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|Title:||Stable microbubbles suspensions injectable into living organisms|
|Abstract:||Gas or air filled microbubble suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. They contain laminarized surfactants and, optionally, hydrophilic stabilizers. The laminarized surfactants can be in the form of liposomes. The suspensions are obtained by exposing the laminarized surfactants to air or a gas before or after admixing with an aqueous phase.|
|Inventor(s):||Schneider; Michel (Troinex, CH), Bichon; Daniel (Montpellier, FR), Bussat; Philippe (Collonges S/Saleve, FR), Puginier; Jerone (Le Chable-Beaumont, FR), Hybl; Eva (Geneva, CH)|
|Assignee:||Bracco International B.V. (NL)|
|Filing Date:||Jul 15, 1997|
|Claims:||1. Gas microbubbles prepared by the process of admixing a liposome solution comprising hydrogenated soya lecithin and dicetylphosphate with a mixture comprising water and a physiologically acceptable gas. |
2. Gas microbubbles prepared by the process of sonicating a solution comprising hydrogenated soya lecithin and dicetylphosphate, cooling the solution, adding a viscosity enhancer to the solution, shaking the solution in the presence of a physiologically acceptable gas at above atmospheric pressure.
3. Gas microbubbles prepared by the process of immersing glass beads in a solution of dipalmitoylphosphatidylcholine in chloroform, rotating the beads under reduced pressure to evaporate the chloroform, rotating the beads under atmospheric pressure with a physiologically acceptable gas, adding distilled water to the solution, and removing the beads from the solution.
4. Gas microbubbles prepared by the process of forming a liposome/maltose solution by adding a liposome solution comprising hydrogenated soya lecithin and dicetylphosphate to a maltose solution in distilled water, freezing the liposome/maltose solution, forming lyophilized powder by lyophilizing the liposome/maltose solution under reduced pressure, restoring pressure to the lyophilized powder with a physiologically acceptable gas, dissolving the lyophilized powder in water.
5. Gas microbubbles prepared by the process of forming a mixed solution prepared by mixing a solution of liposome comprising hydrogenated soya lecithin and dicetylphosphate with an aqueous solution of gelatin, humar albumin, dextran, and iopamidol, lyophilizing the mixed solution to form a lyophilized sample, introducing a physiologically acceptable gas into the lyophilized sample, mixing the lyophilized sample with water.
6. Gas microbubbles prepared by the process of forming a mixture by moistening lactose with a solution of chloroform, dimyristoylphosphatidylcholine, cholesterol, dipalmitoylphosphatidic acid, evaporating the mixture under vacuum to form a powder, rotating the powder under a physiologically acceptable gas at normal pressure, and dissolving the powder in water.
7. Gas microbubbles prepared by the process of sonicating an aqueous solution of hydrogenated soya lecithin and a nonionic polyoxyethylene-polyoxypropylene copolymer surfactant, cooling the solution, centrifuging the solution, forming a mixture by adding the aqueous solution to a maltose solution in water, freezing the mixture, evaporating the mixture under reduced pressure, restoring pressure to the mixture with a physiologically acceptable gas.
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