Artificial blood and other gas transport agents

• US 4,443,480 A
• Filed: 04/12/1982
• Issued: 04/17/1984
• Est. Priority Date: 04/12/1982
• Status: Expired

• Current Assignee: Children'S Hospital Research Foundation
• Original Assignee: Children's Hospital & Medical Center
• Inventors: Clark, Leland C. Jr.
• Primary Examiner(s): Rosen, Sam
• Application Number:
  US06/367,457
• Time in Patent Office: 736 Days
• Field of Search: 424/350, 424/325, 424/330, 424/320, 424/352, 424/353
• US Class Current: 514/772
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/025 carbocyclic
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/16 Amides, e.g. hydroxamic acids
• CPC Class Codes: A61K 9/0026 Blood substitute; Oxygen transporting formulations; Plasma extender
• CPC Class Codes: A61P 7/08 Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04

Abstract

Gas transport agents such as artificial blood containing a perfluorocyclocarbon and an amine oxide are disclosed. These compositions have been found to provide transparent emulsions or solutions for use in oxygen transport, particularly in animals. Large concentrations of perfluorocarbons may be employed even up to 50% or more by volume in preparing emulsions, microemulsions or solutions. The emulsions or solutions have been found to be very stable at room temperature storage conditions thereby providing significant advantages.

Claims

1. A gas transport agent liquid composition containing a perfluorocyclocarbon and an organoamine oxide.

2. The composition of claim 1 wherein said oxide is a fluoroorganoamine oxide.

3. The composition of claim 1 wherein said oxide is a polyfluoroamidoamine oxide.

4. The composition of claim 3 wherein the oxide is defined by the formula ##STR3##

5. The composition of claim 1 wherein the perfluorocyclocarbon is a perfluorinated compound selected from the group consisting of an adamantane, substituted adamantane, decalin, substituted decalin, bicyclononane, substituted bicyclononane, and mixtures thereof.

6. The composition of claim 1 wherein said perfluorocyclocarbon is a solid.

8. The composition of claim 6 wherein said perfluorocyclocarbon is contained in an amount of from about 10 to about 50% and said oxide is present in an amount of from about 1 to 10%.

7. An oxygen transfer agent liquid composition comprising water, a major amount of a perfluorocyclocarbon, and a minor amount of an organoamine oxide.

9. The composition of claim 7 wherein said amine oxide is a polyfluoroorganoamine oxide.

10. The composition of claim 9 wherein said amine oxide is a polyfluoroamidoamine oxide.

11. The composition of claim 7 wherein the perfluorocyclocarbon is selected from a perfluorinated compound selected from the group consisting of an adamantane, substituted adamantane, decalin, substituted decalin, bicyclononane, substituted bicyclononane, and mixtures thereof.

12. The composition of claim 7 wherein said perfluorocyclocarbon is selected from the group consisting of perfluoro(methylcyclohexane), perfluoro(1,3-dimethylcyclohexane), perfluoro(decahydronaphthalene), perfluoro(decahydro-1-methylnaphthalene), perfluoro(decahydrodimethylnaphthalene), perfluorodimethyladamantane, perfluorotrimethylbicyclo[3.3.1.]nonane, perfluorotetrahydrodicyclopentadiene, perfluorobicyclo[5.3.0.]decane and perfluorodimethylbicyclo[3.3.1.]nonane, or mixtures thereof.

13. The composition of claim 7 wherein said perfluorocyclocarbon is a mixture of perfluorodimethyladamantane and perfluorotrimethylbicyclo[3.3.1.]nonane.

14. An artificial blood liquid composition comprising water, a perfluorocyclocarbon and an organoamine oxide.

15. The composition of claim 14 wherein said perfluorocyclocarbon is contained in an amount of from about 10 to about 50% and said oxide is present in an amount of from about 1 to 10%.

16. The composition of claim 14 wherein said amine oxide is a polyfluoroorganoamine oxide.

17. The composition of claim 16 wherein said amine oxide is a polyfluoroamidoamine oxide.

18. The composition of claim 14 wherein the perfluorocyclocarbon is selected from a perfluorinated compound selected from the group consisting of an adamantane, substituted adamantane, decalin, substituted decalin, bicyclononane, substituted bicyclononane, and mixtures thereof.

19. The composition of claim 14 wherein said perfluorocyclocarbon is selected from the group consisting of perfluoro(methylcyclohexane), perfluoro(1,3-dimethylcyclohexane), perfluoro(decahydronaphthalene), perfluoro(decahydro-1-methylnaphthalene), perfluoro(decahydrodimethylnaphthalene), perfluorodimethyladamantane, perfluorotrimethylbicyclo[3.3.1.]nonane, perfluorotetrahydrodicyclopentadiene, perfluorobicyclo[5.3.0.]decane and perfluorodimethylbicyclo[3.3.1.]nonane, or mixtures thereof.

20. The composition of claim 14 wherein said perfluorocyclocarbon is a mixture of perfluorodimethyladamantane and perfluorotrimethylbicyclo[3.3.1.]nonane.

21. A room temperature stable artificial blood liquid composition comprising an aqueous mixture containing a major amount of a perfluorocyclocarbon and a minor amount of an organoamine oxide.

22. The composition of claim 21 wherein said perfluorocyclocarbon is contained in an amount of from about 10 to about 50% and said oxide is present in an amount of from about 1 to 10%.

23. The composition of claim 21 wherein said amine oxide is a polyfluoroorganoamine oxide.

24. The composition of claim 23 wherein said amine oxide is defined by the formula ##STR4##

25. The composition of claim 21 wherein said perfluorocyclocarbon is selected from the group consisting of perfluoro(methylcyclohexane), perfluoro(1,3-dimethylcyclohexane), perfluoro(decahydronaphthalene), perfluoro(decahydro-1-methylnaphthalene), perfluoro(decahydrodimethylnaphthalene), perfluorodimethyladamantane, perfluorotrimethylbicyclo[3.3.1.]nonane, perfluorotetrahydrodicyclopentadiene, perfluorobicyclo[5.3.0.]decane and perfluorodimethylbicyclo[3.3.1]nonane, or mixtures thereof.

26. The composition of claim 21 wherein said perfluorocyclocarbon is a mixture of perfluorodimethyladamantane and perfluorotrimethylbicyclo[3.3.1.]nonane.

27. A room temperature stable artificial blood liquid composition comprising an aqueous mixture containing, a major amount of a perfluorocyclocarbon mixture of perfluorodimethyladamantane and perfluorotrimethylbicyclo[3.3.1.]nonane and a minor amount of a fluoroorganoamine oxide.

28. The composition of claim 27 wherein said amine oxide is a polyfluoroamidoamine oxide.

29. The composition of claim 28 wherein said oxide defined by the formula ##STR5##

30. The composition of claim 29 wherein the perfluorocyclocarbon mixture is contained in an amount of from about 10 to about 50% and the oxide is contained in an amount of from about 1 to 10% to obtain a substantially transparent liquid.