RS51717B - Postupak za dobijanje novog beta-kristalnog oblika tercijalne butilaminske soli perindoprila - Google Patents
Postupak za dobijanje novog beta-kristalnog oblika tercijalne butilaminske soli perindoprilaInfo
- Publication number
- RS51717B RS51717B YU100502A YUP100502A RS51717B RS 51717 B RS51717 B RS 51717B YU 100502 A YU100502 A YU 100502A YU P100502 A YUP100502 A YU P100502A RS 51717 B RS51717 B RS 51717B
- Authority
- RS
- Serbia
- Prior art keywords
- carboxylic acid
- filtration
- perindopril
- formula
- salt
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P7/10—Antioedematous agents; Diuretics
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
-
- 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
- A61P9/12—Antihypertensives
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)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Indole Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Postupak dobijanja kristalnog β oblika tercijalne butilaminske soli perindoprila, formule (I) :naznačen time što se rastvor tercijalne butilaminske soli perindoprila u dihlorometanu zagreva na refluksu i nakon toga se hladi do 0°C i dobijena čvrsta masa se sakuplja filtracijom.Prijava sadrži još 2 patentna zahteva.
Description
Ovaj pronalazak se odnosi na postupak dobijanje (3 kristalnog oblika tercijalne butilaminske soli perindoprila formule (I):
Perindopril, kao i njegove farmaceutski prihvatljive soli, a posebno njegova so terc-butilamina, poseduje farmakološki korisna svojstva.
Njegovo glavno svojstvo je da inhibira enzim konverzije angiotenzina I (ili kinaze II), koji s jedne strane sprečava konverziju dekapeptida angiotenzina I u oktapeptid angiotenzin II (vazokonstriktor) i, sa druge strane, sprečava degradaciju bradikinina (vazodilatator) u neaktivni peptid.
Ova dva dejstva doprinose korisnim efektima perindoprila kod kardiovaskularnih bolesti, naročito arterijske hipertenzije i srčane insuficijencije.
U evropskom patentu EP 0 049 658, opisani su perindopril, njegovo dobijanje i njegovo korišćenje u terapiji.
U pogledu farmaceutske vrednosti ovog jedinjenja, od primarnos je značaja da se ono dobije u izvanredno čistom obliku. Isto tako, bilo je važno omogućiti sintezu pomoću procesa koji se jednostavno može konvertovati na skali industrijskih procesa, pre svega, u obliku koji dozvoljava brzo filtriranje i sušenje. Na kraju, taj oblik mora biti potpuno spreman za ponovno dobijanje, lako formulisan i zadovoljavajuće stabilan kako bi se omogućilo njegovo produženo čuvanje bez posebnih uslova u smislu temperature, svetlosti vlažnosti ili kursa kiseonika.
Patent EP 0 308 341 opisuje jedan industrijski postupak sinteze
perindoprila. Ipak, taj dokument ne precizira uslove dobijanja perindoprila u obliku
koji izražava ove karakteristike nanačinnakojise mogu ponoviti.
Prijavilac je pronašao da se naročita so perindoprila, terc-butilaminska so,
može dobiti u dobro definisanoj kristalnoj formi, savršene reproducibilnosti, koja pre
svega ispoljava korisne karakteristike za formulisanje.
Preciznije, ovaj pronalazak se odnosi na postupak za dobijanje kristalnog
0oblika jedinjenja formule (I), kojeg karakteriše dijagram difrakcije X zraka kroz
prašak koji sledi, meren na drfraktometru Siemens D5005 (bakama antikatoda)i
izražen kao inter-planarna udaljenost d, Braggov ugao 2-teta, intenzitetirelativni
intenzitet (izražen u procentima u odnosu na najintenzivniju prugu):
Pronalazak se odnosi na postupak za dobijanje kristalnog |3 oblika jedinjenja formule (I), koji je naznačen time što se rastvor terc-butilaminske soli perindoprila u dihlorometanu dovodi na refluks, a zatim se rastvor brzo hladi na 0°C i dobijena čvrsta masa sakuplja filtracijom. • Tokom postupka kristalizacije prema pronalasku, može se koristiti jedinjenje formule (I) koje je dobijeno ma kojim postupkom. Prednost ima korišćenje jedinjenja formule (I) koje je dobijeno proizvodnim postupkom opisanim u patentu EP 0 308 341. • Koncentracija jedinjenja formule (I) u dihlorometanu je poželjno između 100 i 200 g/L.
Primeri koji slede ilustruju pronalazak ali ga ne ograničavaju ni na koji način.
Spektar difrakcije X-zraka praha je meren pod sledećim eksperimentalnim uslovima:
- Difraktometar Siemens D5005; scintilacioni detektor,
- bakarna antikatoda (X=1,5405A), voltaže 40KV, intenziteta 40mA,
- sklapanje 6 - 6,
- opseg merenja : 5° do 30°,
- rast između svakog merenja : 0,02°,
- vreme merenja po koraku : 2s,
- promenljivi prorezi: v6,
- filter Kp (Ni),
- bez unutrašnje reference,
- nulta procedura sa Siemensovim prorezima,
- eksperimentalni podaci obrađeni sa softverom EVA (verzija 5.0).
PRIMER 1 : p kristalni oblik tercijalne butilaminske soli perindoprila
135 g tercijalne butilaminske soli perindoprila, koja je dobijena prema postupku koji je opisan u patentu EP 0 308 341 je rastvoreno u 1100 ml_ dihlorometana i rastvor je doveden do refluksa. Rastvor je zatim ohlađen na 0°C i dobijena čvrsta masa je sakupljena filtracijom.
Dijagram difrakcije X- zraka praha:
Profil difrakcije X-zraka praha (uglovi difrakcije)poblika tercijalne
butilaminske soli perindoprila dat je preko značajnih vrednosti rendgenskih zraka
zbirno prikazanih u sledećoj tabeli, zajedno sa intenzitetomirelativnim intenzitetom
(izražen kao procenat u odnosu na najintenzivniji X-zrak).
Claims (3)
1. Postupak dobijanja kristalnog (3 oblika tercijalne butilaminske soli perindoprila, formule (I) :
naznačen time što se rastvor tercijalne butilaminske soli perindoprila u dihlorometanu zagreva na refluksu i nakon toga se hladi do 0°C i dobijena čvrsta masa se sakuplja filtracijom.
2. Postupak, kao u patentnom zahtevu 1,naznačen time što se jedinjenje formule (I) koje se koristi, dobija sledećim postupkom: - sa jedne strane, redukcijom etil estra indol-2-karboksilne kiseline pomoću para kalaj / hlorovodonična kiselina, koju zatim prati reakcija hidrolize, proizvodi se racemična indolin-2-karboksilna kiselina, čiji se (S) izomer izdvaja dodavanjem racemata u rastvor (+)-a-metilbenzilamina u etanolu da bi se dobio talog soli (S)-indolin-2-karboksilne kiseline sa a-metilbenzilaminom, koji se posle filtriranja rastvara u vodi i zakiseljava kako bi se dobila (S)-indolin-2-karboksilna kiselina, koja se, posle filtracije i ispiranja, podvrgava hidrogenizaciji u prisustvu rodijuma-na-ugljenu, pod pritiskom vodonika od 30 bara, uz zagrevanje na temperaturi od 60°C, da bi se, posle kristalizacije, proizvela optički čista (2S,3aS,7aS)-perhidroindol-2-karboksilna kiselina, koja u reakciji sa benzil alkoholom, u prisustvu para-toluensulfonske kiseline, proizvodi odgovarajući benzil estar, - sa druge strane, (S)-L-norvalin se esterifikuje sa etanolom kako bi se dobio etil (S)-norvalinat, koji se kondenzuje sa piruvičnom kiselinom pod pritiskom vodonika od 30 bara, u prisustvu paladijuma-na-ugljenu, kako bi se dobio, posle kristalizacije, hlađenja i filtracije, optički čist N-[(S)-1-etoksikarbonilbutil]-(S)-alanin,
zatim se benzil estar (2S,3aS,7aS)-perhidroindol-2-karboksilne kiseline i N-[(S)-1-etoksikarbonilbutil]-(S)-alanina, koji je dobijen na takav način, kondenzuje u alkalnom medijumu, u prisustvu dicikloheksilkarbodiimida i 1-hidroksibenzotriazola kako bi se dobio odgovarajući amid, koji se podvrgava uklanjanju zaštite sa karboksilne grupe heterocikla, konverziji u so upotrebom terc-butilamina i, kristalizaciji.
3. Postupak, kao u patentnom zahtevu 1, naznačen time što je koncentracija jedinjenja formule (I) u dihlorometanu između 100 i 200 g / litar.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0008792A FR2811319B1 (fr) | 2000-07-06 | 2000-07-06 | Nouvelle forme cristalline beta du sel de tert-butylamine du perindopril, son procede de preparation et les compositions pharmaceutiques qui la contiennent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| YU100502A YU100502A (sh) | 2003-08-29 |
| RS51717B true RS51717B (sr) | 2011-10-31 |
Family
ID=8852171
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| YU100502A RS51717B (sr) | 2000-07-06 | 2001-07-06 | Postupak za dobijanje novog beta-kristalnog oblika tercijalne butilaminske soli perindoprila |
Country Status (35)
| Country | Link |
|---|---|
| US (2) | US20040029813A1 (sr) |
| EP (2) | EP1294689B1 (sr) |
| JP (2) | JP3592297B2 (sr) |
| KR (1) | KR100513571B1 (sr) |
| CN (1) | CN1328260C (sr) |
| AP (1) | AP1407A (sr) |
| AR (1) | AR029571A1 (sr) |
| AT (1) | ATE324367T1 (sr) |
| AU (2) | AU7641901A (sr) |
| BG (1) | BG66131B1 (sr) |
| BR (1) | BR0112244A (sr) |
| CA (1) | CA2415442C (sr) |
| CZ (1) | CZ301765B6 (sr) |
| DE (1) | DE60119107T2 (sr) |
| DK (1) | DK1294689T3 (sr) |
| EA (1) | EA004874B1 (sr) |
| EE (1) | EE05285B1 (sr) |
| ES (1) | ES2262666T3 (sr) |
| FR (1) | FR2811319B1 (sr) |
| GE (1) | GEP20043360B (sr) |
| HR (2) | HRP20060361A8 (sr) |
| HU (1) | HU227673B1 (sr) |
| ME (1) | ME00440B (sr) |
| MX (1) | MXPA02012921A (sr) |
| NO (1) | NO323446B1 (sr) |
| NZ (1) | NZ523234A (sr) |
| OA (1) | OA12305A (sr) |
| PL (1) | PL348493A1 (sr) |
| PT (1) | PT1294689E (sr) |
| RS (1) | RS51717B (sr) |
| SI (1) | SI1294689T1 (sr) |
| SK (1) | SK286918B6 (sr) |
| UA (1) | UA57189C2 (sr) |
| WO (1) | WO2001087836A1 (sr) |
| ZA (1) | ZA200300024B (sr) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2811318B1 (fr) * | 2000-07-06 | 2002-08-23 | Adir | Nouvelle forme cristalline gamma du sel de tert-butylamine du perindopril, son procede de preparation et les compositions pharmaceutiques qui la contiennent |
| FR2811320B1 (fr) * | 2000-07-06 | 2002-08-23 | Adir | Nouvelle forme cristalline alpha du sel de tert-butylamine du perindopril, son procede de preparation et les compositions pharmaceutiques qui la contiennent |
| GB2395195A (en) | 2002-11-18 | 2004-05-19 | Cipla Ltd | Preparation of perindopril from carboxy-protected precursor, & perindopril monohydrates for use as angiotensin converting enzyme (ACE) inhibitors |
| CN100395235C (zh) | 2003-06-24 | 2008-06-18 | 瑟维尔实验室 | 培哚普利特丁胺的新晶形 |
| ES2336554T3 (es) * | 2003-10-21 | 2010-04-14 | Les Laboratoires Servier | Nuevo metodo para la preparacion de perindopril erbumina cristalina. |
| SI21703A (en) | 2004-01-14 | 2005-08-31 | Lek Farmacevtska Druzba Dd | Inclusion complexes of perindopril, procedure of their preparation, pharmaceutical compositions containing these complexes and their application in treatment of hypertensia |
| HRP20161602T1 (hr) * | 2004-03-29 | 2016-12-30 | Les Laboratoires Servier | Postupak priprave čvrstog farmaceutskog pripravka |
| SI21800A (sl) | 2004-05-14 | 2005-12-31 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Nov postopek sinteze perindoprila |
| SI21881A (sl) | 2004-10-15 | 2006-04-30 | Diagen, Smartno Pri Ljubljani, D.O.O. | Nove kristalne oblike perindopril erbumin hidratov, postopek za njihovo pripravo in farmacevtske oblike, ki vsebujejo te spojine |
| SG125976A1 (en) * | 2005-03-11 | 2006-10-30 | Servier Lab | New gama crystalline form of perindopril tert-butylamine salt, a process for its preparation and pharmaceutical compositions containing it |
| SG125975A1 (en) * | 2005-03-11 | 2006-10-30 | Servier Lab | New alpha crystalline form of perindopril tert-butylamine salt, a process for its preparation and pharmaceutical compositions containing it |
| JP2006290825A (ja) * | 2005-04-13 | 2006-10-26 | Shiono Chemical Co Ltd | アルファ型ペリンドプリルエルブミンの製造法 |
| WO2007017894A2 (en) * | 2005-05-05 | 2007-02-15 | Arch Pharmalabs Limited | PREPARATION OF NOVEL CRYSTALLINE η(ETA) FORM OF PERINDOPRIL ERBUMINE |
| WO2007020009A1 (en) * | 2005-08-12 | 2007-02-22 | Sandoz Ag | New crystalline form of perindopril erbumine |
| WO2007020012A1 (en) * | 2005-08-12 | 2007-02-22 | Lek Pharmaceuticals D.D. | A process for the preparation of perindopril erbumine |
| EP1815857A1 (en) | 2006-02-02 | 2007-08-08 | LEK Pharmaceuticals D.D. | A pharmaceutical composition comprising perindopril |
| WO2007092758A2 (en) * | 2006-02-03 | 2007-08-16 | Dr. Reddy's Laboratories Ltd. | Crystalline forms of perindopril erbumine |
| FR2897865B1 (fr) | 2006-02-28 | 2008-04-18 | Servier Lab | Forme cristalline beta du sel d'arginine du perindopril, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
| FR2897866B1 (fr) | 2006-02-28 | 2008-04-18 | Servier Lab | Forme cristalline alpha du sel d'arginine du perindopril, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
| WO2008050185A2 (en) * | 2006-10-26 | 2008-05-02 | Glenmark Pharmaceuticals Limited | Novel polymorphs of perindopril erbumine |
| WO2008120241A2 (en) * | 2007-03-29 | 2008-10-09 | Ipca Laboratories Limited | Novel alcohol solvates of perindopril erbumine |
| SI22543A (sl) | 2007-06-27 | 2008-12-31 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Nove soli perindoprila |
| AU2009263737B2 (en) * | 2008-06-24 | 2013-10-24 | Tianish Laboratories Private Limited | Novel polymorphic forms of Perindopril (L)-Arginine and process for the preparation thereof |
| SI23149A (sl) | 2009-09-21 | 2011-03-31 | Silverstone Pharma | Nove benzatinske soli ACE inhibitorjev, postopek za njihovo pripravo in njihova uporaba za zdravljenje kardiovaskularnih bolezni |
| PT105315B (pt) | 2010-09-29 | 2013-01-16 | Inst Superior Tecnico | Uma nova forma cristalina hidratada de erbumina de perindopril, métodos para a sua preparação e sua utilização em preparações farmacêuticas |
| CN106432042A (zh) * | 2015-08-13 | 2017-02-22 | 南京华威医药科技开发有限公司 | 尼达尼布乙磺酸水合物的药物新晶型 |
| EP3842035A1 (en) | 2019-12-23 | 2021-06-30 | KRKA, d.d., Novo mesto | Composition for the preparation of perindopril arginine granules, a method for their preparation and pharmaceutical composition comprising the granules |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2620709B1 (fr) * | 1987-09-17 | 1990-09-07 | Adir | Procede de synthese industrielle du perindopril et de ses principaux intermediaires de synthese |
| FR2771010B1 (fr) * | 1997-11-19 | 2003-08-15 | Adir | Utilisation d'une combinaison d'un inhibiteur de l'enzyme de conversion de l'angiotensine et d'un diuretique pour le traitement des desordres microcirculatoires |
| FR2811320B1 (fr) * | 2000-07-06 | 2002-08-23 | Adir | Nouvelle forme cristalline alpha du sel de tert-butylamine du perindopril, son procede de preparation et les compositions pharmaceutiques qui la contiennent |
| FR2811318B1 (fr) | 2000-07-06 | 2002-08-23 | Adir | Nouvelle forme cristalline gamma du sel de tert-butylamine du perindopril, son procede de preparation et les compositions pharmaceutiques qui la contiennent |
-
2000
- 2000-07-06 FR FR0008792A patent/FR2811319B1/fr not_active Expired - Fee Related
-
2001
- 2001-06-07 UA UA2003021021A patent/UA57189C2/uk unknown
- 2001-07-05 HU HU0102813A patent/HU227673B1/hu not_active IP Right Cessation
- 2001-07-06 EP EP01954059A patent/EP1294689B1/fr not_active Expired - Lifetime
- 2001-07-06 PL PL01348493A patent/PL348493A1/xx not_active Application Discontinuation
- 2001-07-06 HR HR20060361A patent/HRP20060361A8/xx not_active Application Discontinuation
- 2001-07-06 CA CA002415442A patent/CA2415442C/fr not_active Expired - Fee Related
- 2001-07-06 JP JP2001584233A patent/JP3592297B2/ja not_active Expired - Fee Related
- 2001-07-06 CN CNB018123554A patent/CN1328260C/zh not_active Expired - Fee Related
- 2001-07-06 HR HR20030079A patent/HRP20030079B8/xx not_active IP Right Cessation
- 2001-07-06 WO PCT/FR2001/002168 patent/WO2001087836A1/fr not_active Ceased
- 2001-07-06 AU AU7641901A patent/AU7641901A/xx active Pending
- 2001-07-06 RS YU100502A patent/RS51717B/sr unknown
- 2001-07-06 AP APAP/P/2002/002710A patent/AP1407A/en active
- 2001-07-06 CZ CZ20030356A patent/CZ301765B6/cs not_active IP Right Cessation
- 2001-07-06 EA EA200300103A patent/EA004874B1/ru not_active IP Right Cessation
- 2001-07-06 OA OA1200200398A patent/OA12305A/en unknown
- 2001-07-06 GE GE5076A patent/GEP20043360B/en unknown
- 2001-07-06 DE DE60119107T patent/DE60119107T2/de not_active Expired - Lifetime
- 2001-07-06 EP EP06075789A patent/EP1676839A3/fr not_active Withdrawn
- 2001-07-06 ES ES01954059T patent/ES2262666T3/es not_active Expired - Lifetime
- 2001-07-06 US US10/312,902 patent/US20040029813A1/en not_active Abandoned
- 2001-07-06 MX MXPA02012921A patent/MXPA02012921A/es active IP Right Grant
- 2001-07-06 ME MEP-2008-669A patent/ME00440B/me unknown
- 2001-07-06 AR ARP010103225A patent/AR029571A1/es unknown
- 2001-07-06 AU AU2001276419A patent/AU2001276419B2/en not_active Ceased
- 2001-07-06 PT PT01954059T patent/PT1294689E/pt unknown
- 2001-07-06 EE EEP200300002A patent/EE05285B1/xx not_active IP Right Cessation
- 2001-07-06 SK SK148-2003A patent/SK286918B6/sk not_active IP Right Cessation
- 2001-07-06 BR BR0112244-4A patent/BR0112244A/pt not_active Application Discontinuation
- 2001-07-06 DK DK01954059T patent/DK1294689T3/da active
- 2001-07-06 AT AT01954059T patent/ATE324367T1/de active
- 2001-07-06 KR KR10-2003-7000116A patent/KR100513571B1/ko not_active Expired - Fee Related
- 2001-07-06 SI SI200130535T patent/SI1294689T1/sl unknown
- 2001-07-06 NZ NZ523234A patent/NZ523234A/en not_active IP Right Cessation
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2003
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2004
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2005
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