Ultrasound Contrast Agents And Process For The Preparation Thereof
AssigneeBracco Suisse SA
InventorsMichel Schneider, Philippe Bussat, Feng Yan, Christian Guillot
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Abstract
Injectable aqueous suspension of microbubbles filled with a biocompatible gas and a method of preparation thereof. At least 10% of the total volume of gas contained in the microbubbles is contained in microbubbles with a diameter of 1.5 μm or less. The microbubbles can be obtained by preparing an emulsion comprising an aqueous medium, a phospholipid and a water immiscible organic solvent. The emulsion is then freeze-dried and then reconstituted in an aqueous suspension of gas-filled microbubbles.
Claims13
An injectable aqueous suspension of microbubbles filled with a biocompatible gas and comprising a stabilizing layer predominantly comprising a phospholipid, wherein at least 10% of the total volume of gas contained in the microbubbles is contained in microbubbles with a diameter of 1.5 μm or less.
The aqueous suspension according to any one of the preceding claims obtainable by a method which comprises the steps of:
- a) preparing an aqueous-organic emulsion comprising i) an aqueous medium including water, ii) an organic solvent substantially immiscible with water, iii) an emulsifying composition of amphiphilic materials comprising more than 50% by weight of a phospholipid and iv) a lyoprotecting agent;
- b) lyophilizing said emulsified mixture, to obtain a lyophilized matrix comprising said phospholipid;
- c) contacting said lyophilized matrix with a biocompatible gas;
- and reconstituting said lyophilized matrix by dissolving it in a physiologically acceptable aqueous carrier liquid.
A method for preparing a lyophilized matrix which, upon contact with an aqueous carrier liquid and a gas, is reconstitutable into a suspension of gas-filled microbubbles stabilized predominantly by a phospholipid, said method comprising the steps of:
- a) preparing an aqueous-organic emulsion comprising i) an aqueous medium including water, ii) an organic solvent substantially immiscible with water comprising, dispersed therein, an emulsifying composition of amphiphilic materials comprising more than 50% by weight of a phospholipid and iv) a lyoprotecting agent;
- b) lyophilizing said emulsified mixture, to obtain a lyophilized matrix comprising said phospholipid.
Dependencies are inferred from the claim text.