U.S. patent application number 16/101634 was filed with the patent office on 2019-04-25 for nasal delivery.
The applicant listed for this patent is OptiNose AS. Invention is credited to Per Gisle DJUPESLAND, Colin David Sheldrake.
Application Number | 20190117918 16/101634 |
Document ID | / |
Family ID | 38091075 |
Filed Date | 2019-04-25 |
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United States Patent
Application |
20190117918 |
Kind Code |
A1 |
DJUPESLAND; Per Gisle ; et
al. |
April 25, 2019 |
NASAL DELIVERY
Abstract
A nasal delivery device for and method of delivering substance
to a nasal cavity of a subject, the delivery device comprising: a
nosepiece for fitting to a nostril of a subject, wherein the
nosepiece comprises a tip element which includes a delivery
aperture from which substance is in use delivered into the nasal
cavity, and the tip element is at least in part tapered such as to
be inclined to a longitudinal axis of the nosepiece, with the
delivery aperture extending both laterally across the tip element
and along a longitudinal extent of the tip element; a nozzle
through which substance is in use delivered, preferably
substantially axially to a longitudinal axis of the nosepiece, to
the respective nasal cavity; and a delivery unit for delivering
substance through the nozzle of the nosepiece.
Inventors: |
DJUPESLAND; Per Gisle;
(Oslo, NO) ; Sheldrake; Colin David; (Wiltshire,
GB) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
OptiNose AS |
Oslo |
|
NO |
|
|
Family ID: |
38091075 |
Appl. No.: |
16/101634 |
Filed: |
August 13, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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14618273 |
Feb 10, 2015 |
10076615 |
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16101634 |
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12594361 |
Jul 16, 2010 |
8978647 |
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PCT/GB08/01217 |
Apr 7, 2008 |
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14618273 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 2210/0625 20130101;
A61M 15/0098 20140204; A61M 15/0021 20140204; A61M 2202/064
20130101; A61M 15/08 20130101; A61M 15/085 20140204 |
International
Class: |
A61M 15/08 20060101
A61M015/08; A61M 15/00 20060101 A61M015/00 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 5, 2007 |
GB |
0706863.8 |
Claims
1-81. (canceled)
82. A nosepiece for fitting to a nostril of a subject, comprising:
a tip element which includes a delivery aperture from which a
substance is in use delivered into a nasal cavity of the subject;
wherein the tip element comprises a flexible structure, and
includes an outer body part formed of a flexible material and an
inner body part which structurally supports the outer body part;
wherein the tip element is at least in part tapered so as to be
inclined to a longitudinal axis of the nosepiece, with the delivery
aperture extending both laterally across the tip element and along
a longitudinal extent of the tip element in relation to the
longitudinal axis of the nosepiece.
83. The nosepiece of claim 82, wherein the tip element has an
elongate lateral section which has a longer dimension in a first,
sagittal direction than a second direction orthogonal to the
sagittal direction, such that, when the nosepiece is inserted in
the nasal cavity of the subject, the longer dimension of the tip
element is configured to engage lower and upper surfaces of the
nasal cavity.
84. The nosepiece of claim 83, wherein the longer dimension of the
tip element is configured to expand the nasal cavity in a sagittal
plane.
85. The nosepiece of claim 83, wherein the elongate lateral section
of the tip element is substantially elliptical.
86. The nosepiece of claim 83, wherein the elongate lateral section
of the tip element is substantially rectangular.
87. The nosepiece of claim 82, wherein the tip element extends
substantially axially to the longitudinal axis of the
nosepiece.
88. The nosepiece of claim 82, wherein the delivery aperture has an
asymmetric shape when viewed along the longitudinal axis of the
nosepiece.
89. The nosepiece of claim 88, wherein the delivery aperture has a
narrower section adjacent a forwardmost section of the tip element
and a wider section adjacent a rearwardmost section of the tip
element.
90. The nosepiece of claim 89, wherein the delivery aperture has a
teardrop shape when viewed along the longitudinal axis of the
nosepiece.
91. The nosepiece of claim 89, wherein the delivery aperture has a
triangular shape when viewed along the longitudinal axis of the
nosepiece.
92. The nosepiece of claim 82, further comprising a base section
from which the tip element extends.
93. The nosepiece of claim 92, wherein the tip element extends
substantially axially from the base section to the longitudinal
axis of the nosepiece.
94. The nosepiece of claim 92, wherein the base section defines a
shoulder that is configured to form a seal with a nare of a
nostril.
95. The nosepiece of claim 82, wherein the tip element of the
nosepiece has differing lengths adjacent forwardmost and
rearwardmost sections thereof.
96. The nosepiece of claim 95, wherein a ratio of lengths of the
tip element adjacent the forwardmost and rearwardmost sections
thereof is less than 2:1.
97. The nosepiece of claim 95, wherein a ratio of lengths of the
tip element adjacent the forwardmost and rearwardmost sections
thereof is greater than 2:1.
98. The nosepiece of claim 95, wherein the delivery aperture
comprises a substantially orthogonal-directed section adjacent the
forwardmost section of the tip element.
99. The nosepiece of claim 82, wherein the outer body part of the
tip element is formed from a resilient material.
100. A nasal delivery device comprising the nosepiece of claim 82.
Description
[0001] The present invention relates to a nasal delivery device for
and a method of delivering a 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. 1(a), the nasal airway 1 comprises the two
nasal cavities separated by the nasal septum, which airway 1
includes numerous ostia, such as the paranasal sinus ostia 3 and
the tubal ostia 5, and olfactory cells, and is lined by the nasal
mucosa. The nasal airway 1 can communicate with the nasopharynx 7,
the oral cavity 9 and the lower airway 11, with the nasal airway 1
being in selective communication with the anterior region of the
nasopharynx 7 and the oral cavity 9 by opening and closing of the
oropharyngeal velum 13. The velum 13, which is often referred to as
the soft palate, is illustrated in solid line in the closed
position, as achieved by providing a certain positive pressure in
the oral cavity 9, such as achieved 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 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.
[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] 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. For diabetes, and, indeed, for many other conditions, the
dosage of the pharmaceutical is preferably based on actual
real-time measurements. Currently, blood samples are most
frequently used, but the analysis of molecules in the exhalation
breath of subjects has been proposed as an alternative to blood
analysis for several conditions. Breath analysis is currently used
for the diagnosis of conditions such as helicobacter pylori
infections which cause gastric ulcers.
[0012] WO-A-00/51672 discloses a delivery device for delivering a
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.
[0013] It is an aim of the present invention to provide improved
nasal delivery devices and nasal delivery methods for providing for
the improved delivery of substance to a nasal cavity of
subject.
[0014] One particular aim of the present invention is to optimize
the shape, direction and particle distribution of the plume of a
delivered dose, in order to reach targeted regions and reduce
deposition outside these regions.
[0015] Another particular aim of the present invention is to
provide for improved targeting of specific regions of the nasal
airway and improved reproducibility and consistency of dosing.
[0016] The present inventors have recognized that an increased
delivery of substance to the posterior region of the nasal airway,
and in particular the upper posterior region of the nasal airway,
as illustrated in FIG. 1(b), relative to the anterior region of the
nasal airway, surprisingly provides for a disproportionately
greater effect, in particular a CNS effect, which is suggestive of
a greater uptake of substance into the CNS than would be predicted
from the blood plasma concentration of the substance, but also
systemic absorption and local action.
[0017] The posterior region of the nasal airway is that region
which is posterior of the nasal valve NV, as illustrated in FIG.
1(b).
[0018] 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.
[0019] In human subjects, the upper lateral wall of the nasal valve
NV collapses to form a collapsed region, as illustrated in FIG.
1(b), which significantly narrows the upper part of the nasal valve
NV and obstructs access to the upper posterior region of the nasal
cavity, and in particular the olfactory region. This collapsed
region, in combination with the upper lateral wall of the nasal
valve NV having a curved shape, makes the insertion of a rigid
structure into the lumen of the nasal valve NV particularly
difficult and uncomfortable. This discomfort is in part caused by
the very sensitive lining at the nasal valve NV, and the act of
insertion is also liable to cause sneezing which is induced by a
"tickling" effect, which can be diminished by configuring the
nosepiece to have a flexible structure which provides for a firm,
continuous contact.
[0020] 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 which has no or few cilia. 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.
[0021] 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.
[0022] 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.
[0023] 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).
[0024] The upper posterior region is thus that upper posterior
region which is bounded by the above-defined vertical and
horizontal planes VERT1, HORIZ.
[0025] The present inventors have postulated that this increased
concentration within the CNS arises as a result of the veins in the
upper posterior region of the nasal airway draining backwards to
the venous sinuses that surround the brain, which leads to a higher
local concentration in the cerebrovasculature. Although the sinus
cavernous is outside the blood-to-brain barrier, animal models have
shown that substances can be transported by a counter-current
mechanism from the veins therein to the carotid artery which passes
through the sinus cavernous. Other mechanisms have been proposed
which include extra axonal transport along the surface of the
olfactory and trigeminal nerves. This mode of transport is
apparently quite rapid as compared to intra axonal transport.
[0026] The improved efficacy as achieved by the present invention
as compared to existing nasal spray administration systems can
apparently be explained in that such nasal spray administration
systems have been determined initially to deliver largely to the
anterior one-third of the nasal airway, that is, the nasal region
anterior of the nasal valve, from which region drainage is mainly
along the floor of the nose and in which region the veins drain to
the external facial vein, which in turn drains to the external
carotid and in turn to the peripheral circulation.
[0027] In one aspect the present invention provides a nasal
delivery device for delivering substance to a nasal cavity of a
subject, the delivery device comprising: a nosepiece for fitting to
a nostril of a subject, wherein the nosepiece comprises a tip
element which includes a delivery aperture from which substance is
in use delivered into the nasal cavity, and the tip element is at
least in part tapered such as to be inclined to a longitudinal axis
of the nosepiece, with the delivery aperture extending both
laterally across the tip element and along a longitudinal extent of
the tip element; a nozzle through which substance is in use
delivered, preferably substantially axially to a longitudinal axis
of the nosepiece, to the respective nasal cavity; and a delivery
unit for delivering substance through the nozzle of the
nosepiece.
[0028] In another aspect the present invention provides a nosepiece
for delivering substance to a nasal cavity of a subject, the
nosepiece comprising a tip element which includes a delivery
aperture from which substance is in use delivered into the nasal
cavity, preferably substantially axially to a longitudinal axis of
the nosepiece, and the tip element is at least in part tapered such
as to be inclined to a longitudinal axis of the nosepiece, with the
delivery aperture extending both laterally across the tip element
and along a longitudinal extent of the tip element.
[0029] In a further aspect the present invention provides a nasal
delivery device for delivering substance to a nasal cavity of a
subject, the delivery device comprising: a housing; a nosepiece for
fitting to a nostril of a subject, through which substance is in
use delivered into the nasal cavity; a delivery unit for delivering
substance through the nosepiece; and a nose gripping member which
receives a finger of the subject and is configured such as to be
brought into contact with the skin of the nare of the nostril into
which the nosepiece is inserted, such as to allow the skin of the
nare of the nostril to be drawn over the nosepiece and promote
fitting of the nosepiece in the nasal cavity of the subject.
[0030] In a yet further aspect the present invention provides a
method of fitting a nasal delivery device to a nostril of a
subject, the method comprising the steps of: providing a nasal
delivery device which comprises a nosepiece through which substance
is delivered to a nasal cavity of the subject; inserting the
nosepiece into one of the nostrils of the subject; twisting the
nosepiece in the nostril, such as to align the delivery device;
pressing a finger against the skin of the nose, such as to press
the nare of the nostril against the nosepiece; and retracting the
finger, such as to pull the nare of the nostril over the
nosepiece.
[0031] In one embodiment the present invention provides a nosepiece
which provides for expansion in the sagittal plane, opening the
connection of the mucosal surfaces of the nasal valve and isthmus,
in particular by expansion of the collapsed region at the upper
lateral wall of the nasal valve.
[0032] In another embodiment the present invention provides a
nosepiece which includes a flexible tip to fit the cross-sectional
shape of a nasal cavity. In a preferred embodiment the nosepiece
has an internal configuration, at least at the tip, which acts to
prevent collapse and maintain a stable cross-sectional area and a
relatively-stable resistance.
[0033] In a further embodiment the present invention provides a
spray nozzle which provides an asymmetrical spray plume, where
either a powder or a liquid.
[0034] The present invention is particularly advantageous when used
in combination with bi-directional nasal delivery, but is not
restricted to such delivery.
[0035] The present invention can be combined with delivery concepts
which generate a mist, an aerosol, an aerosol spray of particles,
either liquid or powder, drops, droplets, or liquid jet of
liquid.
[0036] An entraining flow can be provided by the exhalation breath
of the subject or from an external flow source, such as from an air
chamber or a compressed air supply.
[0037] The delivery device can be triggered, such that one or both
of the dose and gas flow are triggered by an intraoral pressure
which is such as to close the oropharyngeal velum or by another
event, which may or may not secure velum closure.
[0038] The present invention also finds application in delivery
systems which do not utilize an auxiliary gas flow and even with
inhalation environments which provide for nasal inhalation or a
sniffing manoeuvre through one or both of the nostrils.
[0039] The devices can be a multi-dose or single-dose.
[0040] Preliminary results in models and gamma-scintigraphic pilot
studies show that it is possible to improve the access to and
deposition in the narrow passages of the upper region of the nasal
airway including the olfactory region, the regions with veins
draining to the sinus cavernous and innervated by the trigeminal
nerve.
[0041] Furthermore, experiments in models and humans show that
modification of the plume geometry and/or positioning of the nozzle
provides for optimal delivery.
[0042] U.S. Pat. No. 6,647,980 discloses a device which utilizes a
modified plume in order to attempt to decrease lateral deposition,
and thereby increase the amount of the dose which reaches the upper
region of the nasal airway. Although this device may provide for
reduced deposition in the anterior part of the nasal cavity which
is lined by squamous epithelium, owing to the narrower cone angle,
only a moderate increase in deposition in the upper region of the
nose is expected to be achieved, owing to the difficult and
protected access to this region. Furthermore, narrowing of the nose
during inhalation, as caused by the Bernoulli effect, will further
narrow the nasal cavity to increase the fraction deposited in valve
region.
[0043] In its preferred embodiment the present invention provides
for a bi-directional air flow in the nasal passages in which
optimally-sized particles are entrained and subsequently delivered
to appropriate target sites in the nasal airway.
[0044] The present invention aims further to improve upon the
devices as disclosed in the applicant's earlier WO-A-03/000310, the
content of which is herein incorporated by reference.
[0045] In one embodiment the present invention provides for
optimisation of the delivery to upper parts of the nasal airway,
including the olfactory region, by configuring the nosepiece, in
particular the shape and position thereof, and the emitted plume of
particles or liquid jet in conjunction.
[0046] The present invention provides for significantly enhanced
access and deposition in the upper region of the nasal airway, and
thereby improved dose-to-dose consistency and repeatability of drug
delivery to this region of the nasal airway.
[0047] The delivery device of the present invention provides both
for positioning of the outlet nozzle and the expansion of the upper
lateral and medial surfaces of the valve region of a nasal
cavity.
[0048] By configuring the external and internal shape of the
nosepiece, the nosepiece both ensures the correct positioning of
the outlet nozzle and optimizes the vertical expansion of the nasal
cavity.
[0049] The operative function of the nosepiece of the present
invention, in vertically expanding the nasal cavity, can be
contrasted to that of a conventional, frusto-conical nosepiece,
which, during insertion into a nasal cavity, has been found by the
present inventor to push the soft, nasal tissue rearwardly, which
is particularly disadvantageous where attempting delivery to
posterior regions of the nasal airway.
[0050] In its preferred embodiment the present invention provides a
narrow nosepiece which can be easily slid into a nasal cavity
beyond the nasal valve to the required depth, before expansion in
the vertical or sagittal plane.
[0051] This expanding movement of the nosepiece can either be to
the upper part, the lower part or both the upper and lower
parts.
[0052] In one embodiment the nosepiece comprises two members, that
is, an upper and a lower member, where on one both of the members
is movable relative to the supporting body. Such members are
exemplified by a pair of scissors, a pair of pliers and expansion
screws.
[0053] In another embodiment the nosepiece could comprise an
expanding cuff-like member, which comprises one or both of upper
and lower cuff members which expands in the vertical plane.
[0054] In one embodiment the nosepiece can comprise a
moderately-flexible anterior part such as to allow the nosepiece to
adapt to the curved shape of a nasal passage, and thereby
facilitate deeper insertion into the nasal slit, and even into the
bony part thereof.
[0055] In a preferred embodiment the nosepiece includes internal
features, such as ribs, which prevent collapse of the flow path and
prevents substantial reduction in the internal cross-sectional
area, which would otherwise lead to an increase in flow
resistance.
[0056] This flexibility enables the nosepiece to conform, at least
in part, to the different shapes and directions of the nasal
passage in this region, but at the same time assists in expanding
the isthmus. Though the shape of the anterior part of the nasal
passage normally varies within a pre-defined range, pathological
deviations may cause more pronounced changes which otherwise may
create problems for insertion and positioning of the nosepiece, and
hence efficient delivery.
[0057] Furthermore, this adaptation of the anterior shape of the
nosepiece to conform to the nasal passage provides for reduced
turbulence, which would otherwise lead to unwanted deposition in
the zone of turbulence.
[0058] The present invention also provides for a nozzle, such as
the swirl chamber of a spray pump or a pMDI or a nebulizer, which
delivers a modified, asymmetric plume of particles.
[0059] In its preferred embodiment the plume is an asymmetric plume
which is relatively flat, with a small dimension in one axis and
much greater in the other axis.
[0060] Such a shaped plume reduces deposition in the anterior part
of the valve region and increases the fraction of the dose entering
into the upper, more posterior region of the nasal passage
including the olfactory region and the sinus ostia, which is
located below the middle meatus.
[0061] The present invention also extends to means for securing a
correct and reproducible positioning of nosepiece.
[0062] Positioning of the delivery device can be achieved by the
function of the mouthpiece or an exit resistor in the exit nostril
of a bi-directional device, or as a separate feature with the main
function of assisting positioning of the nosepiece.
Triangular-shaped nose pieces assist in achieving the correct
positioning. The mouthpiece of a device intended for bi-directional
delivery also assists in achieving a reproducible positioning of
the nosepiece. The provision of a nosepiece in the contralateral
nostril also assists in achieving a reproducible positioning of the
nosepiece. The provision of a special cap or the like as applied to
the exterior of the exterior nose also assists in achieving a
reproducible positioning of the nosepiece. Also, tape or vacuum can
be used to assist in positioning of the nose piece and potentially
in addition helps expanding the valve region by external action,
such as an external dilator used to open the nose ("Breath-Right"
nasal strip).
[0063] The present invention extends to devices which are adapted
to bi-directional delivery where driven by the exhalation breath of
the subject or an auxiliary gas source, and conventional nasal
delivery devices which do not utilize an auxiliary gas flow.
[0064] Furthermore, the present invention can be adapted to any
traditional delivery modality, including but not restricted to a
spray pump, a pMDI, a nebulizer or any other means of delivering
liquid jets, particles or drops, either in powder or liquid form,
and is not restricted to bi-directional devices.
[0065] In its preferred embodiment the present invention provides
for expansion in the vertical or sagittal plane, but the expansion
is not restricted to this plane. The expansion can be a combination
of movement in different planes.
[0066] The expansion can be only or predominantly to the upper part
or the lower part of a nasal cavity, or the upper and lower parts
in combination.
[0067] The expansion can be achieved by any possible movement, such
as pushing, pulling, lifting, pressing, rotating, expanding,
flexing, suction (vacuum) and even by secondary chemical reactions
initiated by, for example, pressure, moisture and temperature which
create the desired movement of retraction of a mass or volume.
[0068] In one embodiment, where the nosepiece comprises two movable
members in the form of a speculum, one of the members can provide a
delivery channel through which substance is delivered into the
nasal airway, and the other member can include a pressure-sensitive
release valve or an open channel which allows for the venting of
particles from the nasal airway. Such a configuration has
particular application in relation to a completely obstructed nose,
where the delivered flow would otherwise have no means of
escape.
[0069] Where the substance includes relatively-large particles,
those particles will due to their momentum travel forward and
deposit on an opposing surface, whereas the air flow will deviate
and flow towards the exit valve.
[0070] In having an on/off valve which opens at a predetermined
pressure which is just above the pressure where bi-directional flow
is expected to occur in a moderately-blocked nose, an air flow will
occur suddenly and carry the particles forward, and this will
entrain the particles or at least a large fraction of the particles
into the blocked nose and onto an opposing surface before the
airflow turns around and exits in the opposite direction through
the valve.
[0071] The valve can have a filter to prevent the particles from
escaping to the atmosphere. Using large particles, such as from
about 100 .mu.m to about 200 .mu.m, will also avoid or at least
reduce this problem.
[0072] By providing a relatively-large distance between the point
of emission, which is preferably in the upper member, and the point
of exit, which is preferably in the lower arm, will increase
deposition.
[0073] In a preferred embodiment the positioning of the nosepiece
should preferably occur prior to release of substance, but could
also occur in sequence immediately prior to or simultaneously with
the releasing action.
[0074] The preferred action is as follows. The positioning and
expansion of the specialized nozzle can be achieved by a finger
action. When complete, this action will also open the flow path
permitting delivery of substance into the nasal airway, preferably
by bi-directional delivery, but alternatively also even in the
absence of bi-directional delivery. Alternatively, a pre-charged
spring or similar can be released when the nosepiece is inserted
into a nostril to the correct position. When this positioning
action is complete, a valve is opened, making it possible to blow
through the device or alternatively release the force from a gas
chamber or another stored force, or alternatively allowing a
mechanical action by hand compression, similar to actuation of a
spray pump. In an alternative configuration, which can be utilized
with or without bi-directional flow, for example, when used in
infants and unconscious subjects, the two actions of expansion and
release of substance from, for example, a spray pump can be
integrated. The first part of the mechanical action/compression of
a lever by the finger will secure the expansion of the lever and
positioning of the nosepiece. Then, when a certain trigger point or
resistance is reached the finger force will result in the
generation of a spray or release of a compressed gas by exhalation
against a resistor or from a pressurized compartment or the
combination thereof.
[0075] The following represent potential areas of application.
Delivery to the olfactory epithelium for transport into or along
nerve paths or by diffusion across the cribiform plate. Delivery to
the upper part of the nasal passage including the olfactory region
which drains via veins to the sinus cavernous to achieve higher
concentrations of drugs, with the potential of diffusing into the
carotid artery passing through the sinus cavernous, where diffusing
through the rete mirabile. Delivery to the branches of the
trigeminal nerve for potential peripheral action on the nerves
(analgesics), uptake and transport along the nerves to central
ganglion and potentially into the CNS or with reflectory actions in
other parts of the face or CNS. Improved deposition of drugs in the
middle meatus and infundibulum which includes the sinus ostia. This
region plays a key role in ventilation of the sinuses and in the
development of sinus pathology and consequently for the treatment
of pathology in this region. Delivery of topically-acting
substances, such as decongestants, steroids and antihistamines,
which can reduce the mucosal swelling in the entrances to and in
the narrow slit like passages of the upper part of the nose in
order to improve olfaction or reverse anosmia.
[0076] Preferred embodiments of the present invention will now be
described hereinbelow by way of example only with reference to the
accompanying drawings, in which:
[0077] FIG. 1(a) schematically illustrates the anatomy of the upper
respiratory tract of a human subject;
[0078] FIG. 1(b) illustrates the segmentation of a nasal cavity in
accordance with a preferred embodiment of the present
invention;
[0079] FIG. 2 illustrates a nasal delivery device in accordance
with a first embodiment of the present invention;
[0080] FIGS. 3(a) to (c) illustrate perspective, vertical sectional
and plan views of the nosepiece of the delivery device of FIG.
2;
[0081] FIGS. 4(a) to (f) illustrate the operation of the nasal
delivery device of FIG. 2;
[0082] FIGS. 5(a) to (c) illustrate a first modified nosepiece for
the delivery device of FIG. 2;
[0083] FIGS. 6(a) to (c) illustrate a second modified nosepiece for
the delivery device of FIG. 2;
[0084] FIGS. 7(a) to (c) illustrate a third modified nosepiece for
the delivery device of FIG. 2;
[0085] FIGS. 8(a) to (c) illustrate a fourth modified nosepiece for
the delivery device of FIG. 2;
[0086] FIGS. 9(a) to (c) illustrate a fifth modified nosepiece for
the delivery device of FIG. 2;
[0087] FIGS. 10(a) to (c) illustrate a sixth modified nosepiece for
the delivery device of FIG. 2;
[0088] FIGS. 11(a) to (c) illustrate a seventh modified nosepiece
for the delivery device of FIG. 2;
[0089] FIGS. 12(a) to (c) illustrate an eighth modified nosepiece
for the delivery device of FIG. 2;
[0090] FIGS. 13(a) to (d) illustrate side, front, plan and
sectional (along section I-I in FIG. 13(b)) views of a ninth
modified nosepiece for the delivery device of FIG. 2;
[0091] FIG. 14 illustrates a tenth modified nosepiece for the
delivery device of FIG. 2, as a further modification of the
delivery device of FIG. 13;
[0092] FIGS. 15(a) and (b) illustrate side and end views of a nasal
delivery device in accordance with a second embodiment of the
present invention;
[0093] FIG. 16 illustrates the operation of the delivery device of
FIG. 15;
[0094] FIGS. 17(a) and (b) illustrate side and end views of a nasal
delivery device in accordance with a third embodiment of the
present invention;
[0095] FIG. 18 illustrates the operation of the delivery device of
FIG. 17;
[0096] FIGS. 19(a) and (b) illustrate side and end views of a nasal
delivery device in accordance with a fourth embodiment of the
present invention;
[0097] FIG. 20 illustrates the operation of the delivery device of
FIG. 19;
[0098] FIGS. 21(a) and (b) illustrate side and end views of a nasal
delivery device in accordance with a fifth embodiment of the
present invention;
[0099] FIG. 22 illustrates the operation of the delivery device of
FIG. 21;
[0100] FIGS. 23(a) and (b) illustrate side and end views of a nasal
delivery device in accordance with a sixth embodiment of the
present invention;
[0101] FIG. 24 illustrates the operation of the delivery device of
FIG. 23;
[0102] FIG. 25(a) illustrates a further modification of the
nosepiece of the delivery device of FIG. 2, in an inoperative or
rest state;
[0103] FIG. 25(b) illustrates the nosepiece of FIG. 25(a) following
insertion into a nasal cavity of a subject;
[0104] FIG. 26(a) illustrates a yet further modification of the
nosepiece of the delivery device of FIG. 2, in an inoperative or
rest state;
[0105] FIG. 26(b) illustrates the nosepiece of FIG. 26(a) following
insertion into a nasal cavity of a subject;
[0106] FIG. 27(a) illustrates a still yet further modification of
the nosepiece of the delivery device of FIG. 2, in an inoperative
or rest state; and
[0107] FIG. 27(b) illustrates the nosepiece of FIG. 27(a) following
insertion into a nasal cavity of a subject and inflation to open
the delivery aperture.
[0108] FIGS. 2 and 3 illustrate a nasal delivery device in
accordance with a first embodiment of the present invention.
[0109] The delivery device comprises a housing 15, a nosepiece 17
for fitting in a nasal cavity of a subject, and a mouthpiece 19
through which the subject exhales to actuate the delivery
device.
[0110] The nosepiece 17 is attached to the housing 15 and defines a
delivery channel 23 which is in fluid communication with the
mouthpiece 19 such that an air flow is delivered into and through
the nasal airway of the subject on exhalation by the subject
through the mouthpiece 19.
[0111] As particularly illustrated in FIGS. 3(a) to (c), the
nosepiece 17 comprises a tip element 25 for insertion into the
nasal cavity of the subject, which includes a delivery aperture 26
from which substance is delivered into the nasal cavity of the
subject, and a base section 27 from which the tip element 25
extends, in this embodiment substantially axially to the
longitudinal axis of the nosepiece 17.
[0112] In this embodiment the tip element 25 is of asymmetric,
elongate section, in having a dimension d1 in a first, sagittal
direction which is greater than a dimension d2 in a second, lateral
direction orthogonal to the first, sagittal direction.
[0113] With this configuration, on insertion of the nosepiece 17
into the nasal cavity of the subject, the longer, sagittal section
of the tip element 25 of the nosepiece 17 becomes aligned in the
sagittal plane and acts to engage upper and lower walls of the
nasal cavity of the subject and cause the expansion of the nasal
cavity in the vertical, sagittal plane, in particular the upper
wall of the nasal cavity of the subject, which is a fleshy
structure, as compared to the lower wall of the nasal cavity of the
subject, which is a relatively-hard structure, and also position
the nosepiece 17 in the nasal cavity of the subject, with the lower
wall of the nasal cavity of the subject, in being a relatively-hard
structure, acting as a reference for the expansion. This expansion
further acts to tension the lateral walls of the nasal cavity of
the subject which defines the nasal valve, which causes the lateral
walls of the nasal cavity to be urged into sealing contact with the
nosepiece 17.
[0114] In this embodiment the distal end of the tip element 25 is,
at least in part, tapered, such as to be inclined, here in the
sagittal plane, to the longitudinal axis of the nosepiece 17. With
this configuration, the delivery aperture 26 extends both laterally
across the tip element 25 and along a longitudinal extent of the
tip element 25. The present inventors have recognized that this
configuration is particularly advantageous in ensuring the delivery
of substance from the nosepiece 17 when inserted substantially in
any orient into the nasal cavity of a subject The present inventors
have found that the provision of the delivery aperture 26 in a
conventional sense, that is, in an orthogonal relation to the
longitudinal axis of the nosepiece 17, can lead to obstruction of
the delivery aperture 26 by soft tissue within the nasal cavity,
and that this problem is remarkably overcome by providing that the
delivery aperture 26 is inclined to the longitudinal axis of the
nosepiece 17, thereby in effect extending along a length of the
longitudinal extent of the tip element 25.
[0115] In this embodiment the delivery aperture 26 has an
asymmetric shape in plan view, as illustrated in FIG. 3(c), with
the delivery aperture 26 having a sharper, narrower section 26'
adjacent one, the forwardmost, end of the tip element 25 and a
wider, flatter section 26'' adjacent the other, rearwardmost, end
of the tip element 25. This configuration acts to provide for
greater air flow through the delivery aperture 26 at a location
spaced rearwardly of the forwardmost section of the tip element 25,
which represents that section which is most likely to abut soft
tissue in the nasal cavity of the subject.
[0116] In this embodiment the base section 27 defines a shoulder
29, which provides both a seal with the nares of the nostril of the
subject and determines the extent of the insertion of the nosepiece
17 into the nasal cavity of the subject. In addition, as will be
described in more detail hereinbelow, the shoulder 29 allows for
the nare of the nostril of the subject to be gripped thereagainst
by a finger of the subject, in fixing the position of the delivery
device. The skin of the nose can be particularly slippery due to
excreted oils, and the provision of a gripping surface at the
shoulder 29 is particularly beneficial. This grip can also be
improved by the use of a wipe, such as a tissue, particularly where
impregnated with an agent which removes the excreted oils, such as
to promote the grip with the skin, or alternatively with a grip
enhancer, such as a sticky material, for example, a wax, resin, gel
or liquid, which promotes the adhesion with the skin.
[0117] In this embodiment the nosepiece 17 is formed as a
substantially rigid structure, here formed of a plastics
material.
[0118] The delivery device further comprises an outlet unit 33
which comprises a nozzle 35 at the distal end thereof, in this
embodiment disposed in the nosepiece 17, for delivering substance
to the nasal airway of the subject.
[0119] In a preferred embodiment the nozzle 35 is configured to
extend at least about 2 cm, preferably at least about 3 cm, more
preferably at least about 4 cm, and preferably from about 2 cm to
about 4 cm, into the nasal cavity of the subject on insertion of
the nosepiece 17 into the nasal cavity of the subject.
[0120] In this embodiment the nozzle 35 is configured to provide an
aerosol spray, either as a liquid or powder aerosol.
[0121] In an alternative embodiment the nozzle 35 could be
configured to deliver a jet as a column of substance, either as a
liquid or powder jet.
[0122] In this embodiment the nozzle 35 is configured to deliver a
symmetric aerosol spray.
[0123] In one embodiment the nozzle 35 is configured to deliver an
aerosol spray with a spray angle of not more than about 30.degree.,
preferably not more than about 25.degree., and more preferably not
more than about 30.degree..
[0124] In an alternative embodiment the nozzle 35 could be
configured to deliver an asymmetric aerosol spray, with the aerosol
spray having a significantly greater spray angle in the vertical,
sagittal plane than in the horizontal plane. Such an aerosol spray
has been found to be particularly advantageous in the delivery of
substance to posterior regions of the nasal cavities, in particular
the olfactory region.
[0125] In a preferred embodiment the spray angle in the vertical,
sagittal plane is greater than about 35.degree., more preferably
greater than about 40.degree., still more preferably greater than
about 45.degree. and yet more preferably greater than about
50.degree..
[0126] In a preferred embodiment the spray angle in the horizontal
plane is not more than about 35.degree., more preferably not more
than about 30.degree., still more preferably not more than about
25.degree., yet more preferably not more than about 20.degree., and
still yet more preferably not more than about 15.degree..
[0127] In one embodiment the aerosol spray could present an
elliptical spray zone.
[0128] In another embodiment the aerosol spray could present a
substantially rectangular spray zone.
[0129] The delivery device further comprises a substance supply
unit 37 for delivering metered doses of a substance, which is
fluidly connected to the nozzle 35 of the outlet unit 33 to deliver
substance from the nosepiece 17, in this embodiment as an aerosol
spray.
[0130] In this embodiment the substance supply unit 37 is a
multi-dose unit for delivering a plurality of metered doses of
substance. In another embodiment the substance supply unit 37 could
be a single-dose unit for delivering a single metered dose of
substance.
[0131] The substance supply unit 37 is pre-primeable, in this
embodiment by loading a resilient element, and includes a
breath-actuated release mechanism 39 which, when triggered,
releases the resilient element and actuates the substance supply
unit 37 to deliver a metered dose of substance through the nozzle
35 of the outlet unit 33.
[0132] In this embodiment the release mechanism 39 is configured to
cause actuation .COPYRGT.f the substance supply unit 37 on
generation of a predetermined flow rate through the delivery
channel 23 of the nosepiece 17.
[0133] In another embodiment the release mechanism 39 could be
configured to cause actuation of the substance supply unit 37 on
generation of a predetermined pressure within the delivery channel
23 of the nosepiece 17.
[0134] In a further embodiment the release mechanism 39 could be
configured to cause actuation of the substance supply unit 37 on
generation of either one of a predetermined flow rate through the
delivery channel 23 of the nosepiece 17 or a predetermined pressure
within the delivery channel 23 of the nosepiece 17.
[0135] In this embodiment the substance supply unit 37 comprises a
mechanical delivery pump, in particular a liquid delivery pump or a
powder delivery pump, which delivers metered doses of a substance
on actuation thereof.
[0136] In another embodiment the substance supply unit 37 could
comprise an aerosol canister for delivering metered volumes of a
propellant, preferably a hydrofluoroalkane (HFA) propellant or the
like, containing medicament, either as a suspension or
solution.
[0137] In another alternative embodiment the substance supply unit
37 could comprise a dry powder delivery unit which delivers metered
doses of a substance, as a dry powder, on actuation thereof.
[0138] In yet another alternative embodiment the substance supply
unit 37 could comprise a nebulizer which delivers metered doses of
a substance, as an aerosol spray, on actuation thereof.
[0139] Operation of the delivery device will now be described
hereinbelow with reference to FIGS. 4(a) to (f) of the accompanying
drawings.
[0140] The subject first primes the delivery unit 37, in this
embodiment by loading a biasing element, wipes the nares of his/her
nostril with a tissue or the like, and grips the delivery device
between the thumb and the second, third and fourth fingers, keeping
the first, index finger free, as illustrated in FIG. 4(a).
[0141] The nosepiece 17 is then inserted into one of the nostrils,
in this embodiment the left nostril, with a twisting movement, such
as to align the mouthpiece 19 with the mouth of the subject, and
then the mouthpiece 19 is gripped in the lips of the subject, as
illustrated in FIG. 4(b).
[0142] With the nosepiece 17 so inserted into the nasal cavity of
the subject, the longer, sagittal section of the tip element 25 is
aligned in the sagittal plane and engages upper and lower walls of
the nasal cavity of the subject, which engagement causes the
expansion of the nasal cavity in the vertical, sagittal plane, in
particular the upper wall of the nasal cavity of the subject, which
is a fleshy structure, as compared to the lower wall of the nasal
cavity of the subject, which is a relatively-hard structure, and
also positions the nosepiece 17 in the nasal cavity of the subject,
with the lower wall of the nasal cavity of the subject, in being a
relatively-hard structure, acting as a reference for the expansion.
This expansion acts to prevent the bulging of the fleshy structure
which can cause partial or full obstruction of the nasal valve and
further acts to tension the lateral walls of the nasal cavity of
the subject which defines the nasal valve, which causes the lateral
walls of the nasal cavity to be urged into sealing contact with the
nosepiece 17.
[0143] The subject then extends his/her index finger adjacent the
nare of the nostril, such that the index finger is directed to a
point between the eyes and the tip of the finger is broadly aligned
with the distal end of the nosepiece 17 which is located within the
nasal cavity, as illustrated in FIG. 4(b). In an alternative
embodiment the free finger could be another finger other than the
index finger.
[0144] The index finger is then pressed against the skin of the
nose, such as to press the nare of the nostril against: the
nosepiece 17, and gently retracted, such as to pull the nare of the
nostril onto the shoulder 29 of the nosepiece 17, as illustrated in
FIG. 4(c). This action acts to straighten the flow path and improve
access beyond the nasal valve. In one embodiment the skin of the
nose can be cleaned by the use of a wipe, which can be impregnated
with a cleaning agent to promote the removal of the secreted oils,
or alternatively a grip-enhancing agent can be applied to the skin
of the nose to promote the grip therewith.
[0145] The subject then begins to exhale through the mouthpiece 19,
which exhalation acts to close the oropharyngeal velum of the
subject and drive an air flow through the delivery channel 23 of
the nosepiece 17, with the air flow passing into the one nasal
cavity, around the posterior margin of the nasal septum and out of
the other nasal cavity, thereby achieving a bi-directional air flow
through the nasal airway of the subject.
[0146] In this embodiment, when the flow rate developed through the
delivery channel 23 of the nosepiece 17 reaches a predetermined
value, the release mechanism 39 is triggered to actuate the
substance supply unit 37 to deliver a metered dose of a substance
to the nozzle 35 of the outlet unit 33 and into the nasal cavity of
the subject, in this embodiment as an aerosol spray. In an
alternative embodiment the release mechanism 39 could be triggered
on the generation of a predetermined pressure in the delivery
channel 23 of the nosepiece 17.
[0147] Following exhalation, the subject then releases the
mouthpiece 19 and the nosepiece 17 is withdrawn from the nasal
cavity of the subject.
[0148] In one embodiment, where the delivery device is a
single-dose device, the device can be discarded.
[0149] In another embodiment, as in this embodiment, where the
delivery device is a multi-dose device, the device is ready for
further use following priming of the substance supply unit 37.
[0150] In this embodiment a second dose of substance is delivered
into the other nostril, here the right nostril, in the same manner
as described hereinabove and illustrated in FIGS. 4(d) to (f).
[0151] FIGS. 5(a) to (c) illustrate a modified nosepiece 17 for the
delivery device of the above-described embodiment.
[0152] In this embodiment the tip element 25 has a greater length
than the tip element 25 of the above-described embodiment.
[0153] FIGS. 6(a) to (c) illustrate another modified nosepiece 17
for the delivery device of the above-described embodiment.
[0154] In this embodiment the ratio of the lengths of the sagittal
sections 26', 26'' of the tip element 25 is greater than that of
the above-described embodiment, such as to provide a more elongate
delivery aperture 26. In this embodiment the length 11 of the
forwardmost sagittal section 26' is greater than twice the length
12 of the rearwardmost sagittal section 26''.
[0155] Further, in this embodiment the tip element 25 is shaped
such that the delivery aperture 26 comprises an orthogonal section
adjacent the forwardmost sagittal section 26'.
[0156] FIGS. 7(a) to (c) illustrate a further modified nosepiece 17
for the delivery device of the above-described embodiment.
[0157] In this embodiment the tip element 25 has a greater length
than the tip element 25 of the embodiment of FIGS. 6(a) to (c).
[0158] FIGS. 8(a) to (c) illustrate a yet further modified
nosepiece 17 for the delivery device of the above-described
embodiment.
[0159] In this embodiment the tip element 25 has a greater width at
the proximal end thereof than the tip element 25 of the embodiment
of FIGS. 6(a) to (c). With this configuration, the shoulder 29 acts
to promote sealing with the nares of the nostril of the
subject.
[0160] Further, in this embodiment the length 11 of the forwardmost
sagittal section 26' is about twice the length 12 of the
rearwardmost sagittal section 26''.
[0161] FIGS. 9(a) to (c) illustrate a still further modified
nosepiece 17 for the delivery device of the above-described
embodiment.
[0162] In this embodiment the tip element 25 has a wider,
frusto-conical section than the tip element 25 of the
above-described embodiment. With this configuration, the shoulder
29 acts to promote sealing with the nares of the nostril of the
subject deeper in the nasal cavity.
[0163] Further, in this embodiment the length 11 of the forwardmost
sagittal section 26' is less than twice the length 12 of the
rearwardmost sagittal section 26''.
[0164] FIGS. 10(a) to (c) illustrate a yet still further modified
nosepiece 17 for the delivery device of the above-described
embodiment.
[0165] In this embodiment the proximal section of the tip element
25 has a wider lateral section than the tip element 25 of the
above-described embodiment. With this configuration, the shoulder
29 acts further to promote sealing with the nares of the nostril of
the subject.
[0166] FIGS. 11(a) to (c) illustrate yet another modified nosepiece
17 for the delivery device of the above-described embodiment.
[0167] In this embodiment the nosepiece 17 is formed of two body
parts 41, 43, a first, inner body part 41, here formed of a rigid
material, such as a rigid plastics material, and a second, outer
body part 43 which is disposed about the distal end of the inner
body part 41 and defines the tip element 25.
[0168] In this embodiment the outer body part 43 is formed of a
soft, resilient material, such as a rubber or plastics material,
which confers sufficient flexibility as to facilitate insertion of
the tip element 25 into the nasal valve of the subject, and yet the
inner body part 4:1 confers rigidity in the sagittal plane as to
promote expansion of the fleshy tissues at the nasal valve.
[0169] Further, in this embodiment the tip element 25 is configured
such that the delivery aperture 26 has a symmetric shape, here of
circular shape, in a plane orthogonal to the longitudinal axis of
the nosepiece 17.
[0170] FIGS. 12(a) to (c) illustrate still another modified
nosepiece 17 for the delivery device of the above-described
embodiment.
[0171] In this embodiment the tip element 25 has a greater length
than the tip element 25 of the embodiment of FIGS. 11(a) to
(c).
[0172] Still further, in this embodiment the length 11 of the
forwardmost sagittal section 26' is less than twice the length 12
of the rearwardmost sagittal section 26''.
[0173] FIGS. 13(a) to (d) illustrate still another modified
nosepiece 17 for the delivery device of the above-described
embodiment.
[0174] This embodiment is a modification of the embodiment of FIGS.
11(a) to (c). In this embodiment the nozzle 25 is integrally formed
with the tip element 25, here the inner body part 41 of the tip
element 25.
[0175] FIG. 14 illustrates yet still another modified nosepiece 17
for the delivery device of the above-described embodiment.
[0176] This embodiment is a modification of the embodiment of FIGS.
13(a) to (d). In this embodiment the nozzle 25 is integrally formed
with the tip element 25, but here the inner body part 43 of the tip
element 25.
[0177] FIGS. 15 and 16 illustrate a nasal delivery device in
accordance with a second embodiment of the present invention.
[0178] The delivery device comprises a housing 115, a nosepiece 117
for fitting in a nasal cavity of a subject, and a mouthpiece 119
through which the subject exhales to actuate the delivery
device.
[0179] The nosepiece 117 is attached to the housing 115 and defines
a delivery channel which is in fluid communication with the
mouthpiece 119 such that an air flow is delivered into and through
the nasal airway of the subject on exhalation by the subject
through the mouthpiece 119.
[0180] The delivery device further comprises a substance supply
unit (not illustrated) for delivering metered doses of a substance
from the nosepiece 117, in this embodiment as an aerosol spray.
[0181] In this embodiment the substance supply unit is a multi-dose
unit for delivering a plurality of metered doses of substance. In
another embodiment the substance supply unit could be a single-dose
unit for delivering a single metered dose of substance.
[0182] The substance supply unit is pre-primeable, in this
embodiment by loading a resilient element, and includes a
breath-actuated release mechanism which, when triggered, releases
the resilient element and actuates the substance supply unit to
deliver a metered dose of substance through the nosepiece 117.
[0183] The delivery device further comprises a nose gripping member
151, which receives a finger of the subject, in this embodiment the
index finger, and is configured to be brought into contact with the
skin of the nare of the nostril into which the nosepiece 117 is
inserted, such as to allow the skin of the nare of the nostril to
be drawn down over the nosepiece 117 and promote the fitting and
sealing of the nosepiece 117 in the nasal cavity of the subject and
also straighten the flow path and improve access beyond the nasal
valve. FIG. 16 illustrates the operation of the gripping member
151.
[0184] In this embodiment the gripping member 151 comprises an
attachment element 153 which is attached to the housing 115, and a
gripping element 155 which includes a pocket 157 which receives a
finger of the subject and is configured to allow for pressing into
engagement with the skin of the nare of the nostril.
[0185] In this embodiment the attachment element 153 is adhered to
the housing 115, here by adhesive tape.
[0186] In this embodiment the gripping element 153 comprises a
flexible element. In one embodiment the gripping element 153 is
formed of a fabric material. In another embodiment the gripping
element 153 is formed of a plastics material. In a further
embodiment the gripping element 153 is formed of a resilient
material, such as a rubber material.
[0187] FIGS. 17 and 18 illustrate a nasal delivery device in
accordance with a third embodiment of the present invention.
[0188] The delivery device comprises a housing 215, a nosepiece 217
for fitting in a nasal cavity of a subject, and a mouthpiece 219
through which the subject exhales to actuate the delivery
device.
[0189] The nosepiece 217 is attached to the housing 215 and defines
a delivery channel which is in fluid communication with the
mouthpiece 219 such that an air flow is delivered into and through
the nasal airway of the subject on exhalation by the subject
through the mouthpiece 219.
[0190] The delivery device further comprises a substance supply
unit (not illustrated) for delivering metered doses of a substance
from the nosepiece 217, in this embodiment as an aerosol spray.
[0191] In this embodiment the substance supply unit is a multi-dose
unit for delivering a plurality of metered doses of substance. In
another embodiment the substance supply unit could be a single-dose
unit for delivering a single metered dose of substance.
[0192] The substance supply unit is pre-primeable, in this
embodiment by loading a resilient element, and includes a
breath-actuated release mechanism which, when triggered, releases
the resilient element and actuates the substance supply unit to
deliver a metered dose of substance through the nosepiece 217.
[0193] The delivery device further comprises a nose gripping member
251, which receives a finger of the subject, in this embodiment the
index finger, and is configured to be brought into contact with the
skin of the nare of the nostril into which the nosepiece 217 is
inserted, such as to allow the skin of the nare of the nostril to
be drawn down over the nosepiece 217 and promote the fitting and
sealing of the nosepiece 217 in the nasal cavity of the subject.
FIG. 18 illustrates the operation of the gripping member 251.
[0194] In this embodiment the gripping member 251 comprises a
support element 253 which is attached to the housing 215, here
pivotally coupled to the housing 215, a biasing element 254, here a
spring element, which is operative to bias the support element 253
to an inoperative or rest position, and a gripping element 255
which is attached to the support element 253 and includes a pocket
257 which receives a finger of the subject to allow for pressing
into engagement with the skin of the nare of the nostril.
[0195] In this embodiment the support element 253 is coupled to the
housing 215, such as to allow both for longitudinal and lateral
pivoting of the support element 253 against the bias of the biasing
element 254.
[0196] In this embodiment the gripping element 255 is slideably
disposed to the support element 253, such as to allow the gripping
element 255 to be drawn downwardly by a retracting action of the
finger.
[0197] In one embodiment the gripping element 253 is formed of a
fabric material. In another embodiment the gripping element 253 is
formed of a plastics material. In a further embodiment the gripping
element 253 is formed of a resilient material, such as a rubber
material.
[0198] In one embodiment the gripping element 253 can include a
gripping surface which has chemical or mechanical properties for
enhancing the grip with the skin of the nose, such as provided by
an adhesive material, for example, by an adhesive film or tape or
by the application of a glue, liquid, gel, resin or powder, or a
vacuum. In one embodiment the gripping element 253 can be
impregnated with such an adhesive material, which can allow for
prolonged use of the device.
[0199] FIGS. 19 and 20 illustrate a nasal delivery device in
accordance with a fourth embodiment of the present invention.
[0200] The delivery device comprises a housing 315, a nosepiece 317
for fitting in a nasal cavity of a subject, and a mouthpiece 319
through which the subject exhales to actuate the delivery
device.
[0201] The nosepiece 317 is attached to the housing 315 and defines
a delivery channel which is in fluid communication with the
mouthpiece 319 such that an air flow is delivered into and through
the nasal airway of the subject on exhalation by the subject
through the mouthpiece 319.
[0202] The delivery device further comprises a substance supply
unit (not illustrated) for delivering metered doses of a substance
from the nosepiece 317, in this embodiment as an aerosol spray.
[0203] In this embodiment the substance supply unit is a multi-dose
unit for delivering a plurality of metered doses of substance. In
another embodiment the substance supply unit could be a single-dose
unit for delivering a single metered dose of substance.
[0204] The substance supply unit is pre-primeable, in this
embodiment by loading a resilient element, and includes a
breath-actuated release mechanism which, when triggered, releases
the resilient element and actuates the substance supply unit to
deliver a metered dose of substance through the nosepiece 317.
[0205] The delivery device further comprises a nose gripping member
351, which receives a finger of the subject, in this embodiment the
index finger, and is configured to be brought into contact with the
skin of the nare of the nostril into which the nosepiece 317 is
inserted, such as to allow the skin of the nare of the nostril to
be drawn down over the nosepiece 317 and promote the fitting and
sealing of the nosepiece 317 in the nasal cavity of the subject and
also straighten the flow path and improve access beyond the nasal
valve. FIG. 20 illustrates the operation of the gripping member
351.
[0206] In this embodiment the gripping member 351 comprises an
attachment element 352 which is attached to the housing 315, a
support element 353 which is coupled, here resiliently coupled to
the attachment element 352, and a gripping element 355 which is
attached to the support element 353 and is configured to receive a
finger of the subject to allow for pressing into engagement with
the skin of the nare of the nostril.
[0207] In this embodiment the support element 353 is formed of a
material which has sufficient resilience as to allow the gripping
element 355 normally to maintain an inoperative or rest position
and yet be biased, here by resilient deflection of the support
element 353, into engagement with the skin of the nare of the
nostril.
[0208] In this embodiment the support element 353 comprises an
elongate support section 357, here of circular section, and the
gripping element 355 includes a longitudinal bore 359, here of
circular shape, which receives the support section 357, such as to
allow both for longitudinal sliding of the gripping element 355
along the support section 357 and lateral rotation about the
support section 357.
[0209] In this embodiment the gripping member 351 further comprises
a biasing element 361, here a resilient element, which is disposed
to the support element 353 such as to bias the gripping element 355
in a downward direction relative to the nosepiece 317 and thereby
facilitate the desired downward pulling action on the skin of the
nare of the nostril as achieved by the retracting action of the
finger and also straighten the flow path and improve access beyond
the nasal valve.
[0210] In one embodiment the gripping element 355 is formed of a
fabric material. In another embodiment the gripping element 355 is
formed of a plastics material. In a further embodiment the gripping
element 355 is formed of a resilient material, such as a rubber
material.
[0211] FIGS. 21 and 22 illustrate a nasal delivery device in
accordance with a fifth embodiment of the present invention.
[0212] The delivery device comprises a housing 415, a nosepiece 417
for fitting in a nasal cavity of a subject, and a mouthpiece 419
through which the subject: exhales to actuate the delivery
device.
[0213] The nosepiece 417 is attached to the housing 415 and defines
a delivery channel which is in fluid communication with the
mouthpiece 419 such that an air flow is delivered into and through
the nasal airway of the subject on exhalation by the subject
through the mouthpiece 419.
[0214] The delivery device further comprises a substance supply
unit (not illustrated) for delivering metered doses of a substance
from the nosepiece 417, in this embodiment as an aerosol spray.
[0215] In this embodiment the substance supply unit is a multi-dose
unit for delivering a plurality of metered doses of substance. In
another embodiment the substance supply unit could be a single-dose
unit for delivering a single metered dose of substance.
[0216] The substance supply unit is pre-primeable, in this
embodiment by loading a resilient element, and includes a
breath-actuated release mechanism which, when triggered, releases
the resilient element and actuates the substance supply unit to
deliver a metered dose of substance through the nosepiece 417.
[0217] The delivery device further comprises a nose gripping member
451, which receives a finger of the subject, in this embodiment the
index finger, and is configured to be brought into contact with the
skin of the nare of the nostril into which the nosepiece 417 is
inserted and provide for enhanced grip therewith, such as to allow
the skin of the nare of the nostril to be drawn down over the
nosepiece 417 and promote the fitting and sealing of the nosepiece
417 in the nasal cavity of the subject and also straighten the flow
path and improve access beyond the nasal valve. FIG. 22 illustrates
the operation of the gripping member 451.
[0218] In this embodiment the gripping member 451 comprises a
gripping element 455, here in the form of a finger-receiving
element, typically in the form of a thimble, and an attachment
element 457, here a flexible line, which is attached to the
gripping element 455 and the housing 415, such as to prevent the
gripping element 455 from becoming separated from the housing
415.
[0219] In this embodiment the gripping element 455 is configured to
allow for attachment to one of the nosepiece 417, the mouthpiece
419 or an actuator element. This configuration advantageously
allows for the protection of such components when the device is not
in use.
[0220] In an alternative embodiment the gripping member 451 could
comprise only the gripping element 455, and be provided as a
separate component. In one embodiment the delivery device could be
provided with a plurality of gripping members 451.
[0221] In one embodiment the gripping element 455 is formed of a
fabric material. In another embodiment the gripping element 455 is
formed of a plastics material. In a further embodiment the gripping
element 455 is formed of a resilient material, such as a rubber
material.
[0222] FIGS. 23 and 24 illustrate a nasal delivery device in
accordance with a sixth embodiment of the present invention.
[0223] The delivery device comprises a housing 515, a nosepiece 517
for fitting in a nasal cavity of a subject, and a mouthpiece 519
through which the subject exhales to actuate the delivery
device.
[0224] The nosepiece 517 is attached to the housing 515 and defines
a delivery channel which is in fluid communication with the
mouthpiece 519 such that an air flow is delivered into and through
the nasal airway of the subject on exhalation by the subject
through the mouthpiece 519.
[0225] The delivery device further comprises a substance supply
unit (not illustrated) for delivering metered doses of a substance
from the nosepiece 517, in this embodiment as an aerosol spray.
[0226] In this embodiment the substance supply unit is a multi-dose
unit for delivering a plurality of metered doses of substance. In
another embodiment the substance supply unit could be a singledose
unit for delivering a single metered dose of substance.
[0227] The substance supply unit is pre-primeable, in this
embodiment by loading a resilient element, and includes a
breath-actuated release mechanism which, when triggered, releases
the resilient element and actuates the substance supply unit to
deliver a metered dose of substance through the nosepiece 517.
[0228] The delivery device further comprises a nose gripping member
551, in this embodiment as a member separate to the housing 515 of
the delivery device, which is configured to receive a finger of the
subject, in this embodiment the index finger, such as to allow the
skin of the nare of the nostril to be drawn down over the nosepiece
517 and promote the fitting and sealing of the nosepiece 517 in the
nasal cavity of the subject and also straighten the flow path and
improve access beyond the nasal valve. FIG. 24 illustrates the
operation of the gripping member 551.
[0229] In this embodiment the gripping member 551 comprises a
gripping element 555, which is fixed to the nose of the subject,
such as to allow for gripping by the finger of the subject.
[0230] In this embodiment the gripping member 551 further comprises
an attachment element 557, here a resilient element, which acts to
fasten the gripping element 555 to the nose.
[0231] In an alternative embodiment the attachment element 557
could be in the form of a frame which fits to the face of the
subject, for example, in the manner of spectacles.
[0232] In an alternative embodiment the gripping element 555 could
be adhered to the nose, for example, by adhesive tape.
[0233] In one embodiment the gripping element 555 could take the
form of a nasal dilator which is fixed to the nose.
[0234] 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.
[0235] FIGS. 25(a) and (b) illustrate a further modification of the
nosepiece 17 of the delivery device of FIG. 2.
[0236] In this embodiment the tip element 25 comprises a flexible
nosepiece member 51 and an expansion member 53 which acts to expand
the nosepiece member 51 laterally on the application of an
insertion force F substantially along the longitudinal axis of the
nosepiece 17, as illustrated in FIG. 25(b).
[0237] In this embodiment the expansion member 53 comprises a
plurality of elongate elements 55 which are disposed within the
nosepiece member 51 such as normally to have a first, flat
configuration in which the nosepiece member 51 has a contracted
state, as illustrated in FIG. 25(a), and, on the application of an
insertion force F substantially along the longitudinal axis of the
nosepiece 17, at least one of the elongate elements 55' is
longitudinally displaced relative to the at least one other
elongate element 55'', such as to expand the nosepiece member 51
into an expanded state, as illustrated in FIG. 25(b).
[0238] FIGS. 26(a) and (b) illustrate a yet further modification of
the nosepiece of the delivery device of FIG. 2.
[0239] In this embodiment the tip element 25 comprises a flexible
nosepiece member 61 and an expansion member 63 which acts to expand
the nosepiece member 61 laterally on the application of an
insertion force F substantially along the longitudinal axis of the
nosepiece 17, as illustrated in FIG. 26(b).
[0240] In this embodiment the expansion member 63 comprises a coil
which is disposed within the nosepiece member 61 such as normally
to have a first, flat configuration in which the nosepiece member
61 has a contracted state, as illustrated in FIG. 26(a), and, on
the application of an insertion force F substantially along the
longitudinal axis of the nosepiece 17, the coil is longitudinally
compressed, such as to expand the coil and configure the nosepiece
member 61 in an expanded state, as illustrated in FIG. 26(b).
[0241] FIGS. 27(a) and (b) illustrate a still yet further
modification of the nosepiece of the delivery device of FIG. 2.
[0242] In this embodiment the tip element 25 comprises a flexible
nosepiece member 71 which is inflatable from a first configuration,
as illustrated in FIG. 27(a), in which the delivery aperture 26 is
in a closed configuration, here substantially closed, to an open
configuration, as illustrated in FIG. 27(b), in which the delivery
aperture 26 is open, such as to allow for the delivery of substance
therethrough.
[0243] In this embodiment the nosepiece member 71 includes an
annular chamber 73 which surrounds the delivery channel 23 at the
delivery aperture 26, which is normally in a collapsed, uninflated
state, and, on inflation, acts to define a relatively-rigid annulus
which holds open the delivery aperture 26.
[0244] In one embodiment the inflation chamber 73 can be inflated
by a gas, such as from the exhalation breath of a subject or by
mechanical operation by a subject, either directly, such as by the
application of a manual force with the fingers of the subject, or
through an actuator, such as a spring. In an alternative embodiment
the inflation chamber 73 can be inflated by a liquid.
* * * * *