Ultrasound imaging and treatment

• US 7,078,015 B2
• Filed: 11/08/2004
• Issued: 07/18/2006
• Est. Priority Date: 12/22/1989
• Status: Expired due to Fees

• Current Assignee: Imarx Therapeutics, Inc. (Sycamore Entertainment Group, Inc.)
• Original Assignee: Imarx Therapeutics, Inc. (Sycamore Entertainment Group, Inc.)
• Inventors: Unger, Evan C.
• Primary Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US10/983,406
• Publication Number:
  US 20050123482A1
• Time in Patent Office: 617 Days
• Field of Search: 424/9.52, 424/9.51, 424/9.5, 424/489, 600/441, 600/458
• US Class Current: 424/9.52
• 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 47/6911 the form being a liposome
• CPC Class Codes: A61K 47/6925 the form being a microcapsule, nanocapsule, microbubble or nanobubble
• CPC Class Codes: A61K 49/1815 compo-inhalant, e.g. breath tests
• CPC Class Codes: A61K 49/22 Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
• 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: A61M 5/3145 Filters incorporated in syringes
• CPC Class Codes: A61N 2007/025 interstitial
• CPC Class Codes: A61N 7/02 Localised ultrasound hyperthermia hyperthermia in general A61F7/00

Abstract

Methods of and apparatus for preparing temperature activated gaseous precursor-filled liposomes are described. Gaseous precursor-filled liposomes prepared by these methods are particularly usefull for example, in ultrasonic imaging applications and in therapeutic drug delivery systems.

Gas, gaseous precursors and perfluorocarbons are presented as novel potentiators for ultrasonic hyper-thermia. The gas, gaseous precursors and perfluorocarbons 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 an ultrasound treatment of a patient in need of such treatment, comprising administering, intra-arterially, to said patient a composition comprising stabilized gas bubbles and a therapeutic agent, and applying ultrasound, to treat said patient, wherein the stabilized gas bubbles are formed by a gas or a gas precursor selected from a group consisting of perfluoropropane;

perfluorobutane;

perfluoropentane;

perfluorohexane;

perfluorocyclobutene;

perfluoro-1-butene;

perfluoro-2-butene;

perfluoro-2-butyne;

perfluoropropylene, hexafluoro acetone;

isopropyl acetylene;

allene;

tetrafluoroallene;

boron trifluoride;

1,2-butadiene;

1,3-butadiene;

1,2,3-trichloro-2-fluoro-1,3-butadiene;

2-methyl-1,3 butadiene;

hexafluoro-1,3-butadiene;

butadiyne;

1-fluoro-butane;

2-methyl-butane;

1-butene;

2-butene;

2-methy-1-butene;

2-methyl-2-butene;

3-methyl-1-butene;

1,4-phenyl-3-butene-2-one;

2-methyl-1-butene-3-yne;

butyl nitrate;

1-butyne;

2-butyne;

2-chloro-,1,1,4,4,4-hexafluoro-butyne;

3-methyl-1-butyne;

2-bromo-butyraldehyde;

carbonyl sulfide;

crotononitrile;

cyclobutane;

methyl-cyclobutane;

3-chloro-cyclopentene;

cyclopropane;

1,2-dimethyl-cyclopropane;

1,1-dimethyl cyclopropane;

1,2-dimethyl cyclopropane;

ethyl cyclopropane;

methyl cyclopropane;

diacetylene;

3-ethyl-3-methyl diaziridine;

1,1,1-trifluorodiazoethane;

dimethyl amine;

hexafluoro-dimethyl amine;

dimethylethylamine;

bis-(dimethylphosphine)amine;

2,3-dimethyl-2-norbomane;

perfluorodimethylamine;

dimethyloxonium chloride;

1,3-dioxolane-2-one;

1,1-dichloroethane;

1,1-dichloro-1,2,2,2-tetrafluoro ethane;

1,2-difluoro ethane;

2-chioro-1,1-difluoroethane;

2-chloro-1,1-difluoroethane;

1-chloro-1,1,2,2-tetrafluoroethane;

chloroethane;

chioropentafluoro ethane;

dichlorotrifluoroethane;

fluoroethane;

nitropentafluoro ethane;

nitrosopentafluoro ethane;

perfluoro ethylamine;

ethyl vinyl ether;

1,1-dichloroethylene;

1,2-difluoroethylene;

1,1-dichloro-1,2-difluoro ethylene;

trifluoromethane sulfonyl chloride;

trifluoro tethanesulfonyl fluoride;

trifluoropentafluorothio methane;

bromodifluoronitrosomethane;

bromofluoromethane;

bromochiorofluoromethane;

trifluorobromomethane;

chiorodifluoronitromethane;

chiorodinitromethane;

chiorofluoromethane;

difluorodibromomethane;

fluorodichioromethane;

difluoromethane;

difluorojodomethane;

disilanomethane;

fluoromethane;

iodomethane;

jodotrifluoromethane;

octafluorocyclobutane;

octafluoro-2-butene;

octafluorocyclopentene;

trifluoronitromethane;

trifluoronitrosomethane;

trichiorofluoromethane;

trifluoromethane sulfonyichioride;

2-methylbutane;

methyl ether;

methyl isopropyl ether;

methyl lactate;

methyl nitrite;

methyl sulfide;

methyl vinyl ether;

neon;

neopentane;

nitrous oxide;

1,2,3-nonadecanetricarboxylic acid-2-hydroxytrimethylester;

1-nonene-3-yne;

1,4-pentadiene;

n-pentane;

4-amino-4-methyl-2-pentanone;

1-pentene;

2-pentene (cis);

2-pentene (trans);

3-bromo-1-pentene;

tetrachloro phthalic acid;

2,3,6-trimethyl-piperidine;

propane, 1,2-epoxy-propane;

2,2-difluoro-propane;

2-amino-propane, 2-chloro-propane;

heptafluoro-1-nitro-propane;

heptafluoro-1-nitroso-propane;

propene;

1-chloro-propylene;

2-chloro-propylene;

3-fluoro-propylene-propyne;

3,3,3-trifluoro-propyne;

3-fluoro-styrene;

sulfur hexafluoride;

2,4-diamino-sulfurdecafluoro-toluene;

trifluoroacetonitrile;

trifluoromethyl peroxide;

trifluoromethyl sulfide;

tungsten hexafluoride;

vinyl acetylene;

vinyl ether; and

combinations thereof.

2. A method according to claim 1, wherein said stabilized gas bubbles comprise closed membrane-bounded structures that encompass an enclosed gas bubble.

3. A method according to claim 2, wherein said membrane-bounded structure is an albumin microsphere.

4. A method according to claim 1, wherein said therapeutic agent comprises a chemotherapeutic agent.

5. A method according to claim 1, wherein said composition is administered through a catheter.

6. A method according to claim 1, wherein said composition causes an increase in the rate of absorption of ultrasonic energy.

7. A method according to claim 1, wherein said composition accelerates the process of cavitation during said application of ultrasound.

8. A method according to claim 7, wherein said acceleration in the process of cavitation is produced by a decrease in the cavitation threshold.

9. A method according to claim 1, wherein said composition increases the acoustic heterogeneity and generates cavitation nuclei in said patient.

11. A method according to any one of claims 1–

3, 4, 5, or 6–

10 wherein ultrasound is applied through an intravascular ultrasound catheter.

10. A method for an ultrasound treatment of a patient in need of such treatment, comprising administering, intra-arterially, to said patient a composition comprising a perfluorocarbon and a therapeutic agent, and applying ultrasound, to treat said patient, wherein the perfluorocarbon is selected from a group consisting of perfluoropropane, perfluorobutane, perfluoropentane, perfluorohexane, perfluorocyclobutene, perfluoro-1-butene, perfluoro-2-butene, perfluoro-2-butyne, perfluoropropylene, and combinations thereof.