公开(公告)号：US20170252464A1

公开(公告)日：2017-09-07

申请号：US15500024

申请日：2015-07-22

申请人： BRACCO IMAGING S.P.A. ,  UNIVERSITA DI PAVIA

发明人： Elena ELISEI ,  Attilio CESARO ,  Marta FILIBIAN ,  Pietro CARRETTA ,  Sonia COLOMBO SERRA ,  Alessandro MAIOCCHI ,  Fabio TEDOLDI

IPC分类号： A61K49/10 ,  A61K49/18

CPC分类号： A61K49/10 ,  A61K49/18

摘要： A method for preparing a sample for dynamic nuclear polarization which comprises submitting a solid substrate to a milling process in the presence of a polarizing agent at a temperature lower than the glass-transition temperature (Tg) of said substrate. Preferably said substrate may be in crystalline form.

公开(公告)号：US20160237026A1

公开(公告)日：2016-08-18

申请号：US15033737

申请日：2014-11-04

申请人： BRACCO IMAGING S.P.A.

发明人： Elisa BATTISTINI ,  Federica BUONSANTI ,  Daniela IMPERIO ,  Luciano LATTUADA ,  Roberta NAPOLITANO

IPC分类号： C07C231/14 ,  C07C231/12 ,  C07C227/04 ,  C07C231/02 ,  C07F5/02 ,  C07C201/12

CPC分类号： C07C231/14 ,  C07C201/12 ,  C07C227/04 ,  C07C231/02 ,  C07C231/12 ,  C07F5/025 ,  C07F5/04 ,  C07F5/05 ,  Y02P20/55 ,  Y02P20/582 ,  C07C237/46

摘要： The present invention discloses a process for the preparation of Iopamidol of formula (II) and comprising the following steps: a) reacting the Compound (I) wherein X is OR2 or R3, and wherein R2 and R3 are a Ci-C6 linear or branched alkyl, C3-C6 cycloalkyl, C6 aryl, optionally substituted with a group selected from the group consisting of methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, t-butyl and phenyl, with the acylating agent (S)-2-(acetyloxy)propanoyl chloride in a reaction medium to provide the acetyloxy derivative of Compound (I); b) hydrolyzing the intermediate from step a) with an aqueous solution at a pH comprised from 0 to 7, by adding water or a diluted alkaline solution such as sodium hydroxide or potassium hydroxide, freeing the hydroxyls from the boron-containing protective groups, obtaining the N—(S)-2-(acetyloxy)propanoyl derivative of Compound (II); c) alkaline hydrolysis to restore the (S)-2-(hydroxy)propanoyl group and to obtain Iopamidol (II) and optional recovery of the boron derivative from the solution obtained in step b). The boron-containing protective group is versatile, efficient and recyclable. A one-pot synthesis, without intermediate isolation is provided, leading to a decreasing of recovered and recycled solvents and a significant increasing in the yield, representing a significant advantage in terms of cost-effectiveness of the entire process and environmental awareness.

摘要翻译： 本发明公开了一种制备式（II）的叶帕醇的方法，其包括以下步骤：a）使其中X为OR 2或R 3的化合物（I）反应，其中R 2和R 3为C 1 -C 6直链或支链 烷基，C 3 -C 6环烷基，C 6芳基，任选被选自甲基，乙基，正丙基，异丙基，正丁基，仲丁基，叔丁基和苯基的基团取代，与酰化 （S）-2-（乙酰氧基）丙酰氯在反应介质中提供化合物（I）的乙酰氧基衍生物; b）通过加入水或稀释的碱性溶液如氢氧化钠或氢氧化钾，使水溶液在0至7的pH下水解步骤a）中的中间体，从含硼保护基中释出羟基，得到 化合物（II）的N-（S）-2-（乙酰氧基）丙酰基衍生物; c）碱性水解以还原（S）-2-（羟基）丙酰基并获得Iopamidol（II）并任选地从步骤b）中获得的溶液中回收硼衍生物。 含硼保护基是多功能，高效和可循环利用的。 提供了一种不进行中间隔离的单锅合成，导致回收和再循环溶剂减少，产率显着提高，在整个过程的成本效益和环境意识方面具有显着的优势。

公开(公告)号：US20150329464A1

公开(公告)日：2015-11-19

申请号：US14650868

申请日：2013-12-04

申请人： BRACCO IMAGING S.P.A.

发明人： Silvia CERAGIOLI ,  Pietro DELOGU ,  Armando MORTILLARO ,  Alfonso NARDELLI ,  Stefano SGUASSERO ,  Rosario VELARDI ,  Carlo Felice VISCARDI

IPC分类号： C07C67/313 ,  C07C71/00

CPC分类号： C07C67/313 ,  C07C67/08 ,  C07C67/287 ,  C07C71/00 ,  Y02P20/582 ,  C07C69/14

摘要： The present invention relates to a continuous method for the preparation of (S)-2-acetyloxypropionic acid from an aqueous solution of lactic acid and acetic anhydride, in acetic acid. (S)-2-acetyloxypropionic acid is used for the preparation of (S)-2-acetyloxypropionic acid chloride, an essential intermediate compound for the preparation of lopamidol and has to be industrially produced with high purity and suitable quality for producing lopamidol according to the Pharmacopoeia requirements. The continuous process according to the invention, comprises therefore also the chlorination steps of (S)-2-acetyloxypropionic acid with thionyl chloride to give the corresponding (S)-2-acetyloxypropionic acid chloride which is further distilled to give the suitable purity characteristics for its use for the preparation of non-ionic iodinated contrast agents as lopamidol.

摘要翻译： 本发明涉及在乙酸中由乳酸和乙酸酐的水溶液制备（S）-2-乙酰氧基丙酸的连续方法。 （S）-2-乙酰氧基丙酸用于制备（S）-2-乙酰氧基丙酸氯化物，其是制备洛帕糖醇的必需中间体化合物，并且必须在工业上以高纯度生产，并且根据 药典要求。 根据本发明的连续方法还包括（S）-2-乙酰氧基丙酸与亚硫酰氯的氯化步骤，得到相应的（S）-2-乙酰氧基丙酰氯，进一步蒸馏得到适合的纯度特性， 其用于制备非离子碘化造影剂作为洛帕糖醇。

公开(公告)号：US20150273086A1

公开(公告)日：2015-10-01

申请号：US14437521

申请日：2013-10-24

申请人： BRACCO IMAGING S.P.A.

发明人： Claudia Cabella ,  Lara Caminiti ,  Sonia Colombo Serra ,  Pernille Rose Jensen ,  Magnus Karlsson ,  Mathilde H. Lerche ,  Luigi Miragoli ,  Luisa Poggi ,  Fabio Tedoldi ,  Luca Venturi

IPC分类号： A61K49/10

摘要： Hyperpolarized 1-13C-2-oxoglutarate as contrast agent in 13C Magnetic Resonance diagnostic technique (13C-MRI) for use in the diagnosis of cancer. In particular, upon administration of said 1-13C-2-oxoglutarate, signals of 1-13C-glutamate are detected. More in particular, different MR signals from 13C nuclei are detected and compared, said comparison being useful to determine a difference between tumor and non-tumor tissues, to determine the aggressiveness of a tumor or the efficacy of an anti-tumor therapy.

摘要翻译： 超极化1-13C-2-氧戊酸作为造影剂在13C磁共振诊断技术（13C-MRI）中用于诊断癌症。 特别地，在施用所述1-13C-2-氧戊二酸酯时，检测出1-13C谷氨酸的信号。 更具体地，检测和比较来自13C核的不同MR信号，所述比较可用于确定肿瘤和非肿瘤组织之间的差异，以确定肿瘤的侵袭性或抗肿瘤治疗的功效。

公开(公告)号：US20140301912A1

公开(公告)日：2014-10-09

申请号：US14308468

申请日：2014-06-18

申请人： Bracco Imaging S.p.A

发明人： Robert C. Williams, JR. ,  Patrice Marchildon

IPC分类号： C12Q1/18

CPC分类号： G01M3/2853 ,  A61L2/18 ,  A61L2/28 ,  A61M5/00 ,  A61M5/1408 ,  A61M5/1413 ,  A61M5/14232 ,  C12Q1/18 ,  C12Q1/22 ,  G01N31/226 ,  G01N33/50 ,  G01N2013/003 ,  Y10T436/13

摘要： A fluid delivery system may include a container that houses a medical fluid, a fluid pressurizing unit, and a fluid transfer set that transfers the medical fluid from the container to the fluid pressurizing unit. To validate the integrity and sterility of the fluid delivery system, the system may undergo testing protocols to evaluate the susceptibility of the system to pathogenic ingress, chemical degradation, and/or fluid cross-contamination between patient fluid delivery procedures. The testing protocols may help ensure that delivery system components used during multiple different fluid delivery procedures perform as well as if the components were replaced after each fluid delivery procedure.

公开(公告)号：US20140154671A1

公开(公告)日：2014-06-05

申请号：US14097867

申请日：2013-12-05

申请人： Bracco Imaging S.p.A

发明人： Robert C. Williams, JR. ,  Patrice Marchildon

IPC分类号： C12Q1/22 ,  G01N33/50

CPC分类号： G01M3/2853 ,  A61L2/18 ,  A61L2/28 ,  A61M5/00 ,  A61M5/1408 ,  A61M5/1413 ,  A61M5/14232 ,  C12Q1/18 ,  C12Q1/22 ,  G01N31/226 ,  G01N33/50 ,  G01N2013/003 ,  Y10T436/13

摘要： A fluid delivery system may include a container that houses a medical fluid, a fluid pressurizing unit, and a fluid transfer set that transfers the medical fluid from the container to the fluid pressurizing unit. To validate the integrity and sterility of the fluid delivery system, the system may undergo testing protocols to evaluate the susceptibility of the system to pathogenic ingress, chemical degradation, and/or fluid cross-contamination between patient fluid delivery procedures. The testing protocols may help ensure that delivery system components used during multiple different fluid delivery procedures perform as well as if the components were replaced after each fluid delivery procedure.

公开(公告)号：US12129563B2

公开(公告)日：2024-10-29

申请号：US18694306

申请日：2022-09-22

申请人： BRACCO IMAGING S.P.A.

发明人： Luciano Lattuada ,  Camilla Cavallotti ,  Giovanni Battista Giovenzana ,  Fulvio Uggeri ,  Alessandro Minguzzi ,  Alberto Vertova ,  Letizia Sorti ,  Carlo Morelli

IPC分类号： C25B3/27 ,  C07C231/12 ,  C07C237/46 ,  C25B3/07 ,  C25B3/09 ,  C25B3/11 ,  C25B15/08

CPC分类号： C25B3/27 ,  C07C231/12 ,  C07C237/46 ,  C25B3/07 ,  C25B3/09 ,  C25B3/11 ,  C25B15/081 ,  C25B15/083 ,  C25B15/087

摘要： The invention is related to a process for preparing a iodinating X-rays contrast agent. More specifically, it relates to a process for the preparation of N,N′-bis-(2,3-dihydroxypropyl)-5-hydroxy-2,4,6-triiodo-1,3-benzenedicarboxaniide (I) by electrochemical iodination of N,N′-(2,3-dihydroxypropyl)-5-hydroxy-1,3-benzenedicarboxamide (II) with molecular iodine (I2) which is in situ electrochemically generated from a source of iodide ions (I−). The iodide ions (I−) are obtained by the dissolution of hydrogen iodide (HI) or an alkali metal iodide in the reaction medium or produced during the reaction of N,N′-(2,3-dihydroxypropyl)-5-hydroxy-1,3-benzenedicarboxamide with I2. The invention also relates to the use of the intermediate compound of formula (I), obtained through the above electrochemical iodination of compound (II), in the preparation of N,N′-bis[2,3-dihydroxypropyl]-5(hydroxyacetyl)methylamino]-2,4,6-triiodo-1,3-benzenedicarboxamide (iomeprol).

公开(公告)号：US12036289B2

公开(公告)日：2024-07-16

申请号：US17199122

申请日：2021-03-11

申请人： BRACCO IMAGING S.P.A.

发明人： Roberta Napolitano ,  Luciano Lattuada ,  Zsolt Baranyai ,  Nicole Guidolin ,  Giuseppe Marazzi

IPC分类号： A61B5/055 ,  A61K49/10 ,  C07F5/00 ,  C07D471/08

CPC分类号： A61K49/106 ,  C07F5/003 ,  A61K49/108 ,  C07D471/08

摘要： The present invention relates to the RRR/SSS pair of enantiomers of the of Gd(PCTA-tris-glutaric acid), the single enantiomers of the pair, the pharmaceutically acceptable salts thereof, their amide derivatives, and compositions comprising at least 50% of these compounds.

公开(公告)号：US20240083880A1

公开(公告)日：2024-03-14

申请号：US18388604

申请日：2023-11-10

申请人： BRACCO IMAGING S.P.A.

发明人： Francesco BLASI ,  Federica BUONSANTI ,  Federico CRIVELLIN ,  Andrea FERRARIS ,  Laura ORIO ,  Lorena PIZZUTO ,  Roberta NAPOLITANO ,  Giovanni VALBUSA

IPC分类号： C07D403/10 ,  C07D403/14 ,  C09B23/01

CPC分类号： C07D403/10 ,  C07D403/14 ,  C09B23/0066 ,  C09B23/0075

摘要： The present invention relates to the field of optical imaging. More particularly, it relates to compounds of the cyanine family with near-infrared emission characterized by improved physico-chemical and biological properties and to conjugates with biological ligands thereof.
The invention also relates to the use of these compounds as optical diagnostic agents in imaging or therapy of solid tumors, to the methods for their preparation and to the compositions comprising them.

公开(公告)号：US11851421B2

公开(公告)日：2023-12-26

申请号：US18010905

申请日：2021-06-22

申请人： BRACCO IMAGING S.P.A.

发明人： Francesco Blasi ,  Federica Buonsanti ,  Federico Crivellin ,  Andrea Ferraris ,  Laura Orio ,  Lorena Pizzuto ,  Roberta Napolitano ,  Giovanni Valbusa

IPC分类号： C07D403/10 ,  C09B23/01 ,  C07D403/14

CPC分类号： C07D403/10 ,  C07D403/14 ,  C09B23/0066 ,  C09B23/0075

摘要： The present invention relates to the field of optical imaging. More particularly, it relates to compounds of the cyanine family with near-infrared emission characterized by improved physico-chemical and biological properties and to conjugates with biological ligands thereof. The invention also relates to the use of these compounds as optical diagnostic agents in imaging or therapy of solid tumors, to the methods for their preparation and to the compositions comprising them. The compounds have formula (I), formula (I), wherein X is direct bond or —O—; Y is a group selected from linear or branched C1-C6 alkyl, C3-C7 cycloalkyl and heterocyclyl, substituted by at least two hydroxyl groups; R1 and R2 are each independently a linear or branched C1-C6 alkyl substituted by a group selected from —SO3H, —COOH, —CONH2 and —COO—C1-C6 alkyl; and R3 is hydrogen, —SO3H or a linear or branched C1-C6 alkyl substituted by —COOH or —CONH—Y, wherein Y is a group selected from linear or branched C1-C6 alkyl, C3-C7 cycloalkyl and heterocyclyl, substituted by at least two hydroxyl groups.