Methods of ultrasound treatment using gas or gaseous precursor-filled compositions
First Claim
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1. A method for lysing an intravascular blood clot in the brain of a patient, said method comprising:
- (i) heating a composition comprising lipid vesicles encapsulating a gaseous precursor to a temperature at or above the boiling point of the gaseous precursor, wherein said gaseous precursor is a fluorinated compound, said lipid vesicles comprise at least one phosphatidylcholine, at least one phosphatidylethanolamine, and at least one phosphatidic acid, wherein said phosphatidylcholine is selected from the group consisting of dioleoylphosphatidylcholine, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, and distearoyl-phosphatidylcholine;
said phosphatidylethanolamine is selected from the group consisting of dipalmitoylphosphatidylethanolamine, dioleoyl-phosphatidylethanolamine, and N-succinyl-dioleoyl-phosphatidylethanolamine; and
said phosphatidic acid is dipalmatoylphosphatidic acid, (ii) administering said composition to a patient, and (iii) applying ultrasonic energy to the brain of the patient in an amount sufficient to cavitate or rupture at least a portion of said vesicles.
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Abstract
The present invention describes, among other things, the surprising discovery that gaseous precursor filled compositions are profoundly more effective as acoustically active contrast agents when they are thermally preactivated to temperatures at or above the boiling point of the instilled gaseous precursor prior to their in vivo administration to a patient. Further optimization of contrast enhancement is achieved by administering the gaseous precursor filled compositions to a patient as an infusion. Enhanced effectiveness is also achieved for ultrasound mediated targeting and drug delivery.
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25 Claims
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1. A method for lysing an intravascular blood clot in the brain of a patient, said method comprising:
- (i) heating a composition comprising lipid vesicles encapsulating a gaseous precursor to a temperature at or above the boiling point of the gaseous precursor, wherein said gaseous precursor is a fluorinated compound, said lipid vesicles comprise at least one phosphatidylcholine, at least one phosphatidylethanolamine, and at least one phosphatidic acid, wherein said phosphatidylcholine is selected from the group consisting of dioleoylphosphatidylcholine, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, and distearoyl-phosphatidylcholine;
said phosphatidylethanolamine is selected from the group consisting of dipalmitoylphosphatidylethanolamine, dioleoyl-phosphatidylethanolamine, and N-succinyl-dioleoyl-phosphatidylethanolamine; and
said phosphatidic acid is dipalmatoylphosphatidic acid, (ii) administering said composition to a patient, and (iii) applying ultrasonic energy to the brain of the patient in an amount sufficient to cavitate or rupture at least a portion of said vesicles. - 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)
- (i) heating a composition comprising lipid vesicles encapsulating a gaseous precursor to a temperature at or above the boiling point of the gaseous precursor, wherein said gaseous precursor is a fluorinated compound, said lipid vesicles comprise at least one phosphatidylcholine, at least one phosphatidylethanolamine, and at least one phosphatidic acid, wherein said phosphatidylcholine is selected from the group consisting of dioleoylphosphatidylcholine, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, and distearoyl-phosphatidylcholine;
Specification