Emulsions as contrast agents and method of use

• US 5,716,597 A
• Filed: 06/04/1993
• Issued: 02/10/1998
• 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: Widder, Kenneth J., Krishnan, Ashwin M., Lohrmann, Rolf, Meng, Jialun, Hong, Dung Kevin
• Primary Examiner(s): METZMAIER, DANIEL S
• Application Number:
  US08/072,535
• Time in Patent Office: 1,712 Days
• Field of Search: 252/312, 424/9, 424/450, 128/662.02, 128/9.52
• US Class Current: 600/458
• 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 useful as an imaging agent for ultrasonic imaging of an animal, comprising:

(a) water;

(b) at least one water-insoluble gas-forming biocompatable chemical having a boiling point 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

(c) 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, and prior to exposure to ultrasonic energy.

2. The emulsion of claim 1 wherein said stabilizer is a hydrophobic compound.

3. The composition of claim 2 wherein said emulsion includes a surface active agent.

4. The emulsion of claim 1 wherein said stabilizer is amphipathic.

5. The emulsion of claim 4 wherein said amphipathic compound is:

##STR3## wherein the average value of n=75 and the average value of p=30 such that the average molecular weight of said compound is 8350.

6. The composition of claim 1 wherein said emulsion includes a viscosifier.

7. The composition of claim 1 wherein said emulsion includes antioxidants.

8. An ultrasound imaging agent comprising the emulsion of claim 1 and a delivery vehicle.

9. The ultrasound imaging agent of claim 8 wherein said delivery vehicle is selected from the group consisting of:

a natural polymer matrix, a synthetic polymer matrix or a liposome.

10. The ultrasound imaging agent of claim 9 wherein said natural polymer matrix is an albumin matrix.

11. The emulsion of claim 1 wherein said water-insoluble gas-forming chemical is nonafluoro-t-butylmethane.

12. The emulsion of claim 1 wherein said water-insoluble gas forming chemical is perfluoropentane and said stabilizer is lecithin.

13. A site-specific liquid-liquid emulsion useful as an imaging agent for ultrasonic imaging of an animal, comprising:

(a) water;

(b) at least one perfluorocarbon having a boiling point below 37°

C., wherein the perfluorocarbon 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

(c) at least one stabilizer comprising a hydrophobic or amphipathic compound in an amount sufficient to keep the perfluorocarbon in the liquid state at 37°

C., at atmospheric pressure, and prior to exposure to ultrasonic energy.