IL137991A - Container for a medicinal liquid - Google Patents

Abstract

A gas-tight and fluid-tight container for use as a replaceable cartridge for a medicinal fluid in a propellant-free atomiser, which has a discharge connection piece (67) in the form of a hollow piston, wherein the container comprises: a film bag (63) which is closed at both ends, wherein at least one end is closed by a weld seam which extends substantially transversely to the axis of the bag, and the film bag is deformable by external pressure when there is a pressure differential between the internal space of the container and its surroundings of less than 300 hPa; a flange (61, 62) of stable shape which is arranged sealingly on the film bag and which can be designed as a detachable connection element for placing the container on a discharge connection piece, a guide passage in the flange, wherein a sealing location is formed in the guide passage and/or a force fit embracing the discharge connection piece, and a discharge location for the fluid in the region of the guide passage into which the hollow piston plunges during use, so that it is immersed in the medicinal fluid. 1471 א' בתמוז התשס" ד - June 20, 2004

Description

Niai Container for a medicinal liquid Boehringer Ingelheim International GmbH C. 126831 Container for a medical liquid The invention concerns a container for a medical liquid, the container being gas- and liquid-tight.

The invention aims to make the production of such a container which is intended for one-trip use more economical without adversely affecting its usefulness, and to simplify handling thereof.

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 moulding mould. 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 positively locking relationship in the region of the discharge opening. That pack is produced substantially in one working operation.

The filling material is discharged from the container by means of a pump which is disposed in the discharge opening, in which case the inner container suffers deformation 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 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.

A tubular bag of composite foil is described in EP-0 620 165 Al. 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.

EP-0 068 653 Al 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.

The object of the present invention is to provide a container for a medical liquid, which container is gas- and liquid-tight and whose filling volume is suited to the intended purpose of use and which at a given reduced pressure collapses plastically and irreversibly in a predetermined manner and can be approximately completely emptied.

In accordance with the invention that object is attained by a container for a medical liquid, which container is gas - and liquid-tight and which is characterised by: - a foil .bag which is closed at both ends and which, at a differential pressure between the interior of the container and its surroundings below 300 hPa (300 mbar), is deformable by the external pressure and collapses, and - a flange which is stable in respect of shape and which is sealingiy mounted to the foil bag and which is in the form of a releasable connecting element for fitting the container on to a discharge connection member, and - at least one welded seam with which the foil bag is closed at at least one end and which extends substantially transversely with respect to the axis of the bag, and - a sealing location in the flange which is stable in respect of shape, and - a discharge location for the liquid in the region of the flange which is stable in respect of shape.

In a further embodiment the collapsible foil bag can already be deformed by and collapsed due to the external pressure at a differential pressure of below 150 hPa (150 mbar) or preferably below 80 hPa (80. mbar).

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 sealingiy welded to the side of the foil bag, preferably in the proximity of an end of the foil bag. The foil bag however may also be sealingiy closed at one end by a welded seam and at the other end by the flange which is stable in respect of shape. In this case the one end of the foil bag is welded to the flange which is stable in respect of shape, preferably on the periphery thereof.

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 which is stable in respect of shape can be provided with a guide passage into which the discharge connection member can be introduced and in which the discharge connection member is disposed when the container is fitted on.

It may be desirable to provide the guide passage with a press fit which embraces the discharge connection member. The press fit can be 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; 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.

The flange which is stable in respect of shape comprises rubber, metal or plastic material, preferably a thermoplastic material. It may be desirable to produce the flange which is stable in respect of shape from the same plastic material as that forming the foil bag or the inward side of the foil bag.

The welded seam at one or both ends of the foil bag can be of a U-, V- or T-shaped configuration; it extends substantially transversely with respect to the axis of the bag. It can extend 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.

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 0-shaped or substantially rectangular cross-section. The ring is possibly provided with a sealing lip. The ring can comprise 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- and liquid-tightly in relation to the ambient air. It 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.

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 which is stable in respect of shape, 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. It can comprise 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.

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.

The flange which is stable in respect of shape can be in one or more parts. The multi-part flange can preferably be a two-part flange. The 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 they can be connected together by means of a snap-action connection or by ultrasound welding. The one-part flange is of a similar configuration to the two-part flange, but it does not include any connecting elements.

The flange which is stable in respect of shape can be produced at the same time with a press fit, a groove for the sealing location, and a pierceable membrane.

The foil bag can comprise a tube which does not have a welded seam extending in the axial direction of the foil bag. It can also be produced from one foil and may have one or two welded seams extending in the longitudinal direction. It can be in the form of a flat bag or in the form of a bag with side folds. A bag with a welded seam extending in the longitudinal direction is preferred.

The welded seams on the foil bag may be between 0.7 mm and 3 mm in width; their width is selected according to the demands made in terms of sealing integrity and durability of the seam. Wide longitudinal seams on the foil bag can be bent over after the welding operation so that for example they bear externally against the foil bag and the foil bag is only a little wider than its width in the unwelded part between the welded seams.

The foil bag can comprise a foil of metal or metal alloy - preferably, aluminium, gold or copper - or plastic material - preferably a thermoplastic material. In another embodiment the foil bag can comprise 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 vapour deposition. The foils of plastic material or metal are some micrometers thick. The thickness of the vapour-deposition layers of metal, glass or ceramic is in the sub-micrometer range.

The composite foil consisting of two foils can comprise a metal foil and a plastic foil which are joined together. 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.

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 (SiOx), which is produced by vapour deposition on a plastic foil.

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.

In the composite foil, a bonding layer may possibly be provided between two foils.

The foil bag can comprise a plastic foil of a thickness of between 20 pm and 100 pm. It may also comprise a composite foil with an inner foil of plastic material of a thickness of between 20 pm and 100 pm and an outer foil of metal of a thickness of between 8 pm and 20 pm. It may also comprise a composite foil with an inner foil of plastic material of a thickness of between 20 pm and 100 pm, a central foil of metal of a thickness of between 8 pm and 20 pm and an outer foil of plastic material of a thickness of between 10 pm and 40 pm.

The welded seams on the foil bag and the weld location between the foil bag and the flange which is stable in respect of shape 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. Processes of that kind are set forth for example in EP-0 111 131 and EP-0 130 239. A flange which is stable in respect of shape, comprising rubber or metal, can be connected to the foil bag by adhesive or possibly by vulcanisation.

The container may be disposed in a casing which is stable in respect of shape, comprising metal or plastic material, of which one end is releasably or non-releasably connected to the flange which is stable in respect of shape, while the other end of the casing is possibly closed with a bottom. The casing can be substantially closed all around. It includes however at least one opening or there is a gap at the location of connection 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. 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 which is stable in respect of shape, and the limbs are longer than the foil bag.

The container disposed in a casing is connected to the casing only at the flange which is stable in respect of shape. 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.

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 which is stable in respect of shape, into the space between the casing and the foil bag, and provides for pressure equalisation. That means that no valve is required in the foil bag and the liquid in the foil bag does not come into contact with air.

The foil bag is diffusion-tight in relation to the medical liquid and its constituents and in relation to gases. The material for the foil bag and possibly the structure of the composite foil are suitably selected. 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.

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.

One of the foils or a layer which is applied for example by vapour deposition is the diffusion barrier which prevents diffusion of the liquid or the constituents thereof and 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 thereof when the foil is bent by means of a further plastic foil which is applied to the diffusion barrier so that the diffusion of liquid or gases remains durably prevented.

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 thereinto and 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.

The container which is disposed in a substantially closed casing is inaccessible from the exterior and cannot be damaged when it is stored and when it is fitted on to the discharge connection member. The substantially closed casing or 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 and handling thereof when it is fitted on to the discharge connection member and when the empty container is withdrawn from the discharge connection member.

The discharge connection member is for example the hollow plunger of an atomiser for medical liquids. An atomiser of that kind is described in DE-195 36 902.5 and in WO-97/12687 (specifically in Figures 6a and 6b thereof). The hollow plunger of that atomiser is in the form of a discharge connection member for the medical liquid contained in the container according to the invention. The container is fitted on to the hollow plunger which is preferably disposed on the axis of the atomiser, in which case the end of the hollow plunger sticks into the discharge location and thus dips into the medical liquid. The sealing location in the flange which is stable in respect of shape sealingly closes off the interior of the container relative to the outside wall of the hollow plunger. The press fit can hold the container mechanically fast on the hollow plunger.

It may be desirable, in place of or in addition to the press fit (force-locking connection) between the container and the discharge connection memory, 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 atomiser. A connection of that kind can comprise, in the form of a plug-in snap connection, a plurality of snap hooks which are disposed in a connecting portion in the discharge device. When the container is fitted into 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 which is stable in respect of shape. The snap noses are preferably round in shape or bevelled in both directions of movement of the container in order to be able to remove an empty container with the application of a moderate amount of force and in order to be able to insert a full container into the discharge device.

The container according to the invention is particularly suitable as a replaceable cartridge for inhalable medicament solutions in propellent gas-free atomisers. The filling volume of the container can be between 0.5 milliliters and 5 milliliters, preferably between 1 ml and 4 ml and particularly preferably between 1 ml and 3 ml or between 2 ml and 4 ml . Those solutions are discharged in a portion-wise manner with a dosage amount in each case of between 10 microliters and 50 microliters, preferably between 15 μΙ and 20 μΙ.

The casing diameter can be between 10 mm and 30 mm, preferably between 12 mm and 17 mm. The length of the container including the part of the flange which is stable in respect of shape, that projects from the casing, can be between 20 mm and 60 mm, preferably between 30 mm and 50 mm.

The container according to the invention serves as a primary-packaging means for accommodating a medical 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; l-(3,5-dihydroxy-phenyl)-2-[[l-(4-hydroxy-benzyl)-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 tropenolester), Flunisolid, Budesonid, Beclomethason and others.

WO-98/27959 describes stabilised aqueous medicament preparations for the production of propellent gas-free aerosols for inhalation. Reference is directed to the formulations claimed therein and set forth in the Examples.

Suitable medicament preparations in ethanol solution are specified for example in WO-97/01329, in particular attention is directed to the active substances referred to therein (see therein pages 2 and 3) and the stabilised formulations claimed therein.

The container according to the invention has the following advantages: - It is economical to produce, it is suitable for one-trip use and it requires only a small amount of material usage.

- It can be produced in a sterile condition, filled in a sterile condition and sealed in a sterile condition.

- It can be used for medicaments which are intended for inhalation and which occur in the form of solutions in ethanol, ethanol/water or water.

- The liquid is discharged under sterile conditions; when that happens no air is sucked into the container. The liquid does not come into contact with air, oxygen or carbon dioxide.

- The container according to the invention permits the medical liquid to be removed in a condition of being free from gas bubbles.

- It is sealed in relation to the diffusion of liquids and gases.

- It is storable in the filled condition depending on the respective medicament over several years and satisfies the requirements of all official pharmacopoeiae.

- It is already easily deformable at a slightly reduced pressure. In the collapsed condition it remains flat and approximately stretched out, it approximately retains its initial length after emptying.

- It does not require a valve for pressure equalisation after a part of the liquid has been discharged.

- The container can be substantially emptied, even in a fluctuating position and when it is upside down.

- The foil bag is only connected to the flange which is stable in respect of shape. It is not fixed to the casing if such is provided.

- Its filling volume can be easily adjusted to a predetermined value within a certain range by changing the length and/or the diameter of the foil bag.

- It can be filled prior to closure, before the single or the second welded seam is produced; there is no need for a separate closure means.

- The container can be used with or without a casing.

- The container disposed in a casing is protected from external damage.

- The liquid in the foil bag is protected from the effect of light by an opaque foil bag or by an opaque casing which is closed all around.

- It can be fitted into and removed from a discharge device easily and without a rotary movement.

The container according to the invention is described in greater detail with reference to the Figures by way of example.

Figures 1 to 3 are perspective views of various embodiments of the foil bag which is closed at both ends.

Figure 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 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.

Figure 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 centre of the flange is a hole 25 into which a discharge connection member can be inserted.

Figure 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.

Figures- 4 to 7 are sectional views of various embodiments of the flange which is stable in respect of shape.

Figure 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 bevelled while the other end is closed by a membrane 43 which is disposed inclinedly with respect to the axis of the flange. That flange is produced in one working operation. The edge of the flange is connected to a foil bag 44.

Figure 5a shows a multi-part cylindrical flange in longitudinal section and 5b shows a cross-section on the line identified at A-A in Figure 5a. The lower part 51 is connected to a foil bag 53. The upper part 52 fits in an opening in the lower part. The upper part is provided with a guide passage 54 in which there are three elongate ridges 55 extending in the axial direction of the flange as a press fit for a discharge connection member and an annular ridge 56 as a seal. The lower part 51 and the upper part 52 are welded together at their contact surface 57. The entry opening with inclined insertion surface of the guide passage is sealed off by a sealing foil 58.

Figure 6 shows a multi-part cylindrical flange which is stable in respect of shape. The lower part 61 is connected to a foil bag 63. The upper part 62 projects into the annular lower part. Disposed in the upper part as a seal is an O-ring 64 which is held in place by a gland 65 that is pressed into position. The opening in the gland 65 serve as a guide passage for a discharge connection member. Disposed on the inside of the seal on the upper part is a peripherally extending ridge 66 which is in the form of a press fit. A discharge connection member 67 is inserted into the guide passage. The container is held on the discharge connection member by means of the ridge-shaped press fit 66. The lower part 61 and the upper part 62 are welded together at their contact surface 68.

Figure 7 shows a further multi-part flange. The lower part 71 is connected to .a foil bag 73. The upper part 72 is disposed in the annular lower part which is provided with a shoulder. The upper part includes a flat ring 74 as a seal, which is held in place by a gland 75 which is pressed into position. Disposed beneath the flat seal is the guide passage 76 for a discharge connection member. The press fit comprises two ridges 77 within the guide passage, extending therearound in a screwthread-like configuration. Provided in the proximity of the lower end of the guide passage, perpendicularly to the axis of the flange, is a membrane 78 which is pierced when the container is fitted on to the discharge connection member. The membrane is produced with the upper part in one working operation. The lower part and the upper part are connected together at their contact surface 79.

Figure 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. The flange has an opening 83 which serves as a press fit for a discharge connection member. That flange is sealed on its outward side by a sealing foil 84. When the container is fitted on to a discharge connection member 85 with a bevelled end, the foil bag is pierced at the inner end 86 of the guide passage.

Figure 8b shows a view in cross-section through a commercially available laminate foil having three layers making up the foil bag. The inner foil 87 comprises polyethylene (40 pm in thickness), the central foil 88 is the diffusion barrier of aluminium (12 pm in thickness) and the outer foil 89 comprises polyethylene terephthalate (12 pm in thickness).

Figures 9 to 11 show various embodiments of the welded seam with which the foil bag is closed at at least one end, as a side view and in cross-section (Figures 9b and 10b) or as a plan view on to the end of the bag (Figure lib).

Figure 9a shows a U-shaped welded seam 91 which extends partially in the longitudinal direction of the foil bag 92 and on one side goes into a welded seam 93 of the foil bag, with the welded seam 93 extending in the longitudinal direction. Figure 9b is a view in cross-section through the foil bag at the line identified by B-B in Figure 9a. The inner layer of the folded multi-layer foil 94 is welded in the welded seams.

Figure 10a shows a V-shaped welded seam 101 which extends partially in the longitudinal direction of the foil bag. In this case the foil bag comprises a tubular foil without a longitudinal seam. Figure 10b shows a view in cross-section through the foil bag at the line identified by C-C in Figure 10a. The folded single-layer foil 103 is welded in the welded seam. Figure 11a shows a T-shaped welded seam 111 as a side view while Figure lib is a plan view on to the welded end of the foil bag 112. The three limbs of the T-shaped seam are overall as long as the foil bag, in the condition of being collapsed flat, outside the T-shaped seam, is wide.

The foil bag which is welded with a U-, V- and 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.

Manufacture and filling of the container according to the invention is diagrammatically illustrated in perspective views in Figures 12 and 13.

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 (Figure 12a). The lower part, which is produced by an injection moulding process, of a two-part cylindrical flange is welded to the one end of a tubular portion of that kind. The other end of the portion is welded with a U-shaped transverse seam (Figures 12b and 12c). The finished container (Figure 12c) is pushed into a cylindrical casing of aluminium (Figure 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 filled with a fluid through the lower part of the flange, which is provided with an opening (Figure 12e). After the filling operation the upper part of the flange is pressed into the lower part (Figure 12f) and the two parts are sealingly joined together. The finished part (Figure 12g) is ready for being fitted on to a discharge, connection member.

A further production process is illustrated in Figure 13. A portion of a foil tube provided with a longitudinal seam (Figure 13a) is connected at its one end to a one-piece flange which is closed by a sealing foil (Figure 13b). The container is filled with a fluid through the other open end of the foil tube (Figure 13c). The open end of the foil tube is closed by a U-shaped transverse seam (Figure 13d). The filled container is fitted into a casing of plastic material (Figure 13e). The edge of the plastic casing is snap-fitted on to the edge of the flange which is stable in respect of shape. The finished part (Figure 13f) is ready for being fitted on to a discharge connection member.

Figure 14 is a partly cross-sectional view of a typical container 141 according to the invention which is filled with a fluid and which is disposed in a metal casing 142. At its one end the foil bag is welded by a U-shaped seam 143 while at its other end it is welded to the edge 144 of the lower part 145 of a two-part cylindrical flange which is stable in respect of shape. The metal casing has a bottom 146 in which there is a hole through which air can pass into the space between the metal casing and the foil bag. The open end of the casing is pressed into a groove or channel 147 in the edge of the lower part 145. The casing is fixedly connected to the flange. The upper part 148 of the flange is fitted into an opening in the lower part. The lower part and the upper part are connected by a snap-action closure 149 and provided with a flat seal 150. The guide passage 151 is closed at its inner end by a membrane 152 and sealed at its outer end by a sealing foil 153.

The metal casing shown in Figure 14 comprises aluminium. It is 43 mm in length and is of an outside diameter of 17 mm and has a wall which is 0.5 mm in thickness. The two-piece flange comprises polyethylene and is produced by an injection moulding process. The upper part of the flange including the membrane is produced in one step in the process. The guide, passage in the upper part of the flange is of an inside diameter of 2.5 mm at the location of the press fit and fits firmly on to a discharge connection member.

Figures 15a and 15b show a releasable, positively locking plug-in snap connection between the flange of the container, which is stable in respect of shape, and the connecting portion in a discharge device.

Figure 15a is a view in cross-section through the connecting portion 154 which is provided in the discharge device and which on its axis contains the discharge connection member 67. The discharge connection member 67 is surrounded by a plurality of snap hooks 155 with snap noses 156 of round cross-section. The snap hooks are separated from each other by intermediate spaces and can involve an azimuthal width of between 10 degrees and 60 degrees. A portion 157 which does not include any snap nose can be provided between snap hooks 155. That portion 157 bears in positively locking relationship against the outside wall of the inserted container.

Figure 15b is a side view showing 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 the casing. As shown in Figure 14, preferably in the region of the part of the flange which projects into the casing, the casing has a peripherally extending groove 158 into which engage the snap noses 156 of the container when fitted into the connecting portion 154, whereby the container is connected releasably and positively lockingly to the connecting portion.

Figures 16a and 16b show a further embodiment of a releasable positively locking plug-in snap connection.

Figure 16a shows a view in cross-section through the connecting portion 161 which is disposed in the discharge device and which on its axis includes the discharge connection member 67. The discharge connection member is surrounded by a plurality of tongue-shape snap hooks 162 with snap noses 163 whose flanks are bevelled in both directions of movement of the container. The snap hooks are disposed at an azimuthal spacing from each other.

Figure 16b is a side view showing 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 the casing. When the container is fitted into the connecting portion 154 the snap noses 163 engage into the peripherally extending groove 147 of the part, which projects out of the casing, of the flange 148 which is stable in respect of shape, whereby the container is connected releasably and positively lockingly to the connecting portion.

Claims (33)

20 137991/3 CLAIMS:

1. A gas-tight and fluid-tight container for use as a replaceable cartridge for a medicinal fluid in a propellant-free atomiser, which has a discharge connection piece in the form of hollow piston, wherein the container comprises: a film bag which is closed at both ends, wherein at least one end is closed by a weld seam which extends substantially transversely to the axis of the bag, and the film bag is deformable by external pressure when there is a pressure differential between the internal space of the container and its surroundings of less than 300 hPa; a flange of stable shape which is arranged sealingly on the film bag and which can be designed as a detachable connection element for placing the container on a discharge connection piece, a guide passage in the flange, wherein a sealing location is formed in the guide passage and/or a force fit embracing the discharge connection piece, and a discharge location for the fluid in the region of the guide passage into which the hollow piston plunges during use, so that it is immersed in the medicinal fluid.

2. The container according to Claim 1 characterised by: a film bag which is deformable when there is a pressure differential of below 150 hPa, preferably of below 80 hPa.

3. The container according to Claims 1 and 2, wherein the container is characterised by: a film bag which is closed at both ends by a weld seam, and a flange of stable shape which is applied sealingly to the film bag.

4. The container according to Claims 1 and 2, wherein the container is characterised by: a film bag which is sealingly closed at one end by a weld seam and at the other end by the flange of stable shape.

5. The container according to Claims 1 to 4, wherein the container is characterised by: 21 137991/3 a flange of stable shape which is preferably rotationally-symmetrical and which is adapted in size to the size of the film bag, and by means of which the film bag is closed at one end.

6. The container according to Claims 1 to 5, wherein the container is characterised by a guide passage with a sealing location.

7. The container according to Claims 1 to 6, wherein the container is characterised by a flange of stable shape with a force fit inside the guide passage which embraces the discharge connection piece.

8. The container according to Claims 1 to 7, wherein the container is characterised by: a flange of stable shape which consists of a thermoplastic plastic material.

9. The container according to Claims 1 to 8, wherein the container is characterised by : a weld seam which is of a U-shaped or V-shaped configuration and which extends substantially transversely to the axis of the bag, and which extends partly in the direction of the axis of the bag, or a T-shaped weld seam.

10. The container according to Claims 1 to 9, wherein the container is characterised by: a sealing location in the form of a ring of elastic material which is disposed in a groove.

11. The container according to Claims 1 and 10, wherein the container is characterised by: a discharge location which is in the form of a push-up location.

12. The container according to Claims 1 to 11, wherein the container is characterised by: a discharge location which is provided with a pierceable membrane.

13. The container according to Claims 1 to 12, wherein the container is characterised by: a discharge location which is provided with a pierceable membrane, wherein the membrane is arranged at the end of, or inside, the guide passage, or the membrane is a part of the film bag. 22 137991/3

14. The container according to to Claims 1 to 13, wherein the container is characterised by: a discharge location which is sealed with a sealing film.

15. The container according to Claims 1 to 14, wherein the container is characterised by: a film bag consisting of a plastic, metal or metal-alloy film, or a film bag consisting of a composite film of plastics material and metal, or a film bag consisting of a plastic film with a metal, glass or ceramic layer.

16. The container according to Claims 1 to 15, wherein the container is characterised by: a film bag with an inner film of plastics material and an outer film of metal or with two films of different plastics materials.

17. The container according to Claims 1 to 15, wherein the container is characterised by: a film bag with an inner film consisting of a copolymer, preferably a polyethylene copolymer of ethylene-acrylic acid, and a diffusion-tight central film consisting of metal or plastics material, or a diffusion-tight central layer consisting of metal, glass or ceramics material, and an outer film of plastics material, the melting temperature of which is higher than the melting temperature of the inner film, which is preferably polyethylene-terephthalate.

18. The container according to Claims 1 to 17, wherein the container is characterised by: a film bag consisting of a plastic film of between 20:m and 100:m in thickness, or a film bag consisting of a composite film with an inner film of plastics material of between 20:m and 100:m in thickness, and an outer film of metal of between 8:m and 20:m in thickness, or a film bag consisting of a composite film with an inner film of plastics material of between 20 :m and 100:m in thickness, a central film of metal of 137991 / 4 " 23 between 8:m and 20:m in thickness, and an outer film of plastics material of between 10:m and 40:m in thickness.

19. The container according to Claims 1 to 18, wherein the container is characterised by: 5 a filling capacity of between 0.5 millilitres and 5 millilitres, preferably of between 1 ml and 4 ml.

20. The container according to Claims 1 to 19, wherein the container is characterised by a filling capacity of between 1 ml and 4 ml, or of between 2 ml and 4 ml. 10

21. The container according to Claims 1 to 20, characterised in that the container is disposed in a metal or plastic sleeve of stable shape which is connected to the flange.

22. The container according to Claims 1 to 21, characterised in that the container is disposed in a sleeve of stable shape which is between 10 mm and 30 15 mm, preferably between 12 mm and 17 mm, in diameter.

23. The container according to Claims 1 to 22, characterised in that the container is disposed in a sleeve of stable shape from which the flange of stable shape projects, wherein the overall length is between 20 mm and 60 mm, preferably between 30 mm and 50 mm. 20

24. The container according to Claims 21 to 23, wherein the sleeve is characterised in that: it is closed substantially all around, it has an opening, or wherein there is a gap at the connection location to the flange, 25 or that is designed as a basket with many openings or that it is in the form of a stirrup member.

25. The container according to Claims 1 to 24, wherein the container is characterised in that: it has a peripheral groove in the flange of stable shape. 30

26. The container according to Claims 1 to 25: 24 137991/3 as primary packaging for a medicinal fluid which is discharged from the film bag in a plurality of partial quantities.

27. The container according to according to Claims 1 to 26: as a primary packaging for a medicinal fluid which is discharged in portion- 5 wise manner in doses of between 10 microlitres and 50 microlitres, preferably of between 15:1 and 20:1.

28. The container according to Claims 1 to 27: as a cartridge containing an inhalent medicinal preparation which is present as a solution in ethanol or in ethanol/water or in water. 10

29. The container according to Claims 1 to 28: as a cartridge containing an inhalent medicinal preparation with one active substance, or with a plurality of active substances, such as Berotec (Fenoterolhydrobromide; l-(3,5-dihydroxypheny)-2-[l-(4-hydroxy-benzyl)- ethyl]-amino]-ethanol-15 hydrobromide), Atrovent (Ipratropim bromide), Berodual (combination of feneterolhydrobromide and lpratroprium-bromide), Salbutamol (or Albuterol), Combivent, Oxivent (Oxitropium bromide), Ba 679 (Tiotropium bromide), BEA 2108 (Di- (2-thienyl)-glycolic acid tropenol ester), Beclomethason, Flunisolid, Budesonid. 20

30. The container according to Claims 1 to 29: with a medicinal preparation for the treatment of illnesses using inhalant substances.

31. The container according to Claims 1 to 30, characterised in that: the atomiser is a discharge instrument which is provided with a connection 25 piece, into which the container is inserted by means of a releasable, positive, plug- in snap connection between the connection piece in the discharge instrument and the flange of stable shape of the container.

32. The container according to Claim 31, characterised by: 25 137991 / 1 a peripheral groove in the flange of stable shape, into which groove the snap connection lugs of the snap connection hooks arranged on the connection piece engage when the container is inserted into the connection piece.

33. A replaceable cartridge having features defined in any one of Claims 1 to 32 for use in a propellant-free atomiser for a medicinal fluid wherein the inhaler has a discharge connection piece in the form of a hollow piston for discharging the fluid from the container. For the Applicants, REINHOLD COHN AND PARTNERS