Methods of treatment

• US 8,778,383 B2
• Filed: 06/07/2012
• Issued: 07/15/2014
• Est. Priority Date: 06/07/2011
• Status: Active Grant

• Current Assignee: Parion Sciences, Inc.
• Original Assignee: Parion Sciences, Inc.
• Inventors: Boucher, Richard C., Johnson, Michael Ross, Thelin, William R., Button, Brian, Navratil, Tomas
• Primary Examiner(s): BARHAM, BETHANY P
• Application Number:
  US13/491,275
• Publication Number:
  US 20130074842A1
• Time in Patent Office: 768 Days
• Field of Search: None
• US Class Current: 424/434
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
• CPC Class Codes: A61M 11/002 by flow deviation causing inertial separation of transported particles
• CPC Class Codes: A61M 11/003 by passing the aerosol trough sieves or filters
• CPC Class Codes: A61M 11/005 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 11/06 of the injector type
• CPC Class Codes: A61M 15/0085 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 15/0086 Inhalation chambers
• CPC Class Codes: A61M 16/0666 Nasal cannulas or tubing devices for improving normal breathing through the nose A61F5/08; nose filters A62B23/06; outside holding devices A61M25/02
• CPC Class Codes: A61M 16/12 by mixing different gases
• CPC Class Codes: A61M 16/14 by mixing different fluids, one of them being in a liquid phase
• CPC Class Codes: A61M 16/16 Devices to humidify the respiration air A61M16/1045 takes precedence
• CPC Class Codes: A61M 2202/0275 Nitric oxide [NO]
• CPC Class Codes: A61M 2206/14 Static flow deviators in tubes disturbing laminar flow in tubes, e.g. archimedes screws
• CPC Class Codes: A61M 2206/16 Rotating swirling helical flow, e.g. by tangential inflows
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 11/12 Mucolytics
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/14 : for RNA viruses
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention concerns methods, compositions and apparatus for administering active agents to the lungs of a subject.

Claims

1. A method of enhancing hydration of a lung airway surface, comprising:

administering an osmolyte to the lung airway surface of a subject in an amount and at a rate (i) sufficient to hydrate said surface, and (ii) insufficient to substantially dehydrate lung airway epithelial cells therebeneath, the administering being carried out for a time sufficient to enhance hydration of said surface of said subject,

the administering including administering an aerosol comprising aerosol particles having a volume median diameter (VMD) from about 1 μ

m to about 4 μ

m, the aerosol particles including the osmolyte.

2. The method of claim 1, wherein the osmolyte comprises sodium chloride.

3. The method of claim 1, wherein the osmolyte comprises a solution of sodium chloride in water, and wherein the sodium chloride is present in an amount of from about 0.12 percent to about 0.9 percent by weight.

4. The method of claim 1, wherein the osmolyte comprises a solution of sodium chloride in water, and wherein the sodium chloride is present in an amount of from about 0.9 percent to about 7 percent by weight.

5. The method of claim 1, wherein the osmolyte comprises a solution of sodium chloride in water, and wherein the sodium chloride is present in an amount of from about 7 percent to about 12 percent by weight.

6. The method of claim 1, wherein the osmolyte comprises a solution of sodium chloride in water, and wherein the sodium chloride is present in an amount of from about 12 percent to about 21 percent by weight.

7. The method of claim 1, wherein the osmolyte comprises a solution of sodium chloride in water, and wherein the sodium chloride is present in an amount of from about 21 percent to about 40 percent by weight.

8. The method of claim 2, wherein the administering includes depositing the sodium chloride at a rate from about 0.1 mg/minute to about 1 mg/minute to the lung airway surface of the subject.

9. The method of claim 2, wherein the administering includes depositing from about 1 mg to about 5 mg of said sodium chloride to the lung airway surface of said subject per minute.

10. The method of claim 1, wherein the administering is carried out for a time of about 1 minute up to about 30 minutes.

11. The method of claim 1, wherein the administering is carried out for a time of from about 30 minutes up to about 8 hours.

12. The method of claim 1, wherein the administering is carried out for a time from about 8 hours up to about 24 hours.

13. The method of claim 1, wherein the administering is carried out overnight.

14. The method of claim 1, wherein the administering is carried out via one or more of a nasal cannula, face mask, or positive airway pressure mask.

15. The method of claim 13, wherein the administering is carried out while the subject is sleeping.

16. The method of claim 2, wherein the administering includes depositing the sodium chloride at a rate from about 0.01 mg/minute to about 0.1 mg/minute to the lung airway surface of the subject.

17. The method of claim 1, wherein:

not more than about 15% of the aerosol particles are larger than 4 μ

m, based on volume normalized amounts; and

the administering produces a deposition efficiency of greater than about 3% on the lung airway surface.

18. The method of claim 17, wherein the administering is carried out for more than about 30 minutes.

19. The method of claim 17, wherein the administering is carried out at an airflow of from about 0.5 liter per minute to about 5 liters per minute.

20. The method of claim 17, further comprising:

producing the aerosol via an aerosol delivery system, the aerosol delivery system including a housing, a nebulizer and a nasal cannula, the housing defining an entrainment chamber and a particle selection chamber, the nebulizer coupled to the housing in fluid communication with the entrainment chamber, the nasal cannula coupled to the housing in fluid communication with the particle selection chamber,

the administering the aerosol is performed via a nasal cannula.

21. The method of claim 17, wherein the aerosol particles have a volume median diameter (VMD from about 1 μ

m to about 2.5 μ

m.

22. The method of claim 17, wherein not more than about 5% of the aerosol particles are larger than 4 μ

m, based on volume normalized amounts.

23. The method of claim 17, wherein the administering the aerosol produces a deposition efficiency of greater than about 5%.

24. The method of claim 17, wherein the administering the aerosol particles produce a deposition efficiency onto the lung airway surface of up to about 25%.

25. The method of claim 17, wherein the administering the aerosol produces a deposition rate of the osmolyte of less than about 10 μ

g/min/cm² on the lung airway surface.

26. The method of claim 17, further comprising treating a disease or condition associated with either lung of the subject by administering an effective amount of the aerosol to the lung having the disease or condition associated therewith.

27. The method of claim 26, wherein the disease or condition is selected from cystic fibrosis (CF), chronic bronchitis, emphysema, non-CF bronchiectasis, influenza, RSV infection, RSV infection induced bronchiolitis, rhinovirus infection, sinus-related disorders, chronic obstructive pulmonary disease, aspiration pneumonitis, ventilator-associated pneumonia, hospital-acquired or nosocomial pneumonia, sleep apnea, healthcare-associated pneunomonia, asthma, a bacterial infection, a viral infection, primary cilia dyskinesia, and a fungal infection.

28. A method of enhancing hydration of a lung airway surface, comprising:

administering intranasally an osmolyte at a rate (i) sufficient to hydrate said surface, and (ii) insufficient to substantially dehydrate lung airway epithelial cells therebeneath, said rate less than about 1 mg/min and greater than about 0.1 mg/min, said rate of administering selected as a function of a deposition efficiency of the osmolyte onto the lung airway surface such that a rate of deposition of the osmolyte onto the lung airway surface is within a predetermined range.

29. The method of claim 28, wherein the administering the osmolyte includes administering an aerosol comprising aerosol particles, said aerosol particles including the osmolyte.

30. The method of claim 29, wherein the administering the aerosol particles produces the deposition efficiency of the osmolyte of greater than about 5%.

31. The method of claim 30, wherein the administering the aerosol particles produces the deposition efficiency of the osmolyte of up to about 25%.

32. The method of claim 29, further comprising:

producing, before the administering, the aerosol comprising the aerosol particles of the osmolyte.

33. The method of claim 32, wherein the producing includes producing aerosol particles having a VMD from about 1.2 μ

m to about 2.2 μ

m.

34. The method of claim 32, wherein producing includes producing the aerosol particles such that not more than about 5% of the aerosol particles are larger than 4 μ

m, based on volume normalized amounts.

35. The method of claim 28, wherein the osmolyte includes a solution of sodium chloride in water, the sodium chloride being present in an amount from about 2.5 percent by weight to about 21 percent by weight, wherein the rate of administering is further selected as a function of the amount of sodium chloride in the solution of sodium chloride in water.

36. The method of claim 32, wherein the producing includes producing the aerosol via an aerosol delivery system, the aerosol delivery system including a housing, a nebulizer and a nasal cannula, the housing defining an entrainment chamber and a particle selection chamber, the nebulizer coupled to the housing in fluid communication with the entrainment chamber, the nasal cannula coupled to the housing in fluid communication with the particle selection chamber.

37. A method of enhancing hydration of a lung airway surface, comprising:

producing an aerosol including a solution of sodium chloride in water, the sodium chloride being present in an amount of at least about 2.5 percent by weight, the aerosol having a volume median diameter (VMD) of between about 1 μ

m and about 2.0 μ

m; and

administering intranasally the aerosol such that a portion of the aerosol is deposited onto the lung airway surface at a rate (i) sufficient to hydrate said surface, and (ii) insufficient to substantially dehydrate lung airway epithelial cells therebeneath.

38. The method of claim 37, wherein the sodium chloride is present from an amount greater than about 2.5 percent by weight to an amount up to about 21 percent by weight.

39. The method of claim 37, wherein the aerosol further includes one or more active agents.

40. The method of claim 39, wherein each active agent is selected from the group consisting of osmolytes, sodium channel blockers, secretogogues, mucus modifying agents, anti-infective agents, anti-inflammatory agents, bronchiodilators, and therapeutic agents.