Methods for producing microbubbles

摘要

The present invention provides methods for the preparation of gas-filled microbubbles, and methods of using for therapeutic and/or diagnostic applications. In particular, the methods of the invention allow for the preparation of gas-filled microbubbles having narrow size distributions and defined ultrasonic properties.

主权项

1. A method for preparing a plurality of microbubbles filled with a perfluorocarbon gas, the plurality of microbubbles having an average, single microbubble acoustic collapse threshold of about 0.3-30 MPa, at least 80% of the microbubbles having diameters within about 10% of a selected mean diameter, the method comprising:
(a) saturating a solution comprising serum albumin and dextrose with the perfluorocarbon gas; and (b1) delivering a first round of ultrasound energy at a power level of about 150 W within the solution and delivering a second round of ultrasound energy at a power level of about 400-450 W outside the solution, wherein the plurality of microbubbles has a mean diameter of about 1.0 micron; (b2) delivering a first round of ultrasound energy at a power level of about 125-250 W within the solution and delivering a second round of ultrasound energy at a power level of about 300-375 W outside the solution, wherein the plurality of microbubbles has a mean diameter of about 2.0 microns; (b3) delivering a first round of ultrasound energy at a power level of about 250 W within the solution and delivering a second round of ultrasound energy at a power level of about 450 W outside the solution, wherein the plurality of microbubbles has a mean diameter of about 3.0 microns; (b4) delivering a first round of ultrasound energy at a power level of about 250-300 W within the solution and delivering a second round of ultrasound energy at a power level of about 250-350 W outside the solution, wherein the plurality of microbubbles has a mean diameter of about 4.0 microns; (b5) delivering a first round of ultrasound energy at a power level of about 250-300 W within the solution and delivering a second round of ultrasound energy at a power level of about 200-250 W outside the solution, wherein the plurality of microbubbles has a mean diameter of about 5-6 microns; or (b6) delivering only one round of ultrasound energy at a power level of about 400-500 W outside the solution, wherein the plurality of microbubbles has a mean diameter of about 0.5-1.0 micron.