BR112012012497A2 - método para preparar iodixanol - Google Patents
método para preparar iodixanolInfo
- Publication number
- BR112012012497A2 BR112012012497A2 BR112012012497A BR112012012497A BR112012012497A2 BR 112012012497 A2 BR112012012497 A2 BR 112012012497A2 BR 112012012497 A BR112012012497 A BR 112012012497A BR 112012012497 A BR112012012497 A BR 112012012497A BR 112012012497 A2 BR112012012497 A2 BR 112012012497A2
- Authority
- BR
- Brazil
- Prior art keywords
- iodixanol
- product
- recovery
- compound
- chromatographic column
- Prior art date
Links
- NBQNWMBBSKPBAY-UHFFFAOYSA-N iodixanol Chemical compound IC=1C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C(I)C=1N(C(=O)C)CC(O)CN(C(C)=O)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NBQNWMBBSKPBAY-UHFFFAOYSA-N 0.000 title abstract 9
- 229960004359 iodixanol Drugs 0.000 title abstract 9
- 238000000034 method Methods 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 abstract 2
- 239000012043 crude product Substances 0.000 abstract 2
- 239000000047 product Substances 0.000 abstract 2
- 238000011084 recovery Methods 0.000 abstract 2
- 239000011347 resin Substances 0.000 abstract 2
- 229920005989 resin Polymers 0.000 abstract 2
- 238000001179 sorption measurement Methods 0.000 abstract 2
- 238000001308 synthesis method Methods 0.000 abstract 2
- -1 (2,3-dihydroxypropyl) -2,4,6-triiodoisophthalimide Chemical compound 0.000 abstract 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 abstract 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 abstract 1
- 230000002378 acidificating effect Effects 0.000 abstract 1
- 230000029936 alkylation Effects 0.000 abstract 1
- 238000005804 alkylation reaction Methods 0.000 abstract 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 abstract 1
- 239000004327 boric acid Substances 0.000 abstract 1
- 229910052796 boron Inorganic materials 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 abstract 1
- 238000006471 dimerization reaction Methods 0.000 abstract 1
- 239000012046 mixed solvent Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- 239000011541 reaction mixture Substances 0.000 abstract 1
- 238000001953 recrystallisation Methods 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 238000007086 side reaction Methods 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/22—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the construction of the column
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B63/00—Purification; Separation; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/46—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having carbon atoms of carboxamide groups, amino groups and at least three atoms of bromine or iodine, bound to carbon atoms of the same non-condensed six-membered aromatic ring
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/38—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups B01D15/265 - B01D15/36
- B01D2015/3838—Ligand exchange chromatography, e.g. complexation chromatography, chelation chromatography, metal interaction chromatography
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
método para preparar iodixanol. um método de síntese aperfeiçoado para a preparação de iodixanol, e um processo de purificação através de coluna cromatográfica de resina de adsorção macroporosa e recristalização são providos. o método de síntese refere-se á dimerização de 5-acetamido-n,n1-bis(2,3-di-idroxipropil)-2,4,6-tri-iodo-isoftalimida (composto a) para preparar iodixanol, em que as reações colaterais excessivas, tais que a alquilação, são inibidas, de um modo efetivo, através do controle do ph da mistura da reação com uma substânci ácida contendo boro ou sais da mesma, tais que o ácido bórico. deste modo, a taxa de conversão do composto a para iodixanol é de 85-90%. o produto bruto de iodixanol é purificado através de uma coluna cromatográfica de resina de adsorção macroporosa, sendo obtido o produto iodixanol com uma recuperação de 90-95% e uma pureza de 96-98%. o produto bruto iodixanol é recristalizado em solvente misto contendo 2-metoxietanol, sendo obtido o produto iodixanol com uma recuperação de 90-95% e uma pureza superior a 99%.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CN2009/001333 WO2011063551A1 (en) | 2009-11-26 | 2009-11-26 | Preparation and purification of iodixanol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BR112012012497A2 true BR112012012497A2 (pt) | 2016-04-12 |
| BR112012012497B1 BR112012012497B1 (pt) | 2021-09-08 |
Family
ID=44065809
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112012012497-8A BR112012012497B1 (pt) | 2009-11-26 | 2009-11-26 | Método para preparar iodixanol |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US8766002B2 (pt) |
| EP (1) | EP2504298B1 (pt) |
| JP (1) | JP5775524B2 (pt) |
| KR (1) | KR101699226B1 (pt) |
| CN (1) | CN102725249B (pt) |
| AU (1) | AU2009355814B2 (pt) |
| BR (1) | BR112012012497B1 (pt) |
| ES (1) | ES2607481T3 (pt) |
| PT (1) | PT2504298T (pt) |
| WO (1) | WO2011063551A1 (pt) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102079716B (zh) * | 2009-11-26 | 2014-03-05 | 浙江台州海神制药有限公司 | 碘克沙醇的制备与纯化 |
| EP2655318B1 (en) * | 2010-12-21 | 2018-06-20 | GE Healthcare AS | Desalination of a composition comprising a contrast agent |
| CN102875411A (zh) * | 2012-10-30 | 2013-01-16 | 广州牌牌生物科技有限公司 | 一种用大孔树脂分离纯化碘克沙醇注射剂原料的方法 |
| JP6342421B2 (ja) * | 2012-12-19 | 2018-06-13 | ジーイー・ヘルスケア・アクスイェ・セルスカプ | Ｘ線造影剤の精製 |
| PT108524B (pt) * | 2015-06-02 | 2017-12-15 | Hovione Farmaciência S A | Processo para a preparação de intermediários úteis na preparação de agentes de contraste não-iónicos |
| RU2655619C1 (ru) * | 2017-06-13 | 2018-05-29 | Алексей Георгиевич Александров | Способ получения фармацевтической субстанции на основе йогексола |
| CN111777525B (zh) * | 2019-04-04 | 2021-08-27 | 成都西岭源药业有限公司 | 一种碘克沙醇的精制方法 |
| CN109896972B (zh) * | 2019-04-16 | 2021-12-28 | 同舟纵横（厦门）流体技术有限公司 | 一种碘海醇合成液纳滤脱盐的方法及装置 |
| CN112125820B (zh) * | 2019-06-25 | 2023-05-02 | 成都西岭源药业有限公司 | 一种造影剂的纯化方法 |
| CN111100029B (zh) * | 2019-12-30 | 2023-05-05 | 高陵蓝晓科技新材料有限公司 | 一种高载量碘海醇的纯化方法 |
| CN113121377A (zh) * | 2019-12-31 | 2021-07-16 | 江苏汉邦科技有限公司 | 碘克沙醇的纯化方法 |
| CN113495100A (zh) * | 2020-03-19 | 2021-10-12 | 南京正大天晴制药有限公司 | 一种等渗碘造影剂的含量测定方法 |
| CN115554731B (zh) * | 2022-10-24 | 2023-06-30 | 连云港贵科药业有限公司 | 一种吉西他滨的制备装置及制备方法 |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NO161368C (no) * | 1982-11-08 | 1989-08-09 | Nyegaard & Co As | Roentgenkontrastmidler samt radiologiske preparater derav. |
| CA1200785A (en) | 1982-11-08 | 1986-02-18 | Walter G. Berghahn | Dispenser with self-sealing applicator |
| US5204005A (en) | 1990-02-26 | 1993-04-20 | Mallinckrodt, Inc. | Reversed phase chromatographic process |
| IT1282674B1 (it) | 1996-02-23 | 1998-03-31 | Bracco Spa | Processo per la purificazione di agenti contrastografici opacizzanti |
| ES2103252T3 (es) | 1995-05-23 | 1999-04-01 | Fructamine Spa | Procedimiento para la preparacion de un dicloruro de acido dicarboxilico. |
| US5763650A (en) | 1995-05-23 | 1998-06-09 | Fructamine S.P.A. | Process for the preparation of a halosubstituted aromatic acid |
| IT1282653B1 (it) | 1996-02-20 | 1998-03-31 | Bracco Spa | Dispositivo e metodo per la rigenerazione di letti misti di resine a scambio ionico |
| US5705692A (en) | 1996-09-27 | 1998-01-06 | Abbott Laboratories | Process for the preparation of iohexol |
| GB9624612D0 (en) | 1996-11-26 | 1997-01-15 | Nycomed Imaging As | Process |
| IT1290456B1 (it) * | 1997-04-04 | 1998-12-03 | Dibra Spa | Processo per la preparazione di un amminoalcol |
| IT1292037B1 (it) | 1997-05-30 | 1999-01-25 | Bracco Spa | Processo per la preparazione di 5-(acetil 62,3-diidrossipropil)- ammino)-n,n'-bis(2,3-diidrossipropil)-2,4,6-triiodo-1,3-benzen- |
| GB9720969D0 (en) | 1997-10-02 | 1997-12-03 | Nycomed Imaging As | Process |
| GB2331098A (en) * | 1997-11-07 | 1999-05-12 | Nycomed Imaging As | An N-Alkylation process |
| EP0992245A1 (en) * | 1998-09-16 | 2000-04-12 | Goldham Bioglan Pharma GmbH | Radio-contrast agents |
| KR100625222B1 (ko) | 1999-02-11 | 2006-09-19 | 길린 지키 파마슈티컬 컴퍼니 리미티드 | 신규 짐넴산 유도체, 그 제조 방법, 및 그의 약학적 용도 |
| GB9903109D0 (en) | 1999-02-11 | 1999-04-07 | Nycomed Imaging As | Process |
| NO20033058D0 (no) * | 2003-07-03 | 2003-07-03 | Amersham Health As | Prosess |
| KR100524146B1 (ko) | 2003-07-08 | 2005-10-26 | 주식회사태준제약 | 아이오디사놀의 신규 제조방법 |
| KR100539067B1 (ko) | 2003-09-05 | 2005-12-26 | 주식회사태준제약 | Ｘ-선 조영제로서 아이오디사놀의 신규 제조방법 |
| NO20043305D0 (no) | 2004-08-09 | 2004-08-09 | Amersham Health As | Preparation of lodixanol |
| NO20053687D0 (no) * | 2005-07-29 | 2005-07-29 | Amersham Health As | Crystallisation Process. |
| NO20055643D0 (no) | 2005-11-29 | 2005-11-29 | Amersham Health As | Preparation of lodixanol |
| WO2007073202A1 (en) | 2005-12-19 | 2007-06-28 | Ge Healthcare As | Purification process of iodixanol |
| ES2398291T3 (es) | 2006-02-14 | 2013-03-15 | Ge Healthcare As | Agentes de contraste |
| CN101293855B (zh) * | 2007-04-27 | 2012-08-29 | 上海冠杰生物医药科技有限公司 | 一种碘克沙醇的纯化方法 |
| US20110021823A1 (en) * | 2009-07-21 | 2011-01-27 | Ge Healthcare As | Processing crude iodixanol mixture by nanofiltration |
| CN102079716B (zh) * | 2009-11-26 | 2014-03-05 | 浙江台州海神制药有限公司 | 碘克沙醇的制备与纯化 |
-
2009
- 2009-11-26 EP EP09851564.6A patent/EP2504298B1/en active Active
- 2009-11-26 WO PCT/CN2009/001333 patent/WO2011063551A1/en active Search and Examination
- 2009-11-26 ES ES09851564.6T patent/ES2607481T3/es active Active
- 2009-11-26 CN CN200980162617.0A patent/CN102725249B/zh active Active
- 2009-11-26 KR KR1020127016435A patent/KR101699226B1/ko active IP Right Grant
- 2009-11-26 BR BR112012012497-8A patent/BR112012012497B1/pt active IP Right Grant
- 2009-11-26 JP JP2012540249A patent/JP5775524B2/ja active Active
- 2009-11-26 AU AU2009355814A patent/AU2009355814B2/en active Active
- 2009-11-26 US US13/510,432 patent/US8766002B2/en active Active
- 2009-11-26 PT PT98515646T patent/PT2504298T/pt unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR101699226B1 (ko) | 2017-01-24 |
| CN102725249B (zh) | 2014-12-10 |
| AU2009355814B2 (en) | 2016-06-30 |
| BR112012012497B1 (pt) | 2021-09-08 |
| AU2009355814A1 (en) | 2012-06-07 |
| US20120283474A1 (en) | 2012-11-08 |
| ES2607481T3 (es) | 2017-03-31 |
| EP2504298A4 (en) | 2013-05-01 |
| WO2011063551A1 (en) | 2011-06-03 |
| JP2013512196A (ja) | 2013-04-11 |
| KR20120105015A (ko) | 2012-09-24 |
| EP2504298B1 (en) | 2016-09-21 |
| JP5775524B2 (ja) | 2015-09-09 |
| CN102725249A (zh) | 2012-10-10 |
| PT2504298T (pt) | 2016-12-29 |
| US8766002B2 (en) | 2014-07-01 |
| EP2504298A1 (en) | 2012-10-03 |
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Legal Events
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| B07D | Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette] |
Free format text: DE ACORDO COM O ARTIGO 229-C DA LEI NO 10196/2001, QUE MODIFICOU A LEI NO 9279/96, A CONCESSAO DA PATENTE ESTA CONDICIONADA A ANUENCIA PREVIA DA ANVISA. CONSIDERANDO A APROVACAO DOS TERMOS DO PARECER NO 337/PGF/EA/2010, BEM COMO A PORTARIA INTERMINISTERIAL NO 1065 DE 24/05/2012, ENCAMINHA-SE O PRESENTE PEDIDO PARA AS PROVIDENCIAS CABIVEIS. |
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| B07E | Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette] | ||
| B06U | Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette] | ||
| B07A | Application suspended after technical examination (opinion) [chapter 7.1 patent gazette] | ||
| B09A | Decision: intention to grant [chapter 9.1 patent gazette] | ||
| B16A | Patent or certificate of addition of invention granted [chapter 16.1 patent gazette] |
Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 26/11/2009, OBSERVADAS AS CONDICOES LEGAIS. PATENTE CONCEDIDA CONFORME ADI 5.529/DF, QUE DETERMINA A ALTERACAO DO PRAZO DE CONCESSAO. |