Method of making lyophilized microbubble compositions useful as contrast agents
First Claim
1. A process for the preparation of a microbubble-releasing matrix comprising a cryoprotectant/lyoprotectant containing gas-filled substantially spherical cavities or vacuoles surrounded by layers of membrane-forming lipid material, wherein said gas is selected from the group consisting of sulphur hexafluoride, fluorinated low molecular weight hydrocarbons and mixtures of the foregoing, and wherein at least about 70% of said membrane-forming lipid material consists of one or more phosphatidylserines, said process comprising the steps:
- i) dispersing said gas in an aqueous medium containing said membrane-forming lipid material to form a lipid-stabilised dispersion of microbubbles of said gas;
ii) adding said cryoprotectant/lyoprotectant to said dispersion; and
iii) lyophilising said dispersion to yield said microbubble-releasing matrix.
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Abstract
Microbubble dispersions stabilised by phospholipids predominantly comprising molecules which individually have an overall net charge exhibit advantageous stability, rendering them useful both as efficacious contrast agents per se and as intermediates in the preparation of contrast agents wherein the phospholipids are crosslinked or polymerised. An improved process for preparing microbubble-containing contrast agents is also disclosed, this comprising lyophilising an aqueous dispersion of gas microbubbles stabilised by one or more membrane-forming lipids to yield a dried product which may be reconstituted in an injectable carrier liquid to generate a microbubble-containing contrast agent.
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Citations
12 Claims
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1. A process for the preparation of a microbubble-releasing matrix comprising a cryoprotectant/lyoprotectant containing gas-filled substantially spherical cavities or vacuoles surrounded by layers of membrane-forming lipid material, wherein said gas is selected from the group consisting of sulphur hexafluoride, fluorinated low molecular weight hydrocarbons and mixtures of the foregoing, and wherein at least about 70% of said membrane-forming lipid material consists of one or more phosphatidylserines, said process comprising the steps:
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i) dispersing said gas in an aqueous medium containing said membrane-forming lipid material to form a lipid-stabilised dispersion of microbubbles of said gas;
ii) adding said cryoprotectant/lyoprotectant to said dispersion; and
iii) lyophilising said dispersion to yield said microbubble-releasing matrix. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
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Specification