EP1915184A1

EP1915184A1 - Twin-chamber receptacle without a bypass in the cylindrical member

Info

Publication number: EP1915184A1
Application number: EP06792775A
Authority: EP
Inventors: Stefan Bassarab; Alexander Bauer; Nicole Denkinger; Patrick Garidel; Markus Hemminger; Hans-Joachim Kern; Andreas Langer; Ingo Presser
Original assignee: Boehringer Ingelheim International GmbH; Boehringer Ingelheim Pharma GmbH and Co KG
Current assignee: Boehringer Ingelheim International GmbH; Boehringer Ingelheim Pharma GmbH and Co KG
Priority date: 2005-08-13
Filing date: 2006-08-11
Publication date: 2008-04-30
Also published as: US20070060875A1; DE102005038458A1; WO2007020237A1; TW200722072A; KR20080039989A; CA2619225A1; JP2009504293A

Abstract

The invention relates to a twin-chamber receptacle for accommodating and combining two separate components, at least one of which is liquid. Said twin-chamber receptacle comprises a cylindrical member (15) with one respective closure (20, 60) at each of the two ends (5, 70) of the member (15). The closure (60) located on the side of the chamber (5) containing the liquid component can be displaced by applying pressure. The twin-chamber receptacle further comprises a separating plug (40) which is disposed in the cylindrical member (15), defines the volume of the chamber (30, 50) located above and below, is used as a seal between the two chambers (30, 50), and can be displaced only when a greater amount of pressure is applied. The separating plug is provided with a continuous hole (42) which extends along the longitudinal axis of the separating plug (40) and encompasses a top section (42a) and a bottom section (42b). The top section (42a) of the hole (42) is closed in a liquid-tight manner towards the chamber (50) containing the liquid component by means of a molded element (45) that can be displaced by applying a small to a moderate amount of pressure.

Description

Double-chamber container without bypass in the cylindrical body

The present invention relates to a double-chamber container without a bypass in the cylindrical body, a method for its filling and its use.

Background of the invention

There are medicines that lose their effectiveness very quickly in their ready-to-use form. In order to be able to use these drugs despite their short shelf life, two-component systems have been developed to mix them immediately before use.

For example, pharmaceutical preparations which can not be used in solution for a prolonged period can be preserved, for example by lyophilization, and may be stored in the absence of air. The dry matter is not dissolved again until just before use, i. reconstituted.

It is known that lyophilizates are also used in pre-filled syringes with two-chamber systems, wherein lyophilisate and solvent are stored separately and combined only shortly before use. Such dual-chamber prefilled syringes have already been described in "The Lyophilization of Medicaments in Pre-filled Syringes", H. Vetter, The Pharmaceutical Industry, Vol. 46, 1984, No. 10, pp. 1045-1049

Handling effort with two sterile closed vessels and a To reduce syringe and, for example, to avoid confusion with unlabeled disposable syringes.

The prefilled syringes are usually cleaned, siliconized and provided with Kaπülenschutz. The siliconization for coating the

Primary packaging is performed so that the rubber stopper in the glass cylinder is easily displaced. In this case, both the rubber stopper and the inside of the glass cylinder can be coated with a silicone oil. Then the pre-filled syringes are pre-sterilized in batches and filled under sterile conditions. These are then provided with a piston plug and assembled, with the piston rods are mounted. Then it is labeled and packaged. Filling and sealing take place here from the back of the syringe, since the cannula side has too small an opening.

Specifically, such prefilled syringes are constructed so that each of the components is housed in a separate chamber, the chambers being arranged axially one behind the other and being communicated with one another just prior to use so that the liquid component of one chamber becomes the dry component of the other Chamber can transgress. As a result, the desired mixture is formed. It is known for this purpose to provide a bypass, for example in the form of an extension of the inner diameter of the glass cylinder in the syringe over which the liquid component can pass if a separating the two chambers stopper was moved so far into the bypass, that the liquid component the Can flow around plug.

In the prior art, further improved solutions have been sought to allow mixing of the two-component systems while maintaining the sterility of the two components. There are numerous proposals for this, but in the present case only those systems are of interest, which have no previously described bypass: For example, DE 32 13 072 describes a syringe which is subdivided into two compartments for receiving a powdered medicament and its solvent, the mixing taking place by retracting the piston rod of the syringe, whereby the solvent can flow around the piston.

According to DE 1 809 892 a two-chamber syringe is described, the filling of which is facilitated by adding the liquid through a filling channel provided in the piston rod.

In the patents US Pat. No. 5,785,683 and US Pat. No. 6,602,223, the mixing process of the two components in the syringe is achieved by specially shaped valves, which can be controlled by movement of the piston.

Furthermore, EP 1 038 543 discloses a dual-chamber syringe for medical purposes, which contains a piston rod with protruding latching elements, which are arranged diametrically in pairs and / or provide a mixing angle of 90 ° for controlled mixing and sequential administration of the mixture.

It is also known from DE 25 46 495 to connect a syringe via a special plug with a container which is closed by a second plug and pushed out before mixing.

A disadvantage of all the systems described is their very complex structure, which is based on specially designed valves or piston rods. In particular, DE 25 46 495 has in addition to a complex structure that connects a syringe and a container via a connector with each other the serious disadvantage that the plug falls into the container and there not only with the injected solvent, but also with the solid contained over a longer period in contact. In addition, this plug can cause problems with the removal of the mixture, since it can block the discharge opening and possibly restraining or absorbing part of the mixture.

Another disadvantage is that 2 vessels must be connected to each other, with the actual vulnerability is the connector that can slip or fall off during prolonged storage. So there is the danger of contamination from the outside. In addition, this structure is very bulky and therefore not easy to store and handle.

There is therefore still a need for an easy-to-handle device for the reliable storage and mixing of two-component systems, at least one of which is in liquid form. In this case, contamination from the outside should be excluded as far as possible, i. The mixing should be done without removing the components from the sterile interior of the device and without compromising sterility. The device should also be easy to store. Furthermore, a method for easy filling of such a device is to be provided. The device and the method should also be usable on a large industrial scale.

Detailed description of the invention

The above object is solved by the features of claim 1. Thereafter, a dual chamber container is provided for receiving and combining two separate components, at least one of which is liquid, comprising a cylindrical body, each having a closure at each of the two ends of the body, of which the closure is the liquid side Component containing chamber is displaced under pressure, as well as a displaceable only under increased pressure excretion stopper disposed in the cylindrical body, which defines the volume of the above and below arranged chamber, as a seal between the two

Chambers, with a continuous in the longitudinal axis of the separating plug opening, which has an upper portion and a lower

Section, wherein the upper portion of the opening to the side of the liquid component-containing chamber by a light to moderate

Pressure exercise sliding shaped body is liquid-tightly sealed.

Accordingly, an internal "bypass" is virtually provided in the separating stopper between the two chambers of a cylindrical container The special design according to the invention of the separating stopper between the two components in a two-chamber system is such that the function of the bypass, which is usually formed in prefilled syringes, is integrated in it This is achieved by a continuous opening in the longitudinal axis of the separation plug, the opening being divided into an upper section and a lower section, and a shaped body sealing the upper section of the opening in a suitable liquid-tight manner.

When using the inventively designed Trennstopfens with a continuous opening, which is closed at the upper portion to the liquid side by a shaped body, increases by exerting an external force on the liquid, the pressure on the liquid side, resulting in that the molded body from its position in upper portion pressed into the opening or the opening channel and is pushed through this / these and this / these finally releases. The two components can be mixed without the sterile ones Conditions of the dual-chamber container are affected.

Accordingly, the separating stopper "under slight to moderate pressure exercise is not displaced", ie this is to maintain force, for example, with the fingers or a punch on the upper closure and thus on the liquid side substantially its position in the cylindrical container, whereas the molded body "displaceable "should be, ie this should be due to the action of a force sufficient to displace the upper closure, i. a slight to moderate pressure, and thus leave its position with appropriate force on the liquid side to allow mixing of the two components.

The separating stopper is only displaceable on the sealing stopper when "increased pressure is exerted", for example when the upper stopper or stopper has penetrated into the vitreous body so far that it touches the separating stopper and pushes it into the vitreous body with further exertion of force.

Thus, according to the invention, one chamber may contain a liquid and the other chamber a solid. The invention is not limited in terms of the nature of the two components, provided that at least one component is liquid. For example, a solid, powdered medicament, preferably a lyophilisate, ie a lyophilized medicament, may be present. In lyophilization or freeze-drying, a liquid product is frozen and then the frozen product is dried by sublimation. For example, the liquid component is preferably a solution or dispersion medium for the solid; it may, for example, be a reconstitution medium for the lyophilizate. For example, when the solid is a drug, an injection solution can be prepared in either solution or dispersed form. The solvent is preferably water, but may also be another solvent or a mixture of solvents. The cylindrical body according to the invention is a substantially elongate and hollow body with two open ends, which is preferably integral, ie made in one piece, which is divided into chambers by the separating stopper. The "cylindrical" body does not necessarily have to be cylindrical in shape, although this is the most common shape, and any other geometric shape is possible for an elongate hollow body, such as angled or oval, with the closures and separating plugs and the like then attached to the selected one The material of which the cylindrical body is made or contains is not particularly limited in the present invention, for example, the container may be selected from plastics or glass. Glass is preferred for its transparency and compatibility with many medical formulations Cylindrical body is therefore preferably made of or contains glass, since this results in the least impairment of the components contained and the body is preferably transparent., For special requirements but other materials are suitable, such as special plastics or the like In particular, the medical safety plays a role, since the lowest possible interaction with the medium contained is to strive.

Preferably, the cylindrical body has the same diameter over the entire length.

The separating plug disposed in the cylindrical body defines the size / volume / dimensions of the two chambers and, together with the shaped body, acts as a liquid blocking device for the liquid component, which is prevented from passing into the other chamber. The separating stopper, as already explained, is arranged almost "stationary" in the cylindrical body and should therefore not be displaceable when a force is exerted on the chamber with the liquid component sufficient to displace the upper stopper rubbery, elastic material, such as plastic, in particular natural and synthetic rubber, thermoplastics, elastomers, thermoplastic elastomers and the like The separating plug is intended to ensure a seal between the two chambers and have the necessary strength to maintain its position even under moderate pressure.

According to a preferred embodiment of the invention, the separating plug to a suitable shape, dimension and / or a material which prevents the improper displacement from its predetermined and defined position in the cylindrical body. This can conveniently be done by the appropriate provision of a suitable shape with projections, such as knobs, lips, beads or webs and / or for example by the choice of a larger diameter than the inner diameter of the cylindrical body.

In the present invention, the term "shape" is intended to denote the outer shape or geometry, and the term "dimension" is intended to mean the dimensions, i. Size relationships, denote.

When the liquid is pressurized, the separating plug continues to adhere to the inner wall of the cylindrical body due to frictional forces. If the static friction of the separating stopper on the wall of the cylindrical body is not sufficient for a specific application in order to prevent unwanted movement, then this may be provided with small suitable projections and / or, for example, by sealing lips, beads or sealing surfaces for adhesion to the inner wall of the cylindrical body are held. The pressure therefore decreases in the other Chamber not to. This results in a differential pressure between the two chambers, whereby the molded body is moved from the upper portion of the opening toward the other chamber to the lower portion of the opening. As soon as the shaped body releases the opening, the solvent can flow through the opening from one to the other chamber.

The shape of the molded article is not particularly limited. This has a suitable three-dimensional shape, so that the opening in the upper portion is closed. The molding closes at least the upper portion of the opening to the side of the chamber containing the liquid component. In the context of the present invention, an "upper section" means a part of the entire opening with a defined length L1, wherein the opening of the separation stopper is not normally closed over the entire length by the shaped body, but only one through the selected dimensions of the shaped body and / or the opening defined portion of a predetermined length (upper portion), which is followed by another defined portion of the opening (lower portion), is transported through which the molding by applying the external pressure.

The upper and lower sections may have the same shape and dimension, so that the shaped body releases the opening only after leaving both sections.

The shaped body preferably has a larger outer diameter than the inner diameter of the opening in the upper portion, so that sufficient pressure is built up between the inner wall and the molded body to close the interface, but movable in the container under the force applied for mixing, as opposed to the separating plug is. Exemplary suitable three-dimensional shapes for the molded article are round, egg-shaped, cylindrical shapes, cylindrical shapes with rounded side surfaces, dumbbell, cuboid, conical, truncated conical or conical shapes.

According to the invention, a suitable shape and / or dimension of the opening in the separating stopper and a suitable shape and / or dimension of the shaped body are thus selected, so that the shaped body releases the opening when pressure is exerted so that the liquid component can flow into the space of the solid component.

The opening need not be round, like a hole, but may also be oval, any square, such as square or rectangular, or may take any three-dimensional shape.

According to the invention, the geometric shape and / or dimension of the opening and the shaped body are particularly preferably matched to one another in such a way that the shaped body can be conveyed out from its original position in the upper section of the opening, in which it represents a seal to the liquid component, but the opening can not completely leave in the lower section. It is thus preferred if the shaped body does not penetrate into the chamber containing the solid.

This may be accomplished, for example, by having the opening in the upper portion to the side of the chamber with the liquid component of a different geometric shape and / or dimension than in the lower portion to the side of the chamber with the solid component. Thus, the shape of the opening need not be the same over the entire length and / or the inner diameter may change after a certain length.

Particularly preferably, for example, be prevented by a suitable taper on the solids side end of the separating stopper that the Molded body can penetrate into the front chamber with solid and possibly prevents complete removal of the product.

It is therefore preferred that the molded body, after it has allowed the entry of liquid component to the solid component, the

Access channel or lower section does not leave and is held there. Suitable configurations of the lower portion of the opening and of the shaped body may be selected so that the shaped body can not leave the opening of the separating stopper but sufficient space remains for the liquid component to pass to the solid component.

According to the invention, it is particularly preferable that the opening of the upper portion to the side of the liquid component chamber has a smaller inner diameter D1 than the lower portion to the side of the solid component chamber having a larger one

Inside diameter D2. In particular, it is expedient if the opening (in the upper section) has a diameter D1 over a length L1, where L1> D1 and the opening in the upper section extends along the length L1 to the diameter D2 over a length L2 (lower section). where D2> D1 and L2> DK, where DK represents the diameter of the molded article.

Particularly preferably, the opening in the lower portion in the direction of the solids-side end on means to prevent the pushed out of the original position moldings leaving the opening. These may be in the lower portion of the opening and thus mounted in the liquid channel pimples, lips, beads or webs, which may be arranged offset and defined spaced apart, for example. However, these means are not limited in the context of the present invention, as long as they prevent the molding from leaving the opening (the lower portion) of the separating stopper, but at the same time do not prevent the passage of liquid component. The retention of the molding can be achieved not only on the dimensions of opening and molding or additional holding means, but it can also selectively matched geometries of opening and molding selected and adjusted to each other. Thus, the opening can be round at one end (upper portion) and closed with a round molding. By applying pressure, the shaped body then leaves its position and moves in the opening together with the liquid until it reaches, for example, a position, preferably in the direction of the solids side end of the opening where the opening (lower portion) has a shape which does not fit through the molded body and is therefore held. This may be, for example, a quadrangular, star-shaped or oval shape, may be star-shaped with sharp or rounded tips or may assume any three-dimensional shape which can be closed liquid-tight at one end (upper portion of the opening) by the molding and at the other end ( lower portion of the opening) allows passage of liquid. Nevertheless, according to this embodiment, due to the selected geometric conditions, liquid can continue to flow over into the other chamber almost unhindered, since the shaped body can not completely close the opening.

Advantageously, the opening may additionally have one, two or more bypass channels, which may be provided in the lower section below the mold body arranged in the separating plug in the opening channel before the actual mixing of the two components. These may be one or more recesses in the inner wall in the longitudinal direction, such as a groove or groove. These additionally allow the liquid component to flow around the molding. This allows a particularly fast mixing of both components. The mixing can be, for example, the reconstitution of a lyophilisate be. At this step, no other part of the container comes into contact with the liquid or solid component.

The dual-chamber container further comprises 2 closures, one of which is provided at the solids end and the other at the liquid-side end. The closure devices are not limited if the liquid-side closure device allows pressure to be exerted on the liquid so that the shaped article leaves its position in the separating stopper.

The closures may for example be selected from plugs, membranes, discs, in particular sealing discs, optionally with crimp caps made of metal and / or plastic caps.

It is particularly useful if the closure at the liquid-side end of the opening is a stopper, which may be made of rubber or rubbery, elastic material, such as plastic. The closure at the solids side end of the opening may preferably be a pierceable membrane having an outer cap crimped over the outer edge at the emptying end, for example. This can also be provided a removable disc connected to the outer cover. If the container is a carpule or ampoule, one or both sides of a rubber closure is provided, which can be pierced by means of an injection needle. The closures can also be removably attached. In any case, care must be taken to ensure the sterility of the closures.

Preferably, the dual-chamber container is a vessel for the separate storage of 2 substances, such. As a cylindrical ampule or carpule, which is intended for single or multiple use. The dimensions of the double-chamber container depend on the volume of the solution to be prepared, wherein in human medicine rarely 10 ml are exceeded, so that volumes of up to about 20 ml are sufficient. In exceptional cases and in veterinary application, these volumes can be far exceeded.

The invention also provides a method for filling the double-chamber container according to the invention, comprising the steps:

(1) introducing a first displaceable under increased pressure exerting stopper into the cylindrical body having a continuous in the longitudinal axis of the separating stopper opening having an upper portion and a lower portion, wherein the upper portion of the opening by a slight to moderate pressure exerting displaceable Molded body is sealed liquid-tight;

(2) filling a solid component on side B of the cylindrical body provided with the separating plug or

(3) filling a liquid containing the solid component on the side B of the cylindrical body provided with the separation plug, then lyophilizing the liquid to obtain the solid component and closing this chamber on the side B,

(4) filling the liquid component into the cylindrical body over the separating plug (side A) and (5) closing the dual-chamber container.

Subsequently, the method will be explained in detail, wherein the individual features, if they are described for the method, mutatis mutandis apply to the dual-chamber container and vice versa.

In step (1), the introduction of one takes place only under increased pressure slidable Trennstopfens in the cylindrical body having a continuous in the longitudinal axis of the Trenπstopfens opening having an upper portion and a lower portion, wherein the upper portion of the opening is liquid-tightly closed by a displaceable under mild to moderate pressure molding shaped body. This separating plug can preferably be placed centrally in the cylindrical body, but can also be positioned as desired, depending on the application and the desired size of the two chambers.

Then, in step (2) or (3), on the side B, either a solid component is filled or a liquid containing the solid component. In the latter case, the filling of the cylindrical body with a lyophilization solution takes place via the open lower end (side B) of the cylindrical body. This can be any solution that is to be lyophilized. For example, a drug that gets more shelf life through lyophilization. The lyophilization takes place in a manner known to those skilled in the art, wherein the solvent escapes through the lower open end of the cylindrical body. The lyophilizer is commercially available, the process parameters are regulated automatically, for example.

Of course, this "lower" end is directed upwards during filling.The terms "top" and "bottom" do not mean that the designated part in the container is always up or down, this serves primarily to the unique name of the

Lyophilization take place a turning of the container, wherein the original name chosen for reasons of clarity remain.

Subsequently, the lower end or the mouth of the cylindrical body is closed. The lower end can also be a

Have rejuvenation. As a closure, for example, a plug, a membrane, a disc, in particular a sealing disc, optionally with Cover, such as a cover or crimp, or the like. The closure is not particularly limited as long as it provides appropriate tightness, is inert to the medium to be filled in and meets the sterility requirements. The lower closure is most preferably a puncturable membrane

Rubber stopper or elastic disc, optionally with a crimp cap. It can also be provided a removable closure. If the container is a carpule or ampoule, then a rubber closure can be provided which can be pierced by means of an injection needle. However, it is also possible to use any other closure known to the person skilled in the art.

Then the container is inverted and conveyed to a bottling plant where, in step (4), the reconstitution medium is filled via the open top of the cylindrical body, i. the dissolving or dispersing medium is filled into the upper chamber (side A) above the separating stopper. After filling the container with reconstitution medium, i. a solution or dispersion medium for the lyophilizate, the container is provided with a closure (step (5)). Preferably, a plug is used as the top closure. However, it is also possible to use any other closure known to the person skilled in the art, provided that this is displaceable under pressure. It is particularly useful if the upper closure at the liquid-side end (side A) represents a stopper, which may be made of plastic or similar materials. Exemplary materials are rubber or rubbery elastic material such as elastomers, thermoplastics, elastomeric thermoplastics, glass and / or metal such as stainless steel or similar materials.

It is particularly expedient if the plugs and / or closure parts are fed and introduced via a washing and sterilizing device or via an autoclave via sterile corridors. After closing the container is discharged from the sterile area; finally, it is labeled and packaged. It goes without saying that in this process all surfaces and devices are designed for aseptic operation.

The invention further provides a method for mixing two separate components, at least one of which is liquid, in one

A dual-chamber container comprising a cylindrical body, each having a closure at each of the two ends of the body, of which the closure is to the side of the liquid

Component containing chamber (page B) is displaced under pressure, as well as a displaceable only under increased pressure release stopper disposed in the cylindrical body, which defines the volume of above (side A) and below (side B) arranged chambers, as

Sealing between two chambers, with one in the longitudinal axis of the

Trennstopfens continuous opening, which has an upper

Section and a lower portion, wherein the upper portion of the opening to the side of the liquid component-containing chamber by a light to moderate

Pressure exerted sliding moldings liquid-tight,

with the steps:

Applying pressure to the slidable closure; Pushing out the molding from its defined position in the upper portion of the opening;

Passing the liquid component from a chamber into the chamber with the solid component to obtain a mixture of both components. The molded body is preferably, as already explained in detail, retained after pushing out of its defined position in the upper portion of the opening in a position in the lower portion of the opening, in the still access of the liquid component from the upper chamber into the chamber with the fixed component is enabled.

The invention further relates to the use of the container according to the invention in the human and veterinary field.

The present invention has numerous advantages:

Thus, the internal "bypass" in the separating stopper makes it possible to store the two-component system without premature mixing and hence loss of the effectiveness of the components.The two-component system provided according to the invention can be stored in a sterilized and prefilled, ready-to-use state takes place immediately before use after storage The dual chamber container can be thrown away after use.

A device is provided with which the desired solution of the two components is produced immediately prior to use, wherein in addition to speed and reliability, ease of manufacture and filling are possible. By the separating plug, the volume of the two chambers can be set arbitrarily, so that the container according to the invention can be designed in the dimensions for the desired application.

With the aid of the dual-chamber container of the invention, mixing, such as the reconstitution of a lyophilizate can be carried out in a closed two-chamber system, without the container itself with an additional external or internal Bypass must be provided and / or without the mixing of the tightness of the system with regard to unwanted microbial, chemical or physical external influences, repealed.

Accordingly, there is no risk of contamination by foreign bodies that can penetrate from the outside, such as bacteria, dirt particles, splinters, etc. The container can be used as a primary packaging and stored clearly labeled. The use of two-component systems, in particular lyophilized preparations, can thereby be simplified.

Furthermore, there is the possibility of correspondingly adjusting the flow rate or amount of liquid component flowing through per unit of time by appropriate dimensioning of the opening in the separating stopper and of the shaped body. In this way, a correspondingly slow access or a rapid overflow through the size of the opening, for example in the lower section, are controlled in the separating plug from one to the other chamber. A limitation of the flow velocity of the liquid component by additional devices, which would be associated with considerable effort, does not have to be done. The problem, according to which, in the event of excessive pressure on the stopper, the liquid component penetrates too quickly via the bypass to the chamber with the dry substance and thus already dissolved substance leaves the cannula of the syringe, does not occur according to the invention since no syringe is used. Also associated unwanted contamination of the user as well as a loss of the dissolved substance and thus a no longer exactly controlled dosage are thus prevented.

A further advantage of the invention is that the double chamber container required for this system has no external irregularities, in the form of a bypass with one or more protuberances, and is therefore easier and more reliable to process on the usual process equipment. This offers advantages, for example in filling, Lyophilization, attachment of the caps, labeling, and also handling, where a bypass can be a potential breakpoint of the container and requires special technologies that are not required here.

The above description describes a variety of variations and suggests a number of modification possibilities which will be readily apparent to those skilled in the art.

Description of the figures

The enclosed figures illustrate the present device according to the invention as well as the process teachings which can be carried out according to the invention without being limited thereto. In detail shows:

Figure 1 shows an embodiment of the invention of an inventive

Container filled with "bypass" closed in the stopper;

Figure 2 shows an embodiment of the invention of a container according to the invention with open "bypass" in the separating stopper;

FIG. 3 shows a detailed representation of a separating plug according to the invention;

Figure 4 is a plan view of an embodiment of a separating plug according to the invention and

Figure 5 shows various embodiments of a shaped body according to the invention. 1 and 2, the function of a double-chamber container 10 according to the invention with closed and open "bypass" is shown schematically in the separating stopper 40. More specifically, a double-chamber container 10 according to the invention is shown consisting of a cylindrical body 15, for example made of glass, a solids-side closure 20 at the end 5 and a liquid-side closure 60 at the end 70 of the cylindrical body 15. The lower closure 20 in the present case is a rubber closure, which may be a pierceable membrane with an outer cap, for example, over the outer edge of the By way of this, a detachable disk connected to the outer cover can be provided.Of course, any other closure known to the person skilled in the art, in particular removable, can also be provided.

For example, the top closure 60 may be a plug that may be constructed of a suitable resilient and flexible material, such as rubber, plastic, or the like. This closure is also not further limited, as long as it allows a pressure on the liquid component in the chamber 50, so that the molding 45 can be carried out of its position in the upper portion 42 a of the opening 42.

The stopper 40 divides the container 10 into two chambers 30 and 50, the chamber 30 containing a solid component such as a lyophilisate and the other chamber 50 containing a liquid component such as a solid component reconstitution medium. The separating plug 40 has an opening 42 which extends in the axis over the entire length of the separating stopper 40. In the upper portion 42a of this opening 42 is the shaped body 45 which closes the two chambers 30 and 50 against each other tightly.

If the liquid located on the side A in the chamber 50 is under If the static friction of the separating stopper 40 on the wall of the cylindrical body 15 for the intended use should not be sufficient, ie, an accidental slipping or movement of the separating plug 40, it can be preferably held with small nubs (not shown) on the inner surface of the cylindrical body 15. The pressure on the side B therefore does not increase. This results in a differential pressure between the sides A and B, which results in that the shaped body 45 is moved in the opening 42 to the lower portion 42b in the direction of the side B. As soon as the shaped body 45 releases the opening 42 with the diameter D1, the access is opened and the liquid component can flow from the side A through the opening 42. The opening 42 preferably includes bypass channels 47. Preferably, the opening 42 in the lower portion 42b toward the solids side end of the opening 42 (to side B) has a larger inner diameter D2, so that the liquid component is additionally through the bypass channels and the larger inner diameter of Bottom portion 42 b of the opening 42 can flow to the side B, whereby the mixing of the two components results in a simple manner particularly quickly. For example, the reconstitution of a lyophilisate can take place.

In Figure 3, an open and closed bypass stopper 40 is shown to illustrate the function of the internal "bypass." In a first position, the former 45 is disposed in the upper portion 42a (mold body 45) and seals the separator stopper 40 in a liquid-tight manner. In a second position, the shaped body 45 has been pushed out of its defined first position by manual application of force and is located in the lower portion 42b (shaped body 45 ').

The separating plug 40, the chamber 50 with the liquid component (side A) of the two-chamber system of the chamber 30 with the solid Component (page B) is, on its side surface which seals to the wall of the cylindrical body 15, preferably designed as a conventional separating plug.

In the longitudinal axis of the separating plug 40, the internal "bypass", which in the present invention is referred to as an opening which divides into an upper and a lower section, is realized, for example achieved by an upper section 42a starting on side A, over a length L1 having the diameter D1 (with L1> D1) .This upper portion 42a is closed by a shaped body 45 of diameter DK and DK> D1, which is exemplified as a sphere in Figure 3. However, the shaped body 45 can also be designed as a cylinder or as a cylinder with ball-like shell shape or dumbbell-shaped with 2 sealing surfaces, as exemplified in Figure 5.

After the length L1, the diameter of the upper portion 42a widens from D1 to the lower portion 42b with a diameter D2 (with D2> D1 and L2> DK). This is particularly useful in the present case, so that the frictional forces on the molded body 45 decrease so much that this despite pressure equalization between the sides A and B, the opening 42 at the transition from D1 to D2 so far releases that the liquid component of page A to page B can flow. In order to improve the transfer of the liquid component from side A to side B, one or more bypass channels 47 can advantageously be made laterally at the lower section 42b with diameter D2 and length L2. In FIG. 3, by way of example, two bypass channels 47 are shown.

FIG. 4 shows a plan view of a preferred embodiment of a separating stopper 40 according to the invention. The upper portion 42a with the diameter D1 and the lower portion 42b with the larger diameter D2 are shown and 2 bypass channels 47, the better Allow access of the liquid component from the chamber 50 into the other chamber 30.

The preceding description of the figures serves to illustrate the device according to the invention or the method according to the invention. This is to be understood merely as a possible, exemplarily illustrated procedure without restricting the invention to its content.

LIST OF REFERENCE NUMBERS

5 End to solid side (side B)

10 containers

15 cylindrical body

20 closure, mouth

30 chamber with solid component

40 separating plugs

42 opening, channel

42a upper portion of the opening 42 with diameter D1

42b lower portion of the opening 42 with diameter D2

45 shaped bodies

47 Bypass

50 chamber with liquid component

60 stopper, stopper

70 end to the liquid side (side A)

Claims

claims

A dual-chamber container for holding and combining two separate components, at least one of which is liquid, comprising a cylindrical body (15) each having a closure (20, 60) at each of the two ends (5, 70) of the body ( 15), of which the closure (60) to the side of the liquid component containing chamber (50) is displaceable under pressure, and a displaceable only under increased pressure release plugs (40) arranged in the cylindrical body (15), which the volume of above and below arranged chamber (30, 50) defined as a seal between the two chambers (30, 50), with a in the longitudinal axis of the separating stopper (40) continuously extending opening (42) having an upper portion (42 a) and a lower portion (42b), wherein the upper portion (42a) of the opening (42) to the side of the liquid component containing chamber (50) by a shifts under mild to moderate pressure Ren shaped body (45) is sealed liquid-tight.

2. Double-chamber container according to claim 1, characterized in that the chamber (50) has a liquid component and the other chamber

(30) contains a solid component.

3. dual chamber container according to claim 1 or 2, characterized in that the solid component is a drug, in particular a lyophilized drug.

4. Dual-chamber container according to one of claims 1 to 3, characterized in that the liquid component is a solvent or dispersant for the solid component.

5. Double-chamber container according to at least one of the preceding claims 1 to 4, characterized in that the cylindrical body (15) is in one piece.

6. dual-chamber container according to at least one of the preceding claims 1 to 5, characterized in that the separating stopper (40) has a suitable shape, dimension and / or a material which movement from its defined and defined position in the cylindrical body (15 ) prevented.

7. dual chamber container according to at least one of the preceding claims 1 to 6, characterized in that the separating stopper (40), sealing lips, -wülste or sealing surfaces.

8. Double-chamber container according to at least one of the preceding claims 1 to 7, characterized in that the shaped body (45) has a suitable three-dimensional shape, so that the upper portion (42 a) of the opening (42) is closed to the side of the chamber (50) ,

9. dual-chamber container according to at least one of the preceding claims 1 to 8, characterized in that the material of

Shaped body (45) and / or the separating stopper (40) is selected from rubber, rubber, such as natural or synthetic rubber, plastics, such as elastomers, thermoplastics, thermoplastic elastomers, glass and / or stainless steel.

10. Double-chamber container according to at least one of the preceding claims 1 to 9, characterized in that the cylindrical body (15) consists of or contains glass or plastic.

11. Double-chamber container according to claim 10, characterized in that the cylindrical body (15) consists of transparent glass or contains this.

12. A dual-chamber container according to at least one of the preceding claims 1 to 11, characterized in that in the opening (42) means are provided which the molding (45) after leaving its defined (first) position in the upper portion (42 a) hold the opening (42) in another defined (second) position in the lower portion (42b) of the opening (42), without the access of the liquid component from the chamber (50) into the chamber (30) in this (second) position to prevent.

13. Double-chamber container according to claim 12, characterized in that the means are knobs, lips, beads or webs which can be provided offset from one another and spaced from each other.

14. Double-chamber container according to at least one of the preceding claims 1 to 13, characterized in that the geometric shape and / or dimension of opening (42) and shaped body (45) are matched to one another such that the shaped body (45) under pressure its position in the upper portion (42a) is herausbeförderbar, but the shaped body (45) the opening (42) in the lower portion (42b) does not completely leave.

15. Double-chamber container according to at least one of the preceding claims 1 to 14, characterized in that the opening (42) in the upper portion (42 a) to the side of the liquid component (side A) in the chamber (50) has a different geometric shape and or dimension has as the opening (42) in the lower portion (42 b) to the side of the fixed Component (side B) in the chamber (30).

16. A dual chamber container according to at least one of the preceding claims 1 to 15, characterized in that the opening (42) in the upper portion (42 a) to the side of the liquid component (side A) in the chamber (50) has a smaller inner diameter D1 as the opening (42) in the lower portion (42b) to the fixed component side (side B) in the chamber (30) having a larger inner diameter D2.

17. A dual chamber container according to at least one of the preceding claims 1 to 16, characterized in that the opening (42) in the upper portion (42 a) has a diameter D 1 over a length L 1, wherein L 1> D 1 and the opening (42) according to the length L1 extended to the diameter D2 in the lower portion (42b) over a length L2, where: D2> D1 and L2> DK, where DK represents the diameter of the shaped body (45).

18. Double-chamber container according to at least one of the preceding claims 1 to 17, characterized in that the opening (42) in the lower portion (42b) to the side of the fixed component (side B) one, two or more bypasses (47), in particular in the form of depressions.

19. Double-chamber container according to at least one of the preceding claims 1 to 18, characterized in that the shaped body (45) has a round, egg-shaped, cylindrical shape, a cylindrical shape with rounded side surfaces, a dumbbell-shaped, cuboid, conical, truncated cone-shaped or conical shape.

20. Double-chamber container according to at least one of the preceding claims 1 to 19, characterized in that the closures (20, 60) are selected from plugs, membranes, discs, in particular Sealing discs, optionally with metal crimp caps or plastic caps.

21. Double-chamber container according to at least one of the preceding claims 1 to 20, characterized in that the double-chamber container (10) is a cylindrical ampoule or double-chamber carpule or the like.

22. Double-chamber container according to at least one of the preceding claims 1 to 21, characterized in that the double-chamber container (10) is intended for single or multiple use.

23. A method for filling the dual-chamber container according to one of the preceding claims 1 to 22, comprising the steps:

(1) introducing a separating plug (40) displaceable only under elevated pressure into the cylindrical body (15) with an opening (42) extending continuously in the longitudinal axis of the separating plug (40), which has an upper section (42a) and a lower section (42) 42b), wherein the upper portion (42a) of the opening

(42) is closed in a liquid-tight manner by a mold body (45) which is displaceable under slight to moderate pressure;

(2) filling a solid component on side B of the cylindrical body (15) provided with the separating stopper (40) or

(3) filling a liquid containing the solid component on the side B of the cylindrical body (15) provided with the separation plug (40), then lyophilizing the liquid to obtain the solid component and

Closing this chamber (30) on side B, (4) filling the liquid component in the cylindrical body (15) above the separating plug (40) (side A) and

(5) closing the dual-chamber container (10).

A method for mixing two separate components, at least one of which is liquid, in a dual-chamber container according to any of the preceding claims 1 to 22, comprising a cylindrical body (15) each having a closure (20, 60) on each of the two Ends (5, 70) of the body (15), of which the closure (60) to the side of the liquid component containing chamber (50) is displaceable under pressure, and a displaceable only under increased pressure release plugs (40) arranged in the cylindrical body (15), which defines the volume of the above and below arranged chambers (30, 50), as a seal between the two chambers (30, 50), with in the longitudinal axis of the separating stopper (40) continuously extending opening (42), the one upper portion (42a) and a lower portion (42b), wherein the upper portion (42a) of the opening (42) to the side of the liquid component containing chamber (50) by an under it is closed in a liquid-tight manner to light-weight, moderate to moderate pressure-exerting moldings (45), with the following steps:

Applying pressure to the sliding shutter (60); Pushing out the shaped body (45) from its defined position in the upper portion (42a) of the opening (42); Passing the liquid component from the chamber (30) into the chamber (50) with the solid component to obtain a

Mixture of both components.

25. The method according to claim 24, characterized in that the molded body (45) after being pushed out of its defined (first) position in the upper portion (42a) of the opening (42) in a (second) position in the lower portion (42b) of Opening (42) is held without the access of the liquid component from the chamber (50) is prevented in the chamber (30) in this (second) position.

26. Use of the dual-chamber container according to one of the preceding claims 1 to 22 in the human and veterinary field.