Bracco Suisse Sa

Battelle Memorial Institute

Bracco Research Sa

Fisons Ltd.

Bracco International Bv

Ctl-Th Packaging, S.l. Unipersonal

Christian Guillot

Michel Schneider

Philippe Bussat

Feng Yan

Herve Tournier

Bernard Lamy

Peter Frinking

Jean Brochot

Anne Lassus

Stéphane Gorgerat

Daniel Bichon

Samir Cherkaoui

Roland Hyacinthe

Juan Ignacio Valpuesta Landa

Javier Fernandez De Mendiola Quintana

David Lazarus

Stephane Gorgerat

Andre Ayerbe

Pierre Chevreux

Eric Allémann

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

A freeze-dried powder composition comprising a phospholipid and a polyethylene glycol, said polyethylene glycol having a percentage of folded polymeric chains of 40% or higher. The composition is suitable for preparing gas-filled microvesicles.

Freeze-dried formulation for 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

Image enhancing contrast agents for use in diagnostic and/or therapeutic methods, particularly in the form of gas-filled microvesicles, with enhanced stability. The gas-filled microvesicles are stabilized by a layer of amphiphilic material and comprise from 0.15% to 1.0% by moles of a lipid bearing a hydrophilic polymer. The lipid bearing a hydrophilic polymer is preferably a phospholipid linked to polyethyleneglycol.

Gas-filled microvesicles with polymer-modified lipids

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.

The invention relates to a dry deposit as a precursor to liposome vesicles, the precursor being a three dimensional expanded structure with bulk density between 0.01 and 0.001 g/cm.sup.3. The invention also concerns a method of making liposome vesicles with an enhanced entrapment capacity by dissolving one or more film forming lipids in at least one organic solvent to form a solution in a reaction vessel, evaporating the solvent to form an expanded three dimensional porous lipid structure, contacting the lipid deposit with an aqueous carrier phase, and producing liposome vesicles entrapping the carrier phase as well as an apparatus comprising an array of tubing or an inert packing which serves as a material support or a matrix surface for the deposition of lipids produced according to the method.

Liposomes with enhanced entrapment capacity and their use in imaging

Liposome vesicle precursors

Liposomes with enhanced entrapment capacity, method and use

Method for making liposomes of enhanced entrapping capacity toward

Copolymer film deposited on a substrate comprising covalently fixed fragments of heparin having antithrombogenic properties. The polymer further comprises free carboxylic groups intended to neutralize free amine functions which are possibly present and to improve the hemocompatibility of the film.

Substrate with an antithromogenic active surface

A ligand specific to a bioactive substance to be purified is fixed, via a connecting silane, to a mineral particulate carrier chosen from among SiO.sub.2, Al.sub.2 O.sub.3, ZrO.sub.2 and TiO.sub.2, the particles of the carrier being submicronic, non-porous and having a large specific surface. The carrier is contacted with an aqueous extract containing inter alia the bioactive substances, for the time required for the substance to become specifically fixed to the carrier. The carrier is then separated and the desired bioactive substance is isolated by desorption.

Method of purifying bioactive substances by biospecific adsorption

Composition for binding bioactive substances

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Beaumont, France

Christian Guillot