Nasal drug delivery device

• US 9,550,036 B2
• Filed: 09/03/2013
• Issued: 01/24/2017
• Est. Priority Date: 03/03/2011
• Status: Active Grant

• Current Assignee: Woodward Specialty LLC
• Original Assignee: Impel Neuropharma Inc.
• Inventors: Hoekman, John D., Hite, Michael, Brunelle, Alan, Relethford, Joel, Ho, Rodney J. Y.
• Primary Examiner(s): Dixon, Annette
• Application Number:
  US14/017,048
• Publication Number:
  US 20140014104A1
• Time in Patent Office: 1,239 Days
• Field of Search: 128/200.14, 128/200.23, 128/200.24, 128/203.12, 128/203.15
• US Class Current: 1/1
• CPC Class Codes: A61M 11/007 Syringe-type or piston-type sprayers or atomisers
• CPC Class Codes: A61M 11/02 operated by air or other gas pressure applied to the liquid or other product to be sprayed or atomised sprayers for horticulture A01G, A01H; killing insects A01M; air humidifying by nozzles F24F6/14, F24F6/18; cooling by spraying F28B, F28C
• CPC Class Codes: A61M 15/002 with air flow regulating means
• CPC Class Codes: A61M 15/0021 Mouthpieces therefor
• CPC Class Codes: A61M 15/08 Inhaling devices inserted into the nose
• CPC Class Codes: A61M 16/201 Controlled valves
• CPC Class Codes: A61M 2202/0468 non-physiological
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/073 Syringe, piston type
• CPC Class Codes: A61M 2205/276 preventing unwanted use
• CPC Class Codes: A61M 2205/8225 using incorporated gas cartridges for the driving gas
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A compound delivery device for delivering a plume derived from a propellant and a drug formulation. The drug formulation is in an intranasal dosage form in the form of powder, suspension, dispersion or liquid. The propelled intranasal dosage form is deposited within the olfactory region of the nasal cavity. The drug deposited within the olfactory region is delivered to the brain avoiding the blood-brain-barrier. Hydrofluoroalkane propellant from a pressurized canister is channeled to a diffuser and drug-containing chamber where the intra-nasal dosage form is aerosolized. The aerosolized intra-nasal dosage form passes through a nozzle thus delivering a plume to the olfactory region of a user'"'"'s nasal cavity.

Claims

1. A device for delivering a compound to an olfactory region of a nasal cavity, the device comprising:

a canister capable of containing a propellant,

a porous frit in communication with the canister, the porous frit being a disk-shaped member including at least one conical shaped member having a distal aperture,

a compound chamber in communication with the porous frit, the compound chamber configured to hold the compound, and

a nozzle in communication with the compound chamber,

wherein the device is configured to deliver the compound to the olfactory region of the nasal cavity.

2. The device of claim 1, wherein the canister is pressurized.

3. The device of claim 1, wherein the propellant is at least one of a hydrofluoroalkane, nitrogen, or a chlorofluorocarbon.

4. The device of claim 1, wherein the compound is a drug or a diagnostic agent.

5. The device of claim 4, wherein the drug is an oxime.

6. The device of claim 4, wherein the diagnostic agent is an imaging agent.

7. The device of claim 6, wherein the imaging agent is fluorodeoxyglucose or fluorothymidine.

8. The device of claim 4, wherein the drug is a liquid suspension, a liquid dispersion, a powder, a liposome, an aqueous solution or a combination thereof.

9. The device of claim 1, wherein the propellant is a pressurized liquid.

10. The device of claim 9, wherein the pressurized liquid is hydrofluoroalkane.

11. The device of claim 10, wherein upon actuation of the device, the hydrofluoroalkane is released from the canister and comes into communication with the porous frit, whereby the hydrofluoroalkane is converted to gaseous hydrofluoroalkane.

12. The device of claim 11, wherein a minority of the pressurized liquid hydrofluoroalkane is converted to gaseous hydrofluoroalkane.

13. The device of claim 10, wherein a majority of the pressurized liquid hydrofluoroalkane is converted to gaseous hydrofluoroalkane.

14. The device of claim 1, wherein at least 64.2% of the compound is delivered to the olfactory region.

15. The device of claim 1, wherein the canister is a syringe, a syrette, or a barrel.

16. The device of claim 1, wherein the compound is not an imaging agent.

17. The device of claim 1, wherein the compound is not fluorodeoxyglucose.

18. The device of claim 1, further comprising an aiming-guide.

19. The device of claim 18, wherein the aiming guide aides in positioning the nozzle with a user'"'"'s olfactory region.

20. The device of claim 18, wherein the aiming guide is an indicator which indicates the depth of insertion of the device into the user'"'"'s nasal cavity.

21. The device of claim 1, further comprising an insertion port in communication with the compound chamber, the insertion port being configured to receive insertion of a compound from outside the device into the compound chamber.

22. The device of claim 21, wherein the insertion port is constructed from silicone or plastic.

23. The device of claim 1, wherein the porous frit is heterogeneously porous or homogenously porous.

24. The device of claim 1, wherein the canister is a metered dose inhaler (MDI).

25. The device of claim 1, wherein the porous frit comprises porous stainless steel having a pore size of approximately 1 to 100 microns.

26. A device for delivering a compound to an olfactory region of a nasal cavity comprising:

a canister capable of containing a propellant,

a diffuser in communication with the canister,

a compound chamber in communication with the diffuser, the compound chamber capable of containing the compound, wherein the diffuser is extended into the compound in the compound chamber, and

a nozzle in communication with the compound chamber,

wherein the device is capable of delivering the compound to the olfactory region of the nasal cavity.

27. A device for delivering a compound to an olfactory region of a nasal cavity, the device comprising:

a housing body;

a canister configured to contain a propellant,

a diffuser in communication with the canister,

a compound chamber in communication with the diffuser and connected to the housing body by flanges such that there is an area between the compound chamber and the housing body, the compound chamber configured to contain the compound, and

a nozzle in communication with the compound chamber and with the area between the compound chamber and the housing body,

wherein the propellant travels both through the compound chamber and through the area between the compound chamber and the housing body.

28. A method for intranasal delivery of a compound across the blood brain comprising:

inserting at least a portion of a device into a nasal cavity of a subject, the device including a canister containing a propellant, a compound chamber containing the compound, and a nozzle in communication with the compound chamber; and

actuating the device thereby causing delivery of the compound to the nasal cavity, wherein compound is delivered to a brain of the subject with a direct transport percentage of at least 50%.

29. The method of claim 28, wherein the compound is suitable for the treatment of an infectious disease, oncology, or immunological disease.

30. The method of claim 28, wherein the compound is an oxime.

31. The method of claim 28, wherein the direct transport percentage is at least 60%.

32. The method of claim 31, wherein the direct transport percentage is at least 80%.

33. The method of claim 28, wherein delivery of the compound to the nasal cavity comprises deposition of at least 50% of the compound to an olfactory region of the nasal cavity.

34. The method of claim 33, wherein delivery of the compound to the nasal cavity comprises deposition of at least 60% of the compound to an olfactory region of the nasal cavity.

35. The method of claim 34, wherein delivery of the compound to the nasal cavity comprises deposition of at least 70% of the compound to an olfactory region of the nasal cavity.

36. The method of claim 28, wherein the subject is a human.

37. A method for delivering an oxime across the blood-brain barrier to a subject in need thereof comprising:

delivering a therapeutically effective amount of an oxime intranasally to an olfactory region of a nasal cavity of the subject, wherein a concentration of the oxime in a brain of the subject five minutes following administration is higher for intranasal delivery than for intravenous injection of an equal weight of the oxime.

38. The method of claim 37, wherein the therapeutically effective amount of the oxime administered to the subject is about 0.001 mg/kg to about 100 mg/kg.

39. The method of claim 38, wherein the therapeutically effective amount of the oxime administered to the subject is about 0.01 mg/kg to about 10 mg/kg.

40. The method of claim 37, wherein delivery of the oxime provides treatment, prevention, or palliative care of an organophosphate exposure.

41. The method of claim 37, wherein the oxime is at least one of 2-pyridine aldoxime methyl chloride, 1,1-methylenebis[4-[(hydroxyimino)methyl]-pyridinium] dimethanesulfonate, 1-[[[4-(Aminocarbonyl)pyridinio]methoxy]methyl]-2-[(hydroxyimino)methyl]-pyridinium chloride, trimedoxime, or Hlo7.

42. The method of claim 41, wherein the oxime is 2-pyridine aldoxime methyl chloride.

43. The method of claim 37, wherein the oxime is a nasal dosage form.

44. The method of claim 43, wherein the nasal dosage form of the oxime is a powder, an aqueous solution, a suspension, a lipid containing product or combinations thereof.

45. The method of claim 37, wherein the subject has been exposed to an organophosphate.

46. The method of claim 45, wherein the organophosphate comprises sarin, tabun, soman, VX, diisopropylfluorophosphate or combinations thereof.

47. The method of claim 37, wherein a majority of the oxime is delivered to the olfactory region of the nasal cavity.

48. The method of claim 37, further comprising administering to the subject a nasal dosage form of a muscarinic receptor agonist or a muscarinic receptor antagonist.

49. The method of claim 37, further comprising administering to the subject a nasal dosage form of a muscarine antagonist.

50. The method of claim 49, wherein the muscarine antagonist is atropine, scopolamine or combinations thereof.

51. The method of claim 37, further comprising administering to the subject a nasal dosage form of a benzodiazepine antagonist.

52. The method of claim 51, wherein the benzodiazepine antagonist is diazepam, midazolam, lorazepam or combinations thereof.

53. The method of claim 37, further comprising administering to the subject a nasal dosage form of a benzodiazepine antagonist, a muscarinic receptor agonist, a muscarinic receptor antagonist or combinations thereof.

54. The method of claim 53, wherein the nasal dosage form is diazepam, midazolam, lorazepam, atropine, scopolamine or combinations thereof.

55. The method of claim 37, wherein the oxime is delivered to the nasal cavity of the subject before an exposure to an organophosphate.

56. The method of claim 37, wherein the oxime is delivered to the nasal cavity of the subject after an exposure to an organophosphate.

57. The method of claim 37, wherein the oxime is delivered to the nasal cavity of the subject during an exposure to an organophosphate.

58. The method of claim 37, wherein at least 53% direct transport of the oxime is to the brain.

59. The method of claim 37, wherein the oxime is propelled by a propellant to the olfactory region.

60. A device for delivering a compound to an olfactory region of a nasal cavity, the device comprising:

a canister capable of containing a propellant,

a diffuser in communication with the canister, the diffuser configured to convert the propellant from a liquid to a gas,

a compound chamber in communication with the diffuser, the compound chamber configured to hold the compound, and

a nozzle in communication with the compound chamber,

wherein the device is configured to deliver the compound to the olfactory region of the nasal cavity.

61. A device for delivering a compound to an olfactory region of a nasal cavity, the device comprising:

a canister capable of containing a propellant,

a diffuser in communication with the canister, the diffuser being a one way check valve,

a compound chamber in communication with the diffuser, the compound chamber capable of containing the compound, and

a nozzle in communication with the compound chamber,

wherein the device is capable of delivering the compound to the olfactory region of the nasal cavity.