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1. 发明专利

JP2011235125A Responsive paramagnetic mri contrast agent 审中-公开
标题翻译：反应性PARAMAGNETIC MRI对比剂
公开(公告)号：JP2011235125A
公开(公告)日：2011-11-24
申请号：JP2011151981
申请日：2011-07-08
申请人： Bracco Imaging Spa , ブラッコイメージングエッセピアBRACCO IMAGING S.p.A.
发明人： AIME SILVIO , DELLI CASTELLI DANIELA , FEDELI FRANCO , TERRENO ENZO
IPC分类号： A61B5/055 , A61K49/00 , A61K49/06 , A61K49/10 , C07D257/02 , C07D487/08
CPC分类号： A61K49/0002 , A61K49/106
摘要： PROBLEM TO BE SOLVED: To provide a method based on the CEST procedure for the in vivo, in vitro or ex vivo determination of a physical or chemical parameter of diagnostic interest which includes the administration of a responsive paramagnetic CEST contrast agent.SOLUTION: The paramagnetic contrast agent is a responsive agent, i.e. an agent which combines the characterizing features of a CEST agent with the fact that the saturation transfer effect that it enables is sensitive to the physical or chemical parameter of diagnostic interest. Accordingly, the contrast agent is a paramagnetic compound which comprises at least one mobile proton in chemical exchange with the water medium protons and which is able, when a proper radiofrequency irradiating field is applied at the resonance frequency of the exchangeable proton, to generate a saturation transfer (ST) effect between the mobile proton and the water medium protons that only correlates to the physico-chemical parameter of diagnostic interest.
摘要翻译：要解决的问题：提供基于CEST程序的方法，用于体内，体外或离体测定诊断感兴趣的物理或化学参数，其包括施用响应性顺磁性CEST造影剂。解决方案：顺磁造影剂是响应剂，即将CEST试剂的特征特征与其使能的饱和转移效应相结合的诊断感兴趣的物理或化学参数这一事实的试剂。因此，造影剂是顺磁性化合物，其包含与水介质质子化学交换的至少一个可移动质子，并且当以可交换质子的共振频率施加适当的射频照射场时，能够产生饱和度在移动质子和水介质质子之间的转移（ST）效应仅与诊断感兴趣的物理化学参数相关。版权所有（C）2012，JPO＆INPIT

2. 发明专利

JP2010088901A Responsive paramagnetic mri contrast agent 有权
标题翻译：反应性PARAMAGNETIC MRI对比剂
公开(公告)号：JP2010088901A
公开(公告)日：2010-04-22
申请号：JP2009264106
申请日：2009-11-19
申请人： Bracco Imaging Spa , ブラッコイメージングエッセピアBRACCO IMAGING S.p.A.
发明人： AIME SILVIO , DELLI CASTELLI DANIELA , FEDELI FRANCO , TERRENO ENZO
IPC分类号： A61B5/055 , A61K49/00 , A61K49/06 , A61K49/10 , C07D257/02 , G01R33/28
CPC分类号： A61K49/0002 , A61K49/106
摘要： PROBLEM TO BE SOLVED: To provide a method based on a CEST procedure for the in vivo or in vitro determination of physical or chemical parameters using a responsive paramagnetic CEST contrast agent. SOLUTION: The responsive paramagnetic CEST contrast agent including at least one exchangeable proton whose saturation capability is correlated to an important physical or chemical parameter is used to display a CEST MR image which is responsive for the parameter in the organ or tissue under examination. The paramagnetic contrast agent for use is a responsive agent, i.e., an agent which combines the characteristic features of a CEST agent with the fact of sensitivity to the physical or chemical parameter which is diagnostically important. The contrast agent thereby includes at least one mobile proton in chemical exchange with water medium protons and is capable of generating a saturation transfer (ST) effect between the mobile proton and the water medium protons when a proper high frequency impression magnetic field is applied at the resonance frequency of the exchangeable proton. COPYRIGHT: (C)2010,JPO&INPIT
摘要翻译：要解决的问题：提供基于CEST程序的方法，用于使用响应顺磁性CEST造影剂体内或体外测定物理或化学参数。解决方案：响应顺磁性CEST造影剂包括至少一种可重复质子，其饱和能力与重要的物理或化学参数相关，用于显示对所检查的器官或组织中参数的响应的CEST MR图像。用于使用的顺磁造影剂是一种响应剂，即将CEST试剂的特征与对于诊断上重要的物理或化学参数敏感的事实相结合的试剂。因此，造影剂包括与水介质质子化学交换的至少一个可移动质子，并且当在该介质质子上施加适当的高频压印磁场时能够在移动质子和水介质质子之间产生饱和转移（ST）效应可交换质子的共振频率。版权所有（C）2010，JPO＆INPIT

3. 发明专利

JP2017078080A 濃度非依存応答性を示すＣＥＳＴシステム审中-公开
公开(公告)号：JP2017078080A
公开(公告)日：2017-04-27
申请号：JP2016243189
申请日：2016-12-15
申请人：ブラッコ・イメージング・ソシエタ・ペル・アチオニBracco Imaging S.P.A. , Bracco Imaging Spa , ブラッコ・イメージング・ソシエタ・ペル・アチオニBracco Imaging S.P.A.
发明人： AIME SILVIO , TERRENO ENZO , DELLI CASTELLI DANIELA , DARIO LIVIO LONGO , FRANCO FEDELI , FULVIO UGGERI
IPC分类号： A61K49/00 , A61B5/055 , C07D257/02 , G01R33/28
CPC分类号： A61K49/106 , G01R33/5601
摘要：【課題】濃度非依存応答性CEST(化学交換依存性飽和移動)剤の提供。【解決手段】レシオメトリックに基づくCEST画像化法におけるCEST剤のNMRで区別可能な立体異性体、ならびに濃度非依存CEST応答性作用剤として有用な溶液中で少なくとも2つのNMRで区別可能な立体異性体を示しているランタニド(III)錯体化合物、および診断用組成物、またはその非等価可動プロトンの使用による測定方法。式(I)で表されるペンダントアーム上にヒドロキシルプロトン交換基を付与されている大環状キレート配位子を含むランタニド(III)錯体化合物であるCEST剤。好ましくは、ランタニド(III)イオンが、イッテルビウム(III)又はユーロピウム(III)であるCEST剤。【選択図】なし

4. 发明申请

WO2006002873A3 1 , 4 -BIS (CARBOXYMETHYL) -6- ' BIS ( CARBOXYMETHYL) AMINO ! -6 -METHYL- PERHYDRO-1 , 4 DIAZEPINE (AAZTA) DERIVATIVES AS LIGANDS IN HIGH RELAXIVITY CONTRAST AGENTS FOR USE IN MAGNETIC RESONANCE IMAGING (MRI ) 审中-公开
标题翻译： 1,4-BIS（羧甲基）-6-“BIS（羧甲基）氨基！ -6 -METHYL- PERHYDRO-1,4 DIAZTA（AAZTA）衍生物作为用于磁共振成像（MRI）的高松弛对比剂中的配体
公开(公告)号：WO2006002873A3
公开(公告)日：2007-05-10
申请号：PCT/EP2005006956
申请日：2005-06-28
申请人： BRACCO IMAGING SPA , AIME SILVIO , GALLI MATTEO , LATTUADA LUCIANO , MOROSINI PIERFRANCESCO , UGGERI FULVIO , KONDAREDDIAR RAMALINGAM
发明人： AIME SILVIO , GALLI MATTEO , LATTUADA LUCIANO , MOROSINI PIERFRANCESCO , UGGERI FULVIO , KONDAREDDIAR RAMALINGAM
IPC分类号： A61K49/00 , A61K49/06 , A61K49/10 , C07C229/76 , C07D233/02 , C07D257/02 , C07D401/14 , C07D405/14 , C07F9/02
CPC分类号： C07H15/26 , A61K49/085 , A61K49/124 , C07C237/08 , C07D243/08 , C07D243/10 , C07F9/3808 , C07F9/4006 , C07F9/5728 , C07H17/02
摘要： The present invention relates to a novel class of ligands for use in paramagnetic ion-based contrast agents of formula e (III) or (IIIa) wherein: R is, independently, H or a C 2 -C 70 aminopolyol moiety comprising a straight or branched alkyl chain substituted by from 2 to 30 hydroxyl groups, said chain being optionally interrupted by one or more groups selected from -0-, -NH-, -N NC0-; and optionally substituted by one or more C4-C10 cyclic units; L is, independently, a direct bond or a divalent straight or branched linker moiety between R and the rest of the molecule, comprising at most 20 carbon atoms; v is a positive integer from 1 to 7; together with the corresponding protonated forms of the phosphonate (-PO 3 H 2 ) and carboxy (-COOH) groups; or a physiologically acceptable salt of such ligand; with the proviso that at least one of the R groups is other than H; the contrast agents show a pharmacokinetic profile analogous to that of the commonly used Tl -general extravascular agents (NSA) but are further characterized by a higher relaxivity.
摘要翻译：本发明涉及用于式e（III）或（IIIa）的顺磁离子基造影剂的新型配体，其中：R独立地为H或C 2 -C 包含由2-30个羟基取代的直链或支链烷基链的氨基多元醇部分，所述链任选被一个或多个选自-O-，-NH-，-N'， -CO - ， - CONH - ， - NHCO - ， - CONN或NCO-; 并任选地被一个或多个C 4 -C 10环单元取代; L独立地是R和其余分子之间的直接键或二价直链或支链连接体部分，其包含至多20个碳原子; v是1到7的正整数; 以及相应的质子化形式的膦酸酯（-PO 3 H 2）和羧基（-COOH）基团; 或该配体的生理上可接受的盐; 条件是至少一个R基团不是H; 造影剂显示类似于通常使用的T1-一般血管外药物（NSA）的药代动力学特征，但进一步的特征在于较高的弛豫度。

5. 发明申请

WO2006136564A9 MULTIDENTATE AZA LIGANDS ABLE TO COMPLEX METAL IONS AND THE USE THEREOF IN DIAGNOSTICS AND THERAPY 审中-公开
标题翻译：多发AZA配体可复制金属离子及其在诊断和治疗中的应用
公开(公告)号：WO2006136564A9
公开(公告)日：2008-02-07
申请号：PCT/EP2006063368
申请日：2006-06-20
申请人： BRACCO IMAGING SPA , GIOVENZANA GIOVANNI BATTISTA , PALMISANO GIOVANNI , SISTI MASSIMO , CAVALLOTTI CAMILLA , AIME SILVIO , CALABI LUISELLA , SWENSON ROLF , KONDAREDDIAR RAMALINGAM , LATTUADA LUCIANO , MOROSINI PIERFRANCESCO
发明人： GIOVENZANA GIOVANNI BATTISTA , PALMISANO GIOVANNI , SISTI MASSIMO , CAVALLOTTI CAMILLA , AIME SILVIO , CALABI LUISELLA , SWENSON ROLF , KONDAREDDIAR RAMALINGAM , LATTUADA LUCIANO , MOROSINI PIERFRANCESCO
IPC分类号： C07D243/08 , A61K49/00 , A61K49/10 , A61K49/14 , A61K51/00 , A61P35/00 , C07C229/16 , C07C229/26 , C07D243/14 , C07D245/02 , C07F1/08 , C07F1/10 , C07F1/12 , C07F5/00 , C07F7/24 , C07F9/38 , C07F9/645 , C07F9/80 , C07F9/94 , C07F11/00 , C07F13/00 , C07F15/00 , C07F15/02
CPC分类号： C07C209/62 , A61K49/0002 , A61K49/085 , A61K49/106 , A61K49/122 , A61K49/14 , A61K51/088 , C07D243/08 , C07D243/14 , C07F9/301 , C07F9/3808 , C07F9/4816 , C07F9/645 , C07C211/50
摘要： Compounds of general formula (I): in which: R 1 , R 2 , R 3 , R 4 , R 5 and FG are as defined in the specification and claims, optionally conjugated with a suitable molecule able to interact with physiological systems; and their chelates with bi-trivalent ions of the metal elements having atomic number ranging between 20 and 31, 39, 42, 43, 44, 49, and between 57 and 83, and radioisotopes, as well as the salts thereof with physiologically compatible bases or acids.
摘要翻译：通式（I）的化合物：其中：R 1，R 2，R 3，R 4， R 5和FG如说明书和权利要求中所定义，任选地与能够与生理系统相互作用的合适分子缀合; 其螯合物与金属元素的二价离子的原子序数范围在20,31,39,42,43,44,49和57和83之间，放射性同位素以及其与生理上相容的碱基的盐或酸。

6. 发明申请

WO2006095234A2 INTEGRIN TARGETED SYNTHETIC LIGANDS FOR DIAGNOSTIC AND THERAPEUTIC APPLICATIONS 审中-公开
标题翻译：用于诊断和治疗应用的INTEGRIN靶向合成配体
公开(公告)号：WO2006095234A2
公开(公告)日：2006-09-14
申请号：PCT/IB2006000455
申请日：2006-03-03
申请人： BRACCO IMAGING SPA , LATTUADA LUCIANO , MOROSINI PIERFRANCESCO , UGGERI FULVIO , AIME SILVIO , TERRENO ENZO , DELLI CASTELLI DANIELA , SCOLASTICO CARLO , MANZONI LEONARDO , AROSIO DANIELA
发明人： LATTUADA LUCIANO , MOROSINI PIERFRANCESCO , UGGERI FULVIO , AIME SILVIO , TERRENO ENZO , DELLI CASTELLI DANIELA , SCOLASTICO CARLO , MANZONI LEONARDO , AROSIO DANIELA
CPC分类号： C07K7/64 , C07D401/06 , C07D471/04 , C07K5/06139
摘要： The present invention relates to a novel class of diagnostically or therapeutically effective compounds comprising novel aza-bicycloalkane based cyclic peptides, acting as a targeting moiety towards integrin receptors.
摘要翻译：本发明涉及一类新的诊断或治疗有效的化合物，其包含作为针对整联蛋白受体的靶向部分的基于新的氮杂 - 双环烷烃的环状肽。

7. 发明申请

WO2004009134A8 PROCEDURES OF CELLULAR LABELLING WITH PARAMAGNETIC COMPLEXES FOR MRI APPLICATIONS 审中-公开
标题翻译：用于MRI应用的参考复合物的细胞标记的程序
公开(公告)号：WO2004009134A8
公开(公告)日：2005-03-03
申请号：PCT/EP0307962
申请日：2003-07-22
申请人： BRACCO IMAGING SPA , AIME SILVIO , GENINATTI CRICH SIMONETTA , LATTUADA LUCIANO
发明人： AIME SILVIO , GENINATTI CRICH SIMONETTA , LATTUADA LUCIANO
IPC分类号： G01R33/28 , A61B5/055 , A61K49/00 , A61K49/08 , A61K49/12 , A61K49/18
CPC分类号： A61K49/12 , A61K49/101 , A61K49/105 , A61K49/1839 , A61K49/1863 , A61K49/1896
摘要： The present invention relates to paramagnetic complexes based on lantanides or transition metals administered in the form of particulates internalysed by cells and whose presence in the cells can be detected by MRI techniques.
摘要翻译：本发明涉及以细胞形式存在的颗粒形式施用的基于兰丹尼斯或过渡金属的顺磁性复合物，并且可以通过MRI技术检测其在细胞中的存在。

8. 发明申请

WO03013616A8 IONIC AND NON-IONIC RADIOGRAPHIC CONTRAST AGENTS FOR USE IN COMBINED X-RAY AND NUCLEAR MAGNETIC RESONANCE DIAGNOSTICS 审中-公开
标题翻译：用于组合X射线和核磁共振诊断的离子和非离子放射性对比剂
公开(公告)号：WO03013616A8
公开(公告)日：2004-04-08
申请号：PCT/EP0208183
申请日：2002-07-23
申请人： BRACCO IMAGING SPA , AIME SILVIO , BARGE ALESSANDRO , MAINERO VALENTINA
发明人： AIME SILVIO , BARGE ALESSANDRO , MAINERO VALENTINA
IPC分类号： G01R33/28 , A61B5/055 , A61K49/00 , A61K49/04 , A61K49/18
CPC分类号： A61K49/1812 , A61K49/0466
摘要： The invention discloses the use of ionic and non-ionic radiographic contrast agents for combined X-ray and nuclear magnetic resonance (MRI) diagnostics.
摘要翻译：本发明公开了用于组合X射线和核磁共振（MRI）诊断的离子和非离子射线照相造影剂的使用。

9. 发明申请

WO2008071679A1 FIBRIN BINDING PEPTIDE CONJUGATES FOR DIAGNOSTIC AND THERAPEUTIC APPLICATIONS. 审中-公开
标题翻译：纤维蛋白结合肽联合用于诊断和治疗应用。
公开(公告)号：WO2008071679A1
公开(公告)日：2008-06-19
申请号：PCT/EP2007063659
申请日：2007-12-11
申请人： BRACCO IMAGING SPA , MARINELLI EDMUND , RAMALINGAM KONDAREDDIAR , SWENSON ROLF , SONG BO , LATTUADA LUCIANO , UGGERI FULVIO , LORUSSO VITO , AIME SILVIO , MOROSINI PIERFRANCESCO , CHAABANE LINDA
发明人： MARINELLI EDMUND , RAMALINGAM KONDAREDDIAR , SWENSON ROLF , SONG BO , LATTUADA LUCIANO , UGGERI FULVIO , LORUSSO VITO , AIME SILVIO , MOROSINI PIERFRANCESCO , CHAABANE LINDA
IPC分类号： C07K7/06 , A61K49/00 , G01N33/86
CPC分类号： A61K49/14 , A61K49/0043 , A61K49/0056 , A61K49/085 , A61K49/124 , C07K7/06 , G01N33/532 , G01N33/574 , G01N33/86 , G01N2500/04
摘要： The present invention relates to a novel class of diagnostically or therapeutically effective compounds comprising novel peptides able to bind fibrin, to a process for their preparation and to compositions thereof for use in therapy and diagnostics. The compounds of the invention bind, in particular, to fibrin present in the extracellular matrix (EC) of tumor or connective tissue of stroma thus acting as targeting moieties able to bring and successfully bound an active moiety linked thereto to fibrin depositions inside solid tumors.
摘要翻译：本发明涉及一类新的诊断或治疗有效化合物，其包含能够结合纤维蛋白的新肽，其制备方法及其组合物用于治疗和诊断。本发明的化合物特别结合存在于基质的肿瘤或结缔组织的细胞外基质（EC）中的纤维蛋白，因此作为靶向部分，其能够使与其连接的活性部分成功结合固体肿瘤内的纤维蛋白沉积。

10. 发明申请

WO2006117166A3 MRI CONTRAST AGENTS ENDOWED WITH CONCENTRATION INDEPENDENT RESPONSIVENESS 审中-公开
标题翻译： MRI对照药物与浓度独立的反应一致
公开(公告)号：WO2006117166A3
公开(公告)日：2007-04-19
申请号：PCT/EP2006004023
申请日：2006-04-28
申请人： BRACCO IMAGING SPA , AIME SILVIO , TERRENO ENZO
发明人： AIME SILVIO , TERRENO ENZO
IPC分类号： A61K49/14 , A61K49/10
CPC分类号： A61K49/085 , A61K49/10
摘要： The present invention relates to a method for the in vivo, ex vivo, or in vitro determination of physical or chemical parameters of diagnostic interest by use of a slow tumbling paramagnetic agent that is responsive to changes of said physical or chemical parameter through changes in the R 2p /R 1p ratio allowing the determination of the said parameter in a manner that is independent on the actual agent concentration.
摘要翻译：本发明涉及一种通过使用缓慢翻滚顺磁剂体内，离体或体外测定诊断感兴趣的物理或化学参数的方法，所述缓慢翻滚顺磁剂通过改变所述物理或化学参数 R 2p / 2/1/2比例允许以与实际药剂浓度无关的方式确定所述参数。

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