RS51264B - Postupak za proizvodnju 3(r)-(2-hidroksi-2,2-ditien-2-ilacetoksi)-1-(3-fenoksipropil)-1-azoniabiciklo[2.2.2]oktan bromida - Google Patents
Postupak za proizvodnju 3(r)-(2-hidroksi-2,2-ditien-2-ilacetoksi)-1-(3-fenoksipropil)-1-azoniabiciklo[2.2.2]oktan bromidaInfo
- Publication number
- RS51264B RS51264B RSP-2010/0009A RSP20100009A RS51264B RS 51264 B RS51264 B RS 51264B RS P20100009 A RSP20100009 A RS P20100009A RS 51264 B RS51264 B RS 51264B
- Authority
- RS
- Serbia
- Prior art keywords
- hydroxy
- dithien
- solvent
- phenoxypropyl
- ester
- Prior art date
Links
Classifications
-
- 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
- A61K31/439—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 the ring forming part of a bridged ring system, e.g. quinuclidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Postupak za proizvodnju 3(R)-(2-hidroksi-2,2-ditien-2-ilacetoksi)-1-(3-fenoksipropil)-1-azoniabiciklo[2.2.2]oktan bromida reakcijom 1-azabiciklo[2.2.2]okt-3(R)il estra 2-hidroksi-2,2-ditien-2-ilsirćetne kiseline i 3-fenoksipropil bromida, pri čemu se reakcija odvija u rastvaraču ili mešavini rastvarača koji imaju tačku ključanja između 50 i 210°C i odabrani su iz grupe koja se sastoji od ketona i cikličnih etara.Prijava sadrži još 11 patentnih zahteva.
Description
Ovaj pronalazak se odnosi na postupak za proizvodnju 3(R)-(2-hidroksi-2,2-ditien-2-ilacetoksi)-1-(3-fenoksipropil)-1-azoniabiciklo[2.2.2]oktana.
Ovo jedinjenje, kao i postupak za njegovu proizvodnju su opisani u WO 01/04118 A2.
Pronalazači su sada neočekivano otkrili da se ispravnim izborom reakcionih uslova, postupak, koji je opisan u VVO 01/04118 A2, može optimizovati, omogućavajući smanjenje reakcinog vremena i količine rastvarača i korišćenog reaktanta za alkilovanje dok se povećava prinos i održava nivo nečistoća.
Ovi se ciljevi mogu postići izvođenjem reakcije kvaternizacije između 1-azabiciklo[2.2.2]okt-3(R)il estra 2-hidroksi-2,2-ditien-2-ilsirćetne kiseline i 3-fenoksipropil bromida u rastvaraču ili mešavini rastvarača, koji imaju tačku ključanja između 50 i 210°C i izborom iz grupe koja se sastoji od ketona i cikličnih etara. U korisnom ostvarenju ovog pronalaska, koristi se jedan rastvarač.
Slede neki primeri ketona ili cikličnih etara koji se mogu koristiti kao rastvarači za izvođenje pronalaska: aceton, metil etil keton, etil izobutil keton, fenil metil keton, ciklopentanon, dioksan, tetrahidrofuran, etiltetrahidrofuran. Poželjni rastvarači su izabrani iz grupe, koja se sastoji od: acetona, dioksana ili tetrahidrofurana. Posebno poželjan rastvarač je tetrahidrofuran.
Preciznije, pokazalo se korisno korišenje odnosa ekvivalenata između 3-fenoksipropil bromida prema 1-azabiciklo[2.2.2]okt-3(R)il estru 2-hidroksi-2,2-ditien-2-ilsirćetne kiseline u rasponu od 1.0 do 3.0, poželjnije između 1.1 i 1.5, a najbolje, između 1.2 i 1.3.
U sledećem poželjnom ostvarenju, 1-azabiciklo[2.2.2]okt-3(R)il estar 2-hidroksi-2,2-ditien-2-ilsirćetne kiseline se suspenduje (ili rastvori) u zapremini rastvarača ili mešavine rastvarača u opsegu između 1,7 i 7 litara rastvarača po molu 1-azabiciklo[2.2.2]okt-3(R)il estra 2-hidroksi-2,2-ditien-2-ilsirćetne kiseline. Poželjnije, estar se suspenduje (ili rastvara) u zapremini rastvarača ili mešavine rastvarača u opsegu između 2 i 4 litra po molu estra.
Pod ovim uslovima, pokazalo se odgovarajućim omogućavanje reagovanja mešavine u vremenskom periodu koji ne prelazi 24 sata, poželjno ne duže od 12 sati, poželjnije ne duže od 9 sati i najbolje, ne duže od 6 sati.
Posebno se dobri rezultati dobijaju kada se 1-azabiciklo[2.2.2]okt-3(R)il estar 2-hidroksi-2,2-ditien-2-ilsirćetne kiseline suspenduje u 2 do 4 1 tetrahidrofurana po molu 1-azabiciklo[2.2.2]okt-3(R)il estra 2-hidroksi-2,2-ditien-2-ilsirćetne kiseline, u dobijenu suspenziju se dodaju od 1.2 do 1.3 ekvivalenata 3-fenoksipropil bromida i mešavina se meša ne više od 9 sati, poželjno ne više od 6 sati na refluksu u inertnoj atmosferi.
Sledeći primeri prikazuju ilustrativne postupke za proizvodnju jedinjenja koja su u skladu sa ovim pronalaskom i nemaju cilj ograničavanja okvira pronalaska.
Eksperimentalni deo
UPOREDNI PRIMER 1 (u skladu sa WO 01104118)
0.6 mmol 1-azabiciklo[2.2.2]okt-3(R)il estra 2-hidroksi-2,2-ditien-2-ilsirćetne kiseline se suspenduje u 4 ml CH3CN i 6 ml CHCI3, u dobijenu suspenziju se doda 0.48 ml 3-fenoksipropil bromida i smeša se meša u toku 72 h na sobnoj temperaturi u inertnoj atmosferi. Rastvarači se potom upare kako bi se dobio (90%) 3(R)-(2-hidroksi-2,2-ditien-2-ilacetoksi)-1-(3-fenoksipropil)-1-azoniabiciklo[2.2.2]oktan bromid. Proizvod se izoluje filtriranjem na sobnoj temperaturi i odredi se nivo 3-fenoksipropil bromida od 117 ppm.
PRIMERI 2 DO 12
Molovi 1-azabiciklo[2.2.2]okt-3(R)il estra 2-hidroksi-2,2-ditien-2-ilsirćetne kiseline naznačeni u koloni B su suspendovani u količini (kolona E) rastvarača naznačenog u koloni D. Onda je, u nastalu suspenziju, dodata količina 3-fenoksipropil bromida, koja je dobijena množenjem kolone B sa kolonom C i mešavina je mešana u toku 6 h na refluksu u inertnoj atmosferi. Rastvarači su potom upareni kako bi se dobio 3(R)-(2-hidroksi-2,2-ditien-2-ilacetoksi)-1-(3-fenoksipropil)-1-azoniabiciklo[2.2.2]oktan bromid. Proizvod je izolovan filtracijom na sobnoj temperaturi i, zatim su i prinos i nivo 3-fenoksipropil bromida određeni i naznačeni u kolonama F, odnosno G.
Sledeća tabela zbirno prikazuje rezultate uporednog primera 1 i primera 2 do 12 ovog pronalaska.
Kao što se može videti iz rezultata u Tabeli I, oni pokazuju da postupak ovog pronalaska omogućava skraćenje reakcionog vremena i smanjenje količine 3-fenoksipropil bromida koji se koristi, dok se istovremeno povećava prinos i održava količina genotoksične nečistoće 3-fenoksipropil bromida na prihvatljivom nivou od ispod 500 ppm.
Claims (12)
1. Postupak za proizvodnju 3(R)-(2-hidroksi-2,2-ditien-2-ilacetoksi)-1-(3-fenoksipropil)-1-azoniabiciklo[2.2.2]oktan bromida reakcijom 1-azabiciklo[2.2.2]okt-3(R)il estra 2-hidroksi-2,2-ditien-2-ilsirćetne kiseline i 3-fenoksipropil bromida, pri čemu se reakcija odvija u rastvaraču ili mešavini rastvarača koji imaju tačku ključanja između 50 i 210°C i odabrani su iz grupe koja se sastoji od ketona i cikličnih etara.
2. Postupak, kao u patentnom zahtevu 1, gde je odnos ekvivalenata između 3-fenoksipropil bromida i 1-azabiciklo[2.2.2]okt-3(R)il estra 2-hidroksi-2,2-ditien-2-ilsirćetne kiseline u rasponu od 1.0 do 3.0.
3. Postupak, kao u patentnom zahtevu 2, gde je odnos ekvivalenata u rasponu između 1.1 i 1.5.
4. Postupak, kao u patentnom zahtevu 2, gde je odnos ekvivalenata u rasponu između 1.2 i 1.3.
5. Postupak, kao u ma kom od prethodnih patentnih zahteva, gde je 1-azabiciklo[2.2.2]okt-3(R)il estar 2-hidroksi-2,2-ditien-2-ilsirćetne kiseline suspendovan ili rastvoren u zapremini rastvarača ili mešavini rastvarača u rasponu od 1,7 do 7 litara rastvarača po molu 1-azabiciklo[2.2.2]okt-3(R)il estra 2-hidroksi-2,2-ditien-2-ilsirćetne kiseline.
6. Postupak, kao u patentnom zahtevu 5, gde zapremina rastvarača iznosi između 2 i 4 litra po molu 1-azabiciklo[2.2.2]okt-3(R)il estra 2-hidroksi-2,2-ditien-2-il-sirćetne kiseline.
7. Postupak, kao u ma kom od prethodnih patentnih zahteva, gde je rastvarač odabran iz grupe, koja se sastoji od: acetona, dioksana i tetrahidrofurana.
8. Postupak, kao u patentnom zahtevu 7, gde je rastvarač tetrahidrofuran.
9. Postupak, kao u ma kom od prethodnih patentnih zahteva, gde se mešavina ostavlja da reaguje u vremenskom periodu koji nije duži od 24 časa.
10. Postupak, kao u patentnom zahtevu 9, gde vremenski period nije duži od 12 časova.
11. Postupak, kao u patentnom zahtevu 10, gde vremenski period nije duži od 9 časova.
12. Postupak, kao u patentnom zahtevu 11, gde vremenski period nije duži od 6 časova.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200601951A ES2298049B1 (es) | 2006-07-21 | 2006-07-21 | Procedimiento para fabricar bromuro de 3(r)-(2-hidroxi-2,2-ditien-2-ilacetoxi)-1-(3-fenoxipropil)-1-azoniabiciclo (2.2.2) octano. |
| PCT/EP2007/006278 WO2008009397A1 (en) | 2006-07-21 | 2007-07-16 | Process for manufacturing 3(r)-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RS51264B true RS51264B (sr) | 2010-12-31 |
Family
ID=37808353
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RSP-2010/0009A RS51264B (sr) | 2006-07-21 | 2007-07-16 | Postupak za proizvodnju 3(r)-(2-hidroksi-2,2-ditien-2-ilacetoksi)-1-(3-fenoksipropil)-1-azoniabiciklo[2.2.2]oktan bromida |
Country Status (36)
| Country | Link |
|---|---|
| US (1) | US8044205B2 (sr) |
| EP (1) | EP2044067B1 (sr) |
| JP (1) | JP5279708B2 (sr) |
| KR (1) | KR101410198B1 (sr) |
| CN (1) | CN101490048B (sr) |
| AR (1) | AR061933A1 (sr) |
| AT (1) | ATE449096T1 (sr) |
| AU (1) | AU2007276395B2 (sr) |
| BR (1) | BRPI0711500B1 (sr) |
| CA (1) | CA2657679C (sr) |
| CL (1) | CL2007002078A1 (sr) |
| CO (1) | CO6460740A2 (sr) |
| CY (1) | CY1109792T1 (sr) |
| DE (1) | DE602007003375D1 (sr) |
| DK (1) | DK2044067T3 (sr) |
| EC (1) | ECSP099033A (sr) |
| EG (1) | EG25727A (sr) |
| ES (2) | ES2298049B1 (sr) |
| HR (1) | HRP20090652T1 (sr) |
| IL (1) | IL196324A (sr) |
| ME (1) | ME01773B (sr) |
| MX (1) | MX2009000573A (sr) |
| MY (1) | MY145285A (sr) |
| NO (1) | NO20090811L (sr) |
| NZ (1) | NZ573170A (sr) |
| PE (1) | PE20081307A1 (sr) |
| PL (1) | PL2044067T3 (sr) |
| PT (1) | PT2044067E (sr) |
| RS (1) | RS51264B (sr) |
| RU (1) | RU2439070C2 (sr) |
| SI (1) | SI2044067T1 (sr) |
| TW (1) | TWI363057B (sr) |
| UA (1) | UA96453C2 (sr) |
| UY (1) | UY30475A1 (sr) |
| WO (1) | WO2008009397A1 (sr) |
| ZA (1) | ZA200810051B (sr) |
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| CA2608561A1 (en) * | 2007-10-29 | 2009-04-29 | Carl Paluszkiewicz | Motorcycle wind deflector accessory support |
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| EP2100599A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
| EP2510928A1 (en) | 2011-04-15 | 2012-10-17 | Almirall, S.A. | Aclidinium for use in improving the quality of sleep in respiratory patients |
| EP2666465A1 (en) | 2012-05-25 | 2013-11-27 | Almirall, S.A. | Novel dosage and formulation |
| CZ306791B6 (cs) * | 2013-10-29 | 2017-07-12 | Zentiva, K.S. | Průmyslově využitelný způsob přípravy aklidinium bromidu o vysoké čistotě |
| CN103755699A (zh) * | 2014-01-06 | 2014-04-30 | 万特制药(海南)有限公司 | 一种2-羟基-2,2-二噻吩-2-基乙酸-1-氮杂二环[2,2,2]辛-3(r)-基酯制备方法 |
| CN103755698A (zh) * | 2014-01-06 | 2014-04-30 | 万特制药(海南)有限公司 | 一锅法制备阿地溴铵的工艺 |
| CZ2014188A3 (cs) | 2014-03-26 | 2015-10-07 | Zentiva, K.S. | Nové formy aclidinium chloridu a způsob jejich přípravy |
| CN104478871B (zh) * | 2014-12-26 | 2016-09-07 | 东华大学 | 一种胆碱m受体拮抗剂阿地溴铵及其制备方法 |
| PT108370B (pt) * | 2015-03-30 | 2018-10-25 | Hovione Farm S A | Processo de preparação de brometo de aclidínio |
| WO2016162878A1 (en) * | 2015-04-04 | 2016-10-13 | Harman Finochem Limited | An advantageous process for preparing 1-azoniabicyclo[2.2.2]octane,3-[(hydroxydi-2-thienylacetyl)oxy]-1-(3¬phenoxypropyl)-, bromide, (3r)- and its novel crystalline form-i |
| CZ2015257A3 (cs) | 2015-04-16 | 2016-10-26 | Zentiva, K.S. | Způsob pro zmenšování velikosti částic bromidu [(3R)-1-(3-fenoxypropyl)chinuklidin-1-ium-3-yl] 2-hydroxy-2,2-bis(2-thienyl)acetátu |
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| US20100310477A1 (en) | 2000-11-28 | 2010-12-09 | Boehringer Ingelheim Pharma Gmbh & Co. Kg. | Pharmaceutical compositions based on anticholingerics and additional active ingredients |
| NZ526580A (en) | 2000-12-22 | 2005-04-29 | Almirall Prodesfarma Ag | Quinuclidine carbamate derivatives and their use as M3 antagonists |
| WO2002053564A2 (en) * | 2000-12-28 | 2002-07-11 | Almirall Prodesfarma Ag | Quinuclidine derivatives and their use as m3 antagonists |
| DE10104370A1 (de) | 2001-02-01 | 2002-08-08 | Boehringer Ingelheim Pharma | Arzneimittelkompositionen mit geringeren Nebenwirkungen |
| US20020179087A1 (en) | 2001-02-01 | 2002-12-05 | Karl-Heinz Bozung | Pharmaceutical compositions containing an oxitropium salt and a betamimetic |
| US20020189610A1 (en) | 2001-02-01 | 2002-12-19 | Karl-Heinz Bozung | Pharmaceutical compositions containing an ipratropium salt and a betamimetic |
| DE10104367A1 (de) | 2001-02-01 | 2002-08-08 | Boehringer Ingelheim Pharma | Betamimetika enthaltende Arzneimittelkompositionen mit geringeren Nebenwirkungen |
| DE10130371A1 (de) | 2001-06-23 | 2003-01-02 | Boehringer Ingelheim Pharma | Neue Arzneimittelkompositionen auf der Basis von Anticholinergika, Corticosteroiden und Betamimetika |
| US20030018019A1 (en) | 2001-06-23 | 2003-01-23 | Boehringer Ingelheim Pharma Kg | Pharmaceutical compositions based on anticholinergics, corticosteroids and betamimetics |
| ES2206021B1 (es) * | 2002-04-16 | 2005-08-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de pirrolidinio. |
| ES2195785B1 (es) | 2002-05-16 | 2005-03-16 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| ES2204295B1 (es) * | 2002-07-02 | 2005-08-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de quinuclidina-amida. |
| ES2211315B1 (es) | 2002-11-12 | 2005-10-16 | Almirall Prodesfarma, S.A. | Nuevos compuestos triciclicos. |
| ES2211344B1 (es) | 2002-12-26 | 2005-10-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| NZ545443A (en) | 2003-07-29 | 2010-04-30 | Boehringer Ingelheim Int | Combination of an aclidinium salt known as 3-(2-hydroxy-2,2-dithiophen-2-yl-acetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane and a steroid and its use to treat respiratory disorders by inhalation |
| US20050026948A1 (en) | 2003-07-29 | 2005-02-03 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising an anticholinergic and a betamimetic |
| US20050026887A1 (en) | 2003-07-29 | 2005-02-03 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising an anticholinergic and a steroid |
| US20050026886A1 (en) | 2003-07-29 | 2005-02-03 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising an anticholinergic and a PDE IV inhibitor |
| US20050025718A1 (en) | 2003-07-31 | 2005-02-03 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising an anticholinergic and a betamimetic |
| ES2232306B1 (es) | 2003-11-10 | 2006-08-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| ES2239546B1 (es) * | 2004-03-15 | 2006-12-01 | Almirall Prodesfarma, S.A. | Nuevos esteres de quinuclidina cuaternizados. |
| ES2257152B1 (es) | 2004-05-31 | 2007-07-01 | Laboratorios Almirall S.A. | Combinaciones que comprenden agentes antimuscarinicos y agonistas beta-adrenergicos. |
| EP2100598A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
| EP2100599A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
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2006
- 2006-07-21 ES ES200601951A patent/ES2298049B1/es not_active Withdrawn - After Issue
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2007
- 2007-07-09 UY UY30475A patent/UY30475A1/es unknown
- 2007-07-16 ME MEP-2010-9A patent/ME01773B/me unknown
- 2007-07-16 PL PL07786080T patent/PL2044067T3/pl unknown
- 2007-07-16 JP JP2009519845A patent/JP5279708B2/ja active Active
- 2007-07-16 BR BRPI0711500-8A patent/BRPI0711500B1/pt active IP Right Grant
- 2007-07-16 ES ES07786080T patent/ES2336045T3/es active Active
- 2007-07-16 CA CA2657679A patent/CA2657679C/en active Active
- 2007-07-16 PT PT07786080T patent/PT2044067E/pt unknown
- 2007-07-16 AU AU2007276395A patent/AU2007276395B2/en active Active
- 2007-07-16 AT AT07786080T patent/ATE449096T1/de active
- 2007-07-16 RU RU2009105827/04A patent/RU2439070C2/ru active
- 2007-07-16 MX MX2009000573A patent/MX2009000573A/es active IP Right Grant
- 2007-07-16 HR HR20090652T patent/HRP20090652T1/hr unknown
- 2007-07-16 CN CN2007800274230A patent/CN101490048B/zh active Active
- 2007-07-16 US US12/374,185 patent/US8044205B2/en active Active
- 2007-07-16 DE DE602007003375T patent/DE602007003375D1/de active Active
- 2007-07-16 MY MYPI20090241A patent/MY145285A/en unknown
- 2007-07-16 NZ NZ573170A patent/NZ573170A/en unknown
- 2007-07-16 SI SI200730159T patent/SI2044067T1/sl unknown
- 2007-07-16 DK DK07786080.7T patent/DK2044067T3/da active
- 2007-07-16 RS RSP-2010/0009A patent/RS51264B/sr unknown
- 2007-07-16 KR KR1020097001067A patent/KR101410198B1/ko active Active
- 2007-07-16 UA UAA200901336A patent/UA96453C2/uk unknown
- 2007-07-16 WO PCT/EP2007/006278 patent/WO2008009397A1/en not_active Ceased
- 2007-07-16 EP EP07786080A patent/EP2044067B1/en active Active
- 2007-07-17 CL CL2007002078A patent/CL2007002078A1/es unknown
- 2007-07-18 PE PE2007000929A patent/PE20081307A1/es not_active Application Discontinuation
- 2007-07-19 AR ARP070103217A patent/AR061933A1/es unknown
- 2007-07-20 TW TW096126654A patent/TWI363057B/zh active
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2008
- 2008-11-26 ZA ZA200810051A patent/ZA200810051B/xx unknown
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- 2009-01-01 IL IL196324A patent/IL196324A/en active IP Right Grant
- 2009-01-06 EC EC2009009033A patent/ECSP099033A/es unknown
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- 2009-01-21 CO CO09004925A patent/CO6460740A2/es active IP Right Grant
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