Abstract:
The invention provides a dispense interface for an ejection device comprising a first part and a second part, at least a first opening, a second opening and a third opening, a fluidic channel and a connection element for each of the openings, wherein the first part is joined to said second part to form at least a part of said fluidic channel connecting said openings with each other and wherein each connection element is configured to accept a needle assembly for a fluid tight connection with said corresponding opening in order to reduce the complexity and provide an easy usage of the dispense interface and at the same time overcome the problems of material compatibility and cross contamination. The invention also relates to a system comprising a dispense interface according to the invention and a needle assembly for each opening. Furthermore, the invention relates to a method for preparing a dispense interface according to the invention.

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/EP2013/060159 filed May 16, 2013, which claims priority to European Patent Application No. 12168369.2 filed May 16, 2012. The entire disclosure contents of these applications are herewith incorporated by reference into the present application. 
     TECHNICAL FIELD 
     The present patent application relates to an ejection device, for example a medical device, for delivering at least two liquids, such as liquid 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 agents automatically or manually by the user. 
     SUMMARY 
     The medical device can be an injector, for example a hand-held injector, especially a pen-type injector, that is an injector of the kind that provides for administration by injection of medicinal products from one or more multidose cartridges. In particular, the present invention relates to such injectors where a user may set the dose. 
     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. 
     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 may 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 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. 
     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 a 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 from separate reservoirs can be delivered to the body via a double-ended needle assembly. This provides a combination drug injection system that, from a user&#39;s perspective, achieves drug delivery 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 integrated 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. Alternatively, the user can dial or set a desired dose of the secondary compound. 
     5. Optionally, after the second dose has been set, the device may be placed in an armed condition. The optional armed condition may be achieved by pressing and/or holding an “OK” or an “Arm” button on a control panel. The armed condition may be provided for a predefined period of time during which 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. 
     The dispense interfaces in the state of the art are, however, often of complex design. In order to provide the manifold to lead the medicaments from two different reservoirs to a single outlet, multiple complex and/or small parts need to be produced and assembled. In particular, the first and second proximal needle which need to pierce the first and the second reservoir respectively need to be integrated in the manufacture process. A large part count and the corresponding complicated assembly steps can cause the dispense interface to be difficult to manufacture and expensive. 
     Additionally, the dispense interface is regularly kept at the drug delivery device for a longer period of time. This means that only the dose dispenser in form of a double ended needle, for instance, is exchanged for every or nearly every injection procedure. The dispense interface, however, remains at the drug delivery device. An exchange of the dispense interface itself is regularly only necessary, when the reservoirs of the drug delivery device need to be exchanged. 
     This causes requirements for the material and design of the dispense interface to be fulfilled. Since the drug agents from the first and/or the second reservoir remain inside the dispense interface after a dispense procedure, a material compatibility of the parts of the dispense interface being in contact with the drug agents needs to be provided. No harmful substances must diffuse into the drug agents, since these would then be delivered to the patient with the next delivery procedure. Hence a biocompatibility is required, which guarantees that either no or negligible amounts of substances can diffuse into drug agents or are set free into the liquid. 
     Furthermore, if the dispense interface remains attached to the drug delivery device the different drug agents also start to diffuse into each other over time. A cross-contamination of the drug agents from one reservoir into the other reservoir needs to be prevented for the above mentioned reasons of stability, compromised therapeutic performance and toxicology, for example. 
     In order to prevent such cross-contamination, valves that prevent backflow can be implemented in the dispense interface. This, however, increases the part count and thus the complexity and cost during the production of the dispense interface. Additionally, a septum is often provided at the outlet of the dispense interface, since the dispense interface needs to be sealed, when it is connected to the reservoirs but there is no dose dispenser attached. 
     In light of the aforementioned, the invention faces the technical problem of reducing the complexity and providing an easy usage of the dispense interface and at the same time overcoming the problems of material compatibility and cross contamination. 
     The technical problem is solved by a dispense interface for an ejection device comprising a first part and a second part, at least a first opening, a second opening and a third opening, a fluidic channel and a connection element for each of the openings, wherein the first part is joined to the second part to form at least a part of the fluidic channel connecting the openings with each other and wherein each connection element is configured to accept a needle assembly for a fluid tight connection with the corresponding opening. 
     By providing a dispense interface comprising a first and a second part being joined together to form at least part of the fluidic channel, the production and assembly of the dispense interface can be kept simple and cost efficient. 
     At the same time, by providing one connection element for each of the openings connected by the fluidic channel for the connection with a needle assembly each, the production and assembly of the dispense interface is simplified, since the integration of the needles into the dispense interface during the manufacture of the dispense interface does not need to be taken care of. The needle assemblies are thus understood to be separate parts from the dispense interface. 
     Additionally, with the connection elements a convenient way for the user to attach a needle assembly to the dispense interface is provided. 
     The cost efficient and easy production process allows the dispense interface to be replaced frequently, thus reducing the risk of contamination. In particular, it enables the dispense interface to be used as a single-use item. That means that after a single delivery procedure with an ejection of a liquid or a drug agent through dispense interface the dispense interface can be detached from the ejection device and discarded. 
     The ejection device can, for instance, be a medical device such as a drug delivery device. 
     During an ejection procedure, a liquid may enter the dispense interface through the first openings and another liquid may enter the dispense interface through the second opening. Therefore, these opening can be considered as inlets. Guided by the fluidic channel, the liquids can then leave the dispense interface via the third opening, which can be considered as an outlet. The dispense interface can thus be seen as a manifold. 
     The first and second needle assemblies attached to the first and second connection elements, respectively, corresponding to the first and second opening, respectively, can be piercing needles, to pierce for example the septa of the corresponding reservoirs. The needles of the first and second needle assemblies may guide the liquids of the reservoirs to the first and second opening of the dispense interface. The third needle assembly attached to the third connection element corresponding to the third opening can serve as a dose dispenser comprising an injection needle, for example. 
     It is further preferred that the dispense interface comprises precisely three openings, wherein one opening serves as an outlet and two openings serve as inlets. 
     The connection elements can in particular be adapted for the connection of standard needle assemblies. A needle assembly is understood to be a needle with connection means for connecting the needle assembly to the connection elements. Such connection means of the needle assembly can comprise a hub, which can be threaded onto the connection elements for example. The needle assembly can also comprise a cylindrically shaped tapered hub for a friction fit connection. The connection element need to be adapted to the corresponding needle assembly to be attached to the dispense interface. 
     It is preferred that the connection elements are designed identically, although it is also possible to provide different connection elements. 
     Since the dispense interface is only in connection with the reservoirs of the ejection device substantially during the ejection procedure, there is only a short time for possible substances or chemicals in the dispense interface to diffuse into the liquid ejected by the ejection device and guided through the fluidic channel. 
     There is also substantially no time for the liquids within the reservoirs to become cross-contaminated, since the dispense interface is directly detached after the ejection procedure as it can be thrown away. 
     Furthermore there is no need for a septum in the dispense interface, since an exchange of the third needle assembly is not necessary, since after each injection an exchange of the whole dispense interface can take place. New needle assemblies can be attached to the corresponding connection element of a new dispense interface before attaching the dispense interface to the ejection device and establishing a fluid tight connection between the reservoirs and the dispense interface. 
     The channel or a part of the channel can be provided on a surface of the first part and/or the second part. By joining the first and the second part, the fluidic channel is then established. This can facilitate the provision of small fluidic channels in the dispense interface. 
     The joining of the first part and the second part can in particular be realized by gluing or plastic welding. The latter can be realized by laser welding or ultrasonic welding for example. It is also possible to use joining techniques where the used or resulting substances do not show a long lasting biocompatibility, since the liquids are only in contact with the dispense interface for a short period of time. 
     It is also possible to join the first part and the second part by friction and/or positive fit. The connection needs to be tight and long lasting enough to provide leak tightness at least during a single ejection process. 
     Although the dispense interface may comprise more than two parts, it is preferred, that the dispense interface comprises precisely a first and a second part. In this way, the complexity of the production and assembly of the dispense interface can be kept low. 
     As a consequence of the above mentioned, the complexity of the dispense interface is reduced, an easy usage of the dispense interface is provided and at the same time the problems of material compatibility and cross-contamination are overcome. 
     According to one embodiment of the dispense interface according to the invention at least one of the first part and the second part is produced by injection molding. With this manufacturing process at least one of the parts can be produced from plastic, such as a thermoplastic or a thermosetting material. It is preferred that both or all parts are produced from plastic. This reduces the operating expenses and costs of the manufacturing process of the dispense interface making it suitable for a low cost single-use component. 
     For instance, polymer materials may be used in injection moulding of the first and/or second part. Polymer materials are typically biocompatible. For instance, COP (cyclo-olefin polymer) materials may be used in injection moulding of the parts. COP materials have a high biocompatibility. For instance, COP materials have little to no extractables and most COP material can undergo sterilization by gamma radiation, steam and/or ethylene oxide. 
     Potential problems of material compatibility, absorption and contamination between the fluids (e.g. drugs) and the polymer material are thus overcome independently of the time of contact between dispense interface and liquid. 
     The first and/or second part can in particularly be molded including the connection elements as integral parts of either the first or the second part. The connection elements are likewise preferably produced from a plastic material and are an integral component with the first or second part. This reduces the complexity and costs of the manufacture and thus of the dispense interface itself. 
     This production method is particularly advantageous in combination with the first part and the second part forming the fluidic channel connecting the openings with each other. Since it is difficult to provide small fluidic channels within components by means of injection molding, the channel or a part of the channel only needs to be provided on a surface of the first part and/or the second part, for example by a modification in form of a recess. By joining the first and the second part, the fluidic channel is established. 
     When the first part comprises the third opening and the third connection element and when the second part comprises the first opening with the first connection element and the second opening with the second connection element, an advantageous geometric distribution of the openings and the corresponding connection elements can be provided. Furthermore, the first and second openings and connection elements can be provided into one direction on the second part and the third opening and connection element can be provided in another direction. This simplifies the usage of the dispense interface for the user. It is in particular preferred, when the first and second connection elements have a parallel orientation, while the third connection element has an antiparallel orientation with respect to the first and second connection element. 
     A preferred design of the dispense interface can be achieved, when the first part and the second part have an elongate shape, and the first opening is located at a first end of the second part and the second opening is located at a second end of said second part. In this way, a compact design adapted to the fluidic channel is achieved resulting in low cost for the dispense interface, such that the cost and the size of a single-use component can be reduced. The first part and the second part have preferably a substantially plate like design. That means that the parts are substantially constantly thin in a direction perpendicular to the elongate direction. In the same direction perpendicular to the elongate direction the connection elements can protrude from the first and/or second part. Preferably, the first and the second openings are spaced apart by the distance of the reservoirs. 
     It is further advantageous, when the third opening is located between the first end and the second end of the first part. The third opening can in particular be provided substantially in the middle of the first part. This is advantageous in combination with the first opening being located at the first end of the second part and the second opening being located at the second end of the second part. A symmetric design can be achieved in this way resulting in similar or identical lengths of the fluid pathway from the first and the second opening to the third opening in each case. Due to the symmetrical design, the orientation of the dispense interface when attaching it to an ejection device does not need to be cared about. That means it does not make a difference, which of the first and second opening is connected to which reservoir. This increases the ease of use of the dispense interface. 
     When at least one of the connection elements is configured for a releasable connection with a corresponding needle assembly, the needle assembly can be removed before the dispense interface is discarded. Furthermore, this design increases the compatibility with standard needle assemblies, since the needle assemblies according to industrial standard are chiefly provided with releasable connection means, such as a hub. 
     In one exemplary embodiment all of the connection elements are configured for a releasable connection with a corresponding needle assembly. 
     According to another embodiment of the dispense interface according to the invention, the fluidic channel comprises a substantially linear passage with a passage branching off for each opening. Due to a straight, linear connection between the branching-off passages leading to the openings, a short fluidic channel can be provided. This results in a low waste of drug agents, which remain in the fluidic channels after an ejection procedure. The substantially linear passage is preferably oriented in the elongated direction of the dispense interface, while the branching-off passages are preferably oriented perpendicular to the substantial linear passage of the fluidic channel. 
     An easy and quick to use the dispense interface can be provided, when at least one of the connection elements is configured for at least one of a friction fit and a positive fit with a needle assembly. The needle assembly can then be quickly and easily connected to the corresponding connection element, while at the same time a fluid tight connection can be provided. Preferably, all connection elements are configured for at least one of a friction fit and a positive fit with a needle assembly. 
     A safe and at the same time easy connection can in particular be provided, when at least one of the connection element provides the male part of a Luer fitting. Basically, there are two designs of Luer taper connections, a so called Luer-Lok and a so called Luer-Slip. Luer-Lok fittings are securely joined by means of a tabbed hub on the female fitting which screws into threads in a sleeve on the male fitting of the needle assembly. Luer-Slip fittings conform to Luer taper dimensions and are pressed together and held by friction. It is also possible to provide an additional positive fit for Luer-Slip fittings. Such a design of at least one connection element guarantees a high compatibility with needle assemblies available on the market, increasing the ease of use of the dispense interface, since the user generally knows the working principle of a Luer fitting. Preferably all connection elements provide the male part of a Luer fitting. 
     When the fluidic channel is configured such that a liquid can flow freely from any region of higher pressure to any region of lower pressure, the dispense interface is particularly easy and cost efficient to manufacture. No components, in particular valves, are provided in the fluidic channel, which would increase the efforts and expenses during the manufacture of the dispense interface. The risk of a cross-contamination or a diffusion of substances into the liquid guided with the dispense interface is counteracted by the fact that the dispense interface can be produced so efficiently and cost-effectively, that the dispense interface can be used as a single-use item. Hence, there is only a short period of time, in which the guided liquid and the dispense interface are in contact reducing the risk of any contaminations of the dispense interface. 
     Alternatively, it is also possible, that the fluidic channel comprises at least one non-return valve. This prevents or minimizes the back flow of a fluid back into one of the reservoirs. Additionally, the common volume can be reduced, in which both fluids from the reservoirs mix. This is advantageous, in case the user forgets to remove the dispense interface from the ejection device. In that case a cross-contamination can still be prevented. Especially, when the fluids are ejected one after another, the risk of a cross-contamination is higher, since there is a reduced counter pressure for the fluid from the one reservoir to enter the other reservoir compared to when both fluids are ejected simultaneously. Preferably, either a valve, such as a diaphragm valve, for each the first and the second opening is provided or a valve, such as a shuttle valve, which prevents backflow in both the first and the second opening is provided. In case more than two inlets are provided, a corresponding number of valves is preferably provided. 
     The at least one valve can either be an integral part of the dispense interface, for example by over molding the valve to the first and/or the second part. Alternatively the at least one valve can also be designed as a separate part and then assembled with first and second part during the manufacture. Possible valves are for example a diaphragm or flap valve, a shuttle valve, a (molded) duckbill valve, a flat spring, or rotation flap valve. 
     The technical problem is further solved by a system comprising a dispense interface according to the invention and a needle assembly for each opening. Since there are at least three openings provided with the dispense interface, at least three needle assemblies are provided. 
     The user can attach the needle assemblies to the connection elements of the dispense interface directly before an ejection procedure. For this, the connection elements and the corresponding needle assemblies are adapted to each other. The manufacture of the dispense interface is simplified, since an integration of the needles in the dispense interface does not need to be provided during the manufacture of the dispense interface. Hence, the dispense interface can be exchanged more frequently, or even after every use. 
     As a consequence, the complexity of the dispense interface is reduced, an easy usage of the dispense interface is provided and at the same time the problems of material compatibility and cross contamination are overcome. 
     The technical problem is further solved by a method for preparing a dispense interface according to the invention comprising the steps of attaching a needle assembly to each of the connection elements of the dispense interface and attaching the dispense interface to an ejection device having at least two reservoirs such that a fluid tight connection is established between the at least two reservoirs and the dispense interface. 
     By attaching a needle assembly to each of the connection elements of the dispense interface and afterwards attaching the dispense interface to the ejection device, it is possible to provide a dispense interface, the production of which is simplified, since an integration of the needles in the dispense interface does not need to be provided during the manufacture of the dispense interface. That means that the needle assemblies are not integrated into the dispense interface, but attached afterwards. The needle assemblies may be attached to the dispense interface already at the site of the manufacturer. Preferably, the user attaches the needle assemblies to the dispense interface after taking the dispense interface out of a package. It is in particular possible and still economical for the user, to exchange the dispense interface more frequently, or even after every use. 
     Since the needle assemblies are separated from the dispense interface and attached afterward, for example manually by the user, the complexity of the dispense interface is reduced and an easy usage of the dispense interface is provided. At the same time the problems of material compatibility and cross contamination are overcome, since the user establishes the connection of the dispense interface with the reservoirs directly before an ejection and the user can remove it directly afterwards as well. 
     When the user attaches the dispense interface to the ejection device, preferably the first needle assembly provides a fluid tight connection to the first reservoir of the ejection device, for example by piercing a septum of the first reservoir, while the second needle assembly provides a fluid tight connection to the second reservoir of the ejection device, for example by piercing a septum of the second reservoir. 
     The dispense interface may be secured in an engaged position with the ejection device. This can be done by fixing elements provided by the ejection device, for example. Such fixing elements, hooks or protrusions adapted to the dispense interface for instance, may establish a positive fit between the dispense interface and the ejection device. Alternatively, it is also possible that the dispense interface is fixed in the engaged position with the ejection device only by friction fit. 
     In case the needle tips of the first and second needle assemblies are covered with needle covers, the user needs to remove these covers before attaching the dispense interface to the ejection device. In case the needle tip of the third needle assembly is covered with a needle cover, the user needs to remove this cover before performing an ejection procedure. 
     Preferably, the method according to the invention further comprises the steps of ejecting a fluid from at least one of the reservoirs through the dispense interface and then removing the dispense interface form the ejection device. 
     These steps are performed after having attached the dispense interface to the injection device. When the dispense interface is removed after an ejection procedure, for example by the user, the risk of possible contaminations of the fluids and/or the reservoirs is reduced. Preferably, the dispense interface is removed directly after an ejection procedure. The dispense interface can then be discarded with or without the needle assemblies. 
     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, in which: 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         FIG. 1  illustrates a perspective view of a delivery device 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 delivery device illustrated in  FIG. 1 or 2  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 a needle assembly 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 needle assembly mounted onto a drug delivery device, such as the device illustrated in  FIG. 1 ; 
         FIG. 12  illustrates a perspective view of a dispense interface according to the invention with the first part and the second part not joined and with three needle assemblies not attached to the connection elements; 
         FIG. 13  illustrates the dispense interface of  FIG. 12  with the first part joined to the second part and with the needle assemblies attached; 
         FIG. 14  illustrates different embodiments of a valve arrangement, which can be used in a dispense interface according to the invention. 
     
    
    
     DETAILED DESCRIPTION 
     The ejection device in the form of a 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. 
     The drive train may exert a pressure on the bung of each cartridge, respectively, in order to expel the doses of the first and second medicaments. For example, a piston rod may push the bung of a cartridge forward a pre-determined amount for a single dose of medicament. When the cartridge is empty, the piston rod is retracted completely inside the main body  14 , so that the empty cartridge can be removed and a new cartridge can be inserted. 
     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 user interface of the drug delivery device may comprise additional buttons, such as a “menu” button, a “back” button, or a “light” button to switch on an illumination of the display. 
     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  212  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 second cartridge retainers  50 ,  52  may be 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  can be 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  400  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  48  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  408  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  408  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 . 
       FIG. 12  illustrates a perspective view of a dispense interface  500  according to the invention with the first part  502  and the second part  504  not joined to each other and with three needle assemblies  506   a ,  506   b ,  506   c  not attached to the connection elements  508   a ,  508   b ,  508   c.    
     The dispense interface  500  comprising the two parts  502  and  504  is not completely assembled yet. The two parts  502  and  504  are made of plastic and are produced by injection molding. The connection elements  508  are produced together with the first part  502  and the second part  504  respectively in the injection molding process. Both the first part  502  and the second part  504  are substantially plate-like and have a elongated shape. Only the connection elements  508  protrude from the plate-like shape of the first part  502  and the second part  504 . 
     The first part  502  and the second part  504  each comprise a substantially flat surface  510  and  512 , respectively. The surface  510  of the second part  504  comprises a substantially linear recess  514  extending from the first end  516  to the second end  518  of the second part  504 . When the first part  502  and the second part  504  are joined together (as shown in  FIG. 13 ), the surface of the first part  502  in connection with the surface of the second part  504  form a substantial part of the fluidic channel  520 . The first part  502  may comprise a similar recess to the recess  514  provided in the second part  504 . The first part  502  may also be provided without a recess in the substantially flat surface  512 . The cross section of the fluidic channel  520  may thus be circular or in the shape of a semi circle. It is also possible to provide other geometric shapes for the cross section of the fluidic channel  520 , such as a rectangular or oval shape. 
     The fluidic channel  520  comprises two passages  522  and  524  branching-off substantially perpendicularly from the recess  514  in the second part  504 . The passage  522  is located close to the first end  516  of the second part  504  and the passage  524  is provided close to the second end of the second part  504 . The passages  522  and  524  provide the first opening  526  and the second opening  528  respectively. The opening  526  and  528  are covered by the corresponding first connection element  508   a  and second connection element  508   b.    
     The first part  502  also comprises a passage  530  on the surface  512 . This passage  530  also branches off substantially perpendicularly from the recess  514  in the joined state of the first part  502  and second part  504 . The passage  530  provides the third opening  532  of the fluidic channel  520 . The passage  530  is located substantially in the middle of the first part  504 , half way from each the first end  534  and the second end  536  of the first part  502 . This way a similar or identical fluidic pathway is provided between the first opening  526  and the third opening  532  compared to the fluidic pathway between the second opening  528  and the first opening  532 . 
     The three connection elements  508  are design identical in this exemplary embodiment. Thus, only the connection element  508   c  is described here, being representative for the connection elements  508   a  and  508   b . However, it is also possible to provide connection elements differing from each other. 
     The connection element  508   c  comprises a first hollow cylinder  538   c  and a second hollow cylinder  540   c . The first hollow cylinder  538  surrounds the third opening  532  and is the male part of a Luer-Lok. The second cylinder  540   c  comprises an internal thread  542   c  for providing a positive fit with the needle assembly  506   c  to provide a Luer-Lok. 
     The needle assembly  506   c  is described representatively for the needle assemblies  506   a  and  506   b , since the needle assembly  506   c  is in this example identical to the needle assemblies  506   a  and  506   b . However, different needle assemblies can also be provided. 
     The needle assembly  506   c  comprises a needle  544   c  having a first end  546   c  and a second end, which second end is covered by a connection element in form of a needle hub  548   c . The needle hub  548   c  is designed as a tapered cylinder and provides the female part of a Luer fitting, in this case of a Luer-Lok. For this, the needle hub  548   c  comprises to projections  550   c  which can interact with the thread  542   c  of the second cylinder  540   c  of the third connection element  508   c . The tapered needle hub interacts with the first cylinder  536   c  of the first opening  532  to provide a fluid tight connection between the third connection element  508   c  and the third needle assembly  506   c.    
       FIG. 13  illustrates the dispense interface  500  of  FIG. 12  with the first part  502  joined to the second part  504  and with the needle assemblies  506  attached. The first part  502  and the second part  504  can be joined by gluing or welding for example. 
     The user can be provided with the dispense interface  500  as shown in  FIG. 13 , but without the needle assemblies  506  attached to the dispense interface  500 . The user would then take the dispense interface  500  out of the package and attach the needle assemblies  506  to the dispense interface  500  to obtain a system of dispense interface  500  and needle assemblies  506  as shown in  FIG. 13 . It is possible that the needle assemblies  506  are provided with covers for protecting the first ends  546  of each needle  544 . 
     In the state of the dispense interface  500  shown in  FIG. 13 , the user can attach the dispense interface to an ejection device, for example to the cartridge holder  40  of the ejection device  10 . The dispense interface  500  with the needle assemblies  506  then substitute the dispense interface  200  with the dose dispenser  400  (cf.  FIGS. 1-11 ). 
     The needles of the first and second needle assemblies  506   a  and  506   b  provide the piercing needles for the first and the second reservoirs  90 ,  100  (cf.  FIG. 11 ). This establishes a fluid tight connection between the primary medicament  92  from the first reservoir with the outlet opening  532  of the fluidic channel  520  of the dispense interface  500 . Simultaneously, this establishes a fluid tight connection between the secondary medicament  102  from the second reservoir with the outlet opening  532  of the fluidic channel  520  of the dispense interface  500 . 
     The user can then start an ejection procedure with the device 
       10 . The needle assembly  506   c  with the first end  546   c  of the needle  544   c  works as an injection needle. After the ejection of the fluids, the user can detach the dispense interface  500  from the cartridge holder  40 . Since the dispense assembly can be used as a single-use item due to the efficient and simple production, the user can then discard the dispense interface  500 . 
     Although, the dispense interface  500  substitutes the dispense interface  200 , features of the dispense interface  200  can also be combined with the exemplary embodiment  500  of the dispense interface according to the invention. The dispense interface  500  can for example be provided with a wall similar to wall  218  providing recesses  217 ,  218  in order to attachment the dispense interface  500  more securely to the cartridge holder  40 , for example. Instead of the needle assemblies  506 , three needle assemblies  400  with the corresponding connection elements in the form of the needle hub  216  can be provided, as well, for instance. 
     It is also possible to provide a dispense interface with more than three connection elements and needle assemblies to provide the ejection of more than two fluids via a single outlet. It is further possible to provide the non-return valves in the dispense interface  500  such as the non-return valves  262 ,  268 . 
       FIGS. 14 a  to 14 e    illustrate different embodiments of valve arrangements for a dispense interface  200  or  500 . The exemplary valve arrangements can be provided alternatively to the valve seal  260  of dispense interface  200 , for example, or they can be provided in the fluidic channel  520  of the dispense interface  500  similar to the design of dispense interface  200 . In  FIGS. 14 a  to 14 e    the same reference signs are used for parts which may be similar. 
     The valve arrangements may for instance be integrally formed with another part of the dispense interface, such as the first part  205  or the second part  504 . Alternatively, the valve arrangement may for instance be manufactured separately from the other parts of dispense interface. 
     For instance, the valve arrangement may be inserted (e.g. potted/over-molded) into the first part  502  and/or the second part  504 . For instance, the valve arrangement may at least partially be inserted (e.g. potted/over-molded) when the first part  502  and/or the second part  504  are injection molded. For instance, the valve arrangement may at least partially be inserted (e.g. mounted) in a separate step after the first part  502  and/or the second part  504  have been injection molded. 
       FIG. 14 a    illustrates a diaphragm/flap valve arrangement  3000   a . The diaphragm/flap valve arrangement  3000   a  has an inlet  3010  and an outlet  3030 . The inlet  3010  may for instance reside in fluid communication with one of the piercing needles  240 ,  250  of dispense interface  200  or needle assemblies  506   a ,  506   b  of dispense interface  500 , respectively, while the outlet  3030  may for instance reside in fluid communication with holding chamber  280  of dispense interface  200  or injection needle  544   c  of dispense interface  500 . 
     The diaphragm/flap valve arrangement  3000   a  has flexible diaphragm/flap  3040 . When the fluidic pressure in the inlet  3010  is increased (e.g. during a dose priming or a dose injecting step), the diaphragm/flap  3040  will change from an un-stressed state to a stressed state. In the stressed state, the fluidic pressure bends the diaphragm/flap  3040  as indicated by the arrow in  FIG. 14 a    so that the diaphragm/flap valve arrangement  3000   a  opens. In this stressed condition, the diaphragm/flap valve arrangement  3000   a  will allow fluid to flow from the inlet  3010  to the outlet  3030 . When the fluidic pressure in the inlet is removed, the diaphragm/flap  3040  will return to its initial position and seal the inlet  3010 , preventing backflow. 
       FIG. 14 b    illustrates a shuttle valve arrangement  3000   b . The shuttle valve arrangement  3000   b  has a tube  3050 . The tube  3050  has two inlets  3010 ,  3020  and an outlet  3030 . In the tube  3050  a movable element  3060  (e.g a piston or a ball) is arranged. 
     The diameter of the movable element  3060  corresponds to the diameter of the tube  3050  such that the movable element  3060  is movable between a first and a second (longitudinal) position in the tube  3050 . In the first position (illustrated in  FIG. 14 b   ), the movable element  3060  seals the inlet  3010  and allows fluid flow from the inlet  3020  to the outlet  3030 . In the second position (not illustrated), the movable element  3060  seals the inlet  3020  and allows fluid flow from the inlet  3010  to the outlet  3030 . When the fluidic pressure in the inlet  3010  is for instance increased (e.g. during a dose priming or a dose injecting step), the movable element  3060  will be pushed towards the second position as indicated by the arrow in  FIG. 14   b.    
       FIG. 14 c    illustrates a moulded duckbill valve arrangement  3000   c . The moulded duckbill valve arrangement  3000   c  has a first and a second duckbill valve  3080 ,  3090 . When the fluidic pressure in the inlet  3020  is increased (e.g. during a dose priming or a dose injecting step), the second duckbill valve  3090  will change from an un-stressed state to a stressed state. In the stressed state, the fluidic pressure inverts the naturally flattened shape of the duckbill valve as indicated in  FIG. 14 c    so that the duckbill valve opens. In this stressed condition, the second duckbill valve  3090  will allow fluid to flow from the inlet  3020  to the outlet  3030 . When the fluidic pressure in the inlet  3020  is removed, the second duckbill valve  3090  will return to its flattened shape and seal the inlet  3020 , preventing backflow. The first duckbill valve  3080  operates in a similar manner as the second duckbill valve  3090  when the fluidic pressure is increased in the inlet  3010 . 
       FIG. 14 d    illustrates a flat spring valve arrangement  3000   d . The flat spring valve arrangement  3000   d  has a first and a second flat spring  3100 ,  3110 . The first and the second flat spring  3100 ,  3110  may for instance be integrally formed. 
     When the fluidic pressure in the inlet  3010  is increased (e.g. during a dose priming or a dose injecting step), the first flat spring  3100  will change from an un-stressed state to a stressed state. In the stressed state, the fluidic pressure bends the first flat spring  3100  as indicated by the arrow in  FIG. 14 a    so that the flat spring valve arrangement  3000   d  opens. In this stressed condition, the flat spring valve arrangement  3000   d  will allow fluid to flow from the inlet  3010  to the outlet  3030 . When the fluidic pressure in the inlet is removed, the first flat spring  3100  will return to its initial position and seal the inlet  3010 , preventing backflow. The second flat spring  3110  operates in a similar manner as the first flat spring  3100  when the fluidic pressure is increased in the inlet  3020 . 
       FIG. 14 e    illustrates a rotating flap valve arrangement  3000   e . The rotating flap valve arrangement  3000   e  has a flap  3120  which is rotatably mounted in a valve chamber  3130 . The valve chamber has two inlets  3010 ,  3020  and an outlet  3030 . 
     The flap  3120  is rotatable between a first and a second position. In the first position (illustrated in  FIG. 14 e   ), the flap  3120  seals the inlet  3010  and allows fluid flow from the inlet  3020  to the outlet  3030 . In the second position (not illustrated), the flap  3120  seals the inlet  3020  and allows fluid flow from the inlet  3010  to the outlet  3030 . 
     When the fluidic pressure in the inlet  3010  is for instance increased (e.g. during a dose priming or a dose injecting step), the flap  3120  will be pushed towards the second position as indicated by the arrow in  FIG. 14   e.    
     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-carboxyheptadecanoyl)-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(P)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 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.