Liposomes as contrast agents for ultrasonic imaging and methods for preparing the same

• US 5,230,882 A
• Filed: 01/08/1992
• Issued: 07/27/1993
• Est. Priority Date: 12/22/1989
• Status: Expired due to Term

• Current Assignee: Lantheus Medical Imaging, Inc. (Lantheus Holdings, Inc.)
• Original Assignee: Evan C. Unger
• Inventors: Unger, Evan C.
• Primary Examiner(s): Raymond, Richard L.
• Assistant Examiner(s): RUSSELL, MARK
• Application Number:
  US07/818,069
• Time in Patent Office: 566 Days
• Field of Search: 128/662.02, 424/9, 424/450, 514/546, 514/150
• US Class Current: 424/9.51
• CPC Class Codes: A61K 41/0028 Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
• CPC Class Codes: A61K 41/0052 Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
• 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
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1277 Processes for preparing; Proliposomes
• CPC Class Codes: A61K 9/1278 Post-loading, e.g. by ion or pH gradient

Abstract

Liposomes suitable as ultrasound contrast agents which contain media of various types including gases, gaseous precursors activated by pH, temperature or pressure, as well as other solid or liquid contrast enhancing agents, are described. Methods of using the same as ultrasound contrast agents are also disclosed. The present invention also comprises novel methods for synthesizing liposomes having encapsulated therein gases.

Claims

1. A contrast agent for ultrasonic imaging which comprises a liposome having encapsulated therein a photo-activated gaseous precursor.

2. A contrast agent according to claim 1 wherein said photo-activated precursor is a diazonium compound.

5. A contrast agent according to claim 1 wherein the liposome is comprised of lipid selected from the group consisting of fatty acids, lysolipids, dipalmitoylphosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, phosphatidylglycerol, phosphatidic acid, phosphatidylinositol, sphingomyelin, lysolipids, cholesterol, cholesterol hemisuccinate, glycosphingolipids, glycolipids, glucolipids, sulphatides, and tocopherol hemisuccinate.

6. A contrast agent according to claim 5 wherein the liposome is comprised of phosphatidylcholine.

7. A contrast agent according to claim 5 wherein the liposome is comprised of cholesterol and phosphatidylcholine.

8. A contrast agent according to claim 1 wherein the liposome has a mean outer diameter of between about 30 nanometers and about 2 microns.

9. A contrast agent according to claim 1 wherein the liposome has a mean outer diameter of between about 2 microns and about 10 microns.

3. A contrast agent for ultrasonic imaging which comprises a liposome having encapsulated therein a temperature-activated gaseous precursor.

4. A contrast agent according to claim 3 wherein said temperature-activated gaseous precursor is methyllactate.

10. A contrast agent according to claim 3 wherein the liposome is comprised of lipids selected from the group consisting of fatty acids, lysolipids, dipalmitoylphosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, phosphatidylglycerol, phosphatidic acid, phosphatidylinositol, shpingomyelin, lysolipids, cholesterol, cholesterol hemisuccinate, glycosphingolipids, glycolipids, glucolipids, sulphatides, and tocopherol hemisuccinate.

11. A contrast agent according to claim 10 wherein the liposome is comprised of phosphatidylcholine.

12. A contrast agent according to claim 10 wherein the liposome is comprised of cholesterol and phosphatidylcholine.

13. A contrast agent according to claim 3 wherein the liposome has a mean outer diameter of between about 30 nanometers and about two microns.

14. A contrast agent according to claim 3 wherein the liposome has a mean outer diameter of between about 2 microns and about 10 microns.