Methods for providing localized therapeutic heat to biological tissues and fluids using gas filled liposomes

• US 5,209,720 A
• Filed: 06/18/1991
• Issued: 05/11/1993
• Est. Priority Date: 12/22/1989
• Status: Expired due to Term

• Current Assignee: Imarx Therapeutics, Inc. (Sycamore Entertainment Group, Inc.)
• Original Assignee: Evan C. Unger
• Inventors: Unger, Evan C.
• Primary Examiner(s): Rosenbaum, C. Fred
• Assistant Examiner(s): SMITH, CHALIN A
• Application Number:
  US07/716,793
• Time in Patent Office: 693 Days
• Field of Search: 264/4.2, 264/4.1, 264/4.6, 424/9, 424/44, 424/43, 424/450, 436/829, 128/24 EL, 128/24 AA, 128/24 R, 128/660.01-660.07, 128/653, 600/10, 600/12, 604/22, 604/20
• US Class Current: 604/20
• CPC Class Codes: A61B 2017/00716 simulating physical properties
• CPC Class Codes: A61B 2017/22088 ultrasound absorbing, drug activated by ultrasound
• 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 47/6925 the form being a microcapsule, nanocapsule, microbubble or nanobubble
• 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
• CPC Class Codes: A61M 2202/0476 Oxygenated solutions
• CPC Class Codes: A61N 2007/025 interstitial
• CPC Class Codes: A61N 7/00 Ultrasound therapy lithotripsy A61B17/22, A61B17/225; massage using supersonic vibration A61H23/00 ; using ultrasound for introducing media into the body A61M37/0092
• CPC Class Codes: A61N 7/02 Localised ultrasound hyperthermia hyperthermia in general A61F7/00

Abstract

Gas filled liposomes prepared by a vacuum drying gas instillation method and/or gas filled liposomes substantially devoid of liquid in the interior thereof, are presented as novel potentiators for ultrasonic hyperthermia. The liposomes of the present invention, which may be administered into the vasculature, interstitially or into any body cavity are designed to accumulate in cancerous and diseased tissues. When therapeutic ultrasonic energy is applied to the diseased region heating is increased because of the greater effectiveness of sound energy absorption caused by these agents.

Claims

1. A method for heat treating biological tissues and fluids which comprises:

(i) administering to the tissue or fluid to be treated a therapeutically effective amount of a hyperthermia potentiator comprising gas filled liposomes prepared by a vacuum drying gas instillation method; and

(ii) applying ultrasound to said tissue or fluid.

2. A method of claim 1 wherein said liposomes are comprised of lipid materials selected from the group consisting of fatty acids, lysolipids, dipalmitoylphosphatidylcholine, phosphatidylcholine, phosphatidic acid, sphingomyelin, cholesterol, cholesterol hemisuccinate, tocopherol hemisuccinate, phosphatidylethanolamine, phosphatidylinositol, lysolipids, sphingomyelin, glycosphingolipids, glucolipids, glycolipids, sulphatides, lipids with ether and ester-linked fatty acids, and polymerized lipids.

3. A method of claim 2 wherein said liposomes are comprised of dipalmitoylphosphatidylcholine.

4. A method of claim 1 wherein said liposomes are filled with a gas selected from the group consisting of air, nitrogen, carbon dioxide, oxygen, argon, xenon, helium, and neon.

5. A method of claim 4 wherein said liposomes are filled with nitrogen gas.

6. A method of claim 1 wherein said liposomes are suspended in an aqueous medium.

7. A method of claim 6 wherein said aqueous medium is phosphate buffered saline.

8. A method of claim 1 wherein said liposomes are administered to tissue or fluid selected from the group consisting of tumor tissue, muscle tissue, and blood fluid.

9. A method for heat treating biological tissues and fluids which comprises:

(i) administering to the tissue or fluid to be treated a therapeutically effective amount of a hyperthermia potentiator comprising gas filled liposomes substantially devoid of liquid in the interior thereof; and

(ii) applying ultrasound to said tissue or fluid.

10. A method of claim 9 wherein said liposomes are comprised of lipid materials selected from the group consisting of fatty acids, lysolipids, dipalmitoylphosphatidylcholine, phosphatidylcholine, phosphatidic acid, sphingomyelin, cholesterol, cholesterol hemisuccinate, tocopherol hemisuccinate, phosphatidylethanolamine, phosphatidylinositol, lysolipids, sphingomyelin, glycosphingolipids, glucolipids, glycolipids, sulphatides, lipids with ether and ester-linked fatty acids, and polymerized lipids.

11. A method of claim 10 wherein said liposomes are comprised of dipalmitoylphosphatidylcholine.

12. A method of claim 9 wherein said liposomes are filled with a gas selected from the group consisting of air, nitrogen, carbon dioxide, oxygen, argon, xenon, helium, and neon.

13. A method of claim 12 wherein said liposomes are filled with nitrogen gas.

14. A method of claim 9 wherein said liposomes are suspended in an aqueous medium.

15. A method of claim 14 wherein said aqueous medium is phosphate buffered saline.

16. A method of claim 9 wherein said liposomes are administered to tissue or fluid selected from the group consisting of tumor tissue, muscle tissue, and blood fluid.