Abstract:
The invention faces the technical problem of providing a tight connection between a tube and an dispense interface, while at the same time the biocompatibility of the connection can be improved. The technical problem is solved by an apparatus comprising a tube configured to guide a medium and a dispense interface. The tube comprises a first opening and a second opening, while the dispense interface comprises a recess. The recess has a first opening and a second opening and the tube is at least in part inserted into the recess. The tube is permanently affixed to the dispense interface by a combination of an interference fit and an adhesive, such that the interference fit prevents the adhesive from contaminating the medium.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    The present application is a U.S. National Phase Application pursuant to 35 U.S.C. §371 of International Application No. PCT/EP2012/057695 filed Apr. 26, 2012, which claims priority to U.S. Provisional Patent Application No. 61/480,063, filed Apr. 28, 2011 and European Patent Application No. 11173282.2 filed Jul. 8, 2011. The entire disclosure contents of these applications are herewith incorporated by reference into the present application. 
     
    
     FIELD OF INVENTION 
       [0002]    The present patent application relates to medical devices for delivering at least one drug agent from a reservoir, in particular 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 agents automatically or manually by the user. The invention relates in particular to the connection of a tube of a medical device to other parts of a medical device. 
       BACKGROUND 
       [0003]    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. 
         [0004]    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. 
         [0005]    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. 
         [0006]    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). 
       SUMMARY 
       [0007]    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. 
         [0008]    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. 
         [0009]    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. 
         [0010]    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 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).       
 
         [0017]    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. 
         [0018]    The first and the second proximal needle of the injection device need to be permanently fixed to the dispense interface. Moreover they need to be fixed in such a way that the connection between the needle and the dispense interface in this case provides a tight connection as well. This fixation is especially problematic in medical devices, since any contamination of the drug agents with chemical substances must be avoided. The chemical substances can cause undesired side effects for the user if the drug agent comes into contact with it during the process of injection. This makes the use of adhesives problematic, because if the adhesive is used to tightly fix the connection between needle and dispense interface, a contamination of the guided drug agent can not be avoided. 
         [0019]    Other means of fixation, for example purely mechanical means, often do not provide the necessary leak tightness. 
         [0020]    Moreover it is necessary that the needle is fixed in both of its axial directions. Firstly, the needle needs to be fixed during the above mentioned step 1, such that the needle is able to pierce a reservoir. Secondly, the needle also needs to be fixed during a potential removal of the dispense interface from the injection device. The dispense interface needs to be exchanged due to hygienic reasons or because a drug is exchanged and a contamination of drug agents with other drug agents is strictly to be avoided. 
         [0021]    Thus the invention faces the technical problem of providing a tight connection between a tube and a dispense interface, while at the same time the biocompatibility of the connection can be improved. 
         [0022]    The technical problem is solved by an apparatus comprising a tube configured to guide a medium and a dispense interface. The tube comprises a first opening and a second opening, while the dispense interface comprises a recess. The recess has a first opening and a second opening and the tube is at least in part inserted into the recess. The tube is permanently affixed to the dispense interface by a combination of an interference fit and an adhesive, such that the interference fit prevents the adhesive from contaminating the medium. 
         [0023]    By the combination of an interference fit with an adhesive it is possible to prevent the adhesive from contaminating the medium. This provides an improved biocompatibility for the connection of the tube and the dispense interface for the medical device. At the same time it is not necessary to dispense with an adhesive as an effective means for a permanent fixation. Hence, at the same time an effective permanent fixation can be provided without jeopardizing the biocompatibility. 
         [0024]    The term inserting is understood to mean that the tube might be inserted either in part or completely, preferably from the first opening of the recess. In case the tube is in its axial direction longer than the recess, then, if the tube is inserted completely into the recess, still a part of the tube might protrude from the recess. It is also possible that the tube is protruding from the recess on both openings of the recess. 
         [0025]    By the first opening and the second opening the recess in particular connects a first region with a second region. The first region can provide a reservoir containing a medicament, for example, and the second region can be a circular reservoir of a manifold or of a valve pocket. When the tube is inserted into the recess, the tube can especially provide a fluid connection between the reservoir in the first region and the circular reservoir of the manifold. 
         [0026]    The interference fit can in particular also be utilized for a determination, how far the tube can be inserted into the channel. Since the tube might be pulled out from the recess the same way it was inserted, an interference fit often only provides a secure fixation in one axial direction. The adhesive thus has the function of a retaining adhesive permanently fixing the tube. 
         [0027]    It is preferred when the tube is a needle or a cannula. It is especially useful to use needles or cannulas in an apparatus according to the invention, since a needle or cannula is frequently exposed to tensile and compression loads during injections and removals, so that it must be securely fixed. A needle or cannula is furthermore most of the time in direct contact with the guided medium, especially a drug agent or a medicament, and biocompatible connections are mandatory. 
         [0028]    If the dispense interface is a dispense interface of a medical device and in particular of a drug delivery device, an improved biocompatibility can be provided for such a device, where biocompatibility is extremely important, since the medium, which is in most cases a drug agent or a medicament, must not be contaminated with substances, which might cause side effects for the user. 
         [0029]    The dispense interface can in particular be a complete dispense interface or a part of a dispense interface, in particular an inner body of a dispense interface. Due to hygienic and medical reasons the dispense interface must be regularly exchanged, resulting in physical stress. The drug or medicament is guided through the dispense interface, in particular an inner body of the dispense interface. Thus parts of the dispense interface can be in direct contact with medium. Over the tube, in particular the needle or cannula, the dispense interface can be connected to a drug reservoir, for example. It is possible to provide a permanent fixation between the tube and the dispense interface and maintain the necessary biocompatibility for the guided medium. 
         [0030]    It is especially preferred if the recess is at least in part gradually tapering. The recess tapers preferably from the first to the second opening of the recess. By an at least in part gradually tapering of the recess, an easy assembly of the tube and the dispense interface is provided since a centering or alignment during the insertion of the tube takes place. Moreover, the insertion force is evenly distributed and the growing force by the recess on the tube occurs gradually instead of all at once. This also reduces the total force necessary to insert the tube into the recess. Hence the insertion during the assembly process is made smoother and better controllable. 
         [0031]    According to a further embodiment of the invention, the recess comprises a first section configured to accept an adhesive and the recess comprises a second section adjacent to the first section configured to provide the interference fit between the tube and the dispense interface. This way avoidance of the contamination of the guided medium can be realized particularly easily with a cost saving design. While the second section provides the interference fit, which is established first, the first section provides an area to accept the adhesive. This way the adhesive remains close to the tube and mostly in the recess. A contamination of other parts is therefore minimized. The section might be tapered, but a cylindrical geometry is possible as well, for example. 
         [0032]    It is further preferred, if the second section tapers at least in part from the first section towards the second opening. This way an easy assembly, of the tube and the dispense interface is provided since a centering or alignment during the insertion of the tube takes place. Moreover the insertion force is evenly distributed and the growing force by the recess on the tube occurs gradually instead of all at once. This also reduces the total force necessary to insert the tube into the recess. Hence the insertion during the assembly process is made smoother and better controllable. 
         [0033]    The first section can be tapered, cylindrical or exhibit any other suitable shape. 
         [0034]    It is especially preferred, when the second section comprises a substantially cylindrical portion between the first section and the second opening. The cylindrical shape provides a very tight interference fit over a larger area. The cylindrical portion is preferably adjacent to the second opening of the recess. 
         [0035]    It is further especially preferred, if the first section tapers from the first opening towards the second section, the second section in the area of the second opening is cylindrical and the second section tapers between the first section and the cylindrical portion. This way the cylindrical portion provides the interference fit, and the tapered first section and the tapered part of the second section are a guide for the insertion of the tube into the recess and likewise facilitate the insertion of the adhesive. 
         [0036]    It is also possible though that the complete second section is designed cylindrical. 
         [0037]    It is preferred, when the first section tapers at least in part from the first opening towards the second section. The tapering of the first section facilitates the acceptance of an adhesive. The tapering of the first section has preferably a larger angle to the axis of the recess than the tapering of the second recess. This way enough space for the acceptance of an adhesive is provided. Moreover the insertion and alignment of the tube is further facilitated. 
         [0038]    According to another embodiment of the invention, the recess is tapered such that an interference fit is provided when the second opening of the tube is positioned in the region of the second opening of the recess. This way an optimum possible contact area between the inner wall of the recess and the outer wall of the tube is provided. The interference fit can in particular provide a security that tube is in right position. If one could move the tube further into the recess with a too low resistance, a certain uncertainty over position of the second opening of the tube in relation to the second opening of the recess. 
         [0039]    According to another embodiment of the invention, the dispense interface is made from Cyclo Olefin Polymer (COP). COP is a biocompatible material and thus perfectly suitable for the dispense interface. This material can be used to mold the dispense interface, in particular the inner body of a dispense interface. By molding the dispense interface, complex structures can be easily produced. Especially the recess can directly be molded into the dispense interface. 
         [0040]    Moreover, COP can be doped with a laser welding additive increasing the sensitivity to laser light. This way the dispense interface can be laser welded to further elements of the medical device. 
         [0041]    It is further preferred when the tube, in particular the needle or cannula, is made from metal, in particular stainless steel. This material is shows a high degree of biocompatibility and provides the necessary rigidity, in particular for needles. 
         [0042]    It is in particular possible to produce a connection between a tube and a dispense interface, wherein the tube comprises a first opening and a second opening, wherein the dispense interface comprises a recess, wherein the recess has a first opening and a second opening, by the steps of permanently affixing the tube to the dispense interface by inserting the tube at least in part into the recess and affixing the tube to the dispense interface by an interference fit and applying an adhesive in the region of the first opening of the recess. 
         [0043]    Preferably the tube is inserted at least in part into the recess, wherein the tube is affixed to the dispense interface by an interference fit, before an adhesive in the region of the first opening of the recess is applied, which permanently affixes the tube to the dispense interface. This way a contamination of the medium can be completely avoided. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0044]    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: 
           [0045]      FIG. 1  illustrates a perspective view of a delivery device with an end cap of the device removed; 
           [0046]      FIG. 2  illustrates a perspective view of the delivery device distal end showing the cartridge; 
           [0047]      FIG. 3  illustrates a perspective view of the delivery device illustrated in  FIG. 1  or  2  with one cartridge retainer in an open position; 
           [0048]      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 ; 
           [0049]      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 ; 
           [0050]      FIG. 6  illustrates one arrangement of a needle assembly that may be mounted on a distal end of the delivery device; 
           [0051]      FIG. 7  illustrates a perspective view of the dispense interface illustrated in  FIG. 4 ; 
           [0052]      FIG. 8  illustrates another perspective view of the dispense interface illustrated in  FIG. 4 ; 
           [0053]      FIG. 9  illustrates a cross-sectional view of the dispense interface illustrated in  FIG. 4 ; 
           [0054]      FIG. 10  illustrates an exploded view of the dispense interface illustrated in  FIG. 4 ; 
           [0055]      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 ; 
           [0056]      FIG. 12  illustrates a cross-sectional view of an alternative embodiment of a dispense interface; 
           [0057]      FIG. 13  illustrates an exploded view of the alternative embodiment of a dispense interface illustrated in  FIG. 12 ; 
           [0058]      FIG. 14  illustrates a cross-sectional view of the alternative embodiment of a dispense interface illustrated in  FIG. 12  and the dose dispenser mounted onto a drug delivery device, such as the device illustrated in  FIG. 1 ; 
           [0059]      FIG. 15   a  illustrates an enlarged view of the first piercing needle and a part of the dispense interface illustrated in  FIG. 12  without an adhesive; 
           [0060]      FIG. 15   b  illustrates the assembly illustrated in  FIG. 15   a  with an adhesive provided in the recess. 
           [0061]      FIG. 15   c  illustrates another exemplary embodiment of a recess according to the invention. 
       
    
    
     DETAILED DESCRIPTION 
       [0062]    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. 
         [0063]    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. 
         [0064]    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. 
         [0065]    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 ). 
         [0066]    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. 
         [0067]    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 . 
         [0068]    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). 
         [0069]    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 . 
         [0070]    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 . 
         [0071]    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. 
         [0072]      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  402  mounted on the dispense interface  200  in  FIG. 5 . 
         [0073]    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). 
         [0074]    Similarly, a second or proximal piercing end  406  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  406  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 . 
         [0075]    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: 
         [0076]    a. a main outer body  210 , 
         [0077]    b. an first inner body  220 , 
         [0078]    c. a second inner body  230 , 
         [0079]    d. a first piercing needle  240 , 
         [0080]    e. a second piercing needle  250 , 
         [0081]    f. a valve seal  260 , and 
         [0082]    g. a septum  270 . 
         [0083]    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 . 
         [0084]    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. 
         [0085]    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. 
         [0086]    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. 
         [0087]    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 . 
         [0088]    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 . 
         [0089]    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. 
         [0090]    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 . 
         [0091]    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 . 
         [0092]    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. 
         [0093]    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. 
         [0094]    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. 
         [0095]      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. 
         [0096]    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 . 
         [0097]    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 . 
         [0098]      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 . 
         [0099]    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 . 
         [0100]    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 . 
         [0101]      FIGS. 12 to 14  illustrate an embodiment of a dispense interface  2000  alternative to the embodiment of the dispense interface  200  illustrated in  FIGS. 7 to 11 . In  FIGS. 12 to 14  the same reference signs as in  FIGS. 7 to 11  are used for the same parts. Furthermore, at this point, it is mainly referred to the above description of the embodiment of the dispense interface  200  illustrated in  FIGS. 7 to 11  and, basically, the differences are described only. 
         [0102]    One exemplary difference between the dispense interface  200  and the dispense interface  2000  is the outer shape. In particular, the dispense interface  2000  is attachable to a drug deliver device by axial attachment means as described above and at least partially insertable in the drug delivery device. For instance, once the dispense interface  2000  is attached to the distal end of the drug delivery device, the distal end of the main body of the drug delivery device covers a portion of the dispense interface  2000 . 
         [0103]    As will now be discussed in greater detail, in one preferred arrangement, the dispense interface  2000  illustrated in  FIGS. 12 to 14  comprises: 
         [0104]    a. a main outer body  2100 ; 
         [0105]    b. an inner body  2200 ; 
         [0106]    c. a manifold  2300 ; 
         [0107]    d. a first piercing needle  240 ; 
         [0108]    e. a second piercing needle  250 ; 
         [0109]    f. a lock-out spring  2600 ; 
         [0110]    g. a first diaphragm valve (e.g. diaphragm  2700 ); 
         [0111]    h. a second diaphragm valve (e.g. diaphragm  2750 ); and 
         [0112]    i. an outer septum  270 . 
         [0113]    In  FIG. 12  the main outer body  2100  comprises in particular an inner body  2200 . The inner body  2200  comprises a first and a second piercing needle  240  and  250 . The first piercing needle  240  is attached to the inner body  2200  and provides a fluid connection to a first circular reservoir  2050  of the inner body  2200 . Likewise the second piercing needle  250  is attached to the inner body  2200  and provides a fluid connection to a second circular reservoir  2054  of the inner body  2200 . 
         [0114]    In the exploded view illustrated in  FIG. 13 , a more detailed view of the inner body  2200  is given. Moreover, a perspective view of both a first diaphragm  2700  and the second diaphragm  2750  are provided. The first and second diaphragms  2700  and  2750  correlate with the first and second reservoirs  2050  and  2054 . As can be seen from these exploded views, the first diaphragm  2700  is substantially disc shaped and comprises a circular protrusion  2710  near the center of this disc shape. Similarly, the second diaphragm  2750  is substantially disc shaped and comprises a circular protrusion  2760  near the center of this disc shape. The diaphragm  2700  can provide a fluid seal between the first circular reservoir  2050  defined by the inner body  2000  and a fluid groove arrangement in the manifold  2300  (not shown). For instance, a rim of the diaphragm may be pressed on a set-back  2052  of the circular reservoir  2050  such that the diaphragm is in a pre-stressed state. Likewise, the diaphragm  2750  can provide a fluid seal between the second circular reservoir  2054  defined by the inner body  2000  and a fluid groove arrangement in the manifold  2300  (not shown). For instance, a rim of the diaphragm may be pressed on a set-back  2056  of the circular reservoir  2054  such that the diaphragm is in a pre-stressed state. 
         [0115]    The manifold can in particular provide a y-channel which guides a fluid form the first and second circular reservoirs  2050  and  2054  into the holding chamber  280 . 
         [0116]      FIG. 14  illustrates the dispense interface  2000  after it has been mounted onto the distal end of the cartridge holder  40  of a drug delivery device such as the drug delivery device  10  illustrated in  FIG. 1 . As illustrated, the needle assembly  400  is mounted to the distal end of the dispense interface  2000 . Fluid flow will now be explained with respect to  FIG. 14 . 
         [0117]    As illustrated in  FIG. 14 , the dispense interface  2000  is coupled to the distal end of a cartridge holder  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 holder  40 , the dispense interface  2000  essentially provides a mechanism for providing a fluid communication path from the first and second cartridges  90 ,  100  to the holding chamber  280  defined by the inner body  2200 . This holding chamber  280  is illustrated as being in fluid communication with the needle assembly  400  (i.e. the double ended needle assembly  400 ). As illustrated, the proximal needle of the double ended needle assembly  400  is in fluid communication with the holding chamber  280 . 
         [0118]    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 the first reservoir  2050  defined by the inner body  2000 . 
         [0119]    Similarly, the proximal piercing end  254  of the second piercing needle  250  resides in fluid communication with the secondary medicament  102  of the second cartridge  100 . A distal end of the second piercing needle  250  will also be in fluid communication with the second circular reservoir  2054  defined by the inner body  2000 . 
         [0120]    For instance, as pressure builds up in the first cartridge  90  and the second cartridge  100 , fluidic pressure will build up in both the first and second piercing needles  240 ,  250 . As such, the pressure will be built up in both the first and second reservoirs  2050 ,  2054  and this fluidic pressure will invert the first and second diaphragms  2700 ,  2750 . For instance, a fluidic pressure threshold has to be overcome to invert the first and second diaphragm valves. 
         [0121]    This inversion of the first diaphragm  2700  will allow the first medicament  92  to flow out of the first reservoir  2050 , around the now inverted first diaphragm  2700  and then into a fluid groove of the manifold  2300  (not shown). Similarly, this inversion of the second diaphragm  2750  will allow the second medicament  102  to flow out of the second reservoir  100 , around the now inverted second diaphragm  2750  and then into a fluid groove of the manifold  2300 . Under this continued pressure, the medicaments will then flow into the holding chamber  280  of the inner body  2200 . Alternatively or additionally, the medicament may then flow out of the outlet  290  of the dispense interface  2000 . 
         [0122]      FIG. 15   a  provides an enlarged view of the first piercing needle  240  together with the circular reservoir  2050  and a part of the inner body  2200 . The description given with respect to  FIGS. 15   a  and  b  applies likewise to the second piercing needle  250  together with the circular reservoir  2054 . 
         [0123]    Here, the tube is designed as a needle, in particular a piercing needle  240 . The dispense interface, in this case, is the inner body  2200  of the dispense interface  2000 . Though, the dispense interface can as well be the first inner body  220  illustrated in  FIG. 10 , for example. Here, the piercing needle  240  can guide a drug agent  92  from the reservoir  90 , situated in a first region  300 , into a second region  302 , which is in this case the circular reservoir  2050 . A drug agent  92  can enter the piercing needle  240  at the piercing end portion  244  through the first opening  304 . The drug agent  92  can enter the circular reservoir  2050  through the second opening  306  of the needle  240 . 
         [0124]    The needle  240  is inserted into the recess  308 . The recess  308  comprises a first section  310  and a second section  312 . The first section  310  is tapered with a larger angle to the axial direction of the recess  308  or the needle  240  than the second region  312 . The first region gradually tapers from the first opening  314  of the recess  308  towards the second region  312  and provides a volume to accept an adhesive  318 . The second region  312  gradually tapers from the first region  310  towards the second opening  316  of the recess  308  and thus provides the interference fit for the needle  240 . The second opening  306  of the needle  240  is substantially aligned with the second opening  316  of recess  308 . It is as well possible that the tapering is provided in different geometric forms, departing from a gradual tapering. It is also possible to provide a recess  308 , which provides an interference fit, without any tapering at all. Though, by the tapering of the recess  308  an easy assembly of the needle  240  and the inner body  2200  is provided since a centering or alignment during the insertion of the needle  240  takes place. Moreover the insertion force is evenly distributed and the growing force by the recess  308  on the needle  240  occurs gradually instead of all at once. This also reduces the total force necessary to insert the needle  240  into the recess  308 . Hence the insertion during the assembly process is made smoother and better controllable. The state depicted in  FIG. 15   a  is problematic in so far that the needle  240  might be pulled out of the recess  308  in the direction towards the first region  300  under certain circumstance, for example when the dispense interface  2000  is ejected from the cartridge holder  40 . 
         [0125]    Thus  FIG. 15   b  shows the assembly illustrated in  FIG. 15   a  with an adhesive  318  provided in the recess  308 . Due to the interference fit the adhesive  318  cannot get into contact with the medicament  92 . The interference fit prevents the adhesive  318  from flowing into the circular reservoir  2050 . That means that even adhesives  318 , which do not show a sufficient biocompatibility, may be used to fix the piercing needle  240  to the inner body  2200 , because the medicament  92  does not get into contact with the adhesive  318 . 
         [0126]    As illustrated in  FIG. 15   b  the adhesive  318  substantially fills the recess  308 . Though, it is also possible that the adhesive  318  only fills a part of the recess  308 , for example only the second section  308 . It is also possible that the adhesive  318  substantially only fills the first section  310  of the recess  308  for example if in the second section  308  the piercing needle  240  is held by a press fit. The adhesive  318  may also protrude from the recess  308  into the first region  300 . Since there is a fluid tight connection between the reservoir  90  and the needle  240 , an adhesive protruding into the first region  300  does not contaminate any medicament  92 . In this case it is important, that no adhesive  318  leaves the recess  308  through its second opening  316 . 
         [0127]      FIG. 15   c  illustrates another exemplary embodiment of a recess  308  according to the invention. The difference to the embodiment shown in  FIGS. 15   a  and  15   b  is the design of the second section  312 . The second section  312  only tapers in part from the first section  310  towards the second opening  316 . In the area of the second opening  316  the second section  312  has a substantially cylindrical portion  320 . This cylindrical portion  320  provides the interference fit between the needle  240 ,  250  and the inner body  2200  of a dispense interface, while the tapered first section  310  and the tapered part of the second section  312  are a guide for the insertion of the needle  240 ,  250  into the recess  308  and also facilitate the insertion of the adhesive  318 . The length of the tapered portion and the length of the substantially cylindrical portion  320  may vary. For example, the length of the cylindrical portion  320  may be 20 percent of the whole length of the second section  312  of the recess  308 . In other embodiments, the length of the cylindrical portion may be 40, 50, 60, 70, or 80 percent of the second section  312  of the recess  308 . 
         [0128]    The needle  240  and the adhesive  318  can be inserted into the recess the same way as it is illustrated in  FIGS. 15   a  and  15   b.    
         [0129]    The inner body  2200  may be made from Cyclo Olefin Polymer (COP), which is a biocompatible substance and which can be easily molded into the given geometric shape. Since a higher rigidity is needed for the piercing needle  240 , it is preferably made from metal and in particular from steel. The needle  240  and the inner body  2200  can also be made from other materials, as long as a sufficient biocompatibility is guaranteed. 
         [0130]    The term “drug” or “medicament”, as used herein, means a pharmaceutical formulation containing at least one pharmaceutically active compound, 
         [0131]    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, 
         [0132]    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, 
         [0133]    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, 
         [0134]    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. 
         [0000]    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. 
         [0135]    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. 
         [0136]    Exendin-4 for example means Exendin-4(1-39), a peptide of the sequence 
         [0000]    
       
         
               
               
             
           
               
                 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. 
               
             
          
         
       
     
         [0137]    Exendin-4 derivatives are for example selected from the following list of compounds: 
         [0138]    H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2, 
         [0139]    H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2, 
         [0140]    des Pro36 [Asp28] Exendin-4(1-39), 
         [0141]    des Pro36 [IsoAsp28] Exendin-4(1-39), 
         [0142]    des Pro36 [Met(O)14, Asp28] Exendin-4(1-39), 
         [0143]    des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39), 
         [0144]    des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39), 
         [0145]    des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39), 
         [0146]    des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39), 
         [0147]    des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or 
         [0148]    des Pro36 [Asp28] Exendin-4(1-39), 
         [0149]    des Pro36 [IsoAsp28] Exendin-4(1-39), 
         [0150]    des Pro36 [Met(O)14, Asp28] Exendin-4(1-39), 
         [0151]    des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39), 
         [0152]    des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39), 
         [0153]    des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39), 
         [0154]    des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39), 
         [0155]    des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39), 
         [0156]    wherein the group -Lys6-NH2 may be bound to the C-terminus of the Exendin-4 derivative; 
         [0157]    or an Exendin-4 derivative of the sequence 
         [0158]    H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2, 
         [0159]    des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2, 
         [0160]    H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2, 
         [0161]    H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2, 
         [0162]    des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0163]    H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0164]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0165]    H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2, 
         [0166]    H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2, 
         [0167]    H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2, 
         [0168]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2, 
         [0169]    des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0170]    H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0171]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0172]    H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2, 
         [0173]    des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2, 
         [0174]    H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, 
         [0175]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, 
         [0176]    des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0177]    H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0178]    H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0179]    H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2, 
         [0180]    H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25] Exendin-4(1-39)-NH2, 
         [0181]    H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, 
         [0182]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-NH2, 
         [0183]    des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0184]    H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(S1-39)-(Lys)6-NH2, 
         [0185]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2; 
         [0186]    or a pharmaceutically acceptable salt or solvate of any one of the afore-mentioned Exedin-4 derivative. 
         [0187]    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. 
         [0188]    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. 
         [0189]    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. 
         [0190]    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. 
         [0191]    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. 
         [0192]    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. 
         [0193]    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. 
         [0194]    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. 
         [0195]    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 crystallizable 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). 
         [0196]    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. 
         [0197]    Pharmaceutically acceptable solvates are for example hydrates.