NO321792B1 - Gas-tight and fluid-tight container for a medical fluid - Google Patents

Description

The invention relates to a gas-tight and fluid-tight container for a medical liquid.

The purpose of the invention is to provide a container intended for single use which can be produced in an economical way, without compromising its usability, as well as to simplify its handling.

In EP 0 182 094 A2, a bottle-shaped packaging is described which consists of a dimensionally rigid outer container and an inner container which is located in this, and which is designed as an easily malleable bag for the filled material. The raw material is produced by constructing two coaxial snake-shaped segments. Both segments consist of two thermoplastic plastic materials that do not enter into any connection with each other. The raw material is expanded in a blow mold. A weld seam is provided on the flat bottom of the inner container. The flat bottom formed in the outer container contains a slit-like opening. In the area of the outlet opening, the outer and inner container are connected to each other in a form-fitting manner. This packaging is essentially produced in one work operation.

The fill material is taken out with the help of a pump placed in the take-out opening, the inner container being deformed by reducing the volume. Via the open slot in the flat bottom of the outer container, air enters the space between the outer container and the deformed inner container, whereby a negative pressure is prevented from occurring in this space. The inner container has no fixed contact with the outer container, except in the area of the outlet opening. The packaging may be equipped with a diving tube which almost reaches the flat bottom, and which holds the inner container in an extended position. This packaging can only be used satisfactorily and emptied completely under specific spatial conditions.

EP 0 620 165 A1 describes a hose bag made of laminated foil. The laminated foil consists of at least an outer plastic foil and an inner metal foil. The hose bag is closed at both ends in a sack-like manner. The hose bag is equipped with a fixed breaking point, and with the help of this it can be opened in a safe way at this point. Such a hose bag serves to store a hardenable mass which is squeezed out of the hose bag by means of an extrusion device.

EP 0 068 653 A1 describes a flexible and collapsible container made of foil, for single use, which is inserted into a suction bottle which can be used several times. One end of the container is open, and the other end is closed by means of a welding seam and equipped with a latch. The tab is clamped in a slot in the bottom of the suction bottle. In this way, the bag-like container is continuously held in an extended position.

The purpose of the present invention is to provide a container for a medical liquid, which is gas- and liquid-tight, whose filling volume is adapted to the intended purpose of use, and which collapses plastically and irreversibly under slight negative pressure in a predetermined manner and can be emptied almost completely.

This purpose is achieved according to the invention with a gas-tight and fluid-tight container as a replaceable cartridge for a medical liquid in a propellant-free nebulizer, characterized in that it comprises

a foil bag (11,21,31) which is closed at both ends, where at least one end is closed with a welding seam (13, 23, 32) which essentially runs transversely to the bag axis, and the foil bag is malleable by an external pressure when there is a differential pressure between the inner space of the container and its surroundings

which is less than 300 hPa (300 mbar),

a dimensionally stable flange (15, 25, 34) which is placed close to the foil bag, and which can be designed as a detachable connecting element for placing

the container on an outlet tube piece (67),

a guide channel (42, 54) in the flange,

in which a blockage (56, 64, 74) is formed in the guide channel and/or a

press fit (55, 66, 77) which encloses the outlet pipe piece,

and an outlet for the liquid in the area of the guide channel into which the hollow piston protrudes in use, so that it is immersed in the medical liquid.

In a further embodiment, the container comprises a foil bag which is

formable at a differential pressure of less than 150 hPa (150 mbar),

preferably below 80 hPa (80 mbar).

The foil bag can be closed at both ends with the help of a welding seam. In this case, the dimensionally stable flange is tightly welded to the side of the foil bag, preferably near one end of the foil bag. However, the foil bag can also be tightly closed at one end using a welding seam and at the other end using the dimensionally stable flange. In this case, one end of the foil bag is welded together with the shape-stable flange, preferably around its circumference.

The dimensionally stable flange can be shaped in different ways. In the case where it is placed at the end of the foil bag to seal it, it can be shaped rotationally symmetrically and be adapted to the size of the end of the foil bag. The dimensionally stable flange can be provided with a guide channel where the outlet pipe piece is introduced and where the outlet pipe piece is located by the attached container.

It may be appropriate to equip the guide channel with a press fit that encloses the outlet pipe piece. The press fit may be a segment of the guide channel, which consists of a smooth inner wall with an inner diameter that deviates only slightly from the outer diameter of the outlet tube piece. In a further embodiment, several protrusions can be found on the inner wall of a segment of the guide channel. The protrusions can, for example, be three symmetrically arranged elongated protrusions that run in the axial direction. Furthermore, several protrusions arranged at an axial distance from each other and which run in the azimuthal direction, which for example form two rings or which consist of several ring segments, may be provided. Furthermore, the protrusions can have a spiral course; they can consist of several spiral segments distributed on the inner wall of the guide channel, or of a spiral segment whose length is greater than the circumference of the guide channel. Such a press fit enables the container to be set up on the outlet pipe piece as well as a sufficiently firm fit of the dimensionally stable flange on the outlet pipe piece. Furthermore, after emptying, the container can be pulled off the outlet pipe without damaging the outlet pipe.

The dimensionally stable flange consists of rubber, metal or plastic, preferably of a thermoplastic plastic material. It may be appropriate to produce the dimensionally stable flange from the same plastic material that the foil bag or the inside of the foil bag is made of.

The welding seam at one or both ends of the foil bag can be designed as a U-, V- or T-shape; it runs substantially across the axis of the bag. It can partly have an extension in the direction of the bag's axis, whereby the defined deformation of the foil bag is favored when liquid is withdrawn.

A sealing point may be provided inside or at one of the ends of the guide channel. The seal can consist of a ring that lies in a groove placed on the inner wall of the guide channel. The cross section of the ring can be O-shaped or substantially square. The ring is optionally equipped with a sealing lip. The ring can consist of an elastomer, of a thermoplastic elastomer or of rubber. The seal closes the filling space in the container, which is attached to the outlet pipe, against the ambient air in a gas- and liquid-tight manner. It allows the empty container to be withdrawn from the outlet pipe. The sealing point is necessary if the sealing effect of the press fit is not sufficient.

The withdrawal point is preferably designed as an insertion point. A pierceable membrane can be provided at the point of insertion, which is pierced when the container is set up on the outlet pipe piece. The membrane is preferably arranged between the sealing point and the liquid space in the foil bag. The pierceable membrane can be placed at one of the ends of, or inside, the guide channel. It is preferably located immediately at the end of the guide channel or near this end, which faces the liquid space. It can be part of the dimensionally stable flange or part of the foil bag. If it is part of the dimensionally stable flange, it can be manufactured at the same time as the dimensionally stable flange. It can consist of the same plastic material as the dimensionally stable flange. The pierceable membrane acts as an original seal for the foil bag's filling space.

In a further embodiment, the withdrawal point can be sealed with a sealing foil. This is pulled off before putting the container on the outlet pipe, or pierced when putting the container on the outlet pipe.

The dimensionally stable flange can consist of one or more parts. The flange, which consists of several parts, can preferably consist of two parts. The outer part of the flange is tightly connected to the foil bag. The outer part contains an opening which is tightly closed with the inner part. The two parts can be screwed together using a screw thread, or be connected to each other using a snap connection ("Schnappverbindung") or via ultrasonic welding. The one-part flange is designed analogously to the two-part flange; however, it does not contain any connecting elements.

The dimensionally stable flange can also be produced with a press fit, a groove for the sealing point and a pierceable membrane.

The foil bag can consist of a hose that has no welding seam that runs in the axial direction of the foil bag. Furthermore, it can be made from a foil and have one or two welding seams that run in the longitudinal direction. It can be designed as a flat bag or as a bag with side pleats. A bag with a seam that runs lengthwise is preferred.

The welding seams on the foil bag can have a width of from 0.7 to 3 mm; their width is chosen according to the requirements for the tightness and durability of the seam. Wide longitudinal seams on the foil bag can be bent around after welding, so that they lie approximately up to the outside of the foil bag, and that the foil bag is only slightly wider than the width of it in the unwelded part between the welding seams.

The foil bag can consist of a foil of metal or metal alloy - preferably of aluminium, gold or copper - or of plastic - preferably a thermoplastic material. In another embodiment, the foil bag can consist of a laminated foil of plastic and metal. The laminated foil preferably consists of two or three foils which are connected to each other. Furthermore, the foil bag can consist of a plastic foil on which it is

applied a layer of metal, glass or ceramic, for example by vapor deposition. The plastic or metal foils are a few micrometers thick. The thickness of the deposition layers of metal, glass or ceramics is in the submicrometer range.

The laminated foil of two foils can consist of a metal foil and a plastic foil which are connected to each other. The metal foil forms the inside or outside of the laminated foil. In another embodiment, the laminated foil consists of two different plastic materials.

The laminated foil of three foils preferably consists of two plastic foils between which there is a metal foil. All three foils are connected to each other. Instead of the metal foil, a layer of glass or ceramics can be provided, e.g. of silicon oxide (SiOx) which has been evaporated onto a plastic foil.

In a further embodiment, the inner foil in the laminated foil consists of a copolymer, for example a polyethylene copolymer of ethylene acrylic acid. For the outer plastic foil on the laminated foil, a plastic material is preferably used, for example polyethylene terephthalate, whose melting temperature is higher than the melting temperature of the plastic material in the inner foil. Hereby, the seam-like welding of the plastic material in the inner foil is made easier during the production of the foil bag.

In the laminated foil, an adhesiveness-improving layer may optionally be provided between two foils.

The foil bag can consist of a plastic foil with a thickness of from 20 µm to 100 µm. Furthermore, it can consist of a laminated foil with an inner foil of plastic material with a thickness of from 20 µm to 100 µm and an outer foil of metal with a thickness of from 8 nm to 20 pm Furthermore, it may consist of a laminated foil with an inner foil of plastic material with a thickness of from 20 u.m to 100 \ m\, a middle foil of metal with a thickness of from 8 u.m tit 20 \ im and an outer foil of plastic material with a thickness of from 10 µm to 40 µm.

The welding seams on the foil bag as well as the welding point between the foil bag and the dimensionally stable flange are produced according to known methods such as thermal welding, ultrasonic welding or induction welding for laminated foils with metal layers, whereby the welding points are preferably compressed in a heated state. Such methods are, for example, indicated in EP 0 111 131 and EP 0 130 239.

A dimensionally stable rubber or metal flange can be connected to the foil bag by gluing or possibly by vulcanization.

The container can be placed in a shape-stable sleeve made of metal or plastic, one end of which is connected to the shape-stable flange in a detachable or non-detachable way, and the other end of which is possibly closed with a bottom. The sleeve can essentially be closed all the way around. However, it contains at least one opening, or there is a slot at the point of connection with the flange. Furthermore, the sleeve can be designed as a dimensionally stable basket with many openings. The container can be placed in a dimensionally stable U-shaped stand instead of in the sleeve, whereby the end of each shaft of the stand is fixed in the dimensionally stable flange, and the shafts are longer than the foil bag.

The container, which is located in a sleeve, is only connected to the sleeve in the dimensionally stable flange. The end closed with a welding seam, or both ends of the foil bag closed with a welding seam, are not connected to the sleeve.

When liquid is transferred from the container into the outlet pipe, the foil bag is folded flat under the influence of the external pressure. Through the opening in the sleeve or through the gap between the sleeve and the dimensionally stable flange, air enters the space between the sleeve and the foil bag and provides pressure equalization. Consequently, no valve is needed in the foil bag, and the liquid in the foil bag does not come into contact with air.

The foil bag is diffusion-proof for the medical liquid and its components as well as for gases. The material for the foil bag and possibly the structure of the laminated foil is chosen according to this. Diffusion-tight in the meaning of the present invention indicates a loss of liquid (measured with ethanoate at room temperature) in the container by 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, especially less than 0.1 mg per day.

The inner foil or the inside of the foil bag is in contact with the filled liquid. For this foil, a material is chosen that is not attacked by the liquid and that does not damage the liquid. This foil is preferably designed as a foil that can be welded.

One of the foils or a vaporized layer, for example, is the diffusion barrier which prevents the diffusion of the liquid or its components as well as the diffusion of gases out of or into the foil bag. It may be appropriate to protect the diffusion barrier against mechanical damage and against tearing of the diffusion barrier when bending the foil by an additional plastic foil applied to the diffusion barrier, so that the diffusion of liquid or gases is permanently prevented.

Since the foil bag is diffusion-proof to gases, the negative pressure in the foil bag that occurs when the liquid is withdrawn cannot be equalized by gas diffusing in, and the foil bag will certainly collapse, even with very slow withdrawal of liquid from the container. The liquid can also be taken out of the foil bag in several sub-quantities, for example 200 doses, spread over a longer period of time, for example three months.

The container, which is located in a sleeve that is essentially closed, is inaccessible from the outside and cannot be damaged during storage and when attached to the outlet pipe piece. The sleeve which is essentially closed, or the sleeve which is designed as a basket with many openings, or the dimensionally stable stand, makes it easier to store the container with the thin-walled foil bag, as well as to handle it when putting it on the outlet pipe piece and when withdrawing the empty one container from the outlet pipe.

The outlet tube piece is, for example, the hollow piston ("der Hohlkolben") in an atomizer device for medical liquids. Such an atomization device is described in DE 195 36 902.5 and in WO 97/12687 (especially in Figures 6a and 6b therein). The hollow piston in this atomizing device is designed as an outlet tube for the medicinal liquid contained in the container according to the invention. The container is attached to the hollow piston which is placed in the axis of the atomizing device, whereby the end of the hollow piston sticks into the outlet and consequently enters the medical liquid. The sealing point in the dimensionally stable flange tightly closes the inner space in the container against the outer wall of the hollow piston. The press fit can hold the container firmly on the punch.

It may be appropriate, instead of, or in addition to, the press fit (properly dimensioned connection) between the container and the outlet pipe piece to provide a removable, form-fitting connection between the dimensionally stable flange of the container and the outlet device, for example an atomizing device. Such a connection can, as a plug-in snap connection, consist of several snap hooks which are placed in a connecting piece in the outlet device. When inserting the container into the outlet device, the snap hooks engage in a recess in the flange, for example in a circumferential groove or behind an edge of the dimensionally stable flange. The lip protrusions are preferably shaped round or bevelled in both directions of the container's movement so that an empty container can be removed with moderately high power consumption and a full container can be inserted into the withdrawal device.

The container according to the invention is particularly suitable as a replaceable cartridge for inhalable drug solutions in propellant gas-free atomization devices. The filling volume in the container can be from 0.5 milliliters to 5 milliliters, preferably from 1 ml to 4 ml and particularly preferably from 1 ml to 3 ml or from 2 ml to 4 ml. These solutions are withdrawn in portions with a dose in each case of from 10 microliters to 50 microliters, preferably from 15 uJ to 20 uJ.

The sleeve diameter can be from 10 mm to 30 mm, preferably from 12 mm to 17 mm. The length of the container including the part of the dimensionally stable flange which protrudes from the sleeve can be from 20 mm to 60 mm, preferably from 30 mm to 50 mm.

The container according to the invention serves as primary packaging for receiving a medical liquid, for example a drug dissolved in a solvent. Water, ethanol or mixtures of these are, for example, suitable as solvents. 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)-glycolic acid tropenol ester), Flunisolide, Budesonide, Beclometasone and others.

In WO 98/27959, stabilized aqueous pharmaceutical preparations for the production of propellant-free aerosols for inhalation are described. Reference is made to the preparations for which a patent has been applied for and indicated in the examples.

Suitable pharmaceutical preparations in ethanolic solution are, for example, indicated in WO 97/01329; in particular, reference is made to the active ingredients stated herein (see pages 2 and 3 herein) as well as the stabilized preparations for which a patent has been applied for.

The container according to the invention has the following advantages:

It can be manufactured economically, is suitable for single use and

need only a small material application.

It can be manufactured sterile, filled sterile and sealed sterile.

It can be used for medicinal products intended for inhalation, and which

available as solutions in ethanol, ethanol/water or water.

The liquid is withdrawn sterile; in this way, air is not drawn into the container. The liquid

does not come into contact with air, oxygen or carbon dioxide. The container according to the invention enables gas bubble-free extraction of it

medical fluid.

It is impervious to the diffusion of liquids and gases.

It can be stored in a filled state depending on the drug for several years and fulfills

the requirements according to all official drug manuals (pharmacopoeias).

It is easily malleable even with a slight negative pressure. In the collapsed state, it remains flat and approximately in an extended position, and it retains

approximately its output length after emptying.

It does not need a valve for pressure equalization after removing part of the liquid. The container can be emptied to an extensive extent, also in an alternating position and in

position above head height.

The foil bag is only connected to the dimensionally stable flange. It is not attached

to the possibly present sleeve.

Its filling volume can be easily regulated by changing the length and/or

the diameter of the foil bag, to a predetermined value within a certain range. It can be filled before closing, before the only or the second welding seam

be placed; a special closing device is not required.

The container can be used without or with a sleeve.

The container, which is in a sleeve, is protected against external damage

The liquid in the foil bag is protected against the influence of light by an opaque

foil bag or by an opaque sleeve that is closed all the way around.

It can be inserted and removed in a withdrawal device in a simple way and without turning movement.

The container according to the invention will be further illustrated with the help of the example figures. Fig. 1-3 show in diagonal projection different embodiments of the foil bag which is closed at both ends. Fig. 1 shows a hose bag 11 with a cylindrical flange 12 and a U-shaped cross seam 13 which closes one end of the hose bag and partly extends in the lengthwise direction of the hose bag. The edge 14 of the flange is connected to the other end of the hose bag. In the axis of the flange there is a hole 15 where a piece of outlet pipe can be inserted. Fig. 2 shows a bag 21 with a seal edge, which consists of two foils which lie on top of each other. It has two welding seams 22 that run in the longitudinal direction of the bag and at one end a welding seam 23 that runs in the transverse direction. The other end is connected to a fish-shaped, dimensionally stable flange 24. The center of the flange is a hole 25 where the outlet pipe piece can be inserted. Fig. 3 shows a side-fold bag 31 with folds on both longitudinal sides, which is closed at both ends with a transverse welding seam 32. On one flat side of the bag, the dimensionally stable flange 33 is welded on. An outlet pipe piece can be inserted into the opening 34 in the flange.

In fig. 4-7 show different embodiments of the dimensionally stable flange in profile. Fig. 4 shows a longitudinal section through a flange 41 in one piece with a cylindrical guide channel 42 designed as a press fit, for a cylindrical outlet pipe piece. The outer end of the guide channel is inclined, and the other end is closed with a membrane 43 placed at an angle in relation to the axis of the flange. This flange is produced in one work operation. The edge of the flange is connected with a foil bag 44. Fig. 5a shows a cylindrical flange consisting of several parts, in longitudinal section, and fig. 5b in cross-section at the line designated A-A in fig. 5a. The lower part 51 is connected to a foil bag 53. The upper part 52 goes into an opening in the lower part. The upper part is provided with a guide channel 54 where there are three oblong lugs 55 which run in the longitudinal direction of the flange as a press fit for an outlet pipe piece, as well as an annular lug 56 as a seal. The lower part 51 and the upper part 52 are welded together in their contact surfaces 57. The inlet opening with the introduction slope in the guide channel is sealed with a sealing foil 58.

In fig. 6 shows a cylindrical flange that is stable in shape and consists of several parts. The lower part 61 is connected to a foil bag 63. The upper part 62 projects into the annular lower die. In the upper part, there is an O-ring 64 as a seal, which is held by means of a pressed-in stop bushing 65. The opening in the stop bushing serves as a guide channel for an outlet pipe piece. On the inside of the seal, in the upper part, there is a knob 66 that goes around, and which is designed as a press fit. An outlet pipe piece 67 is pushed into the guide channel. The container is held by means of the knob-shaped press fit 66 on the outlet pipe piece. The lower part 61 and the upper part 62 are welded together in their contact surfaces 68.

In fig. 7 shows a further flange consisting of several parts. The lower part 71 is connected to a foil bag 73. The upper part 72 is located in the annular lower part which is equipped with a shoulder. The upper part contains a flat ring 74 as a seal, which is held by means of a pressed-in stop bushing 75. Below the flat seal is the guide channel 76 for an outlet pipe piece. The press fit consists of two lugs 77 which rotate like a screw thread inside the guide channel. Near the lower end of the guide channel, a membrane 78 is placed vertically on the flange axis, which is pierced when the container is placed on the outlet pipe piece. The membrane is produced with the upper part in one work operation. The lower part and the upper part are connected to each other in their contact surfaces 79. Fig. 8a shows in cross-section a dimensionally stable flange 81 in one piece, which is placed on the side of a foil bag 82. The flange contains an opening 83 which serves as a press fit for an outlet pipe piece. This flange is sealed on the outside with a sealing foil 84. When placing the container on an outlet pipe piece 85 with a sloping end, the foil bag in the inner end 86 of the guide channel is pierced. Fig. 8b shows a cross-section through a laminate foil with three layers, which is common in the trade, and of which the foil bag consists. The inner foil 87 consists of polyethylene

(40 nm thick), the middle foil 88 is the diffusion barrier of aluminum (12 nm thick), and the outer foil 89 consists of polyethylene terephthalate (12 µm thick).

In fig. 9-11 show different designs of the welding seam with which the foil bag is closed at at least one end, in side view and in cross-section (fig. 9b and 10b) or in ground view of the bag end (fig. 11b). Fig. 9a shows a U-shaped welding seam 91 which partly extends in the longitudinal direction of the foil bag 92 and on one side merges into a welding seam 93 on the foil bag which runs in the longitudinal direction. Fig. 9b shows a cross-section through the foil bag at the line designated B-B in fig. 9a. In the welding seams, the inner layer of the folded multi-layer foil 94 is welded together. Fig. 10a shows a V-shaped welding seam 101, which partly extends in the longitudinal direction of the foil bag. In this case, the foil bag consists of a hose foil without a seam in the longitudinal direction. Fig. 10b shows a cross-section through the foil bag at the line denoted C-C in fig. 10a. The folded single-layer foil 103 is welded together in the weld seam. Fig. 11 a shows a T-shaped welding seam 111 in side view, and fig. 11 b in plan view of the welded end of the foil bag 112. The three sides in the T-seam are together as long as the flat folded foil bag outside the T-seam is wide.

The foil bag, which is welded together with a U-, V- or T-seam, is not larger in the cross-seam area than the diameter of the sleeve, where the foil bag is possibly inserted.

The manufacture and filling of the container according to the invention is shown schematically in fig. 12 and 13 in diagonal projection.

A folded foil strip is provided on the cut sides with a welding seam in the longitudinal direction, divided into segments and formed into a hose (fig. 12a). The lower part of a cylindrical flange in two parts, produced by the injection molding process, is welded to one end of such a hose segment. The other end of the segment is welded together with a U-shaped cross seam (fig. 12b and 12c). The finished container (fig. 12c) is pushed into a cylindrical aluminum sleeve (fig. 12d), the edge of which is pressed into a groove in the edge of the cylindrical flange. The container is thereby firmly connected to the sleeve. The empty container located in the sleeve is filled with a fluid through the lower part of the flange which has an opening (fig. 12e). After filling, the upper part of the flange is pressed into the lower part (fig. 12f), and the two are tightly connected to each other. The finished part (fig. 12g) is ready to be attached to a piece of outlet pipe.

A further manufacturing method is shown in fig. 13. A segment of a foil tube provided with a seam in the longitudinal direction (Fig. 13a) is connected at one end with a flange in one piece, which is closed with a sealing foil (Fig. 13b). The container is filled with a fluid through the open other end of the foil hose (fig. 13c). The open end of the foil tube is closed with a U-shaped cross seam (fig. 13d). The filled container is pushed into a plastic sleeve (fig. 13e). The edge of the plastic sleeve is pressed against the edge of the dimensionally stable flange. The finished part (fig. 13f) is ready to be attached to a piece of outlet pipe.

In fig. 14 shows a partial cross-section of a typical container according to the invention 141 filled with a fluid, which is located in a metal sleeve 142. The foil bag is welded together at one end with a U-seam 143, and is welded together with the edge 144 at its other end of the lower part 145 of a cylindrical flange in two parts. The metal sleeve has a bottom 146 where there is a hole through which air can enter the space between the metal sleeve and the foil bag. The open end of the sleeve is pressed into a groove 147 in the edge of the lower part 145. The sleeve is firmly connected to the flange. The upper part 148 of the flange is inserted into an opening in the lower part. The lower part and the upper part are connected by a snap closure 149 and equipped with a flat seal 150. The guide channel 151 is closed at its inner end with a membrane 152 and sealed at its outer end with a sealing foil 153.

The metal sleeve shown in fig. 14 consists of aluminium. It is 43 mm long and has an outer diameter of 17 mm and a wall thickness of 0.5 mm. The flange, which consists of two parts, consists of polyethylene and is produced by injection molding. The upper part of the flange, including the membrane, is produced in one process step. The guide channel in the upper flange part has an inner diameter of 2.5 mm at the place of the press fit and fits tightly on an outlet pipe piece.

In fig. 15a and 15b, a removable form-fitting plug-in snap connection is shown between the form-stable flange on the container and the connecting piece in an outlet device.

Fig. 15a shows a cross-section through the connecting piece 154 which is located in the outlet device, and which contains the outlet pipe piece 67 on its axis.

The outlet pipe piece is surrounded by several snap hooks 155 with snap projections 156 with a round cross-section. The bib hooks are separated from each other by spaces and can have an azimuthal width of from 10 degrees to 60 degrees. Between two snap hooks 155 there may be a segment 157 which does not contain any snap projection. This segment conforms to the outer wall of the inserted container.

Fig. 15b shows a side view of the end of a container which is located in a sleeve 142, whose dimensionally stable flange 148 protrudes from the sleeve. The sleeve has - in accordance with fig. 14 - preferably in the area of the part of the flange that enters the sleeve, a circumferential groove 158 into which the snap projections 156 in the container inserted in the connecting piece 154 engage, whereby the container is connected to the connecting piece in a releasable and form-fitting manner.

In fig. 16a and 16b, a further embodiment of a removable, form-fitting, insertable snap connection is shown. Fig. 16a shows a cross-section through the connecting piece 161 which is located in the outlet device, and which on its axis contains the outlet tube piece 67. The outlet tube piece is surrounded by several tongue-shaped snap hooks 162 with snap projections 163, the flanks of which slope off in both directions of movement for the container. The bib hooks are placed at an azimuthal distance from each other. Fig. 16b shows a side view of the end of a container which is located in a sleeve 142, whose dimensionally stable flange 148 protrudes from the sleeve. The lip projections 163 engage in the circumferential groove 147 in the part of the dimensionally stable flange 148 which protrudes from the sleeve, at the container which is inserted in the connecting piece 154, whereby the container is connected to the connecting piece in a detachable and form-fitting manner.

Claims (35)

1. Gas-tight and fluid-tight container as a replaceable cartridge for a medical liquid in a propellant-free atomizer, characterized in that it comprises a foil bag (11,21,31) which is closed at both ends, where at least one end is closed with a welding seam (13, 23, 32) which essentially runs transversely to the bag axis, and the foil bag is formable by an external pressure when there is a differential pressure between the inner space of the container and its surroundings which is less than 300 hPa (300 mbar), a dimensionally stable flange (15, 25, 34) which is placed close to the foil bag, and which can be designed as a detachable connection element for placing the container on an outlet pipe piece (67), - a guide channel (42, 54) in the flange, in which a blockage (56, 64, 74) is formed in the guide channel and/or a press fit (55, 66, 77) which encloses the outlet pipe piece, and an outlet point for the liquid in the region of the guide channel as the hollow the plunger sticks in during use so that it is submerged in the medicinal fluid. 2. Container according to claim 1, characterized in that it comprises a foil bag which is formable at a differential pressure of less than 150 hPa (150 mbar), preferably less than 80 hPa (80 mbar). 3. Container according to claims 1 or 2, characterized in that it comprises a foil bag (31) which is closed at both ends by means of a welding seam (32), and a dimensionally stable flange (34) which is tightly fitted to the foil bag (31). 4. Container according to claims 1 or 2, characterized in that it comprises a foil bag (11, 21) which is tightly closed at one end by means of a welding seam (13, 23) and at the other by means of a dimensionally stable flange (12, 24). 5. Container according to claims 1 to 4, characterized in that it comprises a dimensionally stable, preferably rotationally symmetrical, flange (41, 51, 61) if size is adapted to the size of the foil bag, and with which the foil bag is closed at one end. 6. Container according to claims 1 to 5, characterized in that it comprises a guide channel (42, 54) with a sealing point (56, 64, 74). 7. Container according to claims 1 to 6, characterized in that it comprises a dimensionally stable flange with a press fit (55, 66, 77) inside the guide channel which encloses the outlet pipe piece. 8. Container according to claims 1 to 7, characterized in that it comprises a dimensionally stable flange consisting of a thermoplastic plastic material. 9. Container according to claims 1 to 8, characterized in that it comprises a welding seam (91, 101) which is designed in a U- or V-shape and which essentially runs across the bag axis, and which partly extends in the direction of the bag axis, or a T-shaped welded seam (111). 10. Container according to claims 1 to 9, characterized in that it comprises a sealing point in the form of a ring (54, 76) of elastic material which lies in a groove. 11. Container according to claims 1 and 10, characterized in that it comprises a withdrawal point which is designed as an insertion point. 12. Container according to claims 1 to 11, characterized in that it comprises an outlet which is provided with a pierceable membrane. 13. Container according to claims 1 to 12, characterized in that it comprises an outlet point which is provided with a pierceable membrane, in which the membrane (48, 78) is placed at the end of, or inside, the guide channel, or the membrane (86) is part of the foil bag. 14. Container according to claims 1 to 13, characterized in that it comprises a withdrawal point which is sealed with a sealing foil (58, 84, 151). 15. Container according to claims 1 to 14, characterized in that it comprises a foil bag (11, 21, 31) consisting of a foil made of plastic, metal or metal alloy, or a foil bag made of a laminated plastic and metal foil, or a foil bag made of plastic foil with a layer of metal, glass or ceramic. 16. Container according to claims 1 to 15, characterized in that it comprises a foil bag with an inner foil of plastic and an outer foil of metal, or two foils of different plastic materials. 17. Container according to claims 1 to 15, characterized in that it comprises a foil bag with. an inner foil of a copolymer, preferably a polyethylene copolymer, of ethylene acrylic acid, and a diffusion-tight central foil of metal or plastic, or et diffusion-tight middle layer of metal, glass or ceramic, and an outer foil of plastic, the melting temperature of which is higher than the melting temperature of the inner foil, which is preferably of polyethylene terephthalate. 18. Container according to claims 1 to 17, characterized in that it comprises a foil bag of a plastic foil with a thickness of between 20 µm and 100 u.m, or a foil bag of a laminated foil with an inner plastic foil with a thickness of between 20 nm and 100 µm, and an outer foil of metal with a thickness of between 8 µm and 20 µm, or a foil bag consisting of a laminated foil with a plastic inner foil with a thickness of between 20 µm and 100 µm, a central foil of metal with a thickness of between 8 µm and 20 µm, and an outer foil of plastic with a thickness of between 10 µm and 40 µm. 19. Container according to claims 1 to 18, characterized in that it has a filling capacity of between 0.5 milliliters and 5 milliliters, preferably between 1 ml and 4 ml. 20. Container according to claims 1 to 19, characterized in that it has a filling capacity of between 1 ml and 4 ml, or of between 2 ml and 4 ml. 21. Container according to claims 1 to 20, characterized in that it is located in a dimensionally stable metal or plastic sleeve (142), which is connected to the flange. 22. Container according to claims 1 to 21, characterized in that it is located in a shape-stable sleeve with a diameter of between 10 mm and 30 mm, preferably between 12 mm and 17 mm. 23. Container according to claims 1 to 22, characterized in that it is located in a shape-stable sleeve from which the shape-stable flange projects, in which the total length is between 20 mm and 60 mm, preferably between 30 mm and 50 mm. 24. Container according to claims 1 to 23, characterized in that the sleeve is essentially closed all the way around, contains an opening, or where there is a gap at the point of connection with the flange, or that the sleeve is designed as a basket with many openings, or that it is in the form of a stand (stirrup member). 25. Container according to claims 1 to 24, characterized in that it comprises a circumferential groove (158; 147) in the dimensionally stable flange. 26. Container according to one of claims 1 to 25, characterized in that the atomizer is a dispensing instrument which is equipped with a connecting piece, into which the container is inserted by means of a removable, positive, pluggable snap connection between the connecting piece (154; 161) in the outlet device and the dimensionally stable flange (148) on the container. 27. Container according to claim 26, characterized in that it comprises a circumferential groove (158; 147) in the dimensionally stable flange, where the snap projections (156; 163) on the snap hooks (155, 162) which are placed on the connecting piece (154; 161) engage in at the container inserted in the connector. 28. Use of a gas-tight and fluid-tight container as a replaceable cartridge for a medical liquid in a propellant-free atomizer, comprising a foil bag (11, 21, 31) which is closed at both ends, where at least one end is closed with a welding seam (13, 23, 32) which essentially runs transversely to the bag axis, and the foil bag is formable by an external pressure when there is a differential pressure between the inner space of the container and its surroundings which is less than 300 hPa (300 mbar), a dimensionally stable flange (15, 25, 34) which is placed close to the foil bag, and which can be designed as a detachable connecting element for placing the container on an outlet pipe piece (67), a guide channel (42, 54) in the flange, in which a blockage (56, 64, 74) is formed in the guide channel and/or a press fit (55, 66, 77) enclosing the outlet tube piece, - and an outlet location for the fluid in the area of the guide channel into which the hollow piston protrudes in use, so that it is immersed in the medical fluid, as a replaceable cartridge for a medical fluid in a propellant-free atomizer, which has an outlet connector in the form of a hollow piston. 29. Use of the container according to claim 28, as primary packaging for a medical liquid which is taken out of the foil bag in many sub-quantities. 30. Use of the container according to claims 28 to 29, as primary packaging for a medical liquid which is taken out in portion-wise doses of between 10 microliters and 50 microliters, preferably between 15:1 and 20:1. 31. Use of the container according to claims 28 to 30, as a cartridge containing an inhalable medicinal preparation which is present as a solution in ethanol or in ethanol/water or in water. 32. Use of the container according to claims 28 to 31, as a cartridge containing an inhalable medicinal preparation with an active ingredient or with several active ingredients, such as 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)-glycolic acid tropenol ester), Beclometasone, Flunisolide, Budesonide. 33. Use of the container according to claims 28 to 32, with a pharmaceutical preparation for the treatment of diseases using inhalable active ingredients. 34. Use of the container according to any one of claims 1-33. 35. Propellant-free nebulizer with a replaceable cartridge in the form of a container for a medical liquid with features as defined in one of claims 1 to 32, in which the inhaler has an outlet tube piece in the form of a hollow piston (67) for releasing the fluid from the container.