Abstract: The present invention relates to a method for the acetylation of an aqueous solution of lactic acid to (S)-2-acetyloxypropionic acid. The process comprises in particular removing water from the solution of lactic acid and reacting lactic acid with acetic anhydride in the presence of acetic acid.
Type:
Grant
Filed:
April 5, 2018
Date of Patent:
April 2, 2019
Assignee:
Bracco Imaging S.P.A.
Inventors:
Roberta Fretta, Pietro Delogu, Fernanda Di Giorgio, Alfonso Nardelli, Stefano Sguassero, Carlo Felice Viscardi
Abstract: 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.
Abstract: 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 C1-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 bor
Abstract: 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 N hydrolysis to restore the (S)-2-(hydroxy)propanoyl group and to obtain Iopamidol (II) and optional recovery of the boron de
Abstract: The present invention relates to new class of functionalized macrocycles capable of chelating paramagnetic metal ions, their chelated complexes with metal ions and the use thereof as contrast agents, particularly suitable for Magnetic Resonance Imaging (MRI) analysis.
Type:
Application
Filed:
December 12, 2016
Publication date:
December 20, 2018
Applicant:
BRACCO IMAGING S.P.A.
Inventors:
Luciano LATTUADA, Roberta NAPOLITANO, Valeria BOI, Massimo VISIGALLI, Silvio AIME, Giovanni Battista GIOVENZANA, Alberto FRINGUELLO MINGO
Abstract: The present invention relates to new class of dimeric macrocycles capable of chelating paramagnetic metal ions, their chelated complexes with metal ions and the use thereof as contrast agents, particularly suitable for Magnetic Resonance Imaging (MRI) analysis.
Type:
Application
Filed:
December 12, 2016
Publication date:
December 20, 2018
Applicant:
BRACCO IMAGING S.P.A.
Inventors:
Valeria BOI, Roberta NAPOLITANO, Luciano LATTUADA
Abstract: The present invention relates to a method for the acetylation of an aqueous solution of lactic acid to (S)-2-acetyloxypropionic acid. The process comprises in particular removing water from the solution of lactic acid and reacting lactic acid with acetic anhydride in the presence of acetic acid.
Type:
Application
Filed:
April 5, 2018
Publication date:
August 9, 2018
Applicant:
BRACCO IMAGING S.P.A.
Inventors:
Roberta FRETTA, Pietro DELOGU, Fernanda DI GIORGIO, Alfonso NARDELLI, Stefano SGUASSERO, Carlo Felice VISCARDI
Abstract: The present invention relates to paramagnetic solid lipid nanoparticles (pSLNs) comprising an amphiphilic paramagnetic metal chelating moiety selected from: a diazepine derivative of Formula I and a tetraazocyclododecane derivative of Formula (II): being said chelating moiety complexed to a paramagnetic metal ion selected from the group consisting of: Gd(III), Mn(II), Cr(III), Cu(II), Fe(III), Pr(III), Nd(III), Sm(III), Tb(III), Yb(III), Dy(III), Ho(III) and Er(III), or salts thereof. The invention further relates to the process for preparation of said solid lipid nanoparticles comprising amphiphilic complexes of paramagnetic metals (pSLNs) and to the use of pSLNs as MRI contrast agents in the diagnostic field.
Abstract: The present invention relates to a method for the acetylation of an aqueous solution of lactic acid to (S)-2-acetyloxypropionic acid. The process comprises in particular removing water from the solution of lactic acid and reacting lactic acid with acetic anhydride in the presence of acetic acid.
Type:
Grant
Filed:
June 10, 2015
Date of Patent:
May 8, 2018
Assignee:
Bracco Imaging S.P.A.
Inventors:
Roberta Fretta, Pietro Delogu, Fernanda Di Giorgio, Alfonso Nardelli, Stefano Sguassero, Carlo Felice Viscardi
Abstract: The present invention relates to a process for the preparation of the mono sodium salt of the derivative 3,5-diiodo-O-[3-iodo-4-(sulphooxy)phenyl]-L-tyrosine (T3S) by starting from the corresponding phenolic compound, in the presence of chlorosulfonic acid and dimethylacetamide as a solvent. The so obtained T3S compound may conveniently be isolated in a pure form as a solid in good yields. The present invention further relates to the process for T3S preparation, wherein the starting reagent is T2 and further comprising the formulation of such compound in tablets. Furthermore, the invention discloses non-radioactive immunoassays based on T3S derivatives.
Type:
Application
Filed:
December 22, 2017
Publication date:
May 3, 2018
Applicant:
BRACCO IMAGING S.p.A.
Inventors:
Pier Lucio ANELLI, Maria ARGESE, Valeria BOI, Livio CAVALIERI, Laura GALIMBERTI, Sonia GAZZETTO, Luciano LATTUADA, Federico MAISANO, Giovanni RIVOLTA, Fulvia VELLA
Abstract: The present invention generally relates to paramagnetic contrast agents and a Dynamic Contrast Enhanced-MRI method for the non-invasive estimation of the delivery of a macromolecular anticancer drug or pro-drug within pathological tissues and, especially, in solid tumors and for the optimization of anticancer therapies.
Type:
Grant
Filed:
March 5, 2013
Date of Patent:
April 24, 2018
Assignee:
BRACCO IMAGING S.P.A.
Inventors:
Raffaella Giavazzi, Alessandro Maiocchi, Michele Moschetta, Giovanni Valbusa
Abstract: 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 deri
Abstract: 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.
Type:
Grant
Filed:
December 4, 2013
Date of Patent:
March 27, 2018
Assignee:
BRACCO IMAGING S.P.A.
Inventors:
Silvia Ceragioli, Pietro Delogu, Armando Mortillaro, Alfonso Nardelli, Stefano Sguassero, Rosario Velardi, Carlo Felice Viscardi
Abstract: Method for manufacturing a hyperpolarized amino acid, in particular glutamine, which substantially limits the formation of by-products, with respect to conventional aqueous preparations of sodium hydroxide with amino acids. The amino acid is in particular admixed with the hydroxide in the substantial absence of water and the dry mixture is dissolved in an anhydrous solvent in the presence of a polarizing agent. The obtained mixture is then subjected to a DNP process and can be used in metabolic MR imaging.
Type:
Grant
Filed:
March 28, 2013
Date of Patent:
March 27, 2018
Assignee:
BRACCO IMAGING S.P.A.
Inventors:
Pernille Rose Jensen, Magnus Karlsson, Mathilde H. Lerche
Abstract: The present invention relates to a process for the preparation of the mono sodium salt of the derivative 3,5-diiodo-O-[3-iodo-4-(sulphooxy)phenyl]-L-tyrosine (T3S) by starting from the corresponding phenolic compound, in the presence of chloro-sulfonic acid and dimethylacetamide as a solvent. The so obtained T3S compound may conveniently be isolated in a pure form as a solid in good yields. The present invention further relates to the process for T3S preparation, wherein the starting reagent is T2 and further comprising the formulation of such compound in tablets. Furthermore, the invention discloses non-radioactive immunoassays based on T3S derivatives.
Type:
Grant
Filed:
April 5, 2012
Date of Patent:
February 13, 2018
Assignee:
BRACCO IMAGING S.p.A.
Inventors:
Pier Lucio Anelli, Maria Argese, Luciano Lattuada, Sonia Gazzetto, Laura Galimberti, Valeria Boi, Livio Cavalieri, Fulvia Vella
Abstract: The present invention relates to novel substituted ethylenediaminetetraacetic acid bisamide derivatives, their complexes with Mn(II) ion and the use thereof as contrast agents for Magnetic Resonance Imaging (MRI) analysis.
Type:
Application
Filed:
February 25, 2016
Publication date:
February 8, 2018
Applicant:
Bracco Imaging S.p.A.
Inventors:
Zsolt BARANYAI, Zoltán GARDA, Simona GHIANI, Ferenc Krisztián KÁLMÁN, László KRUSPER, Alessandro MAIOCCHI, Gyula TIRCSÓ, Imre TOTH
Abstract: The present invention relates to the use of a NIR fluorescent probe comprising an aza-bicycloalkane based cyclic peptide labelled with a Cy5.5 dye moiety in the fluorescence- guided surgery of pathologic regions and to an optical imaging method that comprises using this fluorescent probe for the identification and demarcation of tumor margins during the surgical resection.
Type:
Application
Filed:
December 18, 2015
Publication date:
November 30, 2017
Applicant:
BRACCO IMAGING S.P.A.
Inventors:
Alessandro MAIOCCHI, Chiara BRIOSCHI, Fulvio UGGERI, Giovanni VALBUSA
Abstract: The present invention discloses a process for the preparation of gadobenate dimeglumine complex in a solid form. In particular, said solid form is conveniently obtained by spray-drying a corresponding liquid suspension at a given temperature and concentration. The present invention is particularly advantageous for the industrial scale as the solid form may be obtained by employing water as a solvent, which is a non-toxic solvent, easy to handle and basically not requiring troublesome health or safety precautions.
Type:
Grant
Filed:
April 15, 2016
Date of Patent:
October 24, 2017
Assignee:
BRACCO IMAGING S.p.A.
Inventors:
Pier Lucio Anelli, Pierfrancesco Morosini, Silvia Ceragioli, Fulvio Uggeri, Luciano Lattuada, Roberta Fretta, Aurelia Ferrigato
Abstract: 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.
Type:
Application
Filed:
July 22, 2015
Publication date:
September 7, 2017
Applicant:
BRACCO IMAGING S.P.A.
Inventors:
Elena ELISEI, Attilio CESARO, Marta FILIBIAN, Pietro CARRETTA, Sonia COLOMBO SERRA, Alessandro MAIOCCHI, Fabio TEDOLDI
Abstract: The present invention relates to a method for the acetylation of an aqueous solution of lactic acid to (S)-2-acetyloxypropionic acid. The process comprises in particular removing water from the solution of lactic acid and reacting lactic acid with acetic anhydride in the presence of acetic acid.
Type:
Application
Filed:
June 10, 2015
Publication date:
July 27, 2017
Applicant:
BRACCO IMAGING S.P.A.
Inventors:
Roberta FRETTA, Pietro DELOGU, Fernanda DI GIORGIO, Alfonso NARDELLI, Stefano SGUASSERO, Carlo Felice VISCARDI