WO2008148260A1 - Nouvelle forme cristalline d'hydrochlorure d'irinotécan et sa préparation - Google Patents
Nouvelle forme cristalline d'hydrochlorure d'irinotécan et sa préparation Download PDFInfo
- 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
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- irinotecan hydrochloride
- crystal
- ketone solvent
- raw material
- temperature
- Prior art date
Links
- 239000013078 crystal Substances 0.000 title claims abstract description 41
- GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 title claims abstract description 34
- 229960000779 irinotecan hydrochloride Drugs 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title description 5
- 238000000034 method Methods 0.000 claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 20
- 239000002994 raw material Substances 0.000 claims description 13
- 150000002576 ketones Chemical class 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- 238000002425 crystallisation Methods 0.000 claims description 9
- 230000008025 crystallization Effects 0.000 claims description 9
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 8
- 238000004090 dissolution Methods 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 2
- XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims 2
- 239000000356 contaminant Substances 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 206010052358 Colorectal cancer metastatic Diseases 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical class C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 229950010538 irinotecan hydrochloride trihydrate Drugs 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- 235000020138 yakult Nutrition 0.000 description 1
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° ( .
Landscapes
- 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)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (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.
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
ID=40093140
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)
| 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)
| 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)
| 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 |
-
2007
- 2007-06-07 CN CN2007100417382A patent/CN101318964B/zh active Active
- 2007-10-29 WO PCT/CN2007/003071 patent/WO2008148260A1/fr active Application Filing
Patent Citations (3)
| 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)
| 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 |
| EP2399907A1 (fr) | 2009-11-18 | 2011-12-28 | Cadila Healthcare Limited | Forme solide de chlorure de [1,4']-bipipéridinyl-1'-carbonyle |
| 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 |
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101318964A (zh) | 2008-12-10 |
| CN101318964B (zh) | 2010-12-15 |
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