U.S. patent application number 10/429500 was filed with the patent office on 2003-12-11 for system comprising a nozzle and a fixing means therefor.
This patent application is currently assigned to Boehringer Ingelheim International GmbH. Invention is credited to Dunne, Stephen, Geser, Johannes, Hochrainer, Dieter, Wachtel, Herbert.
Application Number | 20030226907 10/429500 |
Document ID | / |
Family ID | 29432128 |
Filed Date | 2003-12-11 |
United States Patent
Application |
20030226907 |
Kind Code |
A1 |
Geser, Johannes ; et
al. |
December 11, 2003 |
System comprising a nozzle and a fixing means therefor
Abstract
The invention relates to a nozzle system for a delivery device
for liquids, wherein the nozzle system comprises a nozzle and a
device which fixes the nozzle in the delivery device. The delivery
device, an atomiser, has a liquid reservoir from which a liquid is
forced through the nozzle under pressure. The nozzle fixing means
may itself be secured by a second fixing, e.g., in the form of a
check nut, or the fixing may itself be a check nut. According to
the invention the fixing means on the nozzle outlet side has a
specific geometry which minimises the proportion of dispensed
liquid deposited on the fixing means. Preferably, the present
invention is part of a propellant-free device for nebulising
pharmaceutical liquids.
Inventors: |
Geser, Johannes; (Ingelheim,
DE) ; Hochrainer, Dieter; (Oberkirchen, DE) ;
Wachtel, Herbert; (Bingen, DE) ; Dunne, Stephen;
(Suffolk, GB) |
Correspondence
Address: |
BOEHRINGER INGELHEIM CORPORATION
900 RIDGEBURY ROAD
P. O. BOX 368
RIDGEFIELD
CT
06877
US
|
Assignee: |
Boehringer Ingelheim International
GmbH
Ingelheim
DE
|
Family ID: |
29432128 |
Appl. No.: |
10/429500 |
Filed: |
May 2, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60382129 |
May 21, 2002 |
|
|
|
Current U.S.
Class: |
239/398 |
Current CPC
Class: |
A61M 15/0065 20130101;
A61M 11/00 20130101; B05B 1/26 20130101; B05B 11/3091 20130101;
B05B 15/65 20180201 |
Class at
Publication: |
239/398 |
International
Class: |
B05B 007/04 |
Foreign Application Data
Date |
Code |
Application Number |
May 16, 2002 |
DE |
102 21 732.7 |
Claims
1. Nozzle system (1) which consists of a nozzle (3) having at least
two nozzle apertures (11) and a nozzle holder (4) and optionally a
check nut (2), wherein the nozzle apertures (11) or the nozzle
channels (9) opening into the nozzle apertures (11) are arranged so
that the jets leaving the nozzle apertures (11) are aimed towards
one another at an angle .alpha., the nozzle (3) is arranged in the
nozzle holder (4) and this is optionally fixed by a check nut (2),
in the assembled state the nozzle holder (4) or the check nut (2)
or both extend at least partially into the area in front of the
nozzle apertures (11), characterised in that in the assembled state
the nozzle holder (4) or, if the nozzle system (1) has a check nut
(2), the nozzle holder (4) together with the check nut (2) has an
inner recess, which begins on the side adjacent to the end face of
the nozzle (3) and extends as far as the outside of the nozzle
holder (4) parallel thereto or, in the case of a check nut (2), as
far as the outside thereof parallel to the end face of the nozzle,
which, viewed from the end face of the nozzle (3), widens out
steadily and continuously in the direction of the outside of the
nozzle holder (4) parallel thereto or, in the case of a check nut
(2), the outside of said check nut parallel thereto.
2. Nozzle system (1) according to claim 1, characterised in that a
check nut (2) is provided.
3. Nozzle system (1) according to claim 1, characterised in that
the recess (5) is funnel-shaped or conical.
4. Nozzle system (1) according to claim 3, characterised in that
the recess (5) of conical construction has a cone angle 2.theta. in
the range between 55.degree. and 155.degree..
5. Nozzle system (1) according to claim 4, characterised in that
the recess (5) of conical construction has a cone angle 2.theta. in
the range between 70.degree. and 140.degree..
6. Nozzle system (1) according to claim 5, characterised in that
the recess (5) of conical construction has a cone angle 2.theta. in
the range between 70.degree. and 85.degree..
7. Nozzle system (1) according to claim 5, characterised in that
the recess (5) of conical construction has a cone angle 2.theta. in
the range between 95.degree. and 140.degree..
8. Nozzle system (1) according to claim 7, characterised in that
the recess (5) of conical construction has a cone angle 2.theta. in
the range between 105.degree. and 125.degree..
9. Nozzle system (1) according to claim 1, characterised in that
the point of collision (10) where the jets meet has a height of
impact h above the nozzle apertures (11) which is in the range
between 20 .mu.m and 85 .mu.m.
10. Nozzle system (1) according to claim 9, characterised in that
the point of collision (10) where the jets meet has a height of
impact h above the nozzle apertures (11) which is in the range
between 25 .mu.m and 75 .mu.m.
11. Nozzle system (1) according to claim 10, characterised in that
the point of collision (10) where the jets meet has a height of
impact h above the nozzle apertures (11) which is in the range
between 35 .mu.m and 75 .mu.m.
12. Nozzle system (1) according to claim 1, characterised in that
the angle .alpha. is in the range between 50.degree. and
110.degree..
13. Nozzle system (1) according to claim 12, characterised in that
the angle .alpha. is in the range between 65.degree. and
95.degree..
14. Nozzle system (1) according to claim 13, characterised in that
the angle .alpha. is in the range between 75.degree. and
90.degree..
15. Nozzle system (1) according to claim 1, characterised in that
the spacing a of the nozzle apertures (11) is in the range between
40 .mu.m and 125 .mu.m.
16. Nozzle system (1) according to claim 15, characterised in that
the spacing a of the nozzle apertures (11) is in the range between
50 .mu.m and 115 .mu.m.
17. Nozzle system (1) according to claim 15, characterised in that
the spacing a of the nozzle apertures (11) is in the range between
60 .mu.m and 105 .mu.m.
18. Nozzle system (1) according to claim 1, characterised in that
in the assembled state only the nozzle holder (4) extends into the
area in front of the nozzle apertures (11).
19. Nozzle system according to claim 1, characterised in that the
nozzle is formed from at least two construction units.
20. Nozzle system according to claim 1, characterised in that the
nozzle is formed from at least two superimposed plates, at least
one of the plates having a second microstructure so that the plates
lying one on top of the other define, on one side, a liquid inlet
connected to a channel system and/or a filter system which then
opens into one or more liquid outlets.
21. Delivery device for liquids, characterised in that it comprises
a nozzle system according to one of claim 1.
22. Delivery device according to claim 21, characterised in that it
is an atomiser for pharmaceutical liquids.
23. Delivery device according to claim 21, characterised in that
the device comprises a lower and an upper housing part mounted to
be rotatable relative to one another, the upper part of the housing
containing a spring housing with spring which is tensioned by
rotating the two housing parts by means of a locking clamping
mechanism preferably in the form of a screw thread or gear and is
released by pressing a release button on the upper part of the
housing, the spring meanwhile moving a power take-off flange
connected to a hollow piston on the lower end of which a container
can be fitted and at the upper end of which are found a valve and a
pressure chamber which is connected for fluid transmission to the
nozzle or the nozzle system formed in the upwardly open part of the
upper housing part.
24. Delivery device according to claim 23, characterised in that
the device is an inhaler or some other atomiser for medicinal
liquids.
Description
RELATED APPLICATIONS
[0001] Benefit of U.S. Provisional Application Serial No.
60/382,129, filed on May 21, 2002 is hereby claimed.
FIELD OF THE INVENTION
[0002] The invention relates to a nozzle system for a delivery
device for liquids, wherein the nozzle system comprises a nozzle
and a device which fixes the nozzle in the delivery device. The
delivery device, an atomiser, has a liquid reservoir from which a
liquid is forced through the nozzle under pressure. The nozzle
fixing means may itself be secured by a second fixing, e.g., in the
form of a check nut, or the fixing may itself be a check nut.
According to the invention the fixing means on the nozzle outlet
side has a specific geometry which minimises the amount of
dispensed liquid deposited on the fixing means.
[0003] Preferably, the present invention is part of a
propellant-free device for nebulising pharmaceutical fluids. A
nebuliser according to the invention is used, for example, to
produce an aerosol of droplets for inhalation through the mouth and
pharyngeal cavity into the lungs of a patient, for nasal
administration or for spraying the surface of the eye.
PRIOR ART
[0004] WO 91/14468 discloses an apparatus for propellant-free
administration of a metered quantity of a liquid pharmaceutical for
application by inhalation. A further development of the device is
described in detail in WO 97/12687. Reference is specifically made
to these publications and the technology described therein is
referred to within the scope of the present invention as
Respimat.RTM. technology. This term refers in particular to the
technology which forms the basis for a device according to FIGS. 6a
and 6b of WO 97/12687 and the associated description.
Propellant-free liquids can easily be atomised using such
devices.
[0005] In an inhaler of this kind liquid pharmaceutical
formulations are stored in a reservoir. From there, they are
conveyed through a riser tube into a pressure chamber from where
they are forced through a nozzle.
[0006] The nozzle is held by a nozzle holder and the latter is
secured by a check nut. The check nut has a liquid inlet side and a
liquid outlet side. On the liquid inlet side is an opening through
which a liquid from the pressure chamber can enter the nozzle. On
the opposite side, the end face of the nozzle, the liquid then
passes through two nozzle apertures which are aligned so that the
jets of liquid leaving the apertures strike one another and are
thereby atomised. The nozzle apertures are arranged in the inhaler
in such a way that they are in direct contact with the outer
environment.
[0007] This is achieved by the fact that the entire region of the
nozzle holder and check nut which is located above the nozzle
apertures has a recess (or hole or bore) through it which provides
a pathway for a jet of liquid leaving the nozzle or an emerging
aerosol to leave the atomiser through the mouthpiece.
[0008] In the region of this nozzle holder this recess is
funnel-shaped while in the region of the check nut this recess is
in the form of a uniform cylinder. The transition between the
nozzle holder and check nut has a sharp edge so that the cross
section of the recess is like an L in which the crossbar is
inclined slightly downwards. The entire recess in front of the
nozzle aperture, which is made up of the recess in the nozzle
holder and the recess of the check nut, has a point of
discontinuity in the elbow region of this L: the recess expands
discontinuously, i.e., viewed from the base it first of all widens
out and then bends sharply vertically in the region of the
transition from the nozzle holder to the check nut. The vertical
direction corresponds to the direction of spraying of the emerging
liquid, i.e., the perpendicular to the outside of the nozzle (end
face).
[0009] These inhalers normally deliver formulations based on water
or mixtures of water and ethanol. They are able to nebulise a small
amount of a liquid formulation in the therapeutically required
dosage within a few seconds to produce an aerosol suitable for
therapeutic inhalation. With the device, quantities of less than
100 microlitres can be nebulised, e.g., with one spray actuation,
to produce an aerosol with an average particle size of less than 20
microns so that the inhalable part of the aerosol corresponds to
the therapeutically effective amount. In these nebulisers with
Respimat.RTM. technology a pharmaceutical solution is converted by
high pressure up to 500 bar into a low-speed aerosol mist destined
for the lungs, which the patient can then breathe in.
[0010] A small amount of the liquid may be deposited from the
outside as a film or as an accumulation of small droplets on the
end face of the nozzle or on the end face of the fixing means for
the nozzle or on the inside of the mouthpiece. This fraction of the
liquid is also referred to as the mouthpiece fraction within the
scope of this specification. This mouthpiece fraction reduces the
amount of liquid dispensed, with the result that the inhalable
fraction of the quantity delivered is reduced by the mouthpiece
fraction.
[0011] The amount of liquid deposited need not be constant in every
spray actuation but may depend on numerous factors such as the
spatial orientation of the device during the aerosol production or
the ambient temperature, relative humidity, etc. This leads on the
one hand to a certain variability, however minor, in the amount
dispensed which is then available for the patient to take in
(delivered dose). Of the delivered dose, some has such a small
particle size that the particles can be breathed deep into the
lungs and this fraction is known as the inhalable fraction.
However, the present specification does not expressly differentiate
between the inhalable fraction and the total quantity of aerosol
available for the patient to breathe in unless otherwise stated or
unless clearly apparent from the context.
[0012] The liquid deposited may also cause contamination of the
outer surface of the nozzle system or of the mouthpiece, which may
in turn affect the pharmaceutical quality of the next aerosol
mist.
[0013] Although these two effects are only slight in devices using
Respimat.RTM. technology it is important for reasons of quality
control to minimise such effects.
[0014] It has now been found that in devices of this kind for
dispensing liquids the proportion of liquid deposited on the
outside of the nozzle system can be reduced by the particular
geometry of the nozzle or nozzle fixing means. In fact, it has been
found, surprisingly, that the mouthpiece fraction can be reduced if
the entire area above the nozzle aperture (i.e., the area through
which the dispensed liquid "flies" on its way to the mouthpiece) is
funnel-shaped and has no edges.
DESCRIPTION OF THE INVENTION
[0015] It is an objective of the invention to reduce the
variability of the proportion of the liquid delivered by means of a
device for delivering pharmaceutical liquids, such as atomisers,
inhalers, etc.
[0016] A further aim of the invention is to reduce the proportion
of liquid which is deposited, from an aerosol mist, on the device
for delivering the pharmaceutical liquid.
[0017] Thus, a further aim of the invention is to increase the
inhalable fraction of the quantity delivered and to reduce the
mouthpiece fraction.
[0018] A further aim is to optimise the quality of delivery of a
liquid using atomisers having the Respimat.RTM. technology.
DETAILED DESCRIPTION OF THE INVENTION
[0019] This objective is achieved by means of a nozzle system which
consists of a nozzle having at least two nozzle apertures and a
nozzle holder and optionally a check nut, wherein
[0020] the nozzle apertures formed on the end face of the nozzle or
the nozzle channels opening into the nozzle apertures are arranged
so that the jets leaving the nozzle apertures are aimed towards one
another at an angle .alpha.,
[0021] the nozzle is arranged in the nozzle holder and this is
optionally fixed by a check nut located above it,
[0022] in the assembled state the nozzle holder or the check nut or
both extend at least partially into the area in front of the nozzle
apertures,
[0023] and the nozzle system is characterised in that in the
assembled state
[0024] the nozzle holder or, if the nozzle system has a check nut,
the nozzle holder together with the check nut has an inner
recess,
[0025] which begins on the side adjacent to the end face of the
nozzle and extends as far as the outside of the nozzle holder
parallel thereto or, in the case of a check nut, as far as the
outside thereof parallel to the end face of the nozzle,
[0026] which, viewed from the end face of the nozzle, widens out
steadily and continuously in the direction of the outside of the
nozzle holder parallel thereto or, in the case of a check nut, the
outside of said check nut parallel thereto,
[0027] so that the recess opens up the area of the nozzle system
between the end face of the nozzle and the outside of the nozzle
holder parallel thereto or, in the case of a check nut, the outside
of said check nut parallel thereto, for a liquid emerging from the
nozzle opening to pass through, so that this liquid can emerge from
the nozzle, unimpeded by the nozzle holder and the check nut, if
applicable, and can be distributed in the surrounding area.
[0028] According to advantageous embodiments of the nozzle system,
the recess is funnel-shaped, preferably conical in
construction.
[0029] The expression "continuously widening recess" refers within
the scope of the present invention to a surface the edge of which
runs continuously in cross section. This refers to the area which
is macroscopically visible. By "runs continuously" is meant that
there are no gaps of more than 0.5 mm, preferably more than 0.1
mm.
[0030] In cross section the edge of this "continuously widening
recess" is preferably in the form of a straight, elliptical,
hyperbolic, convex or concave line. In any case the edge runs
continuously. The recess also widens continuously and does not
merge into a cylindrical area.
[0031] The region of the recess with the smallest diameter, the
base point, is located on the side of the nozzle holder which is
adjacent to the end face of the nozzle.
[0032] The part of the recess with the largest diameter, the apex
or vertex, is on the opposite side, i.e., the outside of the nozzle
holder parallel to the end face of the nozzle or, in the case of a
check nut, the outside of said check nut which is parallel
thereto.
[0033] The small diameter of the recess is between 0.1 mm and 2 mm,
preferably between 0.6 mm and 1.0 mm.
[0034] The larger diameter of the recess is between 3 mm and 10 mm,
preferably between 5 mm and 8 mm.
[0035] The transition of the base end of the recess to the end face
of the nozzle may be constructed as an edge or it may be
continuous, as defined above, i.e., with no edges.
[0036] In the system according to the invention a check nut is not
necessary if the nozzle holder itself takes on this function.
[0037] Preferably, the nozzle system has a check nut. In this case
the transition between the nozzle holder and the check nut is
constructed with no edges, i.e., the continuous run of the recess
is uninterrupted. Preferably, there is no change in the gradient of
the preferably conically widening recess in this area.
[0038] As an aid to solving the problem posed, it is also possible
to vary the spacings of the nozzle aperture and the angle of
inclination at which jets of liquid are delivered from the nozzle
apertures.
[0039] The present invention is based on nozzle systems as
described, for example, in EP 0664733 or EP 1017469. These are
preferably nozzles consisting of at least two superimposed plates,
at least one of the plates having a second microstructure so that
the superimposed plates define on one side a liquid inlet adjoining
a channel system and/or a filter system which then opens into the
liquid outlets.
[0040] Microstructured nozzled bodies of this kind are described
for example in WO 94/07607 or WO 99/16530. Another embodiment is
disclosed in the German Patent application filed under No.
10216101.1. Reference is hereby made to all the documents.
[0041] With regard to WO 94/07607 we refer particularly to FIG. 1
and the associated description. The nozzle body consists, for
example, of two sheets of glass and/or silicon firmly attached to
one another, at least one of these sheets having one or more
microstructured channels which connect the nozzle inlet side to the
nozzle outlet side. On the nozzle outlet side there may be at least
one, preferably, according to the invention, two round or non-round
openings 2 to 10 microns deep and 5 to 15 microns wide, the depth
preferably being 4.5 to 6.5 microns and the length preferably being
7 to 9 microns.
[0042] On the base part, on the flat surface, there may be a set of
channels to create a plurality of filter routes (filter channels)
in collaboration with the substantially flat surface of the top
part. The base part may have a fill chamber the top of which is
again formed by the top part. This fill chamber may be provided
before or after the filter channels. It is also possible to have
two fill chambers of this kind. Another set of channels on the
substantially flat surface of the base part which is provided
downstream of the filter channels forms, together with the top
part, a set of channels which create a plurality of nozzle outlet
routes.
[0043] Preferably, the overall cross sectional area of the nozzle
outlets is 25 to 500 square micrometres. The total cross sectional
area is preferably 30 to 200 square micrometres.
[0044] In another embodiment this nozzle construction has only one
nozzle aperture.
[0045] In other embodiments of this kind the filter channels and/or
the fill chamber are omitted.
[0046] Preferably, the filter channels are formed by projections
arranged in a zigzag shape. Thus, for example, a zigzag
configuration of this kind is formed by at least two rows of
projections. A number of rows of projections may also be formed,
the projections being laterally offset from one another in order to
construct additional rows which are skewed relative to these rows,
these additional rows forming the zigzag configuration. In
embodiments of this kind the inlet and outlet may each have a
longitudinal slot for unfiltered or filtered fluid, each of the
slots being substantially the same width as the filter and
substantially the same height as the projections on the inlet and
outlet sides of the filter. The cross section of the throughflow
passages formed by the projections may be perpendicular to the
direction of flow of the fluid and may decrease from row to row,
viewed in the direction of flow. Also, the projections arranged
closer to the inlet side of the filter may be larger than the
projections arranged closer to the outlet side of the filter.
Additionally, the spacing between the base part and top part may
taper in the region from the nozzle inlet side to the nozzle outlet
side.
[0047] The zigzag configuration which is formed by the minimum of
two rows of projections has an angle of inclination alpha of
preferably 20.degree. to 250.degree..
[0048] Further details of this nozzle construction may be found in
WO 94/07607. We hereby refer specifically to this publication,
particularly FIG. 1 and the associated description.
[0049] In embodiments of the nozzle having a plurality of nozzle
apertures, preferably all of them are formed on a common side. In
such cases the nozzle apertures may be oriented so that the jets of
liquid emerging from them meet in front of the nozzle aperture.
Systems of this kind require nozzles with at least two apertures.
Nozzles of this kind are preferred according to the invention.
[0050] The nozzle may be embedded in an elastomeric sleeve as
described in WO 97/12683. In its simplest form a sleeve of this
kind is a ring or member having an opening into which the nozzle
can be inserted. This opening surrounds the nozzle block over its
entire outer surface, i.e., the surface which is perpendicular to
the preferably linear axis formed by the nozzle inlet side and the
nozzle outlet side. The sleeve is open at the top and bottom so as
not to impede either the supply of liquid to the nozzle inlet side
of the nozzle or the delivery of the liquid. This sleeve may in
turn be inserted in a second sleeve. The external form of the first
sleeve is preferably conical. The opening of the second sleeve is
shaped accordingly. The first sleeve may be made of an
elastomer.
[0051] The nozzle is secured by the device according to the
invention.
[0052] A nozzle of this kind, optionally including the sleeve, is
part of a nozzle system by means of which the nozzle is held at a
defined place in the delivery device, preferably from outside in
the direction of the hollow piston. According to the invention a
nozzle system of this kind therefore consists of a nozzle and a
nozzle holder and optionally a check nut. All the elements have an
end face. This is the side which is oriented away from the side of
the nozzle having the nozzle aperture, i.e., it faces outwards. The
inside of the end face of the nozzle holder or the check nut may
come into contact with the liquid outlet side of the nozzle and
thereby exert the force needed to secure the nozzle in the
direction of the liquid inlet side of the nozzle. The end face of
the nozzle holder and/or of the check nut has or have a
through-bore or hole in the form of a recess through which the
aerosol can escape from the nozzle. Therefore, the nozzle apertures
are in, or in a direct line below, the bore or the recess.
[0053] The recess is preferably constructed as an inner recess
which widens continuously from the nozzle apertures. Embodiments of
the nozzle system wherein the recess is funnel-shaped, preferably
conical, are advantageous.
[0054] In nozzles having at least two nozzle apertures orientated
so that the two jets of liquid leaving the nozzle body meet, the
point of impact, the point where the jets of liquid meet and are
atomised to form an aerosol, is preferably located close to the
base of the recess, i.e., in the region of the nozzle aperture. It
is obvious that in such a case the recess is one of the areas
particularly at risk of liquid being deposited thereon.
[0055] This invention is preferably used in a nebuliser of
Respimat.RTM. technology, which is described in more detail
hereinafter.
[0056] The preferred atomiser essentially comprises a lower and an
upper housing mounted to be rotatable relative to one another, the
upper part of the housing containing a spring housing with spring
which is tensioned by rotating the two housing parts by means of a
locking clamping mechanism preferably in the form of a screw thread
or gear and is released by pressing a release button on the upper
part of the housing. This moves a power take-off flange connected
to a hollow piston on the lower end of which a container can be
fitted and at the upper end of which are found a valve and a
pressure chamber which is connected for fluid transmission to the
nozzle or the nozzle system formed in the upwardly open part of the
upper housing part. The liquid is sucked in by the hollow piston
and pumped to the pressure chamber from where it is expelled
through the nozzle in the form of an aerosol.
[0057] The hollow piston with valve body corresponds to a device
disclosed in WO 97/12687. It projects partially into the cylinder
of the pump housing and is disposed to be axially movable in the
cylinder. Reference is made particularly to FIGS. 1-4--especially
FIG. 3--and the associated parts of the description. At the moment
of release of the spring the hollow piston with valve body exerts,
at its high pressure end, a pressure of 5 to 60 Mpa (about 50 to
600 bar), preferably 10 to 60 Mpa (about 100 to 600 bar) on the
fluid, the measured amount of active substance solution.
[0058] The valve body is preferably mounted at the end of the
hollow piston which faces the nozzle body. The valve body is
connected for fluid transmission with the nozzle. The delivery
device also comprises a locking clamping mechanism. This contains a
spring, preferably a cylindrical helical compression spring, as a
store for the mechanical energy. The spring acts on the power
take-off flange as a spring member the movement of which is
determined by the position of a locking member. The travel of the
power take-off flange is precisely limited by an upper stop and a
lower stop. The spring is preferably tensioned via a stepping-up
gear, e.g., a helical sliding gear, by an external torque which is
generated when the upper housing part is turned relative to the
spring housing in the lower housing part. In this case, the upper
housing part and the power take-off flange contain a single- or
multi-speed spline gear.
[0059] The locking member with the engaging locking surfaces is
arranged in an annular configuration around the power take-off
flange. It consists for example of a ring of plastics or metal
which is inherently radially elastically deformable. The ring is
arranged in a plane perpendicular to the axis of the atomiser.
After the tensioning of the spring, the locking surfaces of the
locking member slide into the path of the power take-off flange and
prevent the spring from being released. The locking member is
actuated by means of a button. The actuating button is connected or
coupled to the locking member. In order to actuate the locking
clamping mechanism the actuating button is moved parallel to the
annular plane, preferably into the atomiser, and the deformable
ring is thereby deformed in the annular plane. Details of the
construction of the locking clamping mechanism are described in WO
97/20590.
[0060] The lower housing part is pushed axially over the spring
housing and covers the bearing, the drive for the spindle and the
storage container for the fluid.
[0061] When the atomiser is operated, the upper part of the housing
is rotated relative to the lower part, the lower part taking the
spring housing with it. The spring meanwhile is compressed and
biased by means of the helical sliding gear, and the clamping
mechanism engages automatically. The angle of rotation is
preferably a whole-number fraction of 360 degrees, e.g., 180
degrees. At the same time as the spring is tensioned, the power
take-off component in the upper housing part is moved along by a
given amount, the hollow piston is pulled back inside the cylinder
in the pump housing, as a result of which some of the fluid from
the storage container is sucked into the high pressure chamber in
front of the nozzle.
[0062] If desired, a plurality of replaceable storage containers
containing the fluid to be atomised can be inserted in the atomiser
one after another and then used. The storage container contains the
propellant-free aerosol preparation.
[0063] The atomising process is initiated by gently pressing the
actuating button. The clamping mechanism then opens the way for the
power take-off component. The biased spring pushes the piston into
the cylinder in the pump housing. The fluid emerges from the nozzle
of the atomiser in the form of a spray. The liquid pharmaceutical
preparation hits the nozzle body at an entry pressure of up to 600
bar, preferably 200 to 300 bar and is atomised through the nozzle
openings into an inhalable aerosol. The preferred particle sizes of
the aerosol are up to 20 microns, preferably 3 to 10 microns.
Volumes of 10 to 50 microlitres are preferably delivered, volumes
of 10 to 20 microlitres are more preferable, whilst a volume of 15
microlitres per spray is particularly preferred.
[0064] The components of the atomiser (nebuliser) consist of a
material which is suited to its purpose. The housing of the
atomiser and--insofar as the operation allows--other parts are also
preferably made of plastics, e.g., by injection moulding. For
medical uses, physiologically harmless materials are used.
[0065] Preferably, a nebuliser according to the invention is
cylindrical in shape and has a handy size of less than 9 to 15 cm
long and 2 to 4 cm wide, so that it can be carried anywhere by the
patient.
[0066] Further details of construction are disclosed in PCT
applications WO 97/12683 and WO 97/20590, to which reference is
made hereby.
[0067] The invention is hereinafter illustrated in more detail with
reference to drawings.
FIGURES
[0068] FIG. 1: Graph for investigating nozzle systems with two
nozzle apertures directed towards one another: dependency of the
mouthpiece fraction ("deposition in the mouthpiece") on the impact
height h for a nozzle system with a discontinuously expanding
recess and for a nozzle system according to the invention with a
conical recess,
[0069] FIG. 2: A graph for investigating nozzle systems with two
nozzle apertures directed towards each other: dependency of the
aerosol quality on the height of impact,
[0070] FIG. 3: A graph for investigating nozzle systems with two
nozzle openings directed towards one another: dependency of the
mouthpiece fraction and the quality of the inhalable fraction on
the height of impact,
[0071] FIG. 4: A graph for investigating nozzle systems with two
nozzle apertures directed towards one another: dependency of the
mouthpiece fraction on the cone angle 2.theta. nozzle fixing
systems with a conical recess,
[0072] FIGS. 5,6: Nozzles with two nozzle apertures directed
towards one another: influence of the angle of impact a on the
inhalable fraction and the mouthpiece fraction in nozzle fixing
systems with a conical recess,
[0073] FIG. 7: A view of a first embodiment of a nozzle system in
side elevation, partially in section,
[0074] FIG. 8: A view of a second embodiment of a nozzle system in
side elevation, partly in section,
[0075] FIG. 9: A diagrammatic view of a nozzle system according to
the invention in side elevation, in section,
[0076] FIG. 10: A diagrammatic view of an embodiment of a nozzle
member in side elevation, in section,
[0077] FIGS. 11a/b: Diagram of the Respimat.RTM. type
nebuliser.
[0078] FIG. 1 shows the dependency of the mouthpiece fraction
("deposition in the mouthpiece") on the height of impact h for a
nozzle system with a discontinuously expanding recess (A) and for a
nozzle system according to the invention with a conical recess (B).
This graph shows the dependency of the mouthpiece fraction on the
height of impact. Accordingly, the mouthpiece fraction can be
reduced by increasing the height of impact h.
[0079] FIG. 1 also shows that the special construction of the
nozzle system according to the invention in the region in front of
the nozzle apertures leads to a substantial reduction in the
mouthpiece fraction compared with conventional systems. Thus, for
example, the mouthpiece fraction can be reduced from about 1.9 mg
to 0.8 mg at an impact height h=25 .mu.m, corresponding to a
reduction of about 60%.
[0080] The reduction in the mouthpiece fraction has two positive
effects. On the one hand, by minimising the amount of mouthpiece
fraction the quantity delivered is maximised, which in turn has a
favourable effect on the inhalable fraction which consequently
becomes larger, in principle. This therefore crucially contributes
to the solution to one of the problems of the invention, namely of
maximising the inhalable fraction.
[0081] Moreover, by reducing the mouthpiece fraction the effects of
variability of the mouthpiece fraction are reduced. Because of the
small amount of mouthpiece fraction fluctuations in this amount
result in only minor fluctuations in the quantity delivered and
hence in the inhalable fraction. The inhalable fraction is now
highly reproducible, i.e., it has low variability. The problem of
the inconstant mouthpiece fraction subject to certain tolerances is
now of only marginal importance. This also solves the second
problem on which the invention is based, namely of ensuring high
reproducibility, i.e., low variability, of the inhalable
fraction.
[0082] However, what is crucial to the success of the nozzle system
according to the invention is that this single measure not only
minimises the mouthpiece fraction but at the same time maximises
the inhalable fraction.
[0083] It is found according to the invention that when reducing
the mouthpiece fraction in nozzle systems comprising nozzles with
two nozzle apertures aligned so that the jets which emerge from
them meet at a point in front of the nozzle (point of impact), it
is pointless to increase the height of impact h on its own (FIG.
1). This is because the two jets actually have to meet, which
requires the smallest possible height of impact h. Moreover, the
jets are supposed to meet in concentrated form before they fall as
droplets. In addition it has surprisingly been found that the
magnitude of the height of impact h also affects the quality of
atomisation and hence the inhalable fraction so that, as the height
of impact h increases, the quality of atomisation or the inhalable
fraction is reduced. Then, as the height of impact h increases,
there are a greater number of larger particles and fewer small
particles. This effect is illustrated in FIG. 2 in which the
inhalable fraction is seen as the part which comprises particles
with a diameter of less than 5.8 .mu.m. Here again, the
advantageous effect of the nozzle system according to the invention
as against a nozzle system with a discontinuously expanding recess
is apparent.
[0084] FIG. 3 shows the mouthpiece fraction in milligrams and the
inhalable fraction in percent by volume (proportion by volume of
the aerosol containing particles with diameters of less than 5.8
.mu.m, as detected by a laser beam) as a function of the height of
impact h. For example, for an impact angle .alpha.=75.degree. the
mouthpiece fraction decreases rapidly as the height of impact h
increases. At the same time, however, the inhalable fraction, i.e.,
the quality of atomisation, is not reduced to the same extent.
[0085] If it is also remembered that not only is the quality of
atomisation--as characterised by the inhalable fraction in percent
by volume--positively affected but also the amount actually
delivered is increased by reducing the absolute quantity of the
mouthpiece fraction, it will be apparent that the absolute
inhalable fraction can be increased substantially.
[0086] It has been found according to the invention that in
advantageous embodiments of the nozzle system the recesses in front
of the nozzle aperture are conical and have a cone angle 2.theta.
in the range between 55.degree. and 155.degree., preferably in the
range between 70.degree. and 140.degree.. Particularly favourable
are nozzle systems wherein the recess of conical construction has a
cone angle 2.theta. which is in the range between 70.degree. and
85.degree. or in the range between 95.degree. and 140.degree.,
especially in the range between 105.degree. and 125.degree..
[0087] The advantages of these embodiments will become apparent
from FIG. 4 which shows, in the form of a bar graph, the mouthpiece
fraction in milligrams for different cone angles 2.theta.. All of
the embodiments have a mouthpiece fraction of not more than 1.75 mg
which is small compared with the prior art (cone angle
2.theta.=90.degree.). The embodiments which have cone angles
2.theta. in the range from 70.degree. to 85.degree. or in the range
between 95.degree. and 140.degree., particularly in the range
between 105.degree. and 125.degree., have even smaller mouthpiece
fractions. The minimum is obtained with a cone angle
2.theta.=110.degree..
[0088] According to another aspect the present invention relates to
particular nozzles which may advantageously be incorporated in the
nozzle systems according to the invention. These nozzles are
characterised in that the point of collision where the jets meet
has a height of impact h above the nozzle apertures in the range
between 20 .mu.m and 85 .mu.m, preferably in the range between 25
.mu.m and 75 .mu.m. If the height of impact is within the range
specified, the various objectives can all advantageously be met, by
achieving in particular a low mouthpiece fraction and reliable
steering of the jets of liquid towards one another whilst obtaining
a high inhalable fraction.
[0089] Nozzles wherein the point of collision where the jets meet
has a height of impact h above the nozzle apertures in the range
between 35 .mu.m and 75 .mu.m are advantageous. With the impact
height in this range the parameters which influence one another are
brought to an optimum level.
[0090] Embodiments of the nozzles wherein the angle .alpha. is in
the range from 50.degree. to 110.degree., preferably from
65.degree. to 95.degree. and more particularly in the range from
75.degree. to 90.degree. are advantageous.
[0091] FIGS. 5 and 6 show the effect of the angle of impact .alpha.
on the inhalable fraction and the mouthpiece fraction. Both these
fractions increase as the angle of impact .alpha. increases. With
regard to the quality of atomisation it is preferable for the jets
to meet head-on if possible. Large angles ensure a high inhalable
fraction, i.e., a high volume proportion of small particles with
diameters less than 5.8 .mu.m in the spray mist.
[0092] However, large angles .alpha. also lead to large mouthpiece
fractions at the same time. The free path along which the jets
travel between leaving the nozzle apertures and meeting one another
should not be too great, to ensure among other things that the jets
do not disperse before the meeting point. If, however, the angle of
impact .alpha. is increased, the height of impact must be reduced
to keep the free path of the jets constant. The effects of this
measure have already been explained. However, even with a constant
height of impact and enlargement of the angle, an increasing
mouthpiece fraction is obtained as the particles of the spray mist
are increasingly driven towards the nozzle system as the angle of
impact increases, eventually resulting in a larger mouthpiece
fraction. The angle regions mentioned above are best able to
accommodate the competing mechanisms.
[0093] In advantageous embodiments of the nozzles according to the
invention, the spacing a of the nozzle apertures is in the range
from 40 .mu.m to 125 .mu.m, preferably in the range from 50 .mu.m
to 115 .mu.m, more particularly in the range from 60 .mu.m to 105
.mu.m.
[0094] Advantageous embodiments of the nozzle system are
characterised in that only the nozzle holder extends into the area
in front of the nozzle apertures in the assembled state. This
avoids any joints between the nozzle holder and check nut in the
region of the nozzle apertures. Joints are a particular problem in
terms of the accumulation of aerosol particles as, once deposited,
any particles here are not generally released again.
[0095] Two embodiments shown in FIGS. 7, 8, 9 and 10 illustrate the
invention in more detail.
[0096] FIG. 7 shows a first embodiment of the nozzle system 1 in
side elevation, partly in section.
[0097] The nozzle 3 or nozzle body as an independent construction
unit--so called uniblock--is disposed in a conical sleeve 6 which
is in turn placed in the nozzle holder 4. The nozzle holder 4 is
clamped to the housing 7 by means of a check nut 2 and this secures
the nozzle 3.
[0098] At the same time the check nut 2 engages from outside in the
nozzle holder 4, although it does not extend into the area in front
of the nozzle apertures. The recess 5 is conical in shape, in that
it widens out continuously as its distance from the nozzle
apertures increases. The recess 5 has a cone angle 2.theta., whilst
FIG. 7 shows by way of example a plurality of different cone
angles, with the result that this Figure shows five different
embodiments of the recess 5 and hence of the nozzle system 1, all
basically the same. Specifically, it shows cone angles 2.theta. of
70.degree., 80.degree., 90.degree., 100.degree. and
110.degree..
[0099] Because the check nut 2 engages in the nozzle holder 4 from
outside, the recess 5 is formed exclusively by the nozzle holder
4.
[0100] In contrast, FIG. 8 shows a second embodiment, again in side
elevation and partly in section, wherein both the nozzle holder 4
and the check nut 2 extend into the area in front of the nozzle
apertures. Otherwise, the nozzle system 1 shown in FIG. 8
corresponds to the nozzle system described above. The same
reference numerals have been used for corresponding components, and
therefore we refer to the description of FIG. 7 with regard to the
components of similar construction.
[0101] FIG. 9 again shows a nozzle system 1 according to the
invention. This comprises a recess 5 of conical shape. Unlike
nozzle systems with a discontinuously expanding recess, the recess
5 does not contain any steps. Such steps may occur in particular in
the area where the check nut engages in the nozzle holder. In such
cases, particles of the spray mist may accumulate on the edges of
the step and thus contribute to the mouthpiece fraction.
[0102] FIG. 10 is a diagrammatic view of a detail of an embodiment
of a nozzle member 3 shown in sectional side view.
[0103] The two nozzle channels 9 are arranged so that the jets
leaving the nozzle apertures 11 of the nozzle channels meet at the
point of collision 10 at an angle .alpha.=90.degree.. The point of
collision 10 has a height of impact h=25 .mu.m above the nozzle
apertures.
[0104] FIG. 11a shows a longitudinal section through the atomiser
with the spring under tension, FIG. 11b shows a longitudinal
section through the atomiser with the spring released.
[0105] The upper housing part (51) contains the pump housing (52),
on the end of which is mounted the holder (53) for the atomiser
nozzle. In the holder is the expanding recess (54) and the nozzle
body (55). The hollow piston (57) fixed in the power take-off
flange (56) of the locking clamping mechanism projects partly into
the cylinder of the pump housing. At its end the hollow piston
carries the valve body (58). The hollow piston is sealed off by the
gasket (59). Inside the upper housing part is the stop (60) on
which the power take-off flange rests when the spring is relaxed.
Located on the power take-off flange is the stop (61) on which the
power take-off flange rests when the spring is under tension. After
the tensioning of the spring, the locking member (62) slides
between the stop (61) and a support (63) in the upper housing part.
The actuating button (64) is connected to the locking member. The
upper housing part ends in the mouthpiece (65) and is closed off by
the removable protective cap (66).
[0106] The spring housing (67) with compression spring (68) is
rotatably mounted on the upper housing part by means of the
snap-fit lugs (69) and rotary bearings. The lower housing part (70)
is pushed over the spring housing. Inside the spring housing is the
replaceable storage container (71) for the fluid (72) which is to
be atomised. The storage container is closed off by the stopper
(73), through which the hollow piston projects into the storage
container and dips its end into the fluid (supply of active
substance solution).
[0107] The spindle (74) for the mechanical counter (optional) is
mounted on the outside of the spring housing. The drive pinion (75)
is located at the end of the spindle facing the upper housing part.
On the spindle is the slider (76).
* * * * *