U.S. patent application number 15/001344 was filed with the patent office on 2016-12-22 for nasal delivery.
The applicant listed for this patent is OptiNose AS. Invention is credited to Per Gisle Djupesland.
Application Number | 20160367771 15/001344 |
Document ID | / |
Family ID | 36384006 |
Filed Date | 2016-12-22 |
United States Patent
Application |
20160367771 |
Kind Code |
A1 |
Djupesland; Per Gisle |
December 22, 2016 |
NASAL DELIVERY
Abstract
A delivery device for and method of delivering a dose of
substance for systemic uptake to a nasal cavity of a subject, the
delivery device comprising: a nosepiece unit for insertion into a
nasal cavity of a subject and comprising an outlet unit which
includes at least one nozzle for delivering substance for systemic
uptake substantially only to surfaces in one or both of the
anterior region and an anterior section of the posterior region of
the nasal cavity of the subject; and a substance supply unit which
is operable to deliver a dose of substance to the at least one
nozzle.
Inventors: |
Djupesland; Per Gisle;
(Oslo, NO) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
OptiNose AS |
Oslo |
|
NO |
|
|
Family ID: |
36384006 |
Appl. No.: |
15/001344 |
Filed: |
January 20, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12293972 |
Aug 27, 2009 |
9272104 |
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PCT/IB07/01998 |
Mar 23, 2007 |
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15001344 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 15/0003 20140204;
A61M 2210/0618 20130101; A61M 2205/075 20130101; A61M 15/08
20130101; A61M 15/0021 20140204; A61M 2202/064 20130101; A61M 11/00
20130101; A61M 15/009 20130101; A61M 15/0098 20140204; A61M 2202/04
20130101; A61M 15/0065 20130101; A61M 2210/0625 20130101 |
International
Class: |
A61M 15/08 20060101
A61M015/08; A61M 11/00 20060101 A61M011/00; A61M 15/00 20060101
A61M015/00 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 23, 2006 |
GB |
GB 0605799.6 |
Claims
1-78. (canceled)
79. A delivery device for delivering a substance to a nasal cavity
of a subject for systemic uptake, the delivery device comprising: a
nosepiece for insertion into the nasal cavity of the subject, the
nosepiece including an outlet unit comprising: a first nozzle; a
posterior nosepiece member configured to obstruct the nasal cavity
and partition the nasal cavity into anterior and posterior regions
such that substantially all of the substance is delivered from the
first nozzle to the anterior region, and a delivery channel through
which a gas flow is delivered to the anterior region; a mouthpiece
in fluid communication with the nosepiece through which the subject
exhales to cause closure of an oropharyngeal velum of the subject;
a substance supply unit operable to deliver the substance to the
first nozzle; and a gas unit operable to supply the gas flow to the
delivery channel.
80. The delivery device of claim 79, wherein the substance supply
unit is breath actuated on oral exhalation by the subject.
81. The delivery device of claim 79, wherein the substance supply
unit is breath actuated on nasal exhalation by the subject.
82. The delivery device of claim 79, wherein the substance supply
unit is manually actuated.
83. The delivery device of claim 79, wherein the outlet unit
further comprises a second nozzle.
84. The delivery device of claim 79, wherein the first nozzle is
substantially laterally directed so as to direct the substance to a
lateral surface within the anterior region of the nasal cavity.
85. The delivery device of claim 79, wherein the nozzle is
configured to deliver a liquid.
86. The delivery device of claim 79, wherein the nozzle is
configured to deliver a powder.
87. The delivery device of claim 79, wherein the posterior region
comprises the region of the nasal cavity posterior of the nasal
valve.
88. The delivery device of claim 79, wherein the posterior
nosepiece member is configured to close the nasal valve of the
subject.
89. A method of delivering a substance to a nasal cavity of a
subject for systemic uptake, the method comprising: inserting a
nosepiece into the nasal cavity of the subject, the nosepiece
including an outlet unit having a first nozzle, a posterior
nosepiece member configured to obstruct the nasal cavity and
partition the nasal cavity into anterior and posterior regions such
that substantially all of the substance is delivered from the first
nozzle to the anterior region, and a delivery channel through which
a gas flow is delivered to the anterior region; inserting a
mouthpiece through which the subject exhales to cause closure of an
oropharyngeal velum of the subject into the mouth of the subject;
delivering the substance from a substance supply unit to the first
nozzle; and supplying the gas flow to the delivery channel.
90. The method of claim 89, wherein the first nozzle is
substantially laterally directed so as to direct the substance to a
lateral surface within the anterior region of the nasal cavity.
91. The method of claim 89, wherein the nozzle is configured to
deliver a liquid.
92. The method of claim 89, wherein the nozzle is configured to
deliver a powder.
93. The method of claim 89, further comprising the step of
delivering the substance through the first nozzle to the anterior
region of the nasal cavity of the subject.
94. The method of claim 89, further comprising the step of
delivering the gas flow through the delivery channel to the
anterior region of the nasal cavity of the subject.
95. The method of claim 93, further comprising the step of
delivering the gas flow through the delivery channel to the
anterior region of the nasal cavity of the subject.
96. The method of claim 95, wherein the step of delivering the gas
flow through the delivery channel to the anterior region of the
nasal cavity of the subject and the step of delivering the
substance through the first nozzle to the anterior region of the
nasal cavity of the subject occur substantially simultaneously.
97. The method of claim 89, wherein the posterior region comprises
the region of the nasal cavity posterior of the nasal valve.
98. The method of claim 89, wherein the posterior nosepiece member
is configured to close the nasal valve of the subject.
Description
[0001] The present Invention relates to a nasal delivery device for
and a method of Intranasally delivering substances for systemic
uptake, as liquids, such as suspensions or solutions, and powders,
where containing medicaments, typically pharmaceuticals, or
vaccines.
[0002] Referring to FIG. 1(a), the nasal airway 1 comprises the two
nasal cavities separated by the nasal septum, which airway 1
includes numerous ostia, such as the paranasal sinus ostia 3 and
the tubal ostia 5, and olfactory cells, and is lined by nasal
mucosa. The nasal airway 1 can communicate with the nasopharynx 7,
the oral cavity 9 and the lower airway 11, with the nasal airway 1
being in selective communication with the anterior region of the
nasopharynx 7 and the oral cavity 9 by opening and closing of the
oropharyngeal velum 13. The velum 13, which is often referred to as
the soft palate, is illustrated in solid line in the closed
position, as achieved by providing a certain positive pressure in
the oral cavity 9, such as achieved on exhalation through the oral
cavity 9, and in dashed line in the open position.
[0003] The nasal cavities each comprise a posterior region which is
that region which is posterior of the nasal valve NV and an
anterior region which is that region which is anterior of the nasal
valve NV, as illustrated in FIG. 1(b).
[0004] The nasal valve NV 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 NV 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
NV is lined in its anterior part with transitional epithelium, with
a gradual transition posterior to respiratory epithelium. The nasal
valve NV and anterior vestibule define roughly the anterior
one-third of the nose.
[0005] 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, and extends to the skin-lined section at the nares of
the nostril. 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.
[0006] As illustrated in FIG. 1(b), the posterior region of the
nasal airway is the nasal region posterior of an imaginary vertical
plane VERT1 which is located at a position corresponding to
one-quarter of the distance between the anterior nasal spine AnS,
which is a pointed projection at the anterior extremity of the
intermaxillary suture, and the posterior nasal spine PnS, which is
the sharp posterior extremity of the nasal crest of the hard palate
and represents the transition between the nose and the nasopharynx,
which corresponds to a distance posterior of the anterior nasal
spine AnS of between 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]. As again illustrated in
FIG. 1(b), the posterior nasal region is bounded posteriorly by an
imaginary vertical plane VERT2 which extends through the posterior
nasal spine PnS.
[0007] The upper posterior region is the region above the inferior
meatus IM, as illustrated in FIG. 1(b), and encompasses the middle
turbinate, the sinus ostia in infundibulum (ostia to maxillary,
frontal and ethmoidal sinuses), the olfactory region, and the upper
branches of the trigeminal nerve, and is that region which includes
veins which drain to the venous sinuses that surround the
brain.
[0008] As further illustrated in FIG. 1(b), 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].
[0009] The upper posterior region is thus that upper posterior
region which is bounded by the above-defined vertical and
horizontal planes VERT1, HORIZ.
[0010] There are many nasal conditions which require treatment. One
such condition is nasal inflammation, specifically rhinitis, which
can be allergic or non-allergic and is often associated with
infection and prevents normal nasal function. By way of example,
allergic and non-allergic inflammation of the nasal airway can
typically effect between 10 and 20% of the population, with nasal
congestion of the erectile tissues of the nasal concha,
lacrimation, secretion of watery mucus, sneezing and Itching being
the most common symptoms. As will be understood, nasal congestion
impedes nasal breathing and promotes oral breathing, leading to
snoring and sleep disturbance. Other nasal conditions include nasal
polyps which arise from the paranasal sinuses, hypertrophic
adenoids, secretory otitis media, sinus disease and reduced
olfaction.
[0011] In the treatment of certain nasal conditions, the topical
administration of medicaments is preferable, particularly where the
nasal mucosa is the prime pathological pathway, such as in treating
or relieving nasal congestion. Medicaments that are commonly
topically delivered include decongestants, anti-histamines,
cromoglycates, steroids and antibiotics. At present, among the
known anti-inflammatory pharmaceuticals, topical steroids have been
shown to have an effect on nasal congestion. Topical decongestants
have also been suggested for use in relieving nasal congestion. The
treatment of hypertrophic adenoids and chronic secretory otitis
media using topical decongestants, steroids and anti-microbial
agents, although somewhat controversial, has also been proposed.
Further, the topical administration of pharmaceuticals has been
used to treat or at least relieve symptoms of Inflammation in the
anterior region of the nasopharynx, the paranasal sinuses and the
auditory tubes.
[0012] Medicaments can also be systemically delivered through the
nasal pathway, the nasal pathway offering a good administration
route for the systemic delivery of pharmaceuticals, such as
hormones, for example, oxytocin and calcitonin, and analgetics,
such as anti-migraine compositions, as the high blood flow and
large surface area of the nasal tissues advantageously provides for
rapid systemic uptake.
[0013] In relation to systemic delivery, studies [Daley-Yates et al
and Harris et al] have shown that significantly increased systemic
bio-availability is achieved by delivery as a nasal spray as
compared to drops.
[0014] Daley-Yates et al investigated the systemic bio-availability
of fluticasone propionate where delivered both as an aqueous spray
and as nasal drops, and the bio-availability of the nasal spray
formulation was about eight times higher than that of the nasal
drop formulation. The authors of the this study have attributed
this increased bio-availability of the nasal spray formulation to
the by-passing of the nose and an increased absorption from the
gastro-intestinal (GI) tract, where the nose is by-passed by one or
both of mucociliary clearance of the substance or sniffing the
substance along the floor of the nose and subsequent
swallowing.
[0015] Harris et al investigated the intranasal administration of
desmopressin as a nasal spray and as nasal drops, and the
bio-availability of the nasal spray formulation was two to three
times higher than that of the nasal drop formulation.
[0016] In line with these studies, the current understanding in the
art is that to achieve maximal absorption of substance to the
systemic circulation, the substance should be delivered to as large
a surface of the nasal cavity as possible.
[0017] The present inventors have now contrarily and surprisingly
recognized that the delivery of substance to the anterior region of
the nasal cavity and an anterior section of the posterior region of
the nasal cavity, in particular the anterior third, and more
particularly the mid-anterior third of the posterior region,
predominantly influences the systemic bio-availability of the
substance, and, by controlling the delivery of the substance to the
anterior region of the nasal cavity and the anterior section of the
posterior region of the nasal cavity, a more uniform and increased
bio-availability can be achieved for a given dose of the substance.
A particular problem of existing delivery regimes is the
significant variability in the systemic bio-availability, which the
present inventors attribute to the significant variation in the
distribution of substance as delivered in subject to subject. The
present inventors have recognized that delivering the dose of
substance in particular to the anterior region of the nasal cavity
can provide a desired uniformity to the systemic
bio-availability.
[0018] Nasal delivery is also expected to be advantageous for the
administration of medicaments requiring a rapid onset of action,
for example, analgetics, anti-emetics, insulin, anti-epileptics,
sedatives and hypnotica, and also other pharmaceuticals, for
example, cardio-vascular drugs. It is envisaged that nasal
administration will provide for a fast onset of action, at a rate
similar to that of injection and at a rate much faster than that of
oral administration. Indeed, for the treatment of many acute
conditions, nasal administration is advantageous over oral
administration, since gastric stasis can further slow the onset of
action following oral administration.
[0019] It is also expected that nasal delivery could provide an
effective delivery route for the administration of proteins and
peptides as produced by modern biotechnological techniques. For
such substances, the metabolism in the intestines and the
first-pass-effect in the liver represent significant obstacles for
reliable and cost-efficient delivery.
[0020] Furthermore, it is expected that nasal delivery using the
nasal delivery technique of the present invention will prove
effective in the treatment of many common neurological diseases,
such as Alzheimer's, Parkinson's, psychiatric diseases and
intracerebral infections, where not possible using existing
techniques.
[0021] Also, it is expected that the nasal delivery technique of
the present invention will allow for the effective delivery of
vaccines.
[0022] Aside from the delivery of medicaments, the irrigation of
the nasal mucosa with liquids, in particular saline solutions, is
commonly practised to remove particles and secretions, as well as
to improve the mucociliary activity of the nasal mucosa. These
solutions can be used in combination with active
pharmaceuticals.
[0023] For any kind of drug delivery, accurate and reliable dosing
is essential, but it is of particular importance in relation to the
administration of potent drugs which have a narrow therapeutic
window, drugs with potentially serious adverse effects and drugs
for the treatment of serious and life-threatening conditions. For
some conditions, it is essential to individualize the dosage to the
particular situation, for example, in the case of diabetes
mellitus. As discussed hereinabove, a particular advantage of the
present invention is the reliability in the dosing. This is
particularly the case even in the event of a congested nose, such
as with a cold or an allergy, as delivery is to the anterior
region, which is not congested, though there may be some
secretion.
[0024] WO-A-00/51672 discloses a delivery device for delivering
substance, in particular a medicament, in a bi-directional flow
through the nasal cavities, that is, an air flow which passes into
one nostril, around the posterior margin of the nasal septum and in
the opposite direction out of the other nostril. This
bi-directional air flow advantageously acts to stimulate the
sensory nerves in the nasal mucosa, thereby conditioning the
subject for the delivery and providing a more comfortable delivery
situation.
[0025] It is an aim of the present invention to provide improved
nasal delivery devices and nasal delivery methods, which in
particular provide for one or both of increased systemic
bio-availability of the delivered substance and improved
dose-to-dose uniformity in the systemic bio-availability.
[0026] In one aspect the present invention provides a delivery
device for delivering a dose of substance for systemic uptake to a
nasal cavity of a subject, the delivery device comprising: a
nosepiece unit for insertion into a nasal cavity of a subject and
comprising an outlet unit which includes at least one nozzle for
delivering substance for systemic uptake substantially only to
surfaces in one or both of the anterior region and an anterior
section of the posterior region of the nasal cavity of the subject;
and a substance supply unit which is operable to deliver a dose of
substance to the at least one nozzle.
[0027] In another aspect the present invention provides a method of
delivering a dose of substance for systemic uptake to a nasal
cavity of a subject, the method comprising the steps of: disposing
a nosepiece unit in the nasal cavity of the subject, the nosepiece
unit comprising at least one nozzle for delivering substance for
systemic uptake to surfaces substantially only in one or both of
the anterior region and an anterior section of the posterior region
of the nasal cavity of the subject; and delivering a dose of
substance from a substance supply unit to the at least one nozzle,
such that the substance is delivered to surfaces substantially only
in one or both of the anterior region and an anterior section of
the posterior region.
[0028] Preferred embodiments of the present Invention will now be
described hereinbelow by way of example only with reference to the
accompanying drawings, in which:
[0029] FIG. 1(a) schematically illustrates the anatomy of the upper
respiratory tract of a human subject;
[0030] FIG. 1(b) illustrates the segmentation of a nasal cavity in
accordance with a preferred embodiment of the present
invention;
[0031] FIG. 2 schematically illustrates a nasal delivery device in
accordance with a first embodiment of the present invention;
[0032] FIG. 3 schematically illustrates the delivery device of FIG.
2 inserted in a nasal cavity of a subject for operation;
[0033] FIG. 4 schematically illustrates the delivery device of FIG.
2 during actuation;
[0034] FIG. 5 schematically illustrates the delivery device of FIG.
2 following actuation;
[0035] FIG. 6 schematically illustrates a nasal delivery device in
accordance with a second embodiment of the present invention;
[0036] FIG. 7 schematically illustrates the delivery device of FIG.
6 inserted in a nasal cavity of a subject for operation;
[0037] FIG. 8 schematically illustrates the delivery device of FIG.
6 during a first actuation phase in which a positive pressure is
created in the anterior region by the exhalation breath;
[0038] FIG. 9 schematically illustrates the delivery device of FIG.
6 during a second actuation phase in which the substance supply
unit is actuated to deliver substance into the anterior region;
[0039] FIG. 10 schematically illustrates the delivery device of
FIG. 6 following actuation;
[0040] FIG. 11 schematically illustrates a nasal delivery device in
accordance with a third embodiment of the present Invention;
[0041] FIG. 12 schematically illustrates the delivery device of
FIG. 11 inserted in a nasal cavity of a subject for operation;
[0042] FIG. 13 schematically illustrates the delivery device of
FIG. 11 during a first actuation phase in which a positive pressure
is created in the anterior region by the exhalation breath;
[0043] FIG. 14 schematically illustrates the delivery device of
FIG. 11 during a second actuation phase in which the substance
supply unit is actuated to deliver substance into the anterior
region;
[0044] FIG. 15 schematically illustrates the delivery device of
FIG. 11 following actuation;
[0045] FIG. 16 schematically illustrates a nasal delivery device in
accordance with a fourth embodiment of the present invention;
[0046] FIG. 17 schematically illustrates the delivery device of
FIG. 16 inserted in a nasal cavity of a subject for operation;
[0047] FIG. 18 schematically illustrates the delivery device of
FIG. 16 during actuation;
[0048] FIG. 19 schematically illustrates the delivery device of
FIG. 16 following actuation;
[0049] FIG. 20 schematically illustrates a nasal delivery device in
accordance with a fifth embodiment of the present invention;
[0050] FIG. 21 schematically illustrates the delivery device of
FIG. 20 inserted in a nasal cavity of a subject for operation;
[0051] FIG. 22 schematically illustrates the delivery device of
FIG. 20 during a first actuation phase in which the second
nosepiece member of the nosepiece unit is inflated by the
exhalation breath of the subject such as to partition the nasal
cavity;
[0052] FIG. 23 schematically illustrates the delivery device of
FIG. 20 during a second actuation phase in which the substance
supply unit is actuated to deliver substance into the anterior
region;
[0053] FIG. 24 schematically illustrates the delivery device of
FIG. 20 following actuation;
[0054] FIG. 25 schematically illustrates a nasal delivery device in
accordance with a sixth embodiment of the present invention;
[0055] FIG. 26 schematically illustrates the delivery device of
FIG. 25 inserted in a nasal cavity of a subject for operation;
[0056] FIG. 27 schematically illustrates the delivery device of
FIG. 25 during actuation;
[0057] FIG. 28 schematically illustrates the delivery device of
FIG. 25 following actuation;
[0058] FIG. 29 schematically illustrates a nasal delivery device in
accordance with a seventh embodiment of the present invention;
[0059] FIG. 30 schematically illustrates the delivery device of
FIG. 29 inserted in a nasal cavity of a subject for operation;
[0060] FIG. 31 schematically illustrates the delivery device of
FIG. 29 during actuation;
[0061] FIG. 32 schematically illustrates the delivery device of
FIG. 29 following actuation;
[0062] FIG. 33 schematically illustrates a nasal delivery device in
accordance with an eighth embodiment of the present invention;
[0063] FIG. 34 schematically illustrates the delivery device of
FIG. 33 inserted in a nasal cavity of a subject for operation;
[0064] FIG. 35 schematically illustrates the delivery device of
FIG. 33 during actuation; and
[0065] FIG. 36 schematically illustrates the delivery device of
FIG. 33 following actuation.
[0066] FIGS. 2 to 5 illustrate a nasal delivery device in
accordance with a first embodiment of the present invention.
[0067] The delivery device comprises a housing 15, a nosepiece unit
17 for fitting in a nasal cavity of a subject through which
substance is delivered to the nasal cavity, and a substance supply
unit 19 which is actuatable to deliver a metered dose of substance
to the nosepiece unit 17.
[0068] The nosepiece unit 17 comprises an outlet unit 21 which
extends into the nasal cavity into which the nosepiece unit 17 is
inserted, a first nosepiece member 23, in this embodiment a
frusto-conical element, which is disposed to one, proximal end of
the outlet unit 21 and is configured to obstruct, in this
embodiment close, the nostril into which the nosepiece unit 17 is
inserted, a second nosepiece member 25 which is disposed to the
other, distal end of the outlet unit 21 and is configured to
obstruct, in this embodiment close, the nasal cavity at a position
therealong, in this embodiment at a position corresponding
substantially to the nasal valve, such as to partition the nasal
cavity into a first, anterior region 27 between the first and
second nosepiece members 23, 25, which corresponds in volume to
about one-third of the nasal cavity, and a second, posterior region
29, which corresponds in volume to about the remaining two-thirds
of the nasal cavity, as illustrated in FIG. 3.
[0069] The outlet unit 21 comprises a support member 31, in this
embodiment a narrow, elongate element, to which the first and
second nosepiece members 23, 25 are supported, and at least one
nozzle 35, in this embodiment a plurality of laterally-directed
nozzles 35a, b, disposed between the first and second nosepiece
members 23, 25 for delivering substance to the anterior region 27
of the nasal cavity.
[0070] In this embodiment the nozzles 35a, b are configured to
provide an aerosol spray. In an alternative embodiment the nozzles
35a, b could be configured to deliver jets as columns of
substance.
[0071] In this embodiment the second nosepiece member 25 comprises
a resilient element 37, here in the form of an annular skirt, which
through its resilience acts to expand to obstruct the nasal cavity
in partitioning the same. In an alternative embodiment the
resilient element 37 could take the form of laterally-directed
wings, which together act to obstruct the nasal cavity in
partitioning the same.
[0072] In this embodiment the substance supply unit 19 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.
[0073] In another alternative embodiment the substance supply unit
19 could comprise a dry powder delivery unit which delivers metered
doses of substance, as a dry powder, on actuation thereof.
[0074] In yet another alternative embodiment the substance supply
unit 19 could comprise an aerosol canister which delivers metered
volumes of a propellant, preferably a hydrofluoroalkane (HFA)
propellant or the like, containing substance, either as a
suspension or solution.
[0075] In yet another alternative embodiment the substance supply
unit 19 could comprise a nebulizer which delivers metered doses of
substance, as an aerosol spray, on actuation thereof.
[0076] In this embodiment the substance supply unit 19 is a
multi-dose unit for delivering a plurality of metered doses of
substance. In another embodiment the substance supply unit 19 could
be a single-dose unit for delivering a single metered dose of
substance.
[0077] In this embodiment the substance supply unit 19 is
pre-primeable, here by loading a resilient element, and includes an
actuation mechanism 41 which, when triggered, releases the
resilient element and actuates the substance supply unit 19 to
deliver a metered dose of substance through the nozzles 35a, b of
the outlet unit 21.
[0078] Operation of the delivery device will now be described
hereinbelow with reference to FIGS. 3 to 5 of the accompanying
drawings.
[0079] Referring to FIG. 3, the nosepiece unit 17 is first inserted
into one of the nasal cavities of a subject until the first
nosepiece member 23 abuts the nares of the nostril, such as
sealingly to engage the skin-lined anterior section of the anterior
region of the nasal cavity. When inserted, the distal end of the
outlet unit 21 extends about 2 cm into the nasal cavity of the
subject, which corresponds in position to that of the nasal valve,
and the second nosepiece member 25 acts to obstruct the nasal
cavity at that point such as to partition the nasal cavity.
[0080] Referring to FIG. 4, the subject then actuates the actuation
mechanism 41, in this embodiment manually, which acts to actuate
the substance supply unit 19 to deliver a metered dose of substance
from the nozzles 35a, 35b of the outlet unit 21.
[0081] The metered dose of substance, in this embodiment in the
form of an aerosol spray, is confined to the anterior region 27 of
the nasal cavity as defined between the first and second nosepiece
members 23, 25. As described hereinabove, the present inventors
have recognized that the systemic uptake of substance as delivered
via the nasal cavity is, contrary to current thinking, enhanced
where delivered through the anterior region of the nasal cavity,
and thus, by confining the delivered dose of substance to the
anterior region, an enhanced systemic effect is obtained per unit
dose of substance as compared to the conventional delivery of
substances into the nasal cavity, such as generally by a nasal
spray or nasal drops.
[0082] Following actuation, as illustrated in FIG. 5, the nosepiece
unit 17 is withdrawn from the nasal cavity of the subject.
[0083] In one embodiment, where the delivery device is a
single-dose device, the device can be discarded.
[0084] In another embodiment, where the delivery device is a
multi-dose device, the device is ready for further use following
priming of the substance supply unit 19. In a preferred embodiment,
where the nosepiece unit 17 is replaceable, the nosepiece unit 17
can be replaced with a new nosepiece unit 17.
[0085] FIGS. 6 to 10 illustrate a nasal delivery device in
accordance with a second embodiment of the present invention.
[0086] The delivery device of this embodiment is very similar to
the delivery device of the above-described embodiment, and thus, in
order to avoid unnecessary duplication of description, only the
differences will be described in detail.
[0087] The delivery device of this embodiment differs from that of
the above-described embodiment in that the support member 31 of the
outlet unit 21 includes a gas delivery port 45 which is disposed at
a position between the first and second nosepiece members 23, 25,
and in further comprising a mouthpiece 47 which is fluidly
connected to the gas delivery port 45, such that, on exhalation
into the mouthpiece 47, an air flow is delivered to the gas
delivery port 45 which acts to develop a pressure in the
partitioned anterior region 27 as defined between the first and
second nosepiece members 23, 25, which acts to expand the anterior
region 27 and thereby promote the delivery of substance
thereto.
[0088] Operation of the delivery device is illustrated in FIGS. 7
to 10 of the accompanying drawings. The operation of the delivery
device of this embodiment is the same as that of the
above-described embodiment, except in that the subject exhales
through the mouthpiece 47 during actuation of the delivery device,
in order to cause expansion of the partitioned anterior
section.
[0089] In one alternative-embodiment the actuation mechanism 41
could be a breath-actuated mechanism, such that the actuation
mechanism 41 acts to actuate the substance supply unit 19 on the
generation of a predetermined pressure at the mouthpiece 47.
[0090] FIGS. 11 to 15 illustrate a nasal delivery device in
accordance with a third embodiment of the present invention.
[0091] The delivery device of this embodiment is very similar to
the delivery device of the above-described embodiment, and thus, in
order to avoid unnecessary duplication of description, only the
differences will be described in detail.
[0092] The delivery device of this embodiment differs from that of
the above-described embodiment in that the support member 31 of the
outlet unit 21 includes a gas delivery port 45 which is disposed at
a position between the first and second nosepiece members 23, 25,
and in further comprising a gas supply unit 49, in this embodiment
a compressible bulb, which is fluidly connected to the gas delivery
port 45 and actuatable to deliver an air flow to the gas delivery
port 45 which acts to develop a pressure in the partitioned
anterior region 27 as defined between the first and second
nosepiece members 23, 25, which acts to expand the anterior region
27 and thereby promote the delivery of substance thereto.
[0093] Operation of the delivery device is illustrated in FIGS. 12
to 15 of the accompanying drawings. The operation of the delivery
device of this embodiment is the same as that of the
above-described embodiment, except in that the subject actuates the
gas supply unit 49, in this embodiment by compressing the bulb,
during actuation of the delivery device, in order to cause
expansion of the partitioned anterior region 27.
[0094] FIGS. 16 to 19 illustrate a nasal delivery device in
accordance with a fourth embodiment of the present invention.
[0095] The delivery device comprises a housing 115, a nosepiece
unit 117 for fitting in a nasal cavity of a subject through which
substance is delivered to the nasal cavity, and a substance supply
unit 119 which is actuatable to deliver a metered dose of substance
to the nosepiece unit 117.
[0096] The nosepiece unit 117 comprises an outlet unit 121 which
extends into the nasal cavity into which the nosepiece unit 117 is
inserted, and a nosepiece member 123, in this embodiment a
frusto-conical element, which is disposed to one, proximal end of
the outlet unit 121 and is configured to obstruct, in this
embodiment close, the nostril into which the nosepiece unit 117 is
inserted.
[0097] The outlet unit 121 comprises a support member 131, in this
embodiment a narrow, elongate element, to which the nosepiece
member 123 is supported, and at least one nozzle 135, in this
embodiment a plurality of laterally-directed nozzles 135a, b, which
is disposed such as to deliver substance substantially entirely to
the anterior region 137 of the nasal cavity relative to the
posterior region of the nasal cavity 139. By configuring the at
least one nozzle 135 such as to direct the substance laterally to
the surfaces of the anterior region 137 of the nasal cavity, the
substance is substantially entirely delivered to the anterior
region 137 of the nasal cavity relative to the posterior region 139
of the nasal cavity.
[0098] In this embodiment the nozzles 135a, b are configured to
provide an aerosol spray. In an alternative embodiment the nozzles
135a, b could be configured to deliver jets as columns of
substance.
[0099] In this embodiment the substance supply unit 119 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.
[0100] In another alternative embodiment the substance supply unit
119 could comprise a dry powder delivery unit which delivers
metered doses of substance, as a dry powder, on actuation
thereof.
[0101] In yet another alternative embodiment the substance supply
unit 119 could comprise an aerosol canister which delivers metered
volumes of a propellant, preferably a hydrofluoroalkane (HFA)
propellant or the like, containing substance, either as a
suspension or solution.
[0102] In yet another alternative embodiment the substance supply
unit 119 could comprise a nebulizer which delivers metered doses of
substance, as an aerosol spray, on actuation thereof.
[0103] In this embodiment the substance supply unit 119 is a
multi-dose unit for delivering a plurality of metered doses of
substance. In another embodiment the substance supply unit 119
could be a single-dose unit for delivering a single metered dose of
substance.
[0104] In this embodiment the substance supply unit 119 is
pre-primeable, here by loading a resilient element, and includes an
actuation mechanism 141 which, when triggered, releases the
resilient element and actuates the substance supply unit 119 to
deliver a metered dose of substance through the nozzles 135a, b of
the outlet unit 121.
[0105] In another embodiment the substance supply unit 119 could be
manually actuated, for example, by manually depressing or
compressing an applicator element.
[0106] Operation of the delivery device will now be described
hereinbelow with reference to FIGS. 17 to 19 of the accompanying
drawings.
[0107] Referring to FIG. 17, the nosepiece unit 117 is first
Inserted Into one of the nasal cavities of a subject until the
nosepiece member 123 abuts the nares of the nostril, such as
sealingly to engage the skin-lined anterior section of the anterior
region of the nasal cavity. When inserted, the distal end of the
outlet unit 121 extends about 2 cm into the nasal cavity of the
subject, which corresponds in position to that of the nasal
valve.
[0108] Referring to FIG. 18, the subject then actuates the
actuation mechanism 141, in this embodiment manually, which acts to
actuate the substance supply unit 119 to deliver a metered dose of
substance from the nozzles 135a, 135b of the outlet unit 121.
[0109] The metered dose of substance, in this embodiment in the
form of an aerosol spray, is confined to the anterior region 127 of
the nasal cavity. As described hereinabove, the present inventors
have recognized that the systemic uptake of substance as delivered
via the nasal cavity is, contrary to current thinking, enhanced
where delivered through the anterior region 127 of the nasal
cavity, and thus, by confining the delivered dose of substance to
the anterior region 127, an enhanced systemic effect is obtained
per unit dose of substance as compared to the conventional delivery
of substances into the nasal cavity, such as generally by a nasal
spray or nasal drops.
[0110] Following actuation, as illustrated in FIG. 19, the
nosepiece unit 117 is withdrawn from the nasal cavity of the
subject.
[0111] In one embodiment, where the delivery device is a
single-dose device, the device can be discarded.
[0112] In another embodiment, where the delivery device is a
multi-dose device, the device is ready for further use following
priming of the substance supply unit 119. In a preferred
embodiment, where the nosepiece unit 117 is replaceable, the
nosepiece unit 117 can be replaced with a new nosepiece unit
117.
[0113] FIGS. 20 to 24 illustrate a nasal delivery device in
accordance with a fifth embodiment of the present invention.
[0114] The delivery device comprises a housing 215, a nosepiece
unit 217 for fitting in a nasal cavity of a subject through which
substance is delivered to the nasal cavity, a substance supply unit
219 which is actuatable to deliver a metered dose of substance to
the nosepiece unit 117, and a mouthpiece unit 2220 through which
the subject exhales.
[0115] The nosepiece unit 217 comprises an outlet unit 221 which
extends into the nasal cavity into which the nosepiece unit 117 is
inserted, a first nosepiece member 223, in this embodiment a
frusto-conical element, which is disposed to one, proximal end of
the outlet unit 221 and is configured to obstruct, in this
embodiment close, the nostril into which the nosepiece unit 217 is
inserted, a second, expandable nosepiece member 225 which is
disposed to the other, distal end of the outlet unit 221 and is
configured, when expanded, to obstruct, in this embodiment close,
the nasal cavity at a position therealong, in this embodiment at a
position corresponding substantially to the nasal valve, such as to
partition the nasal cavity into a first, anterior region 227
between the first and second nosepiece members 223, 225, which
corresponds in volume to about one-third of the nasal cavity, and a
second, posterior region 229, which corresponds in volume to about
the remaining two-thirds of the nasal cavity, as illustrated in
FIG. 22.
[0116] The outlet unit 221 comprises a support member 231, in this
embodiment a narrow, elongate element, to which the first and
second nosepiece members 223, 225 are supported, and at least one
nozzle 235, in this embodiment a plurality of laterally-directed
nozzles 235a, b, disposed between the first and second nosepiece
members 223, 225 for delivering substance to the anterior region
227 of the nasal cavity.
[0117] In this embodiment the nozzles 235a, b are configured to
provide an aerosol spray. In an alternative embodiment the nozzles
235a, b could be configured to deliver jets as columns of
substance.
[0118] In this embodiment the second nosepiece member 225 comprises
an inflatable member which is fluidly connected to the mouthpiece
unit 220, such that, on exhalation by the subject through the
mouthpiece unit 220, the second nosepiece member 225 is expanded to
obstruct the nasal cavity in partitioning the same.
[0119] In this embodiment the substance supply unit 219 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.
[0120] In another alternative embodiment the substance supply unit
219 could comprise a dry powder delivery unit which delivers
metered doses of substance, as a dry powder, on actuation
thereof.
[0121] In yet another alternative embodiment the substance supply
unit 219 could comprise an aerosol canister which delivers metered
volumes of a propellant, preferably a hydrofluoroalkane (HFA)
propellant or the like, containing substance, either as a
suspension or solution.
[0122] In yet another alternative embodiment the substance supply
unit 219 could comprise a nebulizer which delivers metered doses of
substance, as an aerosol spray, on actuation thereof.
[0123] In this embodiment the substance supply unit 219 is a
multi-dose unit for delivering a plurality of metered doses of
substance. In another embodiment the substance supply unit 219
could be a single-dose unit for delivering a single metered dose of
substance.
[0124] In this embodiment the substance supply unit 219 is
pre-primeable, here by loading a resilient element, and includes an
actuation mechanism 241 which, when triggered, releases the
resilient element and actuates the substance supply unit 219 to
deliver a metered dose of substance through the nozzles 235a, b of
the outlet unit 221.
[0125] In this embodiment the actuation mechanism 241 is a
manually-actuated unit, but in another embodiment could be a
breath-actuated unit which is actuated in response to the
generation of a predetermined pressure at the mouthpiece unit 220,
which is sufficient to provide for inflation of the second
nosepiece member 225.
[0126] Operation of the delivery device will now be described
hereinbelow with reference to FIGS. 21 to 24 of the accompanying
drawings.
[0127] Referring to FIG. 21, the nosepiece unit 217 is first
inserted into one of the nasal cavities of a subject until the
first nosepiece member 223 abuts the nares of the nostril, such as
sealingly to engage the skin-lined anterior section of the anterior
region of the nasal cavity. When Inserted, the distal end of the
outlet unit 221 extends about 2 cm into the nasal cavity of the
subject, which corresponds in position to that of the nasal
valve.
[0128] Referring to FIG. 22, the subject then exhales through the
mouthpiece unit 220, and the exhaled air flow acts to generate a
pressure within the second nosepiece member 225, which is inflated
such as to obstruct the nasal cavity and thereby partition the
anterior and posterior regions 227, 229 of the nasal cavity.
[0129] Referring to FIG. 23, the subject then actuates the
actuation mechanism 241, in this embodiment manually, which acts to
actuate the substance supply unit 219 to deliver a metered dose of
substance from the nozzles 235a, 235b of the outlet unit 221.
[0130] The metered dose of substance, in this embodiment in the
form of an aerosol spray, is confined to the anterior region 227 of
the nasal cavity as defined between the first and second nosepiece
members 223, 225. As described hereinabove, the present Inventors
have recognized that the systemic uptake of substance as delivered
via the nasal cavity is, contrary to current thinking, enhanced
where delivered through the anterior region 227 of the nasal
cavity, and thus, by confining the delivered dose of substance to
the anterior region 227, an enhanced systemic effect is obtained
per unit dose of substance as compared to the conventional delivery
of substances into the nasal cavity, such as generally by a nasal
spray or nasal drops.
[0131] Following actuation, as illustrated in FIG. 24, the
nosepiece unit 217 is withdrawn from the nasal cavity of the
subject.
[0132] In one embodiment, where the delivery device is a
single-dose device, the device can be discarded.
[0133] In another embodiment, where the delivery device is a
multi-dose device, the device is ready for further use following
priming of the substance supply unit 219. In a preferred
embodiment, where the nosepiece unit 217 is replaceable, the
nosepiece unit 217 can be replaced with a new nosepiece unit
217.
[0134] In one alternative embodiment the second nosepiece member
225 could instead be mechanically expanded, for example, by
expandable arm members.
[0135] FIGS. 25 to 28 illustrate a nasal delivery device in
accordance with a sixth embodiment of the present invention.
[0136] The delivery device comprises a housing 315, a nosepiece
unit 317 for fitting in a nasal cavity of a subject through which
substance is delivered to the nasal cavity, a substance supply unit
319 which is actuatable to deliver metered doses of first and
second substances to the nosepiece unit 317, and a mouthpiece unit
320 through which the subject exhales.
[0137] The nosepiece unit 317 comprises an outlet unit 321 which
extends into the nasal cavity into which the nosepiece unit 317 is
inserted, a first nosepiece member 323, in this embodiment a
frusto-conical element, which is disposed to one, proximal end of
the outlet unit 321 and is configured to obstruct, in this
embodiment close, the nostril into which the nosepiece unit 317 is
inserted, a second nosepiece member 325 which is disposed to the
other, distal end of the outlet unit 321 and is configured to
obstruct, in this embodiment close, the nasal cavity at a position
therealong, in this embodiment at a position corresponding
substantially to the nasal valve, such as to partition the nasal
cavity into a first, anterior region 327 between the first and
second nosepiece members 323, 325, which corresponds in volume to
about one-third of the nasal cavity, and a second, posterior region
329, which corresponds in volume to about the remaining two-thirds
of the nasal cavity, as illustrated in FIG. 26.
[0138] The outlet unit 321 comprises a support member 331, in this
embodiment a narrow, elongate element, to which the first and
second nosepiece members 323, 325 are supported, at least one
first, anterior nozzle 335, in this embodiment a plurality of
laterally-directed anterior nozzles 335a, b, which is disposed
between the first and second nosepiece members 323, 325 for
delivering substance, in this embodiment substance for systemic
application, to the anterior region 327 of the nasal cavity, and at
least one second, posterior nozzle 336, in this embodiment a
single, axially-directed nozzle, for delivering substance, in this
embodiment substance for topical or CNS application, to the
posterior region 329 of the nasal cavity.
[0139] In this embodiment the anterior nozzles 335a, b are
configured to provide an aerosol spray. In an alternative
embodiment the anterior nozzles 335a, b could be configured to
deliver jets as columns of substance.
[0140] In this embodiment the posterior nozzle 336 is configured to
provide an aerosol spray. In an alternative embodiment the
posterior nozzle 336 could be configured to deliver a jet as a
column of substance.
[0141] In this embodiment the second nosepiece member 325 comprises
a resilient element 337, here in the form of an annular skirt,
which through Its resilience acts to expand to obstruct the nasal
cavity in partitioning the same. In an alternative embodiment the
resilient element 337 could take the form of laterally-directed
wings, which together act to obstruct the nasal cavity in
partitioning the same.
[0142] In this embodiment the substance supply unit 319 comprises a
mechanical delivery pump, in particular a liquid delivery pump or a
powder delivery pump, which delivers metered doses of first and
second substances on actuation thereof.
[0143] In another alternative embodiment the substance supply unit
319 could comprise a dry powder delivery unit which delivers
metered doses of first and second substances, as dry powders, on
actuation thereof.
[0144] In yet another alternative embodiment the substance supply
unit 319 could comprise an aerosol canister which delivers first
and second metered volumes of a propellant, preferably a
hydrofluoroalkane (HFA) propellant or the like, each containing
substance, either as a suspension or solution.
[0145] In yet another alternative embodiment the substance supply
unit 319 could comprise a nebulizer which delivers metered doses of
first and second substances, as aerosol sprays, on actuation
thereof.
[0146] In this embodiment the substance supply unit 319 is a
multi-dose unit for delivering a plurality of metered doses of
first and second substances. In another embodiment the substance
supply unit 319 could be a single-dose unit for delivering a single
metered dose of first and second substances.
[0147] In this embodiment the substance supply unit 319 is
pre-primeable, here by loading a resilient element, and includes an
actuation mechanism 341 which, when triggered, releases the
resilient element and actuates the substance supply unit 319 to
deliver metered doses of first and second substances through the
respective ones of the anterior nozzles 335a, b and posterior
nozzle 336 of the outlet unit 321.
[0148] Operation of the delivery device will now be described
hereinbelow with reference to FIGS. 26 to 28 of the accompanying
drawings.
[0149] Referring to FIG. 26, the nosepiece unit 317 is first
Inserted into one of the nasal cavities of a subject until the
first nosepiece member 323 abuts the nares of the nostril, such as
sealingly to engage the skin-lined anterior section of the anterior
region of the nasal cavity. When inserted, the distal end of the
outlet unit 321 extends about 2 cm into the nasal cavity of the
subject, which corresponds in position to that of the nasal valve,
and the second nosepiece member 325 acts to obstruct the nasal
cavity at that point such as to partition the nasal cavity.
[0150] Referring to FIG. 27, the subject then actuates the
actuation mechanism 341, in this embodiment manually, which acts to
actuate the substance supply unit 319 to deliver a metered dose of
a first substance, in this embodiment substance for systemic
application, from the anterior nozzles 335a, 335b of the outlet
unit 321 and a metered dose of a second substance, in this
embodiment substance for topical or CNS application, from the
posterior nozzle 336 of the outlet unit 321.
[0151] The metered dose of the first substance, in this embodiment
in the form of an aerosol spray, is confined to the anterior region
327 of the nasal cavity as defined between the first and second
nosepiece members 323, 325. As described hereinabove, the present
inventors have recognized that the systemic uptake of substance as
delivered via the nasal cavity is, contrary to current thinking,
enhanced where delivered through the anterior region 327 of the
nasal cavity, and thus, by confining the delivered dose of
substance to the anterior region 327, an enhanced systemic effect
is obtained per unit dose of substance as compared to the
conventional delivery of substances into the nasal cavity, such as
generally by a nasal spray or nasal drops.
[0152] Following actuation, as illustrated in FIG. 28, the
nosepiece unit 317 is withdrawn from the nasal cavity of the
subject.
[0153] In one embodiment, where the delivery device is a
single-dose device, the device can be discarded.
[0154] In another embodiment, where the delivery device is a
multi-dose device, the device is ready for further use following
priming of the substance supply unit 319. In a preferred
embodiment, where the nosepiece unit 317 is replaceable, the
nosepiece unit 317 can be replaced with a new nosepiece unit
317.
[0155] FIGS. 29 to 32 illustrate a nasal delivery device in
accordance with a seventh embodiment of the present invention.
[0156] The delivery device comprises a housing 415, a nosepiece
unit 417 for fitting in a nasal cavity of a subject through which
substance is delivered to the nasal cavity, a substance supply unit
419 which is actuatable to deliver a metered dose of substance to
the nosepiece unit 417, and a mouthpiece unit 420 through which the
subject exhales.
[0157] The nosepiece unit 417 comprises a body unit 421 which
comprises a first nosepiece member 423, in this embodiment a
frusto-conical element, which is disposed at one, proximal end and
is configured to obstruct, in this embodiment close, the nostril
into which the nosepiece unit 417 is inserted, and a second
nosepiece member 425 which is disposed to the other, distal end and
comprises a flexible, elongate element which is sufficiently
compliant to extend into, and in one embodiment, through the nasal
valve. The second nosepiece member 425 has a shape, size and
surface properties which enable the second nosepiece member 425
comfortably to penetrate the nasal valve. In this embodiment, when
the nosepiece unit 417 is fully inserted into a nasal cavity, the
distal end of the second nosepiece member 425 extends from about 3
cm to about 5 cm into the nasal cavity.
[0158] The nosepiece unit 417 further comprises at least one, in
this embodiment a plurality of laterally-directed anterior nozzles
435a, b which are configured such as to deliver substance, in this
embodiment substance for systemic application, to surfaces within
the anterior region of the nasal cavity, and at least one second,
posterior nozzle 436, in this embodiment a single, axially-directed
nozzle, for delivering the substance to surfaces in an anterior
section of the posterior region of the nasal cavity, in this
embodiment an anterior third of the posterior region, and a
preferred embodiment a mid-anterior third of the posterior region,
as illustrated in FIG. 1(b).
[0159] In this embodiment the anterior nozzles 435a, b are
configured to provide an aerosol spray. In an alternative
embodiment the anterior nozzles 435a, b could be configured to
deliver jets as columns of substance.
[0160] In this embodiment the posterior nozzle 436 is configured to
provide an aerosol spray. In an alternative embodiment the
posterior nozzle 436 could be configured to deliver a jet as a
column of substance.
[0161] In this embodiment the substance supply unit 419 comprises a
mechanical delivery pump, in particular a liquid delivery pump or a
powder delivery pump, which delivers a metered dose of substance on
actuation thereof.
[0162] In another alternative embodiment the substance supply unit
419 could comprise a dry powder delivery unit which delivers a
metered dose of substance, as a dry powder, on actuation
thereof.
[0163] In yet another alternative embodiment the substance supply
unit 419 could comprise an aerosol canister which delivers a
metered volume of a propellant, preferably a hydrofluoroalkane
(HFA) propellant or the like, containing substance, either as a
suspension or solution.
[0164] In yet another alternative embodiment the substance supply
unit 419 could comprise a nebulizer which delivers a metered dose
of substance, as an aerosol spray, on actuation thereof.
[0165] In this embodiment the substance supply unit 419 is a
multi-dose unit for delivering a plurality of metered doses of
substance. In another embodiment the substance supply unit 419
could be a single-dose unit for delivering a single metered dose of
substance.
[0166] In this embodiment the substance supply unit 419 is
pre-primeable, here by loading a resilient element, and includes an
actuation mechanism 441 which, when triggered, releases the
resilient element and actuates the substance supply unit 419 to
deliver a metered dose of substance through the anterior nozzles
435a, b and the posterior nozzle 436. In this embodiment the
actuation mechanism 441 is breath actuated in response to
exhalation by the subject through the mouthpiece unit 420.
[0167] Operation of the delivery device will now be described
hereinbelow with reference to FIGS. 30 to 32 of the accompanying
drawings.
[0168] Referring to FIG. 30, the nosepiece unit 417 is first
inserted into one of the nasal cavities of a subject until the
first nosepiece member 423 abuts the nares of the nostril, such as
sealingly to engage the skin-lined anterior section of the anterior
region of the nasal cavity, and the second nosepiece member 425
extends into the nasal valve.
[0169] Referring to FIG. 31, the subject then exhales through the
mouthpiece unit 420, which exhalation triggers the actuation
mechanism 441, which in turn acts to actuate the substance supply
unit 419 to deliver a metered dose of substance, in this embodiment
substance for systemic application, from the anterior nozzles 435a,
435b and the posterior nozzle 436.
[0170] The substance as delivered from the anterior nozzles 435a, b
is delivered to surfaces in the anterior region of the nasal
cavity, and the substance as delivered from the posterior nozzle
436 is delivered to an anterior section of the posterior region of
the nasal cavity, in this embodiment the anterior third of the
posterior region of the nasal cavity, and more preferably
substantially entirely to the mid-anterior third of the posterior
region of the nasal cavity. As described hereinabove, the present
inventors have recognized that the systemic uptake of substance as
delivered via the nasal cavity is, contrary to current thinking,
enhanced where delivered through the anterior region of the nasal
cavity and the anterior third of the posterior region of the nasal
cavity, and thus, by confining the delivered dose of substance to
the anterior region and the anterior third of the posterior region
of the nasal cavity, an enhanced systemic effect is obtained per
unit dose of substance as compared to the conventional delivery of
substances into the nasal cavity, such as generally by a nasal
spray or nasal drops.
[0171] Following actuation, as illustrated in FIG. 32, the
nosepiece unit 417 is withdrawn from the nasal cavity of the
subject.
[0172] In one embodiment, where the delivery device is a
single-dose device, the device can be discarded.
[0173] In another embodiment, where the delivery device is a
multi-dose device, the device is ready for further use following
priming of the substance supply unit 419. In a preferred
embodiment, where the nosepiece unit 417 is replaceable, the
nosepiece unit 417 can be replaced with a new nosepiece unit
417.
[0174] FIGS. 33 to 36 illustrate a nasal delivery device in
accordance with an eighth embodiment of the present invention.
[0175] The delivery device comprises a housing 515, a nosepiece
unit 517 for fitting in a nasal cavity of a subject through which
substance is delivered to the nasal cavity, and a substance supply
unit 519 which is actuatable to deliver a metered dose of substance
to the nosepiece unit 517.
[0176] The nosepiece unit 517 comprises a body unit 521 which
comprises a first nosepiece member 523, in this embodiment a
frusto-conical element, which is disposed at one, proximal end and
is configured to obstruct, in this embodiment close, the nostril
into which the nosepiece unit 517 is inserted, a second nosepiece
member 525 which is disposed to the other, distal end and comprises
a flexible, elongate element which is sufficiently compliant to
extend into, and in one embodiment, through the nasal valve, and a
flow channel 527 which is fluidly connected to an actuation
mechanism 541 of the substance supply unit 519, as will be
described in more detail hereinbelow.
[0177] The nosepiece unit 517 further comprises at least one, in
this embodiment a plurality of laterally-directed anterior nozzles
535a, b which are configured such as to deliver substance, in this
embodiment substance for systemic application, to surfaces within
the anterior region of the nasal cavity, and at least one second,
posterior nozzle 536, in this embodiment a single, axially-directed
nozzle, for delivering the substance to surfaces in an anterior
section of the posterior region of the nasal cavity, in this
embodiment an anterior third of the posterior region, and a
preferred embodiment a mid-anterior third of the posterior region,
as illustrated in FIG. 1(b).
[0178] In this embodiment the anterior nozzles 535a, b are
configured to provide an aerosol spray. In an alternative
embodiment the anterior nozzles 535a, b could be configured to
deliver jets as columns of substance.
[0179] In this embodiment the posterior nozzle 536 is configured to
provide an aerosol spray. In an alternative embodiment the
posterior nozzle 536 could be configured to deliver a jet as a
column of substance.
[0180] In this embodiment the substance supply unit 519 comprises a
mechanical delivery pump, in particular a liquid delivery pump or a
powder delivery pump, which delivers a metered dose of substance on
actuation thereof.
[0181] In another alternative embodiment the substance supply unit
519 could comprise a dry powder delivery unit which delivers a
metered dose of substance, as a dry powder, on actuation
thereof.
[0182] In yet another alternative embodiment the substance supply
unit 519 could comprise an aerosol canister which delivers a
metered volume of a propellant, preferably a hydrofluoroalkane
(HFA) propellant or the like, containing substance, either as a
suspension or solution.
[0183] In yet another alternative embodiment the substance supply
unit 519 could comprise a nebulizer which delivers a metered dose
of substance, as an aerosol spray, on actuation thereof.
[0184] In this embodiment the substance supply unit 519 is a
multi-dose unit for delivering a plurality of metered doses of
substance. In another embodiment the substance supply unit 519
could be a single-dose unit for delivering a single metered dose of
substance.
[0185] In this embodiment the substance supply unit 519 is
pre-primeable, here by loading a resilient element, and includes an
actuation mechanism 541 which, when triggered, releases the
resilient element and actuates the substance supply unit 519 to
deliver a metered dose of substance through the anterior nozzles
535a, b and the posterior nozzle 536. In this embodiment the
actuation mechanism 541 is breath actuated in response to nasal
exhalation by the subject, which nasal exhalation acts to generate
a positive pressure in the nasal cavity, which is fluidly connected
to the actuation mechanism 541 by the flow channel 527 of the
nosepiece unit 517. The generation of a positive pressure in the
nasal cavity also advantageously provides for expansion of the
nasal cavity, which facilitates deposition on the surfaces within
the nasal cavity.
[0186] Operation of the delivery device will now be described
hereinbelow with reference to FIGS. 34 to 36 of the accompanying
drawings.
[0187] Referring to FIG. 34, the nosepiece unit 517 is first
inserted into one of the nasal cavities of a subject until the
first nosepiece member 523 abuts the nares of the nostril, such as
sealingly to engage the skin-lined anterior section of the anterior
region of the nasal cavity, and the second nosepiece member 525
extends into the nasal valve.
[0188] Referring to FIG. 35, the subject then exhales, or at least
attempts to exhale through the nasal cavity, which nasal exhalation
triggers the actuation mechanism 441, which in turn acts to actuate
the substance supply unit 519 to deliver a metered dose of
substance, in this embodiment substance for systemic application,
from the anterior nozzles 535a, 535b and the posterior nozzle
536.
[0189] The substance as delivered from the anterior nozzles 535a, b
is delivered to surfaces in the anterior region of the nasal
cavity, and the substance as delivered from the posterior nozzle
536 is delivered to an anterior section of the posterior region of
the nasal cavity, in this embodiment the anterior third of the
posterior region of the nasal cavity, and more preferably
substantially to the mid-anterior third of the posterior region of
the nasal cavity. As described hereinabove, the present inventors
have recognized that the systemic uptake of substance as delivered
via the nasal cavity is, contrary to current thinking, enhanced
where delivered through the anterior region of the nasal cavity and
the anterior third of the posterior region of the nasal cavity, and
thus, by confining the delivered dose of substance to the anterior
region and the anterior third of the posterior region of the nasal
cavity, an enhanced systemic effect is obtained per unit dose of
substance as compared to the conventional delivery of substances
into the nasal cavity, such as generally by a nasal spray or nasal
drops.
[0190] Following actuation, as illustrated in FIG. 36, the
nosepiece unit 517 is withdrawn from the nasal cavity of the
subject.
[0191] In one embodiment, where the delivery device is a
single-dose device, the device can be discarded.
[0192] In another embodiment, where the delivery device is a
multi-dose device, the device is ready for further use following
priming of the substance supply unit 519. In a preferred
embodiment, where the nosepiece unit 417 is replaceable, the
nosepiece unit 517 can be replaced with a new nosepiece unit
517.
[0193] Finally, it will be understood that the present Invention
has been described in its preferred embodiments and can be modified
in many different ways without departing from the scope of the
invention as defined by the appended claims.
[0194] For example, in one embodiment the substance could be
formulated such as to hinder mucociliary clearance, as would occur
from the dilated mucosal surfaces in the posterior region of the
nasal cavity, and also prevent gravitational flow of the substance
and dripping out of the substance from the nasal cavity. Typically,
the formulation could have adhesive properties, for example, as a
thixotropic formulation, and in one embodiment could be formulated
in the manner of a gel.
[0195] In another embodiment the substance supply units 19, 119,
219, 319, 419, 519 of the above-described embodiments could be
configured to deliver a combination of liquid and powdered
substances.
REFERENCES
[0196] 1. Cole, P, The Respiratory Role of the Upper Airway, Mosby,
1992, pages 7 and 8. [0197] 2. Daley-Yates, P T et al, Systemic
bloavailability of fluticasone propionate administered as nasal
drops and aqueous nasal spray formulations, Br J Clin Pharmacol,
January 2001, 51(1), pages 103 to 105. [0198] 3. Harris A S et al,
intranasal administration of peptides: nasal deposition, biological
response and absorption of desmopressin, 3 Pharm Sci, November
1986, 75(11), pages 1085 to 1088. [0199] 4. 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. [0200] 5. Zacharek, M A et al, Sagittal and
Coronal Dimensions of the Ethmoid Roof: A Radloanatomic Study, Am J
Rhinol 2005, Vol 19, pages 348 to 352.
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