Abstract: Novel compounds containing a heteroatom-bearing bridge and novel complexes of these compounds with metals. The novel compounds and complexes are useful in diagnostic and therapeutic methods.
Abstract: Novel compounds of the formula ##STR1## where G.sup.1 and G.sup.2 are each independently --OH or --N(R.sup.2).sub.2, provided that at least one of G.sup.1 and G.sup.2 is --N(R.sup.2).sub.2, where each R.sup.2 is independently hydrogen, alkyl, aryl, acyl or --(A).sub.p --R.sup.a and the other variables are as defined in the specification and claims, and novel complexes of these compounds with metals are useful in diagnostic and therapeutic methods.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
July 29, 1997
Assignee:
Bracco International B.V.
Inventors:
David P. Nowotnik, Palaniappa Nanjappan
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:
September 26, 1995
Date of Patent:
July 1, 1997
Assignee:
Bracco International B.V.
Inventors:
Michel Schneider, Daniel Bichon, Philippe Bussat, Jerome Puginier, Eva Hybl-Sutherland
Abstract: New nonionic radiographic contrast agents having the formula ##STR1## wherein Y is a single bond, --CH.sub.2 CH.sub.2 --, --CH.sub.2 O--, --OCH.sub.2 --, ##STR2## --CH.sub.2 --, --CH.sub.2 --CH.sub.2 --CH.sub.2 --, --O-- or ##STR3## R.sub.1, R.sub.1 ' and R.sub.2 are the same or different and are hydrogen, alkyl or hydroxyalkyl.Hydroxyalkyl refers to such alkyl groups having 1 or more hydroxy groups. Preferred hydroxyalkyl groups include: ##STR4## R.sub.3 and R.sub.4 are the same or different and are hydrogen, methyl or --CH.sub.2 CH.sub.2 OH; R.sub.5 is hydrogen, alkyl, --CH.sub.2 CH.sub.2 OH, CH.sub.2 OH or OH and R.sub.6 is alkyl, CH.sub.2 CH.sub.2 OH, CH.sub.2 OH, OH or hydrogen and may be the same or different than R.sub.5 and m is zero or one, with the proviso that no methylene or methine carbon atom of the heterocyclic ring is attached to both a nitrogen and an oxygen atom with the additional proviso that when Y is a single bond, m is not zero.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
May 13, 1997
Assignee:
Bracco International B.V.
Inventors:
Ramachandran S. Ranganathan, Thangavel Arunchalam, Edmund R. Marinelli, Radhakrishna K. Pillai
Abstract: Novel compounds containing a heteroatom-bearing bridge and novel complexes of these compounds with metals. The novel compounds and complexes are useful in diagnostic and therapeutic methods.
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 particulates; and (b) filling and assembling said syringe.
Abstract: New nonionic radiographic contrast agents having the formula ##STR1## wherein Y is a single bond, --CH.sub.2 CH.sub.2 --, --CH.sub.2 O--, --OCH.sub.2 --, ##STR2## --CH.sub.2 --, --CH.sub.2 --CH.sub.2 --CH.sub.2 --, --O-- or ##STR3## R.sub.1, R.sub.1 ' and R.sub.2 are the same or different and are hydrogen, alkyl or hydroxyalkyl.Hydroxyalkyl refers to such alkyl groups having 1 or more hydroxy groups. Preferred hydroxyalkyl groups include: ##STR4## R.sub.3 and R.sub.4 are the same or different and are hydrogen, methyl or --CH.sub.2 CH.sub.2 OH; R.sub.5 is hydrogen, alkyl, --CH.sub.2 CH.sub.2 OH, CH.sub.2 OH or OH and R.sub.6 is alkyl, --CH.sub.2 CH.sub.2 OH, CH.sub.2 OH, OH or hydrogen and may be the same or different than R.sub.5 and m is zero or one, with the proviso that no methylene or methine carbon atom of the heterocyclic ring is attached to both a nitrogen and an oxygen atom with the additional proviso that when Y is a single bond, m is not zero.
Type:
Grant
Filed:
June 5, 1992
Date of Patent:
March 25, 1997
Assignee:
Bracco International B.V.
Inventors:
Ramachandran S. Ranganathan, Thangavel Arunchalam, Edmund R. Marinelli, Radhakrishna K. Pillai
Abstract: Novel compounds containing a heteroatom-bearing bridge and novel complexes of these compounds with metals. The novel compounds and complexes are useful in diagnostic and therapeutic methods.
Abstract: Methods wherein the concentration of NMR-detectable xenobiotic compounds may be determined in living subjects by in vivo measurement of one or more magnetic resonance signals. In preferred embodiments, the present invention provides a method for evaluating, in vivo, the clearance rate of a xenobiotic compound from a living subject, thereby providing a noninvasive method for determining the status of the excretory organs of the subject, and a method for determining the proper dosing regimen of a pharmacologically active compound to be administered to the subject.
Type:
Grant
Filed:
December 28, 1994
Date of Patent:
February 18, 1997
Assignee:
Bracco International B. V.
Inventors:
Michael F. Tweedle, Harry W. Strauss, Adrian D. Nunn
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 stabilizer 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 is a method of preparation of the stable suspensions of air or gas filled microbubbles.
Type:
Grant
Filed:
March 31, 1995
Date of Patent:
January 28, 1997
Assignee:
Bracco International B.V.
Inventors:
Michel Schneider, Jean Brochot, Jerome Puginier, Feng Yan
Abstract: New nonionic radiographic contrast agents having the formula ##STR1## wherein Y is a single bond, ##STR2## R.sub.1, R.sub.1 ' and R.sub.2 are the same or different and are hydrogen, alkyl or hydroxyalkyl.Hydroxyalkyl refers to such alkyl groups having 1 or more hydroxy groups. Preferred hydroxyalkyl groups include: ##STR3## R.sub.3 and R.sub.4 are the same or different and are hydrogen, methyl or --CH.sub.2 CH.sub.2 OH; R.sub.5 is hydrogen, alkyl, --CH.sub.2 CH.sub.2 OH, CH.sub.2 OH or OH and R.sub.6 is alkyl, --CH.sub.2 CH.sub.2 OH, CH.sub.2 OH, OH or hydrogen and may be the same or different than R.sub.5 and m is zero or one, with the proviso that no methylene or methine carbon atom of the heterocyclic ring is attached to both a nitrogen and an oxygen atom with the additional proviso that when Y is a single bond, m is not zero. These new contrast agents are water soluble and have desirable low osmolality and anticoagulant properties.
Type:
Grant
Filed:
October 27, 1993
Date of Patent:
January 7, 1997
Assignee:
Bracco International B.V.
Inventors:
Ramachandran S. Ranganathan, Thangavel Arunchalam, Edmund R. Marinelli, Radhakrishna K. Pillai
Abstract: Magnetite particles suitable for injection into the blood stream of patients having enhanced resistance against agglomeration and uptake by the RES of the liver and spleen. The particles essentially consist of an iron oxide core and a phosphoric acid mono alkyl or alkenyl ester or glycerophospholipid/surfactant three dimensional shell surrounding the core. The core and the monoester or a micellar glycerophospholipid form an urchin-like structure which is further interlaced or intertwined with a non-ionic surfactant to produce a protective three dimensional shell which renders particles almost undetectable by the macrophages. Particles prepared according to the invention are kept in the blood circulation for long periods and represent excellent long lasting blood pool agents. Key components in the shell are (a) a polybasic mineral-organic species such as glycero phosphatidic acid in micellar form and (b) a block copolymer having successive hydrophilic and hydrophobic segments.
Type:
Grant
Filed:
April 13, 1995
Date of Patent:
December 24, 1996
Assignee:
Bracco International B.V.
Inventors:
Herve Tournier, Roland Hyacinthe, Michel Schneider
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 aromatic amide compounds comprising a ligand nucleus containing at least one aminocarboxylate, aminophosphonate and/or aminohydroxamate chelating group, substituted with a substituted aromatic amide group of the formula ##STR1## wherein R is ##STR2## or --[(CH.sub.2).sub.2 --Y]--R.sub.13, salts and/or multimers thereof, and metal chelates, particularly useful for MRI of the hepatobiliary system.
Type:
Grant
Filed:
January 11, 1996
Date of Patent:
November 12, 1996
Assignee:
Bracco International B.V.
Inventors:
Ramachandran S. Ranganathan, Edmund R. Marinelli, Radhakrishna Pillai, Michael F. Tweedle
Abstract: In this method, one attaches one or more chelatant molecules to a mono- or polyamino intermediate compound I which is temporarily immobilized on a solid phase by a splittable bond. Thereafter, said bond is split to release the desired conjugate moiety, whereby a reactive site is generated at the splitting site. The conjugate can be coupled to a protein homing factor using said reactive site; the latter being single per chelatant molecule, undesirable cross-linking during conjugation is substantially avoided.
Abstract: Compounds, useful as radiolabeling reagents, including a trihalogenated phenyl ring and having the formula ##STR1## wherein X.sub.1, X.sub.2 and X.sub.3 are halogens, one of which may be a radiohalogen, are disclosed. The invention further includes radiohalogenated proteins as well as processes for preparing such reagents and radiohalogenated proteins.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
October 29, 1996
Assignee:
Bracco International B.V.
Inventors:
Marc Ogan, Frank P. Tomasella, Jan-I Tu
Abstract: Gas or air filled microbubble suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. They contain laminarized surfactants and, optionally, hydrophillc 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:
June 1, 1995
Date of Patent:
October 22, 1996
Assignee:
Bracco International B.V.
Inventors:
Michel Schneider, Daniel Bichon, Philippe Bussat, Jerome Puginier, Eva Hybl-Sutherland
Abstract: The present process involves ring opening and ring closure of compounds containing a tetrahydrofuroyl ##STR1## to provide facile synthesis of compounds containing a piperidin-2-one group of the formula ##STR2##
Type:
Grant
Filed:
July 15, 1994
Date of Patent:
September 24, 1996
Assignee:
Bracco International B.V.
Inventors:
Ramachandran S. Ranganathan, Thangavel Arunachalam, Kenneth J. Natalie, Jr.
Abstract: In accordance with the present invention a novel method and composition for using nonionic contrast media to reduce the risk of clot formation in a diagnostic procedure is disclosed. Novel compositions for such method are also disclosed. The present method comprises employing a triiodinated phenyl contrast agent having a heterocyclic group or a dimeric triiodinated phenyl contrast agent having one or more heterocyclic groups.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
June 18, 1996
Assignee:
Bracco International B.V.
Inventors:
Ramachandran S. Ranganathan, Radhakrishna K. Pillai
Abstract: A method for imaging mammalian tissue utilizing a non-ionic complex of a paramagnetic ion of lanthanide element and a macrocyclic chelating agent.
Type:
Grant
Filed:
December 20, 1994
Date of Patent:
December 12, 1995
Assignee:
Bracco International B.V.
Inventors:
Michael F. Tweedle, Glen T. Gaughan, James J. Hagan