U.S. patent application number 12/871443 was filed with the patent office on 2011-10-27 for delivery devices.
This patent application is currently assigned to OptiNose AS. Invention is credited to Per Gisle Djupesland, Stuart Brian William Kay, Martin Joseph Murphy, Andrew Gordon Pocock.
Application Number | 20110259329 12/871443 |
Document ID | / |
Family ID | 28052518 |
Filed Date | 2011-10-27 |
United States Patent
Application |
20110259329 |
Kind Code |
A1 |
Djupesland; Per Gisle ; et
al. |
October 27, 2011 |
DELIVERY DEVICES
Abstract
A breath-actuated delivery device includes a mouthpiece through
which a subject in use exhales, an air channel which is in fluid
communication with the mouthpiece, and a flexible diaphragm which
is disposed in the air channel. The diaphragm provides for at least
a restricted air flow through the air channel until a
predeterminable actuation pressure is developed in the mouthpiece,
and, on generation of the predeterminable actuation pressure in the
mouthpiece, provides for an air flow through the air channel.
Inventors: |
Djupesland; Per Gisle;
(Oslo, NO) ; Murphy; Martin Joseph; (Letchworth
Garden City, GB) ; Kay; Stuart Brian William;
(Melbourn, GB) ; Pocock; Andrew Gordon; (Royston,
GB) |
Assignee: |
OptiNose AS
Oslo
NO
|
Family ID: |
28052518 |
Appl. No.: |
12/871443 |
Filed: |
August 30, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10568391 |
Dec 21, 2006 |
7784460 |
|
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12871443 |
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Current U.S.
Class: |
128/203.18 ;
128/203.12; 128/203.21 |
Current CPC
Class: |
A61M 11/02 20130101;
A61M 15/0098 20140204; A61M 15/0091 20130101; A61M 15/08 20130101;
A61M 15/00 20130101; A61M 15/0021 20140204; A61M 15/0018
20140204 |
Class at
Publication: |
128/203.18 ;
128/203.21; 128/203.12 |
International
Class: |
A61M 15/08 20060101
A61M015/08; A61M 15/00 20060101 A61M015/00 |
Foreign Application Data
Date |
Code |
Application Number |
Aug 14, 2003 |
GB |
0319119.4 |
Aug 16, 2004 |
IB |
PCT/IB2004/002751 |
Claims
1-66. (canceled)
67. A breath-actuated delivery device, comprising: a mouthpiece
through which a subject in use exhales; an air channel which is in
fluid communication with the mouthpiece; and a flexible diaphragm
which is disposed in the air channel, the diaphragm providing for
at least a restricted air flow through the air channel until a
predeterminable actuation pressure is developed in the mouthpiece,
and, on generation of the predeterminable actuation pressure in the
mouthpiece, providing for an air flow through the air channel.
68. The delivery device of claim 67, wherein the diaphragm at least
substantially closes the air channel until the predeterminable
actuation pressure is developed in the mouthpiece.
69. The delivery device of claim 68, wherein the diaphragm closes
the air channel until the predeterminable actuation pressure is
developed in the mouthpiece.
70. The delivery device of claim 67, further comprising: a
rupturing element for rupturing the diaphragm on generation of the
predeterminable actuation pressure in the mouthpiece.
71. The delivery device of claim 67, wherein the diaphragm is a
resilient element.
72. The delivery device of claim 67, wherein the delivery device is
a nasal delivery device, and further comprising: a nosepiece for
fitting to a nostril of the subject and through which substance is
delivered to the nasal airway of the subject.
73. The delivery device of claim 72, wherein the nosepiece is in
fluid communication with the air channel, and an air flow, when
delivered through the air channel, acts to entrain substance.
Description
[0001] The present invention relates to a delivery device, in
particular a breath-actuated nasal delivery device, for and a
method of delivering substance, in particular one of a liquid, as a
suspension or solution, or a powder containing a medicament,
especially systemic or topical pharmaceuticals, or a vaccine to the
nasal airway of a subject.
[0002] Referring to FIG. 8, the nasal airway 1 comprises the two
nasal cavities separated by the nasal septum, which airway 1
includes numerous ostia, such as the paranasal sinus ostia 3 and
the tubal ostia 5, and olfactory cells, and is lined by the nasal
mucosa. The nasal airway 1 can communicate with the nasopharynx 7,
the oral cavity 9 and the lower airway 11, with the nasal airway 1
being in selective communication with the anterior region of the
nasopharynx 7 and the oral cavity 9 by opening and closing of the
oropharyngeal velum 13. The velum 13, which is often referred to as
the soft palate, is illustrated in solid line in the closed
position, as achieved by providing a certain positive pressure in
the oral cavity 9, such as achieved on exhalation through the oral
cavity 9, and in dashed line in the open position.
[0003] 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.
[0004] 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.
[0005] 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 mucosa advantageously provides for
rapid systemic uptake.
[0006] 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 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.
[0007] 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.
[0008] 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. The nasal delivery technique of the present invention
allows for delivery to the olfactory region, which region is
located in the superior region of the nasal cavities and represents
the only region where it is possible to circumvent the
blood-to-brain barrier (BBB) and enable communication with the
cerebrospinal fluid (CSF) and the brain.
[0009] Also, it is expected that the nasal delivery technique of
the present invention will allow for the effective delivery of
vaccines.
[0010] 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.
[0011] To date, nasal medicaments have been primarily delivered as
drops or by mechanical nasal spray pumps. With mechanical spray
pumps, the mean particle size is typically between 40 .mu.m and 80
.mu.m in order to prevent the inhalation of delivered particles. In
general, particles smaller than 10 .mu.m will bypass the nose and
can be inhaled. Indeed, the new FDA guidelines require that the
fraction of particles less than 10 .mu.m be at most 5%.
[0012] Whilst the provision of a spray having a larger mean
particle size prevents the inhalation of the particles, these
larger particles are not optimal for achieving a good distribution
to the nasal mucosa.
[0013] The applicant has now recognized that the closure of the
oropharyngeal velum during the delivery of a substance to the nasal
airway prevents the possible inhalation of the substance, thereby
enabling the delivery of an aerosol having a much smaller mean
particle size than achieved by traditional nasal spray pumps. In
this way, an aerosol can be generated which has an optimal particle
size distribution.
[0014] In addition, the applicant has recognized that, by
establishing a bi-directional flow through the nasal cavities as
described in WO-A-00/51672, 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, an aerosol having
an optimal flow rate and timing can be generated. Furthermore, the
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.
[0015] A yet further advantage is that the air flow acts to create
a positive pressure inside the nasal passages connected in series,
which tends to expand and widen narrow and congested regions.
[0016] A still yet further advantage is that the two-point fixation
of the device in the nose with a well-fitting nozzle and in the
mouth provides a much more stable and reproducible positioning of
the device as compared to traditional spray pumps. Thus, in
addition to improved deposition and reproducibility, the new
concept provides a more user-friendly and intuitive nasal delivery
method.
[0017] Furthermore, a delivery device, in being pre-primed and
actuatable by the oral exhalation breath of a subject, does not
require the application of an actuation force by the subject at the
time of actuation. Traditionally, mechanical liquid delivery pumps
are operated by the manual compression of a chamber containing a
volume of liquid to expel a flow of a metered volume of liquid, and
mechanical powder delivery pumps are operated by the manual
compression of a chamber containing a volume of air to drive and
expel a flow of a metered amount of a dry powder. Such operation
requires a relatively high actuation force, typically of the order
of 50 N, which high force often leads to significant movement of
the delivery device, it being very difficult to maintain a delivery
device stationary when attempting to apply a high actuation force.
Movement of the delivery device, both in the positioning and
orientation of the nozzle, will lead to poor reproducibility, dose
accuracy and patient compliance. In being pre-primed and actuatable
by the oral exhalation breath of a subject, the delivery device of
the present invention overcomes this problem.
[0018] In addition, by not requiring a subject to apply an
actuation force at the instance of delivery, the delivery device
provides for the same actuation force in each delivery, and also
provides for delivery at an optimal pressure and/or flow rate, and
the delivery of substance having an optimized particle size
distribution.
[0019] Yet furthermore, in providing for the closure of the
oropharyngeal velum of a subject, substance is prevented from
entering the lower airway, and also, in a preferred embodiment,
bi-directional delivery can be achieved through the nasal
cavities.
[0020] In one aspect the present invention provides a
breath-actuated delivery device, comprising: a delivery unit
actuatable to deliver substance on application of a delivery force
thereto; a loading unit actuatable to apply the delivery force to
the delivery unit to actuate the same; a mouthpiece through which a
subject in use exhales; an air channel in fluid communication with
the mouthpiece; and an actuating member disposed in the air
channel, the actuating member comprising a flexible, bi-stable
element actuatable, on exhalation by the subject into the
mouthpiece, between a first, non-actuated state and a second,
actuated state in which the actuating member actuates the loading
unit to apply the delivery force to the delivery unit to actuate
the same.
[0021] In another aspect the present invention provides a delivery
device, comprising: a delivery unit actuatable to deliver substance
on application of a delivery force thereto; and a loading unit
actuatable to apply the delivery force to the delivery unit to
actuate the same, the loading unit comprising a drive member
actuatable from a loaded position to actuate the delivery unit, a
biasing element for loading the drive member with the delivery
force, and a restraining member for normally restraining the drive
member in the loaded position and being configured to be broken on
actuation of the loading unit to release the drive member and cause
the biasing element to drive the drive member to actuate the
delivery unit.
[0022] In a further aspect the present invention provides a
breath-actuated delivery device, comprising: a mouthpiece through
which a subject in use exhales; an air channel in fluid
communication with the mouthpiece; and a flexible diaphragm
disposed in the air channel, the diaphragm providing for at least a
restricted air flow through the air channel until a predeterminable
actuation pressure is developed in the mouthpiece, and, on
generation of the predeterminable actuation pressure in the
mouthpiece, providing for an air flow through the air channel.
[0023] In a yet further aspect the present invention provides a
delivery device, comprising: a delivery unit actuatable to deliver
substance on application of a delivery force thereto; and a loading
unit actuatable to apply the delivery force to the delivery unit to
actuate the same.
[0024] In a still further aspect the present invention provides a
method of delivering substance to a nasal airway of a subject, the
method comprising the steps of: providing a delivery unit
actuatable to deliver substance on application of a delivery force
thereto; loading a loading unit with the delivery force; and
actuating the loading unit to apply the delivery force to the
delivery unit to actuate the same.
[0025] Preferred embodiments of the present invention will now be
described hereinbelow by way of example only with reference to the
accompanying drawings, in which:
[0026] FIG. 1 illustrates a perspective view of a nasal delivery
device in accordance with a first embodiment of the present
invention;
[0027] FIG. 2 illustrates a part cut-away perspective view of the
delivery device of FIG. 1;
[0028] FIG. 3(a) illustrates a vertical sectional view of the
delivery device of FIG. 1, where in a first, rest or inoperative
configuration;
[0029] FIG. 3(b) illustrates a vertical sectional view of the
delivery device of FIG. 1, where in a loaded configuration;
[0030] FIG. 3(c) illustrates a vertical sectional view of the
delivery device of FIG. 1, with the subject commencing exhalation
through the mouthpiece;
[0031] FIG. 3(d) illustrates a vertical sectional view of the
delivery device of FIG. 1, where the actuating member of the
breath-actuation mechanism is operated by the exhalation of the
subject developing an actuation force;
[0032] FIG. 3(e) illustrates a vertical sectional view of the
delivery device of FIG. 1, where the delivery unit is actuated to
open the substance reservoir thereof;
[0033] FIG. 3(f) illustrates a vertical sectional view of the
delivery device of FIG. 1, where the delivery unit is actuated to
deliver substance from the nosepiece;
[0034] FIG. 3(g) illustrates a vertical sectional view of the
delivery device of FIG. 1, following operation of the delivery
device;
[0035] FIG. 4 illustrates a nasal delivery device in accordance
with a second embodiment of the present invention;
[0036] FIG. 5(a) illustrates the delivery device of FIG. 4, where
in a first, rest or inoperative configuration;
[0037] FIG. 5(b) illustrates the delivery device of FIG. 4, with
the subject commencing exhalation through the mouthpiece;
[0038] FIG. 5(c) illustrates the delivery device of FIG. 4, where
the actuating member of the breath-actuation mechanism is operated
by the exhalation of the subject developing an actuation force;
[0039] FIG. 5(d) illustrates the delivery device of FIG. 4, where
the delivery unit is actuated to open the substance reservoir
thereof;
[0040] FIG. 5(e) illustrates the delivery device of FIG. 4, where
the delivery unit is actuated to deliver substance from the
nosepiece;
[0041] FIG. 5(f) illustrates the delivery device of FIG. 4,
following operation of the delivery device;
[0042] FIG. 6 illustrates a nasal delivery device in accordance
with a third embodiment of the present invention;
[0043] FIG. 7(a) illustrates the delivery device of FIG. 6, where
in a first, rest or inoperative configuration;
[0044] FIG. 7(b) illustrates the delivery device of FIG. 6, with
the subject commencing exhalation through the mouthpiece;
[0045] FIG. 7(c) illustrates the delivery device of FIG. 6, where
the subject has continued exhaling and the flexible diaphragm is
deflected to a predetermined extent which corresponds to the
exhaled air contained thereby having a predetermined pressure;
[0046] FIG. 7(d) illustrates the delivery device of FIG. 6, where
the flexible diaphragm has been ruptured to release the pressurized
air as contained thereby;
[0047] FIG. 7(e) illustrates the delivery device of FIG. 6,
following operation of the delivery device; and
[0048] FIG. 8 schematically illustrates the anatomy of the upper
respiratory tract of a human subject.
[0049] FIGS. 1 to 3 illustrate a breath-actuated nasal delivery
device in accordance with a first embodiment of the present
invention.
[0050] The delivery device comprises a body unit 14 which comprises
a housing 15, in this embodiment provided by first and second
housing parts 15a, 15b, which is typically gripped in the hand of a
user, a mouthpiece 17 through which the user exhales to actuate the
delivery device, and a nosepiece 19 for fitting to a nostril of the
user and through which substance is delivered to the nasal airway
of the user.
[0051] The housing 15 includes a cavity 21, an inlet passage 23
which is in fluid communication with the cavity 21 and fluidly
connected with the mouthpiece 17 such that an air flow developed by
the user on exhaling into the mouthpiece 17 is delivered through
the inlet passage 23 into the cavity 21, and an outlet passage 25
which is in fluid communication with the cavity 21 and fluidly
connected with the nosepiece 19 such that an air flow delivered
into the cavity 21 is delivered through the nosepiece 19.
[0052] In this embodiment the inlet passage 23 has a narrow,
substantially rectangular section, the downstream end of which
opens into the cavity 21 in the housing 15.
[0053] The housing 15 further includes an aperture 27, in this
embodiment in a lower end thereof, in which a loading member 69 for
priming the delivery device is disposed, as will be described in
more detail hereinbelow.
[0054] The housing 15 further includes a latch element 29, in this
embodiment a detent, for latching the loading member 69 when in the
primed position, again as will be described in more detail
hereinbelow.
[0055] The housing 15 further includes at least one, in this
embodiment a plurality of external venting apertures 30 which
provide for a vent from the cavity 21 in the housing 15 to
atmosphere. The venting apertures 30 are normally isolated from the
atmosphere by a pressure-sensitive release valve 97, as will be
described in more detail hereinbelow, and are opened by opening the
pressure-sensitive release valve 97 when a sufficient flow rate
cannot be developed through the nosepiece 19, for example, as a
result of the nasal passage of the user being congested, and the
pressure in the cavity 21 in the housing 15 exceeds a predetermined
threshold pressure.
[0056] In this embodiment the mouthpiece 17 is configured to be
gripped in the lips of the user. In an alternative embodiment the
mouthpiece 17 could be configured to be gripped by the teeth of the
user and sealed by the lips of the user. In a preferred embodiment
the mouthpiece 17 is specifically configured to have one or both of
a shape and geometry which allows the delivery device to be gripped
repeatedly in the same position, thereby providing for the
nosepiece 19 to be reliably inserted in the same position in a
nasal cavity.
[0057] The nosepiece 19 includes a support member 32 which supports
the outlet member 39 of a delivery unit 37, as will be described in
more detail hereinbelow. The support member 32, in this embodiment
an annular member, includes a central, inner aperture 33 in which
the nozzle block 41 of the outlet member 39 of the delivery unit 37
is disposed to deliver substance therefrom, and defines at least
one, in this embodiment a plurality of outer apertures 35 about the
central aperture 33 through which an air flow developed by an
exhalation breath of the user is delivered. In this embodiment the
outer apertures 35 are configured, here shaped and dimensioned,
such as to direct air flows at the delivered substance as delivered
from the nozzle outlet 43 of the nozzle block 41 of the outlet
member 39, which air flows interact with the delivered substance
such as to optimise the delivery characteristics of the delivered
substance.
[0058] The delivery device further comprises a delivery unit 37, in
this embodiment a pump unit, which is actuatable to deliver a
metered dose of substance.
[0059] The delivery unit 37 comprises an outlet member 39 which is
supported, in this embodiment in a fixed position, by the
supporting member 32 of the nosepiece 19, and a container member 40
which contains substance to be delivered and is slideably disposed
to the outlet member 39 to deliver a metered volume of substance on
driving the container member 40 relative to the outlet member
39.
[0060] The outlet member 39 comprises a nozzle block 41 at one, the
forward, end thereof which includes a nozzle outlet 43 from which
substance is delivered, a piston block 45 at the other, rear end
thereof, and a hollow needle 47 which extends from the rear end of
the piston block 45 and is fluidly connected to the nozzle outlet
43.
[0061] In this embodiment the nozzle outlet 43 is configured to
deliver an aerosol of fine liquid droplets of substance on
actuation of the delivery unit 37. In an alternative embodiment the
nozzle outlet 43 could be configured to provide for the delivery of
a liquid jet of substance.
[0062] The container member 40 comprises a body 49 which includes a
cylinder bore 51, in this embodiment having a cylindrical inner
peripheral surface, one, the rear, end of which is closed and the
other, forward end of which is open and receives the piston block
45 of the outlet member 39, and a seal element 55 which is disposed
in sealing engagement with the cylinder bore 51 such as to define
an enclosed chamber 57 containing substance within the cylinder
bore 51. The seal element 55 is configured to be rupturable by the
hollow needle 47 of the outlet member 39, such that, on driving the
container member 40 relative to the outlet member 39, the seal
element 55 is driven onto the hollow needle 47 such as to be
ruptured by the same, with the contained volume of substance in the
chamber 57 being substantially incompressible, and, following
rupture of the seal element 55 and with continued driving of the
container member 40, substance is delivered through the hollow
needle 47 and from the nozzle outlet 43 of the nozzle block 41.
[0063] The delivery device further comprises a loading unit 61
which is configured, when actuated, to apply a delivery force to
the delivery unit 37, which delivery force is such as to drive the
container member 40 of the delivery unit 37 relative to the outlet
member 39 of the delivery unit 37, and effect delivery of substance
from the nozzle outlet 43 of the nozzle block 41.
[0064] The loading unit 61 comprises a drive member 63 which is
operative to transmit the delivery force to the delivery unit 37, a
restraining member 65 which acts normally to restrain the drive
member 63 when loaded by the delivery force and is operable to
release the drive member 63, a biasing element 67, in this
embodiment a resilient element, here a compression spring, which,
when loaded, applies the delivery force to the drive member 63, and
a loading member 69 which is operative to load the biasing element
67 to provide the delivery force. In this embodiment the drive
member 63 and the restraining member 65 are formed as a single
integral unit.
[0065] In this embodiment the drive member 63 comprises a cradle 71
in which the container member 40 of the delivery unit 37 is
disposed and an outwardly-directed flange 73 which is engaged by
the biasing element 67.
[0066] In this embodiment the restraining member 65 comprises a
tether 75, one end of which is attached to the cradle 71 of the
drive member 63 and the other end of which is attached to the
housing 15, such that, on loading the cradle 71 with the delivery
force, the tether 75 is tensioned. In this embodiment the tether 75
comprises a single filament which is configured to be cut by a
cutter element 93 of an actuating member 89, as will be described
in more detail hereinbelow, with the cutting of the tether 75
acting to release the restraining member 65. In another embodiment
the tether 75 could comprise a plurality of filaments. In preferred
embodiments the or each filament could comprise a strand or a
sheet.
[0067] In this embodiment the restraining member 65 is formed of a
plastics material, here Nylon.RTM., and the tether 75 is notch
sensitized by axial stretching.
[0068] In this embodiment the biasing element 67, as compression
spring, is disposed about the tether 75 when in the unloaded state
such as to protect the tether 75, and thereby prevent release of
the restraining member 65 when in the unloaded state.
[0069] In this embodiment the loading member 69 comprises a loading
button 79 at one, the lower, end thereof, which is typically loaded
by the thumb of the user in loading the biasing element 67, an
engagement element 81 at the other, upper end thereof which engages
the biasing element 67 to load the same, and a support element 83
which interconnects the loading button 79 and the engagement
element 81.
[0070] In this embodiment the loading button 79 of the loading
member 69 includes a peripheral seal 85 which is configured to seal
with the aperture 27 in the housing 15 when in the loaded position,
as illustrated in FIG. 3(b), such as to prevent the escape
therefrom of an air flow as delivered into the cavity 21 in the
housing 15.
[0071] In this embodiment the engagement element 81 of the loading
member 69 includes an outwardly-directed flange 87 which acts to
prevent the escape of the loading member 69 from the aperture 27 in
the housing 15 when in the unloaded position, as illustrated in
FIG. 3(a), and engages the latching element 29 on the housing 15 to
latch the loading member 69 in the loaded position, as illustrated
in FIG. 3(b).
[0072] The delivery device further comprises a breath-actuated
actuating member 89 which is disposed in the inlet passage 23 of
the housing 15 and operative, on generation of a predetermined
force by the exhalation breath of the user, to release the
restraining member 65, and thereby effect actuation of the delivery
unit 37.
[0073] In this embodiment the actuating member 89 comprises a
flexible, bi-stable element 91 which is switched from a first,
non-actuated state, as illustrated in FIG. 3(a), to a second,
actuated state, as illustrated in FIG. 3(d), on generation of a
predetermined actuating force thereat, in this embodiment through
the development of a predetermined exhalation flow rate through the
mouthpiece 17, and a cutter element 93 which is fixed to the
bi-stable element 91, with the cutter element 93 acting to cut the
tether 75 of the restraining member 65.
[0074] In this embodiment the bi-stable element 91 comprises an
elongate band, in a preferred embodiment of a plastics material,
here a thermoplastic elastomer (TPE).
[0075] In this embodiment the bi-stable element 91 is configured,
here one or both of shaped and dimensioned relative to the inlet
passage 23 in the housing 15, such as, when in the non-actuated
state, to allow an air flow at a first predetermined flow rate
through the inlet passage 23 on exhalation by the user through the
mouthpiece 17, and, when switched to the actuated state, to be
moved clear of the inlet passage 23 and provide for the delivery of
an air flow at a second, higher flow rate through the inlet passage
23, and hence the nosepiece 19, which interacts with the delivered
substance.
[0076] In alternative embodiments the bi-stable element 91 can be
configured such as to provide alternative flow schemes, for
example, in closing the inlet passage 23 in both the non-actuated
and actuated states, in closing the inlet passage 23 when in the
non-actuated state and providing for an air flow through the inlet
passage 23 when in the actuated state, in providing for an air flow
through the inlet passage 23 when in the non-actuated state and
closing the inlet passage 23 when in the actuated state, and in
providing for a uniform flow rate through the inlet passage 23 when
in the actuated and non-actuated states.
[0077] In this embodiment the delivery device further comprises a
pressure-sensitive release valve 97 which acts to provide for a
flow through the inlet passage 23 in the housing 15 when the
pressure in the cavity 21 in the housing 15 exceeds a predetermined
pressure, as caused by at least partial obstruction of the nasal
airway of the user.
[0078] In this embodiment the pressure-sensitive release valve 97
comprises a resilient flap element 99 which normally doses the
venting apertures 30 in the housing 15, but is displaced from the
venting apertures 30 on the generation of a predetermined pressure
in the cavity 21 in the housing 15, such as to allow an air flow
therethrough.
[0079] Operation of the delivery device will now be described
hereinbelow with reference to FIGS. 3(a) to (g).
[0080] The user first takes the delivery device, as illustrated in
FIG. 3(a), and primes the delivery device by depressing the loading
member 69 until latched in the primed position in the housing 15,
as illustrated in FIG. 3(b). In this embodiment, as described
hereinabove, the loading member 69 is latched in the primed
position by engagement of the flange 87 thereof with the latch
element 29 of the housing 15, in which position the peripheral seal
85 of the loading member 69 is in sealing engagement with the
aperture 27 in the lower end of the housing 15.
[0081] In this configuration, the biasing element 67 is biased,
here through compression of the compression spring, such as to load
the drive member 63 with a predetermined delivery force, with the
tether 75 of the restraining mechanism 65 being tensioned by the
delivery force.
[0082] The user then inserts the nosepiece 19 in one of his/her
nostrils, grips the mouthpiece 17 in his/her lips, and commences
exhaling through the mouthpiece 17, as illustrated in FIG. 3(c).
The air flow developed by exhalation through the mouthpiece 17
passes through the cavity 21 in the housing 15 and into the nasal
airway of the user through the nosepiece 19.
[0083] In this embodiment the delivery device is configured
normally to deliver the exhalation breath through one nostril of
the user such as to flow around the posterior margin of the nasal
septum and out of the other nostril of the user, thereby achieving
a bi-directional flow through the nasal cavities as disclosed in
WO-A-00/51672.
[0084] In exhaling through the mouthpiece 17, the developed air
flow is restricted by the presence of the bi-stable element 91 of
the actuating member 89 in the inlet passage 23 of the housing 15,
such that an actuation force is applied to the bi-stable element
91. On reaching a predetermined flow rate, the actuation force is
such as to switch the bi-stable element 91 from the non-actuated
state, as illustrated in FIG. 3(c), to the actuated state, as
illustrated in FIG. 3(d).
[0085] In being switched to the actuated state, the bi-stable
element 91 acts to drive the cutter element 93, which is fixed
thereto, to cut the tether 75 of the restraining member 65, which
acts to release the drive member 63 to actuate the delivery unit 37
by driving the container member 40 of the delivery unit 37 relative
to the outlet member 39 of the delivery unit 37, and the bi-stable
element 91 is also moved clear of the inlet passage 23 of the
housing 15, such as to provide for the generation of a higher flow
rate through the inlet passage 23, and hence the nosepiece 19,
which interacts with substance which is to be delivered.
[0086] Following release of the drive member 63, in a first phase
as illustrated in FIG. 3(e), the drive member 63 acts to drive the
container member 40 relative to the outlet member 39 such as to
cause the hollow needle 47 of the outlet member 39 to rupture the
seal element 55 and provide for fluid communication between the
chamber 57 of the container member 40 which contains the substance
to be delivered and the nozzle outlet 43 of the nozzle block 41 of
the outlet member 39.
[0087] Following the rupturing of the seal element 55, in a second
phase as illustrated in FIG. 3(f), the drive member 63 acts further
to drive the container member 40 relative to the outlet member 39
such as to expel the metered volume of substance from the chamber
57 of the container member 40 and from the nozzle outlet 43 of the
nozzle block 41 of the outlet member 39, in this embodiment as an
aerosol of liquid droplets of substance.
[0088] Following actuation of the delivery device, as illustrated
in FIG. 3(g), the user then ceases exhaling and removes the device
from his her/her mouth and nostril.
[0089] FIGS. 4 and 5 illustrate a breath-actuated nasal delivery
device in accordance with a second embodiment of the present
invention.
[0090] The delivery device comprises a body unit 114 which
comprises a housing 115, which is typically gripped in the hand of
a user, a mouthpiece 117 through which the user exhales to actuate
the delivery device, and a nosepiece 119 for fitting to a nostril
of the user and through which substance is delivered to the nasal
airway of the user.
[0091] The housing 115 includes a cavity 121, an inlet passage 123
which is in fluid communication with the cavity 121 and fluidly
connected with the mouthpiece 117 such that an air flow developed
by the user on exhaling into the mouthpiece 117 is delivered
through the inlet passage 123 into the cavity 121, and an outlet
passage 125 which is in fluid communication with the cavity 121 and
fluidly connected with the nosepiece 119 such that an air flow
delivered into the cavity 121 is delivered through the nosepiece
119.
[0092] In this embodiment the inlet passage 123 has a narrow,
substantially rectangular section, the downstream end of which
opens into the cavity 121 in the housing 115.
[0093] In this embodiment the mouthpiece 117 is configured to be
gripped in the lips of the user. In an alternative embodiment the
mouthpiece 117 could be configured to be gripped by the teeth of
the user and sealed by the lips of the user. In a preferred
embodiment the mouthpiece 117 is specifically configured to have
one or both of a shape and geometry which allows the delivery
device to be gripped repeatedly in the same position, thereby
providing for the nosepiece 119 to be reliably inserted in the same
position in a nasal cavity.
[0094] The housing 115 includes a support member 132 which supports
the outlet member 139 of a delivery unit 137, as will be described
in more detail hereinbelow. The support member 132, in this
embodiment an annular member, includes a central, inner aperture
133 in which the nozzle block 141 of the outlet member 139 of the
delivery unit 137 is disposed to deliver substance therefrom, and
at least one, in this embodiment a plurality of outer apertures 135
about the central aperture 133 through which an air flow developed
through the cavity 121 in the housing 115 is delivered. In this
embodiment the outer apertures 135 are configured, here shaped and
dimensioned, such as to direct air flows at the delivered substance
as delivered from the nozzle outlet 143 of the nozzle block 141 of
the outlet member 139, which air flows interact with the delivered
substance such as to optimise the delivery characteristics of the
delivered substance.
[0095] The delivery device further comprises a delivery unit 137,
in this embodiment a pump unit, which is actuatable to deliver a
metered dose of substance.
[0096] The delivery unit 137 comprises an outlet member 139 which
is supported, in this embodiment in a fixed position, by the
supporting member 132 of the housing 115, and a container member
140 which contains substance to be delivered and is slideably
disposed to the outlet member 139 to deliver a metered volume of
substance on driving the container member 140 relative to the
outlet member 139.
[0097] The outlet member 139 comprises a nozzle block 141 at one,
the forward, end thereof which includes a nozzle outlet 143 from
which substance is delivered, a piston block 145 at the other, rear
end thereof, and a hollow needle 147 which extends from the rear
end of the piston block 145 and is fluidly connected to the nozzle
outlet 143.
[0098] In this embodiment the nozzle outlet 143 is configured to
deliver an aerosol of fine liquid droplets of substance on
actuation of the delivery unit 137. In an alternative embodiment
the nozzle outlet 143 could be configured to provide for the
delivery of a liquid jet of substance.
[0099] The container member 140 comprises a body 149 which includes
a cylinder bore 151, in this embodiment having a cylindrical inner
peripheral surface, one, the rear, end of which is closed and the
other, forward end of which is open and receives the piston block
145 of the outlet member 139, and a seal element 155 which is
disposed in sealing engagement with the cylinder bore 151 such as
to define an enclosed chamber 157 containing substance within the
cylinder bore 151. The seal element 155 is configured to be
rupturable by the hollow needle 147 of the outlet member 139, such
that, on driving the container member 140 relative to the outlet
member 139, the seal element 155 is driven onto the hollow needle
147 such as to be ruptured by the same, with the contained volume
of substance in the chamber 157 being substantially incompressible,
and, following rupture of the seal element 155 and with continued
driving of the container member 140, substance is delivered through
the hollow needle 147 and from the nozzle outlet 143 of the nozzle
block 141.
[0100] The delivery device further comprises a loading unit 161
which is configured, when actuated, to apply a delivery force to
the delivery unit 137, which delivery force is such as to drive the
container member 140 of the delivery unit 137 relative to the
outlet member 139 of the delivery unit 137, and effect delivery of
substance from the nozzle outlet 143 of the nozzle block 141.
[0101] The loading unit 161 comprises a drive member 163 which is
operative to transmit the delivery force to the delivery unit 137,
a restraining member 165 which acts normally to restrain the drive
member 163 when loaded by the delivery force and is operable to
release the drive member 163, and a biasing element 167, in this
embodiment a resilient element, here a compression spring, which
applies the delivery force to the drive member 163.
[0102] In this embodiment the drive member 163 comprises a support
element 171 which is loaded on one, the rear, side thereof by the
loading force of the biasing element 167 and supported on the
other, forward side thereof by the restraining member 165, and a
drive element 173, in this embodiment a projecting lug, which
extends from the forward side of the support element 171 in opposed
relation to the container member 140 of the delivery unit 137.
[0103] In this embodiment the restraining member 165 comprises a
gas support cushion 175 which, when normally inflated, here with
air, acts to hold the drive member 163 against the bias of the
biasing element 167, and, when punctured, collapses such as to
allow the biasing element 167 to drive the drive member 163. In
this embodiment the gas support cushion 175 is configured such as
to be punctured by a cutter element 193 of an actuating member 189
to actuate the delivery unit 137, as will be described in more
detail hereinbelow, with the puncturing of the gas support cushion
175 acting advantageously to provide a supplementary air flow.
[0104] The delivery device further comprises a breath-actuated
actuating member 189 which is disposed in the inlet passage 123 of
the housing 115 and operative, on generation of a predetermined
force by the exhalation breath of the user, to release the
restraining member 165, and thereby effect actuation of the
delivery unit 137.
[0105] In this embodiment the actuating member 189 comprises a
flexible, bi-stable element 191 which is switched from a first,
non-actuated state, as illustrated in FIGS. 5(a) and (b), to a
second, actuated state, as illustrated in FIG. 5(c), on generation
of a predetermined actuating force thereat, in this embodiment
through the development of a predetermined exhalation flow rate
through the mouthpiece 117, and a cutter element 193 which is fixed
to the bi-stable element 191, with the cutter element 193 acting to
puncture the gas support cushion 175 of the restraining member
165.
[0106] In this embodiment the bi-stable element 191 comprises an
elongate band, in a preferred embodiment of a plastics material,
here a thermoplastic elastomer (TPE).
[0107] In this embodiment the bi-stable element 191 is configured,
here one or both of shaped and dimensioned relative to the inlet
passage 123 in the housing 115, such as, when in the non-actuated
state, to allow an air flow at a first predetermined flow rate
through the inlet passage 123 on exhalation by the user through the
mouthpiece 117, and, when switched to the actuated state, to be
moved clear of the inlet passage 123 and provide for the delivery
of an air flow at a second, higher flow rate through the inlet
passage 123, and hence the nosepiece 119, which interacts with the
delivered substance.
[0108] In alternative embodiments the bi-stable element 191 can be
configured such as to provide alternative flow schemes, for
example, in closing the inlet passage 123 in both the non-actuated
and actuated states, in closing the inlet passage 123 when in the
non-actuated state and providing for an air flow through the inlet
passage 123 when in the actuated state, in providing for an air
flow through the inlet passage 123 when in the non-actuated state
and closing the inlet passage 123 when in the actuated state, and
in providing for a uniform flow rate through the inlet passage 123
when in the actuated and non-actuated states.
[0109] Operation of the delivery device will now be described
hereinbelow with reference to FIGS. 5(a) to (f).
[0110] The user first takes the delivery device, as illustrated in
FIG. 5(a), and inserts the nosepiece 119 in one of his/her
nostrils, and grips the mouthpiece 117 in his/her lips.
[0111] The user then commences exhaling through the mouthpiece 117,
as illustrated in FIG. 5(b). The air flow developed by exhalation
through the mouthpiece 117 passes through the cavity 121 in the
housing 115 and into the nasal airway of the user through the
nosepiece 119.
[0112] In this embodiment the delivery device is configured
normally to deliver the exhalation breath through one nostril of
the user such as to flow around the posterior margin of the nasal
septum and out of the other nostril of the user, thereby achieving
a bi-directional flow through the nasal cavities as disclosed in
WO-A-00/51672.
[0113] In exhaling through the mouthpiece 117, the developed air
flow is restricted by the presence of the bi-stable element 191 of
the actuating member 189 in the inlet passage 123 of the housing
115, such that an actuation force is applied to the bi-stable
element 191. On reaching a predetermined flow rate, the actuation
force is such as to switch the bi-stable element 191 from the
non-actuated state, as illustrated in FIG. 5(b), to the actuated
state, as illustrated in FIG. 5(c).
[0114] In being switched to the actuated state, the bi-stable
element 191 acts to drive the cutter element 193, which is fixed
thereto, to puncture the gas support cushion 175 of the restraining
member 165, which acts to release the drive member 163 to actuate
the delivery unit 137 by driving the container member 140 of the
delivery unit 137 relative to the outlet member 139 of the delivery
unit 137, and the bi-stable element 191 is also moved clear of the
inlet passage 123 of the housing 115, such as to provide for the
generation of a higher flow rate through the inlet passage 123,
which flow as developed by the exhalation breath together with the
flow as developed by the escaping air flow from the gas support
cushion 175 is delivered through the nosepiece 119 to interact with
substance which is to be delivered from the delivery unit 137.
[0115] Following release of the drive member 163, in a first phase
as illustrated in FIG. 5(d), the drive member 163 acts to drive the
container member 140 relative to the outlet member 139 such as to
cause the hollow needle 147 of the outlet member 139 to rupture the
seal element 155 and provide for fluid communication between the
chamber 157 of the container member 140 which contains the
substance to be delivered and the nozzle outlet 143 of the nozzle
block 141 of the outlet member 139.
[0116] Following the rupturing of the seal element 155, in a second
phase as illustrated in FIG. 5(e), the drive member 163 acts
further to drive the container member 140 relative to the outlet
member 139 such as to expel the metered volume of substance from
the chamber 157 of the container member 140 and from the nozzle
outlet 143 of the nozzle block 141 of the outlet member 139, in
this embodiment as an aerosol of liquid droplets of substance.
[0117] Following actuation of the delivery device, as illustrated
in FIG. 5(f), the user then ceases exhaling and removes the device
from his her/her mouth and nostril.
[0118] FIGS. 6 and 7 illustrate a breath-actuated nasal delivery
device in accordance with a third embodiment of the present
invention.
[0119] The delivery device comprises a body unit 214 which
comprises a housing 215, which is typically gripped in the hand of
a user, a mouthpiece 217 through which the user exhales to actuate
the delivery device, and a nosepiece 219 for fitting to a nostril
of the user and through which substance is delivered to the nasal
airway of the user.
[0120] The housing 215 includes a cavity 221, an inlet passage 223
which is in fluid communication with the cavity 221 and fluidly
connected with the mouthpiece 217 such that an air flow developed
by the user on exhaling into the mouthpiece 217 is delivered
through the inlet passage 223 into the cavity 221, and an outlet
passage 225 which is in fluid communication with the cavity 221 and
fluidly connected with the nosepiece 219 such that an air flow
delivered from the cavity 221 is delivered through the nosepiece
219.
[0121] In this embodiment the mouthpiece 217 is configured to be
gripped in the lips of the user. In an alternative embodiment the
mouthpiece 217 could be configured to be gripped by the teeth of
the user and sealed by the lips of the user. In a preferred
embodiment the mouthpiece 217 is specifically configured to have
one or both of a shape and geometry which allows the delivery
device to be gripped repeatedly in the same position, thereby
providing for the nosepiece 219 to be reliably inserted in the same
position in a nasal cavity.
[0122] The delivery device further comprises a delivery unit 237
which provides for the delivery of a metered dose of substance.
[0123] In this embodiment the delivery unit 237 comprises an
impregnated structure, typically a porous mat, as impregnated with
a metered dose of substance, either as a liquid or a powder, with
the substance being entrained in an air flow as delivered
thereover.
[0124] In alternative embodiments the delivery unit 237 could be of
any of the kinds as described hereinabove in relation to the
other-described embodiments which provide for the delivery of
substance.
[0125] The delivery device further comprises a flexible diaphragm
241, in this embodiment a resilient element, which is disposed in
the housing 215 and closes, or at least substantially closes, the
flow path from the mouthpiece 217 to the nosepiece 219, and a
rupturing element 243 which is operative to rupture the diaphragm
241 where the diaphragm 241 is subjected to a predetermined
actuation pressure. With this configuration, exhalation by a user
into the mouthpiece 217 acts to bias the diaphragm 241, as
illustrated in FIGS. 7(b) and (c), much in the manner of inflating
a balloon, and, when the diaphragm 241 is deflected to a
predetermined extent, which corresponds to the generation of a
predetermined pressure upstream of the diaphragm 241, the rupturing
element 243 acts to rupture the diaphragm 241, causing the
contained pressurized air to be driven out of the nosepiece 219, as
illustrated in FIG. 7(d).
[0126] Operation of the delivery device will now be described
hereinbelow with reference to FIGS. 7(a) to (e).
[0127] The user first takes the delivery device, as illustrated in
FIG. 7(a), and inserts the nosepiece 219 in one of his/her
nostrils, and grips the mouthpiece 217 in his/her lips.
[0128] The user then commences exhaling through the mouthpiece 217,
as illustrated in FIG. 7(b). The air flow developed by exhalation
through the mouthpiece 217 passes into the cavity 221 in the
housing 215 and is contained by the diaphragm 241, causing the
diaphragm 241 to be deflected.
[0129] With continued exhalation, the diaphragm 241 is further
deflected until such point as the diaphragm 241 is deflected to a
predetermined extent, which corresponds to the generation of a
predetermined pressure upstream of the diaphragm 241, as
illustrated in FIG. 7(c).
[0130] At this point, the rupturing element 243 acts to rupture the
diaphragm 241, causing the contained pressurized air to be driven
out of the nosepiece 219 as a sudden burst of air, as illustrated
in FIG. 7(d), where this air flow entrains a metered dose of
substance as provided by the delivery unit 237.
[0131] In this embodiment the pressure of the air flow is such as
normally to deliver an air flow through the one nostril, around the
posterior margin of the nasal septum and out of the other nostril
of the user, thereby achieving a bi-directional flow through the
nasal cavities as disclosed in WO-A-00/51672.
[0132] Following actuation of the delivery device, as illustrated
in FIG. 7(e), the user then ceases exhaling and removes the device
from his her/her mouth and nostril.
[0133] 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.
[0134] In one alternative embodiment the delivery unit 37, 137
could comprise an aerosol canister, such as used in a pressurized
metered dose inhaler (pMDI), for delivering a propellant,
preferably a hydrofluoroalkane (HFA) propellant or the like,
containing substance, preferably a medicament either as a
suspension or a solution.
[0135] In another alternative embodiment the delivery unit 37, 137
could comprise a dry powder delivery unit for delivering a metered
dose of substance in a dry powder.
[0136] In other embodiments the delivery unit 37, 137 could be
configured to re-constitute substance on actuation thereof,
typically by admixing at least two liquids to provide a
re-constituted liquid substance, at least one liquid and at least
one powder to provide a re-constituted liquid substance, and at
least two powders to provide a re-constituted powder substance.
[0137] In yet another alternative embodiment the cutter element 93
could be omitted from the actuating member 89, and instead be
disposed to the housing 15 in opposed relation to actuating member
89 such that the actuating member 89 acts to deflect the tether 75
of the restraining member 65 onto the cutter element 93 so as to
cut the tether 75.
[0138] In still another alternative embodiment the tether 75 of the
restraining member 65 could be configured such as to be broken in
some other manner. For example, the tether 75 could be formed of a
brittle material which has a high tensile strength but a low
bending strength, allowing for fracture of the tether 75 by
deflection of the tether 75.
[0139] In yet another alternative embodiment the pressure-sensitive
release valve 97 could be replaced by a flexible diaphragm, where
defining part of the cavity 21 in the housing 15, which is coupled
to the actuating member 89. With this configuration, the diaphragm
is deflected when the pressure in the cavity 21 in the housing 15
exceeds a predetermined pressure, as caused by at least partial
obstruction of the nasal airway of the user, with the deflection of
the diaphragm causing actuation of the coupled actuating member
89.
[0140] In still another alternative embodiment the bi-stable
element 91, 191 of the actuating member 89, 189 could close the
inlet passage 23, 123 of the housing 15, 115 such as to provide for
actuation of the actuating member 89, 189 on generation of a
predetermined actuation pressure in the mouthpiece 17, 117.
[0141] In the described embodiments the bi-stable element 91, 191
of the actuating member 89, 189 has equal bi-stable states, but in
alternative embodiments the bi-stable element 91, 191 of the
actuating member 89, 189 has unequal bi-stable states, whereby the
actuating force required to switch the bi-stable element 91, 191 to
the actuated state is less than the force as would be required to
switch the bi-stable element 91, 191 from the actuated state to the
non-actuated state.
* * * * *