HRP20040647A2 - Polymorphs of clopidogrel hydrogensulfate - Google Patents
Polymorphs of clopidogrel hydrogensulfate Download PDFInfo
- Publication number
- HRP20040647A2 HRP20040647A2 HR20040647A HRP20040647A HRP20040647A2 HR P20040647 A2 HRP20040647 A2 HR P20040647A2 HR 20040647 A HR20040647 A HR 20040647A HR P20040647 A HRP20040647 A HR P20040647A HR P20040647 A2 HRP20040647 A2 HR P20040647A2
- Authority
- HR
- Croatia
- Prior art keywords
- clopidogrel hydrogensulfate
- clopidogrel
- solution
- hydrogensulfate
- maxima
- Prior art date
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- 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 title claims abstract description 376
- 229950010477 clopidogrel hydrogen sulphate Drugs 0.000 title claims abstract description 287
- 238000000034 method Methods 0.000 claims abstract description 103
- 238000002360 preparation method Methods 0.000 claims abstract description 83
- 230000008569 process Effects 0.000 claims abstract description 40
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 166
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 80
- 239000012296 anti-solvent Substances 0.000 claims description 77
- 239000002244 precipitate Substances 0.000 claims description 74
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 claims description 68
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 claims description 67
- 229960003009 clopidogrel Drugs 0.000 claims description 65
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 60
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 52
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims description 52
- 239000002904 solvent Substances 0.000 claims description 51
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 43
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 41
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 40
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 30
- 238000001157 Fourier transform infrared spectrum Methods 0.000 claims description 30
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 28
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
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- 229940080313 sodium starch Drugs 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000005211 surface analysis Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
- 229940057977 zinc stearate Drugs 0.000 description 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Compounds Of Unknown Constitution (AREA)
- Liquid Crystal Substances (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34244001P | 2001-12-18 | 2001-12-18 | |
| US34235101P | 2001-12-21 | 2001-12-21 | |
| US34818202P | 2002-01-11 | 2002-01-11 | |
| US10/074,409 US6767913B2 (en) | 2001-12-18 | 2002-02-12 | Crystal forms iii, iv, v, and novel amorphous form of clopidogrel hydrogensulfate, processes for their preparation, processes for the preparation of form i, compositions containing the new forms and methods of administering the new forms |
| US35915702P | 2002-02-21 | 2002-02-21 | |
| PCT/US2002/040679 WO2003051362A2 (en) | 2001-12-18 | 2002-12-18 | Polymorphs of clopidogrel hydrogensulfate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20040647A2 true HRP20040647A2 (en) | 2005-04-30 |
Family
ID=27536010
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20040647A HRP20040647A2 (en) | 2001-12-18 | 2004-07-15 | Polymorphs of clopidogrel hydrogensulfate |
Country Status (18)
| Country | Link |
|---|---|
| EP (1) | EP1467735B1 (de) |
| JP (2) | JP2005514387A (de) |
| KR (1) | KR100839136B1 (de) |
| CN (1) | CN1620293A (de) |
| AT (1) | ATE417051T1 (de) |
| AU (1) | AU2002366383B2 (de) |
| CA (1) | CA2470479A1 (de) |
| DE (1) | DE60230327D1 (de) |
| ES (1) | ES2316650T3 (de) |
| HR (1) | HRP20040647A2 (de) |
| HU (1) | HUP0402485A3 (de) |
| IL (1) | IL162461A0 (de) |
| IS (1) | IS7319A (de) |
| MX (1) | MXPA04006088A (de) |
| NO (1) | NO20043038L (de) |
| PL (1) | PL370802A1 (de) |
| PT (1) | PT1467735E (de) |
| WO (1) | WO2003051362A2 (de) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ297472B6 (cs) | 2002-08-27 | 2006-12-13 | Zentiva, A.S. | Zpusob výroby clopidogrelu hydrogensulfátu krystalické formy I |
| GB2393181A (en) * | 2002-09-19 | 2004-03-24 | Cipla Ltd | Amorphous clopidogrel |
| ITMI20022228A1 (it) * | 2002-10-21 | 2004-04-22 | Dinamite Dipharma S P A | Sali di clopidogrel con acidi alchil-solforici. |
| AU2003285841A1 (en) * | 2002-11-28 | 2004-06-18 | Anpharm Przedsiebiorstwo Farmaceutyczne S.A. | A process for the preparation of crystalline form 1 or clopidogrel hydrogen sulfate |
| AU2003216707A1 (en) * | 2003-03-10 | 2004-09-30 | Hetero Drugs Limited | Amorphous clopidogrel hydrogen sulfate |
| EP1603920A1 (de) | 2003-03-12 | 2005-12-14 | Cadila Healthcare Ltd. | Polymorphe und amorphe form (s)-(+)-clopidogrel-bisulfat |
| ATE461201T1 (de) * | 2003-07-02 | 2010-04-15 | Egis Gyogyszergyar Nyilvanosan | Prozess zur herstellung eines kristallinen polymorphs eines die plättchen aggregation hemmenden arzneistoffs |
| HU0302029D0 (en) * | 2003-07-02 | 2003-09-29 | Egyt Gyogyszervegyeszeti Gyar | Amorphous form of an anticoagulant agent |
| KR20060026121A (ko) | 2003-07-02 | 2006-03-22 | 에지스 지오기스제르기아르 알티. | 혈소판 응집 억제 약물의 무정형 형태를 제조하는 방법 |
| DE10337773A1 (de) * | 2003-08-13 | 2005-03-24 | Krka Tovarna Zdravil, D.D. | Kristallisation von festen Formen von Clopidogrel-Additionssalzen |
| US8907090B2 (en) | 2003-11-03 | 2014-12-09 | Cadila Healthcare Limited | Processes for preparing different forms of (S)-(+)-Clopidogrel bisulfate |
| RU2328501C1 (ru) * | 2004-04-09 | 2008-07-10 | Ханми Фарм. Ко., ЛТД | Кристаллический клопидогрель нафталинсульфонат или его гидрат, способ его получения и содержащая его фармацевтическая композиция |
| 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 |
| CN1997648A (zh) * | 2004-04-20 | 2007-07-11 | 赛诺菲-安万特 | (+)－(S)－α－(2－氯苯基)－6,7－二氢噻吩并[3,2－C]吡啶－5(4H)乙酸甲酯氢溴酸盐，即氯吡格雷氢溴酸盐的多晶型物 |
| JP2007533746A (ja) * | 2004-04-20 | 2007-11-22 | サノフイ−アベンテイス | クロピドグレル塩及びその多形型 |
| WO2005117866A1 (en) * | 2004-06-01 | 2005-12-15 | Ivax Pharmaceuticals S.R.O. | Amorphous clopidogrel hydrochloride and its antithrombotic use |
| EP1693375A1 (de) * | 2005-02-21 | 2006-08-23 | KRKA, tovarna zdravil, d.d., Novo mesto | Verfahren zur Herstellung von Clopidrogel hydrogen sulfat in Form I |
| KR20070009851A (ko) * | 2005-07-14 | 2007-01-19 | 씨제이 주식회사 | 클로피도그렐 황산수소염 함유 약학 조성물 |
| US20090093635A1 (en) * | 2006-03-09 | 2009-04-09 | Sandor Garadnay | PROCESS FOR MAKING POLYMORPH FROM I OF (S) - (+) -METHYL-ALPHA- (2-CHLOROPHENYL) -6, 7-DYHIDRO-THIENO- [3, 2-c] PYRIDINE-5 (4H) -ACETATE HYDROGEN SULFATE |
| 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 |
| HUP0600839A3 (en) * | 2006-11-14 | 2008-09-29 | Egis Gyogyszergyar Nyrt | Solid pharmaceutical composition containing polymorph i of clopidogrel hydrogensulfate and process for the preparation thereof |
| KR101464482B1 (ko) * | 2007-05-08 | 2014-11-26 | 경동제약 주식회사 | 클로피도그렐 황산수소염을 함유하는 약학적 조성물 및 그제조방법 |
| EP2107061A1 (de) | 2008-04-02 | 2009-10-07 | Krka Tovarna Zdravil, D.D., Novo Mesto | Herstellungsverfahren für optisch angereichertes Clopidogrel |
| KR101130445B1 (ko) * | 2009-10-29 | 2012-03-27 | 동아제약주식회사 | 클로피도그랠 황산수소염 ⅰ형 제조방법 |
| CN101962387B (zh) * | 2010-09-13 | 2013-01-30 | 成都雅途生物技术有限公司 | 一种新结晶形态的氯吡格雷硫酸氢盐及其制备方法 |
| 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 |
| CN103006599A (zh) * | 2012-12-31 | 2013-04-03 | 广州白云山天心制药股份有限公司 | 含氯化钠药物载体的抗凝血片剂及其制备方法 |
| CN103408567B (zh) * | 2013-07-18 | 2016-12-28 | 浙江普洛医药科技有限公司 | 一种制备硫酸氢氯吡格雷晶型ⅰ的方法 |
| CN104610274B (zh) * | 2013-11-05 | 2017-04-19 | 亚宝药业集团股份有限公司 | 一种i型氯吡格雷硫酸氢盐的制备方法 |
| EP3578546A1 (de) | 2013-11-15 | 2019-12-11 | Akebia Therapeutics Inc. | Feste formen von {[5-(3-chlorophenyl)-3-hydroxypyridin-2-carbonyl]amino}essigsäure, zusammensetzungen und verwendungen davon |
| CN104045653A (zh) * | 2014-07-15 | 2014-09-17 | 苏州天马精细化学品股份有限公司 | 一种硫酸氢氯吡格雷的纯化方法 |
| KR101710922B1 (ko) | 2015-06-03 | 2017-02-28 | 경동제약 주식회사 | 클로피도그렐 황산염 결정형 i형의 제조방법 |
| 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 |
| CN107337683B (zh) * | 2017-08-16 | 2019-08-16 | 中荣凯特（北京）生物科技有限公司 | 一种噻吩并吡啶类衍生物硫酸氢盐的晶型ⅱ及其制备方法和应用 |
| WO2020013305A1 (ja) * | 2018-07-12 | 2020-01-16 | 有機合成薬品工業株式会社 | クロピドグレル硫酸塩のｉ型結晶の製造方法 |
| KR102220480B1 (ko) * | 2019-02-13 | 2021-02-25 | 한국바이오켐제약 주식회사 | 클로피도그렐황산염의 제조방법 및 이를 포함하는 약학제제 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| FR2664276B1 (fr) * | 1990-07-04 | 1992-10-23 | Sanofi Sa | Derive thienyl-2 glycidique, son procede de preparation et son utilisation comme intermediaire de synthese. |
| US5576328A (en) * | 1994-01-31 | 1996-11-19 | Elf Sanofi | Method for the secondary prevention of ischemic events |
| FR2751540B1 (fr) * | 1996-07-26 | 1998-10-16 | Sanofi Sa | Composition pharmaceutique antithrombotique |
| FR2769313B1 (fr) * | 1997-10-06 | 2000-04-21 | Sanofi Sa | Derives d'esters hydroxyacetiques, leur procede de preparation et leur utilisation comme intermediaires de synthese |
| FR2779726B1 (fr) * | 1998-06-15 | 2001-05-18 | Sanofi Sa | Forme polymorphe de l'hydrogenosulfate de clopidogrel |
| AU2002356430A1 (en) * | 2002-12-09 | 2004-06-30 | Hetero Drugs Limited | A novel polymorph of clopidogrel hydrogen sulfate |
-
2002
- 2002-12-18 ES ES02805215T patent/ES2316650T3/es not_active Expired - Lifetime
- 2002-12-18 PL PL02370802A patent/PL370802A1/xx unknown
- 2002-12-18 HU HU0402485A patent/HUP0402485A3/hu unknown
- 2002-12-18 KR KR1020047009420A patent/KR100839136B1/ko not_active IP Right Cessation
- 2002-12-18 EP EP02805215A patent/EP1467735B1/de not_active Expired - Lifetime
- 2002-12-18 PT PT02805215T patent/PT1467735E/pt unknown
- 2002-12-18 AU AU2002366383A patent/AU2002366383B2/en not_active Expired - Fee Related
- 2002-12-18 CN CNA028282043A patent/CN1620293A/zh active Pending
- 2002-12-18 MX MXPA04006088A patent/MXPA04006088A/es not_active Application Discontinuation
- 2002-12-18 IL IL16246102A patent/IL162461A0/xx unknown
- 2002-12-18 DE DE60230327T patent/DE60230327D1/de not_active Expired - Lifetime
- 2002-12-18 CA CA002470479A patent/CA2470479A1/en not_active Abandoned
- 2002-12-18 WO PCT/US2002/040679 patent/WO2003051362A2/en active Application Filing
- 2002-12-18 JP JP2003552295A patent/JP2005514387A/ja active Pending
- 2002-12-18 AT AT02805215T patent/ATE417051T1/de not_active IP Right Cessation
-
2004
- 2004-06-16 IS IS7319A patent/IS7319A/is unknown
- 2004-07-15 HR HR20040647A patent/HRP20040647A2/hr not_active Application Discontinuation
- 2004-07-16 NO NO20043038A patent/NO20043038L/no not_active Application Discontinuation
-
2009
- 2009-02-19 JP JP2009036569A patent/JP2009108107A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| PL370802A1 (en) | 2005-05-30 |
| JP2005514387A (ja) | 2005-05-19 |
| MXPA04006088A (es) | 2004-09-27 |
| NO20043038L (no) | 2004-09-09 |
| HUP0402485A3 (en) | 2008-10-28 |
| ES2316650T3 (es) | 2009-04-16 |
| WO2003051362A2 (en) | 2003-06-26 |
| DE60230327D1 (de) | 2009-01-22 |
| CN1620293A (zh) | 2005-05-25 |
| HUP0402485A2 (hu) | 2005-04-28 |
| ATE417051T1 (de) | 2008-12-15 |
| AU2002366383B2 (en) | 2007-06-14 |
| IS7319A (is) | 2004-06-16 |
| EP1467735A4 (de) | 2005-11-23 |
| JP2009108107A (ja) | 2009-05-21 |
| KR20040066917A (ko) | 2004-07-27 |
| CA2470479A1 (en) | 2003-06-26 |
| AU2002366383A1 (en) | 2003-06-30 |
| PT1467735E (pt) | 2009-03-10 |
| KR100839136B1 (ko) | 2008-06-20 |
| EP1467735B1 (de) | 2008-12-10 |
| EP1467735A2 (de) | 2004-10-20 |
| IL162461A0 (en) | 2005-11-20 |
| WO2003051362A3 (en) | 2003-08-07 |
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