Concentrated stabilized microbubble-type ultrasonic imaging agent

• US 4,844,882 A
• Filed: 12/29/1987
• Issued: 07/04/1989
• Est. Priority Date: 12/29/1987
• Status: Expired due to Term

• Current Assignee: GE Healthcare As (GE Healthcare Technologies, Inc.)
• Original Assignee: Molecular Biosystems, Inc (Alliance Pharmaceutical Corporation)
• Inventors: Widder, Kenneth J., Westkaemper, Peter J.
• Primary Examiner(s): Robinson, Douglas W.
• Assistant Examiner(s): Henley, III, Raymond J.
• Application Number:
  US07/139,576
• Time in Patent Office: 553 Days
• Field of Search: 424/9, 514/945, 128/660-663
• US Class Current: 424/9.52
• CPC Class Codes: A61B 8/481 involving the use of contrast agent, e.g. microbubbles introduced into the bloodstream analysis of echo signal exploiting properties of a contrast enhancer in devices for short-range imaging with acoustic waves G01S7/52039
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
• CPC Class Codes: A61K 9/5052 Proteins, e.g. albumin

Abstract

A microbubble-type ultrasonic imaging agent is provided comprising a parenterally-administerable aqueous medium containing a dispersion of microspheres predominantly of diameters less than 10 microns, wherein the microspheres consist of gas microbubbles encapsulated with water-insolubilized biocompatible material. The imaging agent is characterized by having a concentration of greater than 100×10⁶ microspheres per milliliter, and a stability such that this concentration is maintained for over 4 weeks at a temperature of 20° to 25° C.

Claims

1. A concentrated, storable ultrasonic imaging agent, comprising an aqueous parenteral medium containing a dispersion of microspheres predominantly of diameters less than 10 microns, said microspheres consisting of gas microbubbles enclosed by solid walls formed from heat-insolubilized biocompatible material, said imaging agent having a homogeneously dispersed concentration of greater than 1×

10⁸ microspheres per milliliter, said microspheres being stable in said medium as evidenced by maintaining a concentration of greater than 1×

10⁸ microspheres per milliliter for over 4 weeks at a temperature of 20°

to 25°

C.

2. The imaging agent of claim 1 in which said biocompatible material is a heat sensitive protein.

3. The imaging agent of claims 1 or 2 in which at least 80% of said microspheres have diameters in the range from 1 to 9 microns.

4. The imaging agent of claim 1 in which said biocompatible material is human serum albumin.

5. The imaging agent of claims 1 or 4 in which said gas is air.

6. A concentrated, storable ultrasonic imaging agent comprising an aqueous parenteral medium containing a dispersion of microspheres at least 80% of which have diameters in the range of 1 to 9 microns, said microspheres consisting of gas microbubbles enclosed by solid walls formed from heat-insolubilized protein, said imaging agent having a homogeneously dispersed concentration of greater than 1×

10⁸ microspheres per milliliter, said microspheres being stabilized in said medium as evidenced by maintaining a concentration of greater than 1×

10⁸ microspheres per milliliter for over 4 weeks at a temperature of 20°

to 25°

C.

7. The imaging agent of claim 6 in which said protein is human serum albumin and said gas is air.

8. The imaging agent of claims 6 or 7 in which said medium is an aqueous solution of the protein of the microsphere walls.