CL2013003045A1 - Proceso para preparar gadobutrol de alta pureza con una pureza de 99,7% por reaccion de cicleno (1,4,7,10-tetraazaciclododecano) con 4,4-dimetil-3,5,8-trioxabiciclo[5.1.0]octano y cloruro de litio en isopropanol; y forma polimorfica i monohidrato i de gadobutrol. - Google Patents
Proceso para preparar gadobutrol de alta pureza con una pureza de 99,7% por reaccion de cicleno (1,4,7,10-tetraazaciclododecano) con 4,4-dimetil-3,5,8-trioxabiciclo[5.1.0]octano y cloruro de litio en isopropanol; y forma polimorfica i monohidrato i de gadobutrol.Info
- Publication number
- CL2013003045A1 CL2013003045A1 CL2013003045A CL2013003045A CL2013003045A1 CL 2013003045 A1 CL2013003045 A1 CL 2013003045A1 CL 2013003045 A CL2013003045 A CL 2013003045A CL 2013003045 A CL2013003045 A CL 2013003045A CL 2013003045 A1 CL2013003045 A1 CL 2013003045A1
- Authority
- CL
- Chile
- Prior art keywords
- gadobutrol
- tetraazacyclododecane
- water
- purity
- ciclene
- Prior art date
Links
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
- C07F5/003—Compounds containing elements of Groups 3 or 13 of the Periodic System without C-Metal linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
- A61K49/106—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
- A61K49/106—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA
- A61K49/108—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA the metal complex being Gd-DOTA
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2123/00—Preparations for testing in vivo
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Radiology & Medical Imaging (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Proceso para producir gadobutrol alta pureza (complejo de gadolinio de N-(1-hidroximetil-2,3-dihidroxipropil)-1,4,7-triscarboximetil-1,4,7,10-tetraazaciclododecano) con una pureza mayor de 99,97% por reacción de cicleno (1,4,7,10-tetraazaciclododecano) con 4,4-dimetil-3,5,8-trioxabiciclo[5.1.0]octano y cloruro de litio en isopropanol a altas temperaturas, luego se destila sobre agua y se alquila con monocloroacetato de sodio en medio alcalino, continuando el trabajo en condiciones clorhídriacas, se separan las sales agregando metanol y se hace reaccionar el ligando crudo con óxido de gadolinio en agua a altas temperaturas, luego se lleva el pH a un valor de 7,1-7,4 con hidróxido de litio, se concentra la solución y se agrega etanol en una cantidad tal que se alcance un contenido de agua de preferiblemente 7,0-9,5%, luego se calienta la mezcla bajo reflujo durante por lo menos 60 minutos y luego del enfriamiento, se aísla el producto crudo y se seca a 46-48 °C, se disuelve después el producto crudo en agua y se purifica en una cascada de intercambiadores de iones, donde la solución se hace pasar primero a través del intercambiador de iones ácido y luego a través del básico, luego se concentra la solución purificada, que tiene conductancia <40µS/cm, se la trata con carbón activado, se somete a filtración estéril y se lleva a un contenido de agua dentro de rango entre 10-12% por agregado dosificado de etanol, luego se lleva a ebullición bajo reflujo y se enfría, se aísla y se seca el producto; y forma polimórfica I monohidrato I de gadobutrol.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102011100128 | 2011-04-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CL2013003045A1 true CL2013003045A1 (es) | 2014-05-02 |
Family
ID=46208435
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CL2013003045A CL2013003045A1 (es) | 2011-04-21 | 2013-10-21 | Proceso para preparar gadobutrol de alta pureza con una pureza de 99,7% por reaccion de cicleno (1,4,7,10-tetraazaciclododecano) con 4,4-dimetil-3,5,8-trioxabiciclo[5.1.0]octano y cloruro de litio en isopropanol; y forma polimorfica i monohidrato i de gadobutrol. |
Country Status (34)
| Country | Link |
|---|---|
| US (2) | US10072027B2 (es) |
| EP (2) | EP2896405B1 (es) |
| JP (3) | JP6096757B2 (es) |
| KR (3) | KR20190079682A (es) |
| CN (1) | CN103547573B (es) |
| AR (1) | AR086190A1 (es) |
| AU (2) | AU2012244791B2 (es) |
| BR (1) | BR112013027028B1 (es) |
| CA (1) | CA2833659C (es) |
| CL (1) | CL2013003045A1 (es) |
| CO (1) | CO6801752A2 (es) |
| CU (2) | CU24439B1 (es) |
| DK (1) | DK2896405T3 (es) |
| DO (1) | DOP2013000245A (es) |
| EA (2) | EA026572B1 (es) |
| EC (1) | ECSP13013010A (es) |
| ES (1) | ES2780599T3 (es) |
| GT (1) | GT201300253A (es) |
| HK (1) | HK1193817A1 (es) |
| HR (1) | HRP20200336T1 (es) |
| IL (1) | IL228885A (es) |
| LT (1) | LT2896405T (es) |
| MX (1) | MX362133B (es) |
| MY (1) | MY163709A (es) |
| NZ (1) | NZ616637A (es) |
| PE (1) | PE20141325A1 (es) |
| PL (1) | PL2896405T3 (es) |
| PT (1) | PT2896405T (es) |
| RS (1) | RS60001B1 (es) |
| SG (1) | SG194511A1 (es) |
| SI (1) | SI2896405T1 (es) |
| TW (1) | TW201249818A (es) |
| WO (1) | WO2012143355A1 (es) |
| ZA (1) | ZA201308706B (es) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RS60001B1 (sr) * | 2011-04-21 | 2020-04-30 | Bayer Ip Gmbh | Pripremanje gadobutrola visoke čistoće |
| US10195295B2 (en) * | 2014-02-06 | 2019-02-05 | T2Pharma Gmbh | Process for purifying 1,4,7,10-tetra-azacyclododecane-1,4,7,10-tetraacetic acid |
| KR101693400B1 (ko) * | 2014-09-17 | 2017-01-05 | 에스티팜 주식회사 | 칼코부트롤의 제조방법 |
| KR101646211B1 (ko) * | 2014-11-12 | 2016-08-05 | (주)디아이테크 | 자기공명영상용 조영제의 제조방법 |
| KR101653064B1 (ko) | 2014-12-26 | 2016-09-09 | 에스티팜 주식회사 | 가도부트롤의 제조방법 |
| PL3519394T3 (pl) | 2016-09-27 | 2020-11-30 | Bayer Pharma Aktiengesellschaft | Sposób wytwarzania krystalicznej postaci o modyfikacji a kalkobutrolu |
| CN106543094A (zh) * | 2016-11-04 | 2017-03-29 | 嘉实（湖南）医药科技有限公司 | 高纯度钆布醇的制备方法 |
| EP3544964B1 (en) | 2016-11-28 | 2020-06-17 | Bayer Pharma Aktiengesellschaft | High relaxivity gadolinium chelate compounds for use in magnetic resonance imaging |
| CN109293592A (zh) * | 2017-07-24 | 2019-02-01 | 天津科伦药物研究有限公司 | 一种制备钆布醇的方法 |
| KR101971435B1 (ko) * | 2017-08-29 | 2019-04-24 | 주식회사 엔지켐생명과학 | 가도부트롤 중간체 및 이를 이용한 가도부트롤의 제조 방법 |
| CN108840832A (zh) * | 2018-06-29 | 2018-11-20 | 广州康瑞泰药业有限公司 | 一种钆布醇中间体的制备方法 |
| EP3820853A4 (en) * | 2018-07-10 | 2022-08-17 | Biophore India Pharmaceuticals Pvt. Ltd. | PROCESS FOR THE PREPARATION OF 2,2',2''-( 10-((2R,3S)-1,3,4-TRIHYDROXY BUTAN-2-YL)-1,4,7,10-TETRAAZACYCLODODECAN-1,4 ,7-TRIYL)-TRIACETIC ACID AND THEIR COMPLEXES |
| KR102167614B1 (ko) * | 2018-08-23 | 2020-10-19 | 에스티팜 주식회사 | 가도부트롤의 제조방법 |
| AU2019382881A1 (en) | 2018-11-23 | 2021-05-20 | Bayer Aktiengesellschaft | Formulation of contrast media and process of preparation thereof |
| JP2022513195A (ja) * | 2018-12-12 | 2022-02-07 | メディビーコン，インク． | 持続的腎代替療法における経皮的糸球体濾過量測定の使用 |
| GB201919073D0 (en) * | 2019-12-20 | 2020-02-05 | Ge Healthcare As | Novel manufacturing process |
| CN113087680A (zh) * | 2020-01-08 | 2021-07-09 | 威智医药有限公司 | Dota晶型及其制备方法 |
| CN113105407A (zh) * | 2020-01-13 | 2021-07-13 | 北京北陆药业股份有限公司 | 一种钆布醇新型晶型及其制备方法 |
| KR20210114742A (ko) * | 2020-03-11 | 2021-09-24 | 주식회사 엔지켐생명과학 | 칼테리돌의 제조방법 |
| CN114539178B (zh) * | 2020-11-26 | 2024-03-15 | 江苏恒瑞医药股份有限公司 | 一种钆布醇的纯化方法 |
| CN114573522A (zh) * | 2020-11-30 | 2022-06-03 | 江苏恒瑞医药股份有限公司 | 一种考布曲钙的新晶型及其制备方法 |
| CN112939806B (zh) * | 2021-03-08 | 2023-05-16 | 山东新华制药股份有限公司 | 一种卡比多巴的精制方法 |
| CN113527223B (zh) * | 2021-06-22 | 2023-05-09 | 安徽普利药业有限公司 | 一种钆布醇的精制方法 |
| CN114105897B (zh) * | 2021-07-29 | 2023-04-04 | 安徽普利药业有限公司 | 一种钆特醇的制备方法 |
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| US4957939A (en) | 1981-07-24 | 1990-09-18 | Schering Aktiengesellschaft | Sterile pharmaceutical compositions of gadolinium chelates useful enhancing NMR imaging |
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| US4885363A (en) | 1987-04-24 | 1989-12-05 | E. R. Squibb & Sons, Inc. | 1-substituted-1,4,7-triscarboxymethyl-1,4,7,10-tetraazacyclododecane and analogs |
| DE3625417C2 (de) | 1986-07-28 | 1998-10-08 | Schering Ag | Tetraazacyclododecan-Derivate |
| DE3640708C2 (de) | 1986-11-28 | 1995-05-18 | Schering Ag | Verbesserte metallhaltige Pharmazeutika |
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| US5410043A (en) | 1991-12-06 | 1995-04-25 | Schering Aktiengesellschaft | Process for the production of mono-N-substituted tetraaza macrocycles |
| DE4237943C2 (de) | 1992-11-06 | 1997-10-23 | Schering Ag | Verfahren zur Herstellung von Metallkomplexen der N-beta-Hydroxyalkyl-tri-N-carboxyalkyl-1,4,7,10-tetraazacyclododecan- und N-beta-Hydroxyalkyl-tri-N-carboxyalkyl-1,4,8,11-tetraazacyclotetradecan-Derivate |
| DE4140779A1 (de) | 1991-12-06 | 1993-06-09 | Schering Ag Berlin Und Bergkamen, 1000 Berlin, De | Verfahren zur herstellung von mono-n-substituierten tetraazamakrocyclen |
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| IT1275426B (it) | 1995-05-16 | 1997-08-07 | Bracco Spa | Recupero del gadolinio e dei suoi agenti complessanti da soluzioni acquose contenenti i loro complessi |
| US5744616A (en) | 1996-02-26 | 1998-04-28 | Schering Aktiengesellschaft | Process for the production of 1,4,7,10-tetraazacyclododecane and its derivatives |
| DE19608307C1 (de) * | 1996-02-26 | 1997-08-28 | Schering Ag | Verfahren zur Herstellung von 1,4,7,10-Tetraazacyclododecan und dessen Derivaten |
| DE19724186C2 (de) | 1997-06-02 | 2002-07-18 | Schering Ag | Verfahren zur Mono- und 1,7-Bis-N-ß-Hydroxyalkylierung von Cyclen und die entsprechenden N-ß-Hydroxyalkyl-1,4,7,10-tetraazacyclododecan-Li-Salz-Komplexe |
| IT1292127B1 (it) | 1997-06-11 | 1999-01-25 | Bracco Spa | Processo per la dissalazione di sostanze instabili a ph acidi |
| IT1292128B1 (it) * | 1997-06-11 | 1999-01-25 | Bracco Spa | Processo per la preparazione di chelanti macrociclici e loro chelati con ioni metallici paramagnetici |
| DE69903603T2 (de) | 1998-09-08 | 2003-08-14 | Kba Giori Sa | Sicherheitsdruckmaschine für Wertpapiere |
| DE10064467C2 (de) * | 2000-12-15 | 2002-10-31 | Schering Ag | Lithium-Komplexe von N-(1-Hydroxymethyl-2,3-dihydroxypropyl)-1,4,7-triscarboxymethyl-1,4,7,10-tetraazacyclododecan, deren Herstellung und Verwendung |
| DE102009053171B4 (de) | 2009-11-04 | 2011-07-21 | Bayer Schering Pharma Aktiengesellschaft, 13353 | Verfahren zur Herstellung des Calcium-Komplexes von Dihydroxy-hydroxy-methylpropyl-tetraazacyclododecan-triessigsäure (Calcobutrol) |
| WO2011054480A1 (de) | 2009-11-09 | 2011-05-12 | Bayer Schering Pharma Aktiengesellschaft | Gadobutrolherstellung mittels keramischer membran |
| DE102010013833A1 (de) | 2010-03-29 | 2011-09-29 | Bayer Schering Pharma Aktiengesellschaft | Herstellung von Gadobutrol mittels Dimethylformamiddimethylacetal |
| DE102010023105A1 (de) | 2010-06-04 | 2011-12-08 | Bayer Schering Pharma Aktiengesellschaft | Gadobutrolherstellung im Eintopfverfahren mittels DMF-acetal und N-Methylimidazol |
| RS60001B1 (sr) * | 2011-04-21 | 2020-04-30 | Bayer Ip Gmbh | Pripremanje gadobutrola visoke čistoće |
| KR101653064B1 (ko) | 2014-12-26 | 2016-09-09 | 에스티팜 주식회사 | 가도부트롤의 제조방법 |
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2012
- 2012-04-17 RS RS20200238A patent/RS60001B1/sr unknown
- 2012-04-17 PE PE2013002379A patent/PE20141325A1/es active IP Right Grant
- 2012-04-17 EP EP14172784.2A patent/EP2896405B1/en active Active
- 2012-04-17 KR KR1020197017528A patent/KR20190079682A/ko active Application Filing
- 2012-04-17 BR BR112013027028-4A patent/BR112013027028B1/pt active IP Right Grant
- 2012-04-17 EA EA201301182A patent/EA026572B1/ru not_active IP Right Cessation
- 2012-04-17 US US14/112,994 patent/US10072027B2/en active Active
- 2012-04-17 EA EA201600272A patent/EA201600272A1/ru unknown
- 2012-04-17 MX MX2013012290A patent/MX362133B/es active IP Right Grant
- 2012-04-17 CA CA2833659A patent/CA2833659C/en active Active
- 2012-04-17 EP EP12725635.2A patent/EP2699556A1/en not_active Ceased
- 2012-04-17 LT LTEP14172784.2T patent/LT2896405T/lt unknown
- 2012-04-17 CN CN201280024781.7A patent/CN103547573B/zh active Active
- 2012-04-17 DK DK14172784.2T patent/DK2896405T3/da active
- 2012-04-17 KR KR1020207014352A patent/KR20200059319A/ko not_active IP Right Cessation
- 2012-04-17 PT PT141727842T patent/PT2896405T/pt unknown
- 2012-04-17 AU AU2012244791A patent/AU2012244791B2/en active Active
- 2012-04-17 SG SG2013077094A patent/SG194511A1/en unknown
- 2012-04-17 KR KR1020137030655A patent/KR102003570B1/ko active IP Right Grant
- 2012-04-17 NZ NZ616637A patent/NZ616637A/en unknown
- 2012-04-17 SI SI201231741T patent/SI2896405T1/sl unknown
- 2012-04-17 WO PCT/EP2012/057013 patent/WO2012143355A1/en active Application Filing
- 2012-04-17 MY MYPI2013701962A patent/MY163709A/en unknown
- 2012-04-17 PL PL14172784T patent/PL2896405T3/pl unknown
- 2012-04-17 JP JP2014505591A patent/JP6096757B2/ja active Active
- 2012-04-17 ES ES14172784T patent/ES2780599T3/es active Active
- 2012-04-17 CU CU2016000163A patent/CU24439B1/es unknown
- 2012-04-20 AR ARP120101354A patent/AR086190A1/es active Pending
- 2012-04-23 TW TW101114466A patent/TW201249818A/zh unknown
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2013
- 2013-10-15 IL IL228885A patent/IL228885A/en active IP Right Grant
- 2013-10-18 GT GT201300253A patent/GT201300253A/es unknown
- 2013-10-21 CO CO13248770A patent/CO6801752A2/es not_active Application Discontinuation
- 2013-10-21 CU CU2013000142A patent/CU20130142A7/es unknown
- 2013-10-21 DO DO2013000245A patent/DOP2013000245A/es unknown
- 2013-10-21 CL CL2013003045A patent/CL2013003045A1/es unknown
- 2013-11-05 EC ECSP13013010 patent/ECSP13013010A/es unknown
- 2013-11-20 ZA ZA2013/08706A patent/ZA201308706B/en unknown
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2014
- 2014-07-15 HK HK14107203.2A patent/HK1193817A1/zh unknown
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2016
- 2016-11-08 JP JP2016217880A patent/JP2017031220A/ja active Pending
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2017
- 2017-06-30 AU AU2017204495A patent/AU2017204495A1/en not_active Abandoned
- 2017-07-31 US US15/664,060 patent/US10435417B2/en active Active
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2018
- 2018-09-05 JP JP2018165787A patent/JP2018188477A/ja active Pending
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2020
- 2020-02-27 HR HRP20200336TT patent/HRP20200336T1/hr unknown
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