Injection device and injection solution transfer system

Abstract

The present disclosure relates to injection devices, particularly microdose injection devices such as, for example, ophthalmic injection devices. An example device includes a solution container having a rotatable plunger, a first end configured to slidably receive the rotatable plunger, and a second end configured to dispense a solution contained within the solution container, a first stop member configured to prevent the rotatable plunger from slidably displacing to a second position while the rotatable plunger is in the first position and in the first orientation, and a second stop member configured to prevent the rotatable plunger from rotating in a first direction about a first axis while the rotatable plunger is in the first position and in the first orientation, such that slidable displacement of the rotatable plunger from the first position to the second position dispenses a quantity of the solution contained within the solution container.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 62 / 947,462, entitled "INJECTION DEVICE AND INJECTION SOLUTION TRANSFERRING SYSTEM," filed December 12, 2019, the contents of which are incorporated by reference in their entirety for all purposes.

[0002] The present disclosure relates to injection devices, in particular microdose injection devices, such as ophthalmic injection devices for use within the eye. Furthermore, the present disclosure relates to an injection solution transfer system for transferring an injection solution from a syringe to such an injection device. [Background technology]

[0003] Typically, an injection solution administered to a patient for a medical treatment is stored in a syringe having a container for receiving the injection solution and a plunger displaceable relative to the container to expel the injection solution from the container. If the medical treatment plan for the patient provides for the administration of a dose of the injection solution corresponding to the fill volume of the syringe, or if the dose of the injection solution is less important for the desired therapeutic effect, the injection solution may be administered directly from the syringe to the patient. However, if the medical treatment plan for the patient requires the administration of a dose of the injection solution different from the fill volume of the syringe and / or if a precise dose of the injection solution is required, the injection solution may be transferred from the syringe prior to administration to an injection device that is ultimately used to inject the desired dose of the injection solution into the patient's body. Summary of the Invention [Problem to be solved by the invention]

[0004] The present disclosure aims to provide an injection device that allows for accurate and reliable administration of small doses of injection solution to a patient, and further aims to provide an injection solution transfer system for transferring the injection solution from a syringe to such an injection device. [Means for solving the problem]

[0005] The injection device comprises an injection solution container. The injection solution container and the protective outer barrel can be made of any suitable material or combination of materials including plastic materials or glass. Suitable plastic materials include, for example, cycloolefin polymers or cycloolefin copolymers. An example of a glass material can be borosilicate glass. Preferably, the glass material does not include tungsten. In one embodiment, the injection solution container can be uncoated. Uncoated means that the injection solution container does not include any other material than the material from which the injection solution container is made. Alternatively, the injection solution container may include an inner coating. An inner coating refers to a coating on the inside of the injection solution container that contacts the injection solution. Examples of such inner coatings include silicone coatings or fluorocarbon films made from modified ethylene-tetrafluoroethylene copolymers. The injection solution container may be silicone-free or substantially silicone-free, or may include low levels of silicone as a lubricant. Preferably, the injection solution container is made from a sterile plastic material. Preferably, the injection solution container is made from a sterile plastic material. Preferably, the injection solution container does not include an inner coating. In one embodiment, the injection solution container is capable of filling USP789.

[0006] The injection solution container can be designed in the form of an inner injection solution container housed in a protective outer barrel. The injection solution container designed in the form of an inner injection solution container can be formed integrally with the protective outer barrel. In the region of its proximal end, the protective outer barrel can be provided with a flange element that can serve to connect the protective outer barrel and the inner injection solution container to the housing of the injection device. For example, the housing of the injection device can comprise a container of suitable shape and dimensions that receives the flange element and thus fastens the protective outer barrel and the inner injection solution container to the housing.

[0007] The distal end of the injection solution container of the injection device can 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 the Luer taper can be provided, for example, at a connection port of an adapter element of a filling adapter, which can be used to connect the injection device to a syringe containing an injection solution to be transferred from the syringe to the injection solution container of the injection device. By means of the Luer taper, a fluid-tight connection can be established in a simple manner between the distal end of the injection solution container of the injection device and the adapter element of the filling adapter. The outer barrel of the injection device can be provided, in the region of its distal end, with a Luer thread, which is adapted to interact with a complementary Luer thread provided at a second connection port of the adapter element of the filling adapter, in particular in the region of its outer periphery. As a result, a reliable connection between the outer barrel of the injection device and the adapter element of the filling adapter can also be achieved.

[0008] The injection device further comprises a plunger. The plunger can be made of polycarbonate. At least a part of the plunger is slidably received in the injection solution container. The plunger is displaceable relative to the injection solution container in a distal direction along its longitudinal axis in order to expel the injection solution contained therein from the injection solution container. At its proximal end, which can protrude proximally from the injection solution container, the plunger can support an actuation button which can be pressed by a user in order to displace the plunger relative to the injection solution container in a distal direction along the longitudinal axis of the plunger. At its distal end, the plunger can be provided with a tip element which can be attached to the plunger rod. The coupling between the plunger rod and the tip element can be effected, for example, by interaction of a tip barb provided at the distal end of the plunger rod with a barb receiver of the tip element. Furthermore, the tip element can be provided with a sealing element, which can be provided, for example, in the region of the outer circumferential surface of the tip element and which sealingly interacts with the inner circumferential surface of the injection solution container.

[0009] The injection device further comprises a first plunger stop mechanism adapted to stop displacement of the plunger relative to the injection solution container in a distal direction at a first dosing position. Additionally, the injection device comprises a second plunger stop mechanism configured to stop displacement of the plunger relative to the injection solution container in a distal direction from the first dosing position at a second dosing position. The first and second dosing positions of the plunger are selected such that the plunger is adapted to expel from the injection solution container a desired dose of injection solution contained therein when the plunger is displaced relative to the injection solution container between the first and second dosing positions.

[0010] After filling the injection solution container with the injection solution to be administered to the patient, a user of the injection device can expel excess injection solution from the injection solution container by displacing the plunger in a distal direction relative to the injection solution container until the plunger reaches a first dosing position. Once the first dosing position is reached, a first plunger stop mechanism stops further displacement of the plunger in the distal direction, thereby preventing the user from expelling too much injection solution from the injection solution container. Residual injection solution contained in the injection solution container can then be administered to the patient by further displacing the plunger in a distal direction until the plunger reaches a second dosing position. Once the second dosing position is reached, a second plunger stop mechanism stops further displacement of the plunger in the distal direction, thereby preventing too much injection solution from being administered to the patient.

[0011] The injection device allows accurate and reliable administration of minute doses of injection solution to a patient. Moreover, the injection device can be easily and comfortably handled by a user. The injection device is therefore particularly suitable for treating pediatric patients. In particular, the injection device can be designed in the form of an ophthalmic injection device for use in the eye.

[0012] In one embodiment, the injection device is loaded with a dosage volume (i.e., the volume of injection solution intended to be delivered to a patient) of about 1 μL to about 50 μL, preferably about 10 μL to about 20 μL of injection solution. In another embodiment, the injection device is loaded with a dosage volume of injection solution of 50 μL to 250 μL. In yet another embodiment, the injection device is loaded with a dosage volume of injection solution of 25 μL to 125 μL. In preferred embodiments, the injection device is loaded with a dosage volume of injection solution of 5 μL, 10 μL, 20 μL or 30 μL.

[0013] The injection device can be loaded with any injection solution, for example, an injectable drug. In one embodiment, the injection device is loaded with an injectable drug containing an active ingredient suitable for treating an ocular disease. Examples of such ocular diseases include retinopathy of prematurity, geographic atrophy, glaucoma, choroidal neovascularization, age-related macular degeneration (both wet and atrophic), macular edema secondary to retinal vein occlusion (RVO) (including both branch RVO (bRVO) and central RVO (cRVO)), choroidal neovascularization secondary to pathological myopia (PM), diabetic macular edema (DME), diabetic retinopathy, retinitis pigmentosa, Leber's congenital amaurosis, Vietti crystalline dystrophy, and proliferative retinopathies. In one embodiment, the drug comprises a small molecule drug. In one embodiment, the drug comprises a biologically active agent. The biologically active agent can be an antibody (or a fragment thereof), a non-antibody protein, a nucleic acid for gene therapy, or a cellular agent for cell therapy. In one embodiment, the agent comprises a VEGF inhibitor. Suitable VEGF inhibitors include ranibizumab (Lucentis TM ), bevacizumab (Avastin TM ), brolucizumab (Beovu®, also known as RTH258), aflibercept (Eylea TM , also known as VEGF-Trap Eye), conbercept (KH902 from Chengdu Kanghong Biotechnologies Co. Ltd., described as FP3 in WO 2005 / 121176, the contents of which are incorporated herein by reference), and the related glycoform KH906 or pazopanib (GlaxoSmithKline).

[0014] In a preferred embodiment, the injection device is loaded with 0.1 mg or 0.2 mg of ranibizumab in 20 μL of injection solution. In a most preferred embodiment, the injection device is loaded with 20 μl of ranibizumab (0.2 mg) and is used for the treatment of retinopathy of prematurity.

[0015] In a preferred embodiment of the injection device, the first plunger stop mechanism comprises a dosing element attached to the plunger and adapted to abut a first dosing surface provided on the housing element, whereas alternatively or additionally the second plunger stop mechanism may comprise a dosing element attached to the plunger and adapted to abut a second dosing surface provided on the housing element.

[0016] Preferably, the dosing element of the first and / or second plunger stop mechanism is integrally formed with the plunger. For example, the dosing element can be designed in the form of a rib that can protrude from the surface of the actuation button of the plunger in the direction of the inner solution container. Basically, it is conceivable that the injection device comprises a first dosing element associated with the first plunger stop mechanism and a second dosing element associated with the second plunger stop mechanism. However, preferably, the injection device comprises only one dosing element, which is attached to the plunger and is associated with both the first and the second plunger stop mechanism. The single dosing element can be adapted to abut first against the first dosing surface when the plunger reaches the first dosing position, during a movement of the plunger in the distal direction, and then against the second dosing surface when the plunger reaches the second dosing position, during a further movement of the plunger from the first dosing position in the distal direction.

[0017] The first and second dosing surfaces can be provided on different housing elements of the injection device. However, in a preferred embodiment of the injection device, the first and second dosing surfaces are both formed on the first housing element, i.e. on the same housing element of the injection device. The first and second dosing surfaces preferably extend substantially parallel to each other, and the second dosing surface can be arranged parallel and offset in the distal direction with respect to the first dosing surface. The distance between the first and second dosing surfaces in the distal direction can correspond to a desired movement distance of the plunger in the distal direction between the first and second dosing positions. Thus, by suitably arranging the first and second dosing surfaces, it is possible to set a desired plunger displacement between the first and second dosing positions and thus a desired injection solution dose to be expelled from the injection solution container when displacing the plunger from the first dosing position to the second dosing position. The first and second dosing surfaces can extend substantially parallel to the abutment surfaces of the dosing elements. For example, the abutment surface of the dosing element together with the first and second dosing surfaces may extend substantially perpendicular to the longitudinal axis of the plunger.

[0018] The first plunger stop mechanism is adapted to stop the displacement of the plunger at the first dosing position, but can be designed to provide a resistance force that can be overcome, for example, by increasing the actuation force acting on the plunger. However, in a particularly preferred embodiment of the injection device, the first plunger stop mechanism is adapted to provide a hard stop for the plunger, i.e. to prevent the plunger from being displaced distally from the first dosing position relative to the injection solution container without damaging the first plunger stop mechanism. In particular, when the first plunger stop mechanism is designed as a hard stop for the plunger, the injection device preferably further comprises a plunger release mechanism, which is adapted to bring the first plunger stop mechanism into a stopped state in order to release the plunger and thus to allow the displacement of the plunger relative to the injection solution container in a distal direction from the first dosing position, i.e. in the direction of the second dosing position.

[0019] The second plunger stop mechanism is also configured to stop the displacement of the plunger at the second dosing position, but can be designed to provide a resistance force that can be overcome, for example, by increasing the actuation force acting on the plunger. However, in a particularly preferred embodiment, the second plunger stop mechanism is adapted to provide a hard stop for the plunger, i.e. to prevent the plunger from displacing distally from the second dosing position relative to the injection solution container without damaging the second plunger stop mechanism. This allows the dose of injection solution to be administered to the patient to be set in a particularly accurate manner.

[0020] Preferably, the plunger release mechanism is adapted to allow movement of at least one of the dosing element and the first dosing surface to disengage the dosing element from the first dosing surface. The movement of the dosing element and / or the first dosing surface can be triggered manually by a user of the injection device. In a particularly preferred embodiment of the injection device, the user only needs to move the first dosing surface to disengage the dosing element from the first dosing surface. As a result, the user does not need to trigger the movement of the plunger to activate the plunger release mechanism. For example, to activate the plunger release mechanism, only the housing element supporting the first dosing surface needs to be moved, while the plunger can remain in its position, which simplifies the use of the injection device.

[0021] The plunger release mechanism may be adapted to allow a rotational movement of at least one of the dosing element and the first dosing surface to disengage the dosing element from the first dosing surface. For example, the plunger release mechanism may be actuable by a manually caused rotation of the plunger and / or the first dosing surface. In particular, the plunger release mechanism may be adapted to allow a rotational movement of a housing element supporting the first dosing surface to actuate the plunger release mechanism. An actuation of a rotational movement of the plunger and / or the first dosing surface, in particular only the first dosing surface, can be easily distinguished by the user from a pressing actuation of the plunger to move the plunger in a distal direction. As a result, the use of the injection device is further simplified.

[0022] In a preferred embodiment of the injection device, the first and second dosing surfaces are arranged offset from one another in the circumferential direction of the plunger, for example on different or the same housing elements. The plunger release mechanism can thus be adapted to displace the first and second dosing surfaces in the circumferential direction of the plunger when the plunger is displaced distally from the first dosing position relative to the injection solution container, in order to disengage the dosing element from the first dosing surface and at the same time align the second dosing surface with the dosing element, so that the dosing element abuts against the second dosing surface when the second dosing position is reached. Such a design of the plunger release mechanism allows a particularly simple and reliable handling of the injection device.

[0023] Preferably, the first and second dosing surfaces are formed on a first housing element which is rotatable relative to the plunger. If the first and second dosing surfaces are arranged offset from one another on the first housing element in the circumferential direction of the plunger, disengagement of the dosing element from the first dosing surface and simultaneous positioning of the second dosing surface in a position ready for engagement with the dosing element can be easily achieved by simply rotating the first housing element by an appropriate amount of rotation when the plunger reaches the second dosing position as it is displaced distally from the first dosing position.

[0024] The second dosing surface can 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, to allow the dosing element to be received in the recess. When the plunger is placed in the first dosing position and the dosing element abuts against the first dosing surface, the recess defined in the first dosing surface can be aligned with the dosing element via a rotational movement of the first housing element. As a result, the dosing element is disengaged from the first dosing surface and the plunger can be further displaced in the distal direction until the dosing element is received in the recess and the abutment surface formed on the dosing element abuts against the second dosing surface defined by the bottom surface of the recess. The depth of the recess, which defines the distance between the first and second dosing surfaces in the distal direction, can correspond to the desired movement distance of the plunger in the distal direction between the first and second dosing positions.

[0025] The first housing element supporting the first and second dosing surfaces, particularly in the region of the outer surface, can be provided with a gripping structure. For example, the gripping structure can be designed in the form of a gripping rib arrangement comprising individual gripping ribs extending substantially in a direction along the longitudinal axis of the plunger depending on the shape of the outer surface of the first housing element. The gripping structure simplifies the handling of the plunger release mechanism.

[0026] Preferably, the plunger release mechanism comprises a marker system adapted to indicate activation of the plunger release mechanism. The marker system may for example comprise a first marker element provided on a first housing element supporting the first and second dosing surfaces, for example in the area of ​​its outer surface. The marker system may further comprise a second marker element provided on a second housing element of the injection device, particularly in the area of ​​its outer surface. The first and second marker elements may be arranged on the first and second housing elements in positions such that when the plunger release mechanism is not activated, they are positioned offset from each other, for example in the circumferential direction of the plunger, but are positioned in alignment with each other when the plunger release mechanism is activated. The marker system provides the user with guidance information on how to activate the plunger release mechanism, thereby simplifying the handling of the injection device.

[0027] The injection device preferably further comprises an activation mechanism adapted to prevent activation of the plunger release mechanism unless the plunger is arranged in the first dosing position and adapted to allow activation of the plunger release mechanism when the plunger is arranged in the first dosing position. The activation mechanism may be adapted to prevent the dosing element and / or the first dosing surface from moving relative to each other unless the plunger is arranged in the first dosing position. In particular, the activation mechanism may be adapted to prevent rotation of the first housing element supporting the first and second dosing surfaces relative to the plunger supporting the dosing element unless the plunger is arranged in the first dosing position.

[0028] In a preferred embodiment of the injection device, the actuation mechanism comprises a guide channel, which is provided on the circumferential surface of the plunger extending along the longitudinal axis of the plunger, and which receives a guide element provided on the housing element in such a manner that the guide channel is displaced relative to the guide element when the plunger is displaced relative to the injection solution container. The interaction of the guide element with the opposing surface of the guide channel can prevent the plunger and the housing element from rotating relative to each other. If the actuation mechanism comprises a guide channel extending along the longitudinal axis of the plunger and a corresponding guide element, the actuation mechanism performs a double function, on the one hand allowing a guided displacement of the plunger in the direction of its longitudinal axis and at the same time preventing the first plunger stop mechanism from being unintentionally stopped when the plunger is not arranged in the first dosing position. The guide element can be provided on the first housing element, which also supports the first dosing surface and preferably the second dosing surface.

[0029] The actuation mechanism may further comprise an actuation channel branching off from the guide channel. For example, the actuation channel may extend in a circumferential direction of the plunger substantially perpendicular to the guide channel. The actuation channel is preferably adapted to receive the guide element when the plunger is placed in the first dosing position and the first housing element, which also supports the guide element and preferably the first and second dosing surfaces, is rotated relative to the plunger. With such a design of the actuation mechanism, the first dosing position of the plunger is defined by the position of the actuation channel along the longitudinal axis of the plunger.

[0030] The first and second dosing surfaces may be formed on a first housing element which is rotatable relative to the plunger. If the first and second dosing surfaces are arranged offset from one another on the first housing element in the circumferential direction of the plunger, disengagement of the dosing element from the first dosing surface and simultaneous positioning of the second dosing surface in a position ready for engagement with the dosing element can be easily achieved by simply rotating the first housing element by an appropriate amount of rotation when the plunger reaches the second dosing position as it is displaced distally from the first dosing position.

[0031] The second dosing surface can 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, to allow the dosing element to be received in the recess. When the plunger is placed in the first dosing position and the dosing element abuts against the first dosing surface, the recess formed in the first dosing surface can be aligned with the dosing element via a rotational movement of the first housing element. As a result, the dosing element is disengaged from the first dosing surface and the plunger can be further displaced in the distal direction until the dosing element is received in the recess and the abutment surface formed on the dosing element abuts against the second dosing surface defined by the bottom surface of the recess.

[0032] The plunger release mechanism may further comprise a locking arrangement adapted to lock the first dosing surface in place relative to the dosing element after the first dosing surface has moved relative to the dosing element to disengage from the dosing element. The locking arrangement therefore ensures that the plunger release mechanism can be used only once to stop the first plunger stop mechanism. As a result, reuse of the injection device is reliably prevented.

[0033] The locking arrangement may comprise an elastic locking clip, which is adapted to be elastically pushed out of the rest position by interaction with the locking element when the first dosing surface is moved relative to the dosing element to disengage from the dosing element. For example, the elastic locking clip may be provided on the second housing element, while the locking element may be provided on the first housing element supporting the first dosing surface and optionally also the second dosing surface. The elastic locking clip may thus be elastically deformed when the first housing element is rotated relative to the second housing element. The locking clip is preferably further adapted to deform back to its rest position after completion of the movement of the first dosing surface, and to interact with the locking element to lock the first dosing surface in place relative to the dosing element. In particular, the locking clip may interact with the locking element to prevent a reverse rotation of the first housing element relative to the second housing element and the plunger after the first housing element has been rotated once to disengage the first dosing surface from the dosing element and to align the second dosing surface with the dosing element.

[0034] The injection device may further comprise a limiting mechanism adapted to limit movement of the dosing element and / or both the first and second dosing surfaces to disengage the dosing element from the first dosing surface and to align 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 second dosing surfaces relative to each other in an excessive manner. Furthermore, the limiting mechanism provides haptic feedback to the user that the dosing element has been properly disengaged from the first dosing surface and aligned with the second dosing surface, i.e. the first plunger stop mechanism has been stopped.

[0035] The limiting mechanism may in particular comprise a first limiting element provided on a first housing element supporting the first and second dosing surfaces. Furthermore, the limiting mechanism may comprise a second limiting element provided on a second housing element, the second housing element being adapted to remain stationary when the first housing element moves, in particular rotates, in order to stop 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.

[0036] When the injection device is equipped with the above-mentioned actuation mechanism including an actuation channel and a guiding element formed in a first housing element that also supports the first and second dosing surfaces, movement of the first dosing surface relative to the dosing element attached to the plunger can also be limited by interaction between the guiding element and an end face of the actuation channel, which can act as an abutment surface for the guiding element when the first housing element, after rotation relative to the plunger, reaches a position where the dosing element is disengaged from the first dosing surface and aligned with the second dosing surface.

[0037] The injection device may further comprise a first drag mechanism, which is adapted to apply a holding force that holds the plunger in its current position relative to the injection solution container. The first drag mechanism thus prevents the plunger from being unintentionally displaced relative to the injection solution container, in other words, due to the presence of the first drag mechanism, active manual actuation, for example by applying a pressing force, is necessary to displace the plunger relative to the injection solution container. The first drag mechanism may comprise an elastic drag element, which may for example be provided on the second housing element. The elastic drag element may be adapted to apply an elastic holding force to the plunger. That is, the elastic drag element may be elastically urged from a rest position to a biased position by interaction with the plunger, and due to its elasticity, may apply an elastic reaction force to the plunger, which holds the plunger in its current position. The elastic drag element may in particular interact with a drag rib, which is provided on the outer circumferential surface of the plunger and extends substantially parallel to the longitudinal axis of the plunger.

[0038] Alternatively or additionally, the injection device may also comprise a second drag mechanism adapted to apply a retaining force that holds the first housing element in its current position, i.e. holds the first housing element in place relative to the second housing element. The second drag mechanism thus prevents unintentional displacement of the first housing element relative to the second housing element and thus unintentional stopping of the first plunger stop mechanism. The second drag mechanism may comprise a friction element that is provided on the first limiting element of the limiting mechanism and adapted to interact with a retaining element of the second housing element.

[0039] The injection device may further comprise a plunger positioning mechanism adapted to prevent the plunger from being displaced in a proximal direction from a proximal end position relative to the injection solution container. The plunger positioning mechanism may, for example, include a distal end face of a guide channel provided in a circumferential surface of the plunger. The proximal end position of the plunger may then be defined by interaction of the distal end face of the guide channel with a guide element received therein.

[0040] The injection device can be pre-filled with the compound via a pre-filled syringe (14), vial or other reservoir.

[0041] In one embodiment, the injection device (whether pre-filled or not) is provided in a sterile, sealed package. In one embodiment, the injection device is pre-filled with a suitable injection solution and terminally sterilized. Such a terminal sterilization step can include known techniques such as ethylene oxide sterilization or hydrogen peroxide sterilization.

[0042] Disclosed herein is an example solution dispensing device having a rotatable plunger and a solution container having a first end configured to slidably receive the rotatable plunger and a second end configured to dispense a solution contained within the solution container, the solution dispensing device configured to allow the rotatable plunger to be slidably displaced along a first axis while in a first orientation to be positioned at a first position relative to the solution container, and to allow the rotatable plunger to be slidably displaced along the first axis from the first position to a second position relative to the solution container while in a second orientation; The device comprises a solution container, the second position being closer to a second end of the solution container than the first position, and a quantity of solution contained in the solution container is dispensed by slidably displacing the rotatable plunger from the first position to the second position; a first stop member configured to prevent the rotatable plunger from being slidably displaced to the second position while the rotatable plunger is in the first position and in a first orientation; and a second stop member configured to prevent the rotatable plunger from rotating in a first direction about a first axis while the rotatable plunger is in the first position and in the first orientation.

[0043] Disclosed herein is an example method of dispensing a solution from a solution dispensing device having a rotatable plunger, a solution container, a first stop member, and a second stop member. The example method includes the steps of slidably inserting the rotatable plunger into a first end of the solution container, the second end of the solution container being configured to dispense a solution contained within the solution container, and slidably displacing the rotatable plunger along a first axis while the rotatable plunger is in a first orientation until the rotatable plunger is in a first position relative to the solution container, where the first stop member prevents the rotatable plunger from slidably displacing, relative to the solution container, to a second position closer to the second end of the solution container than the first position while the rotatable plunger is in the first position and in the first orientation, and the second stop member prevents the rotatable plunger from slidably displacing, relative to the solution container, to a second position closer to the second end of the solution container than the first position while the rotatable plunger is in the first position and in the first orientation. The method includes the steps of: preventing the rotatable plunger from rotating in a first direction about a first axis while the rotatable plunger is in a first position and in a first orientation; rotating the rotatable plunger in a second direction about the first axis until the rotatable plunger is in the first position and in a second orientation; and, while the rotatable plunger is in the second position, slidably displacing the rotatable plunger along the first axis until the rotatable plunger is in a second position relative to the solution container, wherein slidably displacing the rotatable plunger from the first position to the second position causes a quantity of solution contained within the solution container to be dispensed. [Brief description of the drawings]

[0044] [Figure 1] 1 shows an exploded view of an injection solution transfer system including a filling adapter and an injection device. [Diagram 2] FIG. 2 shows a three-dimensional view of the filling adapter and the injection device in the connected state. [Diagram 3] 1 shows a longitudinal cross-sectional view of a filling adapter connected to an injection device. [Figure 4] FIG. 2 shows a detailed three-dimensional view of the hollow sleeve of the filling adapter. [Diagram 5] FIG. 2 shows a detailed three-dimensional view of the hollow sleeve of the filling adapter. [Figure 6] FIG. 2 shows a detailed three-dimensional view of the adapter element of the filling adapter. [Figure 7] FIG. 2 shows a detailed three-dimensional view of the adapter element of the filling adapter. [Figure 8] 1 shows the arrangement of adapter elements in a hollow sleeve of a filling adapter. [Figure 9] 1 shows a three-dimensional longitudinal cut view of an adapter element and a cannula of a filling adapter. [Figure 10] 1 shows a longitudinal section through an adapter element and a cannula of a filling adapter. [Figure 11] FIG. 2 shows a detailed view of the injection solution container of the injection device. [Figure 12] FIG. 2 shows a detailed view of the plunger of the injection device. [Figure 13] A detailed view of the tip element of the plunger is shown. [Figure 14] 1 illustrates 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. [Figure 15] 13 shows the interaction of the guide ribs of the hollow sleeve with the injection solution container of the injection device. [Figure 16] FIG. 2 shows a detailed three-dimensional view of a first housing element of the injection device. [Figure 17] FIG. 2 shows a detailed three-dimensional view of a first housing element of the injection device. [Figure 18] FIG. 2 shows a detailed three-dimensional view of a first housing element of the injection device. [Figure 19] Figures 19a and 19b show the interaction of the plunger with the first housing element. [Figure 20] FIG. 2 shows a detailed three-dimensional view of the second housing element of the injection device. [Figure 21] FIG. 2 shows a detailed three-dimensional view of the second housing element of the injection device. [Figure 22] 1 shows the assembly of the second housing element. [Figure 23] 4 shows the attachment of an injection solution container to the second housing element. [Figure 24]1 illustrates the interaction between a first housing element and a second housing element. [Diagram 25] 1 illustrates the interaction between a first housing element and a second housing element. [Figure 26] 1 illustrates the interaction of the plunger with the second housing element. [Figure 27] FIG. 13 shows a detailed three-dimensional view of a lever element of a plunger locking mechanism that prevents the plunger of an injection device from moving distally from the filling position when the injection device is connected to a filling adapter. [Figure 28] FIG. 13 shows a detailed three-dimensional view of a lever element of a plunger locking mechanism that prevents the plunger of an injection device from moving distally from the filling position when the injection device is connected to a filling adapter. [Figure 29] 1 shows the lever element of the plunger locking mechanism in the active position. [Diagram 30] 1 shows the lever element of the plunger locking mechanism in the inactive position. [Diagram 31] 1 shows an injection solution transfer system with the filling adapter connected to an injection device, a portion of the second housing element removed, and the lever element of the plunger locking mechanism in its active position. [Diagram 32] 13 shows the assembly of the lever element of the plunger locking mechanism in the second housing element. [Diagram 33] 33a-d show the use of the injection solution transfer system when filling an injection device with injection solution from a syringe. [Diagram 34] Figures 34a-d show the use of the injection device when administering an injection solution to a patient. [Figure 35a] FIG. 35a shows an exploded view of an injection device according to various examples. [Figure 35b] FIG. 35b shows an exploded view of an injection device according to various examples. [Figure 35c] FIG. 35c shows an exploded view of an injection device according to various examples. [Diagram 36]36a-c show the use of an injection device according to various examples. [Figure 37a] FIG. 37a shows a flow diagram of a process for using a solution dispensing device, according to various examples. [Figure 37b] FIG. 37b shows a flow diagram of a process for using a solution dispensing device, according to various examples. [Figure 38a] 38a-o and 38q-s show additional views of an injection device and its components, according to various examples. [Figure 38b] FIG. 38b shows a further view of an injection device and its components, according to various examples. [Figure 38c] FIG. 38c shows a further view of an injection device and its components, according to various examples. [Fig. 38d] FIG. 38d shows a further view of an injection device and its components, according to various examples. [Figure 38e] FIG. 38e shows a further view of an injection device and its components, according to various examples. [Fig. 38f] FIG. 38f shows a further view of an injection device and its components, according to various examples. [Figure 38g] FIG. 38g shows a further view of an injection device and its components, according to various examples. [Fig. 38h] FIG. 38h shows a further view of an injection device and its components, according to various examples. [Figure 38i] FIG. 38i shows a further view of an injection device and its components, according to various examples. [Figure 38j] FIG. 38j shows a further view of an injection device and its components, according to various examples. [Figure 38k] FIG. 38k shows a further view of an injection device and its components, according to various examples. [Figure 38l] FIG. 38l shows a further view of an injection device and its components, according to various examples. [Figure 38m]FIG. 38m shows a further view of an injection device and its components, according to various examples. [Figure 38n] FIG. 38n shows a further view of an injection device and its components, according to various examples. [Figure 38o] FIG. 38o shows a further view of an injection device and its components, according to various examples. [Fig. 38q] FIG. 38q shows a further view of an injection device and its components, according to various examples. [Figure 38r] FIG. 38r shows a further view of an injection device and its components, according to various examples. [Figure 38s] FIG. 38s shows a further view of an injection device and its components, according to various examples. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0045] 1 and 2 show an injection solution transfer system 100 comprising 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 in order to fill the injection device 10 with the injection solution from the syringe 14 as shown in Figures 33a to 33d and as will be further described below. The syringe 14 is designed in the form of a pre-filled syringe 14 containing an injection solution for use in the eye.

[0046] The filling adapter 12 comprises a hollow sleeve 16, which is shown in more detail in Figures 4 and 5. The hollow sleeve 16 is made from a pigmented plastic material, for example polycarbonate / acrylonitrile butadiene styrene (PC-ABS), and is provided with an internal lumen dimensioned to allow insertion of at least a distal portion of a syringe 14 at one end and at least a distal portion of an injection device 10 at an opposite end. In the exemplary embodiment of the 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.

[0047] The filling adapter 12 further comprises an adapter element 18, which is received within the hollow sleeve 16 and includes a first connection port 20 and a second connection port 22. The adapter element 18 may be made from polycarbonate, for example, and is shown in more detail in Figures 6-10. As shown particularly in Figure 8, the adapter element 18 is provided with two retention shoulders 23 projecting in opposite directions from an outer circumferential surface of the adapter element 18. Each retention shoulder 23 interacts with a pair of complementary crush ribs 24 projecting from an inner circumferential surface of the hollow sleeve 16 to secure the adapter element 18 in place within the hollow sleeve 16. The retention shoulders 23 and the complementary crush ribs 24 form an interference fit to securely secure the adapter element 18 in place within the hollow sleeve 16.

[0048] When the filling adapter 12 is connected to the syringe 14 as shown in Figures 33a-33c, the first connection port 20 of the adapter element 18 is adapted to be connected to the syringe 14, i.e. to the distal end of the syringe 14. As can be seen particularly from Figure 10, the first connection port 20 of the adapter element 18 forms a female Luer taper 25 adapted to interact with a male Luer taper provided at the distal end of the syringe 14 to establish a fluid-tight connection between the syringe 14 and the adapter element 18. The second connection port 22 of the adapter element 18 is adapted to be connected to the injection device 10.

[0049] The adapter element 18 is provided with a through opening 26 extending through the adapter element 18 in a direction substantially parallel to the longitudinal axis L1 of the filling adapter 12 (see in particular FIG. 10). A cannula 27 protrudes from the second connection 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. However, the hollow sleeve 16 of the filling adapter 12 extends beyond the distal tip of the cannula 27. As a result, the user is protected from the cannula 27 during handling of the filling adapter 12.

[0050] 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 connection port 20 of the adapter element 18 and the injection device 10 is connected to the second connection port 22 of the adapter element 18, as shown in FIG. 33a, the injection solution contained in the syringe 14 can be transferred into the injection device 10 by manually pressing the plunger 28 of the syringe 14, as shown in FIGS. 33b and 33c, so as to be released from the distal end of the syringe 14 into the through opening 26 provided in the adapter element 18 and further into the injection solution container 30 of the injection device 10 via the cannula 27.

[0051] As is particularly evident from figures 4 and 5, the hollow sleeve 16 of the filling adapter 12, in the region of its first end facing the syringe 14 when the syringe 14 engages with the first connection port 20 of the adapter element 18, is provided with at least one elastic clip 32 adapted to engage with a collar 34 of the syringe 14 when the syringe 14 engages with the first connection port 20 of the adapter element 18 (see figures 33a and 33b). In the embodiment of the hollow sleeve 16 shown in the drawings, the hollow sleeve 16 is provided with two elastic clips 32. Each elastic clip 32 comprises an arm 36 which extends in a recess 38 provided in the hollow sleeve 16 substantially parallel to the longitudinal axis L1 of the filling adapter 12 in the direction of the first end of the hollow sleeve 16. A latch nose 40 projects from the inner surface of the arm 36 in the region of its free end.

[0052] When the syringe 14 engages with the first connection port 20, the elastic clip 32 is bent outward due to interaction with the collar 34 of the syringe 14. However, as soon as the syringe 14 reaches 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 connection port 20 of the adapter element 18 and the syringe 14 is in the position shown in Fig. 33b with respect to the hollow sleeve 16, the elastic clip 32 resumes its original position substantially parallel to the longitudinal axis L1 of the filling adapter 12, so that the latch nose 40 engages with the end face of the collar 34 of the syringe 14. As a result, the syringe 14 is rigidly connected to the hollow sleeve 16.

[0053] The outer circumferential surface of the hollow sleeve 16 is provided in the region of its first end with two first gripping structures 42, each of which is designed in the form of a hump arrangement. The first gripping structures simplify the handling of the filling adapter 12 during the connection of the syringe 14 to the filling adapter 12. Furthermore, the hollow sleeve 16 has an outer diameter in the region of its first end and in the region of its second end, which faces the injection device 10 when the injection device 10 engages with the second connection port 22 of the adapter element 18, that is larger than the outer diameter of the hollow sleeve 16 in the intermediate section located between the first and second ends. Such a design of the hollow sleeve 16 further simplifies the gripping and therefore the handling of the filling adapter 12.

[0054] As shown in FIG. 11, the injection solution container 30 of the injection device 10 is designed in the form of an inner injection solution container 30 housed in a protective outer barrel 44. The inner injection solution container 30 and the protective outer barrel 44 are integrally formed with each other and 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. At the distal end of the injection solution container 30, a male luer taper 48 is provided, which interacts with a female luer taper 50 provided at the second connection 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. The luer tapers 48, 50 allow a fluid-tight connection to be established between the distal end of the injection solution container 30 and the adapter element 18 of the filling adapter 12.

[0055] As becomes more apparent from Fig. 11, the outer barrel 44 of the injection device 10 is provided in the region of its distal end with a Luer thread 52. When the filling adapter 12 is connected to the injection device 10 as shown in Figs. 2 and 3, the Luer thread 52 interacts with a complementary Luer thread 54 provided on the outer periphery of the second connection port 22 of the adapter element 18 (see Figs. 6, 8 to 10). As a result, a secure connection between the outer barrel 44 of the injection device 10 and the adapter element 18 of the filling adapter 12 can also be achieved.

[0056] In order to simplify the handling of the filling adapter 12 during engagement of the injection device 10 with the second connection port 22 of the adapter element 18, the hollow sleeve 16 is provided on its outer circumferential surface in the region of the second end facing the injection device 10 when the injection device 10 is engaged with the second connection port 22 of the adapter element 18 with a second gripping structure 56. The second gripping structure 56 is designed in the form of two gripping rib arrangements, the individual gripping ribs extending substantially parallel to the longitudinal axis L1 of the filling adapter 12.

[0057] Furthermore, as shown in Fig. 15, the hollow sleeve 16 is provided with a longitudinal guiding rib 58, which protrudes from the inner circumferential surface of the hollow sleeve 16 and extends substantially parallel to the longitudinal axis L1 of the filling adapter 12. The guiding rib 58 serves to guide the injection device 10 into engagement with the second connection port 22. The guiding function of the guiding rib 58 prevents the cannula 27 from coming into contact with the injection solution container 30 of the injection device 10 when connecting the filling adapter 12 to the injection device 10. The hollow sleeve 16 and the longitudinal guiding rib 58 are designed, i.e. shaped and dimensioned, such that a sliding fit occurs between the guiding rib 58 and the outer surface of the outer barrel 54 of the injection device 10.

[0058] 9 and 10, the through opening 26 extending through the adapter element 18 includes an inlet section 26a arranged adjacent to the first connection port 20. During use of the filling adapter 12, the injection solution discharged from the syringe 14 thereby flows into the through opening 26 via said inlet section 26a, said inlet section 26a having a cross-sectional flow area that decreases in the direction of flow of the injection solution discharged from the syringe 14. Furthermore, the through opening 26 includes an intermediate section 26b, which is arranged downstream of the inlet section 26a in the direction of flow of the injection solution discharged from the syringe 14 during use of the filling adapter 12. The intermediate section 26b of the through opening 26 has a substantially constant cross-sectional flow area that substantially corresponds to the minimum cross-sectional flow area of ​​the inlet section 26a adjacent to the intermediate section 26b. Finally, the through opening 26 includes a receiving section 26c that is located downstream of the intermediate section 26b, i.e., adjacent to the second connection port 22, in the direction of flow of the injection solution expelled from the syringe 14 during use of the filling adapter 12. The receiving section 26c has a larger cross-sectional flow area than the cross-sectional flow area of ​​the intermediate section 26b.

[0059] As will be further apparent from Figures 9 and 10, the cannula 27 extends into at least a portion of the intermediate section 26b of the through opening 26, whereby the intermediate section 26b of the through opening 26 or a portion thereof forms a cannula receiving bore of the adapter element 18, in which the proximal end of the cannula 27 is fixed. The cannula 27 is received in the cannula receiving bore by an interference sliding fit. In addition, the cannula 27 is provided with a beveled end. This design of the cannula 27 and the cannula receiving bore minimizes the generation of wear particles when the cannula 27 is attached to the cannula receiving bore. The final bond between the adapter element 18 and the cannula 27 is performed by a UV-curable adhesive. The cannula 27 extends from the intermediate section 26b of the through opening 26 through the receiving section 26c of the through opening 26 and the second connection port 22, so as to protrude from the second connection port 22. The receiving section 26c of the through opening 26, the second connection 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).

[0060] As shown in particular in FIG. 8 , the adapter element 18 is provided with two retaining shoulders 60 which protrude in opposite directions from the outer circumferential surface of the adapter element 18 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.

[0061] When the filling adapter 12 is connected to the injection device 10, the cannula 27 extends into the injection solution container 30 of the injection device 10, i.e. the distal tip of the cannula 27 is located inside the injection solution container 30 at a distance from the distal end of the injection solution container 30 (see in particular FIG. 3 ). As a result, when transferring the injection solution from the syringe 14 to the injection device 10, the injection solution leaving the syringe 14 via the cannula 27 is supplied to the injection solution container 30 of the injection device 10 not in the region of the distal end of the injection solution container 30 but at a position inside the injection solution container 30 at a distance from the distal end of the injection solution container 30.

[0062] As shown in Figures 33a-c, simply holding the filling adapter 12 and the injection device 10 in an upright position, with the longitudinal axis L1 of the filling adapter 12 and the longitudinal axis L2 of the injection device 10 oriented substantially vertically and the distal end of the injection device 10 facing downward, can cause a gravity-driven flow of the injection solution from the distal tip of the cannula 27 downward in the direction of the distal end of the injection solution container 30 and further in the direction of the adapter element 18. The portion of the injection solution that is discharged from the distal tip of the cannula 27 and flows in a gravity-driven manner back towards the adapter element 18 is received in the receiving section 26c of the opening 26 provided in the adapter element 18. Any air bubbles that are entrapped within the injection solution and are therefore transferred along with the liquid phase of the injection solution from the syringe 14 to the injection solution container 30 are carried along with this gravity-driven flow and are forced by the higher density ratio of the liquid phase of the injection solution toward the distal end of the injection solution container 30 and further toward the adapter element 18.

[0063] 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. into the injection solution container 30 of the injection device 10, via the through opening 26 and the cannula 27 into the surrounding environment. The venting device thus allows trapped gas bubbles, in particular air bubbles, which are carried by the above-mentioned gravity-driven flow of the injection solution back to the adapter element 18 from the distal tip of the cannula 27, into the surrounding environment. The filling adapter 12 thus allows a gas-free filling of the injection device 10 with the injection solution. As a result, manual venting of trapped gas from the syringe 14 before connecting it to the filling adapter 12 can be dispensed with. Furthermore, an accurate and reliable preparation of the desired dose of injection solution in the injection device 10 is possible.

[0064] The venting device 64 comprises two radial bores 66 which connect the through openings 26 extending through the adapter element 18 to the surrounding environment. In particular, the radial bores 66 connect the receiving section 26c of the through openings 26 to the outer circumferential surface of the adapter element 18 and therefore to the surrounding environment. In the embodiment of the filling adapter 18 shown in the drawings, the radial bores 66 of the venting device 64 extend coaxially from the outer circumferential surface of the adapter element 18 to the receiving section 26c of the through openings 26 so as to connect the receiving section 26c of the through openings 26 to the surrounding environment. To ensure that the air bubbles trapped in the injection solution can be vented to the surrounding environment as required, without discharging a substantial amount of the liquid phase of the injection solution to the surrounding environment, the flow cross-sectional area, i.e. the diameter, of the radial bores 66 is selected depending on the physical properties of the injection solution to be transferred from the syringe 14 to the injection device 10, in particular the density ratio, the viscosity and the surface tension.

[0065] To ensure proper functioning of the venting device 64, the retaining shoulder 23 protrudes from the outer circumferential surface of the adapter element 18 in the region of the inlet section 26a and the intermediate section 26b of the through opening 26 extending through the adapter element 18. Such a configuration ensures that a gap 68 exists between the outer circumferential surface of the adapter element 18 and the inner circumferential surface of the hollow sleeve 16 in the region of the receiving section 26c of the through opening 26, thereby allowing unhindered evacuation of gas from the receiving section 26c through the radial bore 66 of the venting device 64.

[0066] The injection device 10 of the injection solution transfer system 100 further comprises a plunger 70, which is shown in more detail in FIG. 12. In the embodiment of the 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 in the injection solution container 30 of the injection device 10. The plunger 70 is displaceable relative to the injection solution container 30 in a distal direction along the longitudinal axis of the plunger 70 in order to expel the injection solution contained therein from the injection solution container 30 of the injection device 10. At its proximal end protruding proximally from the injection solution container 30, the plunger 70 supports an actuation button 72 which can be depressed by a user in order to displace the plunger 70 relative to the injection solution container 30 in a distal direction along the longitudinal axis of the plunger 70.

[0067] 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). The connection between the plunger rod 76 and the tip element 74 is achieved by the interaction of a tip barb 78 provided at the distal end of the plunger rod 76 with a barb receiver 80 of the tip element 74. Furthermore, the tip element 74 is provided with a sealing element 82 which is provided in the region of the outer circumferential surface of the tip element 74 and which sealingly interacts with the inner circumferential surface of the injection solution container 30.

[0068] The plunger 70 of the injection device 10 can be placed in the filling position as shown in Figs. 33a to 33d. When the plunger 70 is placed in the filling position and the injection device 10 engages with the second connection port 22 of the adapter element 18 of the filling adapter 12, the distal tip of the plunger 70, i.e., the distal end face of the tip element 74 provided at the distal tip of the plunger 70, is placed 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 can be designed to set the distance D between the distal tip of the plunger 70 and the distal tip of the cannula 27 to about 1.5 mm ± 0.5 mm. By placing 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 container 30 through the cannula 27 is reliably flowed in the direction of the ventilation device 64. As a result, it is possible to ensure that the injection solution container 30 is filled with the injection solution without air.

[0069] Finally, the hollow sleeve 16 is provided with two observation windows 83 for observing the filling of the injection solution from the syringe 14 into the injection device 10. The observation windows 83 allow an unobstructed view of the interior of the injection device 10 and the distal tip of the cannula 27.

[0070] The plunger 70 is displaceably received in a housing 84 of the injection device 10, which comprises a first housing element 86, shown in more detail in Figs. 16-19, and a second housing element 88, shown in more detail in Figs. 20-23. Both the first and second housing elements 86, 88 are made of polycarbonate / acrylonitrile butadiene styrene but have different colors. The first housing element 86 is provided with a plunger through hole 90, which receives the plunger rod 76 such that the plunger 70 is displaceable relative to the first housing element 86 in a direction along its longitudinal axis. A guide element 92 is provided in the first housing element 86 so as to protrude into the plunger through hole 90. When the plunger 70, i.e., plunger rod 76, is received in the plunger through hole 90 of the first housing element 86, each guide element 92 engages with a guide channel 94 that is provided on the circumferential surface of the plunger 70, i.e., the plunger rod 76, and extends along the longitudinal axis of the plunger 70 (see particularly Figures 19a and 19b).

[0071] To assemble the plunger 70 into the first housing element 86, the plunger rod 76 is provided on its outer circumferential surface with an assembly channel 96 which branches off from a distal region of the guide channel 94 and extends circumferentially about the plunger rod 76 substantially perpendicular to the guide channel 94. When assembling the plunger 70 into the first housing element 86, the guide element 92 engages with the assembly channel 96. The plunger 70 is then rotated until the guide element 92 is received in the guide channel 94 in a guided manner (see Figures 19a and 19b).

[0072] To simplify the handling of the injection solution transfer system 100, the injection device 10 is delivered with the plunger 70 disposed in its filling position, which corresponds to the proximal end position of the plunger 70. The plunger positioning mechanism 98 prevents the plunger 70 from being able to move further in a proximal direction relative to the injection solution container 30 than its proximal end position, i.e., its filling position. However, the plunger positioning mechanism 98 allows the plunger 70 to move distally from its filling position relative to the injection solution container 30. In particular, the plunger positioning mechanism 98 is defined by a distal end face 102 of a guide channel 94 provided in the circumferential surface of the plunger rod 78 and a guide element 92 provided in the first housing element 86. When the plunger 70 is disposed in its proximal end position, which corresponds to its filling position, the guide element 92 abuts against the distal end face 102 of the guide channel 94. Thus, interaction of distal end face 102 of guide channel 94 with guide element 92 prevents further movement of plunger 70 in the proximal direction, thereby defining the proximal end position of plunger 70, i.e., the fill position.

[0073] The second housing element 88 includes two identical parts (see Figs. 20 and 21), each part having an interference pin 104 and an interference receiver 106. The two housing parts of the second housing element 88 are assembled by engaging the interference pin 104 with the respective interference receiver 106 as shown in Fig. 22. To align the parts of the second housing element 88 with each other during assembly, alignment pins 108 are provided, which are received in respective alignment receivers 110 when connecting the parts of the second housing element 88. The injection solution container 30 and the protective outer barrel 44 are connected to the second housing element 88 via a flange element 46 extending from the proximal end of the outer barrel 44. In particular, the flange element 46 is received in a receiver 112 of suitable shape and size of the second housing element 88 (see Fig. 23).

[0074] As shown in particular in Fig. 26, the second housing element 88 is provided with a plunger guide 114, which restrains the plunger rod 76 so as to prevent the plunger 70 from rotating relative to the second housing element 88. A first drag mechanism 116 is adapted to apply a retention force that holds the plunger 70 in position relative to the second housing element 88. The first drag mechanism 116 thus prevents unintentional displacement of the plunger 70 relative to the injection solution container 30, which requires active manual actuation of the plunger 70, for example by applying a pressing force to the actuation button 72, in order to displace the plunger 70 relative to the injection solution container 30. The first drag mechanism 116 comprises a resilient drag element 118 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 from a rest position to a biased position by interaction with the plunger 70, and, due to its resiliency, exerts a resilient reaction force on the plunger 70 that holds the plunger 70 in place. Specifically, the resilient drag element 118 interacts with a drag rib 120 that is disposed on the outer periphery of the plunger rod 76 and extends substantially parallel to the longitudinal axis of the plunger 70.

[0075] 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, to prevent the plunger 70 of the injection device 10 from moving in a distal direction from its filling position, i.e. in the direction of the distal tip of the cannula 27, relative to the injection solution container 30, when the injection device 10 is connected to the filling adapter 12. The plunger locking mechanism 122 serves to prevent inadvertent contact between the plunger 70, i.e. the distal tip of the plunger 70, and the distal tip of the cannula 27. The function of the plunger locking mechanism 122 will now be explained in more detail with reference to Figures 27 to 32.

[0076] In particular, the plunger lock 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 shown in Figs. 29 and 31 and an inactive position shown in Fig. 30. When arranged in its active position, the lever element 124 interacts with the plunger 70 and the hollow sleeve 16 of the filling adapter 12 to prevent the plunger 70 from moving distally from its filling position when the injection device 10 is connected to the filling adapter 12. Conversely, when arranged in its inactive position, the lever element 124 allows the plunger 70 to move distally from its filling position 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 that rotatably mounts the lever element 124 to a pivot point 128 provided in the second housing element 88 .

[0077] The lever element 124 further comprises a pair of foot elements 130 which extend substantially parallel to each other and which contact 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 contact 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 of the locking rim 132 of the hollow sleeve 16 with the foot elements 130, the lever element 124 is pushed proximally, substantially parallel to the longitudinal axis of the plunger 70, into contact with the plunger 70 and is thus held in its active position shown in Figs. 29 and 31.

[0078] The lever element 124 comprises a stop device 134 comprising two tabs extending from a proximal end face of the lever element 124. Furthermore, the proximal portion of the plunger 70 extends further in a direction substantially perpendicular to the longitudinal axis of the plunger 70 than the distal portion of the plunger 70. As a result, a shoulder is formed in the transition region between the distal and proximal portions of the plunger 70, which defines an abutment surface 136. In particular, the abutment surface 136 is defined by an outer portion of the distal end face of the proximal plunger portion that protrudes from the outer circumferential surface of the distal plunger portion. When the lever element 124 is disposed in its active position 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, while at the same time preventing the plunger 70 from moving distally from its loading position.

[0079] The plunger locking mechanism 122 also comprises a retaining device 138, which interacts with the foot element 130 of the lever element 124 in order to prevent the foot element 130 from disengaging from the locking rim 132 of the filling adapter 12 when the lever element 124 is maintained in its active position by the interaction of the locking rim 132 with the foot element 130 (see Figs. 20 and 32). In particular, the retaining device 138 prevents the foot element 130 from sliding around the locking rim 132 of the hollow sleeve 16 and thereby disengaging from the filling adapter 12 when the lever element 124 is pressed into engagement with the plunger 70. The retaining device is provided in the second housing element 88 and is designed in the form of a retaining rib, which prevents the foot element 130 of the lever element 124 from deforming away from the plunger 70 in a direction substantially perpendicular to the longitudinal axis of the plunger 70.

[0080] As described above and as shown in Figures 33a-33c, after the transfer of the injection solution from the syringe 14 to the injection solution container 30 of the injection device 10 is completed with the plunger 70 placed in the filling position, the filling adapter 12 and the syringe 14 are removed from the injection device 10 by disengaging the male luer taper 48 on the distal end of the injection solution container 30 from the female luer taper 50 on the second connection port 22 of the adapter element 18 and by disengaging the luer thread 52 on the distal end of the outer barrel 44 from the complementary luer thread 54 on the second connection port 22 (see Figure 33d).

[0081] As soon as the filling adapter 12 is removed from the injection device 10, the locking rim 132 of the filling adapter 12, i.e. the hollow sleeve 16, is no longer in contact with the foot element 130 of the lever element 124. Thus, when a pressing force is applied to the plunger 70 in order to displace it distally in the injection solution container 30 of the injection device 10, the lever element 124 is displaced to the inactive position shown in FIG. 30. In particular, the lever element 124 rotates about its axis of rotation 128 from its active position to its inactive position, thereby moving out of the way of the plunger 70. As a result, the displacement of the plunger 70 is no longer impeded. As a result, a needle (not shown in the drawings) can be attached to the injection device 10, for example by means of a luer thread 52 provided at the distal end of the outer barrel 44, and the injection device 10 can be operated as described further below.

[0082] In order to administer to a patient an exact dose of the injection solution contained in the injection solution container 30, in particular an exact microdose of, for example, 10 μl, in a first step excess injection solution must be expelled from the injection solution container 30 by displacing the plunger 70 distally relative to the injection solution container 30 as shown in Figure 34a. The desired dose of injection solution can then be injected into the patient.

[0083] Thus, the injection device 10 comprises a first plunger stop mechanism 140 adapted to stop the displacement of the plunger 70 in the distal direction relative to the injection solution container 30 in the first dosing position P1 (see FIG. 34). Furthermore, the injection device 10 comprises a second plunger stop mechanism 142 adapted to stop the displacement of the plunger 70 in the distal direction from the first dosing position P1 relative to the injection solution container 30 in the second dosing position P2 (see FIG. 34d). The first and second dosing positions P1, P2 of the plunger 70 are selected such that, when the plunger 70 is displaced relative to the injection solution container 30 between the first dosing position P1 and the second dosing position P2, it is adapted to expel from the injection solution container 30 a desired dose of the injection solution contained therein.

[0084] This allows a user, during use of the injection device 10, to expel excess injection solution from the injection solution container 30 by displacing the plunger 70 in a distal direction relative to the injection solution container 30 until the plunger 70 reaches a first dosing position P1. Once the first dosing position P1 is reached, the first plunger stop mechanism 140 stops the plunger 70 from further displacing in a distal direction. As a result, the user is prevented from expelling too much injection solution from the injection solution container. Residual injection solution contained in the injection solution container can then be administered to the patient by further displacing the plunger 70 in a distal direction until the plunger 70 reaches a second dosing position P2. Once the second dosing position P2 is reached, the second plunger stop mechanism 142 stops the plunger 70 from further displacing in a distal direction, thereby preventing too much injection solution from being administered to the patient.

[0085] 12, 16 and 18, the first plunger stop mechanism 140 comprises a dosing element 144, which is attached to the plunger 70 and adapted to abut against a first dosing surface 146 provided on the first housing element 86. The dosing element 144 also forms part of the second plunger stop mechanism 142 and, as part of the second plunger stop mechanism 142, is adapted to abut against a second dosing surface 148 also provided on the first housing element 86. The dosing element 144 is integrally formed with the plunger 70 and is designed in the form of a rib protruding from the underside of the actuation button 72 in the direction of the inner solution container 30.

[0086] The first and second dosing surfaces 146, 148 extend substantially parallel to each other and to an abutment surface 150 of the dosing element 144 that is substantially perpendicular to the longitudinal axis of the plunger 70, the second dosing surface 148 being arranged offset and parallel to the first dosing surface 146 in the distal direction. The distance S between the first dosing surface 146 and the second dosing surface 148 in the distal direction corresponds to the desired movement distance of the plunger 70 in the distal direction between the first dosing position P1 and the second dosing position P2 (see in particular FIG. 18). The distance S between the first dosing surface 146 and the second dosing surface 148 in the distal direction thus sets the desired injection container dose to be expelled from the injection solution container 30 when the plunger 70 is displaced from the first dosing position P1 to the second dosing position P2.

[0087] Furthermore, the first and second dosing surfaces 146, 148 are offset from one another in the 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 in the first housing element 86.

[0088] When the plunger 70 moves distally from its filling position shown in FIG. 34a during use of the injection device 10, the abutment surface 150 of the dosing element 144 abuts against the first dosing surface 146 when the plunger 70 reaches the first dosing position P1 as shown in FIG. 34b. Interaction with the first dosing surface 146 of the dosing element 144 prevents the plunger from being displaced further in the distal direction. The first plunger stop mechanism 140 thereby provides a hard stop for the plunger 70 at the first dosing position P1. Thus, the injection device 10 further comprises a plunger release mechanism 154, which is configured to bring the first plunger stop mechanism 140 into a stopped state in order to release the plunger 70 and thus to allow the plunger 70 to be displaced relative to the injection solution container 30 in the distal direction from the first dosing position P1, i.e. in the direction of the second metering position P2.

[0089] The plunger release mechanism 154 is adapted to allow the first dosing surface 146 to move 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 particular, the plunger release mechanism 154 is adapted to allow the first dosing surface 146 to move rotationally 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 allow the first dosing surface 146 to move rotationally relative to the dosing element 144, the first housing element 86 supporting the first and second dosing surfaces 146, 148 is designed to be manually rotatable relative to the second housing element 88 (see FIG. 34c). Because the plunger 70 is prevented from rotating relative to the second housing element 88 by the plunger guide 114, rotation of the first housing element 86 relative to the second housing element 88 necessarily causes the first housing element 86 to rotate relative to the plunger 70.

[0090] 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 Figures 17, 18 and 24), which receives a retaining element 158 ​​formed on the second housing element 88 (see Figure 20). Furthermore, in order to simplify the handling of the plunger release mechanism 154, a gripping structure 159 is provided in the region of the outer surface of the first housing element 86. The gripping structure 159 is designed in the form of a gripping rib arrangement, with the individual gripping ribs extending substantially in a direction along the longitudinal axis of the plunger 70.

[0091] The amount of rotation of the first housing element 86 relative to the second housing element 88, and therefore relative to the plunger 70, is set such that a recess 152 formed in the first dosing surface 146 is aligned with a dosing element 144 protruding from the actuation button 72 of the plunger 70. The plunger release mechanism 154 is thus adapted to displace the first and second dosing surfaces 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 simultaneously align the second dosing surface 148 with the dosing element 144.

[0092] To ensure that, when the user activates the plunger release mechanism 154, the first housing element 86 is rotated in the correct orientation relative to the second housing element 88 the correct amount of rotation required to disengage the dosing element 144 from the first dosing surface 146 and simultaneously align the second dosing surface 148 with the dosing element 144, the plunger release mechanism 154 comprises a marker system 160 adapted to indicate activation of the plunger release mechanism 154. The marker system 160 includes a first marker element 162 provided on an outer surface of the first housing element 86. The marker system 160 further includes a second marker element 164 provided on an outer surface of the second housing element 88. The first and second marker elements 162, 164 are positioned on the first and second housing elements 86, 88 such that they are positioned offset from one another circumferentially about the plunger 70 when the plunger release mechanism 154 is not activated, but are aligned with one another when the plunger release mechanism 154 is activated. Compare Figures 34b and 34c.

[0093] The injection device 10 further comprises a limiting mechanism 166 adapted to limit the movement of the first and second dosing surfaces 146, 148 in order to disengage the dosing element 144 from the first dosing surface 146 and to align 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 provided on the first housing element 86 supporting the first and second dosing surfaces 146, 148. Furthermore, the limiting mechanism 166 comprises a second limiting element 170 provided on the second housing element 88 which remains stationary when the first housing element 86 is rotated to stop the first plunger stop mechanism 140. When the dosing element 144 is disengaged from the first dosing surface 146 and aligned with the second dosing surface 148 by rotating the first housing element 86 relative to the plunger 70, the first limiting element 168 abuts the second limiting element 170. The limiting mechanism 166 prevents a user of the injection device 10 from over-rotating the first housing element 86 relative to the second housing element 88. Furthermore, the limiting mechanism 166 provides tactile feedback to the user that the first plunger stop mechanism 140 has been stopped.

[0094] The second drag mechanism 172 serves to apply a retaining force that holds the first housing element 86 in position relative to the second housing element 88. The presence of the second drag mechanism 172 requires active manual actuation to rotate the first housing element 86 relative to the second housing element 88. Thus, the second drag mechanism 172 prevents unintentional displacement of the first housing element 86 relative to the second housing element 88 and therefore unintentional activation of the plunger release mechanism 154. The second drag mechanism 172 comprises a friction element 174 that is provided on the first limiting element 168 of the limiting mechanism 166 and is adapted to frictionally interact with the retaining element 158 ​​of the second housing element 88.

[0095] The injection device 10 further comprises an actuation mechanism 176 adapted to prevent actuation of the plunger release mechanism 154 until the plunger 70 is located in the first dosing position P1 and adapted to allow actuation of the plunger release mechanism 154 when the plunger 70 is located in the first dosing position P1 (see Figures 12, 16 and 19a). In particular, the actuation mechanism 176 prevents rotation of the first housing element 86 relative to the plunger 70, thereby preventing movement of the dosing element 144 and the first dosing surface 144 relative to each other until the plunger 70 is located in the first dosing position P1.

[0096] The actuation mechanism 176 comprises a guide channel 94, which is provided on the circumferential surface of the plunger 70 extending along the longitudinal axis of the plunger 70, and which receives a guide element 92 provided on the first housing element 86, such that the guide channel 94 is displaced relative to the guide element 92 upon displacement of the plunger 70 relative to the injection solution container 30. The interaction of the guide element 92 with the opposing faces of the guide channel 94 prevents the plunger 70 and the first housing element 86 from rotating relative to each other. The actuation mechanism 176 thus performs a double function, on the one hand to allow a guided displacement of the plunger 70 in the direction of the longitudinal axis, and at the same time to prevent the first plunger stop mechanism 154 from being unintentionally stopped when the plunger 70 is not arranged in the first dosing position.

[0097] The actuation mechanism 176 further comprises an actuation channel 178 that branches off from the guide channel 94 and extends circumferentially about the plunger 70 substantially perpendicular to the guide channel 94. The actuation channel 178 receives the guide element 92 when the plunger 70 is disposed in the first dosing position P1 and the first housing element 86 is rotated relative to the plunger 70. The first dosing position P1 of the plunger 70 is thereby defined by the position of the actuation channel 178 along the longitudinal axis of the plunger 70.

[0098] Finally, the plunger release mechanism 154 further comprises a locking arrangement 180, which locks the first dosing surface 146 in position relative to the dosing element 144 after the first dosing surface 146 has moved relative to the dosing element 144 to disengage from the dosing element 144 (see Figures 17, 21 and 25). In particular, the locking arrangement 180 comprises a resilient locking clip 182, which is provided on the second housing element 88 and which is resiliently pushed out of its rest position due to interaction with a locking element 184 provided on the first housing element 86 when the first dosing surface 146 moves relative to the dosing element 144 to disengage from the dosing element 144, i.e. when the first housing element 86 rotates relative to the second housing element 88.

[0099] The locking clip 182 deforms to return to 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 86, and interacts with the locking element 184 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 to prevent a reverse rotation of the first housing element 86 relative to the second housing element 88 and the plunger 70 after one rotation of the first housing element 86 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. As a result, the first dosing surface 146 is locked in place relative to the dosing element 144. The locking arrangement 180 allows the plunger release mechanism 154 to be used only once to lock the first plunger stop mechanism 140. As a result, reuse of the injection device 10 is prevented.

[0100] After the rotational movement of the first housing element 86 relative to the second housing element 88 is completed with the plunger 70 disposed in the first dosing position P1, the dosing element 144 is aligned with the recess 152 formed in the first dosing surface 146. As a result, the abutment surface 150 of the dosing element 144 is disposed parallel to the second dosing surface 148 at a distance S. As a result, the plunger 70 can be further displaced distally from the first dosing position P1 by a distance S into the second dosing position P2 until the dosing element 144, i.e. its abutment surface 150, abuts against the second dosing surface 148 (compare Fig. 34c with Fig. 34d). Similar to the first plunger stop mechanism 140, the second plunger stop mechanism 142 also provides a hard stop for the plunger 70, i.e. prevents the plunger 70 from being displaced distally from the second dosing position P2 relative to the injection solution container 30. The dose of injection solution to be administered to the patient can therefore be set in a particularly precise manner.

[0101] Figures 35a-c show exploded views of an injection device according to various examples, which are described below with simultaneous reference to Figures 36a-c, which show use of an injection device according to various examples.

[0102] As shown in FIG. 35a, the injection device 200 includes an injection solution container 202, a plunger 204, a tip element 206, and a housing 208. In some examples, the injection solution transfer system 100 includes the injection device 200 instead of the injection device 10. The injection device 200 provides similar functionality as the injection device 10 (e.g., accurately and reliably administering a microdose of injection solution to a patient) and interacts with other components of the injection solution transfer system 100 (e.g., the filling adapter 12) in a similar manner as the injection device 10. However, unlike the injection device 10, the injection device 200 is configured to be reusable (e.g., to be used to dispense and / or inject injection solution more than once). Furthermore, the injection device 200 has a more intuitive design that has been shown to reduce user errors (e.g., when dispensing and / or injecting injection solution).

[0103] Similar to the injection solution container 30 of the injection device 10, the injection solution container 202 of the injection device 200 is designed in the form of an inner injection solution container 210 housed in a protective outer barrel 212. The inner injection solution container 210 and the protective outer barrel 212 are integrally formed with one another and made from a sterile plastic material. The protective outer barrel 212 comprises a flange element 214 in the region of its proximal end.

[0104] In some examples, the surface (e.g., the inner periphery) of the inner injection solution container 210 is coated with a plasma enhanced chemical vapor deposition (PECVD) coating or a treatment useful for providing a smooth lubricious layer. In some examples, the surface (e.g., the inner periphery) of the inner injection solution container 210 is coated with a lubricant coating made from a PECVD process using octamethylcyclotetrasiloxane (OMCTS) as a precursor. In some examples, the injection solution container 202 / inner injection solution container 210 is manufactured by a PECVD process using high frequency power consisting of silicon, carbon, and oxygen according to ISO 14644, at least under ISO class 8 conditions during operation and ISO class 7 conditions during rest. PECVD coatings and processes are known in the art and are described in at least the following U.S. patents, each of which is incorporated herein by reference in its entirety: U.S. Pat. Nos. 10,390,744; 10,363,370; 10,327,986; 10,258,718; 10,201,660; 10,189,603; 10,059,047; 10,016,338; 9,981,794; 9,952,147; 9,937, Nos. 099, 9,903,782, 9,878,101, 9,863,042, 9,855,577, 9,764,093, 9,664,626, 9,662,450, 9,572,526, 9,554,968, 9,545,360, 9,475,225, 9,458,536, 9,381,687, 9,345,846, 9,272,095 and 8,834,954.

[0105] The distal end of the injection solution container 202 is provided with a male Luer taper 216 and a Luer thread 218, which interact with a female Luer taper and a complementary Luer thread, respectively (e.g., a female Luer taper 50 and a complementary Luer thread 54 provided on the second connection port 22 of the adapter element 18 of the fill adapter 12 when the fill adapter 12 is connected to the injection device 200). The Luer taper 216 and the Luer thread 218 can be used to establish a fluid-tight connection between the distal end of the injection solution container 202 and a component having a female Luer taper and a complementary Luer thread (e.g., the adapter element 18 of the fill adapter 12).

[0106] The outer barrel 212 further includes a clip receiver 220. The clip receiver 220 is configured to be releasably connected to a housing clip 234 of the housing 208 (as described in more detail below). In some examples, the outer barrel 212 does not include the clip receiver 220. In these examples, the housing clip 234 is releasably connected directly to the outer circumferential surface of the outer barrel 212.

[0107] In some examples, the diameter 222 of the inner injection solution container 210 is increased or decreased based on the amount (e.g., volume) of injection solution to be dispensed and / or injected. In other words, in some examples, the diameter 222 of the inner injection solution container 210 is increased or decreased to increase or decrease the amount of injection solution dispensed by the injection device 200. For example, as shown in FIG. 35b, the diameter 222 is increased (e.g., doubled) to increase the amount of solution that the inner injection solution container 210 can hold and subsequently dispense. Increasing or decreasing the diameter 222 requires increasing or decreasing the diameter of the outer barrel 212 and the diameter of the tip element 206. For example, as shown in FIG. 35b, the diameter of the outer barrel 212 and the diameter of the tip element 206 are increased such that the outer barrel 212 receives the inner injection solution container 210 and the tip element 206 sealingly interacts with the inner circumferential surface of the inner injection solution container 210 (as described in more detail below) in conjunction with the increase in the diameter 222. In some examples, the length of the injection solution container 202 (and thus the length of the inner injection solution container 210) is increased or decreased based on the amount (eg, volume) of injection solution to be dispensed and / or injected.

[0108] Increasing or decreasing the diameter and / or length of the inner injection solution container 210 as described above increases or decreases the total amount of injection solution that can be accommodated within the inner injection solution container 210. For example, depending on the diameter and length of the inner injection solution container 210, the inner injection solution container 210 can accommodate anywhere between 100 μL and 1000 μL.

[0109] In one embodiment, the inner injection solution container 210 can accommodate at least 100 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate at least 200 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate at least 300 μL of injection solution. The inner injection solution container 210 can accommodate at least 400 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate at least 500 μL of injection solution. The inner injection solution container 210 can accommodate at least 600 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate at least 700 μL of injection solution. The inner injection solution container 210 can accommodate at least 800 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate at least 900 μL of injection solution. The inner injection solution container 210 can accommodate at least 1000 μL of injection solution.

[0110] In one embodiment, the inner injection solution container 210 can accommodate 100 to 900 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 100 to 800 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 100 to 700 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 100 to 600 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 100 to 500 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 100 to 400 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 100 to 300 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 100 to 200 μL of injection solution.

[0111] In one embodiment, the inner injection solution container 210 can accommodate 200 to 1000 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 300 to 1000 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 400 to 1000 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 500 to 1000 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 600 to 1000 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 700 to 1000 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 800 to 1000 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 900 to 1000 μL of injection solution.

[0112] In one embodiment, the inner injection solution container 210 can accommodate 200-900 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 300-800 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 400-700 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 500-600 μL of injection solution.

[0113] In one embodiment, the inner injection solution container 210 can accommodate 100 to 200 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 200 to 300 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 300 to 400 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 400 to 500 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 500 to 600 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 600 to 700 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 700 to 800 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 800 to 900 μL of injection solution. In one embodiment, the inner injection solution container 210 can contain 900-1000 μL of injection solution.

[0114] In one embodiment, the inner injection solution container 210 can accommodate 100 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 200 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 300 μL of injection solution. The inner injection solution container 210 can accommodate 400 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 500 μL of injection solution. The inner injection solution container 210 can accommodate 600 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 700 μL of injection solution. The inner injection solution container 210 can accommodate 800 μL of injection solution. In one embodiment, the inner injection solution container 210 can accommodate 900 μL of injection solution. The inner injection solution container 210 can accommodate 1000 μL of injection solution.

[0115] The injection device 200 can be configured to dispense a predetermined percentage (e.g., a predetermined percentage between 2.5% and 12.5%) of the total volume of the injection solution contained in the inner injection solution container 210, and as described in more detail below with reference to FIG. 36c, a user of the injection device 200 can quickly and easily change the amount (e.g., volume) of the injection solution to be dispensed and / or injected by replacing the injection solution container 202 of the injection device 200 with another injection solution container 202 capable of containing a greater or lesser total volume of the injection solution. For example, if the injection device 200 is configured to deliver 12.5% ​​of the total injection solution volume contained in the inner injection solution container 210, the injection device 200 will dispense and / or inject 50 μL of injection solution if the inner injection solution container 210 contains 400 μL of injection solution, or 25 μL of injection solution if the inner injection solution container 210 contains 200 μL of injection solution.

[0116] Returning to FIG. 35a, the injection device 200 further includes a plunger 204. The plunger 204 includes an actuation button 224, a plunger flange 226, one or more guide channels 227, a plunger rod 228, one or more actuation channels 229, and a tip barb 230. Similar to the plunger 70 of the injection device 10, the plunger 204 is configured such that at least a portion of the plunger 204 (e.g., at least a portion of the plunger rod 228) is slidably received within the inner injection solution container 210 of the injection solution container 202. Furthermore, the plunger 204 is displaceable relative to the injection solution container 202 in a distal direction along a longitudinal axis of the plunger 204 to expel the injection solution contained within the injection solution container 202. However, unlike plunger 70, plunger 204 is configured to rotate (e.g., clockwise and counterclockwise) about the longitudinal axis of plunger 204 after inner injection solution container 210 slidably receives at least a portion of plunger 204 (as described in more detail below).

[0117] The activation button 224 is positioned at a proximal end of the plunger 204 that protrudes proximally from the injection solution container 202. The activation button 224 is pressed by a user to displace the plunger 204 relative to the injection solution container 202 in a distal direction along a longitudinal axis of the plunger 204. As shown in FIG. 35a, the activation button 224 includes a number of ridges that assist the user in rotating the plunger 204. In some examples, the activation button 224 does not include a number of ridges (e.g., similar to the activation button 72).

[0118] A plunger flange 226 is positioned at a proximal end of the plunger 204 below the actuation button 224. As described in more detail below (e.g., with reference to FIGS. 36a and 36b), the plunger flange 226 is configured to interact with a plunger stop mechanism 238 such that, based on the longitudinal position and / or rotational orientation of the plunger flange 226, the plunger stop mechanism 238 prevents the plunger 204 from being displaced distally along the longitudinal axis of the plunger 204 and / or prevents the plunger 204 from rotating clockwise and / or counterclockwise about the longitudinal axis of the plunger 204. Although the plunger flange 226 is rectangular in shape in FIG. 35a, in some examples, the plunger flange 226 has a different shape (e.g., triangular, diamond, oval, etc.). Additionally, although the plunger flange 226 is positioned directly below the actuation button 224, in some examples, the plunger flange 226 is positioned further below the longitudinal axis of the plunger 204 (in the distal direction) on the plunger rod 228. For example, the plunger flange 226 may be positioned at the midpoint of the plunger rod 228.

[0119] The plunger rod 228 of the plunger 204 is connected at its distal end to the tip element 206 of the injection device 200. The tip element 206 is identical to the tip element 74 (described in more detail above with reference to FIG. 13). Moreover, the tip element 206 is connected to the plunger 204 in a similar manner as the tip element 74 is connected to the plunger 70. Specifically, the coupling between the plunger rod 228 and the tip element 206 is provided by the interaction of a tip barb 230 positioned at the distal end of the plunger rod 228 with a barb receiver (e.g., barb receiver 80) of the tip element 206. A sealing element (e.g., sealing element 82) of the tip element 206 sealingly interacts with the inner circumferential surface of the inner injection solution container 210.

[0120] The housing 208 of the injection device 200 includes a flange receiver 232, a housing clip 234, a plunger through hole 236, and a plunger stop mechanism 238. The housing 208 is configured to be releasably connected to the injection solution container 202 and to slidably receive the plunger 204.

[0121] The housing 208 is releasably connected to the injection solution container 202 (e.g., as shown in FIGS. 36a and 36b) via (1) interaction of the flange element 214 with the flange receiver 232 and (2) interaction of the clip receiver 220 with the housing clip 234. Specifically, the flange receiver 232 is suitably shaped and sized to receive the flange element 214 and, in some instances, to hold the flange element 214 in place. Additionally, the housing clip 234 is configured to be releasably connected to the clip receiver 220 of the injection solution container 202 (e.g., as shown in FIGS. 36a and 36b). In the examples discussed above in which the outer barrel 212 does not include the clip receiver 220, the housing clip 234 is releasably connected directly to the outer circumferential surface of the outer barrel 212. By connecting the injection solution container 202 and the housing 208 as described above, the housing 208 can be easily and quickly disconnected from the injection solution container 202 and, in some instances, replaced with a different housing (e.g., when the plunger 204 is not inserted into the injection solution container 202 and the housing 208).

[0122] The plunger throughbore 236 slidably receives the plunger rod 228 (e.g., with the tip element 206 attached to the plunger rod 228) such that the inner injection solution container 210 slidably receives the plunger 204 as it slides through the plunger throughbore 236. In this manner, the plunger 204 is displaceable relative to the housing 208 and the injection solution container 202 in a direction along its longitudinal axis.

[0123] In some examples, the housing 208 includes one or more guide elements (not shown) that protrude into the plunger through bore 236. In some examples, the one or more guide elements of the housing 208 are identical to the guide elements 92 of the first housing element 86 (e.g., as described above with reference to FIG. 16 ). When the plunger 204 is received within the plunger through bore 236 of the housing 208, each guide element engages with a guide channel 227 that is positioned on the surface of the plunger rod 228 and extends along the longitudinal axis of the plunger rod 228. The interaction of the one or more guide elements with the opposing sides of their corresponding guide channels 227 prevents the plunger 204 and the housing 208 from rotating relative to one another until each guide element is aligned with a corresponding actuation channel 229 on the surface of the plunger rod 228.

[0124] Each actuation channel 229 on the surface of the plunger rod 228 branches off from a guide channel 227 and extends circumferentially about the plunger rod 228 substantially perpendicular to its corresponding guide channel 227. In some examples, one or more actuation channels 229 on the surface of the plunger rod 228 are identical to actuation channels 178 of the plunger 70. Each actuation channel 229 receives a guide element when the plunger 204 is (1) disposed in a first dosing position P1 along the longitudinal axis of the plunger 204 and (2) in a first orientation O1 (e.g., a rotational orientation, angular position, or rotational orientation relative to the longitudinal axis) about the longitudinal axis of the plunger 204. For example, FIG. 36a shows the plunger 204 in the first dosing position P1 and in the first orientation O1.

[0125] Thus, in examples where the housing 208 includes one or more guiding elements and the plunger rod 228 includes one or more guiding channels 227 / actuation channels 229, the first dosing position P1 of the plunger 204 is defined at least in part by the position of the one or more actuation channels 229 along the longitudinal axis of the plunger rod 228. In some examples, the one or more actuation channels 229 are positioned on the plunger rod 228 such that the one or more guiding elements are aligned with the one or more actuation channels 229 when the plunger flange 226 contacts the plunger stop mechanism 238 (e.g., as shown in FIG. 36a). Thus, the interaction of the one or more guiding elements with the guiding channels 227 serves a dual function of allowing the plunger 204 to be guided and displaced in a direction along its longitudinal axis, while at the same time preventing the plunger 204 from unintentionally rotating when the plunger 204 is not disposed in the first dosing position P1 in the first orientation O1. This makes the injection device 200 easier to use, thus reducing user error (eg, when dispensing and / or injecting injection solution).

[0126] The plunger stop mechanism 238 is positioned on a proximal surface of the housing 208 adjacent (e.g., at least partially surrounding) the plunger through hole 236. The plunger stop mechanism 238 includes a longitudinal stop member 240, a rotational stop member 242, and a dispensing surface 244. As shown in FIG. 35a, the longitudinal stop member 240, the rotational stop member 242, and the dispensing surface 244 protrude proximally from the proximal surface of the housing 208, and the rotational stop member 242 protrudes further proximally than the longitudinal stop member 240 and the dispensing surface 244. Specifically, the height of the rotational stop member 242 is greater than the height of the longitudinal stop member 240, which is greater than the height of the dispensing surface 244. In some examples, the dispensing surface 244 does not protrude from the proximal surface of the housing 208. In these examples, the proximal surface of the housing 208 between the longitudinal stop member 240 and the rotational stop member 242 serves as the dosing surface 244. In some examples, the plunger stop mechanism 238 includes only a single longitudinal stop member 240 and a single rotational stop member 242 (instead of two longitudinal stop members 240 and two rotational stop members 242 as shown in FIG. 35a). In some examples, the plunger stop mechanism includes three or more longitudinal stop members and three or more rotational stop members.

[0127] In some examples, the injection device 200 is used to dispense and / or inject a precise dose of the solution contained within the inner injection solution container 210 (e.g., a dose in the range of 5 μL to 250 μL of injection solution). In a first step, excess injection solution is expelled from the inner injection solution container 210 by displacing the plunger 204 in a distal direction relative to the inner injection solution container 210 (e.g., while the plunger 204 is in a first orientation O1 about the longitudinal axis of the plunger 204) until the plunger 204 reaches a first dosing position P1 along the longitudinal axis of the plunger 204. As shown in FIG. 36a, the plunger 204 is in the first dosing position P1 and the first orientation O1 when the plunger flange 226 contacts the longitudinal stop member 240 and the rotational stop member 242. The desired dose / amount of injection solution can then be dispensed and / or injected (e.g., into the patient's tissue).

[0128] As shown in FIG. 36a, the longitudinal stop member 240 is configured to prevent the plunger 204 from displacing in a distal direction relative to the injection solution container 202 / inner injection solution container 210 at the first dosing position P1. Specifically, the longitudinal stop member 240 prevents the plunger 204 from displacing in a distal direction when it contacts / abuts the plunger flange 226. Furthermore, the rotation stop member 242 is configured to prevent the plunger 204 from rotating in a counterclockwise direction about the longitudinal axis of the plunger 204 when the plunger 204 is in the first dosing position P1 and in the first orientation O1. Specifically, the rotation stop member 242 prevents the plunger 204 from rotating in a counterclockwise direction when it contacts / abuts the plunger flange 226. In some examples, both rotation stop members 242 are positioned on the other side of their adjacent longitudinal stop members 240 (e.g., opposite their positions shown in FIG. 35a). In these examples, the rotation stop member 242 prevents the plunger 204 from rotating in a clockwise direction when it contacts / abuts the plunger flange 226 .

[0129] Thus, during use of the injection device 200, a user can expel excess injection solution from the inner injection solution container 210 by displacing the plunger 204 in a distal direction relative to the inner injection solution container 210 until the plunger 204 reaches a first dosing position P1 (e.g., until the plunger flange 226 contacts the longitudinal stop member 240). Once the first dosing position P1 is reached, the longitudinal stop member 240 blocks the plunger 204 from further displacing in a distal direction. As a result, the user of the injection device 200 is prevented from expelling too much injection solution from the inner injection solution container 210. Residual injection solution contained in the inner injection solution container 210 can then be dispensed and / or injected by further displacing the plunger 204 in a distal direction until the plunger 204 reaches a second dosing position P2. 36c, the plunger 204 reaches the second dosing position P2 when the plunger flange 226 (e.g., a bottom / distal surface of the plunger flange 226) contacts / abuts the dosing surface 244. Upon reaching the second dosing position P2, the dosing surface 244 prevents further displacement of the plunger 204 in the distal direction, thus preventing excessive dispensing and / or injection of the injection solution.

[0130] However, before the plunger 204 can be displaced to the second dosing position P2, the user of the injection device 200 must manually rotate the plunger 204 clockwise about the longitudinal axis of the plunger 204 (e.g., using the actuation button 224) from the first orientation O1 to the second orientation O2, as shown in Fig. 36b. Specifically, the plunger 204 is in the second orientation O2 when the plunger flange 226 again contacts / abuts the rotation stop member 242 after rotating in the clockwise direction. Although Fig. 36b shows the plunger 204 rotated 90 degrees in the clockwise direction from the first orientation O1 to the second orientation O2, in some instances the user must rotate the plunger 204 more or less than 90 degrees (e.g., 110 degrees or 45 degrees) to get from the first orientation O1 to the second orientation O2. In these examples, the longitudinal stop member 240, the rotational stop member 242 and the dispensing surface 244 are shaped and positioned on the proximal surface of the housing 208 to accommodate greater or lesser rotational movement of the plunger 204. In this manner, the plunger flange 226 still contacts / abuts the rotational stop member 242 when in, for example, the first orientation O1 and when in the second orientation O2.

[0131] When the plunger 204 is rotated from the first orientation O1 to the second orientation O2 (while the plunger 204 is in the first dispensing position P1), the plunger flange 226 is aligned directly above the dispensing surface 244 (and the recess formed between the longitudinal member 240 / rotation stop member 242 and the dispensing surface 244 due to the height difference between the longitudinal member 240 / rotation stop member 242 and the dispensing surface 244). In other words, as shown in FIG. 36b, when the plunger 204 is in the second orientation O2, the distal / bottom surface of the plunger flange 226 is disposed parallel to the dispensing surface 244. As a result, the user of the injection device 200 can further displace the plunger 204 in the distal direction from the first dispensing position P1 to the second dispensing position P2 until the plunger flange 226 contacts / abuts the dispensing surface 244. The dosing surface 244 provides a hard stop for the plunger 204 and prevents the plunger 204 from being displaced further distally (relative to the injection solution container 202 / inner injection solution container 210) from the second dosing position P2. Thus, the dose of injection solution to be administered to the patient can be set in a particularly precise manner.

[0132] Specifically, the distance between the first and second dosing positions P1 and P2 of the plunger 204 is selected such that the plunger 204 expels a predetermined percentage (e.g., a predetermined percentage between 2.5% and 12.5%) of the total volume of injection solution contained within the inner injection solution container 210 when the plunger 204 is displaced from the first dosing position P1 to the second dosing position P2. In other words, the distance between the top / proximal surface of the longitudinal stop member 240 in the distal direction (e.g., in contact with the bottom / distal surface of the plunger flange 226) and the dosing surface 244 sets the desired dose of injection solution to be expelled from the inner injection solution container 210 when the plunger 204 is displaced from the first dosing position P1 to the second dosing position P2.

[0133] Thus, by changing the height of the longitudinal stop member 240 (e.g., the distal distance from the top / proximal surface of the longitudinal stop member 240 to the dosing surface 244), the amount of the dose to be dispensed and / or injected changes (e.g., if the total volume of injection solution contained within the inner injection solution container 210 does not change). For example, as shown in FIG. 35c, the height of the longitudinal member 240 (e.g., the proximal distance from the proximal / top surface of the housing 208) (and thus the height of the rotational stop member) can be increased without changing the dosing surface 244. Thus, in this example, increasing the distal distance between the proximal / top surface of the longitudinal member 240 and the dosing surface 244 causes the plunger 204 to move a greater distance along its longitudinal axis, thus dispensing more of the injection solution contained within the inner injection solution container 210, resulting in a greater percentage of the total volume of injection solution contained within the inner injection solution container 210 being dispensed and / or injected. For example, if the inner injection solution container 210 contains 200 μL of injection solution, by increasing the distal distance between the proximal / upper surface of the longitudinal member 240 and the dispensing surface 244 so that the plunger 204 dispenses 12.5% ​​of the total volume of the injection solution instead of 2.5%, the amount of injection solution that the plunger 204 expels from the inner injection solution container 210 when the plunger 204 is displaced from the first dispensing position P1 to the second dispensing position P2 increases by 20 μL (e.g., because 2.5% of 200 μL is 5 μL and 12.5% ​​of 200 μL is 25 μL).

[0134] The ability of the longitudinal stop member 240 and the rotational stop member 242 to prevent the plunger 204 from displacing distally (when the plunger 204 is in the first dosing position P1 and in the first orientation O1) and to prevent certain rotation of the plunger 204 (when the plunger 204 is in the first dosing position P1 and in the first orientation O1 or the second orientation O2), respectively, provides various benefits with respect to dispensing and / or injecting precise microdoses of injection solution. For example, the longitudinal stop member 240 and the rotational stop member 242 allow a user of the injection device 200 to easily and comfortably deliver precise microdoses of injection solution. In particular, because the longitudinal stop member 240 prevents the plunger 204 from slidably displacing distally beyond the extent necessary to prime the injection device, the longitudinal stop member 240 allows a user to quickly and easily prime the injection device 200 without erroneously dispensing and / or injecting the injection solution to the desired microdosage. Furthermore, when the plunger 204 is in the first dosing position P1 and in the first orientation O1, the rotation stop member 242 prevents a user from accidentally rotating the plunger 204 in a counterclockwise direction (or in some examples a clockwise direction) and subsequently displacing the plunger 204 to the second dosing position P2 (and dispensing and / or injecting the injection solution). In this manner, the rotation direction member 242 forces a user of the injection device 200 to intentionally rotate the plunger 204 in a single direction (e.g., clockwise or counterclockwise) towards the second orientation O2 for subsequently displacing the plunger 204 to the second dosing position P2 and thereby dispensing and / or injecting the injection solution.

[0135] Thus, for at least the reasons described above, the longitudinal stop member 240 and the rotational stop member 242 guide the user's displacement of the plunger 204 and prevent the user from erroneously dispensing and / or injecting the injection solution (e.g., accidentally dispensing / injecting too much injection solution and / or dispensing / injecting the injection solution at an improper time and / or in an incorrect location (e.g., incorrect patient tissue)). This makes the injection device 200 particularly easy to use, thus reducing user error. For example, Table (1) below includes results of a simulated use study of the injection device 200. As shown, the simulated use study evaluated various tasks for the use of the injection device 200. Prior to the evaluation, representative training was provided to the ophthalmologists / retinal surgeons (i.e., participants), and after a decay period of 1 to 7 weeks, the evaluation session was conducted. Overall, based on the evaluation, n=25 / 30 (83%) participants successfully performed the first injection without any use error, and n=24 / 30 (80%) participants successfully performed the second injection without any use error. A total of 22 out of 26 steps (84.6%) were successfully performed without any use error. Thus, for at least the above reasons, the injection device 200 is particularly suitable for injecting injection solutions into, for example, pediatric patients (e.g., pediatric ophthalmic injections), because pediatric patients are typically not very still when receiving an injection (due to fear of the injection and / or pain caused by the injection), and erroneous and inaccurate injections are more likely with standard injection devices that do not induce user-induced displacement of the injection device's plunger.

[0136] [Table 1]

[0137] Returning to FIG. 35a, as described above, the housing 208 can be easily and quickly separated from the injection solution container 202 and, in some instances, replaced with another housing. This allows the housing 208 to be quickly replaced with another housing, for example, based on the amount of injection solution to be dispensed and / or injected. For example, the housing 208 of FIG. 35a can be replaced with a housing having a longitudinal stop member with a greater height (such as the housing 208 of FIG. 35c). In this manner, the injection device 200 can be reused multiple times to accurately dispense and / or inject microdoses of injection solution, even if different amounts of injection solution are desired for each individual use of the injection device 200 (because the housing 208 is a modular component that can be replaced based on the desired microdoses). Furthermore, the modularity of the housing 208 allows a user to quickly replace the housing 208, for example, based on the desired amount of injection solution to be dispensed and / or injected during a patient treatment (e.g., if the patient treatment requires multiple injections of different amounts of injection solution).

[0138] In some examples, the plunger stop mechanism 238 (specifically, the longitudinal stop member 240, the rotational stop member 242 and / or the dispensing surface 244) is positioned / fixed on the plunger 204 rather than on the proximal / top surface of the housing 208. In these examples, the plunger stop mechanism 238 faces in a distal direction (e.g., toward the housing 208) rather than in a proximal direction. In other words, the longitudinal stop member 240 and the rotational stop member 242 protrude in a distal direction.

[0139] In some examples, the plunger stop mechanism 238 is positioned / secured to a distal / bottom surface of the actuation button 224 of the plunger 204 such that the longitudinal stop member 240, the rotational stop member 242 and / or the dosing surface 244 protrude distally from the distal / bottom surface of the actuation button 224 toward the housing 208 (and thus adjacent and / or surrounding the plunger rod 228). In some examples, only the longitudinal stop member 240 and the rotational stop member 242 protrude distally from the distal / bottom surface of the actuation button 224. In these examples, the dosing surface 244 is the distal / bottom surface of the actuation button 224.

[0140] In some examples, the plunger stop mechanism 238 is positioned / fixed on the plunger rod 228. In these examples, the plunger stop mechanism 238 has a proximal / top surface that attaches the plunger stop mechanism 238 to the plunger rod 228 (from which the longitudinal stop member 240, the rotational stop member 242, and / or the dosing surface 244 project distally). Specifically, the plunger rod 228 intersects through the proximal / top surface, and the plunger stop mechanism is permanently (e.g., non-slidably) attached to the plunger rod 228 at the intersection. In some examples, the plunger stop mechanism 238 replaces the plunger flange 226 of the plunger 204 (and thus the plunger stop mechanism 238 is positioned where the plunger flange 226 is positioned in FIGS. 35a-36b). In some examples, the plunger stop mechanism 238 is positioned on the plunger rod 228 further down (in the distal direction) the longitudinal axis of the plunger 204. For example, the plunger stop mechanism 238 may be positioned at the midpoint of the plunger rod 228.

[0141] It should be noted that the various embodiments of the plunger stop mechanism 238 described above (e.g., having higher / lower longitudinal stop members 240, different degrees of rotation of the plunger 204 to reach the second orientation O2, and different numbers of longitudinal stop members 240 and / or rotational stop members 242) are still applicable in the above example in which the plunger stop mechanism 238 is positioned on the plunger 204.

[0142] When the plunger stop mechanism 238 is positioned on the plunger 204 (e.g., on a distal / bottom surface of the actuation button 224 or on the plunger rod 228), the housing 208 is configured to interact with components of the plunger stop mechanism 238 in the same manner that the plunger flange 226 interacts with components of the plunger stop mechanism 238 when the plunger stop mechanism 238 is positioned on the housing 208. For example, the housing 208 is configured to interact with the longitudinal stop member 240 to prevent the plunger 204 from further displacing in the distal direction when the plunger 204 is in the first dosing position P1 and in the first orientation O1. As another example, the housing 208 is configured to interact with the rotation stop member 242 to prevent the plunger 204 from rotating in a counterclockwise direction (or in some examples, a clockwise direction) about the longitudinal axis of the plunger 204 when the plunger 204 is in the first dosing position P1 and in the first orientation O1.

[0143] Specifically, in some examples, at least a portion of the proximal / top surface of the housing 208 that surrounds the plunger throughbore 236 protrudes proximally toward the plunger mechanism 238 along the longitudinal axis of the plunger 204 (such that the plunger throughbore 236 can still slidably receive the plunger rod 228). In these examples, the protruding proximal / top surface of the housing 208 has a height at least equal to the distal distance between the dosing surface 244 and the distal surface of the rotation stop member 242 (i.e., the surface of the rotation stop member 242 that faces distally toward the housing 208). In this manner, when the dosing surface 244 contacts / abuts the protruding proximal / upper surface of the housing 208 (at the second dosing position P2), the distal surface of the rotation stop member 242 is either (1) flush with the proximal non-projecting portion of the proximal / upper surface of the housing 208 (e.g., if the height of the protruding proximal / upper surface of the housing 208 is equal to the distal distance between the dosing surface 244 and the distal surface of the rotation stop member 242) or (2) does not contact the proximal non-projecting portion of the proximal / upper surface of the housing 208 (e.g., if the height of the protruding proximal / upper surface of the housing 208 is greater than the distal distance between the dosing surface 244 and the distal surface of the rotation stop member 242). Furthermore, the protruding proximal / upper surface of the housing 208 is shaped to fit into a recess formed between the longitudinal member 240 / rotation stop member 242 and the dosing surface 244. In some examples, the protruding proximal / top surface of the housing 208 has the same rectangular shape as the plunger flange 226 of Figures 35a-c. In some examples, the protruding proximal / top surface of the housing 208 has a different shape (e.g., triangular, diamond, oval, etc.) depending on the shape of the recess formed between the longitudinal member 240 / rotation stop member 242 and the dispensing surface 244.

[0144] In the above example where the plunger stop mechanism is on the plunger 204, the plunger 204 may be replaced with another plunger 204, for example, based on the amount of injection solution to be dispensed and / or injected (similar to how the housing 208 may be replaced if the plunger stop mechanism 238 is on the proximal / top surface of the housing 208). In other words, the plunger 204 may be replaced with another plunger 204 having a different (e.g., higher or lower) longitudinal member 240, rotational stop member 242 and / or dosing surface 244. In this manner, the injection device 200 may be reused multiple times to accurately dispense and / or inject microdoses of injection solution (because the plunger 204 is a modular component that may be replaced based on the desired microdoses), even if a different amount of injection solution is desired for each individual use of the injection device 200. Additionally, the modularity of the plunger 204 (including the plunger stop mechanism 238) allows, for example, a user to quickly replace the plunger 204 based on the desired amount of injection solution to be metered and / or injected during a patient treatment (e.g., if the patient treatment requires multiple injections of different injection solution volumes).

[0145] 37a and 37b show flow diagrams of a process for dispensing an amount of a solution using a solution dispensing device, according to various embodiments. Process 3700 is performed, for example, using injection device 10 or injection device 200. In process 3700, some blocks are optionally combined, the order of some blocks is optionally changed, and some blocks are optionally omitted. In some examples, additional steps may be performed in combination with process 3700.

[0146] At block 3702, a rotatable plunger (e.g., plunger 204) is slidably inserted into a first end of a solution container (e.g., inner injection solution container 30 or inner injection solution container 210), where a second end of the solution container (e.g., male luer taper 48 or luer taper 216) is configured to expel a solution contained within the solution container. In some examples, the solution includes a vascular endothelial growth factor (VEGF) antagonist (e.g., ranibizumab (i.e., Lucentis TM )). In some examples, the solution includes a nucleic acid, as shown in block 3706. In some examples, the solution includes Beovu® (brolucizumab). In some examples, the solution includes Eylea® (aflibercept). In some examples, the solution includes Luxturna® (boretigene neparvovec).

[0147] In block 3708, while the rotatable plunger is in a first orientation (e.g., rotational orientation, angular position, rotational attitude relative to a first axis) (e.g., first orientation O1), the rotatable plunger is slidably displaced along the first axis until the rotatable plunger is in a first position (e.g., first dosing position P1) relative to the solution container.

[0148] In block 3710, a first stop member (e.g., longitudinal stop member 240) prevents the rotatable plunger from being slidably displaced to a second position (e.g., second dosing position P2) relative to the solution container closer to a second end of the solution container than the first position while the rotatable plunger is in the first position and in the first orientation (e.g., the rotatable plunger is slidably displaced further into the solution container when in the second position than when in the first position).

[0149] In some examples, the first stop member is positioned on the rotatable plunger, as shown in block 3712. In some examples, the first stop member is positioned on a bottom surface of an activation button (e.g., activation button 72 or activation button 224) positioned at an end of the rotatable plunger that is not slidably received by the solution container (e.g., the bottom surface is closer to the first end of the solution container (along the first axis) than a top surface of the activation button). In some examples, the first stop member is positioned at a point along the shaft of the rotatable plunger (e.g., at a midpoint of the rotatable plunger).

[0150] In some examples, the rotatable plunger includes a flange (e.g., a flange having a first shape (e.g., rectangular, oval, diamond, etc.) secured to the rotatable plunger and rotating with the rotatable plunger about a first axis) (e.g., flange 226) that contacts a first stop member and prevents the rotatable plunger from being slidably displaced to a second position while the rotatable plunger is in a first position and in a first orientation, as shown in block 3714. In some examples, the flange is positioned at an end of the rotatable plunger that is not slidably received by the solution container (e.g., directly below a bottom surface of an actuation button of the rotatable plunger). In some examples, the flange is positioned at a point along the shaft of the rotatable plunger (e.g., a midpoint of the shaft of the rotatable plunger).

[0151] At block 3716, a second stop member (e.g., rotational stop member 242) prevents the rotatable plunger from rotating in a first direction about the first axis (e.g., rotating in the first direction (e.g., counterclockwise) to reach the second orientation) while the rotatable plunger is in the first position and in the first orientation.

[0152] In some examples, the second stop member is positioned on the rotatable plunger, as shown in block 3718. In some examples, the second stop member is positioned on a bottom surface of an activation button positioned at an end of the rotatable plunger that is not slidably received by the solution container (e.g., the bottom surface is closer to the first end of the solution container (along the first axis) than a top surface of the activation button). In some examples, the second stop member is positioned at a point along the shaft of the rotatable plunger (e.g., at a midpoint of the rotatable plunger).

[0153] In some examples, the rotatable plunger includes a flange (e.g., a flange having a first shape (e.g., rectangular, oval, diamond, etc.) fixed to the rotatable plunger and rotating with the rotatable plunger about the first axis) that contacts the second stop member and prevents the rotatable plunger from rotating about the first axis while the rotatable plunger is in the first position and in the first orientation, as shown in block 3720.

[0154] In some examples, the solution dispensing device is configured to prevent the rotatable plunger from rotating about the first axis (e.g., prevent the rotatable plunger from rotating in any direction (e.g., first or second direction)) until the rotatable plunger is positioned at the first position, as shown in block 3722. In some examples, the solution dispensing device further includes one or more guide elements (e.g., guide element 92) configured to engage with one or more guide channels (e.g., guide channel 227) of the rotatable plunger and to prevent the rotatable plunger from rotating about the first axis until the rotatable plunger is positioned at the first position. In some examples, the solution container includes a guide element (e.g., at the first end). In some examples, the housing includes a guide element (e.g., at the plunger through hole).

[0155] At block 3724, the rotatable plunger is rotated in a second direction about the first axis until the rotatable plunger is in the first position and in a second orientation (e.g., the second orientation O2). In some examples, a third stop member (e.g., the rotating member 242) prevents the rotatable plunger from rotating in the second direction about the first axis (e.g., rotating in the second direction (e.g., clockwise) to reach the first orientation) while the rotatable plunger is in the first position and in the second orientation, as shown in block 3726.

[0156] At block 3728, while the rotatable plunger is in the second orientation, the rotatable plunger is slidably displaced along the first axis until the rotatable plunger is in a second position relative to the solution container, where a quantity (e.g., a fixed volume, a metered volume) of solution contained within the solution container is dispensed by slidably displacing the rotatable plunger from the first position to the second position. In some examples, the amount of solution dispensed when the rotatable plunger is slidably displaced from the first position to the second position is selected from the group consisting of 5 μL, 10 μL, and 20 μL, as shown in block 3730.

[0157] In some examples, the solution container contains between 100 μL and 1000 μL of solution. In some examples, the amount of solution dispensed when the rotatable plunger is slidably displaced from the first position to the second position is between 2.5% and 12.5% ​​of the solution contained in the solution container.

[0158] In some examples, the method (e.g., process 3700) is used for pediatric ophthalmic injections, as shown in block 3732. In some examples, the method (e.g., process 3700) is used for gene therapy, as shown in block 3734.

[0159] In some examples, as shown in block 3736, the solution dispensing device further includes a housing (e.g., a fixed housing that does not rotate about a first axis) (e.g., housing 208) configured to be releasably connected to the solution container (e.g., connected to the solution container using a releasable clip included in the housing), where the housing includes a plunger through hole (e.g., plunger through hole or plunger through hole 236) configured to slidably receive the rotatable plunger and to enable the solution container to slidably receive the rotatable plunger.

[0160] In some examples, as shown in block 3738, the first stop member is positioned on the housing (e.g., positioned adjacent the plunger through hole on an upper surface of the housing, the upper surface being farther from the first end of the solution container than a bottom surface of the housing).

[0161] In some examples, as shown in block 3740, the second stop member is positioned on the housing (e.g., positioned adjacent the plunger through hole on an upper surface of the housing, the upper surface being farther from the first end of the solution container than the bottom surface of the housing).

[0162] In some examples, as shown in block 3742, the first stop member has a first height, and the amount of solution dispensed when the rotatable plunger is slidably displaced from the first position to the second position is based at least in part on the first height.

[0163] 38a-38s show additional views of an injection device (eg, injection device 200) and its components, according to various examples.

[0164] Exemplary solution dispensing devices and methods are described in the following sections. 1. A solution dispensing device (200), comprising: A rotatable plunger (204); a solution container (202) having a first end configured to slidably receive a rotatable plunger and a second end configured to dispense a solution contained within the solution container; enabling the rotatable plunger to be slidably displaced along a first axis while in a first orientation (O1) so as to be positioned at a first position (P1) relative to the solution container; enabling the rotatable plunger to be slidably displaced along a first axis from a first position to a second position (P2) relative to the solution container while in a second orientation (O2); It is configured as follows: the second position being closer to a second end of the solution container than the first position; a solution container, wherein slidable displacement of the rotatable plunger from a first position to a second position causes dispensing of a quantity of solution contained within the solution container; a first stop member (240) configured to prevent slidable displacement of the rotatable plunger to the second position while the rotatable plunger is in the first position and in the first orientation; a second stop member (242) configured to prevent the rotatable plunger from rotating in the first direction about the first axis while the rotatable plunger is in the first position and in the first orientation; A solution dispensing device (200) comprising: 2. a third stop member (242) configured to prevent the rotatable plunger from rotating in a second direction about the first axis while the rotatable plunger is in the first position and in the second orientation. Item 2. The solution dispensing device according to item 1, further comprising: 3. A solution dispensing device according to item 1 or 2, wherein the first stop member is positioned on the rotatable plunger. 4. A solution dispensing device according to any one of claims 1 to 3, wherein the second stop member is positioned on the rotatable plunger. 5. A solution dispensing device as described in any one of items 1 to 4, comprising a housing (208) configured to be releasably connected to a solution container, the housing (208) including a plunger through hole (236) configured to slidably receive a rotatable plunger and to enable the solution container to slidably receive the rotatable plunger. 6. The solution dispensing device according to item 5, wherein the first stop member is positioned on an upper surface of the housing, the first stop member protruding proximally from the upper surface of the housing along the first axis. 7. The solution dispensing device according to item 5 or 6, wherein the second stop member is positioned on an upper surface of the housing, the second stop member protruding proximally from the upper surface of the housing along the first axis. 8. The solution dispensing device of any one of items 5 to 7, wherein the first stop member has a first height relative to an upper surface of the housing, and an amount of solution dispensed when the rotatable plunger is slidably displaced from the first position to the second position is based at least in part on the first height. 9. The solution dispensing device according to item 8, wherein the second stop member has a second height relative to the upper surface of the housing that is greater than the first height. 10. The exterior surface of the solution container includes a clip receiving element (220); the housing includes a housing clip (234); 10. The solution dispensing device according to any one of items 5 to 9, wherein the housing clip is releasably connected to the clip receiving element. 11. The solution dispensing device of item 10, wherein the first end of the solution container includes a flange element (214), and the housing is configured to slidably receive the flange element when the housing clip is releasably connected to the clip receiving element. 12. The rotatable plunger includes a flange (226); a flange contacting the first stop member to prevent the rotatable plunger from slidably displacing to the second position while the rotatable plunger is in the first position and in the first orientation; Item 12. The solution dispensing device according to any one of items 1 to 11, wherein the flange contacts the second stop member and prevents the rotatable plunger from rotating about the first axis in the first direction while the rotatable plunger is in the first position and in the first orientation. 13. A solution dispensing device according to any one of items 1 to 12, configured to prevent the rotatable plunger from rotating about the first axis until the rotatable plunger is positioned in the first position. 14. A solution dispensing device according to any one of items 1 to 13, wherein the amount of solution dispensed when the rotatable plunger is slidably displaced from the first position to the second position is selected from the group consisting of 5 μL, 10 μL and 20 μL. 15. A solution dispensing device according to any one of items 1 to 14, wherein the inner surface of the solution container (210) is coated with a plasma enhanced chemical vapor deposition (PECVD) coating, the PECVD coating providing a smooth lubricious layer on the inner surface. 16. The solution dispensing device of any one of items 1 to 15, wherein the inner surface of the solution container is coated with a lubricant coating made from a PECVD process using octamethylcyclotetrasiloxane (OMCTS) as a precursor. 17. The solution dispensing device according to any one of items 1 to 16, wherein the solution container is manufactured in accordance with ISO 14644 by a PECVD process using high-frequency power consisting of silicon, carbon and oxygen under at least ISO class 8 conditions during operation and ISO class 7 conditions during rest. 18. A method of dispensing a solution from a solution dispensing device (200), the solution dispensing device having a rotatable plunger (204), a solution container (202), a first stop member (240), and a second stop member (242); Slidably inserting a rotatable plunger into a first end of a solution container, the second end of the solution container being configured to dispense a solution contained within the solution container; While the rotatable plunger is in a first orientation (O1), slidably displacing the rotatable plunger along a first axis until the rotatable plunger is in a first position (P1) relative to the solution container, a first stop member prevents the rotatable plunger from being slidably displaced relative to the solution container to a second position (P2) closer to a second end of the solution container than the first position while the rotatable plunger is in the first position and in the first orientation; a second stop member preventing the rotatable plunger from rotating in the first direction about the first axis while the rotatable plunger is in the first position and in the first orientation; rotating the rotatable plunger in a second direction about the first axis until the rotatable plunger is in a second orientation (O2) at the first position; While the rotatable plunger is in the second position, slidably displacing the rotatable plunger along the first axis until the rotatable plunger is in a second position relative to the solution container, where slidably displacing the rotatable plunger from the first position to the second position dispensing a quantity of solution contained within the solution container; A method comprising: 19. The method of claim 18, wherein a third stop member (242) prevents the rotatable plunger from rotating in the second direction about the first axis while the rotatable plunger is in the first position and in the second orientation. 20. The method of claim 18 or 19, wherein the first stop member is positioned on the rotatable plunger. 21. The method of any one of items 18-20, wherein a second stop member is positioned on the rotatable plunger. 22. The method of any one of items 18 to 21, wherein the solution dispensing device further comprises a housing (208) configured to be releasably connected to a solution container, the housing comprising a plunger through hole (236) configured to slidably receive a rotatable plunger and to enable the solution container to slidably receive the rotatable plunger. 23. The method of claim 22, wherein the first stop member is positioned on the housing. 24. The method of claim 22 or 23, wherein the second stop member is positioned on the housing. 25. The method of any one of items 22-24, wherein the first stop member has a first height, and the amount of solution dispensed when the rotatable plunger is slidably displaced from the first position to the second position is based at least in part on the first height. 26. The rotatable plunger includes a flange (226); a flange contacting the first stop member while the rotatable plunger is in the first position and in the first orientation to prevent the rotatable plunger from slidably displacing to the second position; 26. The method of any one of items 18 to 25, wherein the flange contacts the second stop member while the rotatable plunger is in the first position and first orientation to prevent the rotatable plunger from rotating about the first axis in the first direction. 27. The method of any one of items 18 to 26, wherein the solution dispensing device is configured to prevent the rotatable plunger from rotating about the first axis until the rotatable plunger is positioned in the first position. 28. The method according to any one of items 18 to 27, wherein the amount of solution dispensed when the rotatable plunger is slidably displaced from the first position to the second position is selected from the group consisting of 5 μL, 10 μL and 20 μL. 29. The method according to any one of items 18 to 28, wherein the solution container holds 100 μL to 1000 μL of solution. 30. The method according to any one of items 18 to 29, wherein the amount of solution dispensed when the rotatable plunger is slidably displaced from the first position to the second position is between 2.5% and 12.5% ​​of the solution contained in the solution container. 31. The method according to any one of items 18 to 30, wherein the solution comprises a vascular endothelial growth factor (VEGF) antagonist. 32. The method according to any one of items 18 to 31, wherein the solution comprises Beovu® (brolucizumab). 33. The method according to any one of items 18 to 32, wherein the solution comprises Eylea® (aflibercept). 34. The method according to any one of items 18 to 33, wherein the solution comprises Luxturna® (boretigene neparvovec). 35. The method according to any one of items 18 to 34, wherein the solution contains nucleic acids. 36. The method according to any one of items 18 to 35, for use in pediatric ophthalmic injections. 37. The method according to any one of items 18 to 36, for use in gene therapy.

Claims

1. A solution dispensing device, comprising: A rotatable plunger; a solution container having a first end configured to slidably receive the rotatable plunger and a second end configured to dispense a solution contained within the solution container, the solution dispensing device comprising: allowing the rotatable plunger to be slidably displaced along a first axis while in a first orientation to be positioned at a first position relative to the solution container; allowing the rotatable plunger to be slidably displaced along a first axis from the first position to a second position relative to the solution container while in a second orientation; It is configured as follows: the second position is closer to the second end of the solution container than the first position; a solution container, wherein slidable displacement of the rotatable plunger from the first position to the second position causes a quantity of the solution contained within the solution container to be dispensed; a first stop member configured to prevent the rotatable plunger from slidably displacing to the second position while the rotatable plunger is in the first position and in the first orientation; a second stop member configured to prevent the rotatable plunger from rotating in a first direction about the first axis while the rotatable plunger is in the first position and in the first orientation; a housing configured to be releasably connected to the solution container, the housing including a plunger throughbore configured to slidably receive the rotatable plunger and to allow the solution container to slidably receive the rotatable plunger; Equipped with the first stop member is positioned on a top surface of the housing, the first stop member protruding proximally from the top surface of the housing along the first axis. A device for dispensing a fixed amount of solution.

2. a third stop member configured to prevent the rotatable plunger from rotating in a second direction about the first axis while the rotatable plunger is in the first position and in the second orientation. The solution dispensing device of claim 1 further comprising:

3. 3. A solution dispensing device according to claim 1 or 2, wherein the first stop member is positioned on the rotatable plunger.

4. A solution dispensing device according to any one of claims 1 to 3, wherein the second stop member is positioned on the rotatable plunger.

5. The solution dispensing device of any one of claims 1 to 4, wherein the second stop member is positioned on an upper surface of the housing, and the second stop member protrudes proximally from the upper surface of the housing along the first axis.

6. 6. The solution dispensing device of claim 1, wherein the first stop member has a first height relative to the top surface of the housing, and the amount of the solution dispensed when the rotatable plunger is slidably displaced from the first position to the second position is based at least in part on the first height.

7. The solution dispensing device of claim 6 , wherein the second stop member has a second height relative to the top surface of the housing that is greater than the first height.

8. an exterior surface of the solution container including a clip receiving element; the housing includes a housing clip; A solution dispensing device according to any one of claims 1 to 7, wherein the housing clip is releasably connected to the clip receiving element.

9. 9. The solution dispensing device of claim 8, wherein the first end of the solution container includes a flange element, and the housing is configured to slidably receive the flange element when the housing clip is releasably connected to the clip receiving element.

10. the rotatable plunger includes a flange; the flange contacts the first stop member to prevent the rotatable plunger from slidably displacing to the second position while the rotatable plunger is in the first position and in the first orientation; A solution dispensing device according to any one of claims 1 to 9, wherein the flange contacts the second stop member to prevent the rotatable plunger from rotating about the first axis in the first direction while the rotatable plunger is in the first position and in the first orientation.

11. A solution dispensing device according to any one of claims 1 to 10, configured to prevent the rotatable plunger from rotating about the first axis until the rotatable plunger is positioned at the first position.

12. 12. A solution dispensing device according to any one of claims 1 to 11, wherein the amount of solution dispensed when the rotatable plunger is slidably displaced from the first position to the second position is selected from the group consisting of 5 μL, 10 μL and 20 μL.

13. 13. A solution dispensing device according to any one of claims 1 to 12, wherein the inner surface of the solution container is coated with a plasma enhanced chemical vapor deposition (PECVD) coating, the PECVD coating providing a smooth lubricious layer on the inner surface.

14. 14. The solution dispensing device of any one of claims 1 to 13, wherein the inner surface of the solution container is coated with a lubricant coating made from a PECVD process using octamethylcyclotetrasiloxane (OMCTS) as a precursor.

15. The solution dispensing device according to any one of claims 1 to 14, wherein the solution container is manufactured in accordance with ISO 14644 by a PECVD process using high frequency power consisting of silicon, carbon and oxygen under at least ISO class 8 conditions during operation and ISO class 7 conditions at rest.

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