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1. 发明申请

US20110178393A1 Process for the Preparation of Aqueous Solutions of Hyperpolarized Molecules 有权
标题翻译：超极化分子水溶液的制备方法
公开(公告)号：US20110178393A1
公开(公告)日：2011-07-21
申请号：US13122209
申请日：2009-09-30
申请人： Francesca Reineri , Alessandra Viale , Giovanni Battista Goivenzana , Daniela Santelia , Walter Dastr , Roberto Gobetto , Silvio Aime , Fulvio Uggeri
发明人： Francesca Reineri , Alessandra Viale , Giovanni Battista Goivenzana , Daniela Santelia , Walter Dastr , Roberto Gobetto , Silvio Aime , Fulvio Uggeri
IPC分类号： A61B5/055 , A61K49/06
CPC分类号： A61K49/10
摘要： The invention relates to a one-step process for the preparation of aqueous solutions of hyperpolarized molecules in which, in a single step, the said hyperpolarized molecules are separated from the crude solution by means of a fast phase-transfer extraction and isolated in an impurity-free aqueous solution, ready for use in the MRI diagnostic imaging of organs, region or tissues of the human or animal body.
摘要翻译：本发明涉及一种用于制备超极化分子水溶液的一步法，其中在单步骤中，所述超极化分子通过快速相转移萃取与粗溶液分离，并在杂质中分离 - 水溶液，可用于人体或动物体的器官，区域或组织的MRI诊断成像。

2. 发明授权

US08961933B2 Process for the preparation of aqueous solutions of hyperpolarized molecules 有权
标题翻译：制备超极化分子水溶液的方法
公开(公告)号：US08961933B2
公开(公告)日：2015-02-24
申请号：US13122209
申请日：2009-09-30
申请人： Francesca Reineri , Alessandra Viale , Giovanni Battista Giovenzana , Daniela Santelia , Walter Dastru′ , Roberto Gobetto , Silvio Aime , Fulvio Uggeri
发明人： Francesca Reineri , Alessandra Viale , Giovanni Battista Giovenzana , Daniela Santelia , Walter Dastru′ , Roberto Gobetto , Silvio Aime , Fulvio Uggeri
IPC分类号： A61B5/055 , A61K49/10 , A61K49/00
CPC分类号： A61K49/10
摘要： The invention relates to a one-step process for the preparation of aqueous solutions of hyperpolarized molecules in which, in a single step, the said hyperpolarized molecules are separated from the crude solution by means of a fast phase-transfer extraction and isolated in an impurity-free aqueous solution, ready for use in the MRI diagnostic imaging of organs, region or tissues of the human or animal body.
摘要翻译：本发明涉及一种用于制备超极化分子水溶液的一步法，其中在单步骤中，所述超极化分子通过快速相转移萃取与粗溶液分离，并在杂质中分离 - 水溶液，可用于人体或动物体的器官，区域或组织的MRI诊断成像。

3. 发明授权

US07988950B2 Contrast agents endowed with high relaxivity for use in magnetic resonance imaging (MRI) which contain a chelating moiety with polyhydroxylated substituents 有权
标题翻译：对比剂具有高的放松性，用于磁共振成像（MRI），其含有具有多羟基化取代基的螯合部分
公开(公告)号：US07988950B2
公开(公告)日：2011-08-02
申请号：US11630605
申请日：2005-06-28
申请人： Silvio Aime , Matteo Galli , Luciano Lattuada , Pierfrancesco Morosini , Fulvio Uggeri , Kondareddiar Ramalingam
发明人： Silvio Aime , Matteo Galli , Luciano Lattuada , Pierfrancesco Morosini , Fulvio Uggeri , Kondareddiar Ramalingam
IPC分类号： A61B5/055 , A61K49/10 , C07F5/00
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 paramagnetic ion-based contrast i agents of formula (I), wherein a chelating backbone moiety is highly functionalized by the presence of one or more polyhydroxylated chain, that show a pharmacokinetic i profile analogous to that of the commonly used T1-general extravascular agents (NSA) but are further characterized by a higher relaxivity. Formula (I): A(LR)v wherein: A is a linear or cyclic chelating backbone moiety; R is, independently, H or a C2-C70aminopolyol moiety comprising a ‘straight or branched alkyl chain substituted by from 2 to 30 hydroxyl groups, the said chain being optionally interrupted by one or more groups selected from -0-, —NH—, —N NCO—; 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 A and R, at most comprising 20 carbon atoms; V is a positive integer from 1 to 7; with the proviso that at least one of the R groups is other than H; or a physiologically acceptable salt of such ligand.
摘要翻译：本发明涉及一类新颖的式（I）的顺磁离子型对比剂，其中螯合骨架部分通过存在一个或多个多羟基化链而被高度官能化，其显示类似于常用的T1一般血管外药物（NSA），但其进一步特征在于较高的松弛度。式（I）：A（LR）v其中：A是直链或环状螯合骨架部分; R独立地是H或包含被2至30个羟基取代的“直链或支链烷基链”的C2-C70氨基多酚部分，所述链任选地被一个或多个选自-O-，-NH-， -N'， - CO - ， - CONH - ， - NHCO-，-CON'或> NCO-; 并任选地被一个或多个C 4 -C 10环单元取代; L独立地是直接键或“A和R之间的二价直链或支链连接体部分，最多包含20个碳原子; V是1到7的正整数; 条件是至少一个R基团不是H; 或这种配体的生理上可接受的盐。

4. 发明授权

US10232060B2 CEST systems exhibiting a concentration independent responsiveness 有权
公开(公告)号：US10232060B2
公开(公告)日：2019-03-19
申请号：US13879083
申请日：2011-11-04
申请人： Silvio Aime , Daniela Delli Castelli , Franco Fedeli , Dario Livio Longo , Enzo Terreno , Fulvio Uggeri
发明人： Silvio Aime , Daniela Delli Castelli , Franco Fedeli , Dario Livio Longo , Enzo Terreno , Fulvio Uggeri
IPC分类号： A61B5/00 , A61B8/00 , A61B10/00 , A61K49/10 , G01R33/56
摘要： The present invention relates to the use of non-equivalent mobile protons belonging to NMR distinguishable stereoisomers of a CEST agent in a ratiometric based CEST imaging procedure and to Lanthanide (III) complex compounds displaying at least two NMR-distinguishable stereoisomers in solution useful as concentration independent CEST responsive agents.

5. 发明申请

US20130195768A1 CEST SYSTEMS EXHIBITING A CONCENTRATION INDEPENDENT RESPONSIVENESS 审中-公开
标题翻译： CEST系统展示独立响应的浓度
公开(公告)号：US20130195768A1
公开(公告)日：2013-08-01
申请号：US13879083
申请日：2011-11-04
申请人： Silvio Aime , Daniela Delli Castelli , Franco Fedeli , Dario Livio Longo , Enzo Terreno , Fulvio Uggeri
发明人： Silvio Aime , Daniela Delli Castelli , Franco Fedeli , Dario Livio Longo , Enzo Terreno , Fulvio Uggeri
IPC分类号： A61K49/10
CPC分类号： A61K49/106 , A61K49/101 , G01R33/5601
摘要： The present invention relates to the use of non-equivalent mobile protons belonging to NMR distinguishable steroisomers of a CEST agent in a ratiometric based CEST imaging procedure and to Lanthanide (III) complex compounds displaying at least two NMR-distinguishable steroisomers in solution useful as concentration independent CEST responsive agents.
摘要翻译：本发明涉及在基于比例的CEST成像方法中属于CEST试剂的NMR可区分立体异构体的非等效移动质子与在可用作浓度的溶液中显示至少两种NMR可区分立体异构体的镧系元素（III）络合物化合物的用途独立的CEST响应代理。

6. 发明申请

US20110256067A1 Contrast agents endowed with high relaxivity 有权
标题翻译：对比剂具有高的放松性
公开(公告)号：US20110256067A1
公开(公告)日：2011-10-20
申请号：US11630600
申请日：2005-06-28
申请人： Silvio Aime , Matteo Galli , Luciano Lattuada , Pierfrancesco Morosini , Fulvio Uggeri , Kondareddiar Ramalingam
发明人： Silvio Aime , Matteo Galli , Luciano Lattuada , Pierfrancesco Morosini , Fulvio Uggeri , Kondareddiar Ramalingam
IPC分类号： A61K49/10 , C07F5/00 , C07D243/10 , C07H15/26 , C07D243/08
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 paramagnetic ion-based contrast agents of formula (I), wherein a chelating backbone moiety is highly functionalized by the presence of one or more polyhydroxylated chain, that show a pharmacokinetic profile analogous to that of the commonly used T1-general extravascular agents (NSA) but are further characterized by a higher relaxivity.
摘要翻译：本发明涉及式（I）的新型顺磁离子型造影剂，其中螯合骨架部分通过存在一个或多个多羟基化链而被高度官能化，其显示类似于常规的药代动力学特征使用T1一般血管外药物（NSA），但其进一步的特征是较高的松弛度。

7. 发明授权

US09333272B2 Fibrin binding peptide conjugates for diagnostic and therapeutic applications 有权
标题翻译：用于诊断和治疗应用的纤维蛋白结合肽缀合物
公开(公告)号：US09333272B2
公开(公告)日：2016-05-10
申请号：US12448102
申请日：2007-12-11
申请人： Silvio Aime , Linda Chaabane , Luciano Lattuada , Vito Lorusso , Edmund R. Marinelli , Pierfrancesco Morosini , Kondareddiar Ramalingam , Bo Song , Rolf E. Swenson , Fulvio Uggeri
发明人： Silvio Aime , Linda Chaabane , Luciano Lattuada , Vito Lorusso , Edmund R. Marinelli , Pierfrancesco Morosini , Kondareddiar Ramalingam , Bo Song , Rolf E. Swenson , Fulvio Uggeri
IPC分类号： A61K38/36 , A61K49/14 , A61K49/00 , A61K49/08 , A61K49/12 , C07K7/06 , G01N33/532 , G01N33/574 , 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，因此作为能够使与其连接的活性部分与实质瘤内的纤维蛋白沉积成功结合的靶向部分。

8. 发明授权

US08611981B2 MRI-CEST diagnostic technique based on non-punctual analysis 有权
标题翻译：基于非准时分析的MRI-CEST诊断技术
公开(公告)号：US08611981B2
公开(公告)日：2013-12-17
申请号：US13060397
申请日：2009-08-18
申请人： Silvio Aime , Daniela Delli Castelli , Dario Livio Longo , Joseph Stancanello , Enzo Terreno , Fulvio Uggeri
发明人： Silvio Aime , Daniela Delli Castelli , Dario Livio Longo , Joseph Stancanello , Enzo Terreno , Fulvio Uggeri
IPC分类号： A61B5/05 , G01V3/00
CPC分类号： G01R33/5601 , G01R33/5608
摘要： An embodiment in the MRI-CEST field is proposed for analyzing a body-part, which includes a CEST agent providing a magnetization transfer with a bulk substrate of the body-part. A corresponding diagnostic system includes input means for providing an input map including a plurality of input elements each one for a corresponding location of the body-part; each input element is indicative of a spectrum of a magnetic response of the location, which spectrum includes the magnetic response at an agent frequency of resonance of the contrast agent (with the agent frequency that is at an agent offset of frequency from a bulk frequency of resonance of the bulk substance), and at a reference frequency at the opposite of the agent offset from the bulk frequency. The system further includes calculation means for calculating an agent value and a reference value for each one of a set of selected locations; the agent value is calculated according to the magnetic responses of the selected location in a non-punctual agent range of frequencies including the agent frequency, and the reference value is calculated according to the magnetic responses of the selected location in a non-punctual reference range of frequencies including the reference frequency (with the reference range that is symmetric to the agent range with respect to the bulk frequency). Comparison means is then provided for calculating a parametric value for each selected location; the parametric value is calculated according to a comparison between the agent value and the reference value of the selected location.
摘要翻译：提出了MRI-CEST领域中的一个实施例，用于分析身体部位，其包括提供磁化转移的CEST代理与身体部位的体基底。相应的诊断系统包括输入装置，用于提供包括多个输入元件的输入图，每个输入元件各自用于身体部位的对应位置; 每个输入元件指示该位置的磁响应的频谱，该频谱包括在造影剂的谐振的代理频率处的磁响应（代理频率在代理偏移量的频率与主频率散装物质的共振），并且在与体积偏移的试剂相反的参考频率处。该系统还包括用于计算一组选定位置中的每一个的代理值和参考值的计算装置; 根据所选择的位置在包括代理频率的非准时代理频率范围内的磁响应来计算代理值，并且根据所选择的位置在非准时参考范围内的磁响应来计算参考值的频率，其包括参考频率（参考范围与代理范围相对于体频率对称）。然后提供比较装置，用于计算每个选定位置的参数值; 根据代理值与所选位置的参考值之间的比较来计算参数值。

9. 发明申请

US20110152671A1 MRI-CEST DIAGNOSTIC TECHNIQUE BASED ON NON-PUNCTUAL ANALYSIS 有权
标题翻译：基于非泛素化分析的MRI-CEST诊断技术
公开(公告)号：US20110152671A1
公开(公告)日：2011-06-23
申请号：US13060397
申请日：2009-08-18
申请人： Silvio Aime , Daniela Delli Castelli , Dario Livio Longo , Joseph Stancanello , Enzo Terreno , Fulvio Uggeri
发明人： Silvio Aime , Daniela Delli Castelli , Dario Livio Longo , Joseph Stancanello , Enzo Terreno , Fulvio Uggeri
IPC分类号： A61B5/055 , G06F19/00 , G01R33/54
CPC分类号： G01R33/5601 , G01R33/5608
摘要： An embodiment in the MRI-CEST field is proposed for analyzing a body-part, which includes a CEST agent providing a magnetization transfer with a bulk substrate of the body-part. A corresponding diagnostic system includes input means for providing an input map including a plurality of input elements each one for a corresponding location of the body-part; each input element is indicative of a spectrum of a magnetic response of the location, which spectrum includes the magnetic response at an agent frequency of resonance of the contrast agent (with the agent frequency that is at an agent offset of frequency from a bulk frequency of resonance of the bulk substance), and at a reference frequency at the opposite of the agent offset from the bulk frequency. The system further includes calculation means for calculating an agent value and a reference value for each one of a set of selected locations; the agent value is calculated according to the magnetic responses of the selected location in a non-punctual agent range of frequencies including the agent frequency, and the reference value is calculated according to the magnetic responses of the selected location in a non-punctual reference range of frequencies including the reference frequency (with the reference range that is symmetric to the agent range with respect to the bulk frequency). Comparison means is then provided for calculating a parametric value for each selected location; the parametric value is calculated according to a comparison between the agent value and the reference value of the selected location.
摘要翻译：提出了MRI-CEST领域中的一个实施例，用于分析身体部位，其包括提供磁化转移的CEST代理与身体部位的体基底。相应的诊断系统包括输入装置，用于提供包括多个输入元件的输入图，每个输入元件各自用于身体部位的对应位置; 每个输入元件指示该位置的磁响应的频谱，该频谱包括在造影剂的谐振的代理频率处的磁响应（代理频率在代理偏移量的频率与主频率散装物质的共振），并且在与体积偏移的试剂相反的参考频率处。该系统还包括用于计算一组选定位置中的每一个的代理值和参考值的计算装置; 根据所选择的位置在包括代理频率的非准时代理频率范围内的磁响应来计算代理值，并且根据所选择的位置在非准时参考范围内的磁响应来计算参考值的频率，其包括参考频率（参考范围与代理范围相对于体频率对称）。然后提供比较装置，用于计算每个选定位置的参数值; 根据代理值与所选位置的参考值之间的比较来计算参数值。

10. 发明授权

US09694090B2 Process for preparing hyperpolarized substrates and method for MRI 有权
公开(公告)号：US09694090B2
公开(公告)日：2017-07-04
申请号：US13639682
申请日：2011-04-08
申请人： Silvio Aime , Giovanni Battista Giovenzana , Fabio Tedoldi , Alessandro Maiocchi , Fulvio Uggeri , Pernille Rose Jensen , Magnus Karlsson , Mathilde H. Lerche , Massimo Visigalli , Marco Crosetti , Luisa Poggi
发明人： Silvio Aime , Giovanni Battista Giovenzana , Fabio Tedoldi , Alessandro Maiocchi , Fulvio Uggeri , Pernille Rose Jensen , Magnus Karlsson , Mathilde H. Lerche , Massimo Visigalli , Marco Crosetti , Luisa Poggi
IPC分类号： A61K49/10 , A61B5/05 , A61M5/00 , A61B5/055
CPC分类号： A61K49/10 , A61B5/055 , A61M5/007
摘要： The present invention generally relates to a process for the preparation of aqueous solutions of hyperpolarized molecules ready for use in in-vivo MR diagnostic imaging, the use thereof as MRI contrast agent in investigation methods for producing diagnostic MR images of a human or non-human animal body organ, region or tissue.

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