CA2623117C - Novel crystal forms of irinotecan hydrochloride - Google Patents
Novel crystal forms of irinotecan hydrochloride Download PDFInfo
- Publication number
- CA2623117C CA2623117C CA2623117A CA2623117A CA2623117C CA 2623117 C CA2623117 C CA 2623117C CA 2623117 A CA2623117 A CA 2623117A CA 2623117 A CA2623117 A CA 2623117A CA 2623117 C CA2623117 C CA 2623117C
- Authority
- CA
- Canada
- Prior art keywords
- irinotecan hydrochloride
- irinotecan
- forms
- crystalline form
- hydrochloride
- 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.)
- Expired - Fee Related
Links
- 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 79
- 229960000779 irinotecan hydrochloride Drugs 0.000 title claims abstract description 40
- 239000013078 crystal Substances 0.000 title description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 28
- 238000002441 X-ray diffraction Methods 0.000 claims description 7
- 229960004768 irinotecan Drugs 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 210000001072 colon Anatomy 0.000 abstract description 7
- 208000011645 metastatic carcinoma Diseases 0.000 abstract description 7
- 206010061289 metastatic neoplasm Diseases 0.000 abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 7
- 210000000664 rectum Anatomy 0.000 abstract description 7
- 201000001275 rectum cancer Diseases 0.000 abstract description 7
- 238000000034 method Methods 0.000 abstract description 6
- 238000002360 preparation method Methods 0.000 abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- 239000000203 mixture Substances 0.000 description 15
- 239000000243 solution Substances 0.000 description 11
- 239000007787 solid Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 8
- 238000001914 filtration Methods 0.000 description 6
- 238000005464 sample preparation method Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- 229950010538 irinotecan hydrochloride trihydrate Drugs 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229940127557 pharmaceutical product Drugs 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000008355 dextrose injection Substances 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000037317 transdermal delivery Effects 0.000 description 2
- CUGZEDSDRBMZMY-UHFFFAOYSA-N trihydrate;hydrochloride Chemical compound O.O.O.Cl CUGZEDSDRBMZMY-UHFFFAOYSA-N 0.000 description 2
- QDVBKXJMLILLLB-UHFFFAOYSA-N 1,4'-bipiperidine Chemical compound C1CCCCN1C1CCNCC1 QDVBKXJMLILLLB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 1
- FJHBVJOVLFPMQE-QFIPXVFZSA-N 7-Ethyl-10-Hydroxy-Camptothecin Chemical compound C1=C(O)C=C2C(CC)=C(CN3C(C4=C([C@@](C(=O)OC4)(O)CC)C=C33)=O)C3=NC2=C1 FJHBVJOVLFPMQE-QFIPXVFZSA-N 0.000 description 1
- 241000759905 Camptotheca acuminata Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 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
- 238000004440 column chromatography Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000009093 first-line therapy Methods 0.000 description 1
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 1
- 235000008191 folinic acid Nutrition 0.000 description 1
- 239000011672 folinic acid Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960001691 leucovorin Drugs 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000012956 testing procedure Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US71882705P | 2005-09-20 | 2005-09-20 | |
| US60/718,827 | 2005-09-20 | ||
| PCT/US2006/036437 WO2007035709A2 (en) | 2005-09-20 | 2006-09-19 | Novel crystal forms of irinotecan hydrochloride |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2623117A1 CA2623117A1 (en) | 2007-03-29 |
| CA2623117C true CA2623117C (en) | 2013-12-10 |
Family
ID=37889452
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2623117A Expired - Fee Related CA2623117C (en) | 2005-09-20 | 2006-09-19 | Novel crystal forms of irinotecan hydrochloride |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US7435818B2 (enExample) |
| EP (2) | EP2082741A1 (enExample) |
| JP (1) | JP5119153B2 (enExample) |
| KR (1) | KR101150504B1 (enExample) |
| CN (1) | CN101277694B (enExample) |
| AR (1) | AR056082A1 (enExample) |
| AT (1) | ATE460162T1 (enExample) |
| AU (1) | AU2006292328B2 (enExample) |
| BR (1) | BRPI0616308A2 (enExample) |
| CA (1) | CA2623117C (enExample) |
| DE (1) | DE602006012871D1 (enExample) |
| ES (1) | ES2343204T3 (enExample) |
| NZ (1) | NZ566807A (enExample) |
| WO (1) | WO2007035709A2 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101318964B (zh) * | 2007-06-07 | 2010-12-15 | 上海迪赛诺医药发展有限公司 | 盐酸伊立替康新晶型及其制备方法 |
| US7572803B2 (en) * | 2007-10-25 | 2009-08-11 | The Christus Stehlin Foundation For Cancer Research | Hydrated crystalline esters of camptothecin |
| IT1391757B1 (it) * | 2008-11-11 | 2012-01-27 | Antibioticos Spa | Irinotecan cloridrato cristallino e metodi per la sua preparazione |
| US8546573B2 (en) | 2009-11-18 | 2013-10-01 | Cadila Healthcare Limited | Process for the preparation of 7-ethyl-10-[4-(1-piperidino)-1-piperdino] carbonyloxy-camptothecin hydrochloride trihydrate |
| WO2012007952A1 (en) * | 2010-07-12 | 2012-01-19 | Hetero Research Foundation | Novel polymorph of irinotecan hydrochloride |
| 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 |
| CN102617584B (zh) * | 2012-03-14 | 2013-10-16 | 海南锦瑞制药股份有限公司 | 一种盐酸伊立替康化合物及其药物组合物 |
| CN102850363B (zh) * | 2012-09-18 | 2013-07-10 | 山东罗欣药业股份有限公司 | 盐酸伊立替康化合物及其药物组合物 |
| CA2909642A1 (en) * | 2013-04-15 | 2014-10-23 | Regeneron Pharmaceuticals, Inc. | Markers of tumor cell response to anti-cancer therapy |
| CN105713004A (zh) * | 2016-03-23 | 2016-06-29 | 杭州华东医药集团新药研究院有限公司 | 一种高品质盐酸伊立替康三水合物晶型的制备方法 |
| US10919905B2 (en) * | 2019-05-16 | 2021-02-16 | Scinopharm Taiwan, Ltd. | Polymorphism for irinotecan free base |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6019790A (ja) | 1983-07-14 | 1985-01-31 | Yakult Honsha Co Ltd | 新規なカンプトテシン誘導体 |
| MA24682A1 (fr) * | 1997-10-23 | 1999-07-01 | Smithkline Beecham Corp | Formes polymorphes nouvelles de cipamfylline, procede pour leur preparation et compositions les contenant |
| AU2930501A (en) * | 2000-01-07 | 2001-07-24 | Transform Pharmaceuticals, Inc. | High-throughput formation, identification, and analysis of diverse solid-forms |
| DE60314378T2 (de) * | 2002-03-01 | 2008-02-28 | Pfizer Italia S.R.L. | Kristalline polymorphe form von irinotecanhydrochlorid |
| CZ20022250A3 (cs) * | 2002-06-27 | 2004-02-18 | Pliva-Lachema A. S. | Způsob výroby irinotekanu |
| KR101095382B1 (ko) | 2003-02-25 | 2011-12-16 | 가부시키가이샤 야쿠르트 혼샤 | 이리노테칸 염산염의 결정다형의 제조방법 |
| WO2006016203A1 (en) * | 2004-08-09 | 2006-02-16 | Shilpa Medicare Limited | An improved process for the preparation of irinotecan hydrochloride trihydrate |
| US20060046993A1 (en) * | 2004-09-01 | 2006-03-02 | Pharmacia Italia S.P.A. | Crystalline polymorphic form of irinotecan hydrochloride |
| EP1846412B1 (en) * | 2005-02-07 | 2009-10-21 | Fermion Oy | Process for the manufacturing of 7-ethyl-10-hydroxy camptothecin |
| JP5133704B2 (ja) * | 2005-02-08 | 2013-01-30 | フェルミオン オサケ ユキチュア | 製造方法 |
-
2006
- 2006-09-19 WO PCT/US2006/036437 patent/WO2007035709A2/en not_active Ceased
- 2006-09-19 EP EP09155420A patent/EP2082741A1/en not_active Withdrawn
- 2006-09-19 CA CA2623117A patent/CA2623117C/en not_active Expired - Fee Related
- 2006-09-19 CN CN2006800345941A patent/CN101277694B/zh not_active Expired - Fee Related
- 2006-09-19 NZ NZ566807A patent/NZ566807A/en unknown
- 2006-09-19 US US11/523,367 patent/US7435818B2/en not_active Expired - Fee Related
- 2006-09-19 ES ES06803842T patent/ES2343204T3/es active Active
- 2006-09-19 AU AU2006292328A patent/AU2006292328B2/en not_active Ceased
- 2006-09-19 DE DE602006012871T patent/DE602006012871D1/de active Active
- 2006-09-19 KR KR1020087009534A patent/KR101150504B1/ko not_active Expired - Fee Related
- 2006-09-19 JP JP2008531427A patent/JP5119153B2/ja not_active Expired - Fee Related
- 2006-09-19 BR BRPI0616308-4A patent/BRPI0616308A2/pt not_active IP Right Cessation
- 2006-09-19 EP EP06803842A patent/EP1951235B1/en not_active Not-in-force
- 2006-09-19 AT AT06803842T patent/ATE460162T1/de not_active IP Right Cessation
- 2006-09-21 AR ARP060104123A patent/AR056082A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN101277694A (zh) | 2008-10-01 |
| EP1951235B1 (en) | 2010-03-10 |
| EP2082741A1 (en) | 2009-07-29 |
| BRPI0616308A2 (pt) | 2011-06-14 |
| ES2343204T3 (es) | 2010-07-26 |
| AU2006292328A1 (en) | 2007-03-29 |
| CA2623117A1 (en) | 2007-03-29 |
| CN101277694B (zh) | 2011-04-20 |
| JP2009508874A (ja) | 2009-03-05 |
| NZ566807A (en) | 2011-05-27 |
| JP5119153B2 (ja) | 2013-01-16 |
| WO2007035709A2 (en) | 2007-03-29 |
| US20070072890A1 (en) | 2007-03-29 |
| KR20080059244A (ko) | 2008-06-26 |
| AU2006292328B2 (en) | 2012-12-20 |
| EP1951235A4 (en) | 2008-10-29 |
| WO2007035709A3 (en) | 2007-10-25 |
| AR056082A1 (es) | 2007-09-19 |
| EP1951235A2 (en) | 2008-08-06 |
| ATE460162T1 (de) | 2010-03-15 |
| US7435818B2 (en) | 2008-10-14 |
| DE602006012871D1 (de) | 2010-04-22 |
| KR101150504B1 (ko) | 2012-07-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20220322 |
|
| MKLA | Lapsed |
Effective date: 20200921 |