Methods of preparing gas-filled liposomes
First Claim
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1. A method of making gas-filled liposome microspheres, comprising the steps of:
- a) introducing an aqueous solution comprising a lipid into a vessel;
b) introducing a gas into said vessel;
c) shaking said aqueous lipid solution in the presence of said gas so as to instill at least a portion of said gas into said aqueous solution, said shaking performed with sufficient intensity and duration to produce a gas-filled-liposome-containing foam above said aqueous solution; and
d) extracting at least a portion of said gas-filled-liposome-containing foam from said vessel.
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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.
253 Citations
48 Claims
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1. A method of making gas-filled liposome microspheres, comprising the steps of:
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a) introducing an aqueous solution comprising a lipid into a vessel; b) introducing a gas into said vessel; c) shaking said aqueous lipid solution in the presence of said gas so as to instill at least a portion of said gas into said aqueous solution, said shaking performed with sufficient intensity and duration to produce a gas-filled-liposome-containing foam above said aqueous solution; and d) extracting at least a portion of said gas-filled-liposome-containing foam from said vessel. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32)
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33. A gas-filled microsphere prepared by a gel state shaking gas instillation method comprising a polymer, a polysaccharide, fatty acids, lysolipids, dioleoylphosphatidylcholine, dimyristoylphosphatidylcholine, dipentadecanoylphosphatidyl-choline, dilauroylphosphatidylcholine, dioleoylphosphatidyl-choline, dipalmitoylphosphatidylcholine, distearoyl-phosphatidylcholine, phosphatidylethanolamines, phosphatidylserine, phosphatidylqlycerol, phosphatidylinositol, sphingolipids, glycolipids, glucolipids, sulfatides, glycosphingolipids, phosphatidic acid, palmitic acid, stearic acid, arachidonic acid, oleic acid, lipids bearing polymers, lipids bearing sulfonated mono-, di-, oligo- or polysaccharides, cholesterol, cholesterol sulfate, cholesterol hemisuccinate, tocopherol hemisuccinate, lipids with ether-linked fatty acids, lipids with ester-linked fatty acids, polymerized lipids, diacetyl phosphate, stearylamine, cardiolipin, phospholipids with short chain fatty acids of 6-8 carbons in length, synthetic phospholipids with asymmetric acyl chains, 6-(5-cholesten-3β
- -yloxy)-1-thio-β
-D-galactopyranoside, digalactosyldiqlyceride, 6-(5-cholesten-3β
-yloxy)hexyl-6-amino-6-deoxy-1-thio-β
-D-galactopyranoside, 6-(5-cholesten-3β
-yloxy)hexyl-6-amino-6-deoxyl-1-thio-α
-D-mannopyranoside, 12-(((7'"'"'-diethylaminocoumarin-3-yl)carbonyl)methylamino)-octadecanoic acid, N- 12-(((7'"'"'-diethylaminocoumarin-3-yl)carbonyl)methyl-amino) octadecanoyl!-2-aminopalmitic acid, cholesteryl)4'"'"'-trimethyl-ammonio)butanoate, N-succinyldioleoylphosphatidylethanol-amine, 1,2-dioleoyl-sn-glycerol, 1,2-dipalmitoyl-sn-3-succinylglycerol, 1,3-dipalmitoyl-2-succinylglycerol,1-hexadecyl-2-palmitoylglycerophosphoethanolamine, or palmitoylhomocysteine, or combinations thereof. - View Dependent Claims (34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45)
- -yloxy)-1-thio-β
- 46. A microsphere prepared by a gel state shaking gas instillation method wherein the microsphere comprises a phospholipid.
Specification