Homogeneous water-in-perfluorochemical stable liquid dispersion for administration of a drug to the lung of an animal

• US 5,770,585 A
• Filed: 05/08/1995
• Issued: 06/23/1998
• Est. Priority Date: 05/08/1995
• Status: Expired due to Term

• Current Assignee: Hemagen/Pfc
• Original Assignee: Hemagen/Pfc
• Inventors: Kaufman, Robert J., Stephens, Richard A., Allen, John S., Richard, Thomas J., Goodin, Thomas H., Layton, Tony E.
• Primary Examiner(s): Seidleck, James J.
• Assistant Examiner(s): Williamson, Michael A.
• Application Number:
  US08/438,098
• Time in Patent Office: 1,142 Days
• Field of Search: 514/320, 514/199, 514/200, 514/601, 514/34, 514/35, 514/357, 514/772, 514/778, 514/78
• US Class Current: 514/78
• CPC Class Codes: A61K 9/0026 Blood substitute; Oxygen transporting formulations; Plasma extender

Abstract

This invention is directed to a homogenous water-in-perfluorochemical stable liquid dispersion for acceptable therapeutic administration of a drug to the lung of an animal. The dispersion includes a perfluorochemical liquid, water, surfactant and drug, wherein the water is homogeneously dispersed in the perfluorochemical to form a stable water-in-perfluorochemical liquid dispersion. The perfluorochemical constitutes greater than 50% by volume of the dispersion, and the drug is contained in the dispersion in an effective therapeutic amount.

The invention further includes a method of delivering a drug to the lung of an animal. This aspect of the invention includes administering a stable homogenous water-in-perfluorochemical liquid dispersion to the animal lung or a section thereof. If desired, the method may further include delivering a breathable gas to the lung with a mechanical ventilator during the administration.

Claims

1. A homogenous water-in-perfluorochemical stable liquid dispersion, for acceptable therapeutic administration of a drug to the lung of an animal, comprising:

a perfluorochemical liquid, water, surfactant and drug, wherein said water is homogeneously dispersed in said perfluorochemical to form a stable water-in-perfluorochemical liquid dispersion, said perfluorochemical constituting greater than 50% by volume of said dispersion, said drug contained in said dispersion in an effective therapeutic amount.

2. The dispersion of claim 1 wherein said perfluorochemical is selected from the group consisting of perfluoro-n-butyltetrahydrofuran, perfluorodichlorooctane, perfluorobischlorobutylether, perfluorodecalin, perfluoromethyldecalin, perfluorodimethyldecalin, perfluorodimethyladamantane, perfluorooctylbromide, perfluoro-4-methyl-octahydroquinolidizine, perfluoro-N-methyl-decahydroquinoline, F-methyl-1-oxa-decalin, perfluoro-bicyclo(5.3.0)-decane, perfluorooctahydroquinolidizine, perfluoro-5,6-dihydro-5-decene, and perfluoro-4,5-dihydro-4-octene, chlorinated perfluorocarbons, and mixtures thereof.

3. The dispersion of claim 1 wherein said surfactant is selected from the group consisting of egg yolk phospholipid, a perfluorochemical alcohol, a polyalkyleneoxide, a 1,2-dialkylglycero-3-phosphoryl choline, a 1,3-dialkylglycero-2-phosphoryl choline, a fluorinated polyoxyethylene, and mixtures thereof.

4. The dispersion of claim 1 wherein said drug is selected from the group consisting of doxorubicin, deoxyribonuclease enzyme, a vector containing a normal cystic fibrosis transmembrane conductance regulator gene, pentamidine isethionate, amphotericin, a β

₂ agonist, methotrexate, etoposide, a phospholipid surfactant, a penicillin, a cephalosporin, a sulphadrug, and a prodrug of any of the foregoing drugs, and mixtures thereof.

5. The dispersion of claim 1 wherein said perfluorochemical is present in an amount of from about 50% to about 99% by volume and said water is present in an amount of from about 50% to about 1% by volume.

6. The dispersion of claim 5 wherein said perfluorochemical is present in an amount of from about 85% to about 99% by volume and said water is present in an amount of from about 15% to about 1% by volume.

7. The dispersion of claim 1 wherein said surfactant is present in an amount of from about 0.5% to about 10% by weight.

8. The dispersion of claim 7 wherein said surfactant is present in an amount of from about 1% to about 4% by weight.

9. The dispersion of claim 1 wherein said drug is present in an amount of from about 0.001% to about 3% by weight.

10. The dispersion of claim 1 wherein said drug is present in an amount sufficient to treat a lung condition selected from the group consisting of cystic fibrosis, infant respiratory distress syndrome, a bacterial or fungal infection, asthma and lung cancer.

11. A method of delivering a drug to the lung of an animal comprising the step of:

administering a stable homogeneous, water-in-perfluorochemical liquid dispersion to the animal lung or a section thereof, said dispersion comprising a perfluorochemical liquid, water, surfactant and drug, said perfluorochemical constituting greater than 50% by volume of said dispersion, said drug contained in said dispersion in an effective therapeutic amount.

12. The method of claim 11 further comprising the step of delivering a breathable gas to the lung with a mechanical ventilator during said administration.

13. The method of claim 11 wherein said perfluorochemical is selected from the group consisting of perfluoro-n-butyltetrahydrofuran, perfluorodichlorooctane, perfluoro-bischlorobutylether, perfluorodecalin, perfluoromethyldecalin, perfluorodimethyldecalin, perfluorodimethyladamantane, perfluorooctylbromide, perfluoro-4-methyl-octahydroquinolidizineperfluoro-N-methyl-decahydroquinoline, F-methyl-1-oxa-decalin, perfluoro-bicyclo(5.3.0)-decane, perfluorooctahydroquinolidizine, perfluoro-5,6-dihydro-5-decene, and perfluoro-4,5-dihydro-4-octene, chlorinated perfluorocarbons, and mixtures thereof.

14. The method of claim 11 wherein said surfactant is selected from the group consisting of egg yolk phospholipid, a perfluorochemical alcohol, a polyalkyleneoxide, a 1,2-dialkylglycero-3-phosphoryl choline, a 1,3-dialkylglycero-2-phosphoryl choline, a fluorinated polyoxyethylene, and mixtures thereof.

15. The method of claim 11 wherein said drug is selected from the group consisting of doxorubicin, deoxyribonuclease enzyme, a vector containing a normal cystic fibrosis transmembrane conductance regulator gene, pentamidine isethionate, amphotericin, a β

₂ agonist, methotrexate, etoposide, a phospholipid surfactant, a penicillin, a cephalosporin, a sulfadrug, and a prodrug of any of the foregoing drugs, and mixtures thereof.

16. The method of claim 11 wherein said perfluorochemical is present in an amount of from about 50% to about 99% by volume and said water is present in an amount of from about 50% to about 1% by volume.

17. The method of claim 16 wherein said perfluorochemical is present in an amount of from about 85% to about 99% by volume and said water is present in an amount of from about 15% to about 1% by volume.

18. The method of claim 11 wherein said surfactant is present in an amount of from about 0.5% to about 10% by weight.

19. The method of claim 18 wherein said surfactant is present in an amount of from about 1% to about 4% by weight.

20. The method of claim 11 wherein said drug is present in an amount of from about 0.001% to about 3% by weight.

21. The method of claim 11 conducted for treating a lung condition selected from the group consisting of cystic fibrosis, infant respiratory distress syndrome, a bacteria or fungal infection, asthma and lung cancer.