Ultrasound contrast agents and process for the preparation thereof
AssigneeBracco International B.V.
InventorsMichel Schneider, Philippe Bussat, Feng Yan, Christian Guillot
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Abstract
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.
Claims61
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;
- 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.
2-40. (canceled)
46) The method of any of the preceding claims, wherein the amount of organic solvent is from about 1% to about 50% by volume with respect to the amount water.
66) A method for preparing an injectable contrast agent comprising a liquid aqueous suspension of gas-filled microbubbles stabilized predominantly by a phospholipids, which comprises:
- 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;
- lyophilizing said emulsified mixture, to obtain a lyophilized matrix comprising said phospholipids;
- b) contacting said lyophilized matrix with a biocompatible gas;
- and
- c) reconstituting said lyophilized matrix by dissolving it in a physiologically acceptable aqueous carrier liquid, to obtain a suspension of gas-filled microbubbles stabilized predominantly by said phosopholipid.
70) An injectable aqueous suspension of microbubbles filled with a biocompatible gas and comprising a stabilizing layer predominantly comprising a phospholipid, wherein said microbubbles have a number mean diameter (DN) of less than 1.70 μm and a volume median diameter (DV50) such that the DV50/DN ratio is of about 2.00 or lower.
Dependencies are inferred from the claim text.