DELIVERY DEVICE AND METHOD

• US 20100057047A1
• Filed: 02/14/2007
• Published: 03/04/2010
• Est. Priority Date: 02/14/2006
• Status: Active Application

• Current Assignee: OptiNose, Inc.
• Original Assignee: OptiNose AS (OptiNose, Inc.)
• Inventors: Djupesland, Per Gisle, Hafner, Roderick Peter, Sheldrake, Colin David
• Application Number:
  US12/279,285
• Publication Number:
  US 20100057047A1
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61M 11/00 Sprayers or atomisers specially adapted for therapeutic purposes in general B05B; aerosol containers B65D83/14
• CPC Class Codes: A61M 15/0021 Mouthpieces therefor
• CPC Class Codes: A61M 15/009 using medicine packages with incorporated spraying means, e.g. aerosol cans pocket atomiser of the injector type A61M11/08
• CPC Class Codes: A61M 15/0091 mechanically breath-triggered
• 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 2210/0681 Sinus (maxillaris)
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system

Abstract

A nasal delivery device for and method of delivering substance to the middle meatus in a nasal cavity of a subject in the treatment of a condition, in particular an inflammatory or infectious condition, thereof, the delivery device comprising: a nosepiece unit (17) including a nosepiece (20) for fitting to a nostril of a subject and a nozzle (25) through which substance is in use delivered to the respective nasal cavity; and a delivery unit (29) for delivering substance through the nozzle of the nosepiece; wherein the delivery device is configured to provide for deposition of a significant fraction of the delivered dose on, around and in the vicinity of the middle meatus.

Claims

1. A nasal delivery device for delivering substance to the middle meatus in a nasal cavity of a subject in the treatment of a condition, in particular an inflammatory or infectious condition, thereof, preferably rhinosinusitis and/or nasal polyps, the delivery device comprising:

a nosepiece unit including a nosepiece for fitting to a nostril of a subject and a nozzle through which substance is in use delivered to the respective nasal cavity; and

a delivery unit for delivering substance through the nozzle of the nosepiece;

wherein the delivery device is configured such that at least 50% of the dose as initially deposited in the nasal airway is deposited in a region of the nasal cavity which is posterior of the nasal valve and at least 30% of the dose as initially deposited in the nasal cavity is deposited in an upper posterior region of the nasal cavity which is posterior of the nasal valve and above the inferior meatus.

2. 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.

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

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

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

6. The delivery device of claim 5, further comprising:

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

or

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.

8. The delivery device of claim 1, wherein the nozzle provides for the delivery of a single jet or a plurality of jets, wherein the one or more jets comprise a liquid jet or a powder jet.

12. The delivery device of claim 1, wherein the nozzle provides for the delivery of an aerosol spray, wherein the aerosol spray comprises a liquid spray or a powder spray.

15. The delivery device of claim 12, wherein the nozzle provides for the delivery of an aerosol spray having a cone angle of not more than about 50 degrees, preferably not more than about 40 degrees, preferably not more than about 35 degrees, preferably not more than about 30 degrees, preferably not more than about 25 degrees, preferably not more than about 20 degrees, and preferably not more than about 15 degrees.

22. The delivery device of claim 1, wherein the delivery unit is manually actuatable.

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

an actuation mechanism for actuating the delivery unit in response to oral exhalation by the subject, and preferably the actuation mechanism is configured such as to be actuated in response to generation of a predeterminable pressure in the nasal cavity.

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

an actuation mechanism for actuating the delivery unit in response to nasal exhalation by the subject, and preferably the actuation mechanism is configured such as to be actuated in response to generation of a predeterminable pressure in the nasal cavity.

26. The delivery device of claim 1, wherein the delivery device is configured such that at least 55% of the dose as initially deposited in the nasal cavity is deposited in the region posterior of the nasal valve.

27. The delivery device of claim 26, wherein the delivery device is configured such that at least 60% of the dose as initially deposited in the nasal cavity is deposited in the region posterior of the nasal valve.

28. The delivery device of claim 27, wherein the delivery device is configured such that at least 65% of the dose as initially deposited in the nasal cavity is deposited in the region posterior of the nasal valve.

29. The delivery device of claim 28, wherein the delivery device is configured such that at least 70% of the dose as initially deposited in the nasal cavity is deposited in the region posterior of the nasal valve.

30. The delivery device of claim 1, wherein the delivery device is configured such that at least 35% of the dose as initially deposited in the nasal cavity is deposited in the upper posterior region thereof.

31. The delivery device of claim 30, wherein the delivery device is configured such that at least 40% of the dose as initially deposited in the nasal cavity is deposited in the upper posterior region thereof.

32. The delivery device of claim 31, wherein the delivery device is configured such that at least 45% of the dose as initially deposited in the nasal cavity is deposited in the upper posterior region thereof.

33. The delivery device of claim 32, wherein the delivery device is configured such that at least 50% of the dose as initially deposited in the nasal cavity is deposited in the upper posterior region thereof.

41. The delivery device of claim 1, where containing substance, preferably the substance comprises a steroid, such as fluticasone, budesonide, mometasone, betamethasone, beclomethasone, triamcinolone and flunisoloide, and the pharmaceutically-acceptable salts and derivatives thereof, a decongestant, such as ephedrine, pseudoephedrine, oxymetazoline, xylometazoline, phenylephrine and phenylpropanolamine, and the pharmaceutically-acceptable salts and derivatives thereof, a non-steroidal anti-inflammatory, such as sodium cromoglycate, nedocromil sodium, ibuprofen, salicylates, indomethacin, dexketoprofen, ketoprofen, fenbufen, naproxen and diclofenac, and the pharmaceutically-acceptable salts and derivatives thereof, an anti-cholinergic, such as ipratropium, tiotropium and oxitropium, and the pharmaceutically-acceptable salts and derivatives thereof, an anti-histamine, such as azelastine, loratidine, brompheniramine, chlorpheniramine, mizolastine, promethazine, doxylamine, desloratidine, triprolidine, clemastine, fexofenadine, cetirizine and levocetirizine, and the pharmaceutically-acceptable salts and derivatives thereof, a mast cell stabilizer, such as ketotifen, and the pharmaceutically-acceptable salts and derivatives thereof, a leukotriene antagonist, such as zafirlukast and montelukast, and the pharmaceutically-acceptable salts and derivatives thereof, a diuretic, such as frusemide, and the pharmaceutically-acceptable salts and derivatives thereof, an anti-biotic, such as amikacin, azithromycin, aztreonan, cefazolin, cefepine, cefonicid, cefaperazone, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cerfuroxime, cephapirin, ciprofloxacin, clindamycin, doxycycline, erthyromycin lactobionate, gentamicin, kanamycin, linezolid, mezlocillin, mupirocin, nafcillin, netilmicin, neomycin, oxacillin, paromomycin, piperacillin, streptomycin, ticarcillin, tobramycin and vancomycin, and the pharmaceutically-acceptable salts and derivatives thereof, an anti-fungal, such as polyene macrolides, tetraene macrolides, pentaenic macrolides, fluorinated pryimidines, imidazoles, triazoles, azoles, halogenated phenolic ethers, thiocarbamates, allylamines, sterol inhibitor, amphotericin B, ketoconazole, itraconazole, saperconazole, voriconazole, flucytosine, miconazole, fluconazole, griseofulvin, clotrimazole, econazole, terconazole, butoconazole, oxiconazole, sulconazole, ciclopirox olamine, haloprogin, tolnaftate, naftifine, terbinafine hydrochloride, morpholines, nystatin, natamycin, butenafine, undecylenic acid, Whitefield'"'"'s ointment, propionic acid, caprylic acid, and the pharmaceutically-acceptable salts and derivatives thereof, an immuno-modulator, wherein the immuno-modulator comprises an antigen, such as an allergen, in particular a polypeptide antigen or any part of an antigen, where natural or synthesized, or a nucleic acid molecule or polypeptide for modulation or suppression of the immune response or one or more steps in the immune cascade or process, an ionic transport control substance which acts to normalize or counteract an imbalance in the ionic transport across the cell membranes, such as benzalkonium chloride, or a biofilm-destroying agent for destroying bacterial biofilms, wherein the biofilm-destroying agent comprises an anti-biotic, such as tetracycline, linezolid and moxifloxacin, and the pharmaceutically-acceptable salts and derivatives thereof, a disinfectant, such as chlorohexidine, and the pharmaceutically-acceptable salts and derivatives thereof or is included as a preservative, such as benzalkonium chloride, within the substance formulation.

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

a further nosepiece unit including a nosepiece for fitting to the other nostril of the subject and a nozzle through which substance is in use delivered to the respective nasal cavity.

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63. A nasal delivery device for delivering substance to the middle meatus in a nasal cavity of a subject in the treatment of a condition, in particular an inflammatory or infectious condition, thereof, preferably rhinosinusitis and/or nasal polyps, the delivery device comprising:

a nosepiece unit including a nosepiece for fitting to a nostril of a subject and a nozzle through which substance is in use delivered to the respective nasal cavity; and

a delivery unit for delivering substance through the nozzle of the nosepiece;

wherein the nozzle provides for delivery of the substance as at least one liquid jet or an aerosol spray having a cone angle of not more than about 50 degrees.

64. The delivery device of claim 63, wherein the nosepiece is configured, when inserted into the nasal cavity, to extend into the nasal valve and provide for expansion thereof.

65. The delivery device of claim 63, wherein the nosepiece is configured such as to obstruct the nasal valve, and preferably close the nasal valve, and thereby prevent deposition of substance anteriorly of the same.

67. The delivery device of claim 63, further comprising:

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

68. The delivery device of claim 67, further comprising:

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

or

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.

70. The delivery device of claim 63, wherein the nozzle provides for the delivery of a single jet or a plurality of jets, wherein the one or more jets comprise a liquid jet or a powder jet.

74. The delivery device of claim 63, wherein the nozzle provides for the delivery of an aerosol spray, wherein the aerosol spray comprises a liquid spray or a powder spray.

77. The delivery device of claim 74, wherein the nozzle provides for the delivery of an aerosol spray having a cone angle of not more than about 40 degrees.

78. The delivery device of claim 77, wherein the nozzle provides for the delivery of an aerosol spray having a cone angle of not more than about 35 degrees.

79. The delivery device of claim 78, wherein the nozzle provides for the delivery of an aerosol spray having a cone angle of not more than about 30 degrees.

80. The delivery device of claim 79, wherein the nozzle provides for the delivery of an aerosol spray having a cone angle of not more than about 25 degrees.

81. The delivery device of claim 80, wherein the nozzle provides for the delivery of an aerosol spray having a cone angle of not more than about 20 degrees.

82. The delivery device of claim 81, wherein the nozzle provides for the delivery of an aerosol spray having a cone angle of not more than about 15 degrees.

83. The delivery device of claim 63, wherein the delivery unit is manually actuatable.

84. The delivery device of claim 63, further comprising:

an actuation mechanism for actuating the delivery unit in response to oral exhalation by the subject, and preferably the actuation mechanism is configured such as to be actuated in response to generation of a predeterminable pressure in the nasal cavity.

85. The delivery device of claim 63, further comprising:

an actuation mechanism for actuating the delivery unit in response to nasal exhalation by the subject, and preferably the actuation mechanism is configured such as to be actuated in response to generation of a predeterminable pressure in the nasal cavity.

87. The delivery device of claim 63, wherein the delivery device is configured such that at least 50% of the dose as initially deposited in the nasal cavity is deposited in the region posterior of the nasal valve preferably at least 55%, preferably at least 60%, preferably at least 65%, and preferably at least 70%.

92. The delivery device of claim 63, wherein the delivery device is configured such that at least 30% of the dose as initially deposited in the nasal cavity is deposited in the upper posterior region thereof, preferably at least 35%, preferably at least 40%, preferably at least 45%, and preferably at least 50%.

104. The delivery device of claim 63, where containing substance, preferably the substance comprises a steroid, such as fluticasone, budesonide, mometasone, betamethasone, beclomethasone, triamcinolone and flunisoloide, and the pharmaceutically-acceptable salts and derivatives thereof, a decongestant, such as ephedrine, pseudoephedrine, oxymetazoline, xylometazoline, phenylephrine and phenylpropanolamine, and the pharmaceutically-acceptable salts and derivatives thereof, a non-steroidal anti-inflammatory, such as sodium cromoglycate, nedocromil sodium, ibuprofen, salicylates, indomethacin, dexketoprofen, ketoprofen, fenbufen, naproxen and diclofenac, and the pharmaceutically-acceptable salts and derivatives thereof, an anti-cholinergic, such as ipratropium, tiotropium and oxitropium, and the pharmaceutically-acceptable salts and derivatives thereof, an anti-histamine, such as azelastine, loratidine, brompheniramine, chlorpheniramine, mizolastine, promethazine, doxylamine, desloratidine, triprolidine, clemastine, fexofenadine, cetirizine and levocetirizine, and the pharmaceutically-acceptable salts and derivatives thereof, a mast cell stabilizer, such as ketotifen, and the pharmaceutically-acceptable salts and derivatives thereof, a leukotriene antagonist, such as zafirlukast and montelukast, and the pharmaceutically-acceptable salts and derivatives thereof, a diuretic, such as frusemide, and the pharmaceutically-acceptable salts and derivatives thereof, an anti-biotic, such as amikacin, azithromycin, aztreonan, cefazolin, cefepine, cefonicid, cefaperazone, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cerfuroxime, cephapirin, ciprofloxacin, clindamycin, doxycycline, erthyromycin lactobionate, gentamicin, kanamycin, linezolid, mezlocillin, mupirocin, nafcillin, netilmicin, neomycin, oxacillin, paromomycin, piperacillin, streptomycin, ticarcillin, tobramycin and vancomycin, and the pharmaceutically-acceptable salts and derivatives thereof, an anti-fungal, such as polyene macrolide, tetraene macrolide, pentaenic macrolide, fluorinated pryimidine, imidazole, azole, triazole, halogenated phenolic ether, thiocarbamate, allylamine, sterol inhibitor, amphotericin B, ketoconazole, itraconazole, saperconazole, voriconazole, flucytosine, miconazole, fluconazole, griseofulvin, clotrimazole, econazole, terconazole, butoconazole, oxiconazole, sulconazole, ciclopiroxolamine, halprogin, tolnaftate, naftifine, terbinafine hydrochloride, morpholines, nystatin, natamycin, butenafine, undecylenic acid, Whitefield'"'"'s ointment, propionic acid, caprylic acid, and the pharmaceutically-acceptable salts and derivatives thereof, an immuno-modulator, wherein the immuno-modulator comprises an antigen, such as an allergen, in particular a polypeptide antigen or any part of an antigen, where natural or synthesized, or a nucleic acid molecule or polypeptide for modulation or suppression of the immune response or one or more steps in the immune cascade or process, an ionic transport control substance which acts to normalize or counteract an imbalance in the ionic transport across the cell membranes, such as benzalkonium chloride, or a biofilm-destroying agent for destroying bacterial biofilms, wherein the biofilm-destroying agent comprises an anti-biotic, such as tetracycline, linezolid and moxifloxacin, and the pharmaceutically-acceptable salts and derivatives thereof, a disinfectant, such as chlorohexidine, and the pharmaceutically-acceptable salts and derivatives thereof or is included as a preservative, such as benzalkonium chloride, within the substance formulation.

125. The delivery device of claim 63, further comprising:

a further nosepiece unit including a nosepiece for fitting to the other nostril of the subject and a nozzle through which substance is in use delivered to the respective nasal cavity.

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127. A method of delivering substance to the middle meatus in a nasal cavity of a subject in the treatment of a condition, in particular an inflammatory or infectious condition, thereof, the method comprising the steps of:

fitting a nosepiece unit to one nostril of a subject, the nosepiece unit including a nosepiece which is inserted into the one nostril of a subject and a nozzle through which substance is delivered to the respective nasal cavity; and

delivering substance through the nozzle into the nasal cavity, wherein at least 50% of the dose as initially deposited in the nasal airway is deposited in a region of the nasal cavity which is posterior of the nasal valve and at least 30% of the dose as initially deposited in the nasal cavity is deposited in an upper posterior region of the nasal cavity which is posterior of the nasal valve and above the inferior meatus.

128. The method of claim 127, further comprising the step of:

expanding the nasal valve, and preferably the nosepiece is configured to extend into the nasal valve and provide for expansion thereof.

130. The method of claim 127, wherein the nosepiece is configured such as to obstruct the nasal valve, and preferably close the nasal valve, and thereby prevent deposition of substance anteriorly of the same.

132. The method of claim 127, further comprising the step of:

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

133. The method of claim 132, wherein the nosepiece is fluidly connected to the mouthpiece unit, such that exhaled air from an exhalation breath is delivered through the nosepiece.

134. The method of claim 127, further comprising the step of:

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

135. The method of claim 127, wherein the nozzle provides for the delivery of a single jet or a plurality of jets, wherein the one or more jets comprise a liquid jet or a powder jet.

139. The method of claim 127, wherein the nozzle provides for the delivery of an aerosol spray wherein the aerosol spray comprises a liquid spray or a powder spray.

142. The method of claim 127, wherein the nozzle provides for the delivery of an aerosol spray having a cone angle of not more than about 50 degrees, preferably not more than about 40 degrees, preferably not more than about 35 degrees, preferably not more than about 30 degrees, preferably not more than about 25 degrees, preferably not more than about 20 degrees, and preferably not more than about 15 degrees.

149. The method of claim 127, further comprising the step of:

manually actuating the delivery unit.

150. The method of claim 127, further comprising the step of:

actuating the delivery unit in response to oral exhalation by the subject, and preferably actuation is in response to the generation of a predeterminable pressure in the nasal cavity.

151. The method of claim 127, further comprising the step of:

actuating the delivery unit in response to nasal exhalation by the subject, and preferably actuation is in response to the generation of a predeterminable pressure in the nasal cavity.

153. The method of claim 127, wherein at least 55% of the dose as initially deposited in the nasal cavity is deposited in the region posterior of the nasal valve.

154. The method of claim 153, wherein at least 60% of the dose as initially deposited in the nasal cavity is deposited in the region posterior of the nasal valve.

155. The method of claim 154, wherein at least 65% of the dose as initially deposited in the nasal cavity is deposited in the region posterior of the nasal valve.

156. The method of claim 155, wherein at least 70% of the dose as initially deposited in the nasal cavity is deposited in the region posterior of the nasal valve.

157. The method of claim 127, wherein at least 35% of the dose as initially deposited in the nasal cavity is deposited in the upper posterior region thereof.

158. The method of claim 157, wherein at least 40% of the dose as initially deposited in the nasal cavity is deposited in the upper posterior region thereof.

159. The method of claim 158, wherein at least 45% of the dose as initially deposited in the nasal cavity is deposited in the upper posterior region thereof.

160. The method of claim 159, wherein at least 50% of the dose as initially deposited in the nasal cavity is deposited in the upper posterior region thereof.

188. The method of claim 127, further comprising the step of:

fitting a further nosepiece unit to the other nostril of the subject, the nosepiece unit including a nosepiece for insertion into the other nostril of a subject and a nozzle through which substance is delivered to the respective nasal cavity.

224. The method of claim 127 or 189, in the treatment of rhinosinusitis.

225. The method of claim 224, in the treatment of acute rhinosinusitis.

226. The method of claim 224, in the treatment of chronic rhinosinusitis.

227. The method of claim 127 or 189, in the treatment of nasal polyps.

228. The method of claim 127 or 189, in the treatment of sinus pains.

229. The method of claim 127 or 189, in the treatment of auto-immune diseases, including viral, bacterial, allergic and non-allergic diseases, such as antigen-induced diseases.

230. The method of claim 127 or 189, in the treatment of the common cold.

231. The method of claim 127 or 189, wherein the substance comprises a steroid, such as fluticasone, budesonide, mometasone, betamethasone, beclomethasone, triamcinolone and flunisoloide, and the pharmaceutically-acceptable salts and derivatives thereof.

232. The method of claim 127 or 189, wherein the substance comprises a decongestant, such as ephedrine, pseudoephedrine, oxymetazoline, xylometazoline, phenylephrine and phenylpropanolamine, and the pharmaceutically-acceptable salts and derivatives thereof.

233. The method of claim 127 or 189, wherein the substance comprises a non-steroidal anti-inflammatory, such as sodium cromoglycate, nedocromil sodium, ibuprofen, salicylates, indomethacin, dexketoprofen, ketoprofen, fenbufen, naproxen and diclofenac, and the pharmaceutically-acceptable salts and derivatives thereof.

234. The method of claim 127 or 189, wherein the substance comprises an anti-cholinergic, such as ipratropium, tiotropium and oxitropium, and the pharmaceutically-acceptable salts and derivatives thereof.

235. The method of claim 127 or 189, wherein the substance comprises an anti-histamine, such as azelastine, loratidine, brompheniramine, chlorpheniramine, mizolastine, promethazine, doxylamine, desloratidine, triprolidine, clemastine, fexofenadine, cetirizine and levocetirizine, and the pharmaceutically-acceptable salts and derivatives thereof.

236. The method of claim 127 or 189, wherein the substance comprises a mast cell stabilizer, such as ketotifen, and the pharmaceutically-acceptable salts and derivatives thereof.

237. The method of claim 127 or 189, wherein the substance comprises a leukotriene antagonist, such as zafirlukast and montelukast, and the pharmaceutically-acceptable salts and derivatives thereof.

238. The method of claim 127 or 189, wherein the substance comprises a diuretic, such as frusemide, and the pharmaceutically-acceptable salts and derivatives thereof.

239. The method of claim 127 or 189, wherein the substance comprises an anti-biotic, such as amikacin, azithromycin, aztreonan, cefazolin, cefepine, cefonicid, cefaperazone, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cerfuroxime, cephapirin, ciprofloxacin, clindamycin, doxycycline, erthyromycin lactobionate, gentamicin, kanamycin, linezolid, mezlocillin, mupirocin, nafcillin, netilmicin, neomycin, oxacillin, paromomycin, piperacillin, streptomycin, ticarcillin, tobramycin and vancomycin, and the pharmaceutically-acceptable salts and derivatives thereof.

240. The method of claim 127 or 189, wherein the substance comprises an anti-fungal, such as polyene macrolide, tetraene macrolide, pentaenic macrolide, fluorinated pryimidine, imidazole, azole, triazole, halogenated phenolic ether, thiocarbamate, allylamine, sterol inhibitor, amphotericin B, ketoconazole, itraconazole, saperconazole, voriconazole, flucytosine, miconazole, fluconazole, griseofulvin, clotrimazole, econazole, terconazole, butoconazole, oxiconazole, sulconazole, ciclopiroxolamine, halprogin, tolnaftate, naftifine, terbinafine hydrochloride, morpholines, nystatin, natamycin, butenafine, undecylenic acid, Whitefield'"'"'s ointment, propionic acid, caprylic acid, and the pharmaceutically-acceptable salts and derivatives thereof.

241. The method of claim 127 or 189, wherein the substance comprises an immuno-modulator.

242. The method of claim 241, wherein the immuno-modulator comprises an antigen, such as an allergen, in particular a polypeptide antigen or any part of an antigen, where natural or synthesized.

243. The method of claim 241, wherein the immuno-modulator comprises a nucleic acid molecule or polypeptide for modulation or suppression of the immune response or one or more steps in the immune cascade or process.

244. The method of claim 127 or 189, wherein the substance comprises an ionic transport control substance which acts to normalize or counteract an imbalance in the ionic transport across the cell membranes, such as benzalkonium chloride.

245. The method of claim 127 or 189, wherein the substance comprises a biofilm-destroying agent for destroying bacterial biofilms.

246. The method of claim 245, wherein the biofilm-destroying agent comprises an anti-biotic, such as tetracycline, linezolid and moxifloxacin, and the pharmaceutically-acceptable salts and derivatives thereof.

247. The method of claim 245, wherein the biofilm-destroying agent comprises a disinfectant, such as chlorohexidine, and the pharmaceutically-acceptable salts and derivatives thereof.

248. The method of claim 245, wherein the biofilm-destroying agent is included as a preservative, such as benzalkonium chloride, within the substance formulation.

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184. (canceled)

185. (canceled)

186. (canceled)

187. (canceled)

189. A method of delivering substance to the middle meatus in a nasal cavity of a subject in the treatment of a condition, in particular an inflammatory or infectious condition, thereof, the method comprising the steps of:

fitting a nosepiece unit to one nostril of a subject, the nosepiece unit including a nosepiece which is inserted into the one nostril of a subject and a nozzle through which substance is delivered to the respective nasal cavity; and

delivering substance through the nozzle into the nasal cavity, wherein the nozzle provides for delivery of the substance as at least one liquid jet or an aerosol spray having a cone angle of not more than about 50 degrees.

190. The method of claim 189, further comprising the step of:

expanding the nasal valve, and preferably the nosepiece is configured to extend into the nasal valve and provide for expansion thereof.

192. The method of claim 189, wherein the nosepiece is configured such as to obstruct the nasal valve, and preferably close the nasal valve, and thereby prevent deposition of substance anteriorly of the same.

194. The method of claim 189, further comprising the step of:

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

195. The method of claim 194, wherein the nosepiece is fluidly connected to the mouthpiece unit, such that exhaled air from an exhalation breath is delivered through the nosepiece.

196. The method of claim 189, further comprising the step of:

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

197. The method of claim 189, wherein the nozzle provides for the delivery of a single jet or a plurality of jets, wherein the one or more jets comprise a liquid jet or a powder jet.

201. The method of claim 189, wherein the nozzle provides for the delivery of an aerosol spray, wherein the aerosol spray comprises a liquid spray or a powder spray.

204. The method of claim 189, wherein the nozzle provides for the delivery of an aerosol spray having a cone angle of not more than about 40 degrees.

205. The method of claim 204, wherein the nozzle provides for the delivery of an aerosol spray having a cone angle of not more than about 35 degrees.

206. The method of claim 205, wherein the nozzle provides for the delivery of an aerosol spray having a cone angle of not more than about 30 degrees.

207. The method of claim 206, wherein the nozzle provides for the delivery of an aerosol spray having a cone angle of not more than about 25 degrees.

208. The method of claim 207, wherein the nozzle provides for the delivery of an aerosol spray having a cone angle of not more than about 20 degrees.

209. The method of claim 208, wherein the nozzle provides for the delivery of an aerosol spray having a cone angle of not more than about 15 degrees.

210. The method of claim 189, further comprising the step of:

manually actuating the delivery unit.

211. The method of claim 189, further comprising the step of:

actuating the delivery unit in response to oral exhalation by the subject, and preferably actuation is in response to the generation of a predeterminable pressure in the nasal cavity.

212. The method of claim 189, further comprising the step of:

actuating the delivery unit in response to nasal exhalation by the subject, and preferably actuation is in response to the generation of a predeterminable pressure in the nasal cavity.

214. The method of claim 189, wherein at least 50% of the dose as initially deposited in the nasal cavity is deposited in the region posterior of the nasal valve, preferably at least 55%, preferably at least 60%, preferably at least 65%, and preferably at least 70%.

219. The method of claim 189, wherein at least 30% of the dose as initially deposited in the nasal cavity is deposited in the upper posterior region thereof, preferably at least 35%, preferably at least 40%, preferably at least 45%, and preferably at least 50%.

251. The method of claim 189, further comprising the step of:

fitting a further nosepiece unit to the other nostril of the subject, the nosepiece unit including a nosepiece for insertion into the other nostril of a subject and a nozzle through which substance is delivered to the respective nasal cavity.

191. (canceled)

193. (canceled)

198. (canceled)

199. (canceled)

200. (canceled)

202. (canceled)

203. (canceled)

213. (canceled)

215. (canceled)

216. (canceled)

217. (canceled)

218. (canceled)

220. (canceled)

221. (canceled)

222. (canceled)

223. (canceled)

249. (canceled)

250. (canceled)

252. (canceled)