U.S. patent application number 09/933722 was filed with the patent office on 2002-01-17 for container for a medicinal liquid.
Invention is credited to Eicher, Joachim, Essing, Martin, Freund, Bernhard, Geser, Johannes, Hochrainer, Dieter, Kladders, Heinrich, Reinecke, Holger, Zierenberg, Bernd.
Application Number | 20020007155 09/933722 |
Document ID | / |
Family ID | 27218175 |
Filed Date | 2002-01-17 |
United States Patent
Application |
20020007155 |
Kind Code |
A1 |
Freund, Bernhard ; et
al. |
January 17, 2002 |
Container for a medicinal liquid
Abstract
Foil bags are used as a primary packaging for liquids, the bags
permitting the liquid to be taken therefrom without the application
of a considerable amount of force. A container is provided for a
medicinal liquid, the container being gas-tight and liquid-tight so
that it is storable over many months. The container includes a
collapsible foil bag on which a flange, which is stable in respect
of shape, is disposed. The flange is designed for fitting onto a
discharge connection member. The container can be disposed in a
casing which is stable in respect of shape. The medicinal liquid
does not come into contact with air and is protected from the
effect of light. The medicinal liquid may be dispensed from the
foil bag in many partial quantities over a prolonged period of
time, with a respective partial amount thereof being converted into
an aerosol by means of an atomizer.
Inventors: |
Freund, Bernhard;
(Gau-Algesheim, DE) ; Hochrainer, Dieter; (Bingen
am Rhein, DE) ; Kladders, Heinrich; (Muelheim,
DE) ; Zierenberg, Bernd; (Bingen am Rhein, DE)
; Eicher, Joachim; (Dortmund, DE) ; Geser,
Johannes; (Dortmund, DE) ; Essing, Martin;
(Dortmund, DE) ; Reinecke, Holger; (Dortmund,
DE) |
Correspondence
Address: |
STERNE, KESSLER, GOLDSTEIN & FOX PLLC
1100 NEW YORK AVENUE, N.W., SUITE 600
WASHINGTON
DC
20005-3934
US
|
Family ID: |
27218175 |
Appl. No.: |
09/933722 |
Filed: |
August 22, 2001 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
09933722 |
Aug 22, 2001 |
|
|
|
09258357 |
Feb 26, 1999 |
|
|
|
60093772 |
Jul 23, 1998 |
|
|
|
Current U.S.
Class: |
604/232 ;
604/408 |
Current CPC
Class: |
A61M 2207/00 20130101;
A61J 1/14 20130101; B65D 83/62 20130101; B65D 75/5883 20130101;
B65D 83/0061 20130101; B65D 75/5877 20130101; A61J 1/10 20130101;
B65D 2575/583 20130101 |
Class at
Publication: |
604/232 ;
604/408 |
International
Class: |
A61M 005/00; A61B
019/00 |
Foreign Application Data
Date |
Code |
Application Number |
Feb 27, 1998 |
DE |
19808295.9 |
Claims
What is claimed is:
1. A container for a medicinal liquid, the container being
gas-tight and liquid-tight, comprising: a foil bag closed at both
ends and which is deformable at a differential pressure below 300
hPa (300 mbar); a flange sealingly disposed on said foil bag,
wherein said flange is in the form of a releasable connecting
element for fitting the container on to a discharge connection
member; at least one welded seam for closing at least one end of
said foil bag, wherein said welded seam extends substantially
transversely with respect to an axis of said foil bag; a sealing
location in said flange; and a discharge location for the liquid in
the region of said flange.
2. A container according to claim 1 wherein said foil bag is
deformable at a differential pressure below 150 hPa (150 mbar).
3. A container according to claim 1, where said foil bag is
deformable at a differential pressure below 80 hPa (80 mbar).
4. A container according to claim 1 wherein said foil bag is closed
at both ends by said welded seam, and wherein said flange is
sealingly mounted to said foil bag.
5. A container according to claim 1 wherein said foil bag is
sealingly closed at a first end by said welded seam and is
sealingly closed at a second end by said flange.
6. A container according to claim 1 wherein said flange is a
rotationally symmetrical flange, and wherein the size of said
rotationally symmetrical flange is adapted to the size of said foil
bag such that said flange closes said foil bag at an end
thereof.
7. A container according to claim 1, wherein said flange which
comprises a guide passage.
8. A container according to claim 7 wherein said flange comprises a
press fit within said guide passage.
9. A container according to claim 1 wherein said flange comprises a
thermoplastic material.
10. A container according to claim 1, wherein said welded seam is
of a U-shaped or V-shaped configuration and extends substantially
transversely with respect to and axis of said foil bag and extends
partially in the direction of the axis of said foil bag.
11. A container according to claim 1, wherein said welded seam is
of a T-shaped configuration.
12. A container according to claim 1 wherein said sealing location
is in the form of a ring of elastic material, which is disposed in
a groove.
13. A container according to claim 1 wherein said discharge
location is in the form of a perforation location.
14. A container according to claim 1 wherein said discharge
location is provided with a pierceable membrane.
15. A container according to claim 14 wherein said flange comprises
a guide passage, and wherein said pierceable membrane is disposed
at the end of or within said guide passage.
16. A container according to claim 14, wherein said pierceable
membrane is part of said foil bag.
17. A container according to claim 1 wherein said discharge
location is sealed with a scaling foil.
18. A container according to claim 1 wherein said foil bag is made
from material selected from the group consisting of one or more of
the following: a foil of plastic material, a foil of metal, a foil
of metal alloy, a composite foil of plastic material, a composite
foil of metal, a plastic foil with a layer of metal, a plastic foil
with a layer of glass, and a plastic foil with a layer of
ceramic.
19. A container according to claim 18, wherein said metal alloy is
selected from the group consisting of one or more of the following:
aluminum, gold and copper.
20. A container according to claim 1, wherein said foil bag
comprises an inner foil of plastic material and an outer foil of
metal.
21. A container according to claim 1, wherein said foil bag
comprises two foils of different plastic materials.
22. A container according to claim 1, wherein said foil bag
comprises: an inner foil made of a copolymer; a diffusion-tight
central layer; and an outer foil of plastic material, wherein the
melting temperature of said plastic material is higher than the
melting temperature of said inner foil.
23. A container according to claim 22, wherein said copolymer is a
polyethylene copolymer of ethylene-acrylic acid.
24. A container according to claim 22, wherein said diffusion-tight
central layer is made from a material selected from the group
consisting of one or more of the following: a foil made of metal, a
foil made of plastic material, metal, glass and ceramic.
25. A container according to claim 22, wherein said outer foil is
made of polyethylene terephthalate.
26. A container according to claim 1, wherein said foil bag
comprises a plastic foil of a thickness of between 20 .mu.m and 100
.mu.m.
27. A container according to claim 1, wherein said foil bag
comprises a composite foil having an inner layer of plastic
material of a thickness of between 20 .mu.m and 100 .mu.m and an
outer layer of metal of a thickness of between 8 .mu.m and 20
.mu.m.
28. A container according to claim 1, wherein said foil bag
comprises a composite foil having an inner foil of plastic material
of a thickness of between 20 .mu.m and 100 .mu.m, a central foil of
metal of a thickness of between 8 .mu.m and 20 .mu.m, and an outer
foil of plastic material of a thickness of between 10 .mu.m and 40
.mu.m.
29. A container according to claim 1, wherein the container has a
filling volume of 0.5 ml to 5 ml.
30. A container according to claim 1, wherein the container has a
filling volume of 1 ml to 4 ml.
31. A container according to claim 1, wherein the container has a
filling volume of 1 ml to 3 ml.
32. A container according to claim 1, wherein the container has a
filling volume of 2 ml to 4 ml.
33. A container according to claim 1, wherein the container is
disposed in a casing made of metal or plastic material, and wherein
said casing is connected to said flange.
34. A container according to claim 33, wherein said casing has a
diameter within a range of 10 mm to 30 mm.
35. A container according to claim 33, wherein said casing has a
diameter within a range of 12 mm to 17 mm.
36. A container according to claim 33, wherein said casing has an
overall length within a range of 20 mm to 60 mm.
37. A container according to claim 33, wherein said casing has an
overall length within a range of 30 mm to 50 mm.
38. A container according to claim 33, wherein said casing is
closed substantially all around its periphery and has an opening
formed therein.
39. A container according to claim 33, wherein said casing is
closed substantially all around its periphery and has a gap at the
location where said casing is connected to said flange.
40. A container according to claim 33, wherein said casing is in
the form of a basket having a plurality of openings
41. A container according to claim 1, wherein the container is
configured to be fit into a discharge device having a connecting
portion, and wherein said connecting portion comprises a
releasable, positively locking, push-in snap connection between
said connecting portion in said discharge device and said flange of
the container.
42. A container according to claim 41, wherein said snap connection
comprises snap noses and snap hooks, and wherein said flange has a
peripherally extending groove into which said snap noses of said
snap hooks engage when the container is fit into said connecting
portion.
43. The container according to claim 1, wherein the container is
used as packaging for a medicinal liquid, whereby the medicinal
liquid is taken in a plurality of partial quantities from said foil
bag.
44. The container according to claim 1, wherein the container is
used as packaging for a medicinal liquid, whereby the medicinal
liquid is taken in a dosage of 10 .mu.l to 50 .mu.l.
45. The container according to claim 1, wherein the container is
used as packaging for a medicinal liquid, whereby the medicinal
liquid is taken in a dosage of 15 .mu.l to 20 .mu.l.
46. The container according to claim 1, wherein the container is
used as a cartridge containing an inhalable medicament preparation
in a propellant gas-free atomizer.
47. The container according to claim 1, wherein the container is
used as a cartridge containing an inhalable medicament preparation
which is present in the form of a solution in ethanol, water, or a
mixture thereof.
48. The container according to claim 1, wherein the container is
used as a cartridge containing an inhalable medicament preparation
with at least one active substance selected from the group
consisting of one or more of the following: Berotec
(fenoterol-hydrobromide; 1-(3,5-dihydroxyphenyl)-2-
-[[1-(4-hydroxybenzyl) -ethyl]-amino]-ethanol-hydrobromide),
Atrovent (ipratropium bromide), Berodual (combination of
fenoterol-hydrobromide and ipratropium-bromide), Salbutamol (or
Albuterol), Combivent, Oxivent (oxitropium bromide), Ba 679
(tiotropium bromide), BEA 2108 (di-(2-thienyl)-glycol acid tropenol
ester), Flunisolid, Budesonid, Beclomethason.
49. The container according to claim 1, wherein the container is
used with a medicament preparation for the treatment of ailments by
means of inhalable active substances.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of Appl. No. 60/093,772,
filed Jul. 23, 1998.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to a container for a medicinal
liquid, more particularly to a container for a medicinal liquid,
wherein the container is gas-tight and liquid-tight.
[0004] 2. Related Art
[0005] EP-0 182 094 A2 sets forth a bottle-shaped pack comprising
an outer container which is stiff in respect of shape and an inner
container which is disposed in the outer container and which is in
the form of an easily deformable bag for containing the filling
material. The preform is produced by co-extrusion of two coaxial
tubular portions. The two portions comprise two thermoplastic
materials which are not joined together. The preform is expanded in
a blow molding mold. A welded seam is provided at the flat bottom
of the inner container. The flat bottom which is formed on the
outer container has an opening in the form of a slot. The outer
container and the inner container are connected together in a
positively locking relationship in the region of the discharge
opening. That pack is produced substantially in one working
operation.
[0006] The filling material is discharged from the container by
means of a pump which is disposed in the discharge opening. The
pump causes the inner container to deform as its volume decreases.
Air passes into the space between the outer container and the
deformed inner container, through the open slot in the flat bottom
of the outer container, thereby preventing the occurrence of a
reduced pressure in that intermediate space. The inner container
does not involve a fixed contact with respect to the outer
container, except in the region of the discharge to opening. The
pack can be provided with a dip tube which extends almost as far as
the flat bottom and which holds the inner container in the extended
condition. That pack can be satisfactorily used and completely
emptied, only when it is in a given position in space.
[0007] A tubular bag of composite foil is described in EP-0 620 165
A1. The composite foil comprises at least an outwardly disposed
plastic foil and an inwardly disposed metal foil. The tubular bag
is closed at both ends in a sack-like configuration. The bag is
provided with a desired-rupture location, by means of which it can
be reliably opened at that point. A tubular bag of that kind serves
to store a hardenable material which is expelled from the tubular
bag by means of an expelling device.
[0008] EP-0 068 653 A1 describes a flexible and collapsible
container which is intended for one-trip use and which is made from
a foil and which is used in a suction or feeding bottle which can
be used a plurality of times. The one end of the container is open
while the other end is closed by means of a welded seam and
provided with a tongue portion. The tongue portion is clamped in a
gap provided at the bottom of the suction or feeding bottle. That
provides that the bag-like container is constantly held in an
extended condition in the suction or feeding bottle.
SUMMARY OF THE INVENTION
[0009] The invention aims to make the production of a container
which is intended for one-rip use more economical without adversely
affecting its usefulness, and to simplify handling thereof.
[0010] The object of the present invention is to provide a
container for a medicinal liquid, which is gas-tight and
liquid-tight, and which has a filling volume that is suited to the
intended purpose of use. The container plastically and irreversibly
collapses under a slightly reduced pressure in a predetermined
manner such that it can be substantially emptied.
[0011] The container of the present invention includes a foil bag
which is closed at both ends. At a differential pressure between
the interior of the container and its surroundings below 300 hPa
(300 mbar), the foil bag is deformable by the external pressure and
collapses. The container further includes a flange which is stable
in respect of shape and which is sealingly mounted to the foil bag.
The flange is a releasable connecting element for fitting the
container on to a discharge connection member.
[0012] The foil bag is closed at at least one end with at least one
welded seam which extends substantially transversely with respect
to the axis of the bag. The flange has a sealing location which is
stable in respect of shape. A discharge location for the liquid in
the region of the flange is also provided, the discharge location
being is stable in respect of shape.
[0013] The container of the present invention has several
advantages over conventional containers. For example, the container
of the present invention is economical to produce, is suitable for
one-trip use and requires only a small amount of material
usage.
[0014] Further, the container of the present invention can be
produced in a sterile condition and filled and sealed in a sterile
condition. It can also be used for medicaments intended for
inhalation, which are typically provided as solutions in ethanol,
water, or an ethanol and water mixture.
[0015] The liquid is discharged from the container of the present
invention under sterile conditions, such that no air is sucked into
the container upon discharge. As such, the liquid does not come
into contact with air, oxygen or carbon dioxide.
[0016] Further, the container of the present invention permits gas
and bubble-free discharge of the medicinal liquid.
[0017] The container of the present invention is sealed so that
diffusion of liquids and gases is minimized. The container can be
filled and then stored over several years, depending on the
particular medicament involved, and still satisfy the requirements
of all official pharmacopoeiae.
[0018] The container is easily deformable at a slightly reduced
pressure. Further, in the collapsed condition the container of the
present invention remains flat and stretched out, such that it
retains its initial length after emptying.
[0019] Further, the container of the present invention does not
require a valve for pressure equalization after a portion of the
liquid has been discharged, and the container can be substantially
emptied, even in a fluctuating position and when it is upside
down.
[0020] The foil bag of the present invention is connected only to
the flange which is stable in respect of shape and is not fixed to
any casing, if such is provided.
[0021] The filling volume of the container can be easily adjusted
to a predetermined value within a certain range by changing the
length and/or the diameter of the foil bag. Further, the container
can be filled prior to closure, before the single or the second
welded seam is produced. As such, there is no need for a separate
closure means.
[0022] The container can be used with or without a casing. If the
container is disposed in a casing, it is protected from external
damage.
[0023] The liquid is stored in the container of the present
invention such that it is protected from the effect of light by an
opaque foil bag or by an opaque casing which is closed all
around.
[0024] Further, the container of the present invention can be
fitted into and removed from a discharge device in a simple fashion
and without rotary movement.
BRIEF DESCRIPTION OF THE FIGURES
[0025] The foregoing and other features and advantages of the
invention will be apparent from the following, more particular
description of a preferred embodiment of the invention, as
illustrated in the accompanying drawings.
[0026] FIG. 1 is a perspective view of a first embodiment of a foil
bag of the present invention which is closed at both ends.
[0027] FIG. 2 is a perspective view of a second embodiment of a
foil bag of the present invention which is closed at both ends.
[0028] FIG. 3 is a perspective view of a third embodiment of a foil
bag of the present invention which is closed at both ends.
[0029] FIG. 4 is a sectional view of a first embodiment of a flange
of the present invention.
[0030] FIG. 5a is a sectional view of a second embodiment of a
flange of the present invention.
[0031] FIG. 5b is a sectional view of the second embodiment of the
flange taken along a line 5-5 of FIG. 5a.
[0032] FIG. 6 is a sectional view of a third embodiment of a flange
of the present invention.
[0033] FIG. 7 is a sectional view of a fourth embodiment of a
flange of the present invention.
[0034] FIG. 8a is a view of a one-part flange of the present
invention, which is disposed on the side of a foil bag.
[0035] FIG. 8b is an exploded view of a cross-section of laminate
foil used to make up the foil bag of FIG. 8a.
[0036] FIG. 9a is a side view of first embodiment of a welded seam
of the present invention.
[0037] FIG. 9b is a sectional view of the welded seam taken along a
line 9-9 of FIG. 9a.
[0038] FIG. 10a is side view a second embodiment of a welded seam
of the present invention.
[0039] FIG. 10b is a sectional view of the welded seam taken along
a line 10-10 of FIG. 10a.
[0040] FIG. 11a is a side view of a third embodiment of the welded
seam of the present invention.
[0041] FIG. 11b is a plan view of the welded seam of FIG. 11a.
[0042] FIGS. 12a-12g show a series of perspective views of
manufacturing and filling of a container according a first
embodiment of the present invention.
[0043] FIGS. 13a-13f show a series of perspective views of
manufacturing and filling of a container according a second
embodiment of the present invention.
[0044] FIG. 14 is a partial sectional view of a container according
to the present invention.
[0045] FIG. 15a is a sectional view of a first embodiment of a
connecting portion of a container of the present invention.
[0046] FIG. 15b is a side view of one end of the container of FIG.
15a.
[0047] FIG. 16a is a sectional view of a second embodiment of a
connecting portion of a container of the present invention.
[0048] FIG. 16b is a side view of one end of the container of FIG.
16a.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0049] A preferred embodiment of the present invention is now
described with reference to the figures where like reference
numbers indicate identical or functionally similar elements. While
specific configurations and arrangements are discussed, it should
be understood that this is done for illustrative purposes only. A
person skilled in the relevant art will recognize that other
configurations and arrangements can be used without departing from
the spirit and scope of the invention.
[0050] The object of the present invention is to provide a
container for a medicinal liquid, which is gas-tight and
liquid-tight, and which has a filling volume that is suited to the
intended purpose of use. The container plastically and irreversibly
collapses under a slightly reduced pressure in a predetermined
manner such that it can be substantially emptied.
[0051] The container of the present invention includes a foil bag
which is closed at both ends. At a differential pressure between
the interior of the container and its surroundings below 300 hPa
(300 mbar), the foil bag is deformable by the external pressure and
collapses. The container further includes a flange which is stable
in respect of shape and which is sealingly mounted to the foil bag.
The flange is a releasable connecting element for fitting the
container on to a discharge connection member.
[0052] The foil bag is closed at at least one end with at least one
welded seam which extends substantially transversely with respect
to the axis of the bag. The flange has a sealing location which is
stable in respect of shape. A discharge location for the liquid in
the region of the flange is also provided, the discharge location
being is stable in respect of shape.
[0053] In a further embodiment, the collapsible foil bag can be
deformed by and collapsed due to an external pressure at a
differential pressure of below 150 hPa (150 mbar) or preferably
below 80 hPa (80 mbar).
[0054] The foil bag can be closed by a welded seam at both ends. In
that case, the flange, which is stable in respect of shape, is
sealingly welded to the side of the foil bag, preferably in the
proximity of one end of the foil bag. The foil bag, however, may
also be sealingly closed at one end by a welded seam and at the
other end by the flange. In this case, the one end of the foil bag
is welded to the flange, preferably on the periphery thereof.
[0055] The foil bag can be made of a tube which does not have a
welded seam extending in the axial direction of the foil bag. In an
alternate embodiment, the foil bag may have one or two welded seams
extending in the longitudinal direction. The foil bag can be in the
form of a flat bag or a bag with side folds. A bag with a welded
seam extending in the longitudinal direction is preferred.
[0056] In one embodiment, the foil bag is made of a foil of metal
or metal alloy, preferably aluminum, gold or copper, or plastic
material, preferably a thermoplastic material. In another
embodiment, the foil bag is made of a composite foil of plastic
material and metal. The composite foil preferably comprises two or
three foils which are joined together. The foil bag may further
comprise a plastic foil to which a layer of metal, glass or ceramic
is applied, for example by vapor deposition. The foils of plastic
material or metal are several micrometers thick. The thickness of
the vapor-deposition layers of metal, glass or ceramic is in the
sub-micrometer range.
[0057] A composite foil consisting of two foils can be made of a
metal foil and a plastic foil which are joined together. In this
embodiment, the metal foil forms the inward side or the outward
side of the composite foil. In another embodiment, the composite
foil comprises two different plastic foils.
[0058] The composite foil comprising three foils preferably
comprises two plastic foils, between which there is a foil
comprising metal. All three foils are joined together. In place of
the metal foil, the composite foil may have a layer of glass or
ceramic, for example of silicon oxide (SiO.sub.x ), which is
produced by vapor deposition on a plastic foil.
[0059] In a further embodiment the inner foil of the composite foil
comprises a copolymer, for example a polyethylene copolymer of
ethylene-acrylic acid. The outer plastic foil of the composite foil
is preferably a plastic material, for example polyethylene
terephthalate, the melting temperature of which is higher than the
melting temperature of the plastic material of the inner foil. That
facilitates seam-wise welding of the plastic material of the inner
foil, in the production of the foil bag.
[0060] In the composite foil, a bonding layer may possibly be
provided between two foils.
[0061] The foil bag can comprise a plastic foil of a thickness of
between 20 .mu.m and 100 .mu.m. It may also comprise a composite
foil with an inner foil of plastic material of a thickness of
between 20 .mu.m and 100 .mu.m and an outer foil of metal of a
thickness of between 8 .mu.m and 20 .mu.m. It may also comprise a
composite foil with an inner foil of plastic material of a
thickness of between 20 .mu.m and 100 .mu.m, a central foil of
metal of a thickness of between 8 .mu.m and 20 .mu.m and an outer
foil of plastic material of a thickness of between 10 .mu.m and 40
.mu.m.
[0062] The container according to the invention is described in
greater detail with reference to the Figures by way of example.
[0063] FIGS. 1 to 3 are perspective views of various embodiments of
the foil bag which is closed at both ends. FIG. 1 shows a tubular
bag 11 with a cylindrical flange 12 which is stable in respect of
shape, and a U-shaped transverse seam 13 which closes the one end
of the tubular bag and which at least partially extends in the
longitudinal direction thereof. The edge 14 of the flange is
connected to the other end of the tubular bag. Disposed on the axis
of the flange is a hole 15 into which a discharge connection member
can be introduced.
[0064] FIG. 2 shows a sealed-edge bag (21) which comprises two
foils which are disposed one upon the other. It has two welded
seams 22 extending in the longitudinal direction of the bag and, at
its one end, a welded seam 23 extending in the transverse
direction. The other end is connected to a flange 24 which is
stable in respect of shape and which is of a fish-like form.
Disposed at the center of the flange is a hole 25 into which a
discharge connection member can be inserted.
[0065] FIG. 3 shows a side fold bag 31 with folds at both
longitudinal sides, which is closed at each of its two ends by a
respective transversely extending welded seam 32. The flange 33
which is stable in respect of shape is welded on to the bag on a
flat side thereof. A discharge connection member can be inserted
into the hole 34 of the flange.
[0066] The flange which is stable in respect of shape can be of
different shapes. If it is disposed at the end of the foil bag as
the closure means thereof, it can be of a rotationally symmetrical
form and can be adapted to the size of the end of the foil bag. The
flange can also be provided with a guide passage into which the
discharge connection member can be introduced. The discharge
connection member is disposed within this guide passage when the
container is fit thereon.
[0067] In one embodiment, the guide passage is provided with a
press fit which embraces the discharge connection member. In one
embodiment, the press fit is a portion of the guide passage which
comprises a smooth inside wall of an inside diameter which only
slightly differs from the outside diameter of the discharge
connection member. In a further embodiment, a plurality of bulge
portions can be provided in a portion of the guide passage on the
inside wall thereof. The bulge portions can be for example three
bulge portions which are of an elongate configuration and which are
arranged symmetrically extending in the axial direction. It is
further possible to provide a plurality of bulge portions which are
arranged at an axial spacing from each other and which extend in
the azimuthal direction and which for example form two rings or
which comprise a plurality of ring portions. Furthermore, the bulge
portions can extend in a helical configuration, such that they can
comprise a plurality of helix portions distributed on the inside
wall of the guide passage or a helix portion whose length is
greater than the periphery of the guide passage. A press fit of
that kind permits the container to be fitted on to the discharge
connection member and can provide for a sufficiently firm fit of
the flange on the discharge connection member. Furthermore, after
it has been emptied, the container can be withdrawn from the
discharge connection member without damaging the latter.
[0068] The flange can be in one or more parts. A multi-part flange
is preferably a two-part flange. An outwardly disposed part of the
flange is sealingly connected to the foil bag. The outer part
contains an opening which is sealingly closed with the inner part.
The two parts can be screwed together by means of a screwthread or
can be connected together by means of a snap-action connection or
by ultrasonic welding. A one-part flange is of a similar
configuration to the two-part flange, but it does not include any
connecting elements. The flange can be produced at the same time
with a press fit, a groove for the sealing location, and a
pierceable membrane.
[0069] The flange can be made of rubber, metal or plastic material,
preferably a thermoplastic material. It may be desirable to produce
the flange from the same plastic material as that used to form the
foil bag or the inward side of the foil bag. A flange which is made
of rubber or metal can be connected to the foil bag by gluing or
possibly by vulcanization.
[0070] FIGS. 4 to 7 are sectional views of various embodiments of
the flange. FIG. 4 is a view in longitudinal section through a
one-piece flange 41 having a cylindrical guide passage 42, which is
in the form of a press fit, for a cylindrical discharge connection
member. The outer end of the guide passage is beveled while the
other end is closed by a membrane 43 which is disposed at an
incline to the axis of the flange. Flange 41 is produced in one
working operation. The edge of flange 41 is connected to a foil bag
44.
[0071] FIG. 5a shows a longitudinal section through a multi-part
cylindrical flange, and FIG. 5b shows a cross-section taken along a
line 5-5 of FIG. 5a. A lower part 51 of the flange is connected to
a foil bag 53. An upper part 52 of the flange fits in an opening in
lower part 51. Upper part 52 is provided with a guide passage 54 in
which there are three elongate ridges 55, as shown in FIG. 5b,
extending in the axial direction of the flange. The elongate ridges
55 act as a press fit for a discharge connection member. An annular
ridge 56 acts as a seal. Lower part 51 and upper part 52 are welded
together at their contact surface 57. Guide passage 54 has an entry
opening with an inclined insertion surface. This entry opening is
sealed off by a sealing foil 58.
[0072] FIG. 6 shows a multi-part cylindrical flange which is stable
in respect of shape. A lower part 61 of the flange is connected to
a foil bag 63. An upper part 62 of the flange projects into the
annular lower part 61. Disposed in upper part 62 as a seal is an
0-ring 64 which is held in place by a gland 65 that is pressed into
position. The opening in gland 65 serves as a guide passage for a
discharge connection member. A peripherally extending ridge 66 is
disposed on the inside of the seal on upper part 62, which provides
a press fit. A discharge connection member 67 is inserted into the
guide passage of gland 65. The container is held on discharge
connection member 67 by means of peripherally extending ridge press
fit 66. Lower part 61 and upper part 62 are welded together at
their contact surface 68.
[0073] FIG. 7 shows another embodiment of a multi-part flange of
the present invention. A lower part 71 of the flange is connected
to a foil bag 73. An upper part 72 of the flange is disposed in the
annular lower part 71 which is provided with a shoulder. Upper part
72 includes a flat ring 74 as a seal, which is held in place by a
gland 75 which is pressed into position. A guide passage 76 for a
discharge connection member is disposed beneath flat ring 74. A
press fit is formed by two ridges 77 within guide passage 76,
extending therearound in a screwthread-like configuration. A
membrane 78 is provided in the proximity of the lower end of guide
passage 76 and perpendicular to the axis of the flange. Membrane 78
is pierced when the container is fit onto the discharge connection
member. Membrane 78 is produced with upper part 72 in one working
operation. Lower part 71 and upper part 72 are connected together
at their contact surface 79.
[0074] FIG. 8a is a view in cross-section of a one-part flange 81
which is stable in respect of shape and which is disposed on the
side of a foil bag 82. Flange 81 has a guide passage 83 which
serves as a press fit for a discharge connection member. Flange 81
is sealed on its outward side by a sealing foil 84. When the
container is fitted on to a discharge connection member 85, having
a beveled end, the foil bag is pierced at an inner end 86 of guide
passage 83.
[0075] FIG. 8b shows an exploded view in cross-section through a
commercially available laminate foil having three layers making up
the foil bag. An inner foil 87 comprises polyethylene (40 .mu.m in
thickness), a central foil 88 acts as the diffusion barrier of
aluminum (12 .mu.m in thickness) and an outer foil 89 comprises
polyethylene terephthalate (12 .mu.m in thickness).
[0076] The welded seam at one or both ends of the foil bag can be
of a U-, V- or T-shaped configuration. The seam extends
substantially transversely with respect to the axis of the bag. In
one embodiment, the welded seam extends partially in the direction
of the axis of the bag, whereby the defined deformation of the foil
bag is promoted when liquid is drawn therefrom.
[0077] A sealing location or sealing means can be provided within
or at one of the ends of the guide passage. The sealing location
can comprise a ring which is disposed in a groove provided on the
inside wall of the guide passage. The ring can be of an O-shaped or
substantially rectangular cross-section. The ring may be provided
with a sealing lip. The ring is made of an elastomer, a
thermoplastic elastomer or rubber. The sealing location closes the
filling space or chamber of the container which is fitted on to the
discharge connection member gas-tightly and liquid-tightly in
relation to the ambient air. Further, the sealing location permits
the emptied container to be withdrawn from the discharge connection
member. The sealing location is required if the sealing effect of
the press fit is not sufficient.
[0078] The welded seams on the foil bag can be from 0.7 mm to 3 mm
wide. The width of the welded seams is selected in accordance with
the requirements for sealing integrity and durability of the seam.
Wide, longitudinal seams on the foil bag can be bent over after the
welding operation so that they are disposed on the outside against
the foil bag and so that the foil bag is only a little wider than
its width in the unwelded part between the welded seams.
[0079] The welded seams on the foil bag and the weld location
between the foil bag and the flange are produced using known
processes such as thermal welding, ultrasonic welding or induction
welding in the case of composite foils with a metal layer, wherein
the weld locations are preferably pressed together in the heated
condition. Such processes are set forth for example in EP-0 111 131
and EP-0 130 239, the disclosures of which are incorporated herein
by reference in their entireties.
[0080] FIGS. 9a, 9b, 10a and 10b show cross-section and side views
of various embodiments of the welded seam with which the foil bag
is closed at at least one end. FIGS. 11a and 11b show a side view
and plan view of an alternate embodiment of the welded seam on the
end of the bag.
[0081] FIG. 9a shows a U-shaped welded seam 91 which extends
partially in the longitudinal direction of a foil bag 92. On one
side of foil bag 92, welded seam 91 merges with a welded seam 93 of
the foil bag, with the welded seam 93 extending in the longitudinal
direction. FIG. 9b is a view in cross-section through the foil bag
taken along a line 9-9 of FIG. 9a. The inner layer of the folded
multi-layer foil 94 is welded in welded seams 91 and 93.
[0082] FIG. 10a shows a V-shaped welded seam 101 which extends
partially in the longitudinal direction of a foil bag 102. In this
case foil bag 102 comprises a tubular foil without a longitudinal
seam. FIG. 10b shows a view in cross-section through the foil bag
taken along a line 10-10 of FIG. 10a. The folded single-layer foil
103 is welded in welded seam 101.
[0083] FIG. 11a shows a T-shaped welded seam 111 as a side view,
and FIG. 11b is a plan view of the welded end of a foil bag 112.
The three limbs of the T-shaped seam 111 are overall as long as the
foil bag is wide, when the foil bag 112 is collapsed flat, outside
the T-shaped seam.
[0084] A foil bag which is welded with a U-, V- or T-shaped seam is
no greater in the region of the transverse seam than the diameter
of the casing into which the foil bag is possibly inserted.
[0085] The discharge location is preferably in the form of a
puncture or perforation location. A pierceable membrane can be
provided at the puncture or perforation location, the membrane
being pierced when the container is fitted on to the discharge
connection member. The membrane is preferably arranged between the
sealing location and the liquid chamber or space in the foil bag.
The pierceable membrane can be disposed at one of the ends or
within the guide passage. It is preferably disposed directly at the
end of the guide passage or in the proximity of that end which is
towards the liquid space. It can be a part of the flange or a part
of the foil bag. If it is a part of the flange, it can be produced
at the same time as the flange, and can be made of the same plastic
material as the flange. The pierceable membrane acts as an original
closure means for the filling space or chamber in the foil bag.
[0086] In a further embodiment the discharge location can be sealed
with a sealing foil which is pulled off before the container is
fitted on to the discharge connection member or which is pierced
when the container is fitted on to the discharge connection
member.
[0087] The container may be disposed in a casing which is stable in
respect of shape, and which is made of metal or plastic material.
One end of the casing is releasably or non-releasably connected to
the flange, while the other end of the casing may be closed with a
bottom. In one embodiment, the casing is substantially closed all
around, however, it includes at least one opening. Alternatively, a
gap may be provided at the location of connection of the casing to
the flange. The casing can also be in the form of a basket which is
stable in respect of shape and which has many openings. In an
alternate embodiment, instead of the casing, the container may be
disposed in a U-shaped holder which is stable in respect of shape,
wherein the end of each limb of the U-shaped holder is secured to
the flange, and the limbs are longer than the foil bag.
[0088] In a preferred embodiment, the container disposed in a
casing is connected to the casing only at the flange. The end which
is closed with a welded seam or the two ends of the foil bag, which
are closed with a welded seam, are not connected to the casing.
[0089] Upon the transfer of liquid out of the container into the
discharge connection member the foil bag collapses flat due to the
action of the external pressure. Air passes through the opening in
the casing or through the gap between the casing and the flange,
into the space between the casing and the foil bag, and provides
for pressure equalization. As such, no valve is required in the
foil bag and the liquid in the foil bag does not come into contact
with air.
[0090] Manufacture and filling of the container according to the
invention is diagrammatically illustrated in perspective views in
FIGS. 12a-12g and 13a-13f.
[0091] As shown in FIG. 12a, a folded foil strip is provided at the
cut sides with a welded seam in the longitudinal direction, divided
into portions and shaped to form a tube. The lower part of a
two-part cylindrical flange, which is produced by an injection
molding process, is welded to one end of the tub, as shown in FIG.
12b. The other end of the tube is welded with a U-shaped transverse
seam as shown in FIG. 12c. The finished container is pushed into a
cylindrical casing of aluminum, as shown in FIG. 12d, the edge of
which is pressed into a groove or channel in the edge of the
cylindrical flange. The container is fixedly joined to the casing
in that way. The empty container which is disposed in the casing is
then filled with a fluid through the lower part of the flange,
which is provided with an opening, as shown in FIG. 12e. After the
filling operation the upper part of the flange is pressed into the
lower part, as shown in FIG. 12f, and the two parts are sealingly
joined together. The finished part, as shown in FIG. 12g, is ready
for being fit onto a discharge connection member.
[0092] An alternate production process is illustrated in FIGS.
13a-13f. A portion of a foil tube is provided with a longitudinal
seam, as shown in FIG. 13a. The tube is connected at one end to a
one-piece flange which is closed by a sealing foil, as shown in
FIG. 13b. The container is filled with a fluid through the other
open end of the foil tube, as shown in FIG. 13c. The open end of
the foil tube is closed by a U-shaped transverse seam, as shown in
FIG. 13d. The filled container is fit into a casing of plastic
material, as shown in FIG. 13e. The edge of the plastic casing is
snap-fit onto the edge of the one-piece flange. The finished part,
as shown in FIG. 13f, is ready for being fit onto a discharge
connection member.
[0093] FIG. 14 is a partly cross-sectional view of a typical
container 141 according to the present invention which is filled
with a fluid and which is disposed in a metal casing 142. At one
end, a foil bag is welded by a U-shaped seam 143. At its other end,
the foil bag is welded to an edge 144 of a lower part 145 of a
two-part cylindrical flange which is stable in respect of shape.
Metal casing 142 has a bottom 146 in which there is a hole formed
therein, through which air can pass into the space between metal
casing 142 and the foil bag. The open end of metal casing 142 is
pressed into a groove or channel 147 in the edge of lower part 145
of the flange. Metal casing 142 is fixedly connected to the flange.
An upper part 148 of the flange is fit into an opening in lower
part 145. Lower part 145 and upper part 148 are connected by a
snap-action closure 149 and provided with a flat seal 150. A guide
passage 151 is closed at its inner end by a membrane 152 and sealed
at its outer end by a sealing foil 153.
[0094] The metal casing shown in FIG. 14 is preferably made of
aluminum. In one embodiment, it is 43 mm in length and has an
outside diameter of 17 mm and a wall which is 0.5 mm in thickness.
The two-piece flange is preferably made of polyethylene and is
produced by an injection molding process. The upper part of the
flange including the membrane is preferably produced in one step in
the process. The guide passage in the upper part of the flange
preferably has an inside diameter of 2.5 mm at the location of the
press fit and fits firmly onto a discharge connection member.
[0095] The foil bag is diffusion-tight with respect to the
medicinal liquid and its constituents and with respect to gases.
The material for the foil bag and possibly the structure of the
composite foil are suitably selected for use with the liquid.
Diffusion-tight in accordance with the present invention denotes a
loss of liquid (measured with ethanol at ambient temperature) of
the container due to diffusion of less than 0.6 mg per day,
preferably less than 0.4 mg per day, particularly preferably less
than 0.2 mg per day, in particular less than 0.1 mg per day.
[0096] The inner foil or the inward side of the foil bag is in
contact with the liquid introduced into the bag. The material
adopted for that foil is a material which is not attacked by the
liquid and which does not adversely affect the liquid. That foil is
preferably in the form of a weldable foil.
[0097] One of the foils or a layer which is applied for example by
vapor deposition is the diffusion barrier. This barrier prevents
diffusion of the liquid or the constituents thereof and prevents
the diffusion of gases from or into the foil bag. It may be
desirable to protect the diffusion barrier from mechanical damage
and from tearing when the foil is bent. One method of protection is
to apply a further plastic foil to the diffusion barrier so that
the diffusion of liquid or gases remains durably prevented.
[0098] As the foil bag is diffusion-tight in relation to gases, the
reduced pressure which occurs in the foil bag due to the discharge
of liquid therefrom cannot be compensated by gas diffusing therein.
As such, the foil bag reliably collapses even when liquid is very
slowly discharged from the container. The liquid can also be drawn
from the foil bag in a large number of partial quantities, for
example 200 metered amounts, distributed over a prolonged period of
time, for example three months.
[0099] The container, which is disposed in a substantially closed
casing, is inaccessible from the exterior and cannot be damaged
when stored or when it is fit onto the discharge connection member.
The substantially closed casing, the casing which is provided in
the form of a basket with many openings, or the holder which is
stable in respect of shape facilitates storage of the container
with the thin-gauge foil bag. These casings also facilitate
handling thereof when it is fit onto the discharge connection
member and when the empty container is withdrawn from the discharge
connection member.
[0100] One example of a discharge connection member is the hollow
plunger of an atomizer for medicinal liquids. An atomizer of that
kind is described in DE-195 36 902.5 and in WO-97/12687, the
disclosures of which are incorporated herein by reference in their
entireties. An exemplary atomizer is shown in FIGS. 6a and 6b of
these disclosures. The hollow plunger of the atomizer is in the
form of a discharge connection member for the medicinal liquid
contained in the container according to the invention. The
container is fit onto the hollow plunger which is preferably
disposed on the axis of the atomizer. In such a configuration, the
end of the hollow plunger sticks into the discharge location and
thus dips into the medicinal liquid. The sealing location in the
flange sealingly closes off the interior of the container relative
to the outside wall of the hollow plunger. The press fit holds the
container sufficiently mechanically fast on the hollow plunger.
[0101] It may be desirable instead of or in addition to the press
fit (force-locking connection) between the container and the
discharge connection member to provide a releasable, positively
locking connection between the flange which is stable in respect of
shape of the container and the discharge device, for example an
atomizer. A connection of that kind can be in the form of a push-in
snap connection comprising a plurality of snap hooks which are
mounted in a connecting portion in the discharge device. When the
container is fit onto the discharge device the snap hooks engage
into an opening in the flange, for example into a peripherally
extending groove or behind an edge of the flange. The snap noses
are preferably of a round shape or are beveled in both directions
of movement of the container so that an empty container can be
removed with the application of a moderate amount of force and a
full container can be fit onto the discharge device with a moderate
amount of force.
[0102] FIGS. 15a and 15b show a releasable, positively locking,
push-in snap connection between the flange which is stable in
respect of shape of the container and the connecting portion in a
discharge device.
[0103] FIG. 15a is a view in cross-section through a connecting
portion 154 which is disposed in the discharge device and which on
its axis includes discharge connection member 67. Discharge
connection member 67 is surrounded by a plurality of snap hooks 155
with snap noses 156 of round cross-section. Snap hooks 155 are
separated from each other by intermediate spaces and may involve an
azimuthal width of 10 degrees to 60 degrees. A portion 157 which
does not include any snap nose can be provided between two snap
hooks 155. Portion 157 bears in positively locking relationship
against the outside wall of the inserted container.
[0104] FIG. 15b is a side view of the end of a container which is
disposed in a casing 142 and whose flange 148, which is stable in
respect of shape, projects out of casing 142. As shown in FIG. 14,
casing 142 has a peripherally extending groove 158, preferably in
the region of the flange part projecting into casing 142. Snap
noses 156 of the container when fitted into the connecting portion
154 engage into groove 158, whereby the container is releasably and
positively lockingly connected to connecting portion 154.
[0105] FIGS. 16a and 16b show a further embodiment of a releasable,
positively locking, push-in snap connection.
[0106] FIG. 16a is a view in cross-section through a connecting
portion 161 which is disposed in the discharge device and which on
its axis includes discharge connection member 67. Discharge
connection member 67 is surrounded by a plurality of tongue-shaped
snap hooks 162 with snap noses 163 whose flanks are beveled in both
directions of movement of the container. Snap hooks 162 are
disposed at an azimuthal spacing from each other.
[0107] FIG. 16b is a side view of the end of a container which is
disposed in a casing 142 and whose flange 148, which is stable in
respect of shape, projects out of casing 142. When the container is
fitted into connecting portion 154, snap noses 163 engage into
peripherally extending groove 147 of the part, which projects out
of the casing, of the flange 148, whereby the container is
releasably connected to the connecting portion in positively
locking relationship.
[0108] The container according to the invention is particularly
suitable as an interchangeable cartridge for inhalable medicament
solutions in propellant-free atomizers. The filling volume of the
container can be from 0.5 ml to 5 ml, preferably from 1 ml to 4 ml
and particularly preferably from 1 ml to 3 ml or from 2 ml to 4 ml.
Those solutions are discharged in a portion-wise manner with a
respective dosage of 10 .mu.l to 50 .mu.l, preferably from 15 .mu.l
to 20 .mu.l.
[0109] The casing diameter can be from 10 mm to 30 mm, preferably
from 12 mm to 17 mm. The length of the container including the
part, which projects out of the casing, of the flange which is
stable in respect of shape can be from 20 mm to 60 mm, preferably
from 30 mm to 50 mm.
[0110] The container according to the invention serves as a primary
packaging means for accommodating a medicinal liquid which for
example contains a medicament dissolved in a solvent. Suitable
solvents are for example water, ethanol or mixtures thereof. The
medicaments used are for example Berotec (fenoterol-hydrobromide;
1-(3,5-dihydroxyphenyl)-2-[[1-(4-
-hydroxybenzyl)-ethyl]-amino]-ethanol-hydrobromide), Atrovent
(ipratropium bromide), Berodual (combination of
fenoterol-hydrobromide and ipratropium-bromide), Salbutamol (or
Albuterol), Combivent, Oxivent (oxitropium bromide), Ba 679
(tiotropium bromide), BEA 2108 (di-(2-thienyl)-glycol acid tropenol
ester), Flunisolid, Budesonid, Beclomethason and others.
[0111] WO-98/27959 describes stabilized aqueous medicament
preparations for the production of propellant-free aerosols for
inhalation, the disclosure of which is incorporated herein by
reference in its entirety. In particular, reference is directed to
the formulations claimed therein and set forth in the examples.
[0112] Suitable medicament preparations in ethanol solution are set
forth for example in WO-97/01329, the disclosure of which is
incorporated herein by reference in its entirety. In particular,
reference is directed to the active substances specified therein
(see therein pages 2 and 3) and the stabilized formulations claimed
therein.
* * * * *