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Details for Patent: 5,469,854

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Details for Patent: 5,469,854

Title: Methods of preparing gas-filled liposomes
Abstract:Methods of and apparatus for preparing gas-filled liposomes are described. Gas-filled liposomes prepared by these methods are particularly useful, for example, in ultrasonic imaging applications and in therapeutic drug delivery systems.
Inventor(s): Unger; Evan C. (Tucson, AZ), Fritz; Thomas A. (Tucson, AZ), Matsunaga; Terry (Tucson, AZ), Ramaswami; VaradaRajan (Tucson, AZ), Yellowhair; David (Tucson, AZ), Wu; Guanli (Tucson, AZ)
Assignee: ImaR.sub.x Pharmaceutical Corp. (Tucson, AZ)
Filing Date:Jun 11, 1993
Application Number:08/076,239
Claims:1. A method for preparing gas-filled lipid microspheres comprising shaking an aqueous solution comprising a lipid in the presence of a gas at a temperature below the gel state to liquid crystalline state phase transition temperature of the lipid.

2. A method as in claim 1 wherein the shaking step comprises vortexing.

3. A method as in claim 1 further comprising filtering and heat sterilizing said aqueous lipid solution.

4. A method as in claim 1 further comprising extruding the microspheres through at least one filter of a selected pore size.

5. A method as in claim 4 wherein the pore size is about 10 .mu.m or smaller.

6. A method as in claim 1 further comprising hydrating a dried lipid to form an aqueous solution comprising a lipid.

7. The method of claim 1 wherein said microsphere comprises a lipid selected from the group consisting of dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylethanolamine, and a phosphatidic acid, and said microsphere further comprising polyethylene glycol.

8. The method of claim 1 wherein said lipid comprises at least one dipalmitoyl lipid.

9. The method of claim 1 wherein said lipid comprises dipalmitoylphosphatidylethanolamine and polyethylene glycol.

10. The method of claim 1 wherein said lipid comprises dipalmitoylphosphatidylcholine, phosphatidic acid, dipalmitoylphosphatidylethanolamine, and polyethylene glycol.

11. The method of claim 1 wherein said microsphere comprises a gas selected from the group consisting of a fluorine gas and a nitrogen gas.

12. The method of claim 1 wherein said microsphere comprises a gas which is a fluorine gas.

13. The method of claim 1 wherein said microsphere comprises a gas which is nitrogen.

14. The method of claim 1 wherein said microsphere comprises a gas selected from the group consisting of a fluorine gas and a nitrogen gas and a lipid selected from the group consisting of dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylethanolamine, and a phosphatidic acid, and said microsphere further comprising polyethylene glycol.

15. The method of claim 1 wherein said microsphere comprises a gas selected from the group consisting of a fluorine gas and a nitrogen gas and a lipid comprising dipalmitoylphosphatidylcholine, phosphatidic acid, dipalmitoylphosphatidylethanolamine, and polyethylene glycol.

16. The method of claim 1 wherein said microsphere comprises a gas which is a fluorine gas and a lipid comprising dipalmitoylphosphatidylethanolamine and polyethylene glycol.

17. The method of claim 1 wherein said microsphere comprises 90% gas.

18. The method of claim 1 wherein said microsphere comprises a gas which is a fluorine gas and a lipid comprising dipalmitoylphosphatidylethanolamine and polyethylene glycol, said microsphere comprising 90% gas.

19. The method of claim 1 performed at a pressure above ambient pressure.
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