Stopper device, medicament container, and method for mixing two substances in a medicament container

Description

[0001] The invention relates to a stopper device, a drug container with such a stopper device and a method for mixing two substances stored separately from each other in such a drug container.

[0002] Stopper devices, drug containers, and methods of the type discussed here are known. Typically, two substances, stored separately in a two-chamber drug container, are mixed together. The first substance is located in a first, proximal chamber, and the second substance is located in a second, distal chamber.

[0003] In such a medication container, the first, proximal chamber is bounded proximally by a first stopper device, in particular an end stopper, distally by a second stopper device, in particular a middle stopper, and radially by an inner wall of the medication container. The second, distal chamber is bounded proximally by the second stopper device, radially by the inner wall of the medication container, and distally by the tip of the medication container, which is preferably closed by a cap.

[0004] Prior to initialization of the drug container, the proximal chamber is fluidically sealed off from the distal chamber and the surrounding environment. Only during initialization is the second stopper moved into a mixing position, thereby establishing a fluidic connection between the two chambers via a bypass, allowing the two substances to mix as long as the second stopper remains in the mixing position.In particular, by applying pressure, especially manually, to the first stopper device, the contents of the proximal chamber, i.e., the first substance, are forced out of the proximal chamber and transported via the bypass into the distal chamber, whereby the volume of the proximal chamber decreases and the second stopper device remains in the mixing position until the first stopper device collides with the second stopper device.

[0005] Initialization involves applying pressure to the first stopper in a distal direction, causing it to shift. Due to this shift and the flow-related seal of the proximal chamber, the second stopper is also pressurized, causing it to shift distally into the mixing position. In this position, pressure equalization occurs via the bypass, ensuring the second stopper is no longer subjected to unilateral pressure. Therefore, with conventional drug containers, initialization and subsequent mixing of the two substances requires the shifting of both stoppers.

[0006] Prior to initialization, i.e., the application of the known method for mixing the substances, the two substances are stored separately, thereby increasing their safety and / or shelf life. Initialization is only carried out before a planned application, particularly an injection, whereby the stopper devices in the drug container are moved into an axial position – along a central axis of the drug container – in which mixing, particularly via a bypass, is possible.

[0007] To increase the sliding properties of the stopper devices in the medication container and thus achieve a safe medication container that ensures aseptic storage and / or administration of a medicinal product, the inner wall of the medication container is siliconized. However, this makes it impossible, or at least not safe, to place substances in such known medication containers that react undesirably upon contact with the siliconized inner wall. Filling the respective chambers separately, either in time and / or space, is complex, as the medication container must be rotated and / or closed after the first chamber is filled, and / or the filling of the second chamber must be completed before the first chamber can be filled.Furthermore, the mixing of the two substances in such a drug container is not optimal, particularly due to the typically small dimensions of the bypass.

[0008] Furthermore, with such conventional stopper devices, it is not possible, or only possible under difficult conditions, to design an ampoule or injection vial as a multi-chamber system, especially a double-chamber system, since these vessels are only open at one end. Therefore, when axially sealing stoppers are moved within such vessels, pressure fluctuations occur, which make axial movement difficult and ultimately limit it. In particular, the second stopper, which acts as the middle stopper, cannot easily be moved far enough into such a vessel. Moreover, due to the resulting pressure fluctuations, moving the second stopper into the mixing position within such vessels is either impossible or at least significantly more difficult and therefore impractical.

[0009] A plugging device according to the preamble of claim 1 is disclosed in US 2,688,966 A. Further plugging devices are disclosed in DE 36 35 574 A1 and US 4,254,768 A.

[0010] The object of the invention is to provide a stopper device, a medication container, and a method for mixing two substances in a medication container, thereby avoiding the aforementioned disadvantages. In particular, the object of the invention is to provide a medication container and a stopper device in which unstable substances, especially powdered medications that must not come into contact with a siliconized inner wall, can be safely stored and mixed with a second substance.

[0011] The problem is solved by providing a stopper device according to claim 1 for sealing a drug container. Further embodiments are described in the dependent claims.

[0012] The stopper device has a stopper element, wherein the stopper device is designed to seal the drug container in an axial direction of a central axis of the drug container, in particular by means of the stopper element, wherein the stopper device is at least partially insertable into the drug container and the stopper element is designed to be displaceable along the central axis of the drug container when installed in the intended position, and wherein the stopper device, in particular the stopper element, has a holding area with at least one holding means.The stopper device is characterized by the fact that, in a first operating state of the stopper device, a closure element is held in a fixed position relative to the stopper element, particularly directly at the stopper element, by means of the holding means, such that a cavity is formed between the closure element on the one hand and the stopper element on the other. Thus, a substance, particularly one intended for mixing, can be placed in this cavity of the stopper device and stored sealed from the environment, without the need for a medication container. Filling a medication container with two substances can be carried out simply in two separate steps, which are largely independent of each other.It is also possible to safely store unstable substances, especially powdered medications, in such a stopper device, as contact with silicone, particularly a siliconized inner wall of a medication container, is avoided. Furthermore, such a stopper device makes it possible and easier to create a dual-chamber system in an injection vial and / or ampoule, since no intermediate stopper is required to separate the two chambers.

[0013] In this context, a substance is understood to mean in particular a medical substance, especially a medical active ingredient and / or excipient.

[0014] The plug device, in particular the closure element and the plug element, is / are designed to receive such a substance, in particular a medicinal active ingredient, preferably aseptically in the cavity, wherein the cavity is preferably designed to be flow-tight. Preferably the plug device comprises or consists of a plastic.

[0015] A plug element, as used here, is understood to be a plug, in particular an end plug, for a medication container. The plug element preferably comprises or consists of an elastic material. Particularly preferably, the plug element consists of an elastomer and / or soft plastic. In a sealing area, the plug element is preferably at least partially elastic and / or designed along a circumferential surface in the sealing area, which, when installed as intended in a medication container, faces an inner wall of the medication container and / or an insertion sleeve and is in close contact with it, to form a sealing seal against the inner wall and / or the insertion sleeve.The drug container is therefore sealed in the axial direction, in particular by the tight fit of the stopper element and / or the stopper device to an inner wall of the drug container, so that at least one chamber of the drug container designed to hold a substance is limited in the axial, preferably proximal, direction.

[0016] In this context, a medication container refers specifically to a syringe, cartridge, ampoule, and / or injection vial. Such medication containers, particularly syringes and cartridges, are designed as single-chamber systems or as multi-chamber systems, especially dual-chamber systems.

[0017] The stopper device and / or the stopper element are preferably at least partially, and particularly preferably completely, insertable into the medication container. In the inserted state, i.e., in its intended installation position within the medication container, the stopper element is preferably displaceable along the central axis by means of a piston rod and / or a dispensing device.

[0018] The retaining element in the holding area is preferably formed integrally with the plug element. Preferably, the retaining element has a radially elastic section, so that the closure element – ​​in the first functional state – is held by radial holding forces. Particularly preferably, the retaining element and the plug element are made of an elastic material, especially rubber and / or soft plastic.

[0019] In the first operating state, the locking element is preferably held in the holding position such that a displacement of the plug element is not possible without a simultaneous displacement of the locking element. Preferably, therefore, there is mechanical contact between the plug element and the locking element, at least in the first operating state of the plug device.

[0020] According to a further development of the invention, the cavity is fluidically sealed against a wall, in particular an inner wall, of the drug container in the first functional state. This prevents contact with a siliconized surface and ensures a high level of safety for any substance stored in the cavity.

[0021] In its first operating state, the cavity is preferably limited and formed exclusively by the closure element and the plug element. It is specifically provided that the cavity is formed by a recess in the plug element and / or in the closure element, and that the cavity can be closed by means of the closure element, and is closed, particularly in the first operating state. The closure element thus seals the cavity, so that a substance stored therein is fluidically sealed from its surroundings, especially the medication container. In particular, a fluidic seal is thus created against the inner wall of a medication container when installed in the intended position within the container. Therefore, even without a medication container, a sealed cavity for the safe storage of a substance is created.

[0022] According to a further development of the invention, the cavity is open in a second functional state, with the closure element not held in the holding position by the retaining means. This makes it possible to open the cavity and thus mix a first substance stored therein with a second substance stored in a chamber of a medication container. With the stopper device installed in the medication container in its intended position, the cavity in the second functional state is therefore open, particularly with respect to the chamber of the medication container, creating a flow-related connection between the cavity and the chamber in which the second substance is preferably stored. Thus, mixing two substances, especially the first and second substances, in a medication container using such a stopper device is simple and safe.

[0023] Alternatively, it is also possible that in the second functional state the closure element is not completely released from the holding means, but instead remains at least partially attached to the plug element, particularly in the holding area, whereby the closure element no longer seals the cavity, so that a flow-technical connection to the outside of the cavity, in particular into the chamber of the drug container, exists.

[0024] Alternatively or additionally, it is provided that even when the stopper device is not inserted into the medication container, the sealing element remains fixed in its initial functional state relative to the stopper element. This allows for flexible use of the stopper device, eliminating the need for a medication container for the safe storage of the initial substance within the stopper device.

[0025] Particularly preferably, the stopper element of the stopper device is designed as an end stopper for a medication container, wherein the stopper device and – at least in the first functional state – the stopper element are arranged terminally, in particular at the proximal end of a chamber of a medication container. A terminally arranged end stopper in a medication container is understood here to be, in particular, a stopper that seals the medication container, wherein, extending distally from the stopper, all substances contained by the medication container, especially medicinal substances, and / or all chambers provided for this purpose, are arranged. In contrast, extending proximally from the terminally arranged end stopper, no chambers or areas are provided that are designed to safely store a substance, especially a medicinal substance.Thus, such an end plug separates an aseptic area distal to the end plug from an area proximal to the end plug, which is subject to only minor, and in particular no, purity requirements.

[0026] According to the invention, the closure element is designed as a mixing body, as a sphere, for the drug container.

[0027] According to a further development of the invention, the closure element is arranged to be freely movable within the medication container in the second functional state – in particular, independently of the stopper element. Preferably, the spherical closure element is loosely arranged within the medication container in the second functional state. This improves the mixing of the first substance with the second substance by shaking the medication container, whereby the mixing element causes additional turbulence within the medication container.

[0028] According to the invention, the stopper element—in its first functional state—has a dispensing projection on its side facing the closure element, which is at least partially oriented towards the closure element. While the dispensing projection may be elastic at least in one longitudinal direction along a central axis when installed as intended in a drug container, it is nevertheless designed to be sufficiently stable to allow the closure element to be displaced from the holding position, in which the cavity is tightly sealed, by the dispensing projection in an axial direction, particularly distal to the drug container, thereby overcoming the holding forces applied by the holding means. Thus, the axial resistance force, i.e., the strength of the dispensing projection that counteracts axial deformation of the dispensing projection, is greater than the holding force applied by the holding means.

[0029] An axial force, particularly in the distal direction, required to release the closure element from its holding position is preferably applied by a piston rod and manual pressure on the piston rod. The release projection preferably extends distally. Thus, even after positioning the closure element within the medication container, it can be easily moved out of its holding position, thereby transitioning the stopper device into its second functional state. The cavity and the substance contained therein, and—when installed as intended in a medication container—the chamber of the medication container and the second substance stored therein, are always fluidically sealed from the surrounding environment of the medication container, which is typically closed with a cap.

[0030] Preferably, when arranged as intended in the rotationally symmetrical, and in particular at least substantially cylindrical, drug container, the dispensing projection is arranged concentrically to a longitudinal axis of the drug container. Thus, the forces to be applied in the distal direction are minimal, and the seal between the stopper device and an inner wall of the drug container is particularly high due to the resulting symmetry.

[0031] Preferably, the outer wall of the stopper element in the holding area is offset radially inwards compared to the outer wall in the sealing area, so that – when installed as intended in a medication container – a circumferential clearance is formed between the stopper element and the inner wall of the medication container to allow the retaining element to move. This clearance simplifies the removal of the closure element from the holding area, as the material of the stopper element in the holding area is less compressed and instead only needs to be deformed into the clearance.

[0032] According to a further development of the invention, the dispensing projection – at least in one ejection state of the plug device, but preferably also in the first functional state – bears against the closure element with a side and / or tip and / or end face facing the closure element. The ejection state thus denotes the state of the plug device in which the closure element is just barely in the first functional state, but would transition directly into the second functional state due to a minimal force on the plug device in the distal direction and the resulting pressure exerted by the dispensing projection on the closure element. The ejection state is therefore the limiting state between the first and second functional states.Thus, the forces required in the distal direction are minimal, and the release of the locking element from the holding area is particularly controlled.

[0033] According to a further development of the invention, the closure element has at least one first locking element, wherein the holding element of the plug device has at least one second locking element corresponding to the first locking element, which is arranged in the holding area on a side of the plug element facing the closure element, wherein the first locking element and the second locking element – ​​in the first operating state – interlock in a locking manner. Thus, the closure element is securely held on the plug element.

[0034] Preferably, the closure element has at least one detent, in particular an annular detent groove, wherein the retaining element of the stopper has at least one detent projection corresponding to the detent, which is arranged in the holding area on a side of the stopper element facing the closure element, the detent projection engaging in the detent in the first operating state. In this case, the first detent means is thus designed as a detent and the second detent means as a detent projection. Preferably, the detent is designed circumferentially around a central axis of the medication container when the stopper is installed in the intended position. Thus, the closure element is held particularly reliably in the holding position.

[0035] Alternatively, the first locking element can be designed as a locking projection and the second as a locking receptacle, so that the holding element has the locking receptacle and the locking element the locking projection. In this case, too, the locking element is securely held in the holding position.

[0036] According to a further development of the invention, the stopper device comprises an insertion sleeve that encloses the stopper element, particularly in the circumferential direction. Preferably, an outer surface of the sleeve wall is designed to form a tight seal against an inner wall of the medication container. The stopper element rests tightly against an inner surface of the sleeve wall opposite the outer surface. Preferably, the insertion sleeve is rotationally symmetrical, and in particular, at least partially cylindrical. The sleeve wall has a finite, defined thickness in the radial direction, such that, when the stopper device is installed in the medication container in its intended position, a recessed, radially expanding area is formed at the distal end of the insertion sleeve.Preferably, the retaining area of ​​the plug device is radially pre-tensioned inwards when inserted into the insertion sleeve by being radially compressed by the sleeve. After the retaining area shifts into this retracted position, the pre-tension is less pronounced, preferably relaxed. Thus, the retaining area expands radially outwards, and the closure element is no longer held. In particular, the detent projection disengages from the detent recess in this displaced position of the plug element or the retaining area, thereby eliminating the positive locking connection of the closure element to the plug element.Thus, a particularly easy-to-operate release mechanism for the closure element has been created, with the help of which two substances can be mixed, especially in a cylindrically symmetrical drug container without a bypass, whereby only the stopper element has to be moved distally.

[0037] The insertion sleeve of the stopper device is preferably wedge-shaped at its distal end, particularly in the recessed area, and features a circumferentially extending chamfer for the stopper element, ensuring a uniform and smooth radial expansion in the recessed area. This simplifies the manufacture of the stopper device, where the closure element is positioned in a first functional state. Furthermore, it improves safety, particularly the sealing of the cavity and / or chamber of the medication container, as well as ease of handling during mixing and / or dispensing of the mixed substances.

[0038] According to a further development of the invention, the insertion sleeve is designed as a finger rest and has at least one radially projecting finger plate at a proximal end, which is designed to be grasped from behind by a finger. The finger plate is preferably designed to extend completely around a central axis or to be divided into at least two separate, opposing plates. It is important that the finger plate projects radially, particularly from the outer wall of a medication container in which the stopper device can be arranged, so that it can be grasped from behind and thus the handling of the medication container is simplified.

[0039] According to a further development of the invention, the insertion sleeve has a fastening structure for attaching it to a medication container. This fastening structure preferably includes a receptacle for the medication container, into which the medication container, with its proximal end (in particular a proximal radial thickening), can be received in a snap-fit ​​and / or clamping manner. Preferably, the fastening structure is formed by an axially extending recess, circumferential around the central axis and open in the distal direction, into which the proximal end of the medication container can be inserted, ultimately resulting in a snap-fit ​​and / or clamping engagement. Thus, the plug device can be attached to a medication container easily and quickly.

[0040] The stopper element, in particular the retaining element, is preferably arranged in the retaining area – when installed as intended in a medication container – at a distance from an inner wall of the medication container and / or from an inner surface of the insertion sleeve. This allows the retaining element to be forced radially apart in the retaining area, particularly when force is applied to the stopper element, thereby releasing the closure element.

[0041] The problem is also solved by creating a medication container according to claim 10, comprising a preferably cylindrical base body, which is in particular made of glass, and a stopper device according to the invention or a stopper device according to one or more of the embodiments described above. Further embodiments are described in the dependent claims.

[0042] The stopper device is positioned within the medication container such that the stopper element seals a proximal end of the medication container against a chamber of the base body, which is preferably tightly sealable. This chamber is bounded radially by an inner wall of the base body and distally by a sealable outlet opening of the base body and / or a cap. The chamber is also preferably rotationally symmetrical and essentially cylindrical. Viewed from the stopper device, the chamber is located distally within the medication container and is designed to hold a medicinal substance, in particular an active pharmaceutical ingredient and / or excipient, and especially a solvent for a powdered medication.

[0043] Preferably, the chamber forms a closed, and in particular sterile, volume for receiving the second substance. In the second operating state of the stopper device, the closure element of the stopper device is preferably loosely arranged in this chamber. Preferably, the closure element is larger than the outlet opening of the base body, so that the closure element cannot be displaced from the chamber through the outlet opening. The closure element is thus designed as a mixing element.

[0044] According to a further development of the invention, the outlet opening of the base body has a geometry, in particular a cross-shaped cross-section, at least on its side facing the chamber, which differs from a side facing the outlet opening, in particular from each side of the closure element, in such a way that a flow-tight closure of the outlet opening by the closure element is prevented. Preferably, the closure element is round, in particular spherical. This prevents the outlet opening from being blocked by the closure element – ​​in the second functional state. In particular, the closure element is unsuitable for creating a flow-tight closure of the outlet opening, so that the release of the first and / or second substance from the drug container – especially in the second functional state – cannot be prevented by the closure element.

[0045] Preferably, the radial extent of the non-circular geometry is greater than the radial extent of a side of the closure element suitable for contact with the outlet opening. Alternatively or additionally, the closure element has a curvature on its outer surface that differs from the curvature of the bottom wall of the drug container that has the outlet opening.

[0046] If the locking element has detent recesses, the locking element is round, in particular spherical, with the exception of these detent recesses. In particular, it is provided that the annular detent groove is arranged equatorially on the spherical locking element, with an upper hemisphere of the locking element being separated from a lower hemisphere by the detent groove.

[0047] Preferably, the closure cap is arranged distally on the base body to close the outlet opening. Here, a closure cap is understood to be an element that closes the chamber, and in particular also a sealed injection device.

[0048] A first substance is arranged in the cavity of the stopper device, a second substance is arranged in the chamber of the drug container, these two substances are intended to be mixed and the time of mixing can be selected by a user, since the two substances are arranged in volumes that are fluidically sealed from each other, namely the chamber of the drug container and the cavity of the stopper device, the seal between the chamber and the cavity can be released by the user by pressing on the stopper device.

[0049] Preferably, the medication container has a finger rest suitable for applying a suitable force to a dispensing device, in particular a piston rod, when dispensing the active substances from the medication container. The finger rest is formed integrally with the base body or – if the stopper device is arranged in an insertion sleeve containing the finger plate – separately from the base body. In both cases, however, the finger rest is firmly attached to the base body, so that the application, in particular the dispensing of a substance, or in particular both substances, from the medication container is identical in both embodiments.

[0050] According to a further development of the invention, a dispensing device, in particular a piston rod, is provided, wherein a convex, in particular spherical, conical and / or cone-shaped projection is provided at the distal end of the dispensing device. The distal end here refers to the end of the dispensing device facing the stopper device, which acts directly on the proximal end of the stopper device when the substances are dispensed from the drug container. Preferably, the projection is centered relative to the central axis of the drug container, so that when the dispensing device acts on the stopper device, it exerts a maximum force on the latter in its central region.

[0051] According to a further development of the invention, the plug element is elastically designed and deformable by means of the projection of the dispensing device, particularly by applying manual pressure in a distal direction. The dispensing projection of the plug element has an axial strength greater than that required for dispensing the closure element. This axial strength is achieved through the plug element's structural design and / or material. In particular, the dispensing projection is conical in shape. This allows for easy dispensing of the closure element from the holding area.

[0052] Here, strength is understood in particular as mechanical resistance that prevents elastic and / or plastic material failure. Strength can preferably be quantified as mechanical stress, especially pressure, or as force, and preferably converted into pressure. In this case, the strength in the axial direction is preferably greater than the pressure required to deploy the closure element. The strength of the deployment projection thus prevents, in particular, elastic and / or plastic deformation of the deployment projection.

[0053] The problem is also solved by providing a method according to claim 14 for mixing two substances stored separately from each other in terms of flow characteristics in a drug container according to the invention or a drug container according to one or more of the embodiments described above, with a stopper device according to the invention or a stopper device according to one or more of the embodiments described above. Further embodiments are described in the dependent claims.

[0054] A first substance of the two substances is arranged in the cavity of the plug device, and a second substance of the two substances is arranged in the chamber of the base body. The plug device is subjected to a force in the distal direction, thereby breaking the fluid separation between the two substances. Due to the distal force, the plug device, and in particular the plug element in the holding area, is at least partially deformed, especially radially, to such an extent that the sealing element is displaced from its holding position. It is particularly advantageous that the force applied and the resulting deformation and / or displacement are sufficient to break the fluid seal between the first and second substances, allowing the two substances to be mixed easily and reliably.Furthermore, the advantages already mentioned previously regarding the embodiments of the drug container and the stopper device result.

[0055] In particular, a method for mixing two fluidically separated substances in a drug container is provided, particularly according to one of the previously described embodiments, using a stopper device, wherein a first substance of the two substances is arranged in the cavity of the stopper device and a second substance of the two substances is arranged in the chamber of the base body, wherein the stopper device is subjected to pressure in a distal direction, in particular finger pressure, whereby the fluidic separation of the two substances is eliminated, wherein the stopper device, in particular the stopper element in the holding area, is at least partially deformed by the distal pressure, in particular radially, to such an extent that the closure element is displaced from the holding position.It is particularly advantageous that repositioning the stopper device and / or the stopper element to open the cavity and thus mix the substances is neither necessary nor, in particular, intended. Applying pressure and the resulting deformation are sufficient to break the flow seal between the first and second substances. Therefore, mixing can be easily carried out in a medication container, especially a syringe or cartridge, with a sealed outlet, as well as in an injection vial or ampoule using such a stopper device, while avoiding large pressure fluctuations within the containers.

[0056] Preferably, the plug element is deformed at its proximal end, particularly by the action of the protrusion of the dispensing device on the plug device. Due to the elastic design and the conical, especially conical, shape of the protrusion, the holding area of ​​the plug element is radially widened to such an extent that the closure element held by the holding means is released.

[0057] To ensure sufficient radial expansion of the holding area, it is preferably provided that – when the stopper device is installed in the medication container as intended – the stopper device does not directly contact an inner wall of the medication container within the holding area. Instead, a space is provided between the inner wall of the medication container and an outer wall of the stopper element within the holding area, into which the stopper element, and in particular the holding element, is forced to release the closure element.

[0058] As already explained in connection with the medication container, the locking element closes the cavity in the holding position, with the cavity being sealed in particular against the chamber of the medication container.

[0059] In particular, a method for mixing two fluidically separated substances in a drug container is provided, particularly according to one of the previously described embodiments, using a stopper device, wherein a first substance of the two substances is arranged in the cavity of the stopper device and a second substance of the two substances is arranged in the chamber of the base body, wherein the stopper device is displaced distally, thereby eliminating the fluidic separation of the two substances, wherein the holding area relaxes radially during the distal displacement of the stopper device, and wherein the holder of the closure element is released in the holding position.The holding area of ​​the plug device, in particular the plug element, is preferably under radial preload by being compressed relative to a relaxed position. In a relaxation area, especially the recessed area at the distal end of the insertion sleeve, which has a wider inner radius compared to the insertion sleeve, the holding area is relaxed after the plug element has been inserted. This allows the closure element to be easily removed from the holding area, thereby opening the cavity. Here, relaxation refers specifically to an expanding deformation of the preloaded plug device, particularly the plug element, within the holding area.

[0060] It is particularly preferred that, in a method according to one of the previously described embodiments, the drug container is shaken after the cavity has been opened, i.e., after the stopper device has been moved into its second functional state. This improves the mixing of the two substances.

[0061] According to a further development of the invention, in a method according to one of the previously described embodiments, the stopper device in the medication container is moved to a distal end position for the complete dispensing of the first and / or second substance, in particular a medication. In this end position, the closure element is preferably completely received in the cavity and / or the cavity is completely filled by the closure element. A distal end position is understood here to mean, in particular, a position of the stopper element at the distal end of the chamber of the base body, with the stopper element being in contact with the outlet opening. Thus, the dead volume is minimal when using a medication container of the type described here, especially when carrying out the methods described here.

[0062] The descriptions of the method, the stopper device, and the medication container are to be understood as complementary to one another. In particular, features of the stopper device and / or the medication container that have been explicitly or implicitly described in connection with the method are preferably, individually or in combination, features of the stopper device and / or the medication container. Preferably, the stopper device and / or the medication container are configured to carry out at least one of the method steps described in connection with the method. Method steps that have been explicitly or implicitly described in connection with the stopper device and the medication container are preferably, individually or in combination, steps of a preferred embodiment of the method.In particular, the procedure preferably includes at least one step that results from at least one feature of the stopper device and / or the drug container.

[0063] Overall, it is evident that the described stopper device, medication container, and method improve the mixing of two substances within a single medication container. Handling, particularly during a manufacturing process, is also improved, as the filling of the cavity with the first substance can occur independently of the filling of the medication container with the second substance. In particular, the cavity of the stopper device is flow-sealed even without a medication container, ensuring that a substance stored within it is not only safely contained but also—when the stopper device is installed correctly within the medication container—prevents contact with the siliconized inner wall of the container.Therefore, aseptic powder filling in a two-chamber system is possible, particularly in a previously siliconized medication container, using the stopper device, medication container, and procedure described herein, while ensuring the safety and chemical stability of the filled powder. Furthermore, the shelf life of the substances is increased with the stopper device, medication container, and procedures described herein.

[0064] The invention will be explained in more detail below with reference to the drawing. The drawing shows: Figure 1 shows a longitudinal section of a stopper device according to a first example not belonging to the invention; Figure 2 shows a longitudinal section of a stopper device according to a second example not belonging to the invention; Figure 3 shows a longitudinal section of a drug container according to a first example not belonging to the invention with a stopper device according to the second example not belonging to the invention; Figure 4 shows a longitudinal section of a stopper device according to a first embodiment; Figure 5 shows a longitudinal section of a drug container according to a first embodiment with a stopper device according to the first embodiment in a first operating state; Figure 6 shows a longitudinal section of a drug container according to the first embodiment with a stopper device according to the first embodiment in a second operating state.Figure 7 shows a longitudinal section of a medication container according to the first embodiment with a stopper device according to the first embodiment in an end position of the stopper device in the medication container.

[0065] Figure 1Figure 1, in a first example not belonging to the invention, shows a stopper device 1 in a longitudinal section view with a stopper element 3, a retaining means 5, and a closure element 7. The stopper element 3 has a sealing area 9 in which a circumferential surface 11 of the stopper element 3 is designed to seal. In the sealing area 9, the stopper element 3 rests particularly tightly against an inner surface 13 of an insertion sleeve 15, so that after the stopper device 1 is installed in a medication container (not shown here), the medication container is sealed in an axial direction. The stopper device 1 shown here is rotationally symmetrical about an axis of rotation A. In a suitable installation position in a medication container, the axis of rotation coincides with a central axis of the medication container.The insertion sleeve 15 thus surrounds the plug element 3 in the circumferential direction around the axis of rotation A and lies close to the plug element 3 in the radial direction.

[0066] The insertion sleeve 15 has on its Figure 1 At its upper, proximal end, a finger plate 19 surrounds a proximal opening 17. This finger plate 19 can be used to hold the stopper device 1 and / or a medication container, in particular to apply a force in a distal direction to the stopper element 3. At its Figure 1 At its lower, distal end, the insertion sleeve 15 has a recessed area 21, wherein the ends of the insertion sleeve 15 in the recessed area 21 are wedge-shaped, in particular as a drain slope, in the longitudinal section through the plug device 1 shown here.

[0067] The retaining element 5 is provided here in a retaining area 23 of the plug device 1, wherein the retaining area 23 is defined by a Figure 1 The lower axial section of the plug element 3 is formed. In this holding area 23, the plug element 3, which is elastically designed, is compressed relative to a relaxed position, so that the holding means 5 is radially pre-tensioned.

[0068] The plug element 3 is oriented along the axis of rotation - in Figure 1 The plug element 3 is arranged to be displaceable upwards and / or downwards in the insertion sleeve 15. After insertion of the plug device 1 into the medication container (not shown here), the plug element 3 can be displaced, in particular downwards, in a distal direction, whereby the medication container is axially sealed in every distal displacement position by means of the plug device 1, in particular the plug element 3 and the insertion sleeve 15.

[0069] The plug device 1 is in Figure 1 In a first functional state, the closure element 7 is shown, wherein the locking element 7 is held in a fixed position relative to the plug element 3 by means of the holding means 5, but releasably in a holding position. In the example shown here, which is not part of the invention, the closure element 7 is held in a specific way, in particular by frictional engagement, wherein the holding means 5, particularly due to its rotationally symmetrical design, exerts a radially inward force K on the closure element 7 from all sides in the holding area 23. The closure element 7, which here is specifically designed as a ball 25, is thus clamped in a lower, distal opening 27 of the plug element 3.

[0070] The lower, distal opening 27 of the plug element 3 is fluidically sealed by the closure element 7. A cavity 29 is thus formed between the closure element 7 and the plug element 3, in which a first substance 31, in particular a powdered medication, is arranged. This creates a fluidically sealed cavity 29 in which the first substance 31 can be safely stored, eliminating the need for a separate medication container to achieve the fluidic seal.

[0071] As in Figure 1As can be seen, the sealing element 7 does not protrude beyond a lower, distal end of the insertion sleeve 15, so that the sealing element 7 is protected against unintentional displacement, in particular towards the cavity 29, or against any other disruptive displacement that could compromise the seal of the cavity 29. Thus, the first substance 31 can be safely stored in this stopper device 1 and mounted in a drug container at any later time.

[0072] Figure 2Figure 1 shows a plugging device 1 in a lateral sectional view according to a second example not belonging to the invention. The plugging device 1 is shown here in a second functional state, in which the closure element 7 is not held in the holding position by the retaining means 5. Identical and functionally equivalent parts are provided with the same reference numerals, so reference is made to the preceding figure description.

[0073] Unlike in the Figure 1 The first example shown, which does not belong to the invention, is shown here in Figure 2 The cavity 29 is open. The closing element 7 is not held in the holding position by the retaining means 5. The first substance 31 located in the cavity 29 can therefore escape from the cavity 29.

[0074] The plug element 3 here - as also in Figure 1 - the sealing area 9 and the holding area 23. Also in Figure 2It is intended that the retaining area 23, at least in the first functional state (not shown here), is pre-tensioned by compression radially inwards, so that the closure element 7 is clamped in the lower, distal opening 27 of the plug element 3. By moving the plug element 3 into the second functional state shown here, a part of the plug element 3, in particular the retaining area 23, is displaced from the insertion sleeve 15, so that the plug element 3, and thus also the retaining means 5, can relax radially outwards in the retaining area 23. Due to the radial relaxation, the holding forces K on the closure element 7 decrease, and the closure element 7 is no longer held in the retaining position.

[0075] In addition to the holding mechanism described above, which is the same as in the first example not belonging to the invention, which is in Figure 1 is depicted, is realized, is in Figure 2A locking receptacle 33 is provided on the locking element 7. This locking receptacle 33 is formed here in particular by an equatorially circumferential locking groove 35. Corresponding to this locking groove 35, the retaining element 5 is provided with a locking projection 37 circumferential to the lower, distal opening 27, which – in the first functional state – engages positively in the locking groove 35. Thus, an additional locking mechanism is created to hold the locking element 7 in the retaining position.

[0076] To release the locking element 7 from the holding position, it is located in the Figure 2In the second example of the plug device 1, which is not part of the invention, it is necessary that the holding area 23 is compressed in the first operating state at least as far as the detent projection 37 is long. The length of the detent projection is understood here to mean, in particular, its radial extent. This ensures that the restoring force resulting from the preload expands the holding element 5, in particular the detent projection 37, radially at least to the extent that the detent projection 37 is no longer engaged with the detent groove 35. Furthermore, it is preferably provided that the thickness of a wall 39 of the insertion sleeve 15 is equal to or greater than the length of the detent projection 37.This ensures that the holding area 23 - when installed in the intended position in a medicine container with a cylindrical interior - can relax sufficiently to release the positive locking between locking groove 35 and locking projection 37.

[0077] In Figure 2It is further evident that the insertion sleeve 15 has a fastening structure 41 for attaching the insertion sleeve 15 to a medication container. This fastening structure 41 has a receptacle 43 for a medication container, in which the medication container can be inserted with its proximal end in a snap-in and / or clamping manner. Thus, the plug device 1 can be easily attached to the medication container, in particular by clipping it on. Alternatively or additionally, the plug device 1 can preferably be materially bonded to the medication container by means of the fastening structure 41, in particular by welding, welding and / or gluing it to the medication container, thereby ensuring particularly reliable sterility in the interior of the medication container.

[0078] The in Figure 2The illustrated receptacle 43 extends in the direction of the central axis only over a small section of the insertion sleeve 15. Preferably, however, in an alternative embodiment not shown here, the receptacle 43 extends over the entire axial extent of the insertion sleeve 15. In this alternative embodiment, this is preferably achieved by an outer wall 44 of the receptacle 43 extending, in particular parallel to the inner surface 13 of the insertion sleeve 15, over the entire axial extent of the insertion sleeve 15. Particularly preferably, the outer wall 44 of the receptacle 43 extends – in the first functional state – over the entire axial extent of the locking element 7, and preferably – in the distal direction – beyond it.This allows for an additional seal to be created between the outer wall 44 of the receptacle 43 and an outer wall of the drug container, thus increasing the sterility and safety of the drug container.

[0079] Figure 3 shows a drug container 45 with a stopper device 1 according to the one in Figure 2 The described example, not belonging to the invention, shows the drug container 45 having a cylindrical base body 47 and a proximal end 49. A chamber 51 of the drug container 45, designed to hold a medicinal substance, is bounded by an inner wall 53 of the base body 47, which is in particular siliconized, the stopper device 1, and – in a distal direction – by a distal outlet opening 55. The distal outlet opening 55 is shown here in Figure 3The chamber 51 is closed by means of a cap 57. A second substance 59, in particular a solvent for the powdered drug, is arranged in the chamber 51.

[0080] By installing the stopper device 1 in the drug container 45 as intended, the axis of rotation A of the stopper device 1 coincides with a central axis M of the drug container 45, wherein the stopper element 3 can be displaced along the central axis A, particularly in the distal direction.

[0081] For the sake of clarity, the following are listed: Figure 2 shown locking structures, namely the locking groove 35 and the locking projection 37, here in Figure 3 Not shown, but nevertheless included. The holding forces K are also included here, but are not shown for the sake of clarity.

[0082] The stopper device 1 is in its first functional state, so that the cavity 29 is tightly sealed. The first substance 31 arranged in the cavity 29 is thus fluidically sealed from the chamber 51, the second substance 59 arranged therein, and also, in particular, the siliconized inner wall 53 of the drug container 45. A reaction between the silicon and the first substance 31 is therefore prevented.

[0083] The outlet opening 55 of the base body 47 has a geometry on its side facing the chamber 51 that differs from the shape of the closure element 7. In particular, this geometry is realized here by a non-circular cross-section 60, so that the closure element 7, which is spherically shaped except for the locking groove 35, cannot seal against the outlet opening 55 and the outlet opening 55 therefore always remains unsealed on its side facing the chamber 51. Preferably, the cross-section 60 is at least partially cruciform.

[0084] Figure 4 Figure 1 shows a plugging device 1 in a side sectional view according to a first embodiment. Identical and functionally equivalent parts are provided with the same reference numerals, so reference is made to the preceding figure description.

[0085] The plug device 1 shown here, unlike the first and second examples of the plug device 1 which do not belong to the invention, does not have an insertion sleeve 19.

[0086] Like the previously described examples of the plug device 1 not belonging to the invention, the first embodiment of the plug device 1, which is described in Figure 4 The figure shows a plug element 3, which is designed to seal a medication container 45 in an axial direction. The plug device 1 shown here is particularly capable of being fully inserted into a medication container 45, wherein the plug element 3, in particular the complete plug device 1, is designed to be displaceable along the central axis 11 in the medication container 45.

[0087] The plug device 1 has a holding area 23 with a holding means 5 and a sealing area 9, which has a plurality of circumferential surfaces 11 of the plug element 3. Preferably, each of the plurality of circumferential surfaces 11 is designed to abut against an inner wall 53 of the medication container 45 when the plug device 1 is installed in the intended position within the medication container 45.

[0088] The holding element 5 holds a closure element 7 in a holding position. The closure element 7, which is designed as a ball 25, is held directly against the plug element 3.

[0089] A cavity 29 is formed between the closure element 7 and the plug element 3, which is in Figure 4 Due to the lateral section view, it appears to be divided into two parts, but due to the rotational symmetry around the rotational axis A, it is a continuous, ring-shaped cavity 29.

[0090] The retaining element 5 holds the closure element 7 in the holding position, particularly by means of a force-fit connection, by exerting holding forces K radially inwards from the holding area 23 of the plug element 3, thereby clamping the closure element 7 in a lower, distal opening 27. Furthermore, this ensures a tight seal between the plug element 3 and the closure element 7 in the holding area 23, thus sealing the cavity 29.

[0091] In addition to this clamping effect of the holding element 5, the following applies to the Figure 4In the illustrated embodiment of the plug device 1, the holding area 23 of the plug element 3 – in the first functional state shown here – extends at least partially beyond an equator 61 of the sphere 25 in a distal direction, with the holding area 23 bearing against the closure element 7, so that the closure element 7 is engaged distally by the holding means 5. Thus, the closure element is also positively locked.

[0092] In particular, an equator 61 is understood to be a closed circumferential line around the closure element 7, which encloses a surface that is perpendicular to the axis of rotation A and has a radius corresponding to a radius of the closure element 7, wherein the radius is maximal at least locally, preferably globally, with respect to the longitudinal extent of the central axis.

[0093] The plug element 3, unlike the two previously described examples not belonging to the invention, has in the Figures 1, 2 and 3 - on its side facing the closure element 7, a dispensing projection 63 is at least partially oriented towards the closure element 7. This dispensing projection 63 juts out from the plug element 3 in a conical shape – in particular, in a frustoconical shape – and abuts with a front, in Figure 4 lower end face 65 of the dispensing projection 63 against the closure element 7.

[0094] Thus, the plug device 1 is found here in an ejection state in which even a slight deformation, in particular an axial action of the ejection projection 63 on the closure element 7, can cause the closure element 7 to be ejected from the holding position.

[0095] The Figures 5 to 7 show a drug container 45 with a stopper device 1 according to the one in Figure 4The described embodiment shows the stopper device 1 arranged in its intended installation position in the medication container in various functional states. With reference to these figures, a method for mixing two fluidically separated substances, namely a first substance 31 and a second substance 59, in the medication container 45 is explained below.

[0096] In Figure 5 The first substance 31 is enclosed in the cavity 29 of the plug device in a flow-tight manner by the plug element 3 and the closure element 7. The in Figure 5 The depicted plug device 1 is therefore in its first functional state.

[0097] To release the locking element 7 from its holding position and thus open the cavity 29, the following steps are taken – as shown in Figure 6As shown, the plug element 3 is subjected to pressure in a distal direction. The resulting deformation, particularly in the proximal region of the plug element 3, causes a distal end, and thus also the lower distal opening 27 of the plug element 3, to spread radially outwards. This eliminates both the frictional connection provided by the retaining element 5 and the positive connection created by the engagement beyond the equator 61 of the closure element 7. Consequently, the closure element 7 is no longer held in the retaining position and is displaced from it by gravity and / or a shaking motion. The cavity 29 is now open, and the first substance 31 mixes with the second substance 59 due to the fluid-flow opening of the cavity 29.The closure element 7 is designed here in particular as a mixing body which, when the drug container 45 is shaken, leads to additional turbulence in the chamber 51 of the drug container 45, which accelerates and / or improves the mixing.

[0098] It should be emphasized here that relocating the plug element 3 is not absolutely necessary to open the cavity 29. Rather, simply applying pressure in a distal direction is sufficient to bring about a suitable deformation of the plug element 3.

[0099] The deformation of the stopper element 3 is effected here in particular by means of a dispensing device 67, which is designed as a piston rod 69. A convex, spherical segment-shaped projection 73 is provided at a distal end 71 of the dispensing device 67. This projection 73 is rotationally symmetrical about a central axis M of the drug container 45. The projection 73 is maximally extended centrally on the central axis M. Thus, when the stopper element 3 is pressurized by means of the dispensing device 67, the deformation is greatest in a central area in the immediate vicinity of the central axis M, so that the retaining element 5 in the retaining area 23 is spread open in a lever-like manner in at least two preferably opposing radial directions, and particularly preferably in all radial directions.

[0100] Figure 7Figure 1 shows the drug container 45 in an end position, with the closure element 7 almost completely enclosed in the cavity 29, so that the cavity 29 is in turn almost completely filled by the closure element 7. Thus, the residual amount of the first substance and / or the second substance in the chamber 51 of the drug container 45 is minimal. For this purpose, the stopper element 3, in particular the dispensing projection 63, is elastically designed so that the dispensing projection 63 deforms in the end position, minimizing the residual volume 75 of the cavity 29. Nevertheless, the dispensing projection 63 has sufficient strength to—as shown in the Figures 5 and 6 shown - to displace the locking element 7 from the holding position against the holding forces K, wherein the holding forces K are preferably reduced by a deformation of the plug element 3.

[0101] Overall, it is evident that, using such a stopper device 1 and such a medication container 45, a first, particularly unstable, substance 31 can be safely and reaction-free pre-filled in the stopper device 1 in a flow-tight manner, and, in particular, using such a method, it can be mixed with a second substance 59 in the medication container 45, whereby the risk of a reaction, especially an unwanted reaction with a siliconized inner wall 53 of the medication container 45, is minimal. Furthermore, handling is improved compared to conventional stopper devices 1 and / or medication containers 45, since the stopper device 1 can be pre-filled with the first substance 31 and, if necessary, packaged independently of the medication container 45, without the need for a medication container 45.Furthermore, in such a drug container 45 the dead volume, i.e. a residual amount of the first substance 31 and / or the second substance 59 in the chamber 51, is minimized.

Claims

1. Stopper device (1) for sealing off a medicament container (45), with a stopper element (3), wherein the stopper device (1) is embodied to seal off the medicament container (45) in an axial direction of a center axis (M) of the medicament container (45), wherein the stopper device (1) is at least partially insertable into the medicament container (45) and in the intended installation position in the medicament container (45) the stopper element (3) is displaceable along the center axis (M) of the medicament container (45), wherein the stopper device (1) has a retention region (23) with at least one retention means (5), wherein - in a first functional state of the stopper device (1) - a closure element (7) is releasably retained in a fixed position relative to the stopper element (3) by means of the retention means (5), in particular on the stopper element (3), in such a way that a cavity (29) is formed between the closure element (7) on the one hand and the stopper element (3) on the other hand, wherein the closure element (7) is designed as a spherical mixing body for the medicament container (45), characterized in that - in the first functional state - the stopper element (3) has a discharge projection (63) on its side facing the closure element (7) and the discharge projection (63) is at least partially oriented in the direction of the closure element (7).

2. Stopper device (1) according to claim 1, characterized in that in the first functional state the cavity (29) is fluidically sealed off with respect to a wall, in particular an inner wall (53), of the medicament container (45).

3. Stopper device (1) according to one of the preceding claims, characterized in that in a second functional state the cavity (29) is open, wherein the closure element (7) is not retained in the retention position by the retention means (5).

4. Stopper device (1) according to one of the preceding claims, characterized in that the closure element (7) is - in the second functional state - arranged freely movable in the medicament container (45).

5. Stopper device (1) according to one of the preceding claims, characterized in that - at least in an ejection state of the stopper device (1) - the discharge projection (63), with a side and / or tip facing the closure element (7), is positioned against the closure element (7).

6. Stopper device (1) according to one of the preceding claims, characterized in that the closure element (7) has at least one first locking means, wherein the retention means (23) of the stopper device (1) has at least one second locking means embodied corresponding to the first locking means and arranged in the retention region (23) on a side of the stopper element (3) facing the closure element (7), wherein - in the first functional state - the first locking means and the second locking means engage in one another in a locking manner.

7. Stopper device (1) according to one of the preceding claims, characterized in that the stopper device (1) has an insertion sleeve (15) enveloping the stopper element (3), wherein an outer side of a sleeve wall is preferably embodied for tight contact against an inner wall (53) of the medicament container (45).

8. Stopper device (1) according to claim 7, characterized in that the insertion sleeve (15) is designed as a finger rest and has at least one radially protruding finger plate (19) at a proximal end, which finger plate (19) can be grasped from behind by a finger.

9. Stopper device (1) according to claim 7 or 8, characterized in that the insertion sleeve (15) has a fastening structure (41) for fastening the insertion sleeve (15) to the medicament container (45), wherein the fastening structure (41) preferably has a receptacle (43) for the medicament container (45), in which receptacle (43) the proximal end (49) of the medicament container (45) can be received in a locking and / or clamping manner.

10. Medicament container with a base body (47) and a stopper device (1) according to one of the preceding claims, wherein the stopper device (1) is arranged moved into the medicament container (45) such that the stopper element (3) seals off a proximal end (49) of the medicament container (45) with respect to a chamber (51) of the base body (47), wherein the chamber (51) is delimited in the radial direction by an inner wall (53) of the base body (47) and in the distal direction by an outlet opening (55) of the base body (47) and / or a closure cap (57).

11. Medicament container according to claim 10, characterized in that the outlet opening (55) of the base body (47) has a geometry, in particular a cruciform cross-section (60), at least on its side facing the chamber (51), which differs from a side of the closure element (7) facing the outlet opening such that a fluidically tight closure of the outlet opening (55) is prevented by the closure element (7).

12. Medicament container according to claim 10 or 11, characterized by a dispensing device (67), wherein a projection (73) is provided at a distal end (71) of the dispensing device (67).

13. Medicament container according to claim 12, characterized in that the stopper element (3) is elastic, wherein it is deformable by means of the projection (73) of the dispensing device (67), in particular using manual exertion of pressure on the dispensing device (67) in the distal direction, wherein the discharge projection (63) of the stopper element (3) has a greater strength in the axial direction than the pressure required to move the closure element (7).

14. Method for mixing two substances (31, 59) stored separately from one another in terms of flow in a medicament container (45) according to one of claims 10 to 13 with a stopper device (1) according to one of claims 1 to 9, wherein a first substance (31) of the two substances (31,59) is arranged in the cavity (29) of the stopper device (1) and a second substance (59) of the two substances (31,59) is arranged in the chamber (51) of the base body (47), wherein the stopper element (3) is acted upon with a force in the distal direction, wherein the fluidic separation of the two substances (31, 59) is eliminated, characterized in that the stopper device (1), in particular the stopper element (3), is deformed, at least partially, due to the distal force application, such that the closure element (7) is moved out of the retention position.

15. Method according to claim 14, characterized in that the stopper element (3) is displaced in the distal direction, wherein the fluidic separation of the two substances (31, 59) is eliminated, wherein the retention region (23) relaxes radially during the distal displacement of the stopper device (1), and wherein the retention of the closure element (7) in the retention position is released.

16. Method according to claim 14 or 15, characterized in that the medicament container (45) is shaken after the cavity (29) has been opened.

17. Method according to one of claims 14 to 16, characterized in that the stopper device (1) is displaced into an end position for the complete discharge of the two substances (31, 59) in the medicament container (45), wherein the closure element (7) is received in the end position in the cavity (29), and wherein the cavity (29) is completely filled by the closure element (7).