Abstract:
The invention is related to an apparatus comprising a valve body comprising at least two inlet channels and at least one outlet channel and forming a central cavity connecting the at least two inlet channels and the at least one outlet channel, wherein the central cavity encloses a blocking assembly arranged for closing each of the at least two inlet channels by default and for opening an inlet channel when fluid pressure is applied from that inlet channel; wherein each of the at least two inlet channels is configured for fluid communication with a respective reservoir of at least two reservoirs. The invention is further related to a medical device for delivering at least two drug agents from at least two separate reservoirs comprising an apparatus of the aforementioned kind.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     The present application is a U.S. National Phase Application pursuant to 35 U.S.C. §371 of International Application No. PCT/EP2012/059623 filed May 23, 2012, which claims priority to European Patent Application No. 11167354.7 filed May 24, 2011. The entire disclosure contents of these applications are herewith incorporated by reference into the present application. 
     TECHNICAL FIELD 
     The present patent application relates to medical devices of delivering at least two drug agents from separate reservoirs. Such drug agents may comprise a first and a second medicament. The medical device includes a dose setting mechanism for delivering the drug automatically or manually by the user. In particular, the present invention relates to a check valve arrangement as for example usable in such a medical drug delivery device. 
     The drug agents may be contained in two or more multiple dose reservoirs, containers or packages, each containing independent (single drug compound) or pre-mixed (co-formulated multiple drug compounds) drug agents. 
     BACKGROUND 
     Certain disease states require treatment using one or more different medicaments. Some drug compounds need to be delivered in a specific relationship with each other in order to deliver the optimum therapeutic dose. The present patent application is of particular benefit where combination therapy is desirable, but not possible in a single formulation for reasons such as, but not limited to, stability, compromised therapeutic performance and toxicology. 
     For example, in some cases it might be beneficial to treat a diabetic with a long acting insulin (also may be referred to as the first or primary medicament) along with a glucagon-like peptide-1 such as GLP-1 or GLP-1 analog (also may be referred to as the second drug or secondary medicament). 
     Accordingly, there exists a need to provide devices for the delivery of two or more medicaments in a single injection or delivery step that is simple for the user to perform without complicated physical manipulations of the drug delivery device. The proposed drug delivery device provides separate storage containers or cartridge retainers for two or more active drug agents. These active drug agents are then only combined and/or delivered to the patient during a single delivery procedure. These active agents may be administered together in a combined dose or alternatively, these active agents may be combined in a sequential manner, one after the other. 
     SUMMARY 
     The drug delivery device also allows for the opportunity of varying the quantity of the medicaments. For example, one fluid quantity can be varied by changing the properties of the injection device (e.g., setting a user variable dose or changing the device&#39;s “fixed” dose). The second medicament quantity can be changed by manufacturing a variety of secondary drug containing packages with each variant containing a different volume and/or concentration of the second active agent. 
     The drug delivery device may have a single dispense interface. This interface may be configured for fluid communication with the primary reservoir and with a secondary reservoir of medicament containing at least one drug agent. The drug dispense interface can be a type of outlet that allows the two or more medicaments to exit the system and be delivered to the patient. 
     The combination of compounds as discrete units or as a mixed unit can be delivered to the body via a double-ended needle assembly. This would provide a combination drug injection system that, from a user&#39;s perspective, would be achieved in a manner that closely matches the currently available injection devices that use standard needle assemblies. One possible delivery procedure may involve the following steps: 
     1. Attach a dispense interface to a distal end of the electro-mechanical injection device. The dispense interface comprises a first and a second proximal needle. The first and second needles pierce a first reservoir containing a primary compound and a second reservoir containing a secondary compound, respectively. 
     2. Attach a dose dispenser, such as a double-ended needle assembly, to a distal end of the dispense interface. In this manner, a proximal end of the needle assembly is in fluidic communication with both the primary compound and secondary compound. 
     3. Dial up/set a desired dose of the primary compound from the injection device, for example, via a graphical user interface (GUI). 
     4. After the user sets the dose of the primary compound, the micro-processor controlled control unit may determine or compute a dose of the secondary compound and preferably may determine or compute this second dose based on a previously stored therapeutic dose profile. It is this computed combination of medicaments that will then be injected by the user. The therapeutic dose profile may be user selectable. 
     5. Optionally, after the second dose has been computed, the device may be placed in an armed condition. In such an optional armed condition, this may be achieved by pressing and/or holding an “OK” button on a control panel. This condition may provide for greater than a predefined period of time before the device can be used to dispense the combined dose. 
     6. Then, the user will insert or apply the distal end of the dose dispenser (e.g., a double ended needle assembly) into the desired injection site. The dose of the combination of the primary compound and the secondary compound (and potentially a third medicament) is administered by activating an injection user interface (e.g., an injection button). 
     Both medicaments may be delivered via one injection needle or dose dispenser and in one injection step. This offers a convenient benefit to the user in terms of reduced user steps compared to administering two separate injections. 
     Because two or more different liquid drug components may pass through the body of the valve during the process of injection at different times, there is a risk that during the passing of a first drug component the reservoir of another drug component is contaminated by a reverse flow of the first drug component into the reservoir of the other component. This risk is particularly acute if and when the injection needle, and consequently also the outlet of the dispense interface, is blocked. 
     In some conventional valves which are constructed so as to block either one of two inlet channels, the effective blocking of a first inlet channel may depend on ongoing fluid flow from a second inlet channel into the valve&#39;s central cavity and out to the outlet channel. When the outlet channel is blocked and consequently fluid flow from the second inlet channel stops, the blocking mechanism may arrive in an equilibrium position in which neither inlet channel is effectively blocked, consequently resulting in possible fluid flow from the central cavity into the first inlet channel and contamination of the reservoir corresponding to the first inlet channel. 
     To prevent this from happening, additional precautions against any flow of the drug component to be currently injected from the dispense interface into any of the reservoirs of the other drug components are appropriate. 
     Thus it is an object of the invention to provide a valve arrangement for the dispense interface which eliminates or minimizes the possibility of a drug component flowing from a first reservoir and contaminating the reservoir of another drug component, especially for the situation in which the output needle of the injection device is blocked. 
     This object is solved by an apparatus comprising: a valve body comprising at least two inlet channels and at least one outlet channel and forming a central cavity connecting the at least two inlet channels and the at least one outlet channel, wherein the central cavity encloses a blocking assembly arranged for closing each of the at least two inlet channels by default and for opening an inlet channel when fluid pressure is applied from that inlet channel, wherein each of the at least two inlet channels is configured for fluid communication with a respective reservoir of at least two reservoirs. 
     This valve arrangement acts as a check valve. The blocking assembly closes each inlet channel by mechanically blocking the respective inlet channel. The blocking assembly may comprise blocking means. By having all inlet channels be closed by default, this valve arrangement ensures that liquid from a first reservoir entering the central cavity through one of the inlet channels does not flow into another reservoir through one of the other inlet channels. This holds true even when the outlet channel is directly or indirectly obstructed and the liquid from the first reservoir cannot escape through the outlet channel. The effective blocking of any inlet channel does not depend on ongoing flow from another inlet channel to the outlet channel but is always ensured as long as there is no fluid pressure from inside the respective blocked inlet channel. Thus the blocking of the inlet channel corresponding to the drug component that is currently not supposed to be delivered through the outlet channel occurs even when the needle is blocked and contamination of the reservoirs is avoided. 
     This valve arrangement may have any number of inlet channels and outlet channels. Each inlet channel may receive a fluid such as a drug component from a respective reservoir. The fluid may then be disposed through an injection mechanism connected to the outlet channel or outlet channels. At any given time, only fluid from one of the inlet channels is supposed to be flowing from that inlet channel into the central cavity and out through the outlet channel. The central cavity of the valve body houses an assembly configured for closing each of the inlet channels by default. This is done by mechanically blocking each inlet channel. That is, in the absence of fluid pressure from any of the inlet channels, each of the inlet channels is mechanically blocked such that no liquid can enter into any inlet channel from the central cavity. Therefore the opening of any inlet channel is not a prerequisite condition for the closing of the other inlet channels. However, the opening of any inlet channel may further reinforce the closing of the other inlet channels. The blocking mechanism is further arranged such that increasing pressure within the central cavity corresponds to boosted closing pressure on each of the inlet channels. 
     When a liquid such as a drug component flows from an inlet channel to the central cavity, the raised pressure from inside the inlet channel causes the blocking mechanism to open that inlet channel. The other inlet channels remain blocked and thus closed, thereby preventing liquid flow from the other inlet channels into the central cavity as well as from the central cavity into the other inlet channels. The liquid from the open inlet channel can then flow into the central cavity and out through the outlet channel. Once the flow from the reservoir via the inlet channel stops, pressure equilibrium between the central cavity and that inlet channel is restored and the blocking mechanism returns to blocking that inlet channel. But even if the liquid from the inlet channel cannot flow through the outlet channel, for example because of an accidental block in the outlet channel itself or in a needle attached to the outlet channel, flow into the other inlet channels is prevented because of the ongoing block of the other inlet channels. Thereby mixing of the liquids from the individual reservoirs and the according contamination is avoided. 
     A preferred embodiment is characterized in that the blocking assembly is configured to apply bias pressure on the at least two inlet channels. Thus the blocking assembly has geometric and material properties ensuring that by default, i.e. in the absence of any fluid pressure from any of the inlet channels or the outlet channels, the blocking assembly exerts pressure on all of the inlet openings acting to close the inlet openings. This can be achieved for example by using a deformable object as a blocking assembly, which deformable object is fit into the central cavity under strain. By straining to expand, the deformable object exerts pressure on the inlet openings. Using the geometry for providing blocking pressure on the inlet openings in the default state has the advantage that this mechanism is on the one hand cheap and simple to implement and on the other hand robust and reliable. 
     A further preferred embodiment is characterized in that the blocking assembly arranged such that the application of sufficient fluid pressure from an inlet channel of the at least two inlet channels to open that inlet channel causes an increase of closing pressure applied to at least one of the other inlet channels of the at least two inlet channels by the blocking assembly. Thus there is a mechanical link between those parts of the blocking assembly which close at least two inlet channels. This link is such that the fluid pressure from an inlet channel applied to the blocking assembly, which causes the blocking assembly to at least partially budge and open that inlet channel, is mechanically transmitted through the blocking assembly such that it increases the closing effect of the blocking assembly on at least one other inlet channel. Therefore, in the case of flow from an inlet channel into the central cavity and out of an outlet channel, the pressure with which the blocking assembly closes the other inlet channels is actually greater than in the state without any liquid flow from the inlet channels. Consequently, the presence of liquid flow from one inlet channel improves the blocking of the other inlet channels and the risk of contamination of the other reservoirs during operation of the injection device is further reduced. 
     In a further preferred embodiment, the blocking assembly comprises an element of adaptable shape of sufficient size to simultaneously close the at least two inlet channels. The element of adaptable shape may be so large that it only fits into the central cavity under strain. Thereby the pressure to expand of the element of adaptable shape causes a simultaneous blocking pressure on the inlet channels, even in the absence of fluid pressure from any of the inlet channels or outlet channels. The element of adaptable shape may be spherical in its default shape. The element of adaptable shape has sufficient elasticity to budge and open an inlet channel when sufficient liquid pressure is applied from that inlet channel. Using such an adaptable shape as blocking element has the advantage of providing a simple, robust and reliable solution for preventing reverse flow from the central cavity into any inlet channel. 
     In yet another preferred embodiment, the element of adaptable shape comprises a core material and an elastic surface material, wherein the elastic surface material is configured to deform on application of fluid pressure from an inlet channel of the at least two inlet channels such that that inlet channel is opened. In this embodiment the core material is harder and thus less elastic than the outer material. The hardness of the core material prevents the ball from being pressed inside any of the inlet or outlet channels, whereas the elastic outer material ensures a good sealing effect on the inlet channels, even in the presence of unevenness of the rim of the inlet openings. The combination of harder core material and elastic outer material combines the aforementioned respective advantages. The elasticity of the outer material is such that when fluid pressure in one of the inlet channels increases sufficiently, the elastic outer material buckles and thus opens the corresponding inlet channel. This fluid pressure causing the blocking element to open the respective inlet channel also presses the blocking element such that the blocking pressure on the other inlet channels is increased. 
     In a further preferred embodiment, the blocking assembly comprise a rubber seal for each inlet channel, wherein each rubber seal has a concave side facing the respective inlet channel and a convex side. Each rubber seal is cup-shaped. The rubber seals may consist of silicone rubber. Fluid pressure applied from the concave side is focused on the apex of the cup and can therefore act to open the valve at the apex point. Fluid pressure applied from the convex side, on the other hand, is distributed on the circumferential rim and sides of the cup and therefore does not act on a single point of the cup. In the arrangement with the concave side facing the inlet channel and the convex side facing the outlet channel, liquid pressure from the inlet channel causes the rubber seal to open and let the liquid pass, whereas liquid pressure from the outlet channel is blocked by the rubber seal. Thus such a cup-shaped rubber seal provides a check valve that is very simple in its construction and yet effective. It is also easily scaled to any number of inlet channels because only identical rubber seals need to be reproduced for each inlet channel. 
     In another preferred embodiment, each rubber seal comprises at least one slit configured to open and act as a liquid conduit from an inlet channel to one of the at least one outlet channels when fluid pressure is applied to the concave side and further configured to close and block liquid flow when fluid pressure is applied to the convex side. The at least one slit is situated at the apex of the rubber seal, which is cup-shaped. Consequently, the rubber seal expands at the apex when liquid pressure is applied from the concave side, thereby broadening the slit to a liquid conduit through which liquid can pass and further flow out of the outlet channel. Conversely, liquid pressure from the convex side acts primarily on the sides and the circumferential rim of the cup-shaped rubber seal, thereby acting to further compress the slit at the apex and to effectively prevent flow of fluids through the slit. Therefore, the rubber seal blocks liquid flow from the convex side, i.e. from the side facing the outlet channel. This embodiment presents a particularly simple, effective and also scalable implementation of a check valve by means of a rubber seal. 
     In a preferred embodiment, the blocking assembly comprises a blocking element for each inlet channel movable between a first position in which the respective inlet channel is closed and a second position in which the respective inlet channel is open. The blocking element may comprise elastic material and may also comprise rigid material. When the blocking element is in a position to close the inlet channel, liquid flow into the inlet channel is prevented. When the blocking element is in a position in which the inlet channel is open, a liquid may flow from the inlet channel into the central cavity and out of the outlet channel. The pressure of a liquid from an inlet channel on the blocking element of that inlet channel may act to move that blocking element from the closed position to the open position. The movement of the blocking element may be a translation movement, a rotation movement or any combination thereof. A certain part of the blocking element may be rigidly fixed. The movement of the blocking element may also comprise a contortion or deformation of the blocking element. 
     In a further preferred embodiment, the blocking assembly comprises a spring construction configured to provide the bias pressure. The spring construction may comprise spring means. The spring construction is arranged such that it exerts a force on the blocking assembly acting to press the blocking assembly against the respective inlet channel, thereby providing the bias pressure. Liquid pressure from the inlet channel on the blocking assembly needs to overcome this bias pressure in order to open the inlet channel by pushing the blocking element into the open position. When the liquid pressure from the inlet channel ceases, the spring construction acts to push the blocking assembly back into the position closing the inlet channel. Using a dedicated spring construction to provide the bias pressure permits a precise determination of the spring characteristics with which the bias pressure is applied. 
     In a further preferred embodiment, the spring construction comprises a spring for each blocking element. In this embodiment, each blocking element has an associated individual spring. This spring is connected to the blocking element at one end and may be connected to a wall of the central cavity at its other end. Using an individual spring for each blocking element permits applying a different maximum bias pressure and a different displacement-force characteristic curve for each blocking element, which may in particular be advantageous for the case that fluids with different convection properties flow through different inlet channels. 
     In yet a further preferred embodiment, the spring construction comprises at least one spring arranged between at least two blocking elements. The spring construction may also comprise at least one spring arranged between at least three or more blocking elements. The spring construction may comprise the minimum number of springs arranged between the blocking elements required to provide bias pressure to all blocking elements. Being arranged between at least two blocking elements means that the spring is connected with each of the blocking elements it is arranged between in such a way that, when one of the blocking elements is moved to open an inlet channel, the opening force applied to that blocking element is transmitted to the other associated blocking elements by the spring in question such that the pressure with which these other blocking elements are pressed against their respective inlet channels is increased. Therefore opening an inlet channel results in an improved closure of the other inlet channels with which the blocking element of the open inlet channel is connected via the spring. This embodiment provides the advantages that, firstly, a smaller number of springs is required than in the situation in which each blocking element has its own dedicated spring and that, secondly, opening an inlet channel by displacing the blocking element automatically results in an increased closing pressure on the blocking elements with which the blocking element of the opened inlet channel is connected via a spring. Therefore, there is reinforced protection against reverse flow into another inlet channel while a liquid is flowing from a first inlet channel into the central cavity and out of the outlet channel. 
     In a preferred embodiment, the blocking elements are ball-shaped. This means that the blocking elements are round and do not have edges. The blocking elements may be elastic such that they provide tight closure on the rims of the inlet channel, sealing those against the flow of liquid. Using ball-shaped blocking elements ensures that these are adapted to a wide variety of inlet channel geometries, thereby allowing cheap mass production. 
     In a further preferred embodiment, the blocking elements are flaps. The flaps may have the shape of a disc, a rectangular plate or that of some other flat object. The flaps are arranged to cover the inlet channel in the closed position. In the open position, the flaps may be displaced from the inlet channel through a displacement in a direction perpendicular to the inner surface of the central cavity, displacement in a direction parallel to the inner surface of the central cavity, by rotation or by bending. Flaps as blocking element have the advantage of providing good covering of the inlet channel without consuming a lot of volume in the central cavity. 
     In a preferred embodiment of the invention, the flaps are integrally formed with the valve body. This means that the flaps consist of the same material as the valve body and that they are directly connected to the valve body. In this embodiment, the flaps open the inlet channel by being bent by the liquid pressure from the inlet channel. Consequently, the fluid pressure from the inlet channel must overcome the bending stress of the flap in order to open that inlet channel. Further the bending stress of the flap acts as a spring force acting to push the flap back into the closed position. Therefore this embodiment has the advantage that no additional spring element aside from the flap itself is needed. 
     The invention is further directed at a medical device for delivering at least two drug agents from at least two separate reservoirs comprising an apparatus according to any of the aforementioned embodiments. 
     These as well as other advantages of various aspects of the present invention will become apparent to those of ordinary skill in the art by reading the following detailed description, with appropriate reference to the accompanying drawings: 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         FIG. 1  illustrates a perspective view of the delivery device illustrated in  FIGS. 1 a  and 1 b    with an end cap of the device removed; 
         FIG. 2  illustrates a perspective view of the delivery device distal end showing the cartridge; 
         FIG. 3  illustrates a perspective view of the cartridge holder illustrated in  FIG. 1  with one cartridge retainer in an open position; 
         FIG. 4  illustrates a dispense interface and a dose dispenser that may be removably mounted on a distal end of the delivery device illustrated in  FIG. 1 ; 
         FIG. 5  illustrates the dispense interface and the dose dispenser illustrated in  FIG. 4  mounted on a distal end of the delivery device illustrated in  FIG. 1 ; 
         FIG. 6  illustrates one arrangement of the dose dispenser that may be mounted on a distal end of the delivery device; 
         FIG. 7  illustrates a perspective view of the dispense interface illustrated in  FIG. 4 ; 
         FIG. 8  illustrates another perspective view of the dispense interface illustrated in  FIG. 4 ; 
         FIG. 9  illustrates a cross-sectional view of the dispense interface illustrated in  FIG. 4 ; 
         FIG. 10  illustrates an exploded view of the dispense interface illustrated in  FIG. 4 ; 
         FIG. 11  illustrates a cross-sectional view of the dispense interface and dose dispenser mounted onto a drug delivery device, such as the device illustrated in  FIG. 1 ; 
         FIG. 12  illustrates a cross-sectional view of an embodiment of the valve body using ball-shaped blocking elements connected by a spring, which spring is arranged in a guidance opening; 
         FIG. 13  illustrates a cross-sectional view of an embodiment of the valve body using ball-shaped blocking elements connected by a lever arm arrangement; 
         FIG. 14  illustrates a cross-sectional view of an embodiment of the valve body using ball-shaped blocking elements each having their own dedicated curved lever arm. 
         FIG. 15  illustrates a spherical element usable as blocking assembly; 
         FIG. 16  illustrates a cross-sectional view of an embodiment of the valve body with the spherical element of  FIG. 15  used as blocking assembly; 
         FIG. 17  illustrates a cross-sectional view of an embodiment of the valve body using flaps connected by a spring, which spring is arranged in a guidance opening; 
         FIG. 18  illustrates a cross-sectional view of an embodiment of the valve body as in  FIG. 17  in which the flaps are formed integrally with the valve body; 
         FIGS. 19 a  and 19 b    illustrate a cross-sectional view of an embodiment of the valve body using cup-shaped blocking elements. 
     
    
    
     DETAILED DESCRIPTION 
     The drug delivery device illustrated in  FIG. 1  comprises a main body  14  that extends from a proximal end  16  to a distal end  15 . At the distal end  15 , a removable end cap or cover  18  is provided. This end cap  18  and the distal end  15  of the main body  14  work together to provide a snap fit or form fit connection so that once the cover  18  is slid onto the distal end  15  of the main body  14 , this frictional fit between the cap and the main body outer surface  20  prevents the cover from inadvertently falling off the main body. 
     The main body  14  contains a micro-processor control unit, an electro-mechanical drive train, and at least two medicament reservoirs. When the end cap or cover  18  is removed from the device  10  (as illustrated in  FIG. 1 ), a dispense interface  200  is mounted to the distal end  15  of the main body  14 , and a dose dispenser (e.g., a needle assembly) is attached to the interface. The drug delivery device  10  can be used to administer a computed dose of a second medicament (secondary drug compound) and a variable dose of a first medicament (primary drug compound) through a single needle assembly, such as a double ended needle assembly. 
     A control panel region  60  is provided near the proximal end of the main body  14 . Preferably, this control panel region  60  comprises a digital display  80  along with a plurality of human interface elements that can be manipulated by a user to set and inject a combined dose. In this arrangement, the control panel region comprises a first dose setting button  62 , a second dose setting button  64  and a third button  66  designated with the symbol “OK.” In addition, along the most proximal end of the main body, an injection button  74  is also provided (not visible in the perspective view of  FIG. 1 ). 
     The cartridge holder  40  can be removably attached to the main body  14  and may contain at least two cartridge retainers  50  and  52 . Each retainer is configured so as to contain one medicament reservoir, such as a glass cartridge. Preferably, each cartridge contains a different medicament. 
     In addition, at the distal end of the cartridge holder  40 , the drug delivery device illustrated in  FIG. 1  includes a dispense interface  200 . As will be described in relation to  FIG. 4 , in one arrangement, this dispense interface  200  includes a main outer body  210  that is removably attached to a distal end  42  of the cartridge housing  40 . As can be seen in  FIG. 1 , a distal end  214  of the dispense interface  200  preferably comprises a needle hub  216 . This needle hub  216  may be configured so as to allow a dose dispenser, such as a conventional pen type injection needle assembly, to be removably mounted to the drug delivery device  10 . 
     Once the device is turned on, the digital display  80  shown in  FIG. 1  illuminates and provides the user certain device information, preferably information relating to the medicaments contained within the cartridge holder  40 . For example, the user is provided with certain information relating to both the primary medicament (Drug A) and the secondary medicament (Drug B). 
     As shown in  FIG. 3 , the first and a second cartridge retainers  50 ,  52  comprise hinged cartridge retainers. These hinged retainers allow user access to the cartridges.  FIG. 3  illustrates a perspective view of the cartridge holder  40  illustrated in  FIG. 1  with the first hinged cartridge retainer  50  in an open position.  FIG. 3  illustrates how a user might access the first cartridge  90  by opening up the first retainer  50  and thereby having access to the first cartridge  90 . 
     As mentioned above when discussing  FIG. 1 , a dispense interface  200  is coupled to the distal end of the cartridge holder  40 .  FIG. 4  illustrates a flat view of the dispense interface  200  unconnected to the distal end of the cartridge holder  40 . A dose dispenser or needle assembly that may be used with the interface  200  is also illustrated and is provided in a protective outer cap  420 . 
     In  FIG. 5 , the dispense interface  200  illustrated in  FIG. 4  is shown coupled to the cartridge holder  40 . The axial attachment means between the dispense interface  200  and the cartridge holder  40  can be any known axial attachment means to those skilled in the art, including snap locks, snap fits, snap rings, keyed slots, and combinations of such connections. The connection or attachment between the dispense interface and the cartridge holder may also contain additional features (not shown), such as connectors, stops, splines, ribs, grooves, pips, clips and the like design features, that ensure that specific hubs are attachable only to matching drug delivery devices. Such additional features would prevent the insertion of a non-appropriate secondary cartridge to a non-matching injection device. 
       FIG. 5  also illustrates the needle assembly  400  and protective cover  420  coupled to the distal end of the dispense interface  200  that may be screwed onto the needle hub of the interface  200 .  FIG. 6  illustrates a cross sectional view of the double ended needle assembly  400  mounted on the dispense interface  200  in  FIG. 5 . 
     The needle assembly  400  illustrated in  FIG. 6  comprises a double ended needle  406  and a hub  401 . The double ended needle or cannula  406  is fixedly mounted in a needle hub  401 . This needle hub  401  comprises a circular disk shaped element which has along its periphery a circumferential depending sleeve  403 . Along an inner wall of this hub member  401 , a thread  404  is provided. This thread  404  allows the needle hub  401  to be screwed onto the dispense interface  200  which, in one preferred arrangement, is provided with a corresponding outer thread along a distal hub. At a center portion of the hub element  401  there is provided a protrusion  402 . This protrusion  402  projects from the hub in an opposite direction of the sleeve member. A double ended needle  406  is mounted centrally through the protrusion  402  and the needle hub  401 . This double ended needle  406  is mounted such that a first or distal piercing end  405  of the double ended needle forms an injecting part for piercing an injection site (e.g., the skin of a user). 
     Similarly, a second or proximal piercing end  407  of the needle assembly  400  protrudes from an opposite side of the circular disc so that it is concentrically surrounded by the sleeve  403 . In one needle assembly arrangement, the second or proximal piercing end  407  may be shorter than the sleeve  403  so that this sleeve to some extent protects the pointed end of the back sleeve. The needle cover cap  420  illustrated in  FIGS. 4 and 5  provides a form fit around the outer surface  403  of the hub  401 . 
     Referring now to  FIGS. 4 to 11 , one preferred arrangement of this interface  200  will now be discussed. In this one preferred arrangement, this interface  200  comprises: 
     a. a main outer body  210 , 
     b. an first inner body  220 , 
     c. a second inner body  230 , 
     d. a first piercing needle  240 , 
     e. a second piercing needle  250 , 
     f. a valve seal  260 , and 
     g. a septum  270 . 
     The main outer body  210  comprises a main body proximal end  212  and a main body distal end  214 . At the proximal end  212  of the outer body  210 , a connecting member is configured so as to allow the dispense interface  200  to be attached to the distal end of the cartridge holder  40 . Preferably, the connecting member is configured so as to allow the dispense interface  200  to be removably connected the cartridge holder  40 . In one preferred interface arrangement, the proximal end of the interface  200  is configured with an upwardly extending wall  218  having at least one recess. For example, as may be seen from  FIG. 8 , the upwardly extending wall  218  comprises at least a first recess  217  and a second recess  219 . 
     Preferably, the first and the second recesses  217 ,  219  are positioned within this main outer body wall so as to cooperate with an outwardly protruding member located near the distal end of the cartridge housing  40  of the drug delivery device  10 . For example, this outwardly protruding member  48  of the cartridge housing may be seen in  FIGS. 4 and 5 . A second similar protruding member is provided on the opposite side of the cartridge housing. As such, when the interface  200  is axially slid over the distal end of the cartridge housing  40 , the outwardly protruding members will cooperate with the first and second recess  217 ,  219  to form an interference fit, form fit, or snap lock. Alternatively, and as those of skill in the art will recognize, any other similar connection mechanism that allows for the dispense interface and the cartridge housing  40  to be axially coupled could be used as well. 
     The main outer body  210  and the distal end of the cartridge holder  40  act to form an axially engaging snap lock or snap fit arrangement that could be axially slid onto the distal end of the cartridge housing. In one alternative arrangement, the dispense interface  200  may be provided with a coding feature so as to prevent inadvertent dispense interface cross use. That is, the inner body of the hub could be geometrically configured so as to prevent an inadvertent cross use of one or more dispense interfaces. 
     A mounting hub is provided at a distal end of the main outer body  210  of the dispense interface  200 . Such a mounting hub can be configured to be releasably connected to a needle assembly. As just one example, this connecting means  216  may comprise an outer thread that engages an inner thread provided along an inner wall surface of a needle hub of a needle assembly, such as the needle assembly  400  illustrated in  FIG. 6 . Alternative releasable connectors may also be provided such as a snap lock, a snap lock released through threads, a bayonet lock, a form fit, or other similar connection arrangements. 
     The dispense interface  200  further comprises a first inner body  220 . Certain details of this inner body are illustrated in  FIG. 8-11 . Preferably, this first inner body  220  is coupled to an inner surface  215  of the extending wall  218  of the main outer body  210 . More preferably, this first inner body  220  is coupled by way of a rib and groove form fit arrangement to an inner surface of the outer body  210 . For example, as can be seen from  FIG. 9 , the extending wall  218  of the main outer body  210  is provided with a first rib  213   a  and a second rib  213   b . This first rib  213   a  is also illustrated in  FIG. 10 . These ribs  213   a  and  213   b  are positioned along the inner surface  215  of the wall  218  of the outer body  210  and create a form fit or snap lock engagement with cooperating grooves  224   a  and  224   b  of the first inner body  220 . In a preferred arrangement, these cooperating grooves  224   a  and  224   b  are provided along an outer surface  222  of the first inner body  220 . 
     In addition, as can be seen in  FIG. 8-10 , a proximal surface  226  near the proximal end of the first inner body  220  may be configured with at least a first proximally positioned piercing needle  240  comprising a proximal piercing end portion  244 . Similarly, the first inner body  220  is configured with a second proximally positioned piercing needle  250  comprising a proximally piercing end portion  254 . Both the first and second needles  240 ,  250  are rigidly mounted on the proximal surface  226  of the first inner body  220 . 
     Preferably, this dispense interface  200  further comprises a valve arrangement. Such a valve arrangement could be constructed so as to prevent cross contamination of the first and second medicaments contained in the first and second reservoirs, respectively. A preferred valve arrangement may also be configured so as to prevent back flow and cross contamination of the first and second medicaments. 
     In one preferred system, dispense interface  200  includes a valve arrangement in the form of a valve seal  260 . Such a valve seal  260  may be provided within a cavity  231  defined by the second inner body  230 , so as to form a holding chamber  280 . Preferably, cavity  231  resides along an upper surface of the second inner body  230 . This valve seal comprises an upper surface that defines both a first fluid groove  264  and second fluid groove  266 . For example,  FIG. 9  illustrates the position of the valve seal  260 , seated between the first inner body  220  and the second inner body  230 . During an injection step, this seal valve  260  helps to prevent the primary medicament in the first pathway from migrating to the secondary medicament in the second pathway, while also preventing the secondary medicament in the second pathway from migrating to the primary medicament in the first pathway. Preferably, this seal valve  260  comprises a first non-return valve  262  and a second non-return valve  268 . As such, the first non-return valve  262  prevents fluid transferring along the first fluid pathway  264 , for example a groove in the seal valve  260 , from returning back into this pathway  264 . Similarly, the second non-return valve  268  prevents fluid transferring along the second fluid pathway  266  from returning back into this pathway  266 . 
     Together, the first and second grooves  264 ,  266  converge towards the non-return valves  262  and  268  respectively, to then provide for an output fluid path or a holding chamber  280 . This holding chamber  280  is defined by an inner chamber defined by a distal end of the second inner body both the first and the second non return valves  262 ,  268  along with a pierceable septum  270 . As illustrated, this pierceable septum  270  is positioned between a distal end portion of the second inner body  230  and an inner surface defined by the needle hub of the main outer body  210 . 
     The holding chamber  280  terminates at an outlet port of the interface  200 . This outlet port  290  is preferably centrally located in the needle hub of the interface  200  and assists in maintaining the pierceable seal  270  in a stationary position. As such, when a double ended needle assembly is attached to the needle hub of the interface (such as the double ended needle illustrated in  FIG. 6 ), the output fluid path allows both medicaments to be in fluid communication with the attached needle assembly. 
     The hub interface  200  further comprises a second inner body  230 . As can be seen from  FIG. 9 , this second inner body  230  has an upper surface that defines a recess, and the valve seal  260  is positioned within this recess. Therefore, when the interface  200  is assembled as shown in  FIG. 9 , the second inner body  230  will be positioned between a distal end of the outer body  210  and the first inner body  220 . Together, second inner body  230  and the main outer body hold the septum  270  in place. The distal end of the inner body  230  may also form a cavity or holding chamber that can be configured to be fluid communication with both the first groove  264  and the second groove  266  of the valve seal. 
     Axially sliding the main outer body  210  over the distal end of the drug delivery device attaches the dispense interface  200  to the multi-use device. In this manner, a fluid communication may be created between the first needle  240  and the second needle  250  with the primary medicament of the first cartridge and the secondary medicament of the second cartridge, respectively. 
       FIG. 11  illustrates the dispense interface  200  after it has been mounted onto the distal end  42  of the cartridge holder  40  of the drug delivery device  10  illustrated in  FIG. 1 . A double ended needle  400  is also mounted to the distal end of this interface. The cartridge holder  40  is illustrated as having a first cartridge containing a first medicament and a second cartridge containing a second medicament. 
     When the interface  200  is first mounted over the distal end of the cartridge holder  40 , the proximal piercing end  244  of the first piercing needle  240  pierces the septum of the first cartridge  90  and thereby resides in fluid communication with the primary medicament  92  of the first cartridge  90 . A distal end of the first piercing needle  240  will also be in fluid communication with a first fluid path groove  264  defined by the valve seal  260 . 
     Similarly, the proximal piercing end  254  of the second piercing needle  250  pierces the septum of the second cartridge  100  and thereby resides in fluid communication with the secondary medicament  102  of the second cartridge  100 . A distal end of this second piercing needle  250  will also be in fluid communication with a second fluid path groove  266  defined by the valve seal  260 . 
       FIG. 11  illustrates a preferred arrangement of such a dispense interface  200  that is coupled to a distal end  15  of the main body  14  of drug delivery device  10 . Preferably, such a dispense interface  200  is removably coupled to the cartridge holder  40  of the drug delivery device  10 . 
     As illustrated in  FIG. 11 , the dispense interface  200  is coupled to the distal end of a cartridge housing  40 . This cartridge holder  40  is illustrated as containing the first cartridge  90  containing the primary medicament  92  and the second cartridge  100  containing the secondary medicament  102 . Once coupled to the cartridge housing  40 , the dispense interface  200  essentially provides a mechanism for providing a fluid communication path from the first and second cartridges  90 ,  100  to the common holding chamber  280 . This holding chamber  280  is illustrated as being in fluid communication with a dose dispenser. Here, as illustrated, this dose dispenser comprises the double ended needle assembly  400 . As illustrated, the proximal end of the double ended needle assembly is in fluid communication with the chamber  280 . 
     In one preferred arrangement, the dispense interface is configured so that it attaches to the main body in only one orientation, that is it is fitted only one way round. As such as illustrated in  FIG. 11 , once the dispense interface  200  is attached to the cartridge holder  40 , the primary needle  240  can only be used for fluid communication with the primary medicament  92  of the first cartridge  90  and the interface  200  would be prevented from being reattached to the holder  40  so that the primary needle  240  could now be used for fluid communication with the secondary medicament  102  of the second cartridge  100 . Such a one way around connecting mechanism may help to reduce potential cross contamination between the two medicaments  92  and  102 . 
     In the following embodiments of the present invention will be described in detail with reference to  FIGS. 12 to 19   a  and  19   b.    
     In  FIGS. 12 and 13  cross-sectional views of an embodiment of the valve body are shown, comprising two inlet channels  302  and  304 , one outlet channel  306  and a central cavity  308  connecting the inlet channels  302 ,  304  and the outlet channel  306 . A first ball-shaped blocking element  310  and a second ball-shaped blocking element  312  are contained within the central cavity  308  and connected by a spring  314 . The spring  314  is arranged in a guidance opening formed integrally with the valve body. The ball-shaped blocking elements  310 ,  312  and the spring  314  are arranged such that in the absence of outside pressure, the spring provides a bias pressure to press the first ball-shaped blocking element  310  against the first inlet channel  302  and the second ball-shaped blocking element  312  against the second inlet channel  304  respectively, thereby closing both inlet channels  302 ,  304 . 
     The inlet channels  302  and  304  are in fluid communication with a first reservoir and with a second reservoir (generally shown for example in  FIG. 11  as reservoirs  90  and  100 ). Moreover, outlet channel  306  is configured for fluid connection with a septum  270 , which has been also discussed with reference to  FIG. 11 . 
     The functionality of the valve is as follows: when a liquid from the first reservoir, for example a drug component, is to be passed through the valve, for example as the first part of an injection procedure for the sequential injection of two different drug components, the liquid enters the first inlet channel  302  from the reservoir. As the liquid enters the first inlet channel  302 , the pressure therein increases until it suffices to push the first ball-shaped blocking element  310  away from the first inlet channel  302  against the pressure applied to the first ball-shaped blocking element  310 . Now the liquid can enter the central cavity  308  and flow outwards through the outlet channel  306 . The liquid cannot enter the second inlet channel  304 , because the second ball-shaped blocking element  312  is pressed against the second inlet channel  304  by the spring  314 , thereby closing the second inlet channel  304  from liquid flow. The closing pressure applied by the spring  314  on the second ball-shaped blocking element  312  is a combination of the bias pressure with which the spring presses the second ball-shaped blocking element  312  against the second inlet channel  304  in the equilibrium state and the force with which the first ball-shaped blocking element  310  is pushed in the open position, because this force is transmitted at least in part to the second ball-shaped blocking element  312  by the spring  314 . 
     Even if the liquid is prevented from flowing out of the outlet channel  306 , for example because of an obstruction in a needle fluidly connected to the outlet channel  306 , there is no reverse flow in the second inlet channel  304 . This is for the following reasons: As long as liquid flows from the first inlet channel  302  into the central cavity  308 , a force sufficient to open the first inlet channel  302  acts on the first ball-shaped blocking element  310  and this force is added at least in part to the force with which the second ball-shaped blocking element  312  is pressed against the second inlet channel  304 , thereby closing the second inlet channel  304 . But even if the liquid flow from the first inlet channel  302  stops and the first ball-shaped blocking element  310  returns to a position blocking the first inlet channel  302  because of the restored pressure equilibrium, there is always at the very least the bias pressure applied by the spring  314  acting on the second ball-shaped blocking element  312  to block the second inlet channel  304 . Therefore reverse flow from the central cavity  308  into the second inlet channel  304  is prevented. 
     Due to its symmetry with respect to the first inlet channel  302  and the second inlet channel  304 , the valve functions according to the analogous principle as just described when liquid from the second reservoir, such as a second drug component for the second part of the injection procedure, passes through the central cavity  308  and further out of the outlet channel  306 , with the first and second ball-shaped blocking elements  310 ,  312  and first and second inlet channels  302 ,  304 , respectively, switching their roles. 
     In the valve body illustrated in  FIG. 13 , the first ball-shaped blocking element  310  and the second ball-shaped blocking element  312  are connected to the valve body by an approximately T-shaped lever arm arrangement  316  made of plastic material. The base of the lever arm arrangement  316  is integrally connected to the valve body whereas the end of each arm of the lever arm arrangement  316  is connected to the first ball-shaped blocking element  310  or the second ball-shaped blocking element  312 , respectively. The lever arm arrangement  316  is constructed such that already in the equilibrium state, i.e. in the absence of fluid pressure, strain in the lever arm arrangement  316  acts to exert a bias force on the ball-shaped blocking elements  310 ,  312 , pressing them against the first and second inlet channel  302  and  304 , respectively, such that both inlet channels  302 ,  304  are closed. The lever arm arrangement  316  is further configured such that the force required for a displacement of the first ball-shaped blocking element  310 , as occurs when the first inlet channel  302  is opened through fluid pressure from within the first inlet channel  302 , is at least partially transmitted to the second ball-shaped blocking element  312  by the lever arm arrangement  316  such that the force with which the second ball-shaped blocking element  312  is pressed against the second inlet channel  304  is increased. Because of symmetry, the same effect occurs in the opposite direction when the second ball-shaped blocking element  312  is displaced. Therefore the lever arm arrangement  316  corresponds in its mechanical effect to the spring  314  of  FIG. 12 . 
       FIG. 14  illustrates the cross-section of a further embodiment of a valve body. This valve body corresponds to that of  FIG. 13  with the difference that instead of a single approximately T-shaped lever arm arrangement  316  the valve body comprises a first and second curved lever arm  318 ,  320  made of plastic material and separately connecting the first and second ball-shaped blocking elements  310 ,  312  to the valve body. The curved lever arms  318 ,  320  are constructed such that they are strained to provide a bias force pressing the first and second ball-shaped blocking elements  310 ,  312  against the first and second inlet channels  302 ,  304 , respectively. Likewise, displacement of a ball-shaped blocking elements  310 ,  312  further strains the associated curved lever arm  318 ,  320 , thereby resulting in a resetting force greater than the bias force acting on the displaced ball-shaped blocking element  310 ,  312  toward a closing position of the respective inlet channel  302 ,  304 . Because of the lack of a direct mechanical connection in the embodiment of  FIG. 14 —unlike the embodiments of  FIG. 12  and  FIG. 13 —the displacement force on any ball-shaped blocking element  310 ,  312  is not directly transmitted to the respective other ball-shaped blocking element  310 ,  312 . 
       FIG. 15  illustrates a spherical element  322  consisting of a core material  324  and an outer material  326 , wherein the core material  324  is more rigid than the elastic outer material  326 . The elasticity of the outer material  326  makes the shape of the spherical element  322  adaptable. 
       FIG. 16  illustrates a valve body comprising a central cavity  308 , first and second inlet channels  302 ,  304  and an outlet channel  306  as in the embodiments illustrated in  FIGS. 12 to 14 . The other external structures and connections of this valve body are also identical to those of  FIGS. 12 to 14 . 
     Inside the central cavity  308 , there is a spherical element  322  as illustrated in  FIG. 15 . The spherical element  322  is dimensioned such that it is under strain to expand when fit inside the central cavity  308 . In particular, this constriction of the spherical element  322  results in a deformation and corresponding strain of the elastic outer material  326 . Consequently, in an equilibrium state in the absence of any fluid pressure, the spherical element  322  closes the inlet channels  302 ,  304  and exerts bias pressure on the inlet channels  302 ,  304 , thereby ensuring that any unevenness of the rim of the inlet channels  302  and  304  is well sealed. On the other hand, the rigid core material  324  prevents the ball from being pressed inside any inlet channel  302 ,  304  or the outlet channel  306 . Optionally, there may be recesses in the valve body around the openings of the inlet channels  302 ,  304  in order to hold the spherical element  322  in place. 
     The functionality of the valve is similar to that illustrated in  FIG. 12  and described as follows. When a liquid from the first reservoir, for example a drug component, is to be passed through the valve, for example as the first part of an injection procedure for the sequential injection of two different drug components, the liquid enters the first inlet channel  302  from the reservoir. As the liquid enters the first inlet channel  302 , the pressure therein increases until it suffices to counteract the bias pressure acting on the first inlet channel  302  and deform the elastic outer material  326  sufficiently to form a fluid passageway from the first inlet channel to the outlet channel  306 . Now the liquid can enter the central cavity  308  and flow outwards through the outlet channel  306 . The liquid cannot enter the second inlet channel  304 , because the spherical element  322  remains pressed against the second inlet channel  304  by virtue of its strain to expand, thereby closing the second inlet channel  304  from liquid flow. The closing pressure applied by the spherical element  322  on the second inlet channel  304  is a combination of the bias pressure with which the spherical element  322  presses against the second inlet channel  304  in the equilibrium state and the additional pressure with which the elastic outer material  326  is deformed at the first inlet channel  302 . This force is transmitted at least in part to the second inlet channel  304  by the spherical element  322 . 
     Even if the liquid is prevented from flowing out of the outlet channel  306 , for example because of an obstruction in a needle fluidly connected to the outlet channel  306 , there is no reverse flow in the second inlet channel  304 . This is for the following reasons: As long as liquid flows from the first inlet channel  302  into the central cavity  308 , a force sufficient to open the first inlet channel  302  acts on the spherical element  322  and this force is added at least in part to the force with which the spherical element  322  is pressed against the second inlet channel  304 , thereby closing the second inlet channel  304 . But even if the liquid flow from the first inlet channel  302  stops and the elastic outer material  326  expands again to close the first inlet channel  302 , there is always at the very least the bias pressure applied by the spherical element  322  acting to block the second inlet channel  304 . Therefore reverse flow from the central cavity  308  into the second inlet channel  304  is prevented. 
     Due to its symmetry with respect to the first inlet channel  302  and the second inlet channel  304 , the valve functions according to the analogous principle as just described when liquid from the second reservoir, such as a second drug component for the second part of the injection procedure, passes through the central cavity  308  and further out of the outlet channel  306 . 
       FIG. 17  shows the cross-section of a further embodiment of a valve body. This embodiment is identical to that of  FIG. 12  except for the fact that instead of ball-shaped blocking elements  310 ,  312 , a first flap  330  and a second flap  332  is used for blocking the first inlet channel  302  and second inlet channel  304 , respectively. The method of operation of this embodiment is the same as that of  FIG. 12 . 
       FIG. 18  shows a variation of the embodiment of  FIG. 17  in which the flaps  330 ,  332  are formed integrally with the valve body. While the principle of operation of this embodiment is identical to that of the embodiment of  FIG. 17 , because of the integral connection between the flaps  330 ,  332  and the valve body, the opening of the inlet channels  302 ,  304  does not involve a translational movement of the respective flap  330 ,  332 , but rather a bending of the respective flap  330 ,  332 . Therefore in order to open the appropriate inlet channel  302 ,  304 , the fluid pressure must not only overcome the bias pressure of the spring  328  acting on the flap  330 ,  332 , but also the internal strain of the flap  330 ,  332  being bent. Consequently, the resistive force of this bending acts as a restoring force to returning the flap  330 ,  332  to their respective closed position in addition to the force applied by the spring  328 . 
       FIG. 19 a    and  FIG. 19 b    illustrate a further embodiment of the valve body. In this embodiment, the central cavity  308  is just formed by the T-shaped intersection of the inlet channels  302 ,  304  and the outlet channel  306 . The further external fluid connections of the inlet channels  302 ,  304  and the outlet channel  306  as well as the intended mode of operation of this valve body is identical to that of the other embodiments. 
     This embodiment comprises cup-shaped rubber seals  334 ,  336  between each inlet channel  302 ,  304  and the central cavity  308 . The concave side of the rubber seals  334 ,  336  faces the corresponding inlet channel  302 ,  304  and the convex side of the rubber seals  334 ,  336  faces the central cavity  308  and consequently also the outlet channel  306 . Each rubber seal  334 ,  336  comprises a slit at its apex, corresponding to the apex of the cup-shape. 
     In the equilibrium state depicted in  FIG. 19 a   , i.e. in the absence of external pressure, the cup-shape of the rubber seals  334 ,  336  is closed, thereby preventing liquid flow through the slits of the rubber seals  334 ,  336 . 
     The shape and construction of the rubber seals  334 ,  336  ensures that liquid pressure from the concave side focuses on the apex of the rubber seal  334 ,  336 , thereby causing the rubber seal  334 ,  336  to open at its slit and allow liquid flow from the concave side to the convex side.  FIG. 19 b    shows the first rubber seal  334  in this open state and the second rubber seal  336  in the closed state. 
     Once the liquid pressure from the concave side subsides, the rubber seal  334 ,  336  resumes its closed arrangement through its internal torsion forces as depicted in  FIG. 19   a.    
     On the other hand, any liquid pressure from the convex side of a rubber seal  334 ,  336  is distributed on the lateral side of the cup-shape and the rim of the rubber seals  334 ,  336 , thereby acting to further compress the slit in the apex and therefore close the respective rubber seal  334 ,  336  even tighter. 
     Because of these mechanical properties of the rubber seals  334 ,  336 , the rubber seals enable liquid flow from any of the inlet channels  302 ,  304  through the central cavity  308  and out of the outlet channel  306  in the presence of liquid pressure from that inlet channel  302 ,  304 , but effectively prevent any reverse flow into any other inlet channel  302 ,  304 . 
     An example for the operation of this arrangement is given in the following. At the onset, both rubber seals  334 ,  336  are closed as shown in  FIG. 19 a   . When a liquid from the first reservoir, for example a drug component, is to be passed through the valve, for example as the first part of an injection procedure for the sequential injection of two different drug components, the liquid enters the first inlet channel  302  from the reservoir. As the liquid enters the first inlet channel  302 , the pressure therein increases until it suffices to open the first rubber seal  334  as shown in  FIG. 19 b   . Now the liquid can enter the central cavity  308  and flow outwards through the outlet channel  306 . The liquid cannot enter the second inlet channel  304 , because the second rubber seal  336  is closed and is actually shut tighter because of the liquid pressure acting from the central cavity  308  and therefore on the convex side of the rubber seal  336 . 
     Even if the liquid is prevented from flowing out of the outlet channel  306 , for example because of an obstruction in a needle fluidly connected to the outlet channel  306 , there is no reverse flow into the second inlet channel  304 . This is because an obstruction in the outlet channel  306  will cause an increase in the pressure on the convex side of the second rubber seal  336 , thereby making the closure of the second inlet channel  304  ever tighter. Therefore reverse flow from the central cavity  308  into the second inlet channel  304  is prevented. 
     Due to its symmetry with respect to the first inlet channel  302  and the second inlet channel  304 , the rubber seals  334 ,  336  function according to the analogous principle as just described when liquid from the second reservoir, such as a second drug component for the second part of the injection procedure, passes through the central cavity  308  and further out of the outlet channel  306 , with the first and second rubber seals  334 ,  336  and first and second inlet channels  302 ,  304 , respectively, switching their roles. 
     The term “drug” or “medicament”, as used herein, means a pharmaceutical formulation containing at least one pharmaceutically active compound, 
     wherein in one embodiment the pharmaceutically active compound has a molecular weight up to 1500 Da and/or is a peptide, a proteine, a polysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or a fragment thereof, a hormone or an oligonucleotide, or a mixture of the above-mentioned pharmaceutically active compound, 
     wherein in a further embodiment the pharmaceutically active compound is useful for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism, acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis, 
     wherein in a further embodiment the pharmaceutically active compound comprises at least one peptide for the treatment and/or prophylaxis of diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, 
     wherein in a further embodiment the pharmaceutically active compound comprises at least one human insulin or a human insulin analogue or derivative, glucagon-like peptide (GLP-1) or an analogue or derivative thereof, or exedin-3 or exedin-4 or an analogue or derivative of exedin-3 or exedin-4. 
     Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) human insulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28) human insulin; human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin. 
     Insulin derivates are for example B29-N-myristoyl-des(B30) human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyhepta-decanoyl)-des(B30) human insulin and B29-N-(ω-carboxyhepta-decanoyl) human insulin. 
     Exendin-4 for example means Exendin-4(1-39), a peptide of the sequence H His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2. 
     Exendin-4 derivatives are for example selected from the following list of compounds:
     H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2   H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,   des Pro36 [Asp28] Exendin-4(1-39),   des Pro36 [IsoAsp28] Exendin-4(1-39),   des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),   des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),   des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),   des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),   des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),   des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or   des Pro36 [Asp28] Exendin-4(1-39),   des Pro36 [IsoAsp28] Exendin-4(1-39),   des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),   des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),   des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),   des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),   des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),   des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),   wherein the group -Lys6-NH2 may be bound to the C-terminus of the Exendin-4 derivative;   or an Exendin-4 derivative of the sequence   H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,   des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,   H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,   H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,   des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,   H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,   H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,   H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,   H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,   des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,   H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,   H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,   des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,   H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,   des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,   H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,   H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,   H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,   H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25] Exendin-4(1-39)-NH2,   H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,   des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,   H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(S1-39)-(Lys)6-NH2,   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2;   or a pharmaceutically acceptable salt or solvate of any one of the afore-mentioned Exedin-4 derivative.   

     Hormones are for example hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists as listed in Rote Liste, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, Goserelin. 
     A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra low molecular weight heparin or a derivative thereof, or a sulphated, e.g. a poly-sulphated form of the above-mentioned polysaccharides, and/or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium. 
     Antibodies are globular plasma proteins (˜150 kDa) that are also known as immunoglobulins which share a basic structure. As they have sugar chains added to amino acid residues, they are glycoproteins. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit); secreted antibodies can also be dimeric with two Ig units as with IgA, tetrameric with four Ig units like teleost fish IgM, or pentameric with five Ig units, like mammalian IgM. 
     The Ig monomer is a “Y”-shaped molecule that consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds between cysteine residues. Each heavy chain is about 440 amino acids long; each light chain is about 220 amino acids long. Heavy and light chains each contain intrachain disulfide bonds which stabilize their folding. Each chain is composed of structural domains called Ig domains. These domains contain about 70-110 amino acids and are classified into different categories (for example, variable or V, and constant or C) according to their size and function. They have a characteristic immunoglobulin fold in which two β sheets create a “sandwich” shape, held together by interactions between conserved cysteines and other charged amino acids. 
     There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ, and μ. The type of heavy chain present defines the isotype of antibody; these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively. 
     Distinct heavy chains differ in size and composition; α and γ contain approximately 450 amino acids and δ approximately 500 amino acids, while μ and ε have approximately 550 amino acids. Each heavy chain has two regions, the constant region (CH) and the variable region (VH). In one species, the constant region is essentially identical in all antibodies of the same isotype, but differs in antibodies of different isotypes. Heavy chains γ, α and δ have a constant region composed of three tandem Ig domains, and a hinge region for added flexibility; heavy chains μ and ε have a constant region composed of four immunoglobulin domains. The variable region of the heavy chain differs in antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or B cell clone. The variable region of each heavy chain is approximately 110 amino acids long and is composed of a single Ig domain. 
     In mammals, there are two types of immunoglobulin light chain denoted by λ and κ. A light chain has two successive domains: one constant domain (CL) and one variable domain (VL). The approximate length of a light chain is 211 to 217 amino acids. Each antibody contains two light chains that are always identical; only one type of light chain, κ or λ, is present per antibody in mammals. 
     Although the general structure of all antibodies is very similar, the unique property of a given antibody is determined by the variable (V) regions, as detailed above. More specifically, variable loops, three each the light (VL) and three on the heavy (VH) chain, are responsible for binding to the antigen, i.e. for its antigen specificity. These loops are referred to as the Complementarity Determining Regions (CDRs). Because CDRs from both VH and VL domains contribute to the antigen-binding site, it is the combination of the heavy and the light chains, and not either alone, that determines the final antigen specificity. 
     An “antibody fragment” contains at least one antigen binding fragment as defined above, and exhibits essentially the same function and specificity as the complete antibody of which the fragment is derived from. Limited proteolytic digestion with papain cleaves the Ig prototype into three fragments. Two identical amino terminal fragments, each containing one entire L chain and about half an H chain, are the antigen binding fragments (Fab). The third fragment, similar in size but containing the carboxyl terminal half of both heavy chains with their interchain disulfide bond, is the crystalizable fragment (Fc). The Fc contains carbohydrates, complement-binding, and FcR-binding sites. Limited pepsin digestion yields a single F(ab′)2 fragment containing both Fab pieces and the hinge region, including the H-H interchain disulfide bond. F(ab′)2 is divalent for antigen binding. The disulfide bond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, the variable regions of the heavy and light chains can be fused together to form a single chain variable fragment (scFv). 
     Pharmaceutically acceptable salts are for example acid addition salts and basic salts. Acid addition salts are e.g. HCl or HBr salts. Basic salts are e.g. salts having a cation selected from alkali or alkaline, e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), wherein R1 to R4 independently of each other mean: hydrogen, an optionally substituted C1 C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10-heteroaryl group. Further examples of pharmaceutically acceptable salts are described in “Remington&#39;s Pharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), Mark Publishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia of Pharmaceutical Technology. 
     Pharmaceutically acceptable solvates are for example hydrates.