Emulsions as contrast agents and method of use

• US 6,030,603 A
• Filed: 12/23/1997
• Issued: 02/29/2000
• Est. Priority Date: 06/04/1993
• Status: Expired due to Fees

• Current Assignee: Molecular Biosystems, Inc (Alliance Pharmaceutical Corporation)
• Original Assignee: Molecular Biosystems, Inc (Alliance Pharmaceutical Corporation)
• Inventors: Krishnan, Ashwin M., Widder, Kenneth J., Meng, Jialun, Hong, Dung Kevin, Lohrmann, Rolf
• Primary Examiner(s): Dees, Jose' G.
• Assistant Examiner(s): Hartley, Michael G.
• Application Number:
  US08/996,736
• Time in Patent Office: 798 Days
• Field of Search: 424/9.5, 424/9.51, 424/9.52, 424/455, 424/450, 264/4.1, 427/213.3, 600/441, 600/458, 514/937, 514/938, 252/312
• US Class Current: 424/9.52
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
• CPC Class Codes: A61K 49/226 Solutes, emulsions, suspensions, dispersions, semi-solid forms, e.g. hydrogels
• CPC Class Codes: Y10S 516/929 Specified combination of agitation steps, e.g. mixing to make subcombination composition followed by homogenization

Abstract

This invention relates to an oil-in-water emulsion that is of a water-insoluble gas-forming chemical and a stabilizer. The emulsion being capable of forming microbubbles of gas upon application of ultrasonic energy. This composition allows for site specific imaging as the image enhancing microbubbles can be released upon the application of ultrasonic energy at the specific location where the image is desired.

Claims

1. A site specific liquid-liquid emulsion for use as an ultrasonic imaging agent of a mammal comprising:

a) at least one water-insoluble gas-forming chemical having a boiling point at atmospheric pressure below 37°

C., wherein the chemical in said emulsion is in the liquid state at 37°

C. and at atmospheric pressure in the absence of exposure to ultrasonic energy and is present in said emulsion in an amount sufficient to form microbubbles upon exposure to ultrasonic energy; and

b) at least one stabilizer comprising a hydrophobic or amphipathic compound in an amount sufficient to keep the gas-forming chemical in the liquid state at 37°

C. at atmospheric pressure in the absence of ultrasonic energy;

wherein the emulsion forms microbubbles of gas upon application of ultrasonic energy at an energy level which is above the threshold energy of cavitation for microbubbles to be formed.

2. A site specific liquid-liquid emulsion for use as an ultrasonic imaging agent of a mammal comprising:

a) at least one water-insoluble gas-forming chemical having a boiling point at atmospheric pressure below 37°

C., wherein the chemical in said emulsion is in the liquid state at 37°

C. and at atmospheric pressure in the absence of exposure to ultrasonic energy and is present in said emulsion in an amount sufficient to form microbubbles upon exposure to ultrasonic energy; and

b) at least one stabilizer comprising a hydrophobic or amphipathic compound in an amount sufficient to keep the gas-forming chemical in the liquid state at 37°

C. at atmospheric pressure in the absence of ultrasonic energy;

wherein the emulsion forms microbubbles of gas upon application of ultrasonic energy in vitro to a mixture of said emulsion and water at a ratio of 1;

1000 (v/v) emulsion;

water at 37°

C.

3. A method of forming microbubbles in an animal comprising:

a) injecting the animal with a liquid-liquid emulsion capable of forming microbubbles upon application of ultrasound energy at 37°

C.; and

b) applying ultrasound energy in an amount sufficient to cause formation of microbubbles;

wherein the emulsion comprises at least one water-insoluble gas-forming chemical having a boiling point at atmospheric pressure below 37°

C., wherein the chemical in said emulsion is in the liquid state at 37°

C. and at atmospheric pressure in the absence of exposure to ultrasonic energy and is present in said emulsion in an amount sufficient to form microbubbles upon exposure to ultrasonic energy; and

at least one stabilizer comprising a hydrophobic or amphipathic compound in an amount sufficient to keep the gas-forming chemical in the liquid state at 37°

C. at atmospheric pressure in the absence of ultrasonic energy.