Emulsions of highly fluorinated organic compounds

• US 5,171,755 A
• Filed: 04/29/1988
• Issued: 12/15/1992
• Est. Priority Date: 04/29/1988
• Status: Expired due to Term

• Current Assignee: Hemagen/PFC Limited
• Original Assignee: Hemagen/Pfc
• Inventors: Kaufman, Robert J., Richard, Thomas J.
• Primary Examiner(s): Friedman, S. J.
• Application Number:
  US07/187,854
• Time in Patent Office: 1,691 Days
• Field of Search: 514/759, 514/749, 514/832, 514/833, 514/937, 514/975
• US Class Current: 514/749
• CPC Class Codes: A61K 31/02 Halogenated hydrocarbons
• CPC Class Codes: A61K 9/0026 Blood substitute; Oxygen transporting formulations; Plasma extender
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

Improved emulsions of highly fluorinated organic compounds. The emulsions comprise a highly fluorinated organic compound, an oil, that is not substantially surface active and not significantly water soluble, and a surfactant. They are characterized by a well-defined relationship in the relative amounts of the three components.

Claims

1. A physiologically acceptable emulsion comprising a highly fluorinated organic compound, an oil that is not substantially surface active and not significantly water soluble, and a surfactant, wherein

(a) the highly fluorinated organic compound is present in an amount between about 20% and about 60% by volume and

(b) the amounts of the surfactant and oil are dependent on the volume percent of highly fluorinated organic compound and are present in amounts effective to produce emulsions characterized by (1) a particle size distribution of less than 400 nm after sterilization, (2) a serum stability characterized by a particle size distribution of less than 400 nm after 5 days in serum or ionic solutions, (3) an LD₅₀ in rats of at least 16 ml/kg of the highly fluorinated organic compound component of the emulsion, (4) an at least 70% survival upon total exchange in rats and (5) a shelf stability of at least several months at 4°

C.

2. The emulsion according to claim 1, wherein the highly fluorinated organic compound is present in an amount between about 30% and about 55% by volume.

3. The emulsion according to claim 1, wherein the highly fluorinated organic compound is present in about 40% by volume.

4. The emulsion according to any one of claims 1, 2 or 3, wherein the highly fluorinated organic compound is selected from the group consisting of perfluorodecalin and perfluorooctylbromide.

5. The emulsion according to claim 1, wherein the oil is selected from the group consisting of safflower oil and soybean oil.

6. The emulsion according to claim 1, wherein the surfactant is egg yolk lecithin.

7. The emulsion according to claim 1, further comprising at least one compound selected from the group consisting of isotonic agents, osmotic pressure controlling agents, serum extending agents and antioxidants.

8. A red blood cell substitute comprising an amount of an emulsion according to any one of claims 1, 2, 4, 5, or 6, 7, said amount being therapeutically effective for oxygen transport and delivery in humans.

9. A composition for minimizing the adverse effects of coronary balloon angioplasty comprising a therapeutically effective amount of an emulsion according to any one of claims 1, 2, 4, 5, or 6, 7.

10. A composition for preserving organs comprising a preserving effective amount of an emulsion according to any one of claims 1, 2, 4, 5 or 6, 7.

11. A composition for treating heart attack, stroke and vascular occlusions comprising a therapeutically effective amount of an emulsion according to any one of claims 1, 2, 4, 5 or 6, 7.

12. A method for sustaining the oxygen requirements of a living organism comprising administering to the living organism in a therapeutically acceptable manner a red blood cell substitute according to claim 8.

13. A method for minimizing the adverse effects of coronary balloon angioplasty by perfusion of a composition according to claim 9 through the central lumen of the catheter.

14. A method for preserving organs by perfusion of a composition according to claim 10.

15. A method for treating heart attack, stroke and vascular occlusions comprising the step of administering to a patient in a therapeutically acceptable manner a composition according to claim 11.

16. A physiologically acceptable emulsion comprising a highly fluorinated organic compound, an oil that is not substantially surface active and not significantly water soluble, and a surfactant, wherein

(a) the highly fluorinated organic compound is present in an amount between about 20% and about 60% by volume and

(b) the amounts of the surfactant and oil are dependent on the volume percent of highly fluorinated organic compound and are present in amounts effective to produce emulsions characterized by (1) a particle size distribution of less than 300 nm after sterilization, (2) a serum stability characterized by a particle size distribution of less than 300 nm after 5 days in serum or ionic solutions, (3) an LD₅₀ in rats of at least 16 ml/kg of the highly fluorinated organic compound component of the emulsion, (4) an at least 70% survival upon total exchange in rats and (5) a shelf stability of at least several months at 25°

C.