09-04
ECSP099789A (es) 2010-01-29
KR20100022033A (ko) 2010-02-26
TW200916095A (en) 2009-04-16
MX2009013216A (es) 2010-01-25
HN2009003363A (es) 2013-09-18

Similar Documents

Publication Publication Date Title
FR2468577A1 (fr) Nouveaux 5z,8z,11z,14z,17z-eicosapentaenoates d'alkylphenyle, utiles notamment comme inhibiteurs de l'agglomeration des plaquettes sanguines et agents antisecretoires
EP0377381A1 (de) Verfahren zur Herstellung von 1-Phenyl-2-diethyl-aminocarbonyl-2-phthalimidomethyl-cyclopropan Z
EP0059664B1 (de) Verfahren zur Herstellung von Isosorbidmononitraten
FR2688506A1 (fr) Procede de preparation de sels de l'acide clavulanique.
WO2009004188A2 (fr) Dissolution directe du docetaxel dans un solvant dans le poly sorbate 80
CA1216283A (fr) Amino-14 steroides, leur application en therapeutique et procede pour leur preparation
FR2992641A1 (fr) Procede de preparation d'un sel de medicament anti-inflammatoire non steroidien
CA2086925C (fr) Sels derives de la dialcoylaminoalcoylsulfonyl-26 pristinamycine iib
EP0772630B1 (de) Streptograminderivate, ihre herstellung und sie enthaltende pharmazeutische zubereitungen
CH645901A5 (fr) Sel sesqui-sodique d'un diacide d'oxa-beta-lactame antibiotique.
RU2812562C1 (ru) Новый способ получения бензилдиметил[3-(миристоиламино)пропил]аммонийхлорида
FR2482602A1 (fr) Procede pour la preparation d'acide ursodesoxycholique de purete elevee
CH327513A (fr) Procédé de préparation d'un dérivé du prégnane
KR20230173317A (ko) 오라노핀의 제조방법 및 이에 의해 제조된 오라노핀
BE531443A (de)
WO2018051042A1 (fr) Nouveau procede de synthese de l'agomelatine
CN114163309A (zh) 一种多拉韦林中间体的制备方法
CN118480092A (zh) 一种伏环孢素的晶型i及其制备方法
EP1242439A1 (de) Verfahren zur herstellung und isolierung von 9-deoxo-9(z)-hydroxyiminoerythromycin a
FR2616431A1 (fr) Procede de preparation de derives de la (trans)-4-phenyl-l-proline
FR2495144A1 (fr) Nouveaux amino-benzamides, leur procede de preparation et leur application au traitement de l'hypertension
BE445966A (de)
FR2460962A1 (fr) Procede pour la purification de l'acide chenodesoxycholique
BE519389A (de)
CH598285A5 (en) Steroid 21-(4-acetamidomethylcyclohexane carboxylates)

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20100108

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA MK RS

17Q First examination report despatched

Effective date: 20120724

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20130518