Interstitial administration of perfluorochemical emulsions for reoxygenation of hypoxic tumor cells

• US 4,781,676 A
• Filed: 02/20/1987
• Issued: 11/01/1988
• Est. Priority Date: 02/20/1987
• Status: Expired due to Term

• Current Assignee: University of Pennsylvania
• Original Assignee: Air Products and Chemicals Incorporated (Linde Plc)
• Inventors: Schweighardt, Frank K., Woo, David V.
• Primary Examiner(s): NOT, DEFINED
• Assistant Examiner(s): Costantino, Mario
• Application Number:
  US07/016,812
• Time in Patent Office: 620 Days
• Field of Search: 604/19-21, 604/49, 604/51, 128/362, 128/422, 128/1 R, 128/1.3, 128/1.1, 128/1.2, 128/804, 424/320-325, 514/34
• US Class Current: 604/21
• CPC Class Codes: A61K 31/02 Halogenated hydrocarbons
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 9/0026 Blood substitute; Oxygen transporting formulations; Plasma extender
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A method is set forth for treatment of hypoxic tumors by interstitial injection of oxygen bearing fluorocarbon emulsions directly into the hypoxic zone of the tumor followed by radiation treatment.

Claims

1. A method of treating hypoxic mammalian tumor cells in vivo in a mammal comprising administering an oxygenated fluorochemical emulsion interstitially directly into the hypoxic zones within said tumor and thereafter subjecting the administered cells to an amount of radiation effective to initiate destruction of said cells.

2. The method of claim 1 wherein the fluorochemical is a perfluorocarbon.

3. The method of claim 1 wherein the emulsion is injected interstitially directly into the hypoxic zone of the tumor.

4. The method of claim 1 wherein the radiation comprises X-rays.

5. The method of claim 1 wherein the fluorochemical is selected from the group consisting of perfluoroperhydrophenanthrene, perfluoro n-butyl decalin and mixtures thereof.

6. The method of claim 1 wherein the emulsion comprises a perfluorocarbon with a vapor pressure less than 5 torr selected from partially or fully condensed C₉ -C₁₄ perfluoro compounds present in the emulsion in a concentration of 10-90 weight/volume percent, a surfactant selected from the group of lecithins, acetylenic diols, polyoxyethylenes polyoxypropylene polymers, a mixture of lecithin, glycerin and triglycerides or combinations of the above surfactants with the remainder of the emulsion being an aqueous phase wherein the emulsion has a particle size range of 0.005 to 0.20 microns.

7. The method of claim 1 wherein the radiation dose is above approximately 500 up to approximately 2500 rads.

8. The method of claim 1 wherein the radiation is administered up to 15 minutes after the administration of the emulsion.

9. The method of claim 1 wherein the mammal being subjected to radiation is anesthetized.

10. The method of claim 1 wherein the fluorochemical emulsion is administered in a range of approximately 0.009 to 0.055 ml/kg of body weight.

11. The method of claim 1 wherein the emulsion is saturated with oxygen by bubbling oxygen-enriched gas through said emulsion.

12. The method of claim 1 wherein the administered cells are subjected to a plurality of radiation treatments.

13. The method of claim 1 wherein the cells are subjected to a series of emulsion administrations and subsequent radiation treatments.

14. The method of claim 1 wherein the fluorochemical emulsion is administered in a dosage up to the equivalent of 50% of the tumor volume, but less than 2 ml/kg of body weight.

15. A method of decreasing hypoxic mammalian tumors in vivo in a mammal comprising the interstitial injection of an oxygenated perfluorocarbon C₁₄ compound emulsion, having a particle size in the range of 0.005-0.08 microns and a perfluorocarbon content in the range of 25-75 weight/volume percent in a dosage up to the equivalent of 50% of the tumor volume, but less than 2 ml/kg of body weight, directly into the hypoxic zones of said tumor and exposing said tumor to X-ray radiation in an exposure range of above approximately 500 up to 2500 rads within 15 minutes of injection of said emulsion to delay growth of said tumor or decrease the tumor size.

16. The method of claim 15 wherein the emulsion comprises an 85% perfluoroperhydrophenanthrene-15% perfluoro n-butyldecalin mixture in a 67 wt/volume % emulsion of egg yoke lecithin in lactated Ringer'"'"'s solution.

17. The method of claim 15 wherein the emulsion is saturated with oxygen by bubbling oxygen-enriched gas through said emulsion.