U.S. patent application number 14/961851 was filed with the patent office on 2016-03-24 for delivery device and method.
The applicant listed for this patent is OptiNose AS. Invention is credited to Per Gisle Djupesland, Roderick Peter Hafner, Colin David Sheldrake.
Application Number | 20160082207 14/961851 |
Document ID | / |
Family ID | 36141832 |
Filed Date | 2016-03-24 |
United States Patent
Application |
20160082207 |
Kind Code |
A1 |
Djupesland; Per Gisle ; et
al. |
March 24, 2016 |
Delivery Device and Method
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 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 to provide for deposition of a significant
fraction of the delivered dose on, around and in the vicinity of
the middle meatus.
Inventors: |
Djupesland; Per Gisle;
(Oslo, NO) ; Sheldrake; Colin David; (Swindon,
UK) ; Hafner; Roderick Peter; (Oxforshire,
UK) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
OptiNose AS |
Oslo |
|
NO |
|
|
Family ID: |
36141832 |
Appl. No.: |
14/961851 |
Filed: |
December 7, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12279285 |
Nov 13, 2009 |
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PCT/GB2007/000516 |
Feb 14, 2007 |
|
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14961851 |
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Current U.S.
Class: |
128/203.22 ;
128/203.12 |
Current CPC
Class: |
A61P 11/00 20180101;
A61M 15/0091 20130101; A61M 15/08 20130101; A61M 11/00 20130101;
A61M 2210/0681 20130101; A61M 15/009 20130101; A61M 15/0021
20140204; A61M 15/0098 20140204 |
International
Class: |
A61M 15/00 20060101
A61M015/00; A61M 11/00 20060101 A61M011/00; A61M 15/08 20060101
A61M015/08 |
Foreign Application Data
Date |
Code |
Application Number |
Feb 14, 2006 |
GB |
GB 0602980 |
Claims
1-252. (canceled)
253. A method of delivering fluticasone to the middle meatus in
one, first nasal cavity of a subject in the treatment of
rhinosinusitis, the method comprising: fitting a first nosepiece
unit to one, first nostril of a subject, wherein the first
nosepiece unit includes a nosepiece which is inserted into the
first nostril, and a nozzle through which fluticasone is delivered
to the first nasal cavity from a first substance supply unit;
providing a first mouthpiece unit which includes a mouthpiece,
wherein the mouthpiece of the first mouthpiece unit is fluidly
connected to the nosepiece of the first nosepiece unit; the subject
exhaling through the mouthpiece of the first mouthpiece unit so as
to cause closure of the oropharyngeal velum of the subject and
deliver an air flow through the first nostril, around the posterior
margin of the nasal septum and out of the other, second nostril of
the subject; and delivering, during exhalation through the
mouthpiece of the first mouthpiece unit, a liquid aerosol spray
comprising a dose of fluticasone from the first substance supply
unit through the nozzle of the first nosepiece unit into the first
nasal cavity; wherein at least 50% of the dose as initially
deposited in the nasal airway is deposited in a region of the first
nasal cavity which is posterior of the nasal valve and at least 30%
of the dose as initially deposited in the nasal airway is deposited
in an upper posterior region of the first nasal cavity which is
posterior of the nasal valve and above the inferior meatus.
254. The method claim 253, wherein inserting the nosepiece
obstructs the nasal valve so as to obstruct a nasal passage
anteriorly of the nasal valve.
255. The method of claim 253, wherein inserting the nosepiece
closes the nasal valve, preventing deposition of fluticasone
anteriorly of the nasal valve.
256. The method of claim 253, wherein the aerosol spray has a cone
angle of not more than 50 degrees.
257. The method of claim 253, wherein the aerosol spray has a cone
angle of not more than 40 degrees.
258. The method of claim 1253, further comprising: manually
actuating the substance supply unit to release the dose.
259. The method of claim 253, wherein at least 55% of the dose as
initially deposited in the nasal airway is deposited in the region
posterior of the nasal valve.
260. The method of claim 253, wherein at least 60% of the dose as
initially deposited in the nasal airway is deposited in the region
posterior of the nasal valve.
261. The method of claim 253, wherein at least 35% of the dose as
initially deposited in the nasal airway is deposited in the upper
posterior region thereof.
262. The method of claim 253, wherein at least 40% of the dose as
initially deposited in the nasal airway is deposited in the upper
posterior region thereof.
263. The method of claim 253, wherein at least 45% of the dose as
initially deposited in the nasal airway is deposited in the upper
posterior region thereof.
264. The method of claim 253, wherein at least 50% of the dose as
initially deposited in the nasal airway is deposited in the upper
posterior region thereof.
265. The method of claim 253, wherein the nosepiece is inserted
into the first nostril such that the nosepiece extends into the
nasal valve and provides for expansion of the nasal valve.
266. The method of claim 253, further comprising: fitting a second
nosepiece unit to the second nostril, wherein the second nosepiece
unit includes a nosepiece which is inserted into the second
nostril, and a nozzle through which fluticasone is delivered to the
second nasal cavity from a second substance supply unit; providing
a second mouthpiece unit which includes a mouthpiece, wherein the
mouthpiece of the second mouthpiece unit is fluidly connected to
the nosepiece of the second nosepiece unit; the subject exhaling
through the mouthpiece of the second mouthpiece unit so as to cause
closure of the oropharyngeal velum of the subject and deliver an
air flow through the second nostril, around the posterior margin of
the nasal septum and out of the first nostril; and delivering,
during exhalation though the mouthpiece of the second mouthpiece
unit, a liquid aerosol spray comprising a dose of fluticasone from
the second substance supply unit through the nozzle of the second
nosepiece unit into the second nasal cavity; wherein at least 50%
of the dose as initially deposited in the nasal airway is deposited
in a region of the second nasal cavity which is posterior of the
nasal valve and at least 30% of the dose as initially deposited in
the nasal airway is deposited in an upper posterior region of the
second nasal cavity which is posterior of the nasal valve and above
the inferior meatus.
267. The method of claim 266, wherein a single nosepiece unit is
used as the first and second nosepiece units, a single mouthpiece
unit is used as the first and second mouthpiece units, and a single
substance supply unit is used as the first and second substance
supply units.
268. The method of claim 267, wherein the single substance supply
unit comprises a multi-dose pump unit for delivery a plurality of
metered doses of fluticasone, each dose being delivered in response
to a single actuation of the multi-dose pump unit.
269. The method of claim 253, wherein the rhino sinusitis comprises
chronic rhinosinusitis.
270. A method of delivering fluticasone to the middle meatus of
each of first and second nasal cavities of a subject in the
treatment of rhinosinusitis, the method comprising: fitting a
nosepiece unit to one, first nostril of a subject, wherein the
nosepiece unit includes a nosepiece which is inserted into the
first nostril to extend into the nasal valve and expand the nasal
valve, and a nozzle through which fluticasone is delivered to the
first nasal cavity from a substance supply unit; providing a
mouthpiece unit which includes a mouthpiece, wherein the mouthpiece
is fluidly connected to the nosepiece; the subject exhaling through
the mouthpiece so as to cause closure of the oropharyngeal velum of
the subject and deliver an air flow through the first nostril,
around the posterior margin of the nasal septum and out of the
other, second nostril of the subject; and delivering, during
exhalation though the mouthpiece, a liquid aerosol spray comprising
a dose of fluticasone from the substance supply unit through the
nozzle into the first nasal cavity; wherein at least 50% of the
dose as initially deposited in the nasal airway is deposited in a
region of the first nasal cavity which is posterior of the nasal
valve and at least 30% of the dose as initially deposited in the
nasal airway is deposited in an upper posterior region of the first
nasal cavity which is posterior of the nasal valve and above the
inferior meatus; fitting the nosepiece unit to the second nostril,
wherein the nosepiece is inserted into the second nostril to extend
into the nasal valve and expand the nasal valve; the subject
exhaling through the mouthpiece so as to cause closure of the
oropharyngeal velum of the subject and deliver an air flow through
the second nostril, around the posterior margin of the nasal septum
and out of the first nostril; and delivering, during exhalation
through the mouthpiece, a liquid aerosol spray comprising a dose of
fluticasone from the substance supply unit through the nozzle into
the second nasal cavity; wherein at least 50% of the dose as
initially deposited in the nasal airway is deposited in a region of
the second nasal cavity which is posterior of the nasal valve and
at least 30% of the dose as initially deposited in the nasal airway
is deposited in an upper posterior region of the second nasal
cavity which is posterior of the nasal valve and above the inferior
meatus.
271. A method of delivering fluticasone to the middle meatus in
one, first nasal cavity of a subject in the treatment of
rhinosinusitis, the method comprising: fitting a nosepiece unit to
one, first nostril of a subject, wherein the nosepiece unit
includes a nosepiece which is inserted into the first nostril to
extend into the nasal valve and expand the nasal valve, and a
nozzle through which fluticasone is delivered to the first nasal
cavity from a multi-dose pump unit; providing a mouthpiece unit
which includes a mouthpiece, wherein the mouthpiece is fluidly
connected to the nosepiece; the subject exhaling through the
mouthpiece so as to cause closure of the oropharyngeal velum of the
subject and deliver an air flow through the first nostril, around
the posterior margin of the nasal septum and out of the other,
second nostril of the subject; and delivering, during exhalation
through the mouthpiece, a liquid aerosol spray comprising a metered
dose of fluticasone from the multi-dose pump unit through the
nozzle of the nosepiece unit into the first nasal cavity; wherein
at least 50% of the dose as initially deposited in the nasal airway
is deposited in a region of the first nasal cavity which is
posterior of the nasal valve and at least 30% of the dose as
initially deposited in the first nasal airway is deposited in an
upper posterior region of the first nasal cavity which is posterior
of the nasal valve and above the inferior meatus.
272. The method of claim 271, wherein the rhinosinusitis comprises
chronic rhinosinusitis.
Description
[0001] The present invention relates to a delivery device for and a
method of treating conditions of the nasal airway, in particular
inflammatory or infectious conditions relating to the middle
meatus, such as rhinosinusitis (RS), including acute rhinosinusitis
(ARS) and chronic rhinosinusitis (CRS), polyposis, sinus pains,
auto-immune diseases, including viral, bacterial, allergic and
non-allergic diseases, and the common cold.
[0002] RS is a prevalent disease, with CRS being the most common
chronic disease in the US, with 10 to 15% of the population being
affected (US, Vital Health Statistics). In Europe, about 10% of the
population suffer from CRS and about 2 to 3% suffer from polyposis,
with thus 20 to 30% of subjects with CRS also having polyposis.
[0003] The pathology of RS and polyposis generally stems from the
middle meatus, where the sinus ostia open to the nasal cavity. In
subjects with CRS, the mucosal lining becomes swollen, and, if
polyps develop, the polyps obstruct the middle meatus and often the
olfactory cleft which opens to the olfactory region. As the polyps
develop, the polyps normally extend downwards and backwards, though
sometimes forwards. The obstruction becomes more pronounced with
polyp size and is always more prominent in the upper parts of the
nose.
[0004] Currently, treatment is by drops as delivered by pipette or
aerosol sprays as delivered by a conventional spray pump. Studies
have shown that conventional sprays are inadequate in reaching the
middle meatus. Drops can reach the middle meatus, but this requires
rigorous patient compliance, insofar as the patients have to adopt
particular body positions during delivery, such as the "Mecca"
position, which are rarely respected.
[0005] It is an aim of the present invention to provide a delivery
device for and method of delivering substance to the middle meatus,
particularly in the treatment of inflammatory or infectious
conditions relating to the middle meatus, in particular ARS, CRS
and polyposis.
[0006] The present inventors have recognized that an increased
delivery of substance to the posterior region of the nasal airway,
and in particular the upper posterior region of the nasal airway,
as illustrated in FIG. 1, relative to the anterior region of the
nasal airway, surprisingly provides for improved delivery to the
middle meatus, and in particular in subjects with nasal polyps.
[0007] The posterior region of the nasal airway is that region
which is posterior of the nasal valve NV, as illustrated in FIG. 1.
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). These elements combine to form a
dynamic valve, which extends over several millimetres, 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.
[0008] 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.
[0009] The upper posterior region is the region above the inferior
meatus IM, as illustrated in FIG. 1, and encompasses the middle
turbinate, the middle meatus, 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.
[0010] As illustrated in FIG. 1, the posterior region of the nasal
airway is the nasal region posterior of an imaginary vertical plane
VERT which is located at a position corresponding to the lower
angle of the anterior nasal aperture (aperture piriformis), which
corresponds substantially 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 about
13 mm and about 14 mm (Rosenberger defines the distance between the
anterior nasal spine AnS and the posterior nasal spine PnS as being
56 mm in eighteen year old boys and 53.3 mm in eighteen year old
girls).
[0011] As further illustrated in FIG. 1, the upper region of the
nasal airway is an upper segment of the nasal airway which is
bounded by the cribiform plate CP and a horizontal plane HORIZ
which is located at a position corresponding to one-third of the
distance between the nasal floor NF of the nasal airway and the
cribiform plate CP, which corresponds to a height of typically
between about 13 and about 19 mm above the nasal floor NF (Zacharek
et al define the distance from the nasal floor NF to the cribiform
plate CP as 46 +/-4 mm).
[0012] The upper posterior region is thus that upper posterior
region which is bounded by the above-defined vertical and
horizontal planes VERT, HORIZ.
[0013] In one aspect the present invention provides a nasal
delivery device for delivering substance, typically as a
formulation, 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 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.
[0014] In another aspect the present invention provides a nasal
delivery device for delivering substance, typically as a
formulation, 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 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.
[0015] In a further aspect the present invention provides a nasal
delivery device for delivering substance, typically as a
formulation, to a nasal airway of a subject, comprising: a
nosepiece unit including a nosepiece for fitting to a nostril of a
subject, the nosepiece including 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.
[0016] In a still further aspect the present invention provides a
method of delivering substance, typically as a formulation, 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.
[0017] In still another aspect the present invention provides a
method of delivering substance, typically as a formulation, 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 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.
[0018] In yet another aspect the present invention provides a
method of delivering substance, typically as a formulation, to a
nasal airway of a subject, 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 of the nosepiece unit into the nasal cavity.
[0019] In still yet another aspect the present invention provides a
nasal delivery device for and method of delivering substance,
typically as a formulation, 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 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 to provide for deposition of a
significant fraction of the delivered dose on, around and in the
vicinity of the middle meatus.
[0020] In one embodiment the present invention provides for the
treatment of rhinosinusitis (RS), including acute rhinosinusitis
(ARS) and chronic rhinosinusitis (CRS).
[0021] In one embodiment the present invention provides for the
treatment of nasal polyps.
[0022] CRS and polyposis are observed in subjects with Cystic
Fibrosis, both paediatric and adult subjects, where the condition
is associated with an abnormality in the nasal mucosa, and the
present invention has particular application in relation to such
treatment.
[0023] In one embodiment the present invention provides for the
treatment of sinus pains.
[0024] In one embodiment the present invention provides for the
treatment of auto-immune diseases, including viral, bacterial,
allergic and non-allergic diseases, such as antigen-induced
diseases.
[0025] In one embodiment the present invention provides for the
treatment of the common cold.
[0026] In one embodiment the substance comprises a steroid, such as
fluticasone, budesonide, mometasone, betamethasone, beclomethasone,
triamcinolone and flunisoloide, and the pharmaceutically-acceptable
salts and derivatives thereof.
[0027] In one embodiment the substance comprises a decongestant,
such as ephedrine, pseudoephedrine, oxymetazoline, xylometazoline,
phenylephrine and phenylpropanolamine, and the
pharmaceutically-acceptable salts and derivatives thereof.
[0028] In one embodiment 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.
[0029] In one embodiment the substance comprises an
anti-cholinergic, such as ipratropium, tiotropium and oxitropium,
and the pharmaceutically-acceptable salts and derivatives
thereof.
[0030] In one embodiment 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.
[0031] In one embodiment the substance comprises a mast cell
stabilizer, such as ketotifen, and the pharmaceutically-acceptable
salts and derivatives thereof.
[0032] In one embodiment the substance comprises a leukotriene
antagonist, such as zafirlukast and montelukast, and the
pharmaceutically-acceptable salts and derivatives thereof.
[0033] In one embodiment the substance comprises a diuretic, such
as frusemide, and the pharmaceutically-acceptable salts and
derivatives thereof.
[0034] In one embodiment 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.
[0035] In one embodiment the substance comprises 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.
[0036] In one embodiment the substance comprises an
immuno-modulator. In one embodiment the immuno-modulator comprises
an antigen, such as an allergen, in particular a polypeptide
antigen or any part, small or large, of an antigen, where natural
or synthesized. In another embodiment 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.
[0037] In one embodiment 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.
[0038] In one embodiment the substance can comprise a
biofilm-destroying agent which acts to destroy bacterial biofilms
which can tend to form in subjects with conditions associated with
nasal inflammation and infection. In one embodiment the
biofilm-destroying agent comprises an anti-biotic, such as
tetracycline, linezolid and moxifloxacin, and the
pharmaceutically-acceptable salts and derivatives thereof. In
another embodiment the biofilm-destroying agent comprises a
disinfectant, such as chlorohexidine, and the
pharmaceutically-acceptable salts and derivatives thereof. In a
further embodiment the biofilm-destroying agent can be included as
a preservative, such as benzalkonium chloride, within the substance
formulation.
[0039] In preferred embodiments the substances can be administered
separately or in any combination, individually or simultaneously,
within a single formulation.
[0040] Preferred embodiments of the present invention will now be
described hereinbelow by way of example only with reference to the
accompanying drawings, in which:
[0041] FIG. 1 illustrates the segmentation of a nasal cavity in
accordance with a preferred embodiment of the present
invention;
[0042] FIG. 2 schematically illustrates a nasal delivery device in
accordance with a first embodiment of the present invention;
[0043] FIG. 3 illustrates the delivery device of FIG. 2 where
operative to deliver a dose of substance into the nasal airway of
the subject;
[0044] FIG. 4 schematically illustrates a nasal delivery device in
accordance with a second embodiment of the present invention;
[0045] FIG. 5 illustrates the delivery device of FIG. 4 where
operative to deliver a dose of substance into the nasal airway of
the subject;
[0046] FIG. 6 schematically illustrates a nasal delivery device in
accordance with a third embodiment of the present invention;
[0047] FIG. 7 illustrates the delivery device of FIG. 6 where
operative to deliver a dose of substance into the nasal airway of
the subject;
[0048] FIG. 8 schematically illustrates a nasal delivery device in
accordance with a fourth embodiment of the present invention;
[0049] FIG. 9 illustrates the delivery device of FIG. 8 where
operative to deliver a dose of substance into the nasal airway of
the subject;
[0050] FIG. 10 schematically illustrates a nasal delivery device in
accordance with a fifth embodiment of the present invention;
and
[0051] FIG. 11 illustrates the delivery device of FIG. 10 where
operative to deliver a dose of substance into the nasal airway of
the subject.
[0052] FIGS. 2 and 3 illustrate a nasal delivery device in
accordance with a first embodiment of the present invention.
[0053] The delivery device comprises a housing 15, a nosepiece unit
17 for fitting in a nasal cavity of a subject, and a mouthpiece 19
through which the subject exhales to actuate the delivery
device.
[0054] The nosepiece unit 17 comprises a nosepiece 20, in this
embodiment a frusto-conical element, for guiding the nosepiece unit
17 into a nasal cavity of the subject and being configured both to
provide a fluid-tight seal with the nares of the nostril and at
least obstruct, in this embodiment close, the nasal passage at a
position therealong, in this embodiment at a position corresponding
substantially to the nasal valve, thereby obstructing the anterior
one-third of the nasal passage and leaving open the posterior
two-thirds of the nasal cavity, as illustrated in FIG. 3.
[0055] In this embodiment the nosepiece 20 is further configured
such as mechanically to open the nasal valve, thereby facilitating
access to the posterior two-thirds of the nasal cavity, and in
particular the middle meatus.
[0056] The nosepiece unit 17 further comprises an outlet unit 21
for delivering substance, which has an anti-inflammatory or other
therapeutic effect on the middle meatus, into the nasal cavity of
the subject and to the middle meatus, in this embodiment for the
treatment of one or both of RS, in particular CRS, and polyposis.
In this embodiment the substance comprises a formulation containing
a nasal steroid, such as fluticasone.
[0057] In this embodiment the outlet unit 21 comprises a delivery
channel 23 which is in fluid communication with the mouthpiece 19,
such that an air flow is delivered into the nasal airway of the
subject on exhalation by the subject through the mouthpiece 19, and
a nozzle 25 for delivering substance into the nasal cavity of the
subject.
[0058] In this embodiment the nozzle 25 is configured to deliver a
jet, as a column of substance. In delivering the substance as a
jet, the substance can be more readily directed at the middle
meatus, typically as obstructed by RS and nasal polyps.
[0059] In this embodiment the nozzle 25 is configured to deliver a
liquid jet, but in another embodiment could be configured to
deliver a powder jet.
[0060] The delivery device further comprises a substance supply
unit 29 for delivering metered doses of the substance, which is
fluidly connected to the nozzle 25 to deliver the substance from
the nosepiece unit 17, in this embodiment as a jet.
[0061] In this embodiment the substance supply unit 29 comprises a
mechanical delivery pump.
[0062] In this embodiment the substance supply unit 29 is a
multi-dose unit for delivering a plurality of metered doses of the
substance. In another embodiment the substance supply unit 29 could
be a single-dose unit for delivering a single metered dose of the
substance.
[0063] The substance supply unit 29 is pre-primeable, in this
embodiment by loading a resilient element, and includes a
breath-actuated release mechanism 31 which, when triggered,
releases the resilient element and actuates the substance supply
unit 29 to deliver a metered dose of the substance through the
nozzle 25.
[0064] In this embodiment the release mechanism 31 is configured to
cause actuation of the substance supply unit 29 on generation of a
predetermined pressure at the delivery channel 23.
[0065] The generation of a raised pressure in the nasal cavity acts
to expand the region of the nasal cavity anterior of the middle
meatus and posterior of the nasal valve, with one or both of
inflamed mucosa or polyps in the upper region of the nasal cavity
acting to provide a resistance to the anteriorly-delivered air flow
and thus providing an increased pressure anterior of the middle
meatus. This expansion of the region of the nasal cavity anterior
of the middle meatus facilitates access to the middle meatus and
also reduces the deposition of substance in the anterior region.
Deposition in the anterior region has been shown to lead to
crusting and bleeding, which is particularly uncomfortable. In
addition, the increased pressure in the nasal cavity acts to force
substance into ducts and channels leading to the sinuses, which can
be blocked by mucosal inflammation and polyps.
[0066] Operation of the delivery device will now be described
hereinbelow with reference to FIG. 3 of the accompanying
drawings.
[0067] The nosepiece unit 17 is first inserted into one of the
nasal cavities of a subject until the nosepiece 20 abuts the nares
of the nostril such as to establish a fluid-tight seal therewith,
at which point the distal end of the outlet unit 21 extends about 2
cm into the nasal cavity of the subject such as to engage with and
expand the nasal valve, and the mouthpiece 19 is gripped in the
lips of the subject.
[0068] The subject then begins to exhale through the mouthpiece 19,
which exhalation acts to close the oropharyngeal velum of the
subject and drive an air flow through the delivery channel 23 of
the outlet unit 21, with the air flow passing into the one nasal
cavity, around the posterior margin of the nasal septum and out of
the other nasal cavity, thereby achieving a bi-directional air flow
through the nasal airway of the subject, in the manner as described
in WO-2000/051672. Where the middle meatus is obstructed, the flow
is restricted and along the floor of the nose, but, as discussed
hereinabove, acts to generate a pressure in the nasal cavity which
acts to expand the constriction at the middle meatus.
[0069] In this embodiment, when the pressure developed at the
delivery channel 23 reaches a predetermined value, the release
mechanism 31 is triggered to actuate the substance supply unit 29
to deliver a metered dose of the substance to the nozzle 25 and
into the nasal cavity of the subject as a jet.
[0070] In this embodiment the delivery device is configured such
that at least 50% of the dose as initially deposited in the nasal
cavity 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. With such delivery,
improved deposition is obtained on the middle meatus, in particular
at the site of nasal polyps.
[0071] In preferred embodiments the delivery device is configured
such that at least 55%, more preferably at least 60%, still more
preferably at least 65% and yet more preferably 70% of the dose as
initially deposited in the nasal cavity is deposited in the region
posterior of the nasal valve.
[0072] In preferred embodiments the delivery device is configured
such that at least 35%, more preferably at least 40%, still more
preferably at least 45% and yet more preferably 50% of the dose as
initially deposited in the nasal cavity is deposited in the upper
posterior region of the nasal cavity.
[0073] In this embodiment, where the delivery device is a
multi-dose device, the device is ready for further use following
priming of the pump unit 29.
[0074] In one alternative embodiment the nozzle 25 could be
configured to deliver a plurality of jets. This configuration still
facilitates delivery through the nasal valve to the middle meatus
as compared to conventional sprays which have a wide cone
angle.
[0075] In one embodiment the contralateral nostril can be partially
or wholly obstructed, such as to promote the generation of a raised
pressure in the nasal cavity into which substance is to be
delivered. In one embodiment the contralateral nostril can be
obstructed by applying a pressure to the lateral nare of the
contralateral nostril. In another embodiment the nosepiece unit 17
can include a second nosepiece 20 which is configured to be fitted
in the other nostril of the subject such as to obstruct the
same.
[0076] FIGS. 4 and 5 illustrate a nasal delivery device in
accordance with a second embodiment of the present invention.
[0077] The delivery device of this embodiment is very similar to
the delivery device of the above-described first embodiment, and
thus, in order to avoid unnecessary duplication of description,
only the differences will be described in detail, with like
reference signs designating like parts.
[0078] The delivery device of this embodiment differs from that of
the above-described first embodiment in further comprising an oral
exhalation breath-actuatable gas supply unit 33 for delivering a
gas flow through the delivery channel 23 of the outlet unit 21 in
response to exhalation by a subject, and in that the mouthpiece 19
is in fluid communication with the gas supply unit 33 and not the
delivery channel 23 of the outlet unit 21, whereby a gas flow is
delivered to the delivery channel 23 of the outlet unit 21, and
hence the nasal airway of the subject, in response to exhalation
through the mouthpiece 19.
[0079] Operation of the delivery device is the same as for the
above-described first embodiment, with a gas flow being delivered
to the delivery channel 23 of the outlet unit 21 in response to
exhalation through the mouthpiece 19.
[0080] In one alternative embodiment the release mechanism 31 could
be a manually-actuated unit and the mouthpiece 19 omitted.
[0081] FIGS. 6 and 7 illustrate a nasal delivery device in
accordance with a third embodiment of the present invention.
[0082] The delivery device of this embodiment is quite similar to
the delivery device of the above-described first embodiment, and
thus, in order to avoid unnecessary duplication of description,
only the differences will be described in detail, with like
reference signs designating like parts.
[0083] The delivery device of this embodiment differs from that of
the above-described first embodiment in the release mechanism 31
being a manually-actuated unit and the mouthpiece 19 and the
delivery channel 23 of the outlet unit 21 being omitted. With this
configuration, a gas flow is not delivered into the nasal cavity of
the subject, but the substance, in being delivered as a jet, acts
to provide for targeted delivery to the middle meatus without any
deposition anterior of the nasal valve, which would be experienced
with a conventional nasal spray.
[0084] Operation of the delivery device is the same as for the
above-described first embodiment, except that a gas flow is not
delivered into the nasal cavity.
[0085] FIGS. 8 and 9 illustrate a nasal delivery device in
accordance with a fourth embodiment of the present invention.
[0086] The delivery device comprises a housing 115, a nosepiece
unit 117 for fitting in a nasal cavity of a subject, and a
mouthpiece 119 through which the subject exhales to actuate the
delivery device.
[0087] The nosepiece unit 117 comprises a nosepiece 120, in this
embodiment a frusto-conical element, for guiding the nosepiece unit
117 into a nasal cavity of the subject and being configured both to
provide a fluid-tight seal with the nares of the nostril and at
least obstruct, in this embodiment close, the nasal passage at a
position therealong, in this embodiment at a position corresponding
substantially to the nasal valve, thereby obstructing the anterior
one-third of the nasal cavity and leaving open the posterior
two-thirds of the nasal cavity, as illustrated in FIG. 9.
[0088] In this embodiment the nosepiece 120 is further configured
such as mechanically to open the nasal valve, thereby facilitating
access to the posterior two-thirds of the nasal cavity, and in
particular the middle meatus.
[0089] The nosepiece unit 117 further comprises an outlet unit 121
for delivering substance, which has an anti-inflammatory or other
therapeutic effect on the middle meatus, into the nasal cavity of
the subject and to the middle meatus, for the treatment of one or
both of RS, in particular CRS, and polyposis. In this embodiment
the substance comprises a formulation containing a nasal steroid,
such as fluticasone.
[0090] In this embodiment the outlet unit 121 comprises a delivery
channel 123 which is in fluid communication with the mouthpiece 119
such that an air flow is delivered into and through the nasal
airway of the subject on exhalation by the subject through the
mouthpiece 119, and a nozzle 125 for delivering the substance into
the nasal cavity of the subject.
[0091] In this embodiment the nozzle 125 is configured to deliver
an aerosol spray, either as a liquid or powder aerosol, here having
a relatively-narrow cone angle.
[0092] In one embodiment the cone angle is not more than about 50
degrees, preferably not more than about 40 degrees, more preferably
not more than about 35 degrees, still more preferably not more than
about 30 degrees, yet more preferably not more than about 25
degrees, still yet more preferably not more than about 20 degrees,
and still yet more preferably not more than about 15 degrees.
[0093] In delivering the substance as an aerosol spray with a
narrow cone angle, the substance can be more readily directed at
the middle meatus as obstructed by RS and nasal polyps.
[0094] The delivery device further comprises a substance supply
unit 129 for delivering metered doses of the substance, which is
fluidly connected to the nozzle 125 to deliver the substance from
the nosepiece unit 117, in this embodiment as an aerosol spray.
[0095] In this embodiment the substance supply unit 129 comprises a
mechanical delivery pump, in particular a liquid delivery pump or a
powder delivery pump, which delivers metered doses of substance on
actuation thereof.
[0096] In another embodiment the substance supply unit 129 could
comprise a dry powder delivery unit which delivers metered doses of
a substance, as a dry powder, on actuation thereof.
[0097] In a further embodiment the substance supply unit 129 could
comprise an aerosol canister for delivering metered volumes of a
propellant, preferably a hydrofluoroalkane (HFA) propellant or the
like, containing substance on actuation thereof.
[0098] In another alternative embodiment the substance supply unit
129 could comprise a nebulizer which delivers metered doses of a
substance, as an aerosol spray, on actuation thereof.
[0099] In this embodiment the substance supply unit 129 is a
multi-dose unit for delivering a plurality of metered doses of the
substance. In another embodiment the substance supply unit 129
could be a single-dose unit for delivering a single metered dose of
the substance.
[0100] The substance supply unit 129 is pre-primeable, in this
embodiment by loading a resilient element, and includes a
breath-actuated release mechanism 131 which, when triggered,
releases the resilient element and actuates the substance supply
unit 129 to deliver a metered dose of the substance through the
nozzle 125.
[0101] In this embodiment the release mechanism 131 is configured
to cause actuation of the substance supply unit 129 on generation
of a predetermined pressure at the delivery channel 123.
[0102] The generation of a raised pressure in the nasal cavity acts
to expand the region of the nasal cavity anterior of the middle
meatus and posterior of the nasal valve, with one or both of
inflamed mucosa or polyps in the upper region of the nasal cavity
acting to provide a resistance to the anteriorly-delivered air flow
and thus providing an increased pressure anterior of the middle
meatus. This expansion of the region of the nasal cavity anterior
of the middle meatus facilitates access to the middle meatus and
also reduces the deposition of substance in the anterior region.
Deposition in the anterior region has been shown to lead to
crusting and bleeding, which is particularly uncomfortable. In
addition, the increased pressure in the nasal cavity acts to force
substance into ducts and channels leading to the sinuses, which can
be blocked by mucosal inflammation and polyps.
[0103] Operation of the delivery device will now be described
hereinbelow with reference to FIG. 9 of the accompanying
drawings.
[0104] The nosepiece unit 117 is first inserted into one of the
nasal cavities of a subject until the nosepiece 120 abuts the nares
of the nostril, such as to establish a fluid-tight seal therewith,
at which point the distal end of the outlet unit 121 extends about
2 cm into the nasal cavity of the subject such as to engage with
and expand the nasal valve, and the mouthpiece 119 is gripped in
the lips of the subject.
[0105] The subject then begins to exhale through the mouthpiece
119, which exhalation acts to close the oropharyngeal velum of the
subject and drive an air flow through the delivery channel 123 of
the outlet unit 121, with the air flow passing into the one nasal
cavity, around the posterior margin of the nasal septum and out of
the other nasal cavity, thereby achieving a bi-directional air flow
through the nasal airway of the subject, in the manner as described
in WO-2000/051672. Where the middle meatus is obstructed, the flow
is restricted and along the floor of the nose, but, as discussed
hereinabove, acts to generate a pressure in the nasal cavity which
acts to expand the constriction at the middle meatus.
[0106] In this embodiment, when the pressure developed at the
delivery channel 123 reaches a predetermined value, the release
mechanism 131 is triggered to actuate the substance supply unit 129
to deliver a metered dose of the substance to the nozzle 125 and
into the nasal cavity of the subject as an aerosol spray.
[0107] In this embodiment the delivery device is configured such
that at least 50% of the dose as initially deposited in the nasal
cavity 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. With such delivery,
improved deposition is obtained on the middle meatus, in particular
at the site of nasal polyps.
[0108] In preferred embodiments the delivery device is configured
such that at least 55%, more preferably at least 60%, still more
preferably at least 65% and yet more preferably 70% of the dose as
initially deposited in the nasal cavity is deposited in the region
posterior of the nasal valve.
[0109] In preferred embodiments the delivery device is configured
such that at least 35%, more preferably at least 40%, still more
preferably at least 45% and yet more preferably 50% of the dose as
initially deposited in the nasal cavity is deposited in the upper
posterior region of the nasal cavity.
[0110] In this embodiment, where the delivery device is a
multi-dose device, the device is ready for further use following
priming of the pump unit 129.
[0111] In one embodiment the contralateral nostril can be partially
or wholly obstructed, such as to promote the generation of a raised
pressure in the nasal cavity into which substance is to be
delivered. In one embodiment the contralateral nostril can be
obstructed by applying a pressure to the lateral nare of the
contralateral nostril. In another embodiment the nosepiece unit 117
can include a second nosepiece 120 which is configured to be fitted
in the other nostril of the subject such as to obstruct the
same.
[0112] FIGS. 10 and 11 illustrate a nasal delivery device in
accordance with a fifth embodiment of the present invention.
[0113] The delivery device comprises a housing 215, and a nosepiece
unit 217 for fitting in a nasal cavity of a subject and into which
the subject nasally exhales to actuate the delivery device.
[0114] The nosepiece unit 217 comprises a nosepiece 220, in this
embodiment a frusto-conical element, for guiding the nosepiece unit
217 into a nasal cavity of the subject and being configured both to
provide a fluid-tight seal with the nares of the nostril and at
least obstruct, in this embodiment close, the nasal passage at a
position therealong, in this embodiment at a position corresponding
substantially to the nasal valve, thereby obstructing the anterior
one-third of the nasal cavity and leaving open the posterior
two-thirds of the nasal cavity, as illustrated in FIG. 11.
[0115] In this embodiment the nosepiece 220 is further configured
such as mechanically to open the nasal valve, thereby facilitating
access to the posterior two-thirds of the nasal cavity, and in
particular the middle meatus.
[0116] The nosepiece unit 217 further comprises an outlet unit 221
for delivering substance, which has an anti-inflammatory or other
therapeutic effect on the middle meatus, into the nasal cavity of
the subject and to the middle meatus, for the treatment of one or
both of RS, in particular CRS, and polyposis. In this embodiment
the substance comprises a formulation containing a nasal steroid,
such as fluticasone.
[0117] In this embodiment the outlet unit 221 comprises a
communication channel 223 which is in fluid communication with the
nasal cavity of the subject, such as to enable nasal exhalation to
be detected through the generation of an increased pressure
thereat, and a nozzle 225 for delivering a metered dose of
substance into the nasal cavity of the subject.
[0118] In this embodiment the nozzle 225 is configured to deliver a
jet, as a column of substance, either of liquid or powder. In
delivering the substance as a jet, the substance can be more
readily directed at the middle meatus as obstructed by RS and nasal
polyps.
[0119] The delivery device further comprises a substance supply
unit 229 for delivering metered doses of the substance, which is
fluidly connected to the nozzle 225 to deliver the substance from
the nosepiece unit 217, in this embodiment as a jet.
[0120] In this embodiment the substance supply unit 229 comprises a
mechanical delivery pump.
[0121] In this embodiment the substance supply unit 229 is a
multi-dose unit for delivering a plurality of metered doses of the
substance. In another embodiment the substance supply unit 229
could be a single-dose unit for delivering a single metered dose of
the substance.
[0122] The substance supply unit 229 is pre-primeable, in this
embodiment by loading a resilient element, and includes a
breath-actuated release mechanism 231 which, when triggered by
nasal exhalation, releases the resilient element and actuates the
substance supply unit 229 to deliver a metered dose of the
substance through the nozzle 225.
[0123] In this embodiment the release mechanism 231 is configured
to cause actuation of the substance supply unit 229 on generation
of a predetermined pressure at the communication channel 223, which
is developed in response to nasal exhalation.
[0124] The generation of a raised pressure in the nasal cavity acts
to expand the nasal cavity, and in particular the region including
the middle meatus which represents a region of increased resistance
when including one or both of inflamed mucosa or polyps. This
expansion of the region of the nasal cavity including the middle
meatus facilitates access to the middle meatus and also reduces the
deposition of substance in the anterior region. Deposition in the
anterior region has been shown to lead to crusting and bleeding,
which is particularly uncomfortable. In addition, the increased
pressure in the nasal cavity acts to force substance into ducts and
channels leading to the sinuses, which can be blocked by mucosal
inflammation and polyps.
[0125] Operation of the delivery device will now be described
hereinbelow with reference to FIG. 11 of the accompanying
drawings.
[0126] The nosepiece unit 217 is first inserted into one of the
nasal cavities of a subject until the nosepiece 220 abuts the nares
of the nostril, such as to establish a fluid-tight seal therewith,
at which point the distal end of the outlet unit 221 extends about
2 cm into the nasal cavity of the subject such as to engage and
expand the nasal valve.
[0127] The subject then begins to exhale nasally, which exhalation
acts to generate an increased pressure in the one nasal cavity
which acts to expand the constriction at the middle meatus. In this
embodiment the mouth of the subject can be closed, or the mouth can
remain open and the tongue be positioned such as to prevent oral
exhalation, as illustrated in FIG. 11.
[0128] In this embodiment, when the pressure developed at the
communication channel 223 reaches a predetermined value, the
release mechanism 231 is triggered to actuate the substance supply
unit 229 to deliver a metered dose of the substance to the nozzle
225 and into the nasal cavity of the subject as a jet.
[0129] In this embodiment the delivery device is configured such
that at least 50% of the dose as initially deposited in the nasal
cavity 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. With such delivery,
improved deposition is obtained on the middle meatus, in particular
at the site of nasal polyps.
[0130] In preferred embodiments the delivery device is configured
such that at least 55%, more preferably at least 60%, still more
preferably at least 65% and yet more preferably 70% of the dose as
initially deposited in the nasal cavity is deposited in the region
posterior of the nasal valve.
[0131] In preferred embodiments the delivery device is configured
such that at least 35%, more preferably at least 40%, still more
preferably at least 45% and yet more preferably 50% of the dose as
initially deposited in the nasal cavity is deposited in the upper
posterior region of the nasal cavity.
[0132] In this embodiment, where the delivery device is a
multi-dose device, the device is ready for further use following
priming of the pump unit 229.
[0133] In one alternative embodiment the nozzle 225 could be
configured to deliver a plurality of liquid jets. This
configuration still facilitates delivery through the nasal valve to
the middle meatus as compared to conventional sprays which have a
wide cone angle.
[0134] In one embodiment the contralateral nostril can be partially
or wholly obstructed, such as to promote the generation of a raised
pressure in the nasal cavity into which substance is to be
delivered. In one embodiment the contralateral nostril can be
obstructed by applying a pressure to the lateral nare of the
contralateral nostril. In another embodiment the nosepiece unit 217
can include a second nosepiece 220 which is configured to be fitted
in the other nostril of the subject such as to obstruct the
same.
[0135] Finally, it will be understood that the present invention
has been described in its preferred embodiment and can be modified
in many different ways without departing from the scope of the
invention as defined by the appended claims.
[0136] In one modification, the delivery device of the
fifth-described embodiment could be modified to include first and
second nosepiece units 217 for fitting to the respective nostrils
of the subject. With this configuration, an increased pressure is
generated in both of the nasal cavities and substance can be
delivered to both of the nasal cavities in a single operation of
the delivery device.
[0137] In another modification, the delivery device of the
fifth-described embodiment could be modified, in the manner of the
fourth-described embodiment, such that the outlet unit 221 provides
for an aerosol spray, either as a liquid or powder aerosol.
[0138] In preferred embodiments the delivery devices are configured
to deliver an air flow through one nostril of a subject at such a
pressure as to flow around the posterior margin of the nasal septum
and out of the other nostril of the subject, thereby achieving
bi-directional delivery through the nasal cavities as disclosed in
WO-A-00/51672, the content of which is herein incorporated by
reference. In alternative embodiments the delivery device could be
configured to deliver an air flow at a reduced pressure which is
not sufficient to achieve bi-directional delivery through the nasal
cavities. Such embodiments are still advantageous as compared to
known delivery devices in providing for velum closure and being
capable of achieving targeted delivery.
REFERENCES
[0139] 1. Cole, P, The Respiratory Role of the Upper Airways, a
selective clinical and pathophysiological review. 1993, Mosby-Year
Book Inc. ISBN1.55664-390-X. [0140] 2. Rosenberger, H, Growth and
Development of the Naso-Respiratory Area in Childhood, PhD Thesis,
Laboratory of Anatomy, School of Medicine, Western Reserve
University, Presented to the Annual Meeting of the American
Laryngological, Rhinological and Otological Society, Charleston,
S.C., USA, 1934. [0141] 3. Zacharek, M A et al, Sagittal and
Coronal Dimensions of the Ethmoid Roof: A Radioanatomic Study, Am J
Rhino 2005, Vol 19, pages 348 to 352.
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