WO2008148260A1 - Nouvelle forme cristalline d'hydrochlorure d'irinotécan et sa préparation - Google Patents

Nouvelle forme cristalline d'hydrochlorure d'irinotécan et sa préparation Download PDF

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Publication number
WO2008148260A1
WO2008148260A1 PCT/CN2007/003071 CN2007003071W WO2008148260A1 WO 2008148260 A1 WO2008148260 A1 WO 2008148260A1 CN 2007003071 W CN2007003071 W CN 2007003071W WO 2008148260 A1 WO2008148260 A1 WO 2008148260A1
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WO
WIPO (PCT)
Prior art keywords
irinotecan hydrochloride
crystal
ketone solvent
raw material
temperature
Prior art date
Application number
PCT/CN2007/003071
Other languages
English (en)
Chinese (zh)
Inventor
Jinliang Li
Original Assignee
Shanghai Desano Pharmaceutical Holding Co., Ltd.
Shanghai Desano Chemical Pharmaceutical Co., Ltd.
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 Shanghai Desano Pharmaceutical Holding Co., Ltd., Shanghai Desano Chemical Pharmaceutical Co., Ltd. filed Critical Shanghai Desano Pharmaceutical Holding Co., Ltd.
Publication of WO2008148260A1 publication Critical patent/WO2008148260A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to a novel crystalline form of irinotecan hydrochloride; in addition, the present invention also relates to a process for the preparation of the crystalline form. Background technique
  • Irinotecan is a camptothecin derivative jointly developed by Daiichi Seiyaku and Yakult Honsha in Japan. Since its initial market in Japan in 1994, it has attracted worldwide attention as an effective drug for metastatic colorectal cancer. Considering the water solubility problem, it is clinically used in the form of its hydrochloride salt (the trade name of irinotecan hydrochloride is Kaptor ® ), and the structural formula is as follows -
  • WO03074527 discloses a c-type crystal. Its 2 eigenvalue peaks and the corresponding intensity (%) are shown in Table II:
  • a first aspect of the present invention is to provide a novel irinotecan hydrochloride crystal form to overcome the above-mentioned drawbacks of the prior art.
  • the second aspect of the technical problem to be solved by the present invention is to provide a method for preparing the above irinotecan hydrochloride crystal form.
  • the crystal is at (2 ⁇ ) 7.836 under powder X-ray diffraction. , 9.965. , 11.264°, 14.128°, 14.813°, 15.609°, 20.001°, 21.312°, 22.202°, 22.685° have characteristic peaks.
  • the DSC plot shows that there is a large endothermic peak between about 50 and 150 ° C corresponding to the loss of crystallization.
  • Onset temperature is 119.6 ° C; between 200 220 ° C and 260 ⁇ 290 ° C there are two small exothermic peaks corresponding to the crystal transformation process, Onset temperature is 205.7 and 287.5 ° C ; a large endothermic peak between 3 ⁇ 4 300 ⁇ 340 °C corresponds to the process of sample decomposition, Onset temperature is 314.5 °C;
  • the Karl Fischer moisture meter measures the moisture content between 7.9 and 8.5% and should be trihydrate.
  • a method for preparing a novel crystalline form of irinotecan hydrochloride as a second aspect of the present invention which comprises the following
  • the raw material irinotecan hydrochloride (calculated as anhydrate): water: the ratio of the ketone solvent is 1: 5 to 15: 15 to 30 (g / ml / ml), wherein preferably 1: 9 ⁇ 12:18 ⁇ 22 (g/ml/ml).
  • the raw material irinotecan hydrochloride is an amorphous powder or a b-type crystal.
  • the ketone solvent is one of acetone, butanone, butanone or pentanone, of which acetone is preferred.
  • the dissolution temperature in the above step 1) is preferably 75 to 80 °C.
  • the temperature at which the ketone solvent is added in the above step 2) is preferably 20 to 22 °C.
  • the crystallization temperature in the above step 3) is preferably 4 to 6 ° C; the crystallization time is 8 to 16 hours, preferably 11 to 13 hours.
  • irinotecan hydrochloride (amorphous or b-type crystal) can be prepared by referring to J. Org. Chem., 1997, 62, 6588-97.
  • the novel crystalline form of irinotecan hydrochloride provided by the invention has high solubility in water and good storage stability.
  • the product obtained by the method for preparing irinotecan hydrochloride crystal provided by the invention has high purity and high content and less impurities.
  • the HPLC test method can be carried out by the method in the national drug standard.
  • Figure 1 is an X-ray diffraction pattern of irinotecan hydrochloride powder of the present invention
  • Figure 2 is a DSC chart of irinotecan hydrochloride of the present invention. detailed description
  • the crystal powder X-ray diffraction spectrum shows: (2 ⁇ ) 7.84°, 9.96°, 11.26°, 14.13°, 14.81°, 15.61°, 20.00°, 21.31. , 22.20°, 22.68° with characteristic peaks.
  • the DSC spectrum of the crystal shows that there is a large endothermic peak between about 50 and 150 ° C corresponding to the process of losing crystal water, and the Onset temperature is 119.6 ° C; at about 200 °
  • Onset temperature is 205.7 ° C and 287.5 ° C; between about 300 ⁇ 340 ° C a larger one
  • the endothermic peak corresponds to the process of sample decomposition, and the Onset temperature is 314.5° ( .

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

L'invention concerne une nouvelle forme cristalline d'hydrochlorure d'Irinotécan qui présente des crêtes (2θ) à 7.80°, 9.96°,13.28°,15.62°, 19.98°, 20.36°, 22.34°, 22.66°, 26.60°, 30.18° dans la diffraction des rayons X sur poudre. L'invention concerne également un procédé de préparation de la nouvelle forme cristalline de l'hydrochlorure d'Irinotécan. L'hydrochlorure d'Irinotécan obtenu selon le procédé de l'invention présente une bonne solubilité dans l'eau, une excellente stabilité au stockage, une teneur élevée et une haute pureté, et moins de contaminants.
PCT/CN2007/003071 2007-06-07 2007-10-29 Nouvelle forme cristalline d'hydrochlorure d'irinotécan et sa préparation WO2008148260A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN200710041738.2 2007-06-07
CN2007100417382A CN101318964B (zh) 2007-06-07 2007-06-07 盐酸伊立替康新晶型及其制备方法

Publications (1)

Publication Number Publication Date
WO2008148260A1 true WO2008148260A1 (fr) 2008-12-11

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2007/003071 WO2008148260A1 (fr) 2007-06-07 2007-10-29 Nouvelle forme cristalline d'hydrochlorure d'irinotécan et sa préparation

Country Status (2)

Country Link
CN (1) CN101318964B (fr)
WO (1) WO2008148260A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2341046A2 (fr) 2009-11-18 2011-07-06 Cadila Healthcare Limited Procédé pour la préparation d'hydrochlorure de 7-éthyl-10-[4-(1-pipéridino)-1-pipéridino] carbonyloxy-camptothécine trihydrate

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101659667B (zh) * 2009-09-07 2011-11-02 重庆泰濠制药有限公司 一种盐酸伊立替康的纯化方法
CN102311443B (zh) * 2011-08-24 2014-07-16 上海北卡医药技术有限公司 盐酸伊立替康的新晶型及其制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003074527A1 (fr) * 2002-03-01 2003-09-12 Pharmacia Italia S.P.A. Forme polymorphique cristalline de chlorhydrate d'irinotecan
WO2004076460A1 (fr) * 2003-02-25 2004-09-10 Kabushiki Kaisha Yakult Honsha Procede de preparation d'un polymorphisme de chlorhydrate d'irinotecane
WO2007035709A2 (fr) * 2005-09-20 2007-03-29 Scinopharm Singapore Pte, Ltd. Nouvelles formes cristallines de chlorhydrate d'irinotecan

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003074527A1 (fr) * 2002-03-01 2003-09-12 Pharmacia Italia S.P.A. Forme polymorphique cristalline de chlorhydrate d'irinotecan
WO2004076460A1 (fr) * 2003-02-25 2004-09-10 Kabushiki Kaisha Yakult Honsha Procede de preparation d'un polymorphisme de chlorhydrate d'irinotecane
WO2007035709A2 (fr) * 2005-09-20 2007-03-29 Scinopharm Singapore Pte, Ltd. Nouvelles formes cristallines de chlorhydrate d'irinotecan

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2341046A2 (fr) 2009-11-18 2011-07-06 Cadila Healthcare Limited Procédé pour la préparation d'hydrochlorure de 7-éthyl-10-[4-(1-pipéridino)-1-pipéridino] carbonyloxy-camptothécine trihydrate
EP2399908A1 (fr) 2009-11-18 2011-12-28 Cadila Healthcare Limited Forme polymorphe de la 7-éthyl-10[4-(1-pipéridino)-1- pipéridino]carbonyloxy- camptothécine et son utilisation
EP2399919A1 (fr) 2009-11-18 2011-12-28 Cadila Healthcare Limited (S)-4,11-diéthyl-3,14-dioxo-3,4,12,14-tétrahydro-1H-pyrano [3',4':6,7] indolizino [1.2-b]quinoline-4,9-diyl bis([1,4'-bipipéridine]-carboxylate et son utilisation
EP2399907A1 (fr) 2009-11-18 2011-12-28 Cadila Healthcare Limited Forme solide de chlorure de [1,4']-bipipéridinyl-1'-carbonyle

Also Published As

Publication number Publication date
CN101318964A (zh) 2008-12-10
CN101318964B (zh) 2010-12-15

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