U.S. patent application number 10/584636 was filed with the patent office on 2008-10-09 for method and device for filling the dosing chamber of an inhaler for the first time.
This patent application is currently assigned to Boehringer Ingelheim International GmbH. Invention is credited to Georg Boeck, Johannes Geser, Michael Spallek.
Application Number | 20080245758 10/584636 |
Document ID | / |
Family ID | 34706691 |
Filed Date | 2008-10-09 |
United States Patent
Application |
20080245758 |
Kind Code |
A1 |
Geser; Johannes ; et
al. |
October 9, 2008 |
Method And Device For Filling The Dosing Chamber Of An Inhaler For
The First Time
Abstract
The invention relates to the first-time filling of a liquid
conducting system in an inhaler. According to the invention, a
pressure that is built up in the reservoir by mounting the closure
thereupon is released when the reservoir is inserted into the
inhaler so as to displace liquid from the reservoir by means of the
liquid conducting system such that the dead volume of the liquid
conducting system is filled with liquid and the nozzle is connected
in an air-free manner to the liquid store.
Inventors: |
Geser; Johannes; (Ingelheim
am Rhein, DE) ; Boeck; Georg; (Laupheim, DE) ;
Spallek; Michael; (Ingelheim am Rhein, DE) |
Correspondence
Address: |
MICHAEL P. MORRIS;BOEHRINGER INGELHEIM USA CORPORATION
900 RIDGEBURY RD, P. O. BOX 368
RIDGEFIELD
CT
06877-0368
US
|
Assignee: |
Boehringer Ingelheim International
GmbH
Ingelheim
DE
|
Family ID: |
34706691 |
Appl. No.: |
10/584636 |
Filed: |
December 27, 2004 |
PCT Filed: |
December 27, 2004 |
PCT NO: |
PCT/EP04/14726 |
371 Date: |
April 25, 2007 |
Current U.S.
Class: |
215/200 ;
141/2 |
Current CPC
Class: |
A61M 15/0065
20130101 |
Class at
Publication: |
215/200 ;
141/2 |
International
Class: |
B65D 51/00 20060101
B65D051/00; B65B 1/04 20060101 B65B001/04 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 29, 2003 |
DE |
103 61 735.3 |
Claims
1-27. (canceled)
28. Method for applying a pharmaceutical fluid, for the first time,
to an inherently sealed tubular system capable of conveying fluid,
having two open ends, the system being part of a propellant-free
inhaler, characterised in that a container which contains a fluid
pharmaceutical formulation is pushed manually onto the tubular
bottom end of the system in pressuretight manner until the tubular
end projects into the fluid and an excess pressure of at least 1
mbar prevailing in the container at the start or finish of the
pushing-on operation forces some of the pharmaceutical fluid
through the system, thereby reducing the excess pressure, such that
the system is preferably totally filled with fluid.
29. Method according to claim 28, characterised in that by the
pushing-on process at least one and a half times as much fluid is
forced through the system as corresponds to the volume of the
system.
30. Method according to claim 28, characterised in that the excess
pressure in the container is generated by cold-filling the fluid
pharmaceutical formulation at a temperature of less than 10.degree.
C. followed by pressuretight sealing of the container and pushing
the container onto the bottom end of the hollow piston at a
temperature of more than 10.degree. C.
31. Method according to claim 28, characterised in that the excess
pressure in the container is generated by filling the fluid
pharmaceutical formulation at an excess pressure of at least 10
mbar with the inclusion of a residual air bubble with a volume of
at least 0.1 ml to a maximum of 0.5 ml and pushing the container
onto the bottom end of the hollow piston at normal pressure.
32. Method according to claim 28, characterised in that the system
comprises at least one hollow piston having a tubular lower end and
an upper end, a cylinder bore in the lower part of which the upper
region of the hollow piston can be moved back and forth between two
positions and an outlet nozzle which is provided at the upper end
of the cylinder bore.
33. Method according to claim 28, characterised in that the volume
in that part of the system which is above the fluid level after the
immersion of the tubular end is not more than 25 microlitres and
the excess pressure while the cartridge is being pushed onto the
tubular end is generated by the fact that the tubular end of the
system projects so far into the fluid inside the container that it
displaces a volume of at least 25 microlitres, more preferably at
least 34 microlitres.
34. Closure for a fluid-filled container which comprises, in the
closed position, a connector (2) projecting into the container or
located on the container, the top end of which points away from the
container and the bottom end of which is aligned with the interior
of the container and a tubular guide (12) starting from the top
part is formed in the connector (2), characterised in that the
connector (2) has a device which displaces some of the fluid in the
container under the effect of an external force.
35. Closure according to claim 34, characterised in that the guide
(12) comprises at its end an expanded portion, preferably in the
form of a chamber, which can be opened toward the container along
the direction of the guide (12) and in which there is a
displacement member which can be pushed at least partially out of
the chamber in the direction of the interior of the container.
36. Closure according to claim 35, characterised in that the
displacement member has a bore, which is constructed starting from
the top end of the displacement member, is aligned in a straight
line with the guide (12).
37. Closure according to claim 36, characterised in that the bore
passes right through and optionally has a constriction.
38. Closure according to claim 36, characterised in that the bore
does not pass right through and has a constriction underneath which
there is a hollow space closed off at the bottom.
39. Closure according to claim 38, characterised in that the
displacement member is constructed as an integral, capillaried,
open-pored porous storage medium for fluid.
40. Closure according to claim 39, characterised in that the
displacement member is a dimensionally rigid body having a
fluid-pervious wall, filled with sintered or non-sintered powder,
or a woven or knitted or nonwoven structure or a wad of fibers.
41. Closure according to claim 39, characterised in that the
storage medium for fluid in the displacement member consists of
plastics, ceramics, glass, metal or a natural substance.
42. Closure according to claim 35, characterised in that stop means
are provided on the displacement member (14) and on the guide (12),
to prevent the displacement member (14) from being able to leave
the guide (12) completely.
43. Closure according to claim 35, characterised in that the wall
of the displacement member (14) and the wall of the guide (12)
cooperate in fluidtight manner.
44. Closure according to claim 34, characterised in that the
connector comprises at its bottom end at least two sleeves inserted
telescopically one inside the other, of which at least the hollow
part of the innermost sleeve is aligned directly with the guide
(12).
45. Closure according to claim 44, characterised in that the
external diameter of the upper part of a respective inner sleeve is
greater than the internal diameter of the bottom part of the outer
sleeve enclosing it.
46. Closure according to claim 44, characterised in that the
innermost diameter of the innermost sleeve is constructed as a
press fit for a cannula.
47. Closure according to claim 44, characterised in that at least
the bottom wall of the connector is constructed as a bellows made
of an elastic material.
Description
[0001] The present invention relates to medicinal inhalers for
medical purposes which deliver a given amount of a preferably
pharmaceutical fluid over a fairly long period in the form of a
"soft" aerosol mist for inhalation ("soft mist.TM. inhaler" or SMI
for short). A device of this kind may be, for example, an inhaler
of the Respimat.RTM. type, which is described in more detail in WO
97/12687. This type of inhaler is fitted with a cartridge
containing a fairly large amount of the active substance
formulation. The present invention relates to a further development
of the Respimat.RTM. system, in which the fitting of the cartridge
into the device is improved with a view to speeding up the first
use of the spray.
PRIOR ART
[0002] The handy inhalers of the Respimat.RTM. type or inhalers
like the Respimat.RTM. Soft.RTM. Mist.TM. Inhaler (SMI), in which a
small amount of an aqueous formulation is atomised in amounts of a
few microlitres without the use of propellant gases to form an
aerosol mist, are one of the latest innovative developments in the
field of medical atomisation technology. Because of its cylindrical
shape and handy size of less than 9 to 15 cm long and 2 to 4 cm
wide this device can be taken anywhere by the patient, so that it
is always available for regular daily use in a manner which is
convenient to the patient, irrespective of the location.
[0003] The basic technical characteristics of these inhalers are
disclosed for example in WO 91/14468 or WO 97/12687, particularly
in FIGS. 6a and 6b. In these inhalers, the amount of liquid
pharmaceutical formulation to be nebulised by high pressure up to
500 bar is forced through a micronozzle with preferably two nozzle
outlets and thereby converted into an aerosol destined for the
lungs. Reference is specifically made to the above-mentioned
publications, within the scope of the present description.
[0004] The Respimat.RTM. principle is based on two separate
construction units: on the one hand the inhaler which contains all
the mechanical components for producing the aerosol, and on the
other hand a separate cartridge, which contains the pharmaceutical
formulation.
[0005] For use the cartridge is pushed onto a cannula formed in the
inhaler. Liquid is conveyed through this cannula into a compressing
and dosing chamber and from there forced through a micronozzle by
the application of pressure.
[0006] The cartridge consists of a container filled with the fluid
and a closure cap therefor. Essentially, a Respimat.RTM. type
nebuliser consists of an upper housing part at the top, a lower
housing part which is rotatably mounted relative to the upper
housing part and defines the bottom end, a pump housing, the
nozzle, a locking clamping mechanism, a spring housing, a spring
and the storage container.
[0007] The pump housing is in the upper housing part. At the top
end of the pump housing is located the nozzle body with the nozzle
or the nozzle arrangement. Below this is a compression chamber
which may be part of a central tube in the form of a cylindrical
bore. Below the compression chamber is the upper end of a cannula
in the form of a hollow piston, which projects partially into the
central tube and can move axially back and forth therein in a
stroke action. The hollow piston is fixedly connected to a power
takeoff flange outside the central tube. The power takeoff flange
is located on the top end of a spring (helical spring) and is moved
thereby. The helical spring is located in a spring housing, which
is rotatably mounted on the upper housing part by means of a rotary
bearing and can be tensioned and released by means of a locking
clamping mechanism. All the components mentioned in this paragraph
are located in the upper housing part. The hollow piston extends
with its lower, bottom end into the inner space defined by the
compression spring. This hollow space is open at the bottom. At the
top it may be bounded by the power takeoff flange. The
pharmaceutical cartridge is inserted from the bottom end into this
cavity in the helical spring and pushed onto the cannula. The lower
housing part is then pushed axially over the spring housing. The
system comprising the hollow piston, central tube, compression
chamber and nozzle constitutes a system for conveying a fluid. The
connections between the individual components are sealed off to the
outside. The fluid conveying system has only two openings, the
lower opening in the hollow piston and the nozzle opening. One
opening serves to receive a fluid, while the other, the nozzle
opening, serves to deliver said fluid.
[0008] The nozzles used are special nozzles, as described for
example in WO 94/07607 or WO 99/18530. Reference is made
specifically to both these publications.
[0009] The nozzle in the nozzle body is preferably microstructured,
i.e. produced by micro-engineering. Microstructured nozzle bodies
are disclosed for example in WO-94/07607; reference is hereby made
to the contents of this specification, especially FIG. 1 and the
associated description.
[0010] The nozzle body consists for example of two sheets of glass
and/or silicon securely fixed together, at least one of which has
one or more microstructured channels which connect the nozzle inlet
end to the nozzle outlet end. At the nozzle outlet end there is at
least one round or non-round opening 2 to 10 microns deep and 5 to
15 microns wide, the depth preferably being 4.5 to 6.5 microns and
the length being 7 to 9 microns.
[0011] If there is a plurality of nozzle openings, preferably two,
the directions of spraying of the nozzles in the nozzle body may
run parallel to each other or may be inclined relative to one
another in the direction of the nozzle opening. In the case of a
nozzle body having at least two nozzle openings at the outlet end,
the directions of spraying may be inclined relative to one another
at an angle of 20 degrees to 180 degrees, preferably at an angle of
60 to 150 degrees, most preferably 80 to 100.degree..
[0012] The nozzle openings are preferably arranged at a spacing of
10 to 200 microns, more preferably at a spacing of 10 to 100
microns, still more preferably 30 to 70 microns. A spacing of 50
microns is most preferred.
[0013] The directions of spraying therefore meet in the region of
the nozzle openings.
[0014] For the nebulisation, 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.
[0015] 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. The valve body is preferably mounted on the end of the
hollow piston which faces the nozzle body.
[0016] Reference is made particularly to FIGS. 1-4--especially FIG.
3--and the associated passages of 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. Volumes of 10 to
50 microlitres are preferred, volumes of 10 to 20 microlitres are
more preferable, whilst a volume of 10 to 15 microlitres per
actuation is particularly preferred.
[0017] The locking clamping mechanism contains the 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.
[0018] 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 locking 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.
[0019] 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.
[0020] 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.
[0021] 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.
[0022] Further details of the construction are disclosed in PCT
applications WO 97/12683 and WO 97/20590, to which reference is
hereby made.
[0023] The storage container (cartridge) is preferably a container
having a flange or a closure cap via which the hollow piston of the
inhaler can be inserted into the interior. The flange or the
closure cap contains a guide passage for the hollow piston with at
least one sealing point which prevents air from getting into the
container from outside along the hollow piston or fluid from
escaping from the container by the same route. The flange or the
closure cap may be designed to be releasably or non-releasably
connected to the power takeoff flange of the inhaler. Preferably
the container is constructed as a collapsible container which is
preferably surrounded by a fixed, rigid second container which
protects the collapsible first container from damage, inter alia.
Suitable containers are described in EP 0775076 or WO 99/43571.
However, other suitable non-collapsible containers may also be
used. The storage container constitutes a self-contained system
before it is fitted onto the hollow piston, on which there are no
devices to which pressure is to be applied.
[0024] Before the first use the still sealed cartridge (the
container) has to be pushed onto the cannula of the inhaler. In
order to fill the region from the hollow piston to the nozzle with
fluid completely for the first time the inhaler known from the
prior art has to be tensioned and actuated several times.
DESCRIPTION OF THE INVENTION
[0025] One aim of the present invention is to provide an inhaler of
the Respimat.RTM. type, which can be operated more quickly than the
device known from the prior art after the first insertion of the
cartridge.
[0026] A further aim of the present invention is to shorten the
steps prior to the first operation of an inhaler of the
Respimat.RTM. type.
[0027] A further aim of the present invention is to automate the
steps for filling an inhaler of the Respimat.RTM. type with fluid
for the first time.
DETAILED DESCRIPTION OF THE INVENTION
[0028] According to the invention the problem is to speed up and
automate the process of filling the dead volume in the inhaler. The
term dead volume refers to the volume which is created by the
interior of the cannula above the fluid level, the inside of the
valve, the part of the cylinder above it, including the pressure
chamber, and the inner space of the nozzle, minus the part of the
volume which is taken up by the region of the hollow piston. In
other words, that part of the cannula volume which projects into
the fluid after the completion of the insertion process of the
cartridge, which is generally at least 90 vol % full, is not taken
into account. The system of cannula, cylinder, pressure chamber,
nozzle is hereinafter referred to as the fluid conveying system.
Thus the dead volume corresponds to the inner volume of the fluid
conveying system when the spring is relaxed, minus the proportion
filled solely by the principle of the communicating tubes when the
cartridge is pushed onto the cannula. The volume which is to be
expelled through the atomiser is not included either. This volume
is called the fill volume and is generated when the spring of the
device is tension and the piston is moved out of the central tube
without leaving it. The difference between the two volumes
corresponds substantially to the amount of fluid that is to be
nebulised (delivery volume).
[0029] In detail, the preferred nebuliser may be described as
follows. A pump housing is located in a cylindrical upper housing
part. A holder for the atomiser nozzle is mounted on its end. The
holder contains the nozzle body and optionally one or more filters.
The nozzle is located at the upper end of a cylinder tube which is
formed in the pump housing. The hollow piston fixed in a power
takeoff flange of the locking clamping mechanism. At its end the
hollow piston has a valve body. The hollow piston is sealed off to
the outside by means of a gasket.
[0030] Inside the upper housing part is a first stop on which the
power takeoff flange bears when the spring is relaxed. On the power
takeoff flange there is a second stop on which the power takeoff
flange bears when the spring is relaxed. After the tensioning of
the spring a locking member slides between the second stop and a
support in the upper housing part. An actuating button is connected
to the locking member. The upper housing part ends in a mouthpiece
and is closed off by the push-on protective cap.
[0031] A cylindrical spring housing with compression spring is
rotatably mounted on the upper housing part by means of snap-in
lugs and rotary bearing. The cylindrical lower housing part is
pushed over the spring housing. Inside the spring housing is the
exchangeable storage container for the fluid which is to be
atomised. The storage container is sealed off by a stopper through
which the hollow plunger projects into the storage container and is
immersed at its end in the fluid (supply of active substance
solution).
[0032] To solve the problem according to the invention it is
proposed to relax the excess pressure which has spontaneously
formed in the storage vessel (container) or is present therein with
the introduction of the storage vessel into the inhaler, with
displacement of fluid from the container through the fluid
conveying system comprising a hollow piston, cylinder, pressure
chamber and nozzle, so that the dead volume of the fluid conveying
system is filled with fluid and the nozzle is attached to the fluid
supply with the exclusion of air.
[0033] According to the invention the excess pressure is supposed
to be sufficient to more than completely fill the dead volume with
fluid on one side. On the other hand the pressure is only supposed
to be high enough for preferably less than 100 microlitres to leave
the inhaler through the nozzle as a result of the release of
pressure. It is important that at least one and a half times more
fluid is forced through the fluid conveying system than corresponds
to the dead volume of the fluid conveying system. This compensates
any tolerances which may occur as a result of the elasticity of the
storage vessel.
[0034] In a first embodiment of the invention the excess pressure
in the container is generated spontaneously by pushing the
container onto the hollow piston of the non-tensioned inhaler. At
least that part of the cannula of the inhaler which extends into
the container is of a different construction from the embodiment
known from the prior art. According to the invention the region of
the cannula of the inhaler which extends into the container, should
be configured such that this region displaces at least one and a
half times, preferably twice as much fluid as the amount
corresponding to the first dead volume. This measure ensures that
the pressure which is produced by pushing the storage container
onto the cannula inside the container is increased, with the result
that the fluid is forced through the cannula towards the nozzle
under higher pressure and hence more rapidly as a result of the
excess pressure inside the container.
[0035] The dead volume of the fluid conveying system of the known
system is about 17 microlitres, which is made up of about 10
microlitres of dead volume in the central tube when the spring is
not under tension, including the dead space of the pressure
chamber, 7 microlitres of dead volume in the capillary (that is the
proportion of the capillary volume which is above the fluid level
when the totally full cartridge is fitted) and about 100 nanolitres
of dead volume of the nozzle. This volume then has to be displaced
from the region of the cannula which penetrates into the fluid when
the cartridge is fitted onto the cannula. With an outer diameter
for the cannula of 1.5 mm and a wall thickness of 1.1 mm, the part
of the cannula that is immersed in the fluid has to be about 10.8
mm, in order to displace a volume of 18 microlitres.
[0036] However, it has been found that these dimensions do not
solve the problem, as the flexible container partially compensates
the excess pressure produced.
[0037] The problem according to the invention is only completely
solved if the displacement volume of that part of the hollow piston
that penetrates into the interior of the container is at least 23
microlitres, more preferably at least 34 microlitres.
[0038] In order to increase the displacement volume to the
preferred levels mentioned above, while keeping the same internal
and external diameters for the hollow piston, the length of the
hollow piston projecting into the interior of the container must be
increased to at least 13.8 mm, preferably to at least 20.4 mm.
[0039] In another embodiment the external diameter of the cannula
is increased, while keeping the internal diameter and the depth of
penetration into the interior of the container the same. In this
case an external diameter of at least 1.7 mm, preferably at least 2
mm is useful. This has the advantage that because of the broad
effective punching surface of the cannula the initial pressure
inside the container is built up more rapidly, so that the pressure
on the fluid to escape through the cannula is initially increased
more than by extending the piston.
[0040] In another embodiment the piston may be extended and at the
same time its external diameter is increased. Moreover, only that
part of the capillary which dips into the fluid can be shaped
accordingly, e.g. have a larger external diameter than the
remainder of the cannula.
[0041] In every case the length of the hollow piston of 44.2 mm
outside the interior of the container should preferably be
retained.
[0042] In another embodiment the container itself is acted upon by
pressure when filled with the pharmaceutical formulation. This may
be done for example by filling and sealing the container at low
temperatures, e.g. from 4.degree. C. to 10.degree. C. (cold
filling). As it is heated to room temperature the corresponding
excess pressure is then generated by the expansion of the
fluid.
[0043] In yet another embodiment as the container is filled with
the pharmaceutical formulation an excess pressure is generated by
introducing the pharmaceutical formulation under an excess pressure
atmosphere and leaving an air bubble of the corresponding order of
magnitude inside the container. Then the container is sealed. In
this process the air bubble is compressed during the filling. When
the container is pierced with the cannula the air bubble is freed
from tension and forces the fluid through the cannula. According to
the above remarks the volume difference between the compressed and
non-tensioned air bubble is preferably at least 23 microlitres,
more preferably at least 34 microlitres. Preferably an air bubble
of less than 100 microlitres is left in the container. In this
embodiment too the cannula of the inhaler has to dip into the
fluid.
[0044] Further details of the filling operation can be found in the
prior art mentioned above.
[0045] As a result of the measures described, an excess pressure of
preferably more than 1 mbar, particularly preferably more than 5
mbar, is built up inside the container. The maximum pressure built
up should not exceed 50 mbar.
[0046] In another embodiment it is not the inhaler but the matching
cartridge, i.e. the supply system for the fluid consisting of a
container and closure, which is physically changed. A displacement
device is formed which when the cartridge is fitted onto the
cannula of the inhaler is pushed into the inside of the container
and thereby displaces some of the fluid through the fluid conveying
system. Embodiments of this kind are hereinafter illustrated in
more detail by means of FIGS. 1 to 5. The drawings are not to scale
and are in the nature of sketches, in some cases.
[0047] A typical cartridge is described for example by FIG. 1. The
closure (1) comprises a device (2) in the form of a connector. The
connector can optionally displace some of the contents of the
container (3) during the closing process. The immersion connector
(2) for its part comprises a passage or guide (12) for the cannula
(18) of the inhaler. The connector (2) is initially sealed at the
bottom. The immersion connector (2) displaces fluid from the
container when the closure cap is put on and thereby ensures that
after sealing the container is at least 90, preferably 95% full by
volume. The closure cap also has an encircling bead (4) on the
inside (crimp edge) which engages underneath a cylindrical ring (5)
running round the outside of the neck of the container, at the
lower edge of the closure cap (1) in the closure position. While
the closure cap (1) is pushed on the edge of the closure cap is
expanded and the bead (4) abuts on the ring (5) to form a seal, so
that the inside (7) of the cap only communicates with the outside
through one or more vent openings (6). The vent opening(s) is (are)
arranged for example in the outer part of the ring (5). In the
closure position the gap between the flat part of the closure cap
(1) and the upper edge of the neck of the container, which is
optionally provided with an encircling rib (8) to improve the seal,
is filled by a gasket (9) and in this way the interior of the
container (3) is reliably sealed off from the interior (7) of the
cap, which surrounds the sealing ring (9) and the neck of the
container (3). The internal diameter of the sealing ring (9) is
expediently chosen so as to fit tightly against the device (2). The
vent opening(s) (6) may also be located elsewhere on the exterior
of the cap, e.g. laterally in the cylindrical part of the cap. The
immersion connector has a pierceable base (10).
[0048] In a preferred embodiment the container (3) consists of a
dimensionally stable outer container and a readily deformable inner
bag (3b) which collapses when fluid is removed. Containers of this
kind are described for example in European Patent 532 873, the
contents of which are hereby incorporated by reference. The device
(11) serves to attach the deformable inner bag (3b) to the inner
wall of the outer rigid container (3a) facing the bag (3b).
[0049] FIG. 2 shows a preferred embodiment of the closure cap
according to the invention, wherein the inner chamber of the
connector has a special guide (12) for a cannula for removing
fluid. In the present instance, the vent openings (6) are provided
on the upper part of the container (3). The vent openings may
alternatively also be provided on the closure cap. If desired the
guide (12) may be constructed as a press fit for the cannula (18)
or an O-ring seal (13) may be mounted therein.
[0050] FIG. 3a shows an embodiment of the invention wherein
underneath the guide (12) a cavity is formed in the immersion
connector (2), in which there is a displacement member (14) in the
form of, for example, a stopper, cylinder, cork, etc., which is
pushed at least partly into the container (3) when the cannula is
passed through the guide (12) and thereby helps to build up the
desired excess pressure inside the container. A displacement member
of this kind may be located at any point in the guide (12). The
shape of the displacement member is preferably cylindrical. The
displacement member preferably consists of a plastic such as
polyethylene, polypropylene, etc. On its side directed towards the
top end of the closure the displacement member may have a recess in
which the cannula can engage.
[0051] Preferably the displacement member is constructed as a punch
which can only partially emerge from the guide (12). In this case
at least part of the wall of the displacement member (14) and the
wall of the guide (12) may interact to form a fluidtight seal. In
order that the displacement member (14) cannot leave the guide
(12), stop means in the form of an encircling edge, for example,
may be formed at the upper end of the displacement member (14),
which interact with stop means--e.g. again in the form of an
encircling edge--at the lower end of the guide (12). This prevents
fluid from flowing into the space which was previously filled by
the displacement member (14), so that no pressure compensation can
take place in this way. Alternatively, guide channels may be formed
on the displacement member (14), which interact with complementary
means on the guide, the guide channels no longer being formed at
the top of the displacement member (14). Other stop means for a
system of this kind are described inter alia under FIG. 4 or in the
prior art.
[0052] In a preferred embodiment the displacement member may have a
bore (19) (FIG. 3b), in which the cannula engages by the force of
friction. This prevents the displacement member from dropping into
the container after leaving the guide (12). Preferably, the bore
may have a press fit or constriction (21) in which the cannula
engages. The bore is shaped such that the cannula (18) is in
contact with the fluid in the container. For this purpose the bore
may constitute a linear passage.
[0053] In a variant of this embodiment the bore for receiving the
cannula by frictional engagement is not a through-bore and is
constructed so that the capillary can only be partially pushed into
the bore. As a result a cavity (20) is formed underneath the
capillary. For this purpose a constriction (21) may be formed in
the bore, for example, preventing the capillary from being pressed
forward any more. The displacement member then has further
capillaries (22) which lead from the exterior of the displacement
member to the cavity. If these additional capillaries of the
displacement member are in the form of microcapillaries, fluid is
constantly transported from outside into the cavity, thus ensuring
that the cannula of the inhaler is always supplied with fluid even
during the emptying of the container. An embodiment along these
lines is shown, not to scale, in FIGS. 3c and 3d.
[0054] Preferably the displacement member in this variant is
constructed as an integral, capillaried, open-pored, porous storage
medium for fluid. In other words the displacement member
simultaneously acts as a sponge conveying fluid into its interior.
The displacement member may be a dimensionally stable body with a
fluid-pervious wall, filled with sintered or non-sintered powder,
or a woven or knitted or non-woven structure or a wad of fibers. It
may consist of plastics, ceramics, glass, metal or a natural
material.
[0055] FIGS. 4a and 4b show another embodiment in which the
immersion connector is composed of at least two sleeves (15, 15',
15'') fitting telescopically one inside the other. The inner
sleeves in each case have stop means (16) at their upper end, which
cooperate with corresponding inwardly directed stop means at the
lower end (17) of the outer sleeve and thus ensure that an inner
sleeve cannot be pushed right through an outer sleeve. The stop
means are preferably edges. Preferably, the individual
cylinder-like sleeves fit together to form a seal. The bottom of
the innermost sleeve is sealed to begin with, so that, when the
container is pushed on, the cannula (18) pushes apart the sleeves
which are still nesting in one another before it pierces the base
(22) (FIG. 4b). In this way the immersion connector is extended
while the container is being pushed onto the cannula (18), and thus
itself acts as a displacement member which builds up an excess
pressure in the fluid-filled interior of the container.
[0056] The internal diameter of the innermost sleeve may be
constructed as a press fit for the sleeve, or an O-shaped gasket is
provided here, for example, to seal the cannula (18) off to the
outside.
[0057] In the equivalent embodiment according to FIGS. 5a and 5b
the lower region of the immersion connector (19) is pleated in the
manner of an accordion (bellows) (FIG. 5a). The guide (12) extends
from the top part of the closure cap to the pleated end of the
immersion connector. The bottom part of the immersion connector is
constructed, as in all the embodiments, so that it can be pierced
by the cannula. In this embodiment more force is needed to pierce
the bottom part than to pull apart the bellows region. If the
cannula (18) is passed through the guide (12), the pleated region
is opened out before the bottom part is pierced, so that once again
the enlarged immersion connector acts as a displacement member
which creates excess pressure inside the container (FIG. 5b). As
the excess pressure is only slight there is little danger of the
excess pressure being compensated by the compression of the
extended bellows instead of by the displacement of the fluid
through the fluid conveying system. This danger can additionally be
countered by a suitable choice of material.
[0058] In the alternative embodiments in FIGS. 4 and 5 the pressure
needed for piercing is controlled, for example, by means of the
thickness of the bottom part.
[0059] Further details of the basic structure of the closure cap or
the container can be found in EP 0775076.
[0060] These latter embodiments of the invention described above
may be constructed analogously to a closure system according to EP
1058657 in the form of a flange provided on a container.
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