Artificial blood and method for supporting oxygen transport in animals

• US 3,911,138 A
• Filed: 02/26/1973
• Issued: 10/07/1975
• Est. Priority Date: 02/26/1973
• Status: Expired due to Term

• Current Assignee: Children's Hospital & Medical Center
• Original Assignee: Leland C. Clark Jr
• Inventors: Clark, Leland C. Jr.
• Primary Examiner(s): Rosen, Sam
• Application Number:
  US05/335,454
• Time in Patent Office: 953 Days
• Field of Search: 424/352
• US Class Current: 514/746
• CPC Class Codes: A61K 31/025 carbocyclic
• CPC Class Codes: A61K 9/0026 Blood substitute; Oxygen transporting formulations; Plasma extender
• CPC Class Codes: Y10T 436/102499 Blood gas standard or control
• CPC Class Codes: Y10T 436/105831 Protein or peptide standard or control [e.g., hemoglobin, etc.]

Abstract

Perfluorocyclocarbons and emulsions containing emulsified particles of these perfluorocarbons are useful is supporting life as intravascular oxygen and carbon dioxide transport agents. Stable emulsions of perfluorocarbocyclic derivatives are prepared for use as artificial bloods and perfusates for organs. Intravenously infused emulsions containing perfluorocyclocarbons such as perfluoro(methylcyclohexane), perfluoro(1,3dimethylcyclohexane), perfluoro(decahydronaphthalene), perfluoro(decahydro-1-methylnaphthalene), perfluoro(decahydrodimethylnaphthalene), and the like, serve as intravascular oxygen and carbon dioxide transport agents. Fluorocarbon liquids are also useful as an external respiration media for transporting oxygen-carbon dioxide necessary to support intravascular respiration. Perfluorocyclocarbons have been found after intravenous emulsion infusion as artificial bloods to collect in the reticuloendothelial system (RES) of the amimal body. However, it has also been found that perfluorocyclocarbon compounds leave the RES of the animal body and certain of these compounds, e.g., perfluoro(decahydronaphthalene), leave the RES at a much faster rate than others. Furthermore, after the intravenously infused perfluorocyclocarbon emulsions function as artificial bloods, the perfluorocyclocarbons have the capability of leaving the animal body through the tissue, e.g., the lungs and skin.

Claims

1. AN ARTIFICIAL BLOOD COMPRISING AN AQUEOUS EMULSION CONTAINING EMULSIFIED PARTICLES HAVING A PARTICLE SIZE UP TO ABOUT 100 MICRONS OF A RES-PHOBIC PERFLUOROCYCLOCARBON AN EMULSIFYING AGENT IN A NON-TOXIC NON-HEMOLYTIC AMOUNT AND WATER, SAID PARTICLES CONTAINED IN AN AMOUNT SUFFICIENT TO SUPPORT AN OXYGEN CARRING FUNCTION SAID PERFLUOROCLYCLOCARBON HAVING A VAPOR PRESSURE WHICH PERMITS IT TO LEAVE THE RES WITHOUT CAUSING ADVERSE GAS COLLECTION IN ANIMAL TISSUE.

2. The composition of claim 1 wherein said fluorocarbon is selected from the group consisting of perfluoro (methylcyclohexane), perfluoro (1,3-dimethylcyclohexane), perfluoro (decahydronaphthalene), perfluoro (decahydro-1-methylnaphthalene) and perfluoro (decahydrodimethylnaphthalene), or mixtures thereof.

3. The composition of claim 1 wherein said perfluorocyclocarbon has a vapor pressure of within the range of about 1 to about 50 torr at 37.5*C.

4. The composition of claim 1 wherein said perfluorocyclocarbon is perfluoro (decahydronaphthalene).

5. The composition of claim 1 whereiin said perfluorocyclocarbon comprises a mixture of perfluoro (decahydronaphthalene) and perfluoro (1,3-dimethylcyclohexane).

6. The composition of claim 2 wherein said emulsion contains an emulsifying agent comprising polyoxyethylene-polyoxypropylene copolymer.

7. The composition of claim 6 wherein said emulsion contains an ionic component in an amount to provide a non-hypertonic emulsion.

8. A method for supporting intravascular oxygen-carbon dioxide transport in an animal body which comprises the intravascular administration of an artificial blood defined in claim 1.

9. The method of claim 8 wherein said perfluorocyclocarbon has a vapor pressure of within the range of about 1 to about 50 torr at 37.5*C.

10. The method o claim 8 wherein said perfluorocyclocarbon is selected from the group consisting of perfluoro (methylcyclohexane), perfluoro (1,3-dimethylcyclohexane), perfluoro (decahydronaphthalene), perfluoro (decahydro-1-methylnaphthalene) and perfluoro (decahydrodimethylnaphthalene) or mixtures thereof.

11. The method of claim 8 further comprising the step of exposing the animal lungs to an outside environment comprising a perfluorocyclocarbon vapor.

12. The method of claim 11 wherein said intravascularly administerEd perfluorocyclocarbon has a vapor pressure greater than about 40-50 torr at 37.5*C.

13. The method of claim 8 wherein said perfluorocyclocarbon is present in a concentration of about 10 to about 30% by volume of said emulsion.

14. The method of claim 8 wherein said intravascularly administered perfluorocarbon escapes from the animal body by way of the tissue.

15. The method of claim 14 wherein the perfluorocarbon escapes as vapor excreted from the animal lungs.

16. The method of claim 14 wherein the perfluorocarbon escapes as a vapor excreted from the animal skin.

17. The composition of claim 1 wherein said particles have an average particle size within the range of about 0.001 to about 0.1 micron.

18. A method for supporting respiration of an animal which comprises external exposure of the animal to a fluid external respiration medium consisting essentially of a liquid RES-phobic perfluorocyclocarbon having oxygen dissolved therein, said perfluorocyclocarbon having a vapor pressure which permits it to leave the RES without causing adverse gas collection in the animal tissue.

19. A method for supporting oxygen transfer in an animal organ which comprises externally perfusing the animal organ with a liquid RES-phobic perfluorocyclocarbon having oxygen dissolved therein, said perfluorocyclocarbon having a vapor pressure which permits it to leave the organ without causing adverse gas collection in the organ tissue.