COMPOSITIONS FOR THE TREATMENT OF VIRAL PULMONARY INFECTIONS

Abstract

The disclosure relates to a method for treating a viral pulmonary infection (e.g., COVID-19 infection), the method comprising the step of delivering a composition comprising various combinations of (i) at least one of an interferon or an interferon inducer; (ii) at least one bronchodilator or a pharmaceutically acceptable salt thereof; (iii) at least one pulmonary surfactant or a pharmaceutically acceptable salt thereof; and (iv) at least one of particles comprising at least one of metal having antiviral properties and particles comprising metal compounds having antiviral properties; to the airway of a subject in need of treatment for the pulmonary viral infection.

Claims

1. A method for treating a pulmonary infection caused by an enveloped virus, the method comprising the step of delivering a composition comprising at least one of an interferon or an interferon inducer; at least one pulmonary surfactant or a pharmaceutically acceptable salt thereof, and optionally at least one of particles comprising at least one of metal having antiviral properties and particles comprising metal compounds having antiviral properties; to the airway of a subject in need of treatment for the infection.

2. The method of claim 1, wherein the interferon is at least one of a type I or a type II interferon.

3. The method of claim 1, wherein the interferon is at least one of IFN-α and subtypes; IFN-β; IFN-ε; IFN-ω; IFN-τ; and IFN-γ.

4. The method of claim 1, wherein the interferon is at least one of IFN-like cytokines; and IFN-A and subtypes.

5. The method of claim 1, wherein the particles comprising at least one metal having antiviral properties are particles comprising metallic copper, gold, iron, nickel, silver, and combinations thereof.

6. The method of claim 1, wherein the particles comprising metal compounds having antiviral properties are particles comprising Cu.sub.2O.

7. The method of claim 1, wherein the enveloped virus is the novel coronavirus.

8. The method of claim 1, wherein the airway is at least one of the nasal cavity and the lower airway.

9. The method of claim 1, wherein the composition is an aerosolized formulation.

10. The method of claim 1, wherein the bronchodilator is a non-steroidal bronchodilator.

11. The method of claim 1, wherein the at least one bronchodilator is albuterol, salmeterol ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol, reproterol, rimiterol, terbutaline, isoetharine, tulobuterol, 4-hydroxy-7-[2-[[2-[3-(2-phenylethoxy)propyl]sulfonyl]ethyl]amino]ethyl-2(3H)-benzothiazolone, aclidinium, arformoterol, glycopyrrolate, indacaterol, levalbuterol, olodaterol, revefenacin, tiotropium, umeclidinium, or pharmaceutically acceptable salts thereof.

12. The method of claim 1, wherein the at least one pulmonary surfactant is a compound of the formula: ##STR00008## wherein R.sup.1 and R.sup.2 are each independently an alkyl group.

13. The method of claim 1, wherein the at least one pulmonary surfactant is a compound of the formula: ##STR00009## wherein R.sup.1 and R.sup.2 are each independently an alkyl group.

14. The method of claim 1, wherein the at least one pulmonary surfactant is ##STR00010##

15. The method of claim 1, wherein the at least one pulmonary surfactant is phosphatidylcholine, dipalmitoylphosphatidylcholine or pharmaceutically acceptable salts thereof.

16. The method of claim 1, wherein the at least one bronchodilator is albuterol sulfate and the at least one pulmonary surfactant is at least one of POPG and PI or pharmaceutically acceptable salts thereof.

17. The method of claim 1, wherein the compositions comprising the at least one bronchodilator or a pharmaceutically acceptable salt thereof and the at least one pulmonary surfactant or a pharmaceutically acceptable salt thereof, further comprises at least one additional antiviral drug.

18. A method for treating a pulmonary infection caused by an enveloped virus, the method comprising the step of delivering a composition comprising at least one of particles comprising at least one of metal having antiviral properties and particles comprising metal compounds having antiviral properties; optionally, at least one of a pulmonary surfactant or a pharmaceutically acceptable salt thereof and a bronchodilator; and optionally, at least one of an interferon or an interferon inducer; to the airway of a subject in need of treatment for the infection.

19. A method for treating a pulmonary infection caused by an enveloped virus, the method comprising the step of delivering a composition comprising at least one bronchodilator; at least one of an interferon or an interferon inducer; and optionally, at least one pulmonary surfactant or a pharmaceutically acceptable salt thereof; to the airway of a subject in need of treatment for the infection.

20. A method for treating a pulmonary infection caused by an enveloped virus, the method comprising the step of delivering a composition comprising at least one pulmonary surfactant or a pharmaceutically acceptable salt thereof; and optionally, at least one bronchodilator.

Description

EXAMPLES

[0069] The disclosure can be better understood by reference to the following examples which are offered by way of illustration. The disclosure is not limited to the examples given herein.

[0070] An example of a composition comprising at least one bronchodilator and at least one pulmonary surfactant is shown in Table 1.

TABLE-US-00001 TABLE 1 Component % w/w CAS # POPG/PI 1.3 185435-28-3 Albuterol Sulfate 0.1 51022-70-9 Normal Saline 0.9 7647-14-5.

[0071] The present invention provides for the following exemplary embodiments, the numbering of which is not to be construed as designating levels of importance: Embodiment 1 relates to a method for treating a pulmonary infection caused by an enveloped virus, the method comprising the step of delivering a composition comprising [0072] at least one of an interferon or an interferon inducer; [0073] at least one pulmonary surfactant or a pharmaceutically acceptable salt thereof, and [0074] optionally at least one of particles comprising at least one of metal having antiviral properties and particles comprising metal compounds having antiviral properties;
to the airway of a subject in need of treatment for the infection.

[0075] Embodiment 2 relates to the method of Embodiment 1, wherein the interferon is at least one of a type I or a type II interferon.

[0076] Embodiment 3 relates to the method of Embodiments 1-2, wherein the interferon is at least one of IFN-α and subtypes; IFN-β; IFN-ε; IFN-ω; IFN-τ; and IFN-γ.

[0077] Embodiment 4 relates to the method of Embodiments 1-3, wherein the interferon is at least one of IFN-like cytokines; and IFN-A and subtypes.

[0078] Embodiment 5 relates to the method of Embodiments 1-4, wherein the particles comprising at least one metal having antiviral properties are particles comprising metallic copper, gold, iron, nickel, silver, and combinations thereof.

[0079] Embodiment 6 relates to the method of Embodiments 1-5, wherein the particles comprising metal compounds having antiviral properties are particles comprising Cu.sub.2O.

[0080] Embodiment 7 relates to the method of Embodiments 1-6, wherein the enveloped virus is the novel coronavirus.

[0081] Embodiment 8 relates to the method of Embodiments 1-7, wherein the pulmonary infection is COVID-19.

[0082] Embodiment 9 relates to the method of Embodiments 1-8, wherein the airway is at least one of the nasal cavity and the lower airway.

[0083] Embodiment 10 relates to the method of Embodiments 1-10, wherein the composition is an aerosolized formulation.

[0084] Embodiment 11 relates to the method of Embodiments 1-10, wherein the composition is delivered with a metered dose inhaler, a sprayer, a nebulizer, or a dry powder generator.

[0085] Embodiment 12 relates to the method of Embodiments 1-11, wherein the bronchodilator is a non-steroidal bronchodilator.

[0086] Embodiment 13 relates to the method of Embodiments 1-12, wherein the bronchodilator is a beta-2 agonist.

[0087] Embodiment 14 relates to the method of Embodiments 1-13, wherein the at least one bronchodilator is albuterol, salmeterol ephedrine, adrenaline, fenoterol, formoterol, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol, reproterol, rimiterol, terbutaline, isoetharine, tulobuterol, 4-hydroxy-7-[2-[[2-[[3-(2-phenylethoxy)propyl]sulfonyl]ethyl]amino]ethyl-2(3H)-benzothiazolone, aclidinium, arformoterol, glycopyrrolate, indacaterol, levalbuterol, olodaterol, revefenacin, tiotropium, umeclidinium, or pharmaceutically acceptable salts thereof.

[0088] Embodiment 15 relates to the method of Embodiment 1-14, wherein the at least one bronchodilator is albuterol, salmeterol, formoterol, metaproterenol, pirbuterol, reproterol, rimiterol, tulobuterol, arformoterol, indacaterol, levalbuterol, olodaterol, or pharmaceutically acceptable salts thereof.

[0089] Embodiment 16 relates to the method of Embodiment 1-15, wherein the at least one bronchodilator is albuterol or a pharmaceutically acceptable salt thereof.

[0090] Embodiment 17 relates to the method of Embodiments 1-16, wherein the at least one pulmonary surfactant is a compound of the formula:

##STR00005##

[0091] wherein R.sup.1 and R.sup.2 are each independently an alkyl group.

[0092] Embodiment 18 relates to the method of Embodiment 17, wherein the R.sup.1 and R.sup.2 are each a (C.sub.10-C.sub.20)alkyl group.

[0093] Embodiment 19 relates to the method of Embodiment 18, wherein the alkyl group comprises one, two, three, four, five or six unsaturated portions.

[0094] Embodiment 20 relates to the method of Embodiment 19, wherein the unsaturated portions have the formula —CH═CH—.

[0095] Embodiment 21 relates to the method of Embodiments 1-16, wherein the at least one pulmonary surfactant is a compound of the formula:

##STR00006##

wherein R.sup.1 and R.sup.2 are each independently an alkyl group.

[0096] Embodiment 22 relates to the method of Embodiment 21, wherein the R.sup.1 and R.sup.2 are each a (C.sub.10-C.sub.20)alkyl group.

[0097] Embodiment 23 relates to the method of Embodiment 22, wherein the alkyl group comprises one, two, three, four, five or six unsaturated portions.

[0098] Embodiment 24 relates to the method of Embodiment 23, wherein the unsaturated portions have the formula —CH═CH—.

[0099] Embodiment 25 relates to the method of Embodiments 1-24, wherein the at least one pulmonary surfactant is

##STR00007##

[0100] Embodiment 26 relates to the method of Embodiments 1-25, wherein the at least one pulmonary surfactant is phosphatidylcholine, dipalmitoylphosphatidylcholine or pharmaceutically acceptable salts thereof.

[0101] Embodiment 27 relates to the method of Embodiments 1-26, wherein the at least one bronchodilator is albuterol sulfate and the at least one pulmonary surfactant is at least one of POPG and PI or pharmaceutically acceptable salts thereof.

[0102] Embodiment 28 relates to the method of Embodiments 1-27, wherein the compositions comprising the at least one bronchodilator or a pharmaceutically acceptable salt thereof and the at least one pulmonary surfactant or a pharmaceutically acceptable salt thereof, further comprises at least one additional antiviral drug.

[0103] Embodiment 29 relates to a method for treating a pulmonary infection caused by an enveloped virus, the method comprising the step of delivering a composition comprising

[0104] at least one of particles comprising at least one of metal having antiviral properties and particles comprising metal compounds having antiviral properties;

[0105] optionally, at least one of a pulmonary surfactant or a pharmaceutically acceptable salt thereof and a bronchodilator; and

[0106] optionally, at least one of an interferon or an interferon inducer;

to the airway of a subject in need of treatment for the infection.

[0107] Embodiment 30 relates to a method for treating a pulmonary infection caused by an enveloped virus, the method comprising the step of delivering a composition comprising

[0108] at least one bronchodilator;

[0109] at least one of an interferon or an interferon inducer; and

[0110] optionally, at least one pulmonary surfactant or a pharmaceutically acceptable salt thereof;

[0111] to the airway of a subject in need of treatment for the infection.

[0112] Embodiment 31 relates to a method for treating a pulmonary infection caused by an enveloped virus, the method comprising the step of delivering a composition comprising

[0113] at least one pulmonary surfactant or a pharmaceutically acceptable salt thereof; and

[0114] optionally, at least one bronchodilator.