US 6,242,472 B1

 

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United States Patent

6,242,472

Sekins ,   et al.

June 5, 2001

 

Methods for the pulmonary delivery of biological agents

Abstract

Methods of delivering a therapeutic or diagnostic agent in a perfluorochemical liquid carrier are provided. In preferred embodiments, the disclosed methods use compositions in the form of an emulsion or a dispersion for delivery of a biological agent to the pulmonary air passages.

What is claimed is:

 

1.      A method for the delivery of a therapeutic or diagnostic biological agent to pulmonary air passages of a   patient in need thereof comprising the steps of:

      combining said therapeutic or diagnostic biological agent in the form of a solid or immiscible liquid with a perfluorochemical liquid carrier to provide a pharmaceutical preparation; and administering said pharmaceutical preparation to the pulmonary air passages of said patient.

 

2.      The method of claim 1 wherein the biological agent is selected from the group consisting of antibody-linked radionuclides, vasoconstrictors, vasodilators, bronchoconstrictors, bronchodilators, anti-cancer agents, surfactants, steroids, antibiotic agents, chemotactic agents, chemotherapeutic agents, contrast agents, antioxidants and antiproteases, or a combination thereof.

 

3.       The method of claim 1 wherein said perfluorochemical liquid carrier comprises a perfluorocarbon having a boiling point greater than about 55.degree. C.

 

4.      The method of claim 1 wherein said perfluorochemical liquid carrier is selected from the group consisting of FC-84, FC-72, RM-82, FC-75, RM-101, FC-43, RM-175, FC-5311, FC-5312, trimethylbicyclononane, dimethyladamantine and perfluorodecalin, or a combination thereof.

 

5.       The method of claim 1 wherein said pharmaceutical preparation is oxygenated.

 

6.      The method of claim 1 in which the pharmaceutical preparation is administered at a temperature above the body temperature of the patient.

 

7.       The method of claim 1 in which the pharmaceutical preparation is administered at a temperature below the body temperature of the patient.

 

8.      The method of claim 1 wherein the biological agent is a solid.

 

9.       The method of claim 8 wherein the biological agent is selected from the group consisting of antibody-linked radionuclides, vasoconstrictors, vasodilators, bronchoconstrictors, bronchodilators, anti-cancer agents, surfactants, steroids, antibiotic agents, chemotactic agents, chemotherapeutic agents, contrast agents, antioxidants and antiproteases, or a combination thereof.

 

10.   The method of claim 8 wherein the biological agent comprises a chemotherapeutic agent.

 

11.   The method of claim 8 wherein the biological agent comprises an antibiotic.

 

12.   The method of claim 8 wherein the biological agent comprises a bronchodilator.

 

13.   The method of claim 1 wherein the biological agent is in the form of an immiscible liquid.

 

14.    The method of claim 13 wherein the pharmaceutical preparation comprises an emulsion.

 

15.   The method of claim 14 wherein the biological agent is selected from the group consisting of antibody-linked radionuclides, vasoconstrictors, vasodilators, bronchoconstrictors, bronchodilators, anti-cancer agents, surfactants, steroids, antibiotic agents, chemotactic agents, chemotherapeutic agents, contrast agents, antioxidants and antiproteases, or a combination thereof.

16.   The method of claim 14 wherein the biological agent comprises a chemotherapeutic agent.

 

17.   The method of claim 14 wherein the biological agent comprises an antibiotic.

 

18.    The method of claim 14 wherein the biological agent comprises a bronchodilator.

 

19.   The method of claim 14 wherein the biological agent is dispersed in the perfluorochemical liquid carrier.

 

20.   The method of claim 19 wherein the biological agent is selected from the group consisting of antibody-linked radionuclides, vasoconstrictors, vasodilators, bronchoconstrictors, bronchodilators, anti-cancer agents, surfactants, steroids, antibiotic agents, chemotactic agents, chemotherapeutic agents, contrast agents, antioxidants and antiproteases, or a combination thereof.

 

21.   The method of claim 13 wherein the immiscible liquid biological agent comprises the therapeutic or diagnostic agent in an aqueous medium.

 

22.   The method of claim 21 wherein said therapeutic or diagnostic agent is selected from the group consisting of antibody-linked radionuclides, vasoconstrictors, vasodilators, bronchoconstrictors, bronchodilators, anti-cancer agents, surfactants, steroids, antibiotic agents, chemotactic agents, chemotherapeutic agents, contrast agents, antioxidants and antiproteases, or a combination thereof.

 

23.   A method for the delivery of a therapeutic or diagnostic biological agent to pulmonary air passages of a patient in need thereof comprising the steps of:

 

combining a liquid perfluorochemical with an immiscible liquid to form an emulsion wherein said   emulsion further comprises at least one therapeutic or diagnostic biological agent;

 

and administering the emulsion to the pulmonary air passages of said patient.

 

24.   The method of claim 23 wherein said liquid perfluorochemical comprises a perfluorocarbon having a boiling point greater than about 55.degree. C.

 

25.   The method of claim 23 wherein said perfluorochemical liquid carrier is selected from the group consisting of FC-84, FC-72, RM-82, FC-75, RM-101, FC-43, RM-175, RC-5311, FC-5312, trimethylbicyclononane, dimethyladamantine and perfluorodecalin, or a combination thereof.

 

26.   The method of claim 23 wherein said emulsion is oxygenated.

 

27.   The method of claim 23 in which the emulsion is administered at a temperature above the body temperature of the patient.

 

28.   The method of claim 23 in which the emulsion is administered at a temperature below the body temperature of the patient.

 

29.   The method of claim 23 wherein said immiscible liquid is aqueous.

 

30.   The method of claim 23 wherein the biological agent is selected from the group consisting of antibody-linked radionuclides, vasoconstrictors, vasodilators, bronchoconstrictors, bronchodilators, anti-cancer agents, surfactants, steroids, antibiotic agents, chemotactic agents, chemotherapeutic agents, contrast agents, antioxidants and antiproteases, or a combination thereof.

 

31.   The method of claim 23 wherein the biological agent comprises a chemotherapeutic agent.

 

32.   The method of claim 23 wherein the biological agent comprises an antibiotic.

 

33.   The method of claim 23 wherein the biological agent comprises a bronchodilator.

 

34.   The method of claim 23 wherein the biological agent is dispersed in the liquid perfluorochemical.

 

35.   The method of claim 34 wherein the biological agent is selected from the group consisting of antibody-linked radionuclides, vasoconstrictors, vasodilators, bronchoconstrictors, bronchodilators, anti-cancer agents, surfactants, steroids, antibiotic agents, chemotactic agents, chemotherapeutic agents, contrast agents, antioxidants and antiproteases, or a combination thereof.

 

36.   The method of claim 34 wherein the biological agent comprises a chemotherapeutic agent.

 

37.   The method of claim 34 wherein the biological agent comprises an antibiotic.

 

38.   The method of claim 34 wherein the biological agent comprises a bronchodilator.

 

39.   The method of claim 23 wherein the liquid comprises the therapeutic or diagnostic agent in an aqueous medium.

 

40.   The method of claim 39 wherein said therapeutic or diagnostic agent is selected from the group consisting of antibody-linked radionuclides, vasoconstrictors, vasodilators, bronchoconstrictors, bronchodilators, anti-cancer agents, surfactants, steroids, antibiotic agents, chemotactic agents, chemotherapeutic agents, contrast agents, antioxidants and antiproteases, or a combination thereof.

 

41.    A method for the delivery of a therapeutic or diagnostic biological agent to pulmonary air passages of a patient in need thereof comprising the steps of:

 

combining a liquid perfluorochemical with at least one therapeutic or diagnostic biological agent in solid form to provide a dispersion; and

 

administering the dispersion to the pulmonary air passages of said patient.

 

42.   The method of claim 41 wherein said liquid perfluorochemical comprises a perfluorocarbon having a boiling point greater than about 55.degree. C.

 

43.   The method of claim 41 wherein said liquid perfluorochemical is selected from the group consisting of FC-84, FC-72, RM-82, FC-75, RM-101, FC-43, RM-175, FC-5311, FC-5312, trimethylbicyclononane, dimethyladamantine and perfluorodecalin, or a combination thereof.

 

44.   The method of claim 41 wherein said dispersion is oxygenated.

 

45.   The method of claim 41 wherein the solid biological agent comprises a powder.

 

46.   The method of claim 41 wherein the solid biological agent is selected from the group consisting of antibody-linked radionuclides, vasoconstrictors, vasodilators, bronchoconstrictors, bronchodilators, anti-cancer agents, surfactants, steroids, antibiotic agents, chemotactis agents, chemotherapeutic agents, contrast agents, antioxidants and antiproteases, or a combination thereof.

 

47.    The method of claim 41 wherein the solid biological agent comprises a chemotherapeutic agent.

 

48.    The method of claim 41 wherein the solid biological agent comprises an antibiotic.

 

49.   The method of claim 41 wherein the solid biological agent comprises a bronchodilator.

 

50.   The method of claim 41 wherein the solid biological agent comprises a surfactant.