PATENT DOCUMENT

Abstract:
The present invention inter-alia relates to an apparatus comprising a needle guide configured to at last partially receive a needle of a needle assembly in a longitudinal opening and to center the needle of the needle assembly in the longitudinal opening, wherein the needle guide is longitudinally compressible.

Full 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/EP2012/058267 filed May 4, 2012, which claims priority to European Patent Application No. 11165130.3 filed May 6, 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 of delivering at least two drug agents from separate reservoirs. Such drug agents may comprise a first and a second medicament. The medical device includes a dose setting mechanism for delivering the drug automatically or manually by the user. 
       BACKGROUND 
       [0003]    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. 
         [0004]    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. 
         [0005]    For example, in some cases it might be beneficial to treat a diabetic with a long acting insulin (also may be referred to as the first or primary medicament) along with a glucagon-like peptide-1 such as GLP-1 or GLP-1 analog (also may be referred to as the second drug or secondary medicament). 
       SUMMARY 
       [0006]    Accordingly, there exists a need to provide devices for the delivery of two or more medicaments in a single injection or delivery step that is simple for the user to perform without complicated physical manipulations of the drug delivery device. The proposed drug delivery device provides separate storage containers or cartridge retainers for two or more active drug agents. These active drug agents are then only combined and/or delivered to the patient during a single delivery procedure. These active agents may be administered together in a combined dose or alternatively, these active agents may be combined in a sequential manner, one after the other. 
         [0007]    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. 
         [0008]    The drug delivery device may have a single dispense interface. This interface may be configured for fluid communication with the primary reservoir and with a secondary reservoir of medicament containing at least one drug agent. The drug dispense interface can be a type of outlet that allows the two or more medicaments to exit the system and be delivered to the patient. 
         [0009]    The combination of compounds as discrete units or as a mixed unit can be delivered to the body via a double-ended needle assembly. This would provide a combination drug injection system that, from a user&#39;s perspective, would be achieved in a manner that closely matches the currently available injection devices that use standard needle assemblies. One possible delivery procedure may involve the following steps: 
         [0010]    1. Attach/mount 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. 
         [0011]    2. Attach/mount a dose dispenser, such as a double-ended needle assembly, to a connecting part at the 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. For instance, a needle hub of the needle assembly is screwed on the connecting part of the dispense interface and thereby one end of a needle of the double-ended assembly intrudes into an outlet of the connecting part of the dispense interface, pierces a septum of the dispense interface arranged at the outlet and resides in fluid communication with a holding chamber of the dispense interface. The holding chamber may be in fluid communication with the first and second proximal needle. 
         [0012]    3. Dial up/set a desired dose of the primary compound from the injection device, for example, via a graphical user interface (GUI). 
         [0013]    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. 
         [0014]    5. Optionally, after the second dose has been computed, the device may be placed in an armed condition. In such an optional armed condition, this may be achieved by pressing and/or holding an “OK” button on a control panel. This condition may provide for greater than a predefined period of time before the device can be used to dispense the combined dose. 
         [0015]    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). 
         [0016]    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. 
         [0017]    After a specific number of injections (e.g. 1 injection, 3 injections, 5 injections, 10 injections, 20 injections, 50 injections or the like) there is a risk for the dose dispenser and/or the dispense interface to be contaminated and, additionally, the tips of the needles of the dose dispenser and/or the dispense interface may be blunted. For instance, a blunted tip of a needle may not be able to sufficiently pierce a septum and/or tissue, for instance inserting a blunted needle in a desired injection site may be very painful. Furthermore, mechanical parts of the dose dispenser and/or the dispense interface such as a valve arrangement may only proper function for a specific number of injections (e.g. 1 injection, 3 injections, 5 injections, 10 injections, 20 injections, 50 injections or the like). 
         [0018]    Therefore, the dose dispenser and the dispense interface are disposable parts. For instance, the dose dispenser should only be used for one injection and the dispense interface should only be used with one first and second reservoir. However, attaching the dose dispenser to the connecting part of the dispense interface may be fiddly, for instance the diameter of the outlet may be about the diameter of the needle. Furthermore, the double-ended needle can jam (e.g. tilt) and, for instance, collide with side-walls of the holding chamber and damage the dispense interface. For instance, the needle assembly and, in particular, the double-ended needle may initially tilt when screwing the needle assembly on a connecting part of the dispense interface (e.g. because of the helix angle of the thread). 
         [0019]    To facilitate attaching the dose dispenser to the connecting part of the dispense interface and to prevent a collision of the double-ended needle with side-walls of the holding chamber a cross-sectional inner diameter of the outlet and the holding-chamber and/or a length of the holding chamber and/or a length of the double-ended needle may be increased and, correspondingly, the volume of the holding chamber and/or the liquid path is also increased. 
         [0020]    However, it is desired to minimize the liquid dead volume and the liquid path in front of the first and second reservoir, for instance the volume of the fluid communication paths in the dispense interface. For instance, there is a higher risk that a medicament contained in this liquid dead volume may be contaminated and/or cause any other undesired side-effects These side-effects may be for instance due to a lowered stability, compromised therapeutic performance and toxicology of a combination of the first and second medicament. 
         [0021]    Therefore, the present invention inter-alia faces the technical problem of facilitating attaching a dose dispenser to a connecting part such as a connecting part of a dispense interface and/or a medical device such as a drug delivery device and/or to minimize the liquid dead volume thereof. However, the present invention is not limited to a connecting part of a dispense interface and/or a medical device as described above and may basically relate to a connecting part of any dispenser such as a dispenser configured to eject adhesives such as multi-component adhesives (e.g. two-component adhesives) or the like. 
         [0022]    According to the present invention, an apparatus comprises a needle guide configured to at last partially receive a needle of a needle assembly in a longitudinal opening and to center the needle of the needle assembly in the longitudinal opening, wherein the needle guide is longitudinally compressible. 
         [0023]    Furthermore according to the present invention, a method comprises receiving, at an apparatus, a needle of a needle assembly in a longitudinal opening of a needle guide, and centering the needle of the needle assembly in the longitudinal opening, wherein the needle guide is longitudinally compressible. 
         [0024]    The apparatus may be a dispenser. In particular, the apparatus may be a drug delivery device such as a medical device configured to eject a drug agent (e.g. a dose of a medicament) such as an infusion device or an injection device, for instance an insulin injection pen. Injection devices may be used either by medical personnel or by patients themselves. As an example, type-1 and type-2 diabetes may be treated by patients themselves by injection of insulin doses, for example once or several times per day. 
         [0025]    For instance, the apparatus is a medical device configured to eject at least two drug agents from separate reservoirs comprising a first and a second medicament, respectively, but it is not limited thereto. Alternatively, the medical device is for instance a conventional medical device configured to eject a drug agent from a single reservoir such as Applicant&#39;s Solostar insulin injection pen. 
         [0026]    Alternatively, the apparatus may be a disposable part attachable to a dispenser such as a drug delivery device such as a medical device configured to eject a medicament. For instance, the apparatus is a dispense interface attachable to a medical device configured to eject a drug agent. A dispense interface may be configured to be in fluid communication with at least one reservoir of the medical device containing at least one medicament. For instance, the drug dispense interface is a type of outlet that allows the at least one medicament to exit the medical device. The dispense interface may comprise a valve arrangement. Such a valve arrangement may be configured to prevent contamination of the at least one medicament in the at least one reservoir. For instance, the valve arrangement is configured to prevent back flow of the at least one medicament when the medicament is delivered/ejected. 
         [0027]    Alternatively, the apparatus may be the needle guide. The needle guide may be (reversibly and/or irreversibly) attachable to a connecting part such as a connecting part of a dispense interface and/or a dispenser such as a drug delivery device. 
         [0028]    The needle-assembly may be a dose dispenser. For instance, the needle assembly is configured to be in fluid communication with a holding chamber of a dispense interface and/or at least one reservoir of a dispenser such as a drug delivery device. The reservoir may contain at least one fluid such as a medicament. 
         [0029]    For instance, the needle assembly is a double-ended needle assembly and/or a standard needle assembly. The needle assembly may comprise a needle, a needle hub and a removable protecting cover. The needle may be a double-ended needle. One end of the double ended needle may be configured to be inserted into a desired injection site before an injection. The other end of the double ended needle may be configured to pierce a septum of a connecting part such as a connecting part of a dispense interface and/or a drug delivery device as described above. The needle hub may be configured to attach the needle assembly to the connecting part such as a connecting part of the dispense interface and/or the dispenser such as the drug delivery device. For instance, the needle hub comprises an internal thread corresponding to an outer thread of the connecting part. 
         [0030]    According to the present invention, the needle guide is configured to receive a needle of the needle assembly in a longitudinal opening and to center the needle in the longitudinal opening. The needle may be considered to be centered in the longitudinal opening of the needle guide, when the longitudinal axis of the longitudinal opening and the longitudinal axis of the needle are equal, i.e. the needle and the longitudinal opening are coaxial. In particular, the needle may be considered to be centered in the longitudinal opening of the needle guide, when one end of the needle being in the longitudinal opening is in the center of a cross section of the longitudinal opening. 
         [0031]    For instance, when the needle assembly is received in the longitudinal opening, the needle assembly may be laterally secured in the longitudinal opening. For instance, a rim of the longitudinal opening is configured to engage with a corresponding recess of the needle assembly such that, when the rim of the longitudinal opening is in engagement with the corresponding recess of the needle assembly, the needle is centered in the longitudinal opening. Alternatively or additionally, the longitudinal opening may have a (circular) set-back configured to receive a rim of the needle assembly such that, when the rim of the needle resides on the setback of the longitudinal opening, the needle is centered in the longitudinal opening. 
         [0032]    Furthermore, according to the present invention, the needle guide is longitudinally compressible. In particular, the longitudinal opening of the needle guide may be longitudinally compressible. For instance, when a force is applied on the longitudinal opening of the needle guide in direction of the longitudinal axis of the longitudinal opening, the longitudinal length of the longitudinal opening of the needle guide is reduced. 
         [0033]    As an example, the needle guide is arranged at a connecting part of a dispense interface such that the longitudinal opening at least partially encompasses the connecting part of the dispense interface and an outlet of the connecting part is in the center of a cross section of the longitudinal opening. In this example, when a needle assembly is received in the longitudinal opening, one end of a needle of the needle assembly may be spaced from and centered on the outlet of the connecting part. The outlet of the connecting part may be an opening at the center of the connecting part and is configured to receive one end of a needle of the needle assembly. If the needle assembly is pushed in direction of the longitudinal axis of the longitudinal opening in order to attach the needle hub of the needle assembly to the connecting part of the dispense interface as described above, the needle assembly may be laterally secured in the longitudinal opening and the one end of the needle may straightly approach the outlet along the longitudinal axis of the longitudinal opening. 
         [0034]    For instance, the smallest diameter of the longitudinal opening (or of the longitudinally compressible portion thereof) may be at least a third, preferably at least a half, more preferably at least once or twice of the longitudinal length of the longitudinal opening. This is inter-alia advantageous to stablilize the needle guide, when the longitudinal opening is longitudinally compressed, and/or to allow the needle to straightly approach the outlet and/or to prevent a tilting of the needle, when the longitudinal opening is longitudinally compressed. 
         [0035]    For instance, the needle hub of the needle assembly is screwed on the connecting part of the dispense interface and thereby one end of a needle of the double-ended assembly straightly intrudes into the outlet of the connecting part of the dispense interface, pierces a septum of the dispense interface arranged at the outlet and resides in fluid communication with a holding chamber of the dispense interface. Therein, the needle guide centers the needle and prevents a tilting of the needle. In other words, the needle guide may preferably be configured to hold the needle in the center of the longitudinal opening, when the needle guide is longitudinally compressed, such that the needle guide allows the needle to straightly approach the outlet and/or to prevent a tilting of the needle. 
         [0036]    Accordingly, the risk of a collision of the needle with side-walls of the holding chamber and/or the outlet is significantly reduced, such that the cross-sectional inner diameter of the holding-chamber and/or the outlet may correspond to the outer diameter of the needle, for instance the inner diameter of the holding-chamber and/or the outlet is only slightly larger (e.g. 5%, 10% or 25% larger) than the outer diameter of the needle. Alternatively or additionally, the length of the needle and/or the holding chamber can accordingly be decreased such that the one end of the needle of the needle assembly may be completely inside the needle hub and may intrude into the outlet after the needle hub touches the connecting part. 
         [0037]    The present invention is inter-alia advantageous in order to facilitate attaching a dose dispenser to a connecting part such as a connecting part of a dispense interface and/or a dispenser such as a drug delivery device. Furthermore, the present invention is inter-alia advantageous in order to minimize the liquid dead volume in a dispense interface and/or in front of a reservoir of a dispenser such as a drug delivery device. 
         [0038]    In the following, features and embodiments (exhibiting further features) of the present invention will be described, which are understood to equally apply to the apparatus and the method as described above. These single features/embodiments are considered to be exemplary and non-limiting, and to be respectively combinable independently from other disclosed features/embodiments of the apparatus and the method as described above. Nevertheless, these features/embodiments shall also be considered to be disclosed in all possible combinations with each other and with the apparatus and the method as described above. For instance, a mentioning that an apparatus according to the present invention is configured to perform a certain action should be understood to also disclose an according method step of the method according to the present invention. 
         [0039]    According to an embodiment of the present invention, the longitudinal opening has a circular cross-section and/or is cylindrical. Alternatively or additionally, the cross-section of the longitudinal opening may be elliptical and/or round. The longitudinal opening may be a cylinder having a longitudinal opening (e.g. a through opening). 
         [0040]    For instance, standard needle assemblies typically also have a circular cross-section. For instance, an inner diameter of the longitudinal opening may be adapted to an outer diameter of a standard needle assembly. In particular, the inner diameter at a rim of the longitudinal opening may be adapted to an outer diameter of a rim of the standard needle assembly. This embodiment is inter-alia advantageous to enable receiving a standard needle assembly in the longitudinal opening. 
         [0041]    According to an embodiment of the present invention, the longitudinal opening is defined by a longitudinally compressible lateral surface. As described above, when a force is for instance applied on the longitudinal opening of the needle guide in direction of the longitudinal axis of the longitudinal opening, the longitudinal length of the lateral surface defining the longitudinal opening of the needle guide is reduced. This embodiment is inter-alia advantageous in order to allow a longitudinal compression of the longitudinal opening. 
         [0042]    According to an embodiment of the present invention, the lateral surface is foldable. As an example, the lateral surface is (only) foldable in direction of the longitudinal axis of the longitudinal opening such that (only or mainly) the longitudinal stiffness of the lateral surface is decreased. In this example, when a needle assembly is received in the longitudinal opening and is pushed at an angle in direction of the longitudinal axis of the longitudinal opening, the lateral stiffness of the lateral surface may at least partially prevent a tilting/jamming of the needle. 
         [0043]    This embodiment is inter-alia advantageous in order to define a preferred direction for the compression of the longitudinal opening and/or to prevent a jamming/tilting of the needle of the needle assembly. 
         [0044]    According to an embodiment of the present invention, the foldable lateral surface is formed like bellows. The cross-section of the bellows like lateral surface may be “V-shaped”. For instance, the lateral surface has the property of bending and ceasing. Alternatively or additionally, the foldable lateral surface is wavelike. As described above, this embodiment is inter-alia advantageous in order to define a preferred direction for the compression and/or to prevent a jamming/tilting of the needle of the needle assembly. 
         [0045]    According to an embodiment of the present invention, the lateral surface is made from an elastic material. 
         [0046]    For instance, the needle guide is made from elastic plastics such as injection moldable elastic plastics. 
         [0047]    The elasticity of the material may cause an elastic counterforce, when the longitudinal opening and/or the lateral surface thereof is compressed. For instance, the compressed longitudinal opening, like a compressed spring washer, secures a screw connection between a needle hub of the needle assembly and a connecting part of a dispense interface and/or a dispenser such as a drug delivery device. 
         [0048]    Furthermore, the elasticity of the material may also cause an elastic counterforce, when a needle assembly is received in the longitudinal opening and is pushed at an angle in direction of the longitudinal axis of the longitudinal opening. 
         [0049]    This embodiment is inter-alia advantageous to secure a connection between a needle hub of the needle assembly and a connecting part and/or to prevent a jamming/tilting of the needle. 
         [0050]    According to an embodiment of the present invention, the lateral surface has at least one longitudinal slit. The slit may allow to reversibly spread (i.e. enlarge) the longitudinal opening. This embodiment is inter-alia advantageous to reversibly attach the needle guide to a connecting part of a dispense interface and/or a dispenser such as a drug delivery device and/or to receive the needle assembly in the longitudinal opening. 
         [0051]    According to an embodiment of the present invention, the longitudinal opening has a circular set-back configured to receive a rim of the needle assembly. The set-back may be arranged in a plane perpendicular to the longitudinal axis of the longitudinal opening. For instance, the lateral surface of the longitudinal opening has a circular set-back such that the inner diameter of the longitudinal opening is enlarged at the set-back. For instance, the enlarged inner diameter may correspond to the outer diameter of the rim of the needle assembly. For instance, the set-back and/or the longitudinal opening is configured to form a lateral form fit with the needle assembly. The needle assembly may be a standard needle assembly. As described above, this embodiment is inter-alia advantageous to center the needle of the needle assembly and to secure the needle assembly laterally. 
         [0052]    Alternatively or additionally, the longitudinal opening may have a circular notch configured to receive a rim of the needle assembly. In this case, the diameter of the longitudinal opening may be spreadable to allow receiving the rim of the needle assembly in the circular notch. The needle assembly may be (laterally and longitudinally) secured in the longitudinal opening. For instance, the notch and/or the longitudinal opening is configured to form a longitudinal and lateral form fit with the needle assembly. This embodiment is inter-alia advantageous to attach the needle assembly to the needle guide prior to attaching the needle guide to a connecting part of dispenser interface and/or a dispenser such as a drug delivery device or the like. 
         [0053]    According to an embodiment of the present invention, the needle guide is configured to encompass a connecting part of a medical device configured to eject a medicament. The medical device may be a drug delivery device as described above. 
         [0054]    As described above, the longitudinal opening may be configured to at least partially encompass the connecting part of the medical device such that an outlet of the connecting part is in the center of a cross section of the longitudinal opening. The longitudinal opening may be a through opening. For instance, the longitudinal opening is configured to at least partially receive at one end the connecting part of the medical device and at the other end the needle assembly. This embodiment is inter-alia advantageous to allow a reversible or irreversible attachment of the needle guide to the connecting part of the medical device. 
         [0055]    Alternatively, as described above, the longitudinal opening may at least partially encompass the connecting part of the medical device such that an outlet of the connecting part is in the center of a cross section of the longitudinal opening. For instance, the needle guide is irreversibly attached to the connecting part of the medical device and/or the needle guide and the connecting part of the medical device are integrally formed. 
         [0056]    According to an embodiment of the present invention, the apparatus is attachable to the medical device. In particular, the needle guide is (reversibly or irreversibly) attachable to the medical device. For instance, the medical device and the needle guide comprise mating attachment means configured to form a frictional fit, a form fit and/or an interference fit. Examples of mating attachment means include snap locks, snap fits, snap rings, keyed slots, threads and any combinations thereof. Examples of mating attachment means include snap locks, snap fits, snap rings, keyed slots, threads and any combinations thereof. Alternatively or additionally, the apparatus may be configured to be glued to the medical device. 
         [0057]    When the needle guide is attached to the medical device, the longitudinal opening may at least partially encompass a connecting part of the medical device and an outlet of the connecting part may be in the center of a cross section of the longitudinal opening. The medical device may be a drug delivery device as described above. 
         [0058]    This embodiment is inter-alia advantageous to allow an attachment of the needle guide to the connecting part of the medical device. 
         [0059]    According to an embodiment of the present invention, the apparatus is a medical device configured to eject a medicament, wherein the needle guide encompasses a connecting part of the medical device. The medical device may be a drug delivery device as described above. The longitudinal opening may at least partially encompass the connecting part of the medical device such that an outlet of the connecting part is in the center of a cross section of the longitudinal opening. 
         [0060]    According to an embodiment of the present invention, a needle hub of the needle assembly is configured to be attached to the connecting part of the medical device. In particular, the needle assembly may be configured to be reversibly attached to the connecting part of the medical device. The needle hub and the connecting part may comprise mating attachment means configured to form a frictional fit, a form fit and/or an interference fit. Examples of mating attachment means include snap locks, snap fits, snap rings, keyed slots, threads and any combinations thereof. For instance, the needle hub comprises an internal thread corresponding to an outer thread of the connecting part. 
         [0061]    This embodiment is inter-alia advantageous to allow a reversible attachment of the needle assembly to the connecting part of the medical device. 
         [0062]    According to an embodiment of the present invention, one end of a needle of the needle assembly is configured to intrude into an outlet of the connecting part and to pierce a septum of the medical device. For instance, a needle hub of the needle assembly is screwed on the connecting part of the dispense interface and/or the medical device and thereby one end of a needle of the double-ended assembly intrudes into an outlet of the connecting part of the dispense interface, pierces a septum arranged at the outlet and resides in fluid communication with a holding chamber of the dispense interface and/or a reservoir of the medical device. 
         [0063]    According to an embodiment of the present invention, the method comprises longitudinally compressing the needle guide, attaching the needle assembly to a connecting part of the medical device, intruding the needle of the needle assembly into an outlet of the needle hub, and piercing a septum of the medical device. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0064]    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: 
           [0065]      FIG. 1  illustrates a perspective view of the delivery device illustrated in  FIGS. 1   a  and  1   b  with an end cap of the device removed; 
           [0066]      FIG. 2  illustrates a perspective view of the delivery device distal end showing the cartridge; 
           [0067]      FIG. 3  illustrates a perspective view of the cartridge holder illustrated in  FIG. 1  with one cartridge retainer in an open position; 
           [0068]      FIG. 4  illustrates a dispense interface and a dose dispenser that may be removably attached on a distal end of the delivery device illustrated in  FIG. 1 ; 
           [0069]      FIG. 5  illustrates the dispense interface and the dose dispenser illustrated in  FIG. 4  attached on a distal end of the delivery device illustrated in  FIG. 1 ; 
           [0070]      FIG. 6  illustrates one arrangement of the dose dispenser that may be mounted on a distal end of the delivery device; 
           [0071]      FIG. 7  illustrates a perspective view of the dispense interface illustrated in  FIG. 4 ; 
           [0072]      FIG. 8  illustrates another perspective view of the dispense interface illustrated in  FIG. 4 ; 
           [0073]      FIG. 9  illustrates a cross-sectional view of the dispense interface illustrated in  FIG. 4 ; 
           [0074]      FIG. 10  illustrates an exploded view of the dispense interface illustrated in  FIG. 4 ; 
           [0075]      FIG. 11  illustrates a cross-sectional view of the dispense interface and dose dispenser attached to a drug delivery device, such as the device illustrated in  FIG. 1 ; 
           [0076]      FIG. 12  illustrates an arrangement of a needle guide; 
           [0077]      FIG. 13  illustrates a dispense interface that may be removably mounted on a distal end of the delivery device illustrated in  FIG. 1  and a needle assembly that may be removably mounted on the dispense interface by use of a needle guide; 
           [0078]      FIG. 14  illustrates a method for attaching a needle assembly to a dispense interface by use of a needle guide; 
           [0079]      FIG. 15  illustrates a cross-sectional view of the dispense interface, needle guide and dose dispenser attached to a drug delivery device, such as the device illustrated in  FIG. 1 ; 
       
    
    
     DETAILED DESCRIPTION 
       [0080]    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. 
         [0081]    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. 
         [0082]    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 ). 
         [0083]    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. 
         [0084]    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 connecting part such as 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 . The needle hub  216  has an outer diameter  217  at the end  219 . 
         [0085]    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). 
         [0086]    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 . 
         [0087]    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 . The protective cover  420  has a rim  421  and an outer diameter  422  at the rim  421 . 
         [0088]    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. 
         [0089]      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 . 
         [0090]    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 needle hub  216  of 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). 
         [0091]    Similarly, a second or proximal piercing end  407  of the needle assembly  400  protrudes from an opposite side of the circular disc so that it is concentrically surrounded by the sleeve  403 . In one needle assembly arrangement, the second or proximal piercing end  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 . 
         [0092]    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: 
         [0093]    a. a main outer body  210 , 
         [0094]    b. an first inner body  220 , 
         [0095]    c. a second inner body  230 , 
         [0096]    d. a first piercing needle  240 , 
         [0097]    e. a second piercing needle  250 , 
         [0098]    f. a valve seal  260 , and 
         [0099]    g. a septum  270 . 
         [0100]    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 . 
         [0101]    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. 
         [0102]    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. 
         [0103]    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. 
         [0104]    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 . 
         [0105]    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 . 
         [0106]    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. 
         [0107]    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 . 
         [0108]    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 . 
         [0109]    The holding chamber  280  terminates at an outlet of the interface  200 . This outlet  290  is preferably centrally located in the needle hub  216  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. 
         [0110]    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. 
         [0111]    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. 
         [0112]      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. 
         [0113]    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 . 
         [0114]    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 . 
         [0115]      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 . 
         [0116]    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 . 
         [0117]    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 . 
         [0118]      FIG. 12   a  to  c  illustrate an arrangement of a needle guide  500 . The needle guide  500  has a longitudinal through opening  501 . The opening  501  has a round cross section and is defined by a foldable lateral surface  502 . The foldable lateral surface  502  is in direction of the longitudinal axis  503  of the opening  501  bellows like and has a longitudinal cross section comprising two sequentially arranged “V-shaped” portions. The foldable lateral surface  502  allows a reversible compression of the opening  502  in direction of the axis  503 . 
         [0119]    A rim  504  is arranged at one end of the opening  501  and a setback  505  is arranged at the rim  504 . At the setback  505  the opening  501  has an inner diameter  506 . The inner diameter  506  corresponds (e.g. is equal to or less than or, alternatively, equal to or not less than) to the outer diameter  422  at the rim  421  of the needle assembly  400  illustrated in  FIG. 4 . At the other end of the opening  501 , a basis  507  is arranged. At the basis  507  the opening  501  has an inner diameter  508 . The inner diameter  508  corresponds (e.g. is equal to or less than) to the outer diameter at the end  219  of the needle hub  216  of the dispense interface  200  illustrated in  FIG. 4 . 
         [0120]    The needle guide  500  is made from an elastic material such as elastic plastics and the opening  501  has a longitudinal slit  509  which allows to spread the opening  501  and to enlarge the inner diameters (e.g. diameters  506 ,  508 ) of the opening  501 . 
         [0121]      FIG. 13  illustrates the dispense interface  200  illustrated in  FIGS. 7 to 10  that may be removably attached to the distal end  42  of the delivery device  10  illustrated in  FIG. 1  and the needle assembly  400  illustrated in  FIG. 6  that may be removably attached on the dispense interface  200  by use of the needle guide  500  illustrated in  FIG. 12 . 
         [0122]    As illustrated in  FIG. 13  the needle guide  500  is arranged between the needle assembly  400  and the dispense interface  200 . Therein, base  507  of the needle guide  500  is oriented towards the dispense interface  200  and the rim  504  of the needle guide  500  is oriented towards the needle assembly  400  and, additionally, the longitudinal axis  503  of the needle guide  500  is also the longitudinal axis of the drug delivery device  10 , the dispense interface  200  and the needle assembly  400 . 
         [0123]    The inner diameter  508  at the base  507  of the needle guide  500  is equal to or less than the outer diameter  217  at the end  219  of the needle hub  216  of the dispense interface  200 . Furthermore, the inner diameter  506  at the setback  505  (not shown) of the needle guide  500  is equal to or less than the outer diameter  422  at the rim  421  of the needle assembly  400 . 
         [0124]    The needle assembly  400  may be attached to the dispense interface  200  by use of the needle guide  500  as follows. 
         [0125]      FIG. 14  illustrates a method  700  for attaching the needle assembly  400  to the dispense interface  200  by use of the needle guide  500 . 
         [0126]    In a step  701 , the opening  501  of the needle guide  500  is spread by spreading the slit  509  of the opening  501  and thereby the inner diameters of the opening  501  are enlarged. In particular, the inner diameter  508  of the spread opening  501  is enlarged. 
         [0127]    In a step  702 , the needle hub  216  of the dispense interface  200  is received in the spread opening  501 ; and, in a step  703 , the spreading is released. After releasing the spread, the opening  501  returns to its natural shape such that the inner diameter  508  of the spread opening  501  is equal to or less than the outer diameter  217  at the end  219  of the needle hub  216 . Accordingly, the needle guide  500  is attached to the dispense interface  200  by forming a press fit or form fit connection with the end  219  of the of the needle hub  216  such that the opening  501  encompasses the needle hub  216  of the dispense interface  200  and the outlet  290  of the needle hub  216  is in the center of a cross section of the opening  501 . Alternatively or additionally, the base  507  of the needle guide may be bonded (e.g. glued) to the surface of the dispense interface. 
         [0128]    In a step  704 , the needle assembly  400  is at least partially received in the opening  501 . After at least partially receiving the needle assembly  400  in the opening  501 , the rim  421  of the protective cover  420  resides on the setback  505  of the opening  501  and is laterally secured by the rim  504  of the opening  501  such that the double-ended needle  406  of the needle assembly  400  is centered in the opening. In particular, the piercing end  407  of the double-ended needle  406  is spaced from and centered on the outlet  290  of the needle hub  216 . For instance, the needle assembly  400  at least partially forms a form fit connection with the opening  501 . 
         [0129]    In a step  705 , the needle assembly  400  is pushed towards the dispense interface  200  along the longitudinal axis  503 . Since the rim  421  of the protective cap  420  of the needle assembly resides on the setback  505  of the opening  501 , the rim  504  of the opening  501  is also pushed towards the dispense interface  200  along the longitudinal axis  503  such that the lateral surface  502  of the opening  501  is folded and the opening  501  is compressed. Therein, the rim  421  of the protective cap  420  of the needle assembly remains on the setback  505  and is laterally secured by the rim  504  of the opening  501  such that the piercing end  407  of the double-ended needle  406  straightly approaches the outlet  290  along the axis  503 . 
         [0130]    When the needle hub  401  of the needle assembly  400  touches the needle hub  216  of the dispense interface, in a step  706 , the needle assembly  400  is attached to the dispense interface  200 . 
         [0131]    Therein, the rim  421  of the protective cap  420  of the needle assembly still remains on the setback  505  and is laterally secured by the rim  504  of the opening  501 . As described above, the internal thread  404  of the needle hub  401  of the needle assembly is screwed on the outer thread  218  of the needle hub  216  of the dispense interface  200  and thereby the piercing end  407  of the double-ended needle  406  intrudes into the outlet  290  of the needle hub  216 , pierces the septum  270  arranged at the outlet  290  and resides in fluid communication with the holding chamber  280  of the dispense interface  200 . The holding chamber may be in fluid communication with the first and second proximal needle. 
         [0132]    Accordingly, the risk of a collision of the double-ended needle  406  with side-walls of the holding chamber  280  is significantly reduced, such that the cross-sectional inner diameter of the holding-chamber  280  may correspond to the outer diameter of the double ended needle  406 . 
         [0133]    Alternatively, the needle assembly  400  may firstly be received in the opening  501  of the needle guide  500  and, thereafter, the needle guide  500  may be attached to the dispense interface  200 . For instance, firstly the steps  704  to  706  and, thereafter, the steps  701 - 703  may be performed. 
         [0134]      FIG. 15  illustrates a cross-sectional view of the dispense interface  200  illustrated in  FIGS. 7-10 , needle guide  500  illustrated in  FIG. 12  and needle assembly  400  illustrated in  FIG. 6  attached to a drug delivery device  10  illustrated in  FIG. 1 . At this point, it is mainly referred to the above description of the arrangement illustrated in  FIG. 11  and, basically, the differences are described only. 
         [0135]    As illustrated in  FIG. 15 , the needle hub  401  of the needle assembly  400  is screwed onto the needle hub  216  of the dispense interface  200 . Therein, the sleeve  403  of the needle hub  401  resides on the setback  505  of the needle guide  500  and longitudinally compresses the opening  501  such that the lateral surface  502  of the longitudinal opening is folded. In response to the compression, an elastic counterforce in the direction of arrow  1000  is caused by the lateral surface  502 . This counterforce may secure the screw connection between the dispense interface  200  and the needle assembly  400 . 
         [0136]    The present invention is inter-alia advantageous in order to facilitate attaching needle assembly  400  to the needle hub  216  of the dispense interface  200 . Furthermore, the present invention is inter-alia advantageous in order to minimize the liquid dead volume in the dispense interface and/or in front of the cartridges  90  and  100  of the drug delivery device  10  and to secure the screw connection between the dispense interface  200  and the needle assembly  400 . 
         [0137]    The term “drug” or “medicament”, as used herein, means a pharmaceutical formulation containing at least one pharmaceutically active compound, 
         [0138]    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, 
         [0139]    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, 
         [0140]    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, 
         [0141]    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. 
         [0142]    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. 
         [0143]    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. 
         [0144]    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. 
         [0145]    Exendin-4 derivatives are for example selected from the following list of compounds: 
         [0146]    H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2, 
         [0147]    H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2, 
         [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); or 
         [0156]    des Pro36 [Asp28] Exendin-4(1-39), 
         [0157]    des Pro36 [IsoAsp28] Exendin-4(1-39), 
         [0158]    des Pro36 [Met(O)14, Asp28] Exendin-4(1-39), 
         [0159]    des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39), 
         [0160]    des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39), 
         [0161]    des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39), 
         [0162]    des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39), 
         [0163]    des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39), 
         [0164]    wherein the group -Lys6-NH2 may be bound to the C-terminus of the Exendin-4 derivative; 
         [0165]    or an Exendin-4 derivative of the sequence 
         [0166]    H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2, 
         [0167]    des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2, 
         [0168]    H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2, 
         [0169]    H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2, 
         [0170]    des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0171]    H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0172]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0173]    H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2, 
         [0174]    H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2, 
         [0175]    H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2, 
         [0176]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2, 
         [0177]    des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0178]    H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0179]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0180]    H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2, 
         [0181]    des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2, 
         [0182]    H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, 
         [0183]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, 
         [0184]    des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0185]    H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0186]    H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0187]    H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2, 
         [0188]    H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25] Exendin-4(1-39)-NH2, 
         [0189]    H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, 
         [0190]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-NH2, 
         [0191]    des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, 
         [0192]    H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(S1-39)-(Lys)6-NH2, 
         [0193]    H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2; 
         [0194]    or a pharmaceutically acceptable salt or solvate of any one of the afore-mentioned Exedin-4 derivative. 
         [0195]    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. 
         [0196]    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. 
         [0197]    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. 
         [0198]    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. 
         [0199]    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. 
         [0200]    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. 
         [0201]    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. 
         [0202]    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. 
         [0203]    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). 
         [0204]    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. 
         [0205]    Pharmaceutically acceptable solvates are for example hydrates.