Abstract: Gas or air filled microbubble suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. They contain laminarized surfactants and, optionally, hydrophilic stabilizers. The laminarized surfactants can be in the form of liposomes. The suspensions are obtained by exposing the laminarized surfactants to air or a gas before or after admixing with an aqueous phase.
Type:
Application
Filed:
March 22, 2005
Publication date:
September 22, 2005
Applicant:
Bracco International B.V.
Inventors:
Michel Schneider, Feng Yan, Pascal Grenier, Nadine Garcel, Jerome Puginier, Marie-Bernadette Barrau, Philippe Bussat, Eva Hybl, Daniel Bichon
Abstract: The invention provides improved and simplified methods of synthesizing ligands containing a heteroatom-bearing bridge using a novel intermediate compound. The ligands may be used to form metal complexes that are useful in diagnostic and therapeutic applications.
Abstract: Gas or air filled microbubble suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. They contain laminarized surfactants and, optionally, hydrophilic stabilizers. The laminarized surfactants can be in the form of liposomes. The suspensions are obtained by exposing the laminarized surfactants to air or a gas before or after admixing with an aqueous phase.
Type:
Grant
Filed:
August 23, 2002
Date of Patent:
May 24, 2005
Assignee:
Bracco International B.V.
Inventors:
Michel Schneider, Feng Yan, Nadine Garcel, Jerome Puginier, Marie-Bernadette Barrau, Philippe Bussat, Eva Hybl, Daniel Bichon, Pascal Grenier
Abstract: Novel metal-chelate complexes comprising aminocarboxylate ligands including substituted aromatic amide moieties, such as those having the formula wherein R13, A1, R1 and R2 are as defined herein, are disclosed.
Type:
Application
Filed:
October 13, 2004
Publication date:
April 28, 2005
Applicant:
Bracco International B.V.
Inventors:
Radhakrishna Pillai, Sang Kang, Edmund Marinelli, Ramachandran Ranganathan, Michael Tweedle
Abstract: One can impart outstanding resistance against collapse under pressure to gas-filled microvesicle used as contrast agents in ultrasonic echography by using as fillers gases whose solubility in water, expressed in liter of gas by liter of water under standard conditions, divided by the square root of the molecular weight does not exceed 0.003.
Abstract: Novel metal-chelate complexes comprising aminocarboxylate ligands including substituted aromatic amide moieties, such as those having the formula wherein R13, A1, R1 and R2 are as defined herein, are disclosed.
Type:
Grant
Filed:
May 29, 2002
Date of Patent:
April 5, 2005
Assignee:
Bracco International B.V.
Inventors:
Radhakrishna K. Pillai, Sang I. Kang, Edmund R. Marinelli, Ramachandran S. Ranganathan, Michael F. Tweedle
Abstract: Gas or air filled microbubble and microballoon suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. The microbubble suspensions contain laminarized surfactants and, optionally, hydrophilic stabilizers. The laminarized surfactants can be in the form of liposomes. The microbubble suspensions are obtained by exposing the laminarized surfactants to air or a gas before or after admixing with an aqueous phase. The microballoons have a mean size in the range of 0.5 to 1000 microns bounded by a 50 to 500 nm thick polymer membrane. One can impart outstanding resistance against collapse under pressure to these gas-filled microbubbles and gas-filled microballoons used as contrast agents in ultrasonic echography by using as fillers gases whose solubility in water, expressed in liter of gas by liter of water under standard conditions, divided by the square root of the molecular weight does not exceed 0.003.
Type:
Application
Filed:
March 26, 2004
Publication date:
October 21, 2004
Applicant:
Bracco International B.V.
Inventors:
Michel Schneider, Feng Yan, Pascal Grenier, Jerome Puginier, Marie-Bernadette Barrau, Philippe Bussat, Eva Hybl, Daniel Bichon
Abstract: The invention features sincalide formulations that include an effective amount of sincalide, a bulking agent/tonicity adjuster, a stabilizer, a surfactant, a chelator, and a buffer. The invention also features kits and methods for preparing improved sincalide formulations, as well as methods for treating, preventing, and diagnosing gall bladder-related disorders using sincalide formulations.
Type:
Grant
Filed:
August 16, 2002
Date of Patent:
October 12, 2004
Assignee:
Bracco International B.V.
Inventors:
Edmund C. Metcalfe, Jo Anna Monteferrante, Margaret Newborn, Irene Ropiak, Ernst Schramm, Gregory W. White, Julius P. Zodda
Abstract: Disclosed are injectable suspensions of gas filled microbubbles in an aqueous carrier liquid usable as contrast agents in ultrasonic echography. The suspensions comprise amphipathic compounds of which at least one may be a laminarized phospholipid as a stabiliser of the microbubbles against collapse with time and pressure. The concentration of phospholipids in the carrier liquid is below 0.01% wt but is at least equal to or above that at which phospholipid molecules are present solely at the gas microbubble-liquid interface. Also disclosed are methods of preparation of the stable suspensions of gas filled microbubbles, as well as dry formulations which, upon reconstitution in an aqueous carrier liquid, will form the injectable suspensions of gas filled microbubbles of the invention and methods of making and using the same The preferred dry formulations are stable when stored over time and at temperatures above ambient temperature and further comprise a lipid acid preserving agent additive.
Type:
Application
Filed:
February 20, 2004
Publication date:
September 16, 2004
Applicant:
Bracco International B.V.
Inventors:
Michel Schneider, Jean Brochot, Jerome Puginier, Feng Yan
Abstract: Air or gas filled microballoons bounded by an interfacially deposited polymer membrane which can be dispersed in aqueous carrier liquids to be injected into living organisms or administered orally, rectally and urethrally for therapeutic or diagnostic purposes (echography). The properties of the polymeric membrane of the microballoons (elasticity, permeability, biodegradability) can be controlled at will depending on the selected polymer, the interfacial deposition conditions, and the polymer additives.
Type:
Application
Filed:
December 3, 2003
Publication date:
July 1, 2004
Applicant:
Bracco International B.V.
Inventors:
Daniel Bichon, Philippe Bussat, Michel Schneider
Abstract: A novel method for the preparation of a pre-filled plastic syringe, and preferably the preparation of a plastic syringe pre-filled with a diagnostic contrast agent wherein said syringe comprises as components a barrel, a tip seal capable of sealing the nozzle of the barrel and a piston capable of sliding in the barrel and sealing the open end of the barrel opposite the nozzle, comprising the steps of:
(a) providing at least one component of said syringe which is molded under conditions which are substantially free of pyrogens and viable and non-viable articulates; and
(b) filling and assembling said syringe.
Abstract: Novel methods, processes and metal complexes attached to a hypoxia-localizing moiety comprising
a metal, preferably radionuclide of rhenium or technetium;
a hypoxia-localizing moiety; and,
a complexing ligand, wherein said ligand and said radionuclide combined have cell membrane permeabilities greater than that of sucrose, are disclosed.
Type:
Grant
Filed:
November 16, 2001
Date of Patent:
March 2, 2004
Assignee:
Bracco International B.V.
Inventors:
Karen Linder, Adrian D. Nunn, David P. Nowotnik, Kondareddiar Ramalingam, Richard J. DiRocco, William L. Rumsey, John P. Pirro
Abstract: Metal chelates capable of exhibiting an immobilized relativity between about 60 and 200 mM−1s−1/metal atom are useful as magnetic resonance imaging agents. Additionally, a compound which is useful as a metal-chelating ligand has the following formula:
wherein
Q is a 4- to an 8-membered carbocyclic ring which may be fully or partially saturated;
t is an integer from 2 to 16;
each R group is independently hydrogen, —OH, —CH2—A, —OCH2CH(OH)CH2—A or a functional group capable of forming a conjugate with a biomolecule, provided that at least two of the R groups are selected from —CH2—A or —OCH2CH(OH)CH2—A; and
A is a moiety capable of chelating a metal atom.
Type:
Grant
Filed:
May 11, 1994
Date of Patent:
February 17, 2004
Assignee:
Bracco International B.V.
Inventors:
Ramachandran S. Ranganathan, Radhakrishna Pillai, Peter C. Ratsep, Rajesh Shukla, Michael F. Tweedle, Xun Zhang
Abstract: Substituted polycarboxylic ligand molecules and corresponding metal complexes of said ligands, preferably paramagnetic metals complexes for generating responses in the field of magnetic resonance imaging (MRI) The paramagnetic complexes of the polycarboxylic ligands possess advantageous tensioactive properties and are useful as MRI contrast media in formulations for investigating the blood pool.
Abstract: 1,4,7,10-Tetraazacyclodecane, a precursor for the synthesis of macrocylic chelating agents for metal ions such as gadolinium, is prepared efficiently as a highly pure product on an industrial scale.
Type:
Grant
Filed:
October 11, 2001
Date of Patent:
November 25, 2003
Assignee:
Bracco International B.V.
Inventors:
Maria Argese, Giuseppe Manfredi, Fabrizio Rebasti, Giorgio Ripa
Abstract: Gas or air filled microbubble suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. They contain surfactants and, optionally, hydrophilic stabilizers. The surfactants can be in the form of liposomes. The suspensions are obtained by exposing the surfactants to air or a gas before or after admixing with an aqueous phase. One can impart outstanding resistance against collapse under pressure to these gas-filled microbubbles used as contrast agents in ultrasonic echography by using as fillers gases whose solubility in water, expressed in liter of gas by liter of water under standard conditions, divided by the square root of the molecular weight does not exceed 0.003. Contrast agents with particular mixtures of gases are also disclosed that have advantageous properties.
Type:
Application
Filed:
January 6, 2003
Publication date:
October 16, 2003
Applicant:
Bracco International B.V.
Inventors:
Michel Schneider, Feng Yan, Pascal Grenier, Nadine Garcel, Jerome Puginier, Marie-Bernadette Barrau, Philippe Bussat, Eva Hybl, Daniel Bichon
Abstract: Gas or air filled microbubble suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. They contain surfactants and, optionally, hydrophilic stabilizers. The surfactants can be in the form of liposomes. The suspensions are obtained by exposing the surfactants to air or a gas before or after admixing with an aqueous phase. One can impart outstanding resistance against collapse under pressure to these gas-filled microbubbles used as contrast agents in ultrasonic echography by using as fillers gases whose solubility in water, expressed in liter of gas by liter of water under standard conditions, divided by the square root of the molecular weight does not exceed 0.003. Contrast agents with particular mixtures of gases are also disclosed that have advantageous properties.
Type:
Application
Filed:
January 6, 2003
Publication date:
October 2, 2003
Applicant:
Bracco International B.V.
Inventors:
Michel Schneider, Feng Yan, Pascal Grenier, Nadine Garcel, Jerome Puginier, Marie-Bernadette Barrau, Philippe Bussat, Eva Hybl, Daniel Bichon
Abstract: Gas or air filled microbubble suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. They contain surfactants and, optionally, hydrophilic stabilizers. The surfactants can be in the form of liposomes. The suspensions are obtained by exposing the surfactants to air or a gas before or after admixing with an aqueous phase. One can impart outstanding resistance against collapse under pressure to these gas-filled microbubbles used as contrast agents in ultrasonic echography by using as fillers gases whose solubility in water, expressed in liter of gas by liter of water under standard conditions, divided by the square root of the molecular weight does not exceed 0.003. Contrast agents with particular mixtures of gases are also disclosed that have advantageous properties.
Type:
Application
Filed:
March 12, 2003
Publication date:
September 18, 2003
Applicant:
Bracco International B.V.
Inventors:
Michel Schneider, Feng Yan, Pascal Grenier, Jerome Puginier, Marie-Bernadette Barrau, Philippe Bussat, Eva Hybl, Daniel Bichon, Nadine Garcel
Abstract: Gas or air filled microbubble suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. They contain surfactants and, optionally, hydrophilic stabilizers. The surfactants can be in the form of liposomes. The suspensions are obtained by exposing the surfactants to air or a gas before or after admixing with an aqueous phase. One can impart outstanding resistance against collapse under pressure to these gas-filled microbubbles used as contrast agents in ultrasonic echography by using as fillers gases whose solubility in water, expressed in liter of gas by liter of water under standard conditions, divided by the square root of the molecular weight does not exceed 0.003. Contrast agents with particular mixtures of gases are also disclosed that have advantageous properties.
Type:
Grant
Filed:
September 22, 1999
Date of Patent:
September 2, 2003
Assignee:
Bracco International B.V.
Inventors:
Michel Schneider, Feng Yan, Pascal Grenier, Jerome Puginier, Marie-Bernadette Barrau, Philippe Bussat, Eva Hybl, Daniel Bichon
Abstract: One can impart outstanding resistance against collapse under pressure to gas-filled microvesicle used as contrast agents in ultrasonic echography by using as fillers gases whose solubility in water, expressed in liter of gas by liter of water under standard conditions, divided by the square root of the molecular weight does not exceed 0.003.