Stabilized gas emulsion containing phospholipid for ultrasound contrast enhancement

• US 7,141,235 B2
• Filed: 08/28/2001
• Issued: 11/28/2006
• Est. Priority Date: 07/30/1993
• Status: Expired due to Fees

• Current Assignee: Targeson, Inc.
• Original Assignee: IMCOR Pharmaceutical Company
• Inventors: Trevino, Leo A., Kabalnov, Alexey, Klein, David H., Schutt, Ernest George, Weers, Jeffry G., Tarara, Thomas E.
• Primary Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US09/941,395
• Publication Number:
  US 20020031476A1
• Time in Patent Office: 1,918 Days
• Field of Search: 424/9.52, 424/9.51, 424/9.5, 600/441, 600/458
• US Class Current: 424/9.52
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
• CPC Class Codes: A61K 49/227 Liposomes, lipoprotein vesicles, e.g. LDL or HDL lipoproteins, micelles, e.g. phospholipidic or polymeric

Abstract

A gas emulsion forming composition comprising a dry, hollow, particulate, approximately microspherical material permeated with a gas or gas mixture, which upon dissolution in aqueous liquid forms a gas emulsion comprising a plurality of bubbles surrounded by a layer of at least a first and a second surfactant, wherein the first surfactant consists essentially of a phospholipid or mixture of phospholipids having at least one acyl chain which comprises at least 10 carbon atoms, and comprising at least about 5% w/w of total surfactant, and wherein the second surfactant may or may not be a phospholipid and is more water soluble than the first surfactant; kits for preparing such microbubbles; and methods for using such microbubbles as contrast agents.

Claims

1. A system for providing an ultrasound image of at least a part of an object or body comprising:

an ultrasound imaging apparatus;

a kit capable of producing a stabilized microbubble preparation, conprising an aqueous medium, a gas osmotic agent, at least one phospholipid surfactant having at least one acyl chain of at least 10 or more carbon atoms and at least a second surfactant, wherein upon the application of energy the phospholipid surrounds the gas osmotic agent to form a microbubble, wherein the gas osmotic agent is selected from the group consisting of perfluorobutane, perfluorocyclobutane, perfluoropentane, perfluorocyclopentane, perfluoromethylcyclobutane, perfluorohexane, perfluorocyclohexane, perfluoromethylcyclopentane, perfluorodimethylcyclobutane, perfluoroheptane, perfluorocycloheptane, perfluoromethylcyclohexane, perfluorodimethylcyclopentane, perfluorotrimethylcyclobutane, perfluorotriethylamine, perfluoropropane and perfluorohexane.

2. The system of claim 1 wherein the gas osmotic agent is selected from the group consisting of perfluoropropane and perfluorohexane.

3. The system of claim 1 wherein the kit further comprises a modifier gas selected from the group consisting of nitrogen, oxygen, carbon dioxide or mixtures thereof.

4. The system of claim 3 wherein the mixture of the gas osmotic agent and modifier gas is effective to stabilize the microbubble preparation.

5. The system of claim 3 wherein the modifier gas is air.

6. The system of claim 3 wherein the gas osmotic agent is perfluoropropane and the second gas is nitrogen.

7. The system of claim 1 wherein the aqueous solution contains sterile water.

8. The system of claim 1 wherein the microbubble further comprises air.

9. The system of claim 1 wherein the gas osmotic agent is perfluoropropane.

10. The system of claim 1 wherein the kit contains a head space containing perfluoropropane gas.

11. The system of claim 10 wherein the head space contains air.

12. The system of claim 1 wherein the energy applied is mechanical energy.

13. The system of claim 1 wherein the energy applied is sonic energy.