公开(公告)号：US06872380B2

公开(公告)日：2005-03-29

申请号：US09990537

申请日：2001-11-16

申请人： Oskar Axelsson ,  Charlotte Olofsson ,  Axel Morgenstjerne ,  Georg Hansson ,  Haukur Johannesson ,  Jan-Henrik Ardenkjaer-Larsen

发明人： Oskar Axelsson ,  Charlotte Olofsson ,  Axel Morgenstjerne ,  Georg Hansson ,  Haukur Johannesson ,  Jan-Henrik Ardenkjaer-Larsen

IPC分类号： A61K49/00 ,  A61K49/18 ,  C07C67/303 ,  C07C69/675 ,  G01R33/28 ,  G01R33/483 ,  A61B5/055 ,  C07C69/02

CPC分类号： A61K49/1815

摘要： The present invention provides a process for the preparation of an MR contrast agent, said process comprising: i) obtaining a solution in a solvent of a hydrogenatable, unsaturated substrate compound and a catalyst for the hydrogenation of said substrate compound; ii) introducing said solution in droplet form into a chamber containing hydrogen gas (H2) enriched in para-hydrogen (p-1H2) and/or ortho-deuterium (o-2H2) whereby to hydrogenate said substrate to form a hydrogenated imaging agent; iii) optionally subjecting said hydrogenated imaging agent to a magnetic field having a field strength below earth's ambient field strength; iv) optionally dissolving said imaging agent in an aqueous medium; v) optionally separating said catalyst from the solution of said imaging agent in said aqueous medium; vi) optionally separating said solvent from the solution of said imaging agent in said aqueous medium; and vii) optionally freezing the solution of said imaging agent in said aqueous medium.

摘要翻译： 本发明提供一种制备MR造影剂的方法，所述方法包括：i）获得在可氢化不饱和底物化合物的溶剂中的溶液和用于所述底物化合物氢化的催化剂; ii）将所述溶液 以液滴形式进入含有富氢对氢（对 - 氢）和/或邻 - 氘（o- 2 H 2）的氢气（H 2）和/或邻 - 氘（o- 2 H 2）的室中，由此氢化所述基底以形成氢化显像剂 iii）任选地使所述氢化显像剂经受场强低于地球环境场强的磁场; iv）任选地将所述成像剂溶解在水性介质中; v）任选地将所述催化剂与所述成像剂在所述 水性介质; vi）任选地将所述溶剂与所述显影剂的溶液在所述水性介质中分离; 和任选地将所述显像剂的溶液冷冻在所述水性介质中。

公开(公告)号：US20050152840A1

公开(公告)日：2005-07-14

申请号：US11002864

申请日：2004-12-02

申请人： Oskar Axelsson ,  Charlotte Olofsson ,  Axel Morgenstjerne ,  Georg Hansson ,  Haukur Johannesson ,  Jan-Henrik Ardenkjaer-Larsen

发明人： Oskar Axelsson ,  Charlotte Olofsson ,  Axel Morgenstjerne ,  Georg Hansson ,  Haukur Johannesson ,  Jan-Henrik Ardenkjaer-Larsen

IPC分类号： A61K49/00 ,  A61K49/18 ,  C07C67/303 ,  C07C69/675 ,  G01R33/28 ,  G01R33/483

CPC分类号： A61K49/1815

摘要： The present invention provides a process for the preparation of an MR contrast agent, said process comprising: i) obtaining a solution in a solvent of a hydrogenatable, unsaturated substrate compound and a catalyst for the hydrogenation of said substrate compound; ii) introducing said solution in droplet form into a chamber containing hydrogen gas (H2) enriched in para-hydrogen (p-1H2) and/or ortho-deuterium (o-2H2) whereby to hydrogenate said substrate to form a hydrogenated imaging agent; iii) optionally subjecting said hydrogenated imaging agent to a magnetic field having a field strength below earth's ambient field strength; iv) optionally dissolving said imaging agent in an aqueous medium; v) optionally separating said catalyst from the solution of said imaging agent in said aqueous medium; vi) optionally separating said solvent from the solution of said imaging agent in said aqueous medium; and vii) optionally freezing the solution of said imaging agent in said aqueous medium.

摘要翻译： 本发明提供了一种制备MR造影剂的方法，所述方法包括：i）获得在可氢化不饱和底物化合物的溶剂中的溶液和用于所述底物化合物氢化的催化剂; ii）将所述液滴形式的溶液引入含有富氢对二氢的氢气（H 2 S 2 H 2）的室中， ）和/或邻 - 氘（o-2 H 2 H 2），由此氢化所述底物以形成氢化显像剂; iii）任选地使所述氢化成像剂经受场强低于地球环境场强的磁场; iv）任选地将所述成像剂溶解在水性介质中; v）任选地将所述催化剂与所述显影剂的溶液在所述水性介质中分离; vi）任选地将所述溶剂与所述显影剂的溶液在所述水性介质中分离; 和vii）任选地将所述成像剂的溶液冷冻在所述水性介质中。

公开(公告)号：US07459144B2

公开(公告)日：2008-12-02

申请号：US11002864

申请日：2004-12-02

申请人： Oskar Axelsson ,  Charlotte Olofsson ,  Axel Morgenstjerne ,  Georg Hansson ,  Haukur Johannesson ,  Jan-Henrik Ardenkjaer-Larsen

发明人： Oskar Axelsson ,  Charlotte Olofsson ,  Axel Morgenstjerne ,  Georg Hansson ,  Haukur Johannesson ,  Jan-Henrik Ardenkjaer-Larsen

IPC分类号： A61B5/055 ,  B01J10/00

CPC分类号： A61K49/1815

摘要： The present invention provides a process for the preparation of an MR contrast agent, said process comprising: i) obtaining a solution in a solvent of a hydrogenatable, unsaturated substrate compound and a catalyst for the hydrogenation of said substrate compound; ii) introducing said solution in droplet form into a chamber containing hydrogen gas (H2) enriched in para-hydrogen (p-1H2) and/or ortho-deuterium (o-2H2) whereby to hydrogenate said substrate to form a hydrogenated imaging agent; iii) optionally subjecting said hydrogenated imaging agent to a magnetic field having a field strength below earth's ambient field strength; iv) optionally dissolving said imaging agent in an aqueous medium; v) optionally separating said catalyst from the solution of said imaging agent in said aqueous medium; vi) optionally separating said solvent from the solution of said imaging agent in said aqueous medium; and vii) optionally freezing the solution of said imaging agent in said aqueous medium.

摘要翻译： 本发明提供了一种制备MR造影剂的方法，所述方法包括：i）获得在可氢化不饱和底物化合物的溶剂中的溶液和用于所述底物化合物氢化的催化剂; ii）将所述液滴形式的溶液引入含有富氢对二氢（p-1H 2）和/或邻 - 氘（o-2H 2）的氢气（H 2）的室中，从而氢化所述底物以形成氢化显像剂; iii）任选地使所述氢化成像剂经受场强低于地球环境场强的磁场; iv）任选地将所述成像剂溶解在水性介质中; v）任选地将所述催化剂与所述显影剂的溶液在所述水性介质中分离; vi）任选地将所述溶剂与所述显影剂的溶液在所述水性介质中分离; 和vii）任选地将所述成像剂的溶液冷冻在所述水性介质中。

公开(公告)号：US06574495B1

公开(公告)日：2003-06-03

申请号：US09565450

申请日：2000-05-05

申请人： Klaes Golman ,  Oskar Axelsson ,  Haukur Johanneson ,  Charlotte Olofsson ,  Sven Mansson ,  Stefan Petersson

发明人： Klaes Golman ,  Oskar Axelsson ,  Haukur Johanneson ,  Charlotte Olofsson ,  Sven Mansson ,  Stefan Petersson

IPC分类号： A61B505

CPC分类号： A61K49/06 ,  A61K49/08 ,  A61K49/10 ,  A61K49/18 ,  A61K49/1815 ,  G01R33/5601 ,  G01R33/62

摘要： The invention provides a method of magnetic resonance investigation of a sample, said method comprising: (i) reacting para-hydrogen enriched hydrogen with a hydrogenatable MR imaging agent precursor containing a non-hydrogen non-zero nuclear spin nucleus to produce a hydrogenated MR imaging agent; (ii) administering said hydrogenated MR imaging agent to said sample; (iii) exposing said sample to radiation of a frequency selected to excite nuclear spin transitions of said non-zero nuclear spin nucleus in said hydrogenated MR imaging agent; (v) detecting magnetic resonance signals of said non-zero nuclear spin nucleus from said sample; and (vi) optionally, generating an image or biological functional data or dynamic flow data from said detected signals.

摘要翻译： 本发明提供了一种对样品进行磁共振研究的方法，所述方法包括：（i）将富氢氢与含有非氢非零核自旋核的可氢化MR成像剂前体反应以产生氢化MR成像 代理人 （ii）将所述氢化MR成像剂施用于所述样品; （iii）将所述样品暴露于所选择的频率的辐射以激发所述氢化MR成像剂中所述非零核自旋核的核自旋跃迁; （v）从所述样品检测所述非零核自旋核的磁共振信号; 和（vi）可选地，从所述检测到的信号生成图像或生物功能数据或动态流量数据。