Patent Publication Number: US-2023149629-A1

Title: Injection device and injection solution transferring system

Description:
The invention relates to an injection device., in particular a micro dose injection device such as, for example, an ophthalmic injection device for intraocular use. Further, the invention relates to an injection solution transferring system for transferring an injection solution from a syringe to an injection device of this kind. 
     Typically, an injection solution to be administered to a patient for medical treatment is stored within a syringe having a container for accommodating the injection solution and a plunger which is displaceable relative to the container in order to expel the injection solution from the container. In case the medical treatment plan for a patient provides for the administration of a dose of the injection solution which corresponds to the filling volume of the syringe or in case the dosage of the injection solution is of minor importance for the desired therapeutic effect, the injection solution may be administered to the patient directly from the syringe. However, in case the medical treatment plan for a patient requires the administration of a dose of the injection solution which differs from the filling volume of the syringe and/or in case an accurate dosage of the injection solution is necessary, the injection solution, prior to administration, may be transferred from the syringe to an injection device which finally is used to inject the desired dose of the injection solution into the patient. 
     US 2002/052578 A1 describes an injection device for injection of set doses of medicine from a cartridge. The injection device comprises a housing, a threaded piston rod which is linearly displaceable in the housing and a displaceable nut that moves relative to the housing and engages the thread of the piston rod so that the nut can screw along the thread of the piston rod. The displacement of the nut along the piston rod defines a quantity of medication to be injected by the injection device. 
     The invention is directed at the object of providing an injection device which allows the accurate and reliable administration of a micro dose of an injection solution to a patient Further, the invention is directed at the object of providing an injection solution transferring system for transferring an injection solution from a syringe to an injection device of this kind. 
     This object is addressed by an injection device as defined in claim  1  and an injection solution transferring system as defined in claim  15 . 
     An injection device comprises an injection solution receptacle. The injection solution receptacle and the protective outer barrel can be made from any suitable material, or combination of materials, including a plastic material or from glass. Suitable plastic material comprises for example cycloolefin polymer or cycloolefin copolymer. An example of a glass material may be borosilicate glass. Preferably, the glass material is tungsten-free. In one embodiment the injection solution receptacle may be uncoated. Uncoated means that the injection solution receptacle does not contain any other material other than the material of which the injection solution receptacle is made of. Alternatively, the injection solution receptacle may comprise an internal coating. Internal coating means a coating on the inner side of the injection solution receptacle which is in contact with the injection solution. Examples of such an internal coating comprise silicone coating or a fluorocarbon film made from a modified ethylene-tetrafluoroethylene copolymer. The injection solution receptacle may be silicone free, or substantially silicone free, or may comprise a low level of silicone as lubricant. Preferably, the injection solution receptacle is made of a sterile plastic material. Preferably, the injection solution receptacle is made of a sterile plastic material. Preferably, the injection solution receptacle does not comprise an internal coating. In one embodiment, the injection solution receptacle may meet USP789. 
     The injection solution receptacle may be designed in the form of an inner injection solution receptacle which is contained within a protective outer barrel, An injection solution receptacle designed in the form of an inner injection solution receptacle may be formed integral with the protective outer barrel. In the region of its proximal end, the protective outer barrel may be provided with a flange element which may serve to connect the protective outer barrel and the inner injection solution receptacle to a housing of the injection device. For example, the housing of the injection device may comprise a suitably shaped and dimensioned receptacle for receiving the flange element and hence fastening the protective outer barrel and the inner injection solution receptacle to the housing. 
     A distal end of the injection solution receptacle of the injection device may be provided with a male part of a Luer taper which is adapted to interact with a female part of a Luer taper, The female part of a Luer taper may, for example, be provided on a connecting port of an adapter element of a filling adapter which may be used to connect the injection device to a syringe containing an injection solution to be transferred from the syringe to the injection solution receptacle of the injection device. By means of the Liter taper, a fluid-tight connection can be established between the distal end of the injection solution receptacle of the injection device and the adapter element of the filling adapter in a simple manner. The outer barrel of the injection device, in the region of its distal end, may be provided with a Luer thread which is adapted to interact with a complementary Luer thread provided at the second connecting port of the adapter element of the filling adapter, in particular in the region of its outer circumference. As a result, also a reliable connection between the outer barrel of the injection device and the adapter element of the filling adapter can be effected. 
     The injection device further comprises a plunger. The plunger may be made of polycarbonate. At least a portion of the plunger is slidably received within the. injection solution receptacle. The plunger is displaceable relative to the injection solution receptacle in a distal direction along a longitudinal axis of the plunger in order to expel an injection solution contained in the injection solution receptacle from the injection solution receptacle. At its proximal end which may protrude from the injection solution receptacle in a proximal direction, the plunger may carry an actuation button which may be depressed by a user in order to displace the plunger relative to the injection solution receptacle in the distal direction along the longitudinal axis of the plunger. At its distal end, the plunger may be provided with a tip element which may be attached to a plunger rod. A coupling between the plunger rod and the tip element may be effected, for example, by the interaction of a tip barb provided at a distal end of the plunger rod with a barb receptacle of the tip element. Further, the tip element may be provided with a sealing element which, for example, may be provided in the region of an outer circumferential surface of the tip element and which sealingly interacts with an inner circumferential surface of the injection solution receptacle. 
     The injection device further comprises a first plunger stop mechanism which is adapted to stop a displacement of the plunger relative to the injection solution receptacle in the distal direction at a first dosing position. Further, the injection device comprises a second plunger stop mechanism which is adapted to stop a displacement of the plunger relative to the injection solution receptacle from the first dosing position in the distal direction at a second dosing position. The first and the second dosing position of the plunger are selected in such a manner that the plunger), upon being displaced relative to the injection solution receptacle between the first and the second dosing position is adapted to expel a desired dose of the injection solution contained in the injection solution receptacle from the injection Solution receptacle. 
     After filling the injection solution receptacle with the injection solution to be administered to a patient, a user of the injection device can expel excess injection solution from the injection solution receptacle by displacing the plunger relative to the injection solution receptacle in the distal direction until the plunger reaches the first dosing position. Upon reaching the first dosing position, the first plunger stop mechanism stops further displacement of the plunger in the distal direction. Consequently, the user is prevented from expelling too much injection solution from the injection solution receptacle, The residual injection solution contained in the injection solution receptacle can then be administered to a patient by further displacing the plunger in the distal direction until the plunger reaches the second dosing position, Upon reaching the second dosing position, the second plunger stop mechanism stops further displacement of the plunger in the distal direction and hence prevents that too much injection solution is administered to the patient. 
     The injection device allows the accurate and reliable administration of a micro dose of an injection solution to a patient Further, the injection device can easily and comfortably be handled by a user. The injection device therefore is particularly suitable for treating a paediatric patient. In particular, the injection device may be designed in the form of an ophthalmic injection device for intraocular use. 
     In one embodiment, the injection device is filled with a dosage volume (i.e. the volume of injection solution intended for delivery to the patient) of between about 1 μl to about 50 μl, preferably between about 10 μl to about 20 μl, of an injection solution. In a preferred embodiment, the injection device is filled with a dosage volume of 5 μl, or 10 μl, or 20 μl, or 30 μl of an injection solution. 
     The injection device may be filled with any injection solution, for example an injectable medicament. in one embodiment, the injection device is filled with an injectable medicament comprising an active ingredient suitable for the treatment of an ocular disease, Examples of such ocular diseases include retinopathy of prematurity, geographic atrophy, glaucoma, choroidal neovascularisation, age-related macular degeneration (both wet and dry forms), macular edema secondary to retinal vein occlusion (RVO) including both branch RVO (bRVO) and central RVO (cRVO), choroidal neovascularisation secondary to pathologic myopia (PM), diabetic macular edema (DME), diabetic retinopathy, pigmentosa, Lebers congential aumaurosis, Bietti crystalline dystrophy, and proliferative retinopathy. in one embodiment, the medicament comprises a biologic active The biologic active may be an antibody (or fragment thereof), a non-antibody protein, nucleic adds for gene therapy or cellular material for cell therapy. in one embodiment, the medicament comprises a VEGF antagonist Suitable VEGF antagonists include ranibizumab (Lucentis™) bevacizumab (Avastin™) brolucizumab (also known as RTH258), afilbercept (Eylea™, also known as VEGF-Trap Eye), conbercept (KH902 from Chengdu Kan bong Biotechnologies Co. Ltd described as FP3 in WO2005/121176, the contents of which are hereby incorporated by reference) and the related giycoform KH906 or pazopanib (from GlaxoSmithKline). 
     in a preferred embodiment the injection device is filled with 0.1 mg or 0.2 mg ranibizumab in 20 μl injection solution. in a most preferred embodiment, the injection device is filled with 20 μl of ranibizumab (0.2 mg) and used for the treatment of retinopathy of prematurity. 
     in a preferred embodiment of the injection device, the first plunger stop mechanism comprises a dosing element which is attached to the plunger and which is adapted to abut against a first dosing surface provided on a housing element. Alternatively or additionally thereto, the second plunger stop mechanism may comprise a dosing element which is attached to the plunger and which is adapted to abut against a second dosing surface provided on a housing element. 
     Preferably, the dosing element of the first a d or the second plunger stop mechanism is formed integral with the plunger. For example, the dosing element may be designed in the form of a rib which may protrude from a surface of an actuation button of the plunger in the direction of the inner solution receptacle. Basically, it is conceivable that the injection device comprises a first dosing element associated to the first plunger stop mechanism and a second dosing element associated to the second plunger stop mechanism. Preferably, however, the injection device comprises only one dosing element which is attached to the plunger and which is associated to both the first and the second plunger stop mechanism. A single dosing element may be adapted, upon movement of the plunger in the distal direction, to first abut against the first dosing surface when the plunger reaches the first dosing position and then, upon further movement of the plunger from the first dosing position in the distal direction, against the second dosing surface when the plunger reaches the second dosing position. 
     The first and the second dosing surface may be provided on different housing elements of the injection device. In a preferred embodiment of the injection device, the first and the second dosing surface, however, both are formed on a first housing element, i.e. on the same housing element of the injection device. The first and the second dosing surface preferably extend substantially parallel to each other, wherein the second dosing surface may be arranged parallel offset relative to the first dosing surface in the distal direction. A distance between the first and the second dosing surface in the distal direction may correspond to a desired travel distance of the plunger in the distal direction between the first and the second dosing position. Hence, by suitably arranging the first and the second dosing surface, the desired plunger displacement between the first and the second dosing position and hence the desired injection solution dose to be expelled from the injection solution receptacle upon displacing the plunger from the first to the second dosing position can be set. The first and the second dosing surface may extend substantially parallel to an abutting surface of the dosing element. For example, the first and the second dosing surface as well as the abutting surface of the dosing element may extend substantially perpendicular to the longitudinal axis of the plunger. 
     The first plunger stop mechanism may be designed in such a manner that it provides a resistance force that is adapted to stop the displacement of the plunger at the first dosing position, but that can be overcome, for example by increasing the actuation force acting on the plunger. In a particular preferred embodiment of the injection device, the first plunger stop mechanism, however, is adapted to provide a hard stop for the plunger, i.e. is adapted to prevent the plunger from being displaced relative to the injection solution receptacle from the first dosing position in the distal direction without damaging the first plunger stop mechanism. In particular in case the first plunger stop mechanism is designed as a hard stop for the plunger, the injection device preferably further comprises a plunger releasing mechanism which is adapted to deactivate the first plunger stop mechanism in order to release the plunger and to thus allow a displacement of the plunger relative to the injection solution receptacle from the first dosing position in the distal direction, i.e, in the direction of the second dosing position. 
     Also the second plunger stop mechanism may be designed in such a manner that it provides a resistance force that is adapted to stop the displacement of the plunger at the second dosing position, but that can be overcome, for example by increasing the actuation force acting on the plunger. In a particular preferred embodiment, the second plunger stop mechanism, however, is adapted to provide a hard stop for the plunger, i.e. is adapted to prevent the plunger from being displaced relative to the injection solution receptacle from the second dosing position in the distal direction without damaging the second plunger stop mechanism, The dose of the injection solution to be administered to a patient can then be set in a particularly accurate manner. 
     Preferably, the plunger releasing mechanism is adapted to allow a movement of at least one of the dosing element and the first dosing surface in order to disengage the dosing element from the first dosing surface. The movement of the dosing element and/or the first dosing surface may be manually induced by a user of the injection device. In a particular preferred embodiment of the injection device, it is sufficient for a user to move only the first dosing surface for disengaging the dosing element from the first dosing surface. As a result, it is not necessary for the user to induce a movement of the plunger for activating the plunger releasing mechanism.. For example, only the housing element carrying the first dosing surface may be moved for activating the plunger releasing mechanism, whereas the plunger may remain in its position, which simplifies the use of the injection device. 
     The plunger releasing mechanism may be adapted to allow a rotational movement of at least one of the dosing element and the first dosing surface in order to disengage the dosing element from the first dosing surface. For example, the plunger releasing mechanism may be activatable by a manually induced rotation of the plunger and/or the first dosing surface. In particular, the plunger releasing mechanism may be adapted to allow a rotational movement of the housing element carrying the first dosing surface for activating the plunger releasing mechanism. The actuation of a rotational movement of the plunger and/or the first dosing surface and in particular of only the first dosing surface can easily be distinguished by a user from the pressing actuation of the plunger so as to move the plunger in the distal direction. As a result, the use of the injection device is further simplified. 
     In a preferred embodiment of the injection device, the first and the second dosing surface are arranged offset relative to each other, for example on different or the same housing element(s), in a circumferential direction of the plunger. The plunger releasing mechanism then may be adapted to displace the first and the second dosing surface in the circumferential direction of the plunger, in order to disengage the dosing element from the first dosing surface and to simultaneously align the second dosing surface with the dosing element, such that the dosing element abuts against the second dosing surface, when the plunger, upon being displaced relative to the injection solution receptacle from the first dosing position in the distal direction, reaches the second dosing position. Such a design of the plunger releasing mechanism allows a particularly simple and reliable handling of the injection device. 
     Preferably, the first and the second dosing surface are formed on the first housing element which is rotatable relative to the plunger. In case the first and the second dosing surface are arranged offset relative to each other on the first housing element a circumferential direction of the plunger disengagement of the dosing element from the first dosing surface and simultaneous arrangement of the second dosing surface in a position wherein the second dosing surface is ready for engagement with the dosing element, when the plunger, upon being displaced from the first dosing position in the distal direction, reaches the second dosing position can easily be achieved by simply rotating the first housing element by a suitable rotation a mount. 
     The second dosing surface may be defined by a bottom surface of a recess formed in the first dosing surface, Preferably, the recess is designed, i.e. shaped and dimensioned, so as to allow the dosing element to be received in the recess. When the plunger is arranged in its first dosing position and the dosing element abuts against the first dosing surface, the recess defined in the first dosing surface, via a rotational movement of the first housing element, can be brought into alignment with the dosing element. As a result, the dosing element is disengaged from the first dosing surface and the plunger can further be displaced in the distal direction until the dosing element is received in the recess and the abutting surface formed on the dosing element abuts against the second dosing surface defined by the bottom surface of the recess. A depth of the recess which defines the distance between the first and the second dosing surface in the distal direction may correspond to the desired travel distance of the plunger in the distal direction between the first and the second dosing position. 
     The first housing element which carries the first and the second dosing surface, in particular in the region of an outer surface, may be provided with a gripping structure. For example, the gripping structure may be designed in the form of a gripping rib array with individual gripping ribs extending, in dependence on the shape of the outer surface of the first housing element, substantially in a direction along the longitudinal axis of the plunger. The gripping structure simplifies the handling of the plunger releasing mechanism. 
     Preferably, the plunger releasing mechanism comprises a marker system which is adapted to indicate an activation of the plunger releasing mechanism. The marker system may, for example, comprise a first marker element which is provided on the first housing element which carries the first and the second dosing surface, for example in the region of an outer surface thereof. The marker system may further comprise a second marker element which is provided on a second housing element of the injection device, in particular in the region of an outer surface thereof. The first and the second marker element may be arranged on the first and the second housing element in such a position that they are positioned offset relative to each other, for example in a circumferential direction of the plunger, when the plunger releasing mechanism is not activated, but positioned in alignment with each other, when the plunger releasing mechanism is activated. The marker system provides a user with guidance information on how to activate the plunger release mechanism and hence simplifies the handling of the injection device. 
     The injection device preferably further comprises an activation mechanism which is adapted to prevent an activation of the plunger releasing mechanism unless the plunger is arranged at the first dosing position and which is adapted to allow an activation of the plunger releasing mechanism when the plunger is arranged at the first dosing position. The activation mechanism may be adapted to prevent a movement of the dosing element and/or the first dosing surface relative to each other unless the plunger is arranged at the first dosing position. In particular, the activation mechanism may be adapted to prevent a rotation of the first housing element carrying the first and the second dosing surface relative to the plunger carrying the dosing element unless the plunger is arranged at the first dosing position. 
     In a preferred embodiment of the injection device, the activation mechanism comprises a guiding channel which is provided on a circumferential surface of the plunger, which extends along the longitudinal axis of the plunger and which receives a guiding element provided on a housing element in such a manner that the gliding channel, upon displacement of the plunger relative to the injection solution receptacle, is displaced relative to the guiding element, An interaction between the guiding element and opposing side surfaces of the guiding channel may prevent a rotation of the plunger and the housing element relative to each other. When the activation mechanism comprises a guiding channel extending along the longitudinal axis of the plunger and a corresponding guiding element, the activation mechanism fulfills the double function to provide for a guided displacement of the plunger in the direction of its longitudinal axis on the one hand and to simultaneously prevent an unintentional deactivation of the first plunger stop mechanism when the plunger is not arranged at the first. dosing position. The guiding element may be provided on the first housing element which carries the first dosing surface and preferably also the second dosing surface. 
     The activation mechanism may further comprise an activation channel which branches off from the guiding channel. For example, the activation channel may extend in a circumferential direction of the plunger substantially perpendicular to the guiding channel, The activation channel preferably is adapted to receive the guiding element when the plunger is arranged at the first dosing position and the first housing element which carries the guiding element and preferably also the first and the second dosing surface is rotated relative to the plunger. With such a design of the activation mechanism, the first dosing position of the plunger is defined by the position of the activation channel along the longitudinal axis of the plunger. 
     The first and the second dosing surface may be formed on the first housing element which is rotatable relative to the plunger. In case the first and the second dosing surface are arranged offset relative to each other on the first housing element in a circumferential direction of the plunger, disengagement of the dosing element from the first dosing surface and simultaneous arrangement of the second dosing surface in a position wherein the second dosing surface is ready for engagement with the dosing element, when the plunger, upon being displaced from the first dosing position in the distal direction, reaches the second dosing position can easily be achieved by simply rotating the first housing element by a suitable rotation amount. 
     The second dosing surface may be defined by a bottom surface of a recess formed in the first dosing surface. Preferably the recess is designed, i.e. shaped and dimensioned, so as to allow the dosing element to be received in the recess. When the plunger is arranged in its first dosing position and the dosing element abuts against the first dosing surface, the recess defined in the first dosing surface, via a rotational movement of the first housing element, can be brought into alignment with the dosing element. As a result, the dosing element is disengaged from the first dosing surface and the plunger can further be displaced in the distal direction until the dosing element is received in the recess and the abutting surface formed on the dosing element abuts against the second dosing surface defined by the bottom surface of the recess. 
     The plunger release mechanism may further comprise a locking arrangement which is adapted to lock the first dosing surface in its position relative to the dosing element after the first dosing surface has been moved relative to the dosing element in order to become disengaged from the dosing element. The locking arrangement thus allows the plunger release mechanism to be used only once for deactivating the first plunger stop mechanism. As a result, reuse of the injection device is reliably prevented. 
     The locking arrangement may comprise a resilient locking clip which is adapted to be resiliently urged out of a rest position by the interaction with a locking element when the first dosing surface is moved relative to the dosing element so as to become disengaged from the dosing element, For example, the resilient locking clip may be provided on the second housing element whereas the locking element may be provided on the first housing element which carries the first dosing surface and optionally also the second dosing surface. The resilient locking clip then may be resiliently deformed when the first housing element is rotated relative to the second housing element. The locking clip preferably further is adapted to deform back into its rest position after completion of the movement of the first dosing surface and to interact with the locking element so as to lock the first dosing surface in its position relative to the dosing element. In particular, the locking dip may interact with the locking element so as to prevent a counter rotation of the first housing element relative to the second housing element and the plunger, after the first housing element has been rotated once in order to disengage the first dosing surface from the dosing element and to align the second dosing surface with the dosing element. 
     The injection device may further comprise a limiting mechanism which is adapted to limit a movement of the dosing element and/or both the first dosing surface and the second dosing surface for disengaging the dosing element from the first dosing surface and for aligning the dosing element with the second dosing surface. The limiting mechanism prevents a user of the injection device from moving the dosing element and the first and the second dosing surface relative to each other in an excessive manner. Further, the limiting mechanism provides an haptic feedback to the user that the dosing element is properly disengaged from the first dosing surface and aligned with the second dosing surface, i.e. that the first plunger stop mechanism has been deactivated. 
     The limiting mechanism may in particular comprise a first limiting element which is provided on the first housing element carrying the first and the second dosing surface. Further, the limiting mechanism may comprise a second limiting element which is provided on a second housing element, the second housing element being adapted to remain stationary when the first housing element is moved, in particular rotated, for deactivating the first plunger stop mechanism. The first limiting element may be adapted to abut against the second limiting element when the dosing element is disengaged from the first dosing surface and aligned with the second dosing surface. 
     In case the injection device comprises an above-described activation mechanism with an activation channel and a guiding element formed on the first housing element which also carries the first and the second dosing surface, the movement of the first dosing surface relative to the dosing element attached to the plunger may also be limited by an interaction between the guiding element and an end face of the activation channel which may act as an abutting surface for the guiding element when the first housing element, after being rotated relative to the plunger, has reached a position wherein the dosing element is disengaged from the first dosing surface and aligned with the second dosing surface. 
     The injection device may further comprise a first drag mechanism adapted to exert a retaining force which retains the plunger in its current position relative to the injection solution receptacle. The first drag mechanism thus prevents an unintentional displacement of the plunger relative to the injection solution receptacle in other words, due to the presence of the first drag mechanism, active manual actuation, for example by the application of a pressing force, is necessary for displacing the plunger relative to the injection solution receptacle. The first drag mechanism may comprise a resilient drag element which may, for example, be provided on the second housing element. The resilient drag element may be adapted to exert a resilient retaining force on the plunger, i.e. the resilient drag element may be resiliently urged out of a rest position into a biasing position by an interaction with the plunger and, due to its resiliency, may apply a resilient reaction force on the plunger which retains the plunger in its current position. The resilient drag element may in particular interact with a drag rib which is provided on the outer circumferential surface of the plunger and which extends substantially parallel to the longitudinal axis of the plunger. 
     Alternatively or additionally thereto, the injection device may also comprise a second drag mechanism adapted to exert a retaining force which retains the first housing element in its current position, i.e. which retains the first housing element in its position relative to the second housing element The second drag mechanism thus prevents an unintentional displacement of the first housing element relative to the second housing element and hence an unintentional deactivation of the first plunger stop mechanism. The second drag mechanism may comprise a friction element which is provided on the first limiting element of the limiting mechanism and which is adapted to interact with a retaining element of the second housing element. 
     The injection device may further comprise a plunger positioning mechanism which is adapted to prevent a displacement of the plunger relative to the injection solution receptacle from a proximal end position in a proximal direction. The plunger positioning mechanism may, for example, comprise a distal end face of the guiding channel which is provided in the circumferential surface of the plunger, An interaction between the distal end face of the guiding channel and the guiding element received therein then may define the proximal end position of the plunder, 
     The injection device may be pre-filled with a compound, via a pre-filled syringe ( 14 ), a vial, or other reservoir. 
     In one embodiment, the injection device (whether pre-filled or not) is sterilized and provided in a sealed package. In one embodiment, the injection device is pre-filled with a suitable injection solution and terminally sterilized. Such a terminal sterilization step may comprise known techniques such as ethylene oxide sterilization or hydrogen peroxide sterilization. 
    
    
     
       A preferred embodiment of the invention now will be described in greater detail with reference to the appended schematic drawings, wherein; 
         FIG.  1    shows an exploded view of an injection solution transferring system which comprises a filling adapter and injection device, 
         FIG.  2    shows a three-dimensional view of the filling adapter and the injection device in a connected state, 
         FIG.  3    shows a longitudinal section of the filling adapter being connected to the injection device, 
         FIGS.  4  and  5    show detailed three-dimensional views of a hollow sleeve of the filling adapter, 
         FIGS.  6  and  7    show detailed three-dimensional views of an adapter element of the filling adapter, 
         FIG.  8    shows the arrangement of the adapter element in the of sleeve of the filling adapter, 
         FIG.  9    shows a three-dimensional longitudinal cut view of the adapter element and a cannula of the filling adapter, 
         FIG.  10    shows a longitudinal section of the adapter element and the cannula of the filling adapter, 
         FIG.  11    shows a detailed view of an injection solution receptacle of the injection device, 
         FIG.  12    shows a detailed view of the plunger of the injection device, 
         FIG.  13    shows a detailed view of a tip element of the plunger, 
         FIG.  14    shows the arrangement of the cannula of the filling adapter relative to the plunger of the injection device when the filling adapter is connected to the injection device s    
         FIG.  15    shows the interaction between the guiding rib of the hollow sleeve with the injection solution receptacle of the injection device, 
         FIGS.  16  to  18    show detailed three-dimensional views of a first housing element of the injection device, 
         FIGS.  19   a  and  19   b    show the interaction between the plunger and the first housing element, 
         FIGS.  20  and  21    show detailed three-dimensional views of the second housing element of the injection device, 
         FIG.  22    shows the assembly of the second housing element, 
         FIG.  23    shows the attachment of the injection solution receptacle to the second housing element, 
         FIG.  24  and  25    show the interaction between the first and the second housing element, 
         FIG.  26    shows the interaction between the plunger and the second housing element, 
         FIGS.  27  and  28    show detailed three-dimensional views of a lever element of a plunger locking mechanism which prevents the plunger of the injection device from being moved from a filling position in a distal direction when the injection device is connected to the filling adapter, 
         FIG.  29    shows the lever element of the plunger locking mechanism in active position, 
         FIG.  30    shows the lever element of the plunger locking mechanism in an inactive position, 
         FIG.  31    shows the injection solution transferring system with the filing adapter being connected to the injection device, with one part of the second housing element removed and with the lever element of the plunger locking mechanism in its active position, 
         FIG.  32    shows the assembly of the lever element of the plunger locking mechanism in the second housing element, 
         FIG.  33    to show the use of the injection solution transferring system upon filling the injection device with an injection solution from a syringe and 
         FIGS.  34   a  to  34   d    show the use of the injection device upon administering an injection solution to a patient. 
     
    
    
       FIGS.  1  and  2    show an injection solution transferring system  100  which comprises an injection device  10  and a filling adapter  12 . The filling adapter  12  serves to connect a syringe  14  containing an injection solution to the injection device  10  for filling the injection device  10  with the injection solution from the syringe  14  as shown hi  FIGS.  33   a  to  33   d    and as will be described further below. The syringe  14  is designed in the form of a pre-filled syringe  14  which contains an injection solution for intraocular use. 
     The filling adapter  12  comprises a hollow sleeve  16  which is shown in greater detail in  FIGS.  4  and  5   . The hollow sleeve  16  made of a coloured plastic material, for example Polycarbonate/Acrylnitril Butadien Styrol (PC-ABS)) and is provided with an inner lumen which is dimensioned so as to allow the insertion of at least a distal portion of the syringe  14  at one end and of at least a distal portion of the injection device  10  at an opposing end. In the exemplary embodiment of a filling adapter  12  shown in the drawings, the hollow sleeve  16  has a substantially circular hollow cylindrical shape and the lumen extending therethrough has a substantially circular cross-sectional shape. 
     The filling adapter  12  further comprises an adapter element  18  which is accommodated within the hollow sleeve  16  and which comprises a first connecting port  20  and a second connecting port  22  The adapter element  18  may, for example, be made of polycarbonate and is shown in greater detail in  FIGS.  6  to  10   . As shown in particular in  FIG.  8   , the adapter element  18  is provided with two retention shoulders  23  which protrude from an outer circumferential surface of the adapter element  18  in opposing directions. Each retention shoulder  23  interacts with a pair of complementary crush ribs  24  protruding from an inner circumferential surface of the hollow sleeve  16  in order to fix the adapter element  18  in its position within the hollow sleeve  16 . The retention shoulders  23  and the complementary crush ribs  24  create an interference fit so as to reliably fix the adapter element  18  in its position within the hollow sleeve  16 . 
     The first connecting port  20  of the adapter element  18  is adapted to be connected to the syringe  14 , i.e. a distal end of the syringe  14 , when the filling adapter  12  is connected to the syringe  14  as shown in  FIGS.  33   a  to  33   c   . As becomes apparent in particular from  FIG.  10   , the first connecting port  20  of the adapter element  18  forms a female Luer taper  25  which is adapted to interact with a male Luer taper provided at the distal end of the syringe  14  in order to establish a fluid tight connection between the syringe  14  and the adapter element  18 . The second connecting port  22  of the adapter element  18  is adapted to be connected to the injection device  10 . 
     The adapter element  18  is provided with a through-opening  26  extending therethrough in a direction substantially parallel to a longitudinal axis L 1  of the filling adapter  12 , see in particular  FIG.  10   . A cannula  27  protrudes from the second connecting port  22  of the adapter element  18  and is arranged in fluid communication with the through-opening  26  extending through the adapter element  18 , see in particular  FIGS.  9  and  10   , The cannula  27  is made of stainless steel. The hollow sleeve  16  of the filling adapter  12 , however, extends beyond a distal tip of the cannula  27 . As a result, a user is protected from the cannula  27  during handling of the filling adapter  12 . 
     The adapter element  18  serves to establish a fluid connection between the syringe  14  and the injection device  10 , i.e. when the syringe  14  is connected to the first connecting port  20  of the adapter element  18  and the injection device  10  is connected to the second connecting port  22  of the adapter element  18  as shown in  FIG.  33   a   , injection solution contained in the syringe  14  may be transferred into the injection device  10  by manually pushing a plunger  28  of the syringe  14  as shown in  FIGS.  33   b  and  33   c    so as to expel the injection solution from the distal end of the syringe  14  into the through-opening  26  provided in the adapter element  18  and further via the cannula  27  into an injection solution receptacle  30  of the injection device  10 . 
     As becomes apparent in particular from  FIGS.  4  and  5   , the hollow sleeve  16  of the filling adapter  12 , in the region of a first end which faces the syringe  14  when the syringe  14  is brought into engagement with the first connecting port  22  of the adapter element  18 , the hollow sleeve  16  comprises at least one resilient clip  32  which is adapted to engage with a collar  34  of the syringe  14  when the syringe  14  is brought into engagement with the first connecting port  20  of the adapter element  18 , see  FIGS.  33   a  and  33   b   . In the embodiment of a hollow sleeve  16  shown in the drawings, the hollow sleeve  16  is provided with two resilient clips  32 . Each resilient clip  32  comprises an arm  36  which extends in a recess  38  provided in the hollow sleeve  16  substantially parallel to the longitudinal axis L 1  of the filling adapter  12  in the direction of the first end of the hollow sleeve  16 . A latching nose  40  protrudes from an inner surface of the arm  36  in the region of a free end of the arm  36 . 
     When the syringe  14  is brought into engagement with the first connecting port  20 , due to the interaction with the collar  34  of the syringe  14 , the resilient dip  32  is bent outwards. However, as soon as the syringe  14  has reached its final position with respect to the adapter element  18 , i.e. when the distal tip of the syringe  14  is connected to the first connecting port  20  of the adapter element  18  and the syringe  14  assumes the position relative to the hollow sleeve  1 $ which is shown in  FIG.  33   b   , the resilient dip  32  resumes its original position substantially parallel to the longitudinal axis L 1  of the filling adapter  12  such that the latching nose  40  comes into engagement with an end face of the collar  34  of the syringe  14 . As a result, the syringe  14  is firmly connected to the hollow sleeve  16 . 
     In the region of its first end, the hollow sleeve  16  at its outer circumferential surface is provided with two first gripping structures  42  each of which is designed in the form of a nub array. The first gripping structure simplifies the handling of the filling adapter  12  during connecting the syringe  14  to the filling adapter  12 . Further, the hollow sleeve  16 , in the region of its first end and the region of a second end which faces the injection device  10  when the injection device  10  is brought into engagement with the second connecting port  22  of the adapter element  18 , has an outer diameter which is larger than an outer diameter of the hollow sleeve  16  in an intermediate section arranged between the first and the second end. Such a design of the hollow sleeve  16  further simplifies the gripping and thus the handling of the filling adapter  12 . 
     As shown in in  FIG.  11   , the injection solution receptacle  30  of the injection device  10  is designed in the form of an inner injection solution receptacle  30  which is contained within a protective outer barrel  44 . The inner injection solution receptacle  30  and the protective outer barrel  44  are formed integral with each other and are made of a sterile plastic material. In the region of its proximal end, the protective outer barrel  44  is provided with a flange element  46 . A distal end of the injection solution receptacle  30  is provided with a male Luer taper  48  which interacts with a female Luer taper SO provided on the second connecting port  22  of the adapter element  18  of the filling adapter  12  when the filling adapter  12  is connected to the injection device  10  as shown in  FIGS.  2  and  3   . By means of the Luer tapers  48 ,  50 , a fluid-tight connection can be established between the distal end of the injection solution receptacle  30  and the adapter element  18  of the filling adapter  12 . 
     As further becomes apparent from  FIG.  11   , the outer barrel  44  of the injection device  10 , in the region of its distal end, is provided with a Luer thread  52 . The Luer thread  52  interacts with a complementary Luer thread  54  provided at an outer circumference of the second connecting port  22  of the adapter element  18 , see  FIGS.  6  and  8  to  10   , when the filling adapter  12  is connected to the injection device  10  as shown in  FIGS.  2  and  3   . As a result, also a reliable connection between the outer barrel  44  of the injection device  10  and the adapter element  18  of the filling adapter  12  can be effected. 
     In order to simplify the handling of the filling adapter  12  during bringing the injection device  10  into engagement with the second connecting port  22  of the adapter element  18 , the hollow sleeve  18 , in the region of a second end which faces the injection device  10  when the injection device  10  is brought into engagement with the second connecting port  22  of the adapter element  18 , at its outer circumferential surface is provided with a second gripping structure  56 . The second gripping structure  56  is designed in the form of two gripping rib arrays with individual gripping ribs extending substantially parallel to the longitudinal axis L 1  of the filling adapter  12 . 
     Further, as shown in  FIG.  15   , the hollow sleeve  16  is provided with longitudinal guiding ribs  58  which protrude from the inner circumferential surface of the hollow sleeve  16  and which extend substantially parallel to the longitudinal axis L 1  of the filling adapter  12 . The guiding ribs  58  serve to guide the injection device  10  into engagement with the second connecting port  22 . The guiding function of the guiding ribs  58  prevents the cannula  27  from contacting the injection solution receptacle  30  of the injection device  10  upon connecting the filling adapter  12  to the injection device  10 . The hollow sleeve  16  and the longitudinal guiding ribs  58  are designed, i.e. shaped and dimensioned, in such a manner that a close sliding fit is generated between the guiding ribs  58  and an outer surface of the outer barrel  54  of the injection device  10 . 
     Turning back to  FIGS.  9  and  10   , the through-opening  26  extending through the adapter element  18  comprises an inlet section  26   a  which is arranged adjacent to the first connecting port  20 . In use of the adapter  12  injection solution expelled from the syringe  14  thus enters the through-opening  26  via its inlet section  26   a  which has a flow cross-section which decreases in a direction of flow of the injection solution expelled from the syringe  14 . Further, the through-opening  26  comprises an intermediate section  26   b  which, in the direction of flow of the injection solution expelled from the syringe  14  during use of the filling adapter  12 , is arranged downstream of the inlet section  26   a . The intermediate section  26   b  of the through-opening  26  has a substantially constant flow cross-section which substantially corresponds to the smallest flow cross-section of the inlet section  26 a adjacent to the intermediate section  26   b . Finally, the through-opening  26  comprises a receiving section  26   c  which, in the direction of flow of the injection solution expelled from the syringe  14  during use of the filling adapter  12 , is arranged downstream of the intermediate section  26   b , adjacent to the second connecting port  22 . The receiving section  26   c  has a flow cross-section that is larger than the flow cross-section of the intermediate section  26   b.    
     As further becomes apparent from  FIGS.  9  and  10   , the cannula  27  extends into at least a portion of the intermediate section  26   b  of the through-opening  26  so that the intermediate section  26   b  of the through-opening  26  or a portion thereof defines a cannula receiving bore of the adapter element  18  wherein a proximal end of the cannula  27  is fixed. The cannula  27  is received in the cannula receiving bore with a close slide fit. In addition, the cannula  27  is provided with bevelled ends. This design of the cannula  27  and the cannula receiving bare minimizes the generation of wear particles upon attaching the cannula  27  in the cannula receiving bore. The final bonding between the adapter element  18  and the cannula  27  is effected by means of a UV-cured glue. The cannula  27  extends from the intermediate section  26   b  of the through-opening  26 , through the receiving section  26   c  of the through-opening  26  and the second connecting port  22  so as to protrude from the second connecting port  22 . The receiving section  26   c  of the through-opening  26 , the second connecting port  22  and the hollow sleeve  16  of the filling adapter  12  define a concentric arrangement around the cannula  27 , see in particular  FIG.  3   . 
     As shown in particular in  FIG.  8   , the adapter element  18  is provided with two retention shoulders  60  which protrude from an outer circumferential surface of the adapter element  18  in opposing directions in the region of the inlet section  26   a  and the intermediate section  26   b  of the through-opening  26  extending through the adapter element  18 . 
     When the filling adapter  12  is connected to the injection device  10 , the cannula  27  extends into the injection solution receptacle  30  of the injection device  10 , i.e. a distal tip of the cannula  27  is arranged at a distance from the distal end of the injection solution receptacle  30  within the interior of the injection solution receptacle  30 , see in particular  FIG.  3   . As a result, upon transferring injection solution from the syringe  14  to the injection device  10 , injection solution exiting the syringe  14 , via the cannula  27 , is supplied to the injection solution receptacle  30  of the injection device  10  not in the region of the distal end of the injection solution receptacle  30 , but at a position arranged at a distance from the distal end of the injection solution receptacle  30  within the interior of the injection solution receptacle  30 . 
     By simply holding the filling adapter  12  and the injection device  10  in an upright position with the longitudinal axis L 1  of the filling adapter  12  and a longitudinal axis L 2  of the injection device  10  being oriented substantially vertically and with the distal end of the injection device  10  facing downwards as shown in  FIGS.  33   a  to  33   c   , a gravity-driven flow of the injection solution from the distal tip of the cannula  27  downwards in a direction of the distal end of the injection solution receptacle  30  and further in the direction of the adapter element  18  can be induced. A part of the injection solution which is expelled from the distal tip of the cannula  27  and which in a gravity-driven manner flows back in the direction of the adapter element  18  is received in the receiving section  26   c  of the opening  26  provided in the adapter element  18 . Gas bubbles which are entrapped within the injection solution and hence transferred from the syringe  14  to the injection solution receptacle  30  together with the liquid phase of the injection solution are entrained with this gravity-driven flow and, due to the higher specific density of the liquid phase of the injection solution, are forced in the direction of the distal end of the injection solution receptacle  30  and further in the direction of the adapter element  18 . 
     Finally, the adapter element  18  is provided with a venting device  64  which is adapted to vent gas introduced from the syringe  14  into the injection device  10 , i.e, the injection solution receptacle  30  of the injection device  10 , via the through-opening  26  and the cannula  27  into the ambient. The venting device thus allows entrapped gas bubbles, in particular air bubbles, that are conveyed from the distal tip of the cannula  27  back to the adapter element  18  by the above described gravity-driven flow of the injection solution to be expelled into the ambient. The filling adapter  12  thus allows a gas free filling of the injection device  10  with the injection solution. As a result, manually expelling entrapped gas from the syringe  14  prior to connecting the syringe  14  to the filling adapter  12  can be dispensed with. Furthermore, an accurate and reliable preparation of a desired dose of the injection solution within the injection device  10  is made possible. 
     The venting device  64  comprises two radial bores  66  connecting the through-opening  26  extending through the adapter element  18  to the ambient. In particular, the radial bores  66  connect the receiving section  26  of the through-opening  26  to an outer circumferential surface of the adapter element  18  and hence to the ambient. In the embodiment of a filling adapter  18  shown in the drawings, the radial bores  66  of the venting device  64  extend coaxially from an outer circumferential surface of the adapter element  18  to the receiving section  26   c  of the through-opening  26  so as to connect the receiving section  26   c  of the through-opening  26  to the ambient. In order to ensure that gas bubbles entrapped in the injection solution can be vented to the ambient as desired without expelling a substantial amount of the liquid phase of the injection solution to the ambient, the flow cross-section, i.e. the diameter of the radial bores  66  is be selected in dependence on the physical properties, in particular the specific density, the viscosity and the surface tension of the injection solution to be transferred from the syringe  14  to the injection device  10 . 
     In order to ensure proper functioning of the venting device  64 , the retention shoulders  23  protrude from the outer circumferential surface of the adapter element  18  in the region of the inlet section  2 $a and the intermediate section  26   b  of the through-opening  26  extending through the adapter element  18 . Such a configuration ensures that, in the region of the receiving section  26   c  of the through-opening  26 , an air gap  68  is present between the outer circumferential surface of the adapter element  18  and the inner circumferential surface of the hollow sleeve  16  which allows an unhindered exit of gas from receiving section  26 c via the radial bores  66  of the venting device  64 . 
     The injection device  10  of the injection solution transferring system  100  further comprises a plunger  70  which is depicted in greater detail in  FIG.  12   . In the embodiment of an injection device  10  shown in the drawings, the plunger  70  is made of polycarbonate. At least a portion of the plunger  70  is slidably received within the injection solution receptacle  30  of the injection device  10 . The plunger  70  is displaceable relative to the injection solution receptacle  30  in a distal direction along a longitudinal axis of the plunger  70  in order to expel injection solution contained in the injection solution receptacle  30  of the injection device  10  from the injection solution receptacle  30 . At its proximal end which protrudes from the injection solution receptacle  30  in a proximal direction, the plunger  70  carries an actuation button  72  which may be depressed by a user in order to displace the plunger  70  relative to the injection solution receptacle  30  in the distal direction along the longitudinal axis of the plunger  70 . 
     At its distal end, the plunger  70  is provided with a tip element  74  which is attached to a plunger rod  76 , see  FIG.  13   . A coupling between the plunger rod  76  and the tip element  74  is effected by the interaction of a tip barb  78  provided at a distal end of the plunger rod  76  with a barb receptacle  80  of the tip element  74 . Further, the tip element  74  is provided with a sealing element  82  which is provided in the region of an outer circumferential surface of the tip element  74  and which sealingly interacts with an inner circumferential surface of the injection solution receptacle  30 . 
     The plunger  70  of the injection device  1 . 0  can be arranged in a filling position as shown in  FIGS.  33   a  to  33   d   . When the plunger  70  is arranged in its filling position and the injection device  10  is engaged with the second connecting port  22  of the adapter element  18  of the filling adapter  12 , a distal tip of the plunger  70 , i.e. a distal end face of the tip element  74  provided at the distal tip of the plunger  70 , is disposed at a desired close distance D from the distal tip of the cannula  27  of the filling adapter  12 , see  FIG.  14   . For example, the injection device  10  and the filling adapter  12  may be designed so as to set the distance D between the distal tip of the plunger  70  and the distal tip of the cannula  27  to approximately 1.5 mm+/−0.5 mm. By arranging the distal tip of the plunger  70  and the distal tip of the cannula  27  at a close distance, the injection solution supplied to the injection solution receptacle  30  via the cannula  27  is reliably forced to flow in the direction of the venting device  64 . As a result, air-free filling of the injection solution receptacle  30  with the injection solution can be ensured. 
     Finally, the hollow sleeve  16  is provided with two observing windows  83  for observing the filling of the injection device  10  with the injection solution from the syringe  14 . The observing windows  83  allow an unhindered view of interior of the injection device  10  and the distal tip of the cannula  27 . 
     The plunger  70  is displaceably received in a housing  84  of the injection device  10  which comprises a first housing element $ 6  depicted in greater detail in  FIGS.  16  to  19    and a second housing element  88  depicted in greater detail in  FIGS.  20  to  23   . Both the first and the second housing element  86 ,  88  are made of polycarbonate/acrylnitril butadien styrol, but have a different colour. The first housing element  86  is provided with a plunger through hole  90  which receives the plunger rod  76  so that the plunger  70  is displaceable in a direction along its longitudinal axis relative to the first housing element  86 . Guiding elements  92  are provided on the first housing element  86  so as to protrude into the plunger through-hole  90 . When the plunger  70 , i.e. the plunger rod  76 , is received in the plunger through-hole  90  of the first housing element  86 , each guiding element  92  engages with a guiding channel  94  which provided in a circumferential surface of the plunger  70 , i.e. the plunger rod  76 , and which extends along the longitudinal axis of the plunger  70 , see in particular  FIGS.  19   a    and  19   b.    
     For assembling the plunger  70  to the first housing element  86 , assembly channels  96  are provided in the outer circumferential surface of the plunger rod  76  which branch of from the guiding channels  94  in a distal region thereof and extend substantially perpendicular to the guiding channels  94  in a circumferential direction of the plunger rod  76 . Upon assembling the plunger  70  to the first housing element  86 , the guiding elements  92  are brought into engagement with the assembly channels  96 . Thereafter, the plunger  70  is rotated until the guiding elements  92  are received in the guiding channels  94  in a guiding manner, see  FIGS.  19   a    and  19   b.    
     In order to simplify the handling of the injection solution transferring system  100 , the injection device  10  is delivered with the plunger  70  being arranged in its filling position which corresponds to a proximal end position of the plunger  70 . A plunger positioning mechanism  98  prevents that the plunger  70  can be moved further in a proximal direction relative to the injection solution receptacle  30  than into its proximal end position, i.e. its filling position. The plunger positioning mechanism  98 , however, allows a movement of the plunger  70  relative to the injection solution receptacle  30  from its filling position in a distal direction. Specifically the plunger positioning mechanism  98  is defined by a distal end face  102  of the guiding channels  94  which are provided in the circumferential surface of the plunger rod  78  and the guiding elements  92  provided on the first housing element  86 . When the plunger  70  is arranged in its proximal end position which corresponds to its filling position, the guiding elements  90  abut against the distal end faces  102  of the guiding channels  94 . The interaction between the distal end faces  102  of the guiding channels  94  and the guiding elements  92  then prevents a further movement of the plunger  70  in the proximal direction and hence define the proximal end position, i.e. the filling position of the plunger  70 . 
     The second housing element  88  comprises two identical parts, see  FIGS.  20  and  21   , each of which comprises an interference pin  104  and an interference receptacle  106 . The two housing parts of the second housing element  88  are assembled by bringing the interference pins  104  into engagement with the respective interference receptacles  106  as shown in  FIG.  22   . For aligning the parts of the second housing element  88  relative to each other upon assembly, alignment pins  108  are provided which, upon connecting the part of the second housing element  88 , are received in respective alignment receptacles  110 . The injection solution receptacle  30  and the. protective outer barrel  44  are connected to the second housing element  88  via the flange element  46  which extends from the outer barrel  44  at a proximal end thereof. Specifically, the flange elements  46  is received in a suitably shaped and dimensioned receptacle  112  of the second housing element  88 , see  FIG.  23   . 
     As shown in particular in  FIG.  26   , the second housing element  88  is provided with a plunger guide  114  which constrains the plunger rod  76  so that the plunger  70  is prevented from rotating relative to the second housing element  88 . A first drag mechanism  116  is adapted to exert a retaining force which retains the plunger  70  in its current position relative to second housing element  88 . The first drag mechanism  116  thus prevents an unintentional displacement of the plunger  70  relative to the injection solution receptacle  30  so that active manual actuation of the plunger  70 , for example by the application of a pressing force to the actuation button  72 , is necessary for displacing the plunger  70  relative to the injection solution receptacle  30 . The first drag mechanism  116  comprises a resilient drag element  118  which is provided on the second housing element  88 . The resilient drag element  118  exerts a resilient retaining force on the plunger  70 , i.e. the resilient drag element  118  is resiliently urged out of a rest position into a biasing position by an interaction with the plunger  70  and, due to its resiliency, applies a resilient reaction force on the plunger  70  which retains the plunger  70  in its current position. Specifically, the resilient drag element  118  interacts with a drag rib  120  which is provided on the outer circumferential surface of the plunger rod  76  and which extends substantially parallel to the longitudinal axis of the plunger  70 . 
     The injection device  10  further comprises a plunger locking mechanism  122  which interacts with the filling adapter  12 , i.e. the hollow sleeve  16  of the filling adapter  12 , so as to prevent the plunger  70  of the injection device  10  from being moved from its filling position relative to the injection solution receptacle  30  in a distal direction, i.e. in the direction of the distal tip of the cannula  27 , when the injection device  10  is connected to the filling adapter  12 . The plunger locking mechanism  122  serves to prevent an inadvertent contact between the plunger  70 , i.e. the distal tip of the plunger  70 , and the distal tip of the cannula  27 . The functioning of the plunger locking mechanism  122  now will be described in greater detail with reference to  FIGS.  27  to  32   . 
     Specifically, the plunger locking mechanism  122  comprises a lever element  124 , see  FIGS.  27  and  28   , which is displaceable within the second housing element  88  between an active position which is depicted in  FIGS.  29  and  31    and an inactive position depicted in  FIG.  30   , When being arranged in its active position, the lever element  124  interacts with the plunger  70  and the hollow sleeve  16  of the filling adapter  12  so as to prevent the plunger  70  from being moved from its filling position in a distal direction when the injection device  10  is connected to the filling adapter  12 . To the contrary, when being arranged in its inactive position, the lever element  124  allows a movement of the plunger  70  from its filling position in a distal direction when the injection device  10  is not connected to the filling adapter  12 . The lever element  124  is mounted within the second housing element  88  so as to be rotatable between its active position and its inactive position. Specifically, the lever element  124  is provided with a hinge  126  which rotatably attaches the lever element  124  to a rotational axis  128  provided on the second housing element  88 . 
     The lever element  124  further comprises a pair of foot elements  130  which extend substantially parallel to each other and which are contacted by the filling adapter  12  when the injection device  10  is connected to the filling adapter  12 , in order to maintain the lever element  124  in its active position. in particular, as shown in  FIG.  29   , the foot elements  130  face the filling adapter  12  and are contacted by a locking rim  132  of the hollow sleeve  16  which faces the injection device  10  when the injection device  10  is connected to the filling adapter  12 . Due to the interaction between the locking rim  132  of the hollow sleeve  16  and the foot elements  130  the lever element  124  is pushed in a proximal direction substantially parallel to the longitudinal axis of the plunger  70  into contact with the plunger  70  and thus held in its active position shown in  FIGS.  29  and  31   . 
     The lever element  124  comprises a stop device  134  which comprises two tabs extending from a proximal end face of the lever element  124 . Further, a proximal portion of the plunger  70  extends further in a direction substantially perpendicular to the longitudinal axis of the plunger  70  than a distal portion of the plunger  70 . As a result, a shoulder which defines an abutment surface  136  is formed in a transition region between the distal portion and the proximal portion of the plunger  70  Specifically the abutment surface  136  is defined by an outer portion of a distal end face of the proximal plunger portion which protrudes from an outer circumferential surface of the distal plunger portion. When the lever element  124  is arranged in its active position as shown in  FIG.  29   , the two tabs of the stop device  134  abut against the abutment surface  136  of the plunger  70 . As a result, the lever element  124  is held in its active position and, simultaneously, movement of the plunger  70  from its filling position in a distal direction is prevented. 
     The plunger locking mechanism  122  also comprises a retention device  138  which interacts with the foot elements  130  of the lever element  124 , in order to prevent that the foot elements  130  disengage from locking rim  132  of the filling adapter  12  when the lever element  124 , by the interaction between the locking rim  132  and the foot elements  130 , is maintained in its active position, see  FIGS.  20  and  32   . in particular, the retention device  138  prevents that the foot elements  130  slip around the locking rim  132  of the hollow sleeve  16  and hence disengages from the filling adapter  12  when the lever element  124  is pushed into engagement with the plunger  70 . The retention device is provided in the second housing element  88  and is designed in the form of a retention rib which prevents that the foot elements  130  of the lever element  124  deform away from the plunger  70  in a direction substantially perpendicular to the longitudinal axis of the plunger  70 . 
     After completion of the transfer of the injection solution from the syringe  14  to the injection solution receptacle  30  of the injection device  10  with the plunger  70  being arranged in its filling position as described above and as shown in  FIGS.  33   a  to  33   c   , the filling adapter  12  and the syringe  14  are detached from the injection device  10  by disengaging the male Luer taper  48  provided at the distal end of the injection solution receptacle  30  from the female Luer taper  50  provided on the second connecting port  22  of the adapter element  18  and by disengaging the Luer thread  52  provided at the distal end of the outer barrel  44  from the complementary Luer thread  54  provided at the second connecting port  22 , see  FIG.  33     d.    
     As soon as the filling adapter  12  is detached from the injection device  10  the filling adapter  12 , i.e. the locking rim  132  of the hollow sleeve  16 , no longer contacts the foot elements  130  of the lever element  124 . Hence, when a pressing force is applied to the plunger  70  so as to displace the plunger  70  in a distal direction within the injection solution receptacle  30  of the injection device  10 , the lever element  124  is displaced into its inactive position shown in  FIG.  30   . In particular, the lever element.  124  is rotated around its rotational axis  128  from its active position into its inactive position and hence out of the way of the plunger  70 . As a result, the displacement of the plunger  70  is no longer hindered, Consequently, a needle (not shown in the drawings) can be attached to the injection device  10 , for example with the aid of the Luer thread  52  provided at the distal end of the outer barrel  44  and injection device  10  can be operated as will be described further below. 
     For administering an accurate dose, in particular an accurate micro dose of, for example, 10 μl of the injection solution received within the injection solution receptacle  30  to a patient, in a first step, excess injection solution has to be expelled from the injection solution receptacle  30  by displacing the plunger  70  relative to the injection solution receptacle  30  in the distal direction as shown in  FIG.  34   a   . Thereafter, the desired to dose of the injection solution has to be injected into the patient. 
     The injection device  10  therefore comprises a first plunger stop mechanism  140  which is adapted to stop a displacement of the plunger  70  relative to the injection solution receptacle  30  in the distal direction at a first dosing position P 1 , see  FIG.  34   . Further, the injection device  10  comprises a second plunger stop mechanism  142  which is adapted to stop a displacement of the plunger  70  relative to the injection solution receptacle  30  from the first dosing position P 1  in the distal direction at a second dosing position P 2 , see  FIG.  34   d   . The first and the second dosing position P 1 , P 2  of the plunger  70  are selected in such a manner that the plunger  70 , upon being displaced relative to the injection solution receptacle  30  between the first and the second dosing position P 1 , P 2  is adapted to expel a desired dose of the injection solution contained in the injection solution receptacle  30  from the injection solution receptacle  30 . 
     Thus, during use of the injection device  10 , a user can expel excess injection solution from the injection solution receptacle  30  by displacing the plunger  70  relative to the injection solution receptacle  30  in the distal direction until the plunder  70  reaches the first dosing position P 1 . Upon reaching the first dosing position P 1 , the first plunger stop mechanism stops  140  further displacement of the plunger  70  in the distal direction. Consequently, the user is prevented from expelling too much injection solution from the injection solution receptacle. The residual injection solution contained in the injection solution receptacle can then be administered to a patient by further displacing the plunger  70  in the distal direction until the plunger  70  reaches the second dosing position P 2 . Upon reaching the second dosing position P 2 , the second plunger stop mechanism  142  stops further displacement of the plunger  70  in the distal direction and hence prevents that too much injection solution is administered to the patient. 
     As shown in particular in  FIGS.  12 ,  16  and  18   , the first plunger stop mechanism  140  comprises a dosing element  144  which is attached to the plunger  70  and which is adapted to abut against a first dosing surface  146  provided on the first housing element  86 . The dosing element  144  also forms a part of the second plunger stop mechanism  142  and, as a part of the second plunger stop mechanism  142 , is adapted to abut against a second dosing surface  148  which is also provided on the first housing element  86 . The dosing element  144  is formed integral with the plunger  70  and is designed in the form of a rib protrudes from a lower surface of the activation button  72  in the direction of the inner solution receptacle  30 . 
     The first and the second dosing surface  146 ,  148  extend substantially parallel to each other and parallel to an abutting surface  150  of the dosing element  144  substantially perpendicular to the longitudinal axis of the plunger  70 , wherein the second dosing surface  148  is arranged parallel offset relative to the first dosing surface  146  in the. distal direction. A distance S between the first and the second dosing surface  146 ,  148  in the distal direction corresponds to a desired travel distance of the plunger  70  in the distal direction between the first and the second dosing position P 1 , P 2 , see in particular  FIG.  18   . Hence, the distance S between the first and the second dosing surface  146 ,  148  in the distal direction sets the desired injection solution dose to be expelled from the injection solution receptacle  30  upon displacing the plunger  70  from the first to the second dosing position P 1 , P 2 . 
     Further, the first and the second dosing surface  146 ,  148  are arranged offset relative to each other in a circumferential direction of the plunger  70 . Specifically, the second dosing surface  148  is defined by a bottom surface of a recess  152  formed in the first dosing surface  146  provided on the first housing element  86 . 
     When the plunger  70 , during use of the injection device  10 , is moved from its filling position shown in  FIG.  34   a    in the distal direction, the abutting surface  150  of the dosing element  144  abuts against the first dosing surface  146  when the plunger  70  reaches the first dosing position P 1  as depicted in  FIG.  34   b   . The interaction of the dosing element  144  with the first dosing surface  146  prevents the plunger from being displaced further in the distal direction. Hence, the first plunger stop mechanism  140  provides a hard stop for the plunger  70  at the first dosing position P 1 , The injection device  10  therefore further comprises a plunger releasing mechanism  154  which is adapted to deactivate the first plunger stop mechanism  140  in order to release the plunger  70  and to thus allow a displacement of the plunger  70  relative to the injection solution receptacle  30  from the first dosing position P 1  in the distal direction, i.e, in the direction of the second dosing position P 2 . 
     The plunger releasing mechanism  154  is adapted to allow a movement of the first dosing surface  146  relative to the dosing element  144 , i.e. relative to the plunger  70 , in order to disengage the dosing element  144  from the first dosing surface  146 . Specifically, the plunger releasing mechanism  154  is adapted to allow a rotational movement of the first dosing surface  146  relative to the dosing element  144 , i.e. relative to the plunger  70 , in order to disengage the dosing element  144  from the first dosing surface  146 . In order to effect the rotational movement of the first dosing surface  146  relative to the dosing element  144 , the first housing element  86  which carries the first and the second .dosing surface  146 ,  148  is designed so as to be manually rotatable relative to the second housing element  88 , see  FIG.  34   c   . Since the plunger  70  is prevented from rotating relative to the second housing element  88  by means of the plunger guide  114 , a rotation of the first housing element  86  relative to the second housing element  88  inevitably results in a rotation of the first housing element  86  relative to the plunger  70 . 
     In order to be rotatable relative to the second housing element  88  in a guided manner, the first housing element  86  is provided with a retaining recess  156 , see  FIGS.  17 ,  18  and  24   , which receives a retaining element  158  formed on the second housing element  88 , see  FIG.  20   . Further, in order to simplify the handling of the plunger releasing mechanism  154 , the first housing element  86 , in the region of its outer surface is provided with a gripping structure  159 . The gripping structure  159  is designed in the form of a gripping rib array with individual gripping ribs extending substantially in a direction along the longitudinal axis of the plunger  70 . 
     The rotation amount of the first housing element  86  relative to the second housing element  88  and hence relative to the plunger  70  is set such that the recess  152  formed in the first dosing surface  145  is brought into alignment with the dosing element  144  protruding from the activation button  72  of the plunger  70 . The plunger releasing mechanism  154  thus is adapted to displace the first and the second dosing surface  146 ,  148  in the circumferential direction of the plunger  70 , in order to disengage the dosing element  144  from the first dosing surface  146  and to simultaneously align the second dosing surface  148  with the dosing element  144 , in order to ensure that a user, upon activating the plunger releasing mechanism  154 , rotates the first housing element  86  relative to the second housing element  88  and the correct direction and by the correct rotation amount that is necessary to disengage the dosing element  144  from the first dosing surface  146  and to simultaneously align the second dosing surface  148  with the dosing element  144 , the plunger releasing mechanism  154  comprises a marker system  160  which is adapted to indicate an activation of the plunger releasing mechanism  154 . The marker system  160  comprises a first marker element  162  which is provided on an outer surface of the first housing element  86 . The marker system  160  further comprises a second marker element  164  which is provided on an outer surface of the second housing element  88 . The first and the second marker element  162 ,  164  are arranged on the first and the second housing element  86 ,  88  in such a position that they are positioned offset relative to each other a circumferential direction of the plunger  70 , when the plunger release mechanism  154  is not activated, but positioned in alignment with each other, when the plunger release mechanism  154  is activated, compare  FIGS.  34   b    and  34   c.    
     The injection device  10  further comprises a limiting mechanism  166  which is adapted to limit the movement of the first and the second dosing surface  146 ,  148  for disengaging the dosing element  144  from the first dosing surface  146  and for aligning the dosing element  144  with the second dosing surface  146 , see  FIGS.  16  and  20   , The limiting mechanism  166  comprises a first limiting element  168  which is provided on the first housing element  86  carrying the first and the second dosing surface  146 ,  148 . Further, the limiting mechanism  166  comprises a second limiting element  170  which is provided on the second housing element  88  which remains stationary when the first housing element  86  is rotated in order to deactivate the first plunger stop mechanism  140 . The first limiting element  168  abuts against the second limiting element  170  when the dosing element  144 , due to the rotation of the first housing element  86  relative to plunger  70 , is disengaged from the first dosing surface  146  and aligned with the second dosing surface  148 . The limiting mechanism  166  prevents a user of the injection device  10  from excessively rotating the first housing element  86  relative to the second housing element  88 . Further, the limiting mechanism  166  provides an haptic feedback to the user that the first plunger stop mechanism  140  has been deactivated. 
     A second drag mechanism  172  serves to exert a retaining force which retains the first housing element  86  in its current position relative to the second housing element  88 . Due to the presence of the second drag mechanism  172 , active manual actuation is necessary for rotating the first housing element  86  relative to the second housing element  88 . The second drag mechanism  172  thus prevents an unintentional displacement of the first housing element  86  relative to the second housing element  88  and hence an unintentional activation of the plunger releasing mechanism  154 . The second drag mechanism  172  comprises a friction element  174  which is provided on the first limiting element  168  of the limiting mechanism  166  and which is adapted to frictionally interact with the retaining element  158  of the second housing element  88 . 
     The injection device  10  further comprises an activation mechanism  176  which is adapted to prevent an activation of the plunger releasing mechanism  154  unless the plunger  70  is arranged at the first dosing position P 1  and which is adapted to allow an activation of the plunger releasing mechanism  154  when the plunger  70  is arranged at the first dosing position P 1  see  FIGS.  12 ,  16  and  19     a . Specifically, the activation mechanism  176  prevents a rotation of the first housing element  86  relative to the plunger  70  and hence prevents a movement of the dosing element  144  and the first dosing surface  144  relative to each other unless the plunger  70  is arranged at the first dosing position P 1 . 
     The activation mechanism  176  comprises the guiding channel  94  which is provided on the circumferential surface of the plunger  70 , which extends along the longitudinal axis of the plunger  70  and which receives the guiding element  92  provided on the first housing element  86  in such a manner that the guiding channel  94 , upon displacement of the plunger  70  relative to the injection solution receptacle  30 , is displaced relative to the guiding element  92 . An interaction between the guiding element  92  and opposing side surfaces of the guiding channel  94  prevents a rotation of the plunger  70  and the first housing element  86  relative to each other. The activation mechanism  176  thus fulfills the double function to provide for a guided displacement of the plunger  70  in the direction of its longitudinal axis on the one hand and to simultaneously prevent an unintentional deactivation of the first plunger stop mechanism  154  when the plunger  70  is not arranged at the first dosing position. 
     The activation mechanism  176  further comprises an activation channel  178  which branches off from the guiding channel  94  and extends in a circumferential direction of the plunger  70  substantially perpendicular to the guiding channel  94 . The activation channel  178  receives the guiding element  92  when the plunger  70  is arranged at the first dosing position P 1  and the first housing element  86  is rotated relative to the plunger  70 , Hence, the first dosing position P 1  of the plunger  70  is defined by the position of the activation channel  178  along the longitudinal axis of the plunger  70 . 
     Finally, the plunger release mechanism  15 $ further comprises a locking arrangement  180  which locks the first dosing surface  146  in its position relative to the dosing element  144  after the first dosing surface  14 $ has been moved relative to the dosing element  144  in order to become disengaged from the dosing element  144 , see  FIGS.  17 ,  21  and  25   . Specifically, the locking arrangement  180  comprises a resilient locking dip  182  which is provided on the second housing element  88  and which is resiliently urged out of a rest position by the interaction with a locking element  184  provided on the first housing element  86  when the first dosing surface  146  is moved relative to the dosing element  144  so as to become disengaged from the dosing element  144 , i.e. when the first housing element  86  is rotated relative to the second housing element  88 . 
     The locking clip  182  deforms back into its rest position after completion of the movement of the first dosing surface  146 , i.e. after completion of the rotation of the first housing element  85 , and interacts with the locking element  184  so as to lock the first housing element  86  relative to the second housing element  88  and the plunger  70 , in particular, the locking clip  182  interacts with the locking element  184  so as to prevent a counter rotation of the first housing element  86  relative to the second housing element  88  and the plunger  70 , after the first housing element  86  has been rotated once in order to disengage the first dosing surface  146  from the dosing element  144  and to align the second dosing surface  148  with the dosing element  144 . Consequently, the first dosing surface  146  is locked in its position relative to the dosing element  144 . The locking arrangement  180  allows the plunger release mechanism  154  to be used only once for deactivating the first plunger stop mechanism  140 . As a result, reuse of the injection device  10  is prevented. 
     After completion of the rotational movement of the first housing element  86  relative to the second housing element  88  with the plunger  70  being arranged in its first dosing position P 1 , the dosing element  144  is aligned with the recess  152  formed in the first dosing surface  146 . Consequently, the abutting surface  150  of the dosing element  144  is arranged parallel to the second dosing surface  148  at the distance S. As a result, the plunger  70  can further be displaced from the first dosing position P 1 . in the distal direction by the distance S into the second dosing position P 2 , until the dosing element  144 , i.e. its abutting surface  150  abuts against the second dosing surface  148 , compare  FIGS.  34   c  and  34   d   . Like the first plunger stop mechanism  140 , also the second plunger stop mechanism  142  provides a hard stop for the plunger  70 , i.e. prevents the plunger  70  from being displaced relative to the injection solution receptacle  30  from the second dosing position P 2  in the distal direction, The dose of the injection solution to be administered to a patient can thus be set in a particularly accurate manner. 
     LIST OF REFERENCE NUMERALS 
     injection solution transferring system  100 
 
injection device  10 
 
filling adapter  12 
 
syringe  14 
 
hollow sleeve  16 
 
adapter element  18 
 
first connecting port  20 
 
second connecting port  22 
 
retention shoulders  23 
 
crush ribs  24 
 
female Luer taper (of the first connecting port)  25 
 
through-opening  26 
 
inlet section (of the through-opening)  26   a  
 
intermediate section (of the through-opening)  26   b  
 
receiving section (of the through-opening)  25   c  
 
longitudinal axis (of the filling adapter) L 1 
 
longitudinal axis (of the injection device) L 2 
 
cannula  27 
 
plunger (of the syringe)  28 
 
injection solution receptacle  30 
 
resilient clip  32 
 
collar (of the syringe)  34 
 
arm (of the resilient dip)  36 
 
recess  38 
 
latching nose (of the resilient dip)  40 
 
first gripping structure  42 
 
outer barrel  44 
 
flange element  46 
 
male Luer taper (of the injection solution receptacle)  48 
 
female Luer taper (of the second connecting port)  0 
 
Luer thread (of the outer barrel)  52 
 
Luer thread (of the second connecting port) 54 
 
second gripping structure  56 
 
guiding ribs  58 
 
venting device  64 
 
radial bore  66 
 
air gap  68 
 
plunger  70 
 
actuation button  72 
 
tip element  74 
 
plunger rod  76 
 
tip barb  78 
 
barb receptacle  80 
 
sealing element  82 
 
distance distal tip plunger/distal tip cannula D
 
observing windows  83 
 
housing  84 
 
first housing element  86 
 
second housing element  88 
 
plunger through-hole  90 
 
guiding element  92 
 
guiding channel  94 
 
assembly channel  96 
 
plunger positioning mechanism  98 
 
distal end face (of the guiding channel)  102 
 
interference pin  104 
 
interference receptacle  106 
 
alignment pin  108 
 
alignment receptacle  110 
 
receptacle (for receiving flange element)  112 
 
plunger guide  114 
 
first drag mechanism  116 
 
resilient drag element  118 
 
drag rib  120 
 
plunger locking mechanism  122 
 
lever element  124 
 
hinge  126 
 
rotational axis  128 
 
foot elements  130 
 
locking rim  132 
 
stop device  134 
 
abutment surface (of the plunger)  136 
 
retention device  138 
 
first plunger stop mechanism  140 
 
second plunger stop mechanism  142 
 
first dosing position P 1 
 
second dosing position P 2 
 
dosing element  144 
 
first dosing surface  146 
 
second dosing surface  148 
 
distance first dosing surface/second dosing surface S
 
abutting surface (of the dosing element)  150 
 
recess  152 
 
plunger releasing mechanism  154 
 
retaining recess  158 
 
retaining element  158 
 
gripping structure  159 
 
marker system  160 
 
first marker element  168 
 
second marker element  164 
 
limiting mechanism  166 
 
first limiting element  168 
 
second limiting element  170 
 
second drag mechanism  172 
 
friction element  174 
 
actuation mechanism  176 
 
activation channel  178 
 
locking arrangement  180 
 
resilient locking dip  182 
 
locking element  184