# US 5,707,607 A · Phase shift colloids as ultrasound contrast agents

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- Number: US 5,707,607 A
- Document ID: US5707607A
- Status: Granted
- Kind: A
- Application number: 08/469,472
- Filed: 1995-06-06
- Granted: 1998-01-13
- Earliest claimed: 1993-01-25
- Assignees: Sonus Pharmaceuticals, Inc.
- Inventors: Steven C. Quay
- Web page: https://patentgrep.com/patent/US5707607A

## CPC

- A61K 49/226: {Solutes, emulsions, suspensions, dispersions, semi-solid forms, e.g. hydrogels}
- A61K 49/223: {Microbubbles, hollow microspheres, free gas bubbles, gas microspheres}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

Agents for enhancing the contrast in a diagnostic ultrasound procedure comprise colloidal dispersions of the liquid-in-liquid type, i.e., emulsions or microemulsions, in which the dispersed liquid phase is a high vapor pressure chemical which undergoes a phase change from a dispersed liquid to a highly echogenic dispersed gaseous foam or kugelschaum following administration to an organism. The liquid state of the dispersed phase allows one to manufacture extremely stable, pharmaceutically acceptable emulsions with particle sizes typically below 1000 nm. The gaseous state at body temperature yields highly echogenic microbubbles, typically below 10,000 nm in diameter, which are effective as ultrasound contrast agents. Intravenous, intraarterial, oral, intraperitoneal, and intrauterine dosage forms, methods of administration, and imaging techniques are described.

## Claims

### Claim 1

A sterile colloidal dispersion for providing ultrasound contrast in a subject comprising, as the dispersed phase, dodecafluoropentane, said dodecafluoropentane being present in an amount in said dispersion such that, upon administration to said subject of said dodecafluoropentane, dodecafluoropentane gas will be present in an amount diagnostically effective for ultrasound contrast, an aqueous continuous phase, and at least one amphiphilic fluorine-containing surfactant.

### Claim 2 (depends on 1)

The dispersion of claim 1 wherein said fluorine-containing surfactant comprises one or more surfactants selected from the group consisting of telomer B containing surfactants, perfluoroalkylpoly (oxyethylene) surfactants, fluoroalkylthio-ether poly (oxyethylene) surfactants, perfluoroalkylated polyhydroxylated surfactants, and mixtures thereof.

### Claim 3 (depends on 1)

The dispersion of claim 1 wherein said fluorine-containing surfactant is selected from the group consisting of anionic, cationic, nonionic, and zwitterionic surfactants.

### Claim 4 (depends on 1)

The dispersion of claim 1 wherein said fluorine-containing surfactant is present in a quantity sufficient to produce an interfacial tension of 26 dynes/cm.

### Claim 5 (depends on 1)

The dispersion of claim 1 wherein said dodecafluoropentane is present in a concentration range of 0.00001% w/v to 166% w/v.

### Claim 6 (depends on 5)

The dispersion of claim 5 wherein said dodecafluoropentane is present in a concentration range of 0.5% w/v to 5% w/v.