HRP20110418T1 - Kristalizacija čvrstih oblika adicijskih soli klopidogrela - Google Patents
Kristalizacija čvrstih oblika adicijskih soli klopidogrela Download PDFInfo
- Publication number
- HRP20110418T1 HRP20110418T1 HR20110418T HRP20110418T HRP20110418T1 HR P20110418 T1 HRP20110418 T1 HR P20110418T1 HR 20110418 T HR20110418 T HR 20110418T HR P20110418 T HRP20110418 T HR P20110418T HR P20110418 T1 HRP20110418 T1 HR P20110418T1
- Authority
- HR
- Croatia
- Prior art keywords
- clopidogrel
- solvent
- hydrogensulfate
- hydrogen sulfate
- solution
- Prior art date
Links
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 title claims abstract 9
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 title claims abstract 8
- 229960003009 clopidogrel Drugs 0.000 title claims abstract 8
- 238000002425 crystallisation Methods 0.000 title claims 3
- 150000003839 salts Chemical class 0.000 title 1
- 239000007787 solid Substances 0.000 title 1
- 229950010477 clopidogrel hydrogen sulphate Drugs 0.000 claims abstract 19
- FDEODCTUSIWGLK-UHFFFAOYSA-N hydrogen sulfate;hydron;methyl 2-(2-chlorophenyl)-2-(6,7-dihydro-4h-thieno[3,2-c]pyridin-5-yl)acetate Chemical compound OS(O)(=O)=O.C1CC=2SC=CC=2CN1C(C(=O)OC)C1=CC=CC=C1Cl FDEODCTUSIWGLK-UHFFFAOYSA-N 0.000 claims abstract 19
- 238000000034 method Methods 0.000 claims abstract 19
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims abstract 3
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims abstract 3
- IVNFTPCOZIGNAE-UHFFFAOYSA-N propan-2-yl hydrogen sulfate Chemical compound CC(C)OS(O)(=O)=O IVNFTPCOZIGNAE-UHFFFAOYSA-N 0.000 claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims abstract 2
- 239000002904 solvent Substances 0.000 claims 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 2
- 230000008025 crystallization Effects 0.000 claims 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 230000009102 absorption Effects 0.000 claims 1
- 238000010521 absorption reaction Methods 0.000 claims 1
- 150000001735 carboxylic acids Chemical class 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims 1
- 238000002329 infrared spectrum Methods 0.000 claims 1
- 239000000543 intermediate Substances 0.000 claims 1
- 239000013067 intermediate product Substances 0.000 claims 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims 1
- 229940011051 isopropyl acetate Drugs 0.000 claims 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims 1
- 239000003960 organic solvent Substances 0.000 claims 1
- 238000000634 powder X-ray diffraction Methods 0.000 claims 1
- 239000011877 solvent mixture Substances 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Compounds Of Unknown Constitution (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Glass Compositions (AREA)
- Liquid Crystal Substances (AREA)
- Cephalosporin Compounds (AREA)
- Peptides Or Proteins (AREA)
Abstract
Postupak dobivanja kristaliziranog oblika 1 hidrogensulfata klopidogrela iz otopine hidrogensulfata klopidogrela u otapalu, naznačen time što navedeno otapalo je (a) cikloheksanon, etil-acetat ili izopropil-acetat, ili (b) smjesa otapala (a) s u najmanju ruku još jednim drugim otapalom, gdje drugo otapalo u smjesi (b) se bira iz skupine koju čine metanol, etanol, acetonitril i karboksilne kiseline, gdje oblik 1 hidrogensulfat klopidogrela je kristalni oblik klopidogrel-hidrogensulfata čiji difraktogram rendgenskih zraka na prahu pokazuje karakteristične signale, izražene kao interplanarni razmaci od otprilike 9,60; 3,49; 3,83; 3,80; 4,31; 8,13; 4,80; 3,86; 5,80 i 4,95 × 10-10 m, a čiji infracrveni spektar pokazuje karakteristične apsorpcije izražene u cm-1 na 2987, 1753, 1222, 1175 i 841. Patent sadrži još 13 patentnih zahtjeva.
Claims (14)
1. Postupak dobivanja kristaliziranog oblika 1 hidrogensulfata klopidogrela iz otopine hidrogensulfata klopidogrela u otapalu, naznačen time što navedeno otapalo je
(a) cikloheksanon, etil-acetat ili izopropil-acetat, ili
(b) smjesa otapala (a) s u najmanju ruku još jednim drugim otapalom, gdje drugo otapalo u smjesi (b) se bira iz skupine koju čine metanol, etanol, acetonitril i karboksilne kiseline,
gdje oblik 1 hidrogensulfat klopidogrela je kristalni oblik klopidogrel-hidrogensulfata čiji difraktogram rendgenskih zraka na prahu pokazuje karakteristične signale, izražene kao interplanarni razmaci od otprilike 9,60; 3,49; 3,83; 3,80; 4,31; 8,13; 4,80; 3,86; 5,80 i 4,95 × 10–10 m, a čiji infracrveni spektar pokazuje karakteristične apsorpcije izražene u cm–1 na 2987, 1753, 1222, 1175 i 841.
2. Postupak u skladu s patentnim zahtjevom 1, naznačen time što otopina hidrogensulfata klopidogrela se dobiva miješanjem metil-(+)-(S)-α-(o-klorfenil)-6,7-dihidrotieno[3,2-c]piridin-5(4H)-acetata u otapalu sa sumpornom kiselinom.
3. Postupak dobivanja klopidogrel-hidrogensulfata u skladu s bilo kojim od patentnih zahtjeva 1 ili 2, naznačen time što otapalo (a) ili smjesa otapala (b) sadrži najviše 1 %, težinski, vode.
4. Postupak u skladu s patentnim zahtjevom 2 ili 3, naznačen time što miješanje se provodi na temperaturi otapala od 0 do 50 °C, po mogućnosti 22 do 35 °C, poželjnije 24 do 30 °C.
5. Postupak u skladu s patentnim zahtjevom 3, naznačen time što otopinu hidrogensulfata klopidogrela se dobiva otapanjem hidrogensulfata klopidogrela u otapalu.
6. Postupak u skladu s patentnim zahtjevom 5, naznačen time što amorfni hidrogensulfat klopidogrela se otapa u otapalu.
7. Postupak u skladu s bilo kojim od patentnih zahtjeva 3 do 6, naznačen time što otapalo ili otopina sadrži najviše 0,5 %, težinski, po mogućnosti najviše 0,2 %, težinski, vode.
8. Postupak u skladu s patentnim zahtjevom 3, naznačen time što se sastoji u koracima
(1) dobivanja amorfnog klopidogrel-hidrogensulfata, te
(2) prevođenja amorfnog klopidogrel-hidrogensulfata u oblik 1 klopidogrel-hidrogensulfata.
9. Postupak u skladu s patentnim zahtjevom 8, naznačen time što u koraku (1) amorfni klopidogrel-hidrogensulfat se dobiva postupkom u kojem
(a) hidrogensulfat klopidogrela se otapa u organskom otapalu koje se miješa s vodom
(b) dobivenu otopinu se razrjeđuje vodom, te
(c) razrjeđenu otopinu se suši raspršivanjem ili liofilizira.
10. Postupak u skladu s patentnim zahtjevom 8 ili 9, naznačen time što u koraku (2) amorfni klopidogrel-hidrogensulfat je converted u oblik 1 klopidogrel-hidrogensulfata postupkom u skladu s bilo kojim od patentnih zahtjeva 5 do 7.
11. Upotreba 2-propilsulfata klopidogrela sljedeće formule
[image]
ili perklorata klopidogrela sljedeće formule
[image]
naznačena time što se navedene spojeve upotrebljava kao međuprodukte u dobivanju oblika 1 klopidogrel-hidrogensulfata.
12. Upotreba u skladu s patentnim zahtjevom 11, naznačena time što kristalizaciju se provodi postupkom u skladu s bilo kojim od patentnih zahtjeva 1 do 7.
13. Postupak dobivanja oblika 1 klopidogrel-hidrogensulfata, naznačen time što 2-propilsulfat klopidogrela sljedeće formule
[image]
ili perklorat klopidogrela sljedeće formule
[image]
se upotrebljava kao međuprodukt.
14. Postupak u skladu s patentnim zahtjevom 13, naznačen time što kristalizaciju se provodi postupkom u skladu s bilo kojim od patentnih zahtjeva 1 do 7.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10337773A DE10337773A1 (de) | 2003-08-13 | 2003-08-13 | Kristallisation von festen Formen von Clopidogrel-Additionssalzen |
| PCT/EP2004/008989 WO2005016931A2 (en) | 2003-08-13 | 2004-08-11 | Crystallisation of solid forms of clopidogrel addition salts |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20110418T1 true HRP20110418T1 (hr) | 2011-06-30 |
Family
ID=34177655
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20110418T HRP20110418T1 (hr) | 2003-08-13 | 2011-06-03 | Kristalizacija čvrstih oblika adicijskih soli klopidogrela |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP1656381B1 (hr) |
| AT (1) | ATE501153T1 (hr) |
| DE (2) | DE10337773A1 (hr) |
| ES (1) | ES2362660T3 (hr) |
| HR (1) | HRP20110418T1 (hr) |
| PL (1) | PL1656381T3 (hr) |
| PT (1) | PT1656381E (hr) |
| SI (1) | SI1656381T1 (hr) |
| WO (1) | WO2005016931A2 (hr) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005100364A1 (en) * | 2004-04-19 | 2005-10-27 | Krka, Tovarna Zdravil, D.D. Novo Mesto | Processes for the preparation of clopidogrel hydrogen sulfate polymorphic form i |
| EP1693375A1 (en) * | 2005-02-21 | 2006-08-23 | KRKA, tovarna zdravil, d.d., Novo mesto | Process for preparing clopidrogel hydrogen sulfate of form I |
| EP1931682A2 (en) * | 2006-08-03 | 2008-06-18 | Teva Pharmaceutical Industries Ltd. | Process for preparing clopidogrel bisulphate |
| SI22383A (sl) * | 2006-09-22 | 2008-04-30 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Nov postopek sinteze klopidogrela in nove oblike njegovih farmacevtsko sprejemljivih soli |
| KR101378596B1 (ko) | 2006-12-27 | 2014-03-26 | 경동제약 주식회사 | 결정성 클로피도그렐 · 황산염 형태 ｉ의 제조방법 |
| PL382055A1 (pl) * | 2007-03-23 | 2008-09-29 | Koźluk Tomasz Nobilus Ent | Sposób wytwarzania formy krystalicznej 1 wodorosiarczanu klopidogrelu |
| EP2107061A1 (en) | 2008-04-02 | 2009-10-07 | Krka Tovarna Zdravil, D.D., Novo Mesto | Process for the preparation of optically enriched clopidogrel |
| CN102083837B (zh) * | 2008-06-24 | 2013-09-18 | Zach系统股份公司 | 硫酸氢氯吡格雷晶型i的制备方法 |
| WO2011010318A1 (en) * | 2009-07-23 | 2011-01-27 | Praveen Laboratories Private Limited | Process for the preparation of clopidogrel polymorphous form 1 using seed chrystals |
| WO2011042804A2 (en) | 2009-10-08 | 2011-04-14 | Jubliant Life Sciences Limited | An improved process for the preparation of clopidogrel hydrogen sulfate form i |
| CN102432625A (zh) * | 2011-11-05 | 2012-05-02 | 江南大学 | 一种制备高纯度i型氯吡格雷硫酸氢盐的结晶方法 |
| CN102358743A (zh) * | 2011-11-05 | 2012-02-22 | 江南大学 | 一种制备无定形氯吡格雷硫酸氢盐的简便方法 |
| CN103044444B (zh) * | 2013-01-21 | 2015-04-15 | 上海现代哈森（商丘）药业有限公司 | 一种高纯度ⅰ型(+)-(s)-硫酸氢氯吡格雷的合成方法 |
| CN103923100B (zh) * | 2014-04-03 | 2019-05-14 | 浙江华海药业股份有限公司 | 一种硫酸氢氯吡格雷的精制方法 |
| CN104478895B (zh) * | 2014-12-05 | 2017-04-12 | 广东东阳光药业有限公司 | 氯吡格雷硫酸盐的制备方法 |
| CN107163060B (zh) * | 2017-05-24 | 2021-03-02 | 常州制药厂有限公司 | 一种硫酸氢氯吡格雷晶型ii制备方法 |
| CN107118221B (zh) * | 2017-05-24 | 2021-09-07 | 常州制药厂有限公司 | 一种硫酸氢氯吡格雷晶型i制备方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2530247B1 (fr) * | 1982-07-13 | 1986-05-16 | Sanofi Sa | Nouveaux derives de la thieno (3, 2-c) pyridine, leur procede de preparation et leur application therapeutique |
| FR2623810B2 (fr) * | 1987-02-17 | 1992-01-24 | Sanofi Sa | Sels de l'alpha-(tetrahydro-4,5,6,7 thieno(3,2-c) pyridyl-5) (chloro-2 phenyl) -acetate de methyle dextrogyre et compositions pharmaceutiques en contenant |
| FR2779726B1 (fr) * | 1998-06-15 | 2001-05-18 | Sanofi Sa | Forme polymorphe de l'hydrogenosulfate de clopidogrel |
| EP1425681A4 (en) * | 2001-07-02 | 2004-10-20 | Thomas W Wilson | METHOD AND SYSTEM FOR ANALYZING PRODUCT ALLOCATION |
| MXPA04006088A (es) * | 2001-12-18 | 2004-09-27 | Teva Pharma | Polimorfo de sulfato de hidrogeno de clopidogrel. |
| CZ297472B6 (cs) * | 2002-08-27 | 2006-12-13 | Zentiva, A.S. | Zpusob výroby clopidogrelu hydrogensulfátu krystalické formy I |
| WO2004048385A2 (en) * | 2002-11-28 | 2004-06-10 | Instytut Farmaceutyczny | A process for the preparation of crystalline form 1 or clopidogrel hydrogen sulfate |
| EP1603920A1 (en) * | 2003-03-12 | 2005-12-14 | Cadila Healthcare Ltd. | Polymorph and amorphous form of (s)-(+)-clopidogrel bisulfate |
-
2003
- 2003-08-13 DE DE10337773A patent/DE10337773A1/de not_active Withdrawn
-
2004
- 2004-08-11 PL PL04763994T patent/PL1656381T3/pl unknown
- 2004-08-11 DE DE602004031744T patent/DE602004031744D1/de not_active Expired - Lifetime
- 2004-08-11 PT PT04763994T patent/PT1656381E/pt unknown
- 2004-08-11 EP EP04763994A patent/EP1656381B1/en not_active Expired - Lifetime
- 2004-08-11 ES ES04763994T patent/ES2362660T3/es not_active Expired - Lifetime
- 2004-08-11 SI SI200431684T patent/SI1656381T1/sl unknown
- 2004-08-11 WO PCT/EP2004/008989 patent/WO2005016931A2/en active Application Filing
- 2004-08-11 AT AT04763994T patent/ATE501153T1/de not_active IP Right Cessation
-
2011
- 2011-06-03 HR HR20110418T patent/HRP20110418T1/hr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE602004031744D1 (de) | 2011-04-21 |
| EP1656381B1 (en) | 2011-03-09 |
| WO2005016931A2 (en) | 2005-02-24 |
| SI1656381T1 (sl) | 2011-07-29 |
| PT1656381E (pt) | 2011-06-16 |
| DE10337773A1 (de) | 2005-03-24 |
| EP1656381A2 (en) | 2006-05-17 |
| WO2005016931A3 (en) | 2005-04-28 |
| PL1656381T3 (pl) | 2011-08-31 |
| ATE501153T1 (de) | 2011-03-15 |
| ES2362660T3 (es) | 2011-07-11 |
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