Bracco International Bv

Bracco Research Sa

Battelle Memorial Institute

Bracco Suisse Sa

Fisons Ltd.

Sintetica S.a.

Bracco S.p.a.

Bracco Industria Chimica, S.p.a.

Michel Schneider

Feng Yan

Philippe Bussat

Daniel Bichon

Jerome Puginier

Jean Brochot

Christian Guillot

Herve Tournier

Marie-Bernadette Barrau

Eva Hybl-Sutherland

Eva Hybl

Bernard Lamy

Roland Hyacinthe

Pascal Grenier

Peter Frinking

Anne Lassus

Nadine Garcel

J&eacute;r&ocirc;me Puginier

Pascal Grenier, Deceased

Kondareddiar Ramalingam

Adrian D Nunn

Karen E Linder

Michael F Tweedle

Edmund R Marinelli

Palaniappa Nanjappan

Radhakrishna K Pillai

Natarajan Raju

Mathew A Von Wronski

Laurent Jakob

Christophe Golay

Marcel Arditi

Samir Cherkaoui

Blaise Corthesy

Olivier De Pous

Tristan Messager

Van T Nguyen

Gilles Bioley

David Lazarus

Christian Mathieu

Jèróme Puginier

Eric Allémann

Agn&eacute;s Hiver

Anne Senente

Herv E Tournier

Nadine Garcel, Legal Representative

Andre Ayerbe

Pierre Chevreux

Carlos J Gonzalez Oliver

Jerone Puginier

Nadine Gercel, Legal Representative

Maria-Bernadette Barrau

A method of manufacturing a suspension of gas-filled microvesicles by reconstituting a freeze-dried product and a suspension obtained according to said method, where the freeze-dried product has been subjected to a thermal treatment.

Freeze-dried product and gas-filled microvesicles suspension

Lipid formulation particularly for preparing stable gas-filled microvesicles, comprising distearoyl-phosphatidylcholine (DSPC), dipalmitoylphosphatidylethanolamine-PEG5000 (DPPE-PEG5000) and palmitic acid in an advantageous relative molar ratio. The formulation is useful in particular for therapeutic application with ultrasounds.

Gas-filled microvesicles

The present invention relates to a new composition comprising gas-filled microvesicles for contrast imaging which are particularly suitable for providing an effective echo response to at least two selected ultrasound waves having different frequencies. Said composition preferably comprises at least two different preparations of gas-filled microvesicles having respective peaks of non-linear echographic response differing by at least 2 MHz to each other, and preferably have respective size distributions with different median sizes. In particular, said preparations preferably have size distributions with respective Dvalues differing from each other by at least 0.5 &#x3bc;m, more preferably at least 1.0 &#x3bc;m. Alternatively, said composition has a volume size distribution showing a value of Bowley skewness of 0.16 or higher. According to a preferred embodiment, at least 95% of the total volume of gas contained in said microvesicles, calculated on the population of microvesicles up to a diameter of 10 &#x3bc;m, is contained in microvesicles having a diameter of 8 micron or less.

Gas-filled microvesicles composition for contrast imaging

Gas-filled microvesicles comprising an antigen bound thereto and to aqueous suspensions containing said microvesicles, for use in immunomodulating formulations, in particular as a vaccine. The antigen is covalently bound to a component of the microvesicles envelope. The microvesicles of the invention are particularly effective in the uptake by antigen-presenting cells, in particular dendritic cells.

Methods of using gas-filled microvesicles covalently bound to an antigen

Assembly comprising a gas-filled microvesicle and a structural entity which is capable to associate through an electrostatic interaction to the outer surface of said microvesicle (microvesicle associated component&#x2014;MAC), thereby modifying the physico-chemical properties thereof. Said MAC may optionally comprise a targeting ligand, a bioactive agent, a diagnostic agent or any combination thereof. The assembly of the invention can be formed from gasfilled microbubbles or microballoons and a MAC having a diameter of less than 100 pm, in particular a micelle and is used as an active component in diagnostically and/or therapeutically active formulations, in particular for enhancing the imaging in the field of ultrasound contrast imaging, including targeted ultrasound imaging, ultrasound-mediated drug delivery and other imaging techniques such as molecular resonance imaging (MRI) or nuclear imaging.

Gas-filled microvesicle assembly for contrast imaging

Method for preparing a lyophilized matrix and, upon reconstitution of the same, a respective injectable contrast agent comprising a liquid aqueous suspension of gas-filled microbubbles stabilized predominantly by a phospholipid. The method comprises preparing an emulsion from an aqueous medium, a phospholipid and a water immiscible organic solvent. The emulsion is then freeze-dried and subsequently reconstituted in an aqueous suspension of gas-filled microbubbles. The method allows to obtain suspensions comprising microbubbles having a relatively small diameter and a narrow size distribution.

Ultrasound contrast agents and process for the preparation thereof

The present invention relates to a new composition comprising gas-filled microvesicles for contrast imaging which are particularly suitable for providing an effective echo response to at least two selected ultrasound waves having different frequencies. Said composition preferably comprises at least two different preparations of gas-filled microvesicles having respective peaks of non-liner echographic response differing by at least 2 MHz to each other, and preferably have respective size distributions with different mean sizes. In particular, said preparations preferably have size distributions with respective Dvalues differing from each other by at least 0.5 &#x3bc;m, more preferably at least 1.0 &#x3bc;m. Alternatively, said composition has a volume size distribution showing a value of Bowley skewness of 0.16 or higher. According to a preferred embodiment, at least 95% of the total volume of gas contained in said microvesicles, calculated on the population of microvesicles up to a diameter of 10 &#x3bc;m, is contained in microvesicles having a diameter of 8 micron or less.

An embodiment analyzes a body part of a patient, which patient is perfused with a contrast agent that is capable of circulating within the patient and of being substantially immobilized on a biological target. An embodiment of a corresponding system provides an echo signal that is indicative of a response over time to an interrogation signal of the body part, fits the echo signal with a time model function that models an evolution over time of the contrast agent in the body part, the time model function including a combination of a circulation function that models the circulation of the contrast agent and a decay function that models a decay of the echo signal from the immobilized contrast agent, and estimates at least one kinetics indicator of the contrast agent from the time model function.

Quantification analysis of immobilized contrast agent in medical imaging applications

The present invention provides compounds for targeting endothelial cells, tumor cells or other cells that express the NP-1 receptor, compositions containing the same and methods for their use. Additionally, the present invention includes diagnostic, therapeutic and radiotherapeutic compositions useful for visualization, therapy or radiotherapy.

Compounds for targeting endothelial cells, compositions containing the same and methods for their use

Composition for diagnostic or therapeutic use which comprises an assembly comprising an active agent. The assembly comprises a liposome and a plurality of micellar components associated thereto, said micellar components being associated to the outer surface of the envelope of said liposome through a substantially electrostatic interaction, When an active compound is incorporated into the micelles, a substantial amount of said active compound can be linked to a singe liposome. Furthermore, the presence of the outer micellar layer allows to increase the residence time of said liposome in the blood stream.

Liposomal assembly for therapeutic and/or diagnostic use

A power assisted method and injector device for controllably delivering to patients a dispersion medicament or diagnostically active agent, the homogeneity of which is preserved throughout delivery. Diagnostically active agents disclosed are gas microbubble suspensions useful in ultrasonic diagnostic imaging and liposomal formulations in which liposome vesicles are loaded with iodinated compounds.

Automatic liquid injection system and method

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.

Ultrasound contrast agents and methods of making and using them

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.

Long-lasting aqueous dispersions or suspensions of pressure-resistant gas-filled microvesicles and methods for the preparation thereof

Growing community of inventors

Troinex, Switzerland

Michel Schneider