Use of inhaled gaseous nitric oxide as a mucolytic agent or expectorant

• US 20070104653A1
• Filed: 11/10/2006
• Published: 05/10/2007
• Est. Priority Date: 05/11/2004
• Status: Active Grant

• Current Assignee: Beyond Air Ltd. (Beyond Air, Inc.)
• Original Assignee: Pulmonox Technologies Corp.
• Inventors: Miller, Christopher, Murray, Bruce, Hole, Douglas, Perry, Bryan
• Granted Patent: US 8,518,457 B2
• Time in Patent Office: Days
• US Class Current: 424/45
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy

Abstract

Methods and devices for treating excess mucus accumulation in mammals by administering gaseous inhaled nitric oxide or nitric oxide releasing compounds as a mucolytic agent or expectorant are provided. Delivery of gaseous nitric oxide can be made nasally or orally and is preferably substantially coincident with inhalation of the mammal or based on a synchronous parameter of the mammal'"'"'s respiratory cycle. Varying therapeutic profiles may be used for the delivery of gaseous nitric oxide depending on the severity of the excess mucus accumulation. Parameters for the therapeutic profiles may include flow rate of nitric oxide containing gas, duration of administration of nitric oxide containing gas, number of breaths for which nitric oxide containing gas is to be administered, and concentrations of therapeutic NO delivered to the airways.

Claims

1. A method of treating excess mucus accumulation in a mammal'"'"'s airway comprising the steps of:

providing a pressurized source of nitric oxide containing gas; and

administering a therapeutically effective amount of nitric oxide containing gas to a mammal exhibiting excess mucus accumulation in the mammal'"'"'s airway, wherein the nitric oxide containing gas is administered substantially coincident with the inspiration of the mammal.

2. The method of claim 1, further comprising the step of regulating a flow rate of the nitric oxide containing gas depending on the mammal'"'"'s respiratory tidal volume.

3. The method of claim 2, wherein the concentration of nitric oxide containing gas in the mammal'"'"'s airway ranges from about 160 ppm to about 220 ppm.

4. The method of claim 1, wherein the administration of the nitric oxide containing gas is timed according to a synchronous parameter of the mammal'"'"'s respiratory cycle.

5. The method of claim 4, wherein the synchronous parameter is selected from a group consisting of rate of flow of gas directed toward the mammal'"'"'s airway, pressure change at the initiation of a breath, the synchronous movement of the laryngeal, and the synchronous motion of the chest wall.

6. The method of claim 1, wherein the therapeutically effective amount of nitric oxide containing gas is sufficient to reduce an amount of mucus in the mammal'"'"'s airways by at least about 50%.

7. The method of claim 1, wherein the therapeutically effective amount of nitric oxide containing gas is sufficient to effect mucolysis within thirty minutes.

8. A method of treating excess mucus accumulation in a mammal'"'"'s airway comprising the steps of:

identifying a mammal exhibiting excess mucus accumulation;

determining the severity of mucus accumulation in the mammal;

providing a source of nitric oxide containing gas; and

administering the nitric oxide containing gas using a distinct therapeutic profile corresponding to the severity of mucus accumulation in the mammal.

9. The method of claim 8, wherein the severity of mucus accumulation is scored from 0 to 5, with 5 indicating a most severe condition.

10. The method of claim 8, wherein the distinct therapeutic profile is selected from a pre-determined set of therapeutic profiles.

11. The method of claim 10, wherein the distinct therapeutic profile comprises therapeutic parameters selected from a group consisting of flow rate of nitric oxide containing gas, duration of administration of nitric oxide containing gas, number of breaths for which nitric oxide containing gas is to be administered, and concentrations of therapeutic NO delivered to the airways.

12. A portable inhaler comprising:

a pressurized canister comprising gaseous nitric oxide;

a channel adapted for insertion into a mammal'"'"'s mouth or nostril;

a release valve for controllably releasing the gaseous nitric oxide into the channel; and

a label indicating suitable use of gaseous nitric oxide as a mucolytic agent or expectorant.

13. A packaged kit comprising:

the portable inhaler of claim 12;

and

an instruction sheet instructing a user having mucus accumulation to insert the channel into his mouth or nostril and to actuate the release valve substantially coincident with inhalation.

14. A nitric oxide delivery apparatus for treating excess mucus accumulation in a mammal'"'"'s airway, the apparatus comprising:

a source of gaseous nitric oxide;

a delivery interface adapted to deliver gaseous nitric oxide to the mammal'"'"'s airway;

a flow control valve positioned downstream of the source of gaseous nitric oxide and upstream of the delivery interface; and

a controller in communication with and controlling the flow control valve to regulate a flow rate of the gaseous nitric oxide from the source to the delivery interface;

wherein the controller comprises logic for selection of a therapeutic profile of gaseous nitric oxide based on an input value representing a level of severity of mucus accumulation in the mammal'"'"'s airway.

15. The nitric oxide delivery apparatus of claim 14, wherein the controller further comprises a memory device that stores a number of therapeutic profiles of gaseous nitric oxide each corresponding to a level of severity of mucus accumulation in the mammal'"'"'s airways.

16. The nitric oxide delivery apparatus of claim 14, wherein the input value is selected from a group consisting of 0, 1, 2, 3, 4, and 5.

17. The nitric oxide delivery apparatus of claim 15, wherein the therapeutic profiles are pre-determined and comprises therapeutic parameters selected from a group consisting of flow rate of nitric oxide containing gas, duration of administration of nitric oxide containing gas, number of breaths for which nitric oxide containing gas is to be administered, and concentrations of therapeutic NO delivered to the airways.

18. The nitric oxide delivery apparatus of claim 14, further comprising an input device for entering the input value into the controller.

19. A system for treating mucus accumulation, the system comprising:

a pressurized cylinder comprising nitric oxide gas; and

a visible label affixed to the container, wherein the label indicates that the nitric oxide containing gas is suitable as a mucolytic agent or expectorant.

20. The system of claim 19, further comprising an instruction sheet instructing delivery of nitric oxide gas from the pressurized cylinder to a mammal exhibiting excess mucus accumulation substantially coincident with inhalation of the mammal.

21. A method of treating excess mucus accumulation in a mammal'"'"'s airway comprising the steps of:

administering a therapeutically effective amount of NO-releasing compounds to a mammal exhibiting excess mucus accumulation in the mammal'"'"'s airway.

22. The method of claim 21, wherein the NO-releasing compounds is selected from a group consisting of S-nitrosothiols, S-nitroso-N-acetylpenicillamine, S-nitroso-L-cysteine, NONOates, nitroprusside, NO-ferredoxin, NO-heme complex, nitrosoguanidine, arginine, glyceryl trinitrate, isoamyl nitrite, inorganic nitrite, azide, hydroxylamine, polyethyleneimine (PEI)-based polymers exposed to NO gas, molsidomine, nitrate esters, sodium nitrite, iso-sorbide didinitrate, penta erythritol tetranitrate, and nitroimidazoles.

23. The method of claim 21, wherein the NO-releasing compounds is administered to the patient by a route selected from the group consisting of intravenous injection, intraarterial injection, transcutaneous delivery, oral delivery, and inhalation.

24. The method of claim 21, wherein the therapeutically effective amount of NO-releasing compounds is sufficient to reduce an amount of mucus in the mammal'"'"'s airways by at least about 50%.

25. The method of claim 21, wherein the therapeutically effective amount of NO-releasing compounds sufficient to effect mucolysis within thirty minutes.

26. A method of treating excess mucus accumulation in a mammal'"'"'s airway comprising the steps of:

identifying a mammal exhibiting excess mucus accumulation;

determining the severity of mucus accumulation in the mammal; and

administering NO-releasing compounds using a distinct therapeutic profile corresponding to the severity of mucus accumulation in the mammal.

27. The method of claim 26, wherein the NO-releasing compounds, is selected from a group consisting of S-nitrosothiols, S-nitroso-N-acetylpenicillamine, S-nitroso-L-cysteine, NONOates, nitroprusside, NO-ferredoxin, NO-heme complex, nitrosoguanidine, arginine, glyceryl trinitrate, isoamyl nitrite, inorganic nitrite, azide, hydroxylamine, polyethyleneimine (PEI)-based polymers exposed to NO gas, molsidomine, nitrate esters, sodium nitrite, iso-sorbide didinitrate, penta erythritol tetranitrate, and nitroimidazoles.

28. The method of claim 26, wherein the severity of mucus accumulation is scored from 0 to 5, with 5 indicating a most severe condition.

29. The method of claim 26, wherein the distinct therapeutic profile is selected from a pre-determined set of therapeutic profiles.

30. The method of claim 26, wherein the NO-releasing compounds is administered to the patient by a route selected from the group consisting of intravenous injection, intraarterial injection, transcutaneous delivery, oral delivery, and inhalation.

31. The method of claim 26, wherein the therapeutically effective amount of NO-releasing compounds is sufficient to reduce an amount of mucus in the mammal'"'"'s airways by at least about 50%.

32. The method of claim 26, wherein the therapeutically effective amount of NO-releasing compounds sufficient to effect mucolysis within thirty minutes.