Biocompatible stable fluorocarbon emulsions for contrast enhancement and oxygen transport comprising 40-125% wt./volume fluorocarbon combined with a phospholipid

• US 5,077,036 A
• Filed: 03/30/1990
• Issued: 12/31/1991
• Est. Priority Date: 01/14/1986
• Status: Expired due to Term

• Current Assignee: PFC Therapeutics, LLC
• Original Assignee: Alliance Pharmaceutical Corporation
• Inventors: Long, David M. Jr.
• Primary Examiner(s): Hollrah, Glennon H.
• Assistant Examiner(s): Hollinden, Gary E.
• Application Number:
  US07/501,594
• Time in Patent Office: 641 Days
• Field of Search: 424/5, 514/77, 514/78, 514/887, 514/832, 514/941, 514/943, 514/723, 514/759, 514/744, 514/747
• US Class Current: 424/9.4
• CPC Class Codes: A61K 31/02 Halogenated hydrocarbons
• CPC Class Codes: A61K 9/0026 Blood substitute; Oxygen transporting formulations; Plasma extender
• CPC Class Codes: Y10S 977/915 Therapeutic or pharmaceutical composition
• CPC Class Codes: Y10S 977/927 Diagnostic contrast agent

Abstract

Biocompatible fluorcarbon emulsions having fluorocarbon in concentrations of from 75% weight per volume to 125% weight per volume have small, biocompatible particle size stability through heat sterilization with one emulsifying agent, including phospholipids, in concentrations of from 3% to 7% weight per volume. The single emulsifying agent can be hydrogenated lecithins and synthesized lecithins. Fluorocarbon emulsions having fluorocarbon in concentrations of from 40% weight per volume to 125% weight per volume have stability of partial pressure of oxygen and of partial pressure of carbon dioxide through heat sterilization and storage for extended periods of time after having been oxygenated with dissolved oxygen.

Claims

1. A fluorocarbon emulsion comprising a continuous aqueous phase, a fluorocarbon in an amount of from 40% to 125% weight per volume, and an effective amount of an emulsifying agent comprising a phospholipid with substantially saturated carbon bonds.

2. The emulsion of claim 1, wherein said fluorocarbon comprises a mono-brominated fluorocarbon.

3. The emulsion of claim 1, wherein said fluorocarbon comprises a perfluoroalkylated ether or polyether.

4. The emulsion of claim 1, wherein said fluorocarbon comprises a fluorocarbon-hydrocarbon compound.

5. The emulsion of claim 1 having a fluorocarbon concentration of more than 50% weight per volume, and an emulsifying agent in concentration of less than 7% weight per volume.

6. The emulsion of claim 1 having a fluorocarbon concentration of more than 50% weight per volume, and an emulsifying agent in concentration of less than 5% weight per volume.

7. The emulsion of claims 5 or 6, wherein said emulsifying agent is in a concentration of more than 3.5% weight per volume.

8. The emulsion of claims 1, 4 having a substantially stable pH.

9. The emulsion of any one of claims 1, 4, wherein said phospholipid is a synthesized lecithin.

10. The emulsion of claim 9, wherein said phospholipid is 1,2-dimyristoyl-sn-glycero-phosphocholine.

11. The emulsion of claim 9, wherein said phospholipid is 1,2-dipalmitoyl-sn-glycero-phosphocholine.

12. The emulsion of any one of claims 1, 4, wherein said phospholipid is a hydrogenated soybean lecithin.

13. The emulsion of any one of claims 1, 4, wherein said phospholipid is a hydrogenated egg yolk lecithin.

14. The emulsion of any one of claims 1 4, wherein the fluorocarbon in the emulsion has a mean particle size of less than approximately 250 nanometers.

15. The emulsion of any one of claims 1, 4, having a fluorocarbon phase formed of particles, which particles exhibit substantial particle size stability through heat sterilization.

16. The emulsion of any one of claims 1, 4, having a viscosity compatible with whole human blood.

17. The emulsion of any one of claims 1, 4, having a viscosity biologically compatible for intravascular use in an animal.