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US-12616806-B2 - Nasal administration

US12616806B2US 12616806 B2US12616806 B2US 12616806B2US-12616806-B2

Abstract

A method of delivering a substance, such as one or more of a triptan, a nasal steroid or carbon dioxide gas, to the nasal cavity of a subject, in particular for the treatment of headaches, for example, migraine, or rhinosinusitis, for example, chronic rhinosinusitis, optionally with polyps, the method comprising the steps of fitting a nosepiece to one nostril of the subject, delivering the substance through the nosepiece to the posterior region of the nasal cavity of the subject.

Inventors

  • Per Gisle Djupesland
  • Ramy A. Mahmoud
  • John Messina

Assignees

  • OptiNose Inc.

Dates

Publication Date
20260505
Application Date
20221212

Claims (20)

  1. 1 . A method of treating chronic rhinosinusitis with nasal polyps in a patient comprising: placing a nosepiece of a housing into a first nostril of the patient; placing a mouthpiece of the housing into a mouth of the patient, the mouthpiece being fluidly connected to the nosepiece by a flow path, wherein exhalation by the patient into the mouthpiece and out of the nosepiece produces a bi-directional fluid flow of exhalation air into a first nasal passageway of the patient and out of a second nasal passageway of the patient; manually depressing a chamber with the patient's thumb or finger to activate a pump and flow fluticasone propionate from the chamber to the nosepiece; opening a valve in the flow path from the mouthpiece to the nosepiece in response to manually depressing the chamber; administering fluticasone propionate as a liquid aerosol during exhalation by the patient through the nosepiece; delivering carbon dioxide during exhalation by the patient through the nosepiece, to a location at an upper posterior region of the first nasal passageway of the patient; and reducing a pH at the location at the upper posterior region of the first nasal passageway of the patient by an amount ranging from about 0.1 pH units to about 0.2 pH units by controlling the fluid flow to deliver the carbon dioxide at a concentration of from about 5% vol/vol to about 6% vol/vol carbon dioxide and at a fluid flow rate of at least 20 L/min for a duration of from about 2 seconds to about 3 seconds, wherein the carbon dioxide is delivered before or at the same time as the fluticasone propionate.
  2. 2 . The method of claim 1 , wherein the fluticasone propionate is administered in an amount of about 400 μg b.i.d.
  3. 3 . The method of claim 1 , wherein the fluticasone propionate is administered in an amount of about 200 μg b.i.d.
  4. 4 . The method of claim 1 , wherein the fluticasone propionate is administered in an amount of 100 to 400 μg b.i.d.
  5. 5 . The method of claim 1 , wherein the fluid flow is delivered as a burst of air on opening of the valve.
  6. 6 . The method of claim 1 , wherein the chamber, pump and nosepiece are axially aligned.
  7. 7 . The method of claim 1 , further comprising flowing the fluticasone propionate through a nozzle proximate the nosepiece during exhalation by the patient.
  8. 8 . The method of claim 1 , wherein the administering of the fluticasone propionate further comprises simultaneously delivering the fluticasone propionate and exhalation air to the first nasal passageway.
  9. 9 . The method of claim 1 , wherein the manually depressing of the chamber further comprises axially moving the chamber within an aperture in the housing.
  10. 10 . The method of claim 1 , further comprising flowing the exhalation air through a delivery channel of the flow path that extends from the valve towards the nosepiece.
  11. 11 . The method of claim 10 , wherein the delivery channel inwardly tapers as the delivery channel extends from the valve towards the nosepiece.
  12. 12 . The method of claim 5 , further comprising flowing the exhalation air through a delivery channel of the flow path that extends from the valve towards the nosepiece.
  13. 13 . The method of claim 12 , wherein the delivery channel inwardly tapers as the delivery channel extends from the valve towards the nosepiece.
  14. 14 . The method of claim 6 , wherein the manually depressing of the chamber further comprises axially moving the chamber within an aperture in the housing.
  15. 15 . The method of claim 12 , further comprising flowing the fluticasone propionate through a nozzle proximate the nosepiece during exhalation by the patient, wherein the administering of the fluticasone propionate further comprises simultaneously delivering the fluticasone propionate and exhalation air to the first nasal passageway.
  16. 16 . The method of claim 12 , wherein the fluticasone propionate is administered in an amount of about 400 μg b.i.d.
  17. 17 . The method of claim 12 , wherein the fluticasone propionate is administered in an amount of about 200 μg b.i.d.
  18. 18 . The method of claim 12 , wherein the fluticasone propionate is administered in an amount of 100 to 400 μg b.i.d.
  19. 19 . The method of claim 14 , wherein the fluticasone propionate is administered in an amount of about 400 μg b.i.d.
  20. 20 . The method of claim 14 , wherein the fluticasone propionate is administered in an amount of about 200 μg b.i.d.

Description

This application is a continuation of U.S. application Ser. No. 14/315,132, filed Jun. 25, 2014, which is a continuation-in-part of U.S. application Ser. No. 14/226,287, filed Mar. 26, 2014, now abandoned, which claims the benefit of U.S. provisional application Ser. No. 61/805,400 filed Mar. 26, 2013, all of which are incorporated herein by reference in their entirety. FIELD OF THE DISCLOSURE The present disclosure, in one embodiment, relates to the nasal administration of substances, in particular drugs, and in particular substances which require a rapid onset of action, such as in the treatment of pain, including headaches, for example, cluster headaches and migraine, and neuropathic pain. The present disclosure also relates, in other embodiments, to nasal delivery of carbon dioxide gas, nasal removal of NO and/or nasal pH adjustment as a supplemental therapeutic treatment, which can, for example, provide for parasympathetic stimulation, such as for the treatment of pain. SUMMARY OF THE DISCLOSURE Referring to FIG. 1(a), the nasal airway 1 comprises the two nasal cavities separated by the nasal septum, which airway 1 includes numerous ostia, such as the paranasal sinus ostia 3 and the tubal ostia 5, and olfactory cells, and is lined by the nasal mucosa. The nasal airway 1 can communicate with the nasopharynx 7, the oral cavity 9 and the lower airway 11, with the nasal airway 1 being in selective communication with the anterior region of the nasopharynx 7 and the oral cavity 9 by opening and closing of the oropharyngeal velum 13. The velum 13, which is often referred to as the soft palate, is illustrated in solid line in the closed position, as achieved by providing a certain positive pressure in the oral cavity 9, such as achieved by balancing pressures in the oral cavity 9 and the nasal airway 1 on exhalation through the oral cavity 9, and in dashed line in the open position. The present inventors have surprisingly identified that a rapid systemic uptake and a rapid response rate can be achieved, as compared, for example, to conventional delivery of an equivalent substance, by the delivery of substance and at least one gas to the posterior region of the nasal airway. The posterior region of the nasal airway is that region which is posterior of the nasal valve NV, as illustrated in FIG. 1(b). The nasal valve comprises the anterior bony cavum which contains inferior turbinate erectile tissue and septal erectile tissue, which are supported respectively by compliant ala tissue and the rigid cartilaginous septum (Cole, P (The Respiratory Role of the Upper Airways, a selective clinical and pathophysiological review. 1993, Mosby-Year Book Inc. ISBN1.55664-390-X)). These elements combine to form a dynamic valve, which extends over several millimeters, that adjusts nasal airflow, and is stabilized by cartilage and bone, modulated by voluntary muscle and regulated by erectile tissue. The lumen of the nasal valve is the section of narrowest cross-sectional area between the posterior and anterior regions of the nasal airway, and is much longer and narrower dorsally than ventrally, and this lumen defines a triangular entrance which extends to the piriform region of the bony cavum. The nasal valve is lined in its anterior part with transitional epithelium, with a gradual transition posterior to respiratory epithelium. The nasal valve and anterior vestibule define roughly the anterior one-third of the nose. The posterior region of the nasal airway is that region which is lined with respiratory epithelium, which is ciliated, and olfactory epithelium, which comprises nerves which extend downwards through the cribiform plate CP from the olfactory bulb, whereas the anterior region of the nasal airway is that region which is lined with squamous epithelium, which is not ciliated, and transitional epithelium. The olfactory epithelium extends on both the lateral and medial sides of the nasal airway, and typically extends downwards about 1.5 to 2.5 cm. The upper posterior region is the region above the inferior meatus IM, as illustrated in FIG. 1(b), and encompasses the middle turbinate, the sinus ostia in infundibulum (ostia to maxillary, frontal and ethmoidal sinuses), the olfactory region, and the upper branches of the trigeminal nerve, and is that region which includes veins which drain to the venous sinuses that surround the brain. As illustrated in FIG. 1(b), the posterior region of the nasal airway is the nasal region posterior of an imaginary vertical plane VERT1 which is located at a position corresponding to one-quarter of the distance between the anterior nasal spine AnS, which is a pointed projection at the anterior extremity of the intermaxillary suture, and the posterior nasal spine PnS, which is the sharp posterior extremity of the nasal crest of the hard palate and represents the transition between the nose and the nasopharynx, which corresponds to a distance posterior of the anterior nasal spine AnS of between