NASAL ADMINISTRATION

• US 20100288275A1
• Filed: 04/07/2008
• Published: 11/18/2010
• Est. Priority Date: 04/05/2007
• Status: Active Grant

• Current Assignee: OptiNose, Inc.
• Original Assignee: OptiNose AS (OptiNose, Inc.)
• Inventors: Djupesland, Per Gisle, Hafner, Roderick Peter
• Granted Patent: US 9,649,456 B2
• Time in Patent Office: Days
• US Class Current: 128/203.15
• CPC Class Codes: A61K 31/4045 Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
• CPC Class Codes: A61M 15/0005 with means for agitating the medicament
• CPC Class Codes: A61M 15/0008 rotating by airflow
• CPC Class Codes: A61M 15/0021 Mouthpieces therefor
• CPC Class Codes: A61M 15/0028 using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
• CPC Class Codes: A61M 15/003 using capsules, e.g. to be perforated or broken-up
• CPC Class Codes: A61M 15/0035 Piercing means
• CPC Class Codes: A61M 15/0041 with movable piercing or cutting means
• CPC Class Codes: A61M 15/0098 Activated by exhalation
• CPC Class Codes: A61M 15/08 Inhaling devices inserted into the nose
• CPC Class Codes: A61M 16/0808 Condensation traps
• CPC Class Codes: A61M 16/1045 Devices for humidifying or heating the inspired gas by using recovered moisture or heat from the expired gas
• CPC Class Codes: A61M 16/1055 bacterial
• CPC Class Codes: A61M 16/1065 in the expiratory path
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/3606 cooled
• CPC Class Codes: A61M 2210/0618 Nose
• CPC Class Codes: A61M 2210/0625 Mouth

Abstract

A delivery device for and method of delivering a powdered substance, in particular a triptan, such as sumatriptan, to the posterior region of a nasal cavity of a subject, in particular for the treatment of headaches, for example, cluster headaches and migraine, and neuropathic pain, the delivery device comprising: a nosepiece (47) for insertion into a nasal cavity of a subject through which the powdered substance is delivered to the posterior region of the nasal cavity of the subject, in particular the upper posterior two thirds of the nasal cavity; and a substance supply unit (16) which is operable to deliver the powdered substance through the nosepiece (47).

Claims

1. A delivery device for delivering a powdered substance to the posterior region of a nasal cavity of a subject, the delivery device comprising:

a nosepiece for insertion into a nasal cavity of a subject through which a powdered substance is delivered to the posterior region of the nasal cavity of the subject; and

a substance supply unit which is operable to deliver a powdered substance through the nosepiece.

2. The delivery device of claim 1, wherein the substance supply unit comprises a container-receiving unit which comprises a container chamber for receiving a substance-containing container which contains a powdered substance to be delivered to the nasal cavity of the subject, and the container chamber includes an outlet which is in fluid communication with the nosepiece such as to provide for delivery of the powdered substance from the container chamber to the nosepiece.

3. The delivery device of claim 2, wherein the container comprises a capsule, optionally formed from a cellulose derivative, hydroxypropyl methylcellulose (HPMC) or a gelatine derivative.

6. The delivery device of claim 3, wherein the capsule is coated with a hydrophobic material, optionally parylene.

7. The delivery device of claim 1, wherein the nosepiece is configured, when inserted into the nasal cavity, to extend into the nasal valve and provide for expansion thereof.

8. The delivery device of claim 1, wherein the nosepiece is configured such as to obstruct the nasal valve, optionally to close the nasal valve and thereby substantially prevent deposition of substance anteriorly of the same.

10. The delivery device of claim 1, further comprising:

a mouthpiece through which the subject in use exhales to cause closure of the oropharyngeal velum of the subject.

11. The delivery device of claim 10, further comprising:

a flow channel fluidly connecting the nosepiece and the mouthpiece, whereby exhaled air from an exhalation breath is delivered through the nosepiece.

12. The delivery device of claim 11, wherein the substance supply unit comprises a container-receiving unit which comprises a container chamber for receiving a substance-containing container which contains a powdered substance to be delivered to the nasal cavity of the subject, and the container chamber includes an inlet which is fluidly connected to the mouthpiece and an outlet which is fluidly connected to the nosepiece, such that exhaled air from an exhalation breath acts to entrain powdered substance as contained by the container and deliver the same through the nosepiece, optionally the container-containing member includes a flow passage in which the container is disposed, such as to be rotatable therewithin when an air flow is delivered therethrough.

14. The delivery device of claim 1, further comprising:

a flow channel fluidly connected to the nosepiece through which a gas flow, separate to an exhaled air flow from an exhalation breath of the subject, is in use delivered to the nosepiece; and

a gas supply unit for supplying a gas flow to the flow channel.

15. The delivery device of claim 1, where configured such that at least 55%, optionally at least 60%, optionally at least 65%, optionally at least 70%, optionally at least 80%, of the dose as initially deposited in the nasal cavity is deposited in the region posterior of the nasal valve.

20. The delivery device of claim 1, where configured such that at least 35%, optionally at least 40%, optionally at least 45%, optionally at least 50%, optionally at least 55%, of the dose as initially deposited in the nasal cavity is deposited in the upper posterior two thirds thereof.

25. The delivery device of claim 1, wherein the powdered substance contains substantially active substance and no introduced excipients, and in particular adjuvants.

26. The delivery device of claim 1, wherein the powdered substance has a pH of between about 4.5 and about 5.3, optionally about 4.8.

27. The delivery device of claim 1, wherein the powdered substance has a particle size distribution of 10% less than about 20 μ

m, 50% less than about 50 μ

m and 90% less than about 150 μ

m, optionally 10% less than about 10 μ

m, 50% less than about 30 μ

m and 90% less than about 90 μ

m.

28. The delivery device of claim 1, wherein the powdered substance has an untapped bulk density of between about 0.3 g/ml and about 0.5 g/ml, optionally about 0.4 g/ml.

29. The delivery device of claim 1, wherein the powdered substance has a tapped bulk density of between about 0.5 g/ml and about 0.75 g/ml, optionally about 0.63 g/ml.

4. (canceled)

5. (canceled)

9. (canceled)

13. (canceled)

16. (canceled)

17. (canceled)

18. (canceled)

19. (canceled)

21. (canceled)

22. (canceled)

23. (canceled)

24. (canceled)

30. A method of delivering a powdered substance to the posterior region of a nasal cavity of a subject, the method comprising the steps of:

fitting a nosepiece to a nasal cavity of a subject; and

delivering a powdered substance through the nosepiece to the posterior region of the nasal cavity of the subject.

31. The method of claim 30, wherein the powdered substance is delivered from a container chamber which houses a container which contains a powdered substance to be delivered to the nasal cavity of the subject, and the container chamber includes an outlet which is in fluid communication with the nosepiece such as to provide for delivery of the powdered substance from the container chamber to the nosepiece.

32. The method of claim 31, wherein the container comprises a capsule, optionally formed from a cellulose derivative, hydroxypropyl methylcellulose (HPMC) or a gelatine derivative.

35. The method of claim 32, wherein the capsule is coated with a hydrophobic material, optionally parylene.

36. The method of claim 30, wherein the nosepiece is configured, when inserted into the nasal cavity, to extend into the nasal valve and provide for expansion thereof.

37. The method of claim 30, wherein the nosepiece is configured such as to obstruct the nasal valve, optionally to close the nasal valve and thereby substantially prevent deposition of substance anteriorly of the same.

39. The method of claim 30, further comprising the step of:

closing the oropharyngeal velum of the subject.

40. The method of claim 39, further comprising the step of:

the subject exhaling through a mouthpiece to cause closure of the oropharyngeal velum of the subject.

41. The method of claim 40, wherein the mouthpiece is fluidly connected to the nosepiece, whereby exhaled air from an exhalation breath is delivered through the nosepiece.

42. The method of claim 41, wherein the powdered substance is delivered from a container chamber which houses a container which contains a powdered substance to be delivered to the nasal cavity of the subject, and the container chamber includes an inlet which is fluidly connected to the mouthpiece and an outlet which is fluidly connected to the nosepiece, such that exhaled air from an exhalation breath acts to entrain powdered substance as contained by the container and deliver the same through the nosepiece, optionally the container chamber includes a flow passage in which the container is disposed, such as to be rotatable therewithin when an air flow is delivered therethrough.

44. The method of claim 30, further comprising the step of:

delivering a gas flow, separate to an exhaled air flow from an exhalation breath of the subject, to the nosepiece.

45. The method of claim 30, wherein at least 55%, optionally at least 60%, optionally at least 65%, optionally at least 70%, optionally at least 80%, of the dose as initially deposited in the nasal cavity is deposited in the region posterior of the nasal valve.

50. The method of claim 30, wherein at least 35%, optionally at least 40%, optionally at least 45%, optionally at least 50%, optionally at least 55%, of the dose as initially deposited in the nasal cavity is deposited in the upper posterior two thirds thereof.

55. The method of claim 30, wherein the powdered substance contains substantially active substance and no introduced excipients, and in particular adjuvants.

56. The method of claim 30, wherein the powdered substance has a pH of between about 4.5 and about 5.3, optionally about 4.8.

57. The method of claim 30, wherein the powdered substance has a particle size distribution of 10% less than about 20 μ

m, 50% less than about 50 μ

m and 90% less than about 150 μ

m, optionally 10% less than about 10 μ

m, 50% less than about 30 μ

m and 90% less than about 90 μ

m.

58. The method of claim 30, wherein the powdered substance has an untapped bulk density of between about 0.3 g/ml and about 0.5 g/ml, optionally about 0.4 g/ml.

59. The method of claim 30, wherein the powdered substance has a tapped bulk density of between about 0.5 g/ml and about 0.75 g/ml, optionally about 0.63 g/ml.

60. The method of claim 30, wherein the time maximum plasma concentration T_max is less than about 25 minutes.

61. The method of claim 60, wherein the time maximum plasma concentration T_max is less than about 20 minutes.

62. The method of claim 30, wherein the peak plasma concentration C_max for the active substance is at least 10 ngml⁻

1 for a 10 mg dose of the active substance.

63. The method of claim 30, wherein the peak plasma concentration C_max for the active substance is at least 15 ngml⁻

1 for a 20 mg dose of the active substance.

64. The method of claim 30, wherein the ratio of the nasal absorption fraction to total bio-availability (BA) is greater than about 1, optionally greater than about 1.5, optionally greater than about 2.

67. The method of claim 30, wherein the powdered substance comprises a triptan.

68. The method of claim 67, wherein the powdered substance comprises sumatriptan.

69. The method of claim 67, wherein the powdered substance comprises one or more of risatriptan, naratriptan, eletriptan, frovatriptan and zolmitriptan.

70. The method of claim 30, wherein the powdered substance comprises an analgesic, optionally an opioid, an ergotamine, such as one or more of dihydroergotamine mesylate, ergonovine maleate and ergotamine tartarate with caffeine, or one or more of fentanyl, oxycondone, hydromorphone, morphine, codeine, ketobbemidone and cocaine.

74. The method of claim 30, wherein the powdered substance comprises a benzodiazepine, such as midazolam.

75. The method of claim 30, wherein the powdered substance comprises a non-steroidal anti-inflammatory drug (NSAID), such as one or more of aspirin, ibuprofen, naproxen, indomethacin, diclofenac and ketoprofen.

76. The method of claim 30, wherein the powdered substance comprises a peptide or protein, optionally a peptide or protein having a molecular weight greater than about 1000.

78. The method of claim 76, wherein the powdered substance comprises one or more of insulin, including its analogues and derivatives, desmopressin and calcitonin.

79. The method of claim 30, wherein the powdered substance comprises one or more of a vaccine, an immunomodulator and an immunostimulator.

80. The method of claim 30, in the treatment of pain.

81. The method of claim 80, in the treatment of headaches.

82. The method of claim 81, in the treatment of cluster headaches.

83. The method of claim 81, in the treatment of migraine.

84. The method of claim 80, in the treatment of neuropathic pain.

85. The method of claim 30, in inducing sedation.

86. The method of claim 30, in the treatment of a partial or full epilepsy seizure.

87. The method of claim 30, in the treatment of a panic disorder.

88. The method of claim 30, in the treatment of insomnia.

89. The method of claim 30, in the treatment of jet-lag.

90. The method of claim 30, in regulating blood glucose levels.

91. The method of claim 30, in influencing satiety or the sense of satiety.

92. The method of claim 30, in delivering a memory-enhancing agent prior to a learning episode.

33. (canceled)

34. (canceled)

38. (canceled)

43. (canceled)

46. (canceled)

47. (canceled)

48. (canceled)

49. (canceled)

51. (canceled)

52. (canceled)

53. (canceled)

54. (canceled)

65. (canceled)

66. (canceled)

71. (canceled)

72. (canceled)

73. (canceled)

77. (canceled)