Ultrasonic imaging agent and method of preparation

• US 4,774,958 A
• Filed: 10/01/1987
• Issued: 10/04/1988
• Est. Priority Date: 12/05/1985
• Status: Expired due to Term

• Current Assignee: SLF Limited Partnership
• Original Assignee: Steven B. Feinstein
• Inventors: Feinstein, Steven B.
• Primary Examiner(s): JAWORSKI, FRANCIS J
• Application Number:
  US07/103,837
• Time in Patent Office: 369 Days
• Field of Search: 128/660, 424/2, 530/363, 530/427
• US Class Current: 424/9.52
• CPC Class Codes: A61B 2090/3925 ultrasonic
• 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: G01S 15/899 Combination of imaging systems with ancillary equipment

Abstract

An ultrasonic imaging agent is formed by subjecting an aqueous protein solution to high frequency sonication while heating the solution sufficiently to denature portions of the protein, thereby forming a dispersion of microbubbles stabilized by denatured protein. In a preferred embodiment, the protein solution is formed from human serum albumin, and the formed microbubbles have a relatively uniform size in the 2 to 5 micron range, suitable for imaging of pulmonary or small organ vasculature.

Claims

1. The method of producing an ultrasonic imaging agent, comprising the steps of forming an aqueous protein solution, subjecting said solution to high frequency sonication while heating the solution sufficiently to denature portions of the protein, and forming a dispersion of microbubbles of relatively uniform size stabilized by the denatured protein.

2. The method of claim 1 in which said aqueous protein solution is formed from albumin.

3. The method of claims 1 or 2 in which said stabilized dispersion of microbubbles is formed with substantially all of the microbubbles having diameters less than 9 microns.

4. The method of claim 1 in which said stabilized dispersion of microbubbles is formed with the microbubbles having diameters predominantly in the range from 2 to 5 microns.

5. The method of claim 1 in which said solution is heated sufficiently by means of the sonication to denature said protein portions.

6. The ultrasonic imaging agent produced by the method of claims 1 or 2.

7. The method of producing an ultrasonic imaging agent, comprising the steps of forming an aqueous albumin solution, subjecting said solution to high frequency sonication while heating the solution sufficiently to denature portions of the albumin, and forming a dispersion of microbubbles of relatively uniform size stabilized by the denatured albumin, said microbubbles having diameters predominantly in the range from 2 to 5 microns.

8. The method of claim 7 in which said albumin is human serum albumin.

9. The ultrasonic imaging agent produced by the method of claims 7 or 8.

10. The method of producing an ultrasonic imaging agent, comprising the steps of forming an aqueous protein solution, subjecting said solution to high frequency sonication while heating said solution sufficiently by means of the sonication to denature portions of the protein, said sonication being carried out by applying ultrasonic energy in a range from 5,000 to 30,000 Hertz (Hz), and forming a dispersion of microbubbles in said solution of relatively uniform size stabilized by the denatured protein, substantially all of the microbubbles having diameters of less than 9 microns.

11. The method of claim 10 in which said stabilized dispersion of microbubbles is formed with the microbubbles having diameters predominantly in the range from 2 to 5 microns.

12. The method of claim 10 in which said protein solution is formed from albumin.

13. The method of claim 10 in which said protein solution is formed from human serum albumin, and in which said stabilized microbubbles have diameters predominantly in the range from 2 to 5 microns.

14. The ultrasonic imaging agent produced by the method of claims 10, 11, 12 or 13.