Injection device and method for preparing an injection device for injection

Abstract

The present disclosure relates to an injection device (1) for setting and injecting a dose of a medicament, comprising:-a housing (10),-a medicament container (6) containing an injectable medicament (27), the medicament container (6) being sealed in a proximal direction (3) by a movable stopper (7) and comprising an outlet (61) towards a distal end (63),-a drive mechanism (8), and a drive mechanism (20) arranged inside the housing (10) and comprising a piston rod (20) extending in a longitudinal direction and operable to exert distally directed pressure on the stopper (7) in order to expel the dose of medicament through the outlet (61),-wherein in a pre-use configuration of the injection device (1), the piston rod (20) is driven by the drive mechanism (20). The piston rod (20) is in longitudinal and mechanically biased abutment with the stopper (7) prior to expelling a first dose of medicament and / or prior to a first use of the injection device (1).

Description

Technical Field

[0001] The present disclosure relates to the field of injection devices, in particular to the field of pen-type injectors for setting and injecting one or more doses of a medicament. In another aspect, the present disclosure relates to a method of preparing an injection device for injecting a medicament. Background Art

[0002] Drug delivery devices for setting and dispensing single or multiple doses of liquid medicaments are well known in the art per se. Typically, such devices have substantially similar uses to ordinary syringes.

[0003] Drug delivery devices such as pen-type injectors must meet many user-specific requirements. For example, in the case of patients suffering from chronic diseases such as diabetes, the patient may be physically weak and may also be visually impaired. Therefore, suitable drug delivery devices specifically intended for home medication need to be robust and should be easy to use. In addition, the manipulation and general handling of the device and its components should be clear and easy to understand. Such injection devices should provide for the setting and subsequent distribution of doses of equal or variable sizes. In addition, the dose setting and dose distribution procedures must be easy to operate and must be clear and unambiguous.

[0004] Patients with certain diseases may require a certain amount of medication to be injected via a pen-type syringe.

[0005] Some drug delivery devices or injection devices are capable of selecting variable-sized doses of medication and injecting a previously set dose. Other injection devices provide fixed dose setting and dispensing. In this case, the amount of medication that should be injected according to a given prescription schedule is always the same and does not change over time or cannot be changed.

[0006] Some injection devices are implemented as reusable injection devices, allowing users to replace medication containers (such as cartridges). Other injection devices are implemented as disposable injection devices. For disposable injection devices, it is intended that the entire injection device be discarded when the contents (i.e., medication) have been used up.

[0007] In the form of a cartridge widely used with, for example, a handheld injection device, for example, it comprises a tubular barrel sealed in the proximal direction by a movable stopper, piston or bung. The piston rod of the drive mechanism of such an injection device is configured to advance in the distal direction, thereby also pushing the bung in this direction so as to increase the fluid pressure inside the medicament container, which results in dispensing or injecting the medicament via a distally located outlet, which is typically in fluid communication with an injection needle.

[0008] Due to unavoidable manufacturing tolerances and / or assembly tolerances, axial play may occur, for example, between such a piston or stopper and the piston rod of a medicament container. Typically, before using the device for the first time, the end user must perform a so-called priming of the drive mechanism in order to ensure that an accurate amount of the medicinal product has been set in a predefined manner with the initial dose setting and subsequent dose dispensing steps. For this purpose, the user is typically instructed to set a dose of limited size with a dial to perform an initial priming jet or air jet, by which a limited amount of medicament can be expelled through the injection needle. After performing such a priming step or procedure, the device is then ready for use.

[0009] For some devices, such a priming procedure only has to be performed before the device in which the medicament container is assembled is used for the first time. Once the priming procedure has been performed, the injection device can be reused without having to perform such a supplementary priming procedure between each dosage injection procedure.

[0010] Nevertheless, some users tend to perform such priming before each repeated use of the injection device. Such repeated priming procedures are somewhat unnecessary and are accompanied by a waste of medicament. Finally, and in the case of priming procedures that are performed unnecessarily many times, there may not be a sufficient amount of medicament left in the medicament container to set and dispense the final dose. In the case of such incorrect or unintended use of the injection device, a significant risk of underdosing may arise.

[0011] Therefore, it is desirable to provide an improved injection device which allows an improved and simplified use thereof, in particular priming the device before performing a dose setting and injection procedure. In particular, the process of priming the injection device should be simplified for the end consumer or patient.

[0012] In one aspect, the present disclosure relates to an injection device for setting and injecting a dose of a medicament. The injection device includes a housing and a medicament container. The medicament container contains an injectable medicament. The medicament container is sealed toward the proximal direction by a movable stopper and further includes an outlet toward the distal end.

[0013] The injection device further comprises a drive mechanism, which is arranged inside the housing and comprises a piston rod extending in the longitudinal direction. The piston rod and / or the drive mechanism are operable to apply a distally directed pressure to the stopper so as to discharge the dose of the medicament through the outlet of the medicament container.

[0014] The injection device can be converted into a pre-use configuration. When in the pre-use configuration, the piston rod is in longitudinal and mechanically offset abutment with the bung. Thus, in the pre-use configuration, the drive mechanism is offset or pre-tensioned. Here, the piston rod is in offset and therefore pre-tensioned abutment with the bung of the medicament container. In practice and when in the pre-use configuration, any longitudinal tolerances and / or any longitudinal mechanical play of the drive mechanism are eliminated in such a way that an initial and distally directed displacement of the piston rod is irreversibly converted into a corresponding distally directed movement of the bung of the medicament container.

[0015] Typically, the injection device is in a pre-use configuration before a first dose of medicament is expelled and / or before the injection device is used for the first time.

[0016] For some examples, the injection device is subjected to transportation and / or storage when and as long as it is in the pre-use configuration, or in other words, the injection device is in the pre-use configuration and remains in the pre-use configuration at least during transportation and / or storage. When in the pre-use configuration, the drive mechanism or the entire drive train provided by the drive mechanism and longitudinally adjacent to the stopper of the medication container is longitudinally biased or longitudinally pre-tensioned without dispensing or expelling a portion of the injectable medicament through the outlet of the medication container. Therefore, in the pre-use configuration, the medication container is in a fully filled configuration, and the entire medicament initially filled or disposed inside the medication container is still located or contained inside the medication container.

[0017] For some examples, the medicine container includes a tubular barrel, which is sealed by a stopper toward the proximal longitudinal end of the barrel. The distal longitudinal end of the medicine container is provided with an outlet, which can be sealed by a seal (e.g., in the form of an elastomeric sealing disk). Here, the medicine container can be implemented as a cartridge, wherein the outlet is sealed by an elastomeric seal and is configured to be pierced or penetrated by a double-pointed injection needle.

[0018] Typically, and as long as the injection device is in the pre-use configuration, the seal at the outlet of the medicament container is unpunctured or unpenetrated. The seal is completely intact and has not been penetrated by any injection needle or similar piercing structure.

[0019] For the present injection device and in the case where the injection device is converted to the pre-use configuration before using the injection device, the priming step of the drive mechanism and / or the medicament container does not need to be or no longer has to be performed by the user of the injection device. When the injection device is in the pre-use configuration, the patient or user of the injection device can simply request that the needle assembly be attached to the outlet of the medicament container. The pressure level that eventually rises inside the medicament container (which may be due to the longitudinal offset abutment between the piston rod and the stopper) can then be relieved, thus resulting in a small amount (e.g., a few drops) of liquid medicament being eventually discharged through the outlet and therefore through the injection needle of the needle assembly. Despite this and when in the pre-use configuration, it is no longer necessary to perform a priming procedure or air injection separately in a user-induced manner.

[0020] When the injection device is dispensed to a patient or user in a pre-use configuration, and when the user or patient has properly attached the injection needle to the outlet of the medicament container, the increased fluid pressure inside the medicament container may induce the discharge of a small amount (e.g., a few drops) of liquid medicament.

[0021] In any case and due to the longitudinal and mechanically offset abutment between the piston rod and the bung, the drive mechanism or injection device is free of any longitudinal tolerances in the drive train of the drive mechanism, so that in the case of subsequent and first or initial setting and injection procedures using the drive mechanism, the set dose can be fully dispensed or injected.

[0022] Thus, for the currently proposed injection device, the priming, mechanical biasing or pre-tensioning of the drive mechanism can be performed at the end of the manufacture of the injection device or at the end of the assembly, for example by the pharmaceutical manufacturer, thereby bringing the piston rod into longitudinal and mechanically biased abutment with the bung of the cartridge. During transport and storage to the patient or customer, the injection device can remain in the pre-use configuration. Thus, and when the patient or user intends to use the injection device for the first time, it is no longer necessary to instruct the patient or user to perform or execute a separate priming procedure. For the end user or patient, it will only be necessary to correctly assemble the needle assembly to the housing and / or the outlet of the medicament container in order to convert the injection device from the pre-use configuration to the ready-to-use configuration.

[0023] According to another example and when in the pre-use configuration, the piston rod applies a distally directed pre-use pressure to the stopper. The pre-use pressure is greater than or equal to the drive pressure required to move the stopper in the distal direction so as to inject the dose of medicament.

[0024] When the pre-use pressure is applied to the stopper, the stopper may not move in the distal direction despite the fact that the pre-use pressure is greater than the drive pressure (which is required to move the stopper in the distal direction). Here, and as long as the injection device is in the pre-use configuration, the outlet of the medicament container can be sealed and remain sealed.

[0025] Due to the substantial incompressibility of, for example, a liquid medicament contained in the medicament container, applying a relatively large pre-use pressure to the stopper in the distal direction may have no substantial effect other than longitudinal compression of the stopper, which is governed by the elastic material of the stopper, resulting in the generation of increased pressure inside the medicament container.

[0026] It may be that only when an injection needle (eg a double-pointed injection needle) is attached to the outlet of the medicament container, that the pre-use pressure exerted by the piston rod on the bung of the medicament container results in a relatively small amount of medicament being dispensed through the outlet.

[0027] According to another example, the distal end of the medicament container is in longitudinal abutment with the stop face of the housing. Typically, the stop face of the housing is arranged at or near the distal end of the housing. The housing of the injection device may include a single or multiple housing parts. For multiple housing parts, the housing may include a main housing part, which is also denoted as the body forming the proximal housing part of the injection device. A further housing part of the injection device may provide a cartridge holder or cartridge retainer. It may form or constitute the distal housing part of the injection device.

[0028] The cartridge holder or cartridge retainer part of the housing of the injection device may include a mechanical connector at the distal end, which is complementarily shaped with the mating connector of the standardized needle assembly. The cartridge holder is sized and configured to accommodate a medicament container, such as a cartridge. The body of the housing is configured and sized to accommodate a drive mechanism. The proximal end of the cartridge holder may be detachably or non-detachably connectable or fastenable to the distal end of the body of the housing. Typically, and in the final stage of assembling the injection device, the cartridge or medicament container is inserted in the distal direction through the proximal end of the cartridge holder, and then the cartridge holder in which the cartridge or medicament container is assembled is connected and fixed to the distal end of the body. Due to the inevitable geometric tolerance or assembly tolerance of the numerous components of the injection device, a fairly loose fit may occur between the piston rod and the stopper and / or a longitudinal gap may occur between the proximal side of the stopper of the medicament container or cartridge and the distal end of the piston rod. Then and after mechanically securing the cartridge holder to the body of the injection device, the drive mechanism may be used to advance the piston rod in the distal direction until the piston rod reaches mechanically biased abutment with the bung, thereby converting the injection device into the pre-use configuration.

[0029] For some examples, the distally directed stop surface of the dose container (e.g., the distally facing shoulder portion of the dose container) can be in longitudinal abutment with the proximally facing stop surface of the complementary shape of the housing or cartridge holder. In this way, the dose container or cartridge is restrained in the distal direction relative to the housing or cartridge holder. Due to the longitudinally offset abutment between the stopper of the cartridge and the piston rod, the dose container is also longitudinally restrained relative to the housing of the injection device relative to the proximal direction.

[0030] According to another example and when in the pre-use configuration, the outlet of the medicament container is sealed and impenetrable to the medicament. In the pre-use configuration and as long as the injection device is in the pre-use configuration, the outlet remains sealed and also remains substantially impenetrable to the medicament. Here, applying a relatively high force or thrust in the distal direction to the stopper of the medicament container does not result in the discharge of the medicament, because the outlet of the medicament container is sealed and remains sealed.

[0031] The pre-use configuration may be eliminated or the injection device may be converted from the pre-use configuration to the ready-to-use configuration simply by attaching a needle assembly to the distally located outlet, thereby penetrating the seal of the medicament container by, for example, an injection needle.

[0032] According to another example and when the injection device is in the pre-use configuration, the outlet of the medicament container is not punctured and remains unpunctured. Here, the outlet may be covered or closed by a puncturable seal (e.g., an elastomeric sealing disk), which is also represented as or includes a rubber diaphragm. As long as the injection device is in the pre-use configuration, the seal is intact and is not punctured.

[0033] Conversion of the injection device from the pre-use configuration to the ready-to-use configuration may be accompanied by piercing the seal of the outlet port, for example by a double-pointed injection needle.

[0034] According to another example, the medicine container comprises a barrel of, for example, a tubular shape. The outlet of the medicine container is sealed by an elastomeric seal that can be penetrated by a needle. Here, the outlet of the medicine container is provided by the outlet of the barrel. Therefore, the elastomeric seal that can be penetrated by a needle seals and closes the outlet of the barrel of the medicine container. The barrel can have a substantially tubular shape. It can include a neck portion that is radially narrowed or radially contracted toward its distal end and therefore toward the outlet. For example, the outlet at the distal end of the barrel can include a crimping cap. Here, an elastomeric seal (for example, in the form of a pierceable sealing disk) is maintained and fixed to the head portion at the distal end of the barrel of the medicine container.

[0035] According to another example, the medicine container includes a seal that closes or seals the outlet of the medicine container. The seal is fixed to the distal end of the medicine container by a fixed cap. The fixed cap includes an outlet aperture to provide access to the pierceable portion of the seal. Typically, the pierceable portion of the seal is the radial center portion of the seal. The fixed cap can be a curled cap or a crimped cap that covers or encloses the distal free end of the barrel of the medicine container. The fixed cap can be made of a pliable material, such as a pliable metal sheet material, for example aluminum.

[0036] The fixed cap provides a liquid-tight and durable fixation of the pierceable seal to the outlet of the medicine container. In the same way and because the pierceable portion of the seal is uncovered and remains uncovered and is therefore accessible through the outlet orifice of the fixed cap, a direct path is provided, for example, so that a double-pointed injection needle penetrates the seal and thereby obtains a fluid transfer path to the interior of the medicine container. The seal, as provided and / or fixed at the outlet of the medicine container, may be elastically deformable.

[0037] According to other examples and when in use before configuration, the pierceable portion of the seal includes or forms a raised seal, which at least partially protrudes distally through the outlet orifice of the fixed cap. This raised seal may occur due to the pressure applied to the stopper before use. Here, the stopper may be subjected to longitudinal compression. Because the piston rod will be used before pressure is applied to the stopper, the stopper itself may also be subjected to a movement directed distally relative to the sidewall of the medicament container (for example, relative to the barrel of the container), thereby increasing fluid pressure and inducing the seal to bulge outwardly, due to the deformation of the outward bulge, the pierceable portion of the seal begins to protrude distally through the outlet orifice.

[0038] The generation of such an outwardly extending or outwardly protruding pierceable portion of the seal provides a user with visible or tactile feedback that the injection device is in a pre-use configuration. For some examples, the distal end of the housing of the injection device (e.g., the distal end of the cartridge holder) includes an aperture to receive the injection needle therethrough. If not palpable in the aperture of the cartridge holder or housing, the outwardly protruding sealing portion may be at least visible through this aperture.

[0039] By means of the at least partially and distally protruding raised sealing portion of the medicament container, a patient or user of the injection device can visually or tactilely check whether the injection device is in the intended pre-use configuration before a corresponding injection needle is attached to the distal end of the injection device.

[0040] According to another example and when in the pre-use configuration, the hydrostatic pressure inside the medication container is greater than the atmospheric pressure.Therefore, when in the pre-use configuration, the interior of the medication container is subjected to an increased pressure compared to the atmospheric pressure.

[0041] This increased pressure level may cause a raised sealing portion of the pierceable portion of the seal of the medicament container or cartridge to form or generate.

[0042] According to another example of the injection device and when in the pre-use configuration, the hydrostatic pressure inside the medicament container exceeds p times the atmospheric pressure, wherein p>1.1, p>1.2, p>1.3, p>1.4, p>1.5, p>1.6, p>1.7, p>1.8, p>1.9, p>2.0, p>2.1, p>2.2, or p>2.3. By such a pressure increase, a well-defined level of pre-tension can be obtained, which is sufficient to eliminate longitudinal tolerances and / or mechanical play in the injection device and the drive mechanism. On the other hand, the pressure increase is well below an upper threshold level, at which the mechanical structure of the injection device, the drive mechanism or the medicament container may be subject to mechanical damage.

[0043] According to another example and when in the pre-use configuration, the piston rod of the drive mechanism is in longitudinal abutment with the movable bung and the medicament container and applies a longitudinally directed pressure on the bung, which pressure is in the range between 10 kPa and 130 kPa. Thus, there may be a well-defined longitudinal or axial abutment between the piston rod and the bung, wherein the abutment pressure is in the range between 10 kPa and 130 kPa.

[0044] For some examples, the abutment pressure is in a range between 20 kPa and 100 kPa. For some examples, the abutment pressure is in a range between 40 kPa and 80 kPa. For some examples, the abutment pressure is in a range between 50 kPa and 70 kPa.

[0045] For further examples, the longitudinal abutment pressure between the piston rod and the stopper is greater than 10 kPa, greater than 20 kPa, greater than 30 kPa, greater than 40 kPa, greater than 50 kPa, greater than 60 kPa, greater than 70 kPa, greater than 80 kPa, greater than 90 kPa, greater than 100 kPa, greater than 110 kPa, or greater than 120 kPa.

[0046] The longitudinal abutment pressure between the piston and the piston rod can be adjusted depending on the type of medicament, in particular on the viscosity of the medicament and / or on the geometric dimensions or material properties of the medicament container and the stopper.

[0047] According to another example of the injection device and when in the pre-use configuration, the piston rod is in a starting position relative to the housing, which is distally offset compared to the initial position of the piston rod when the injection device is assembled or finally assembled. The piston rod can be easily converted from the initial piston rod position to or towards the pre-use position simply by performing a priming action on the drive mechanism without a needle attached.

[0048] Here, a dose of a predefined size, such as a dose of 1-5 units, can be set by the drive mechanism, and the corresponding dose can be virtually injected simply by performing a corresponding injection or dispensing procedure, thus causing the piston rod to perform a corresponding distally directed displacement according to the predefined size of the previously set dose. In this way, a relatively small dose size, such as 1, 2 or up to 5 international units of medicament, can be set, and the drive mechanism can then be triggered to inject such a dose, thereby causing the piston rod to move from the initial position towards and into a start-up or pre-use position, in which the piston rod enters into the above-mentioned longitudinal and mechanically biased abutment with the stopper. During this virtual injection procedure, the outlet of the medicament container is sealed and remains sealed, and the discharge of liquid medicament is effectively prevented.

[0049] In another aspect, the present disclosure relates to an injection system. The injection system comprises a package providing a receptacle for an injection device. The injection system further comprises an injection device as described above, which is arranged inside the receptacle in its pre-use configuration. The injection system (i.e., the package in which the injection device is disposed) may be intended for transporting and / or storing the injection device.

[0050] By keeping the injection device in its pre-use configuration inside the packaging, the user does not have to perform a separate priming procedure on the injection device before first use. Instead, and in order to convert the injection device from the pre-use configuration to the ready-to-use configuration, the user only has to attach or assemble a suitable needle assembly to the injection device. During or after attaching the needle assembly to the injection device, provision may be made for the proximal end of the double-pointed injection needle to extend through the aperture at the distal end of the injection device and penetrate the seal of the medicament container.

[0051] Due to the increased pre-use pressure inside the medicament container, a relatively small amount of medicament may be initially expelled during the needle attachment step.Since the piston rod of the drive mechanism is in longitudinal abutment with the bung and remains in longitudinal abutment, the injection device is in a ready-to-use configuration immediately after the needle assembly is attached.

[0052] The injection system comprises the injection device as described above.To the extent, all features, effects and benefits as described above in conjunction with the injection device are equally applicable to the injection system.

[0053] The packaging may include one of a blister pack, a foil pack or a cardboard pack. The packaging may contain a single or multiple injection devices. For some examples, the packaging is opaque. For other examples, the packaging or a portion thereof is translucent. Where the packaging is opaque, in particular to electromagnetic radiation within the visible spectrum and / or any one of the infrared or UV spectrum ranges, the medicament contained in the medicament container may be effectively protected from such radiation, thereby allowing the storage period or shelf life of the medicament located inside the medicament container to be extended.

[0054] For another example, the packaging is liquid-tight and / or gas-tight. Therefore, it can be impermeable to liquid substances, gases or gaseous substances. In this way, the injection device can be effectively protected from further environmental influences, such as humidity and / or dust.

[0055] In another aspect, the present disclosure also relates to a method for preparing an injection device for injecting a medicament. The method comprises the following steps: providing an injection device, typically providing an injection device as described above. Subsequently, the method comprises the following steps: converting the injection device into the above-mentioned pre-use configuration by moving the piston rod against the stopper of the medicament container in the distal direction.

[0056] Typically, the advancing movement of the piston rod causes the piston rod to apply a well-defined pressure to the stopper of the piston rod. For some examples, the advancement of the piston rod in the distal direction continues or is continued until a predefined pressure level has been reached between the piston rod and the stopper. For some examples, the advancing movement of the piston rod is pressure controlled. For other examples, the piston rod is advanced in the distal direction by a predefined distance, wherein the predefined distance is greater than the longitudinal tolerance margin between the distal end of the piston rod and the proximal end of the stopper when the injection device is finally assembled.

[0057] In this way and when the piston rod is advanced a predefined distance in distal direction after final assembly of the injection device it can be somehow ensured that the piston rod is not only in longitudinal abutment with the bung, but also that the piston rod applies a well-defined pressure above a predefined threshold to the bung.

[0058] The pressure threshold may be within a range that is higher than a drive pressure that is typically required to move the stopper in a distal direction to inject a dose of medicament when the injection needle is attached to the injection device and when medicament may be discharged through the injection needle through the outlet of the medicament container.

[0059] As described above and in the pre-use configuration, the medicament container is sealed at its outlet and remains sealed so as to prevent uncontrolled dispensing or expulsion of medicament from the medicament container.

[0060] The method of preparing an injection device is particularly intended to be performed or carried out by an injection device as described above.To the extent all features, effects and benefits as described above in connection with the injection device apply equally to the method of preparing an injection device.

[0061] The conversion of the injection device to the pre-use configuration can be performed by the pharmaceutical manufacturer. Here, the conversion of the injection device can be performed on-site by the pharmaceutical manufacturer as a final step after the final assembly of the injection device. The injection device in its pre-use configuration can be stored and shipped or transported to the consumer and / or patient. The consumer or patient then no longer has to perform a separate priming procedure. Instead, it will only be necessary to attach the needle assembly to the injection device in its pre-use configuration, thereby automatically converting the injection device to a ready-to-use configuration.

[0062] Converting the injection device to the pre-use configuration before packaging and shipping the injection device to a consumer or patient has the further benefit of securely securing the medicament container inside the housing of the injection device. In this way, the medicament container can be held inside the housing of the injection device without slack during transport and / or delivery. Furthermore and with a mechanically biased abutment between the piston rod and the stopper, the entire drive mechanism can be held in a somewhat pre-tensioned or pre-biased state, thereby inhibiting any movement of loosely fitting parts of the drive mechanism that might otherwise be subject to vibration or relatively minor movement during transport or delivery.

[0063] According to another example, the method of preparing the injection device further comprises the following steps: after converting the injection device into a pre-use configuration, attaching the needle assembly to the injection device. Typically, the needle assembly comprises a double-pointed injection needle having a proximal end and a distal end. The injection needle is pointed at both its distal end and its proximal end. When attaching the injection needle to the injection device, the proximal end of the injection needle penetrates a seal provided at the outlet of the medicament container.

[0064] According to a further example, when attaching the needle assembly to the injection device, the proximal end of the injection needle penetrates the seal of the medicament container.

[0065] Typically, the needle assembly includes a needle hub or needle holder, which may have a somewhat tubular shape. The needle hub typically includes a mating connector that is complementarily shaped with a connector at the distal end of the injection device. The connector and the mating connector may be implemented as an external thread and a matching internal thread, respectively. For other examples, the connector and the mating connector may form a snap-fit ​​connection or a bayonet connection.

[0066] The injection needle is typically removably fastened to the needle holder. By attaching the needle, in particular by attaching the needle holder to the distal end of the injection device, a fluid transfer connection is established between the injection needle and the interior of the medicament container. In this way and when the injection needle is attached to the injection device, the injection device can be converted into an instant configuration. Due to the mechanical bias abutment between the piston rod and the stopper, there may be increased hydrostatic pressure inside the medicament container before the needle assembly is attached. When the needle assembly is attached to the injection device, a pressure release may occur, thereby causing a limited amount of medicament to be discharged through the injection needle.

[0067] For a further example of the method and during attachment of the needle assembly to the injection device, a portion of the medicament is expelled through the injection needle due to a distally directed pre-use pressure applied by the piston rod to the bung in the pre-use configuration.

[0068] As long as the injection needle is not attached to the medicine container or injection device, applying the pre-use pressure to the stopper may cause the hydrostatic pressure inside the medicine container to increase. Due to the elastic properties of the stopper, applying the pre-use pressure directed to the distal side to the stopper may also cause the stopper to be compressed longitudinally. Since the liquid medicament contained in the medicine container is basically incompressible, the increased pressure applied to the stopper may cause the stopper to widen radially, thereby increasing the sealing function of the sealing ability of the stopper. Therefore, the longitudinal compression of the stopper may cause the stopper to widen radially, by which the stopper applies the increased radially outwardly directed pressure to the sidewall of the tubular barrel of the medicine container.

[0069] In this way and as long as the injection device is and remains in the pre-use configuration, an increased sealing capability of the bung may be provided.

[0070] According to another example, the needle assembly includes at least one of an outer needle cap and an inner needle cap covering the distal end of the injection needle. The outer needle cap or the inner needle cap is further configured to receive or capture the portion of the medicament that is expelled through the distal end of the injection needle during the process of attaching the needle assembly to the injection device when the injection device is in its pre-use configuration. Then, a portion of the medicament that is automatically expelled, for example due to the attachment of the needle assembly to the injection device, may be captured inside the outer needle cap or the inner needle cap, and the patient may not even notice the expulsion of the medicament.

[0071] Furthermore, during needle attachment and before the attachment of the needle assembly to the injection device is completed, a pressure release may occur, resulting in a small amount of medicament being expelled through the injection needle during the process of assembling the injection needle. Therefore, and when the final mutually assembled configuration of the needle assembly and the injection device is reached, the process of expelling a small amount of medicament from the medicament container may have been terminated.

[0072] According to a further example, by attaching a needle assembly to an injection device so as to convert the injection device into a ready-to-use configuration, the injection device may be converted or be converted from a pre-use configuration into a ready-to-use configuration, without requiring the user to perform a separate priming procedure, such as by dialing or setting a dose of a predefined size and by subsequently injecting that dose of medicament, but simply requiring the needle assembly to be attached to the injection device and ultimately capturing a specific amount of medicament expelled through the injection needle.

[0073] When the user then intends to use the injection device and removes the inner and / or outer needle cap, no drops of liquid will appear at the distal end of the injection needle. In this way, the patient or user of the injection device may not even be aware that a priming sequence or air injection has been performed somewhat automatically in order to compensate for or eliminate any tolerances or mechanical play in the drive train of the drive mechanism of the injection device.

[0074] According to another example, after being converted to the pre-use configuration, the injection device is arranged inside the package for transportation and / or storage. Thus, the method of preparing the injection device can be performed at the site of the pharmaceutical manufacturer. After the injection device is finally assembled, it can be converted to its pre-use configuration. Thereafter, the injection device can be packaged or wrapped inside the package, thereby forming an injection system.

[0075] The end user or patient may proceed with the method of preparing the injection device. Here, the injection device may be unfolded or released from the packaging and the needle assembly may be appropriately attached to the injection device. As a further optional method step, at least one of the outer needle cap and the inner needle cap may be detached from the needle assembly after the needle assembly has been attached and secured to the injection device. The injection device is then in a ready-to-use configuration in which the user may then set and inject single or multiple doses of the medicament.

[0076] Since a user-controlled priming procedure is not intended for the present injection device, and since the user is not at all instructed to set a dose and then trigger an injection procedure for the purpose of priming such a redundant and potentially wasteful dispensing procedure of medicament between repeated dose injection procedures, potential misuse of the injection device can be effectively avoided.

[0077] Generally, the scope of the disclosure is defined by the content of the claims. The disclosure is not limited to specific embodiments or examples, but includes any combination of elements of different embodiments or examples. To the extent possible, the disclosure covers any combination of claims and any technically feasible combination of features disclosed in combination with different examples or embodiments.

[0078] In the present context, the term 'distal' or 'distal end' relates to the end of the injection device facing the injection site of a human or animal. The term 'proximal' or 'proximal end' relates to the opposite end of the injection device, which is farthest from the injection site of a human or animal.

[0079] The terms "drug" or "medicament" are used synonymously herein and describe a pharmaceutical preparation comprising one or more active pharmaceutical ingredients or a pharmaceutically acceptable salt or solvate thereof and optionally a pharmaceutically acceptable carrier. In the broadest sense, an active pharmaceutical ingredient ("API") is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used to treat, cure, prevent, or diagnose disease or to otherwise enhance physical or mental health. A drug or medicament may be used for a limited duration, or periodically for a chronic disorder.

[0080] As described below, a drug or medicament may include at least one API or a combination thereof in various types of formulations for treating one or more diseases. Examples of APIs may include small molecules (having a molecular weight of 500 Da or less); polypeptides, peptides, and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double-stranded or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids (e.g., antisense DNA and RNA), small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into a molecular delivery system (e.g., a vector, a plasmid, or a liposome). Mixtures of one or more drugs are also contemplated.

[0081] The drug or medicament can be included in a primary package or "drug container" suitable for use with a drug delivery device. The drug container can be, for example, a cartridge, a syringe, a reservoir or other solid or flexible vessel, which is configured to provide a suitable chamber for storing (for example, short-term or long-term storage) one or more drugs. For example, in some cases, the chamber can be designed to store the drug for at least one day (for example, 1 day to at least 30 days). In some cases, the chamber can be designed to store the drug for about 1 month to about 2 years. Storage can occur at room temperature (for example, about 20 ° C) or refrigerated temperature (for example, about -4 ° C to about 4 ° C). In some cases, the drug container can be or can include a dual-chamber cartridge, which is configured to store two or more components (for example, API and diluent or two different drugs) of the pharmaceutical preparation to be applied separately, and one is stored in each chamber. In such a case, the two chambers of the dual-chamber cartridge can be configured to allow mixing between two or more components before and / or during distribution to the human or animal body. For example, the two chambers can be configured so that they are in fluid communication with each other (e.g., through a conduit between the two chambers) and allow the two components to be mixed when the user needs before dispensing. Alternatively or in addition, the two chambers can be configured to allow mixing when the components are dispensed into the human or animal body.

[0082] The drugs or agents contained in the drug delivery devices as described herein can be used to treat and / or prevent many different types of medical disorders. Examples of obstacles include, for example, diabetes or complications associated with diabetes (e.g., diabetic retinopathy), thromboembolic disorders (e.g., deep vein or pulmonary thromboembolism). Other examples of obstacles are acute coronary syndrome (ACS), angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs are examples as described in the following manuals: such as Rote Liste 2014 (e.g., but not limited to, main group 12 (antidiabetic drugs) or 86 (oncology drugs)), and Merck Index (Merck Index) (15th edition).

[0083] Examples of APIs for treating and / or preventing type 1 or type 2 diabetes or complications associated with type 1 or type 2 diabetes include insulin (e.g., human insulin, or human insulin analogs or derivatives); glucagon-like peptide (GLP-1), GLP-1 analogs or GLP-1 receptor agonists, or analogs or derivatives thereof; dipeptidyl peptidase-4 (DPP4) inhibitors, or pharmaceutically acceptable salts or solvates thereof; or any mixtures thereof. As used herein, the terms "analogs" and "derivatives" refer to polypeptides having a molecular structure that can be derived from the structure of a naturally occurring peptide (e.g., the structure of human insulin) in form by deleting and / or exchanging at least one amino acid residue present in a naturally occurring peptide and / or by adding at least one amino acid residue. The added and / or exchanged amino acid residues can be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogs are also referred to as "insulin receptor ligands." In particular, the term "derivative" refers to a polypeptide having a molecular structure that can be formally derived from the structure of a naturally occurring peptide (e.g., the structure of human insulin), wherein one or more organic substituents (e.g., fatty acids) are conjugated to one or more of the amino acids. Alternatively, one or more amino acids present in the naturally occurring peptide may have been deleted and / or replaced by other amino acids (including non-encodable amino acids), or amino acids (including non-encodable amino acids) have been added to the naturally occurring peptide.

[0084] Examples of insulin analogs are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin, wherein the proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala, and wherein, in position B29, Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0085] Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29)(N-tetradecanoyl)-des(B30) human insulin (insulin detemir, ); B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoylLysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-γ-glutamyl)-des(B30) human insulin, B29-N-ω-carboxypentadecanoyl-γ-L-glutamyl-des(B30) human insulin (degludec insulin, ); B29-N-(N-lithocholyl-γ-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.

[0086] Examples of GLP-1, GLP-1 analogs and GLP-1 receptor agonists are e.g. lixisenatide Exendin-4 A 39-amino acid peptide produced by the salivary glands of the Gila monster), liraglutide Semaglutide, Taspoglutide, Albiglutide Dulaglutide rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C (Efp eglenatide)), HM-15211, CM-3, GLP-1Eligen, ORMD-0901, NN-9423, NN-9709, NN-9924, NN- 9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, M AR-701, MAR709, ZP-2929, ZP-3022, ZP-DI-70, TT-401 (Pegapamodtide), BHM-034. MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Telportide (LY3298176), Bamadutide (SAR425899), Exenatide-XTEN, and Glucagon-Xten.

[0087] Examples of oligonucleotides are: Cholesterol reducing antisense therapeutics for the treatment of familial hypercholesterolemia or RG012 for the treatment of Alport syndrome. Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0088] Examples of hormones include pituitary hormones or hypothalamic hormones or regulatory activity peptides and their antagonists, such as gonadotropins (follicle-stimulating hormone, luteinizing hormone, chorionic gonadotropin, tocopherol), somatropine (growth hormone), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin and goserelin.

[0089] Examples of polysaccharides include glucosaminoglycanes, hyaluronic acid, heparin, low molecular weight heparin or ultra low molecular weight heparin or derivatives thereof, or sulfated polysaccharides (e.g., polysulfated forms of the polysaccharides mentioned above), and / or pharmaceutically acceptable salts thereof. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan GF 20 It is a sodium hyaluronate.

[0090] As used herein, the term "antibody" refers to an immunoglobulin molecule or its antigen binding portion. Examples of antigen binding portions of immunoglobulin molecules include F (ab) and F (ab ') 2 fragments, which retain the ability to bind antigens. The antibody can be a polyclonal antibody, a monoclonal antibody, a recombinant antibody, a chimeric antibody, a deimmunized antibody or a humanized antibody, a fully human antibody, a non-human (e.g., mouse) antibody or a single-chain antibody. In certain embodiments, the antibody has effector functions and can fix complement. In certain embodiments, the ability of the antibody to bind to Fc receptors is reduced or there is no such ability. For example, the antibody can be an isotype or subtype, an antibody fragment or a mutant, which does not support binding to Fc receptors, for example, its Fc receptor binding region has been mutated or missing. The term antibody also includes antigen binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or dual variable region antibody-like binding proteins with cross-binding region orientation (CODV).

[0091] The term "fragment" or "antibody fragment" refers to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy chain and / or light chain polypeptide), which does not include a full-length antibody polypeptide, but still includes at least a portion of a full-length antibody polypeptide that can bind to an antigen. Antibody fragments can include cleavage portions of full-length antibody polypeptides, but the term is not limited to such cleavage fragments. Antibody fragments useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments (e.g., bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., double-chain antibodies, three-chain antibodies, four-chain antibodies)), monovalent or multivalent antibody fragments (e.g., bivalent, trivalent, tetravalent and multivalent antibodies), mini antibodies, chelated recombinant antibodies, three antibodies or double antibodies, intracellular antibodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies and antibodies comprising VHH. Additional examples of antigen-binding antibody fragments are known in the art.

[0092] The term "complementarity determining region" or "CDR" refers to short polypeptide sequences within the variable region of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term "framework region" refers to amino acid sequences within the variable region of both heavy and light chain polypeptides that are not CDR sequences and are primarily responsible for maintaining the correct positioning of the CDR sequences to permit antigen binding. Although the framework region itself is typically not directly involved in antigen binding as known in the art, certain residues within the framework region of certain antibodies may be directly involved in antigen binding or may affect the ability of one or more amino acids in the CDR to interact with the antigen.

[0093] Examples of antibodies are anti-PCSK-9 mAb (eg, Alirocumab), anti-IL-6 mAb (eg, Sarilumab), and anti-IL-4 mAb (eg, Dupilumab).

[0094] Pharmaceutically acceptable salts of any API described herein are also contemplated for use in a drug or medicament in a drug delivery device. Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts.

[0095] Those skilled in the art will appreciate that modifications (additions and / or removals) may be made to the various components, formulations, devices, methods, systems and embodiments of the API described herein without departing from the overall scope and spirit of the invention, and that the invention encompasses such modifications and any and all equivalents thereof.

[0096] An example drug delivery device may involve a needle-based injection system as described in Table 1, Section 5.2 of ISO 11608-1:2014(E). As described in ISO 11608-1:2014(E), needle-based injection systems can be broadly divided into multi-dose container systems and single-dose (partially or completely emptied) container systems. The container may be a replaceable container or an integrated non-replaceable container.

[0097] As further described in ISO 11608-1:2014(E), a multi-dose container system may involve a needle-based injection device with a replaceable container. In such a system, each container holds multiple doses, the sizes of which may be fixed or variable (pre-set by the user). Another multi-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In such a system, each container holds multiple doses, the sizes of which may be fixed or variable (pre-set by the user).

[0098] As further described in ISO 11608-1:2014 (E), a single-dose container system may relate to a needle-based injection device with a replaceable container. In one example of such a system, each container holds a single dose, thereby discharging the entire deliverable volume (completely emptying). In another example, each container holds a single dose, thereby discharging a portion of the deliverable volume (partially emptying). As also described in ISO 11608-1:2014 (E), a single-dose container system may relate to a needle-based injection device with an integrated non-replaceable container. In one example of such a system, each container holds a single dose, thereby discharging the entire deliverable volume (completely emptying). In another example, each container holds a single dose, thereby discharging a portion of the deliverable volume (partially emptying). BRIEF DESCRIPTION OF THE DRAWINGS

[0099] In the following, examples of injection devices and methods of preparing an injection device for injection will be described in more detail by referring to the accompanying drawings, in which:

[0100] Figure 1 schematically illustrates a longitudinal section through an example of an injection device,

[0101] Figure 2 shows the distal end of the medicament container when the injection device is in a pre-use configuration,

[0102] Figure 3 The needle assembly is shown after being attached to the injection device. Figure 2 medicine container,

[0103] Figure 4 Display of injection device and needle assembly,

[0104] Figure 5 - is a further illustration of the injection device, wherein the cartridge holder is detached from the body of the injection device,

[0105] Figure 6 is a flow chart of a method of preparing an injection device for injection of a medicament, and

[0106] Figure 7 An injection device is shown arranged in a package. DETAILED DESCRIPTION

[0107] like Figure 1 , Figure 4 and Figure 5 The injection device 1 shown in is a pre-filled disposable injection device, which includes a housing 10 to which a needle assembly 15 can be attached. The needle assembly 15 includes a double-pointed injection needle 19. The needle 19 is protected by an inner needle cap 16 and an outer needle cap 17 or a protective cap 18, which is configured to enclose and protect the distal section of the housing 10 of the injection device 1. The housing 10 may include and form a main housing portion configured to accommodate a drive mechanism 8. The injection device 1 may further include a distal housing component represented as a cartridge holder 14. The cartridge holder 14 may be permanently or releasably connected to the main housing 10. The cartridge holder 14 is typically configured to accommodate a medicament container 6, which is, for example, implemented as a so-called cartridge filled with a liquid medicament.

[0108] The cartridge or medicament container 6 comprises a cylindrical or tubular barrel 25 which is sealed in the proximal direction 3 by a bung 7 located inside the barrel 25. The bung 7 is displaceable in the distal direction 2 relative to the barrel 25 of the medicament container 6 by a piston rod 20. The distal end of the medicament container 6 is sealed by a pierceable seal 26 which is configured as a septum and which can be pierced by a proximally directed pointed end 67 of an injection needle 19.

[0109] The needle assembly 15 comprises a needle hub 70 comprising a mating connector shaped complementarily to a connector 28 provided at the distal end of the housing 10 or cartridge holder 14. For the example shown presently, the connector 28 comprises a threaded socket having an external thread shaped complementarily to an internal thread provided at or in a side wall of the needle hub 70. In this way, the needle assembly 15 can be attached to and detached from the distal end of the injection device 1 by tightening or loosening.

[0110] By attaching the needle assembly 15 to the distal end of the cartridge holder 14 , the seal 26 of the medicament container 6 is penetrated by the injection needle 19 , thereby establishing a fluid transfer path to the interior of the medicament container 6 .

[0111] When the injection device 1 is configured to administer, for example, human insulin, the dose set by the dose dial 12 at the proximal end of the injection device 1 may be displayed in so-called international units (IU, where 1 IU is the biological equivalent of approximately 45.5 μg pure crystalline insulin (1 / 22 mg)).

[0112] like Figure 1 and Figure 4 As further shown in FIG. 1 , the housing 10 includes a dose window 13, which may be in the form of an aperture in the housing 10. The dose window 13 permits a user to view a limited portion of the number sleeve 50 that is configured to move when the dose dial 12 is rotated to provide a visual indication of the currently set dose. During setting and / or dispensing or expelling a dose, the dose dial 12 rotates on a spiral path relative to the housing 10 when it is rotated.

[0113] The injection device 1 can be configured so that turning the dose knob 12 causes a mechanical click to provide acoustic feedback to the user. The number sleeve 50 mechanically interacts with the piston in the medicament container 6. When the needle 19 pierces the skin portion of the patient, and when the trigger 11 or the injection button is pushed, the dose displayed in the display window 13 will be ejected from the injection device 1. When the needle 19 of the injection device 1 remains in the skin portion for a certain time after pushing the trigger 11, in fact, most of the dose is injected into the patient. The ejection of a dose of the medicament 27 may also cause a mechanical click, however, the mechanical click is different from the sound produced when the dose dial 12 is used.

[0114] In this embodiment, during delivery of the dose of medicament, the dose dial 12 is rotated to its initial position with axial movement (ie, not rotation) and the number sleeve 50 is rotated to return to its initial position, for example to display a dose of zero units.

[0115] The injection device 1 may be used for several injection procedures until the medicament container 6 becomes empty or the expiration date of the medicament in the injection device 1 is reached (eg 28 days after first use).

[0116] like Figure 1The ejection or drive mechanism 8 shown in more detail in Figure 1 comprises numerous mechanically interacting parts. The flange-shaped support of the housing 10 comprises a threaded axial through-opening threadedly engaged with a first thread or distal thread 22 of the piston rod 20. The distal end of the piston rod 20 comprises a bearing 21 on which a pressure foot 23 freely rotates with the longitudinal axis of the piston rod 20 as the axis of rotation. The pressure foot 23 is configured to axially abut against a thrust receiving surface facing the proximal side of the stopper 7 of the medication container 6. During the dispensing action, the piston rod 20 rotates relative to the housing 10, thereby experiencing a distally directed propulsion movement relative to the housing 10 and therefore relative to the barrel 25 of the medication container 6. As a result, due to the threaded engagement of the piston rod 20 with the housing 10, the stopper 7 of the medication container 6 is displaced a well-defined distance in the distal direction 2.

[0117] The piston rod 20 is further provided at its proximal end with a second thread 24. The distal thread 22 and the proximal thread 24 are of opposite hand directions.

[0118] A drive sleeve 30 is further provided, which has a hollow interior to receive the piston rod 20. The drive sleeve 30 comprises an internal thread threadedly engaged with the proximal thread 24 of the piston rod 20. Furthermore, the drive sleeve 30 comprises an external threaded section 31 at its distal end. The threaded section 31 is axially limited between a distal flange portion 32 and another flange portion 33 located at a predefined axial distance from the distal flange portion 32. Between the two flange portions 32, 33, a last dose limiter 35 in the form of a semicircular nut is provided, which has an internal thread cooperating with the threaded section 31 of the drive sleeve 30.

[0119] The last dose limiter 35 further comprises a radial recess or protrusion at its outer circumference to engage with a recess or protrusion of a complementary shape at the inner side of the side wall of the housing 10. In this way, the last dose limiter 35 is splined to the housing 10. Rotation of the drive sleeve 30 in the dose increment direction 4 or clockwise during a continuous dose setting procedure causes the last dose limiter 35 to be cumulatively axially displaced relative to the drive sleeve 30. An annular spring 40 is further provided, which is in axial abutment with the proximal surface of the flange portion 33. In addition, a tubular clutch 44 is provided. At a first end, the clutch 44 is provided with a series of circumferentially directed saw teeth. The radially inwardly directed flange is positioned toward the second opposite end of the clutch 44.

[0120] Furthermore, a dose dial sleeve is provided, which is also indicated as a number sleeve 50. The number sleeve 50 is arranged outside the spring 40 and the clutch 44 and is located radially inside the housing 10. A spiral groove 51 is provided around the outer surface of the number sleeve 50. The housing 10 is provided with a dose window 13, through which a portion of the outer surface of the number 50 can be seen. The housing 10 is further provided with a spiral rib at the inner side wall portion, which spiral rib will be seated in the spiral groove 51 of the number sleeve 50. A first stopper and a second stopper are provided on the housing 10 to limit a dose setting procedure during which the number sleeve 50 rotates in a spiral motion relative to the housing 10.

[0121] A dose dial 12 in the form of a dose dial fixture is arranged around the outer surface of the proximal end of the number sleeve 50. The outer diameter of the dose dial 12 typically corresponds to and matches the outer diameter of the housing 10. The dose dial 12 is fixed to the numbers 50 to prevent relative movement therebetween. The dose dial 12 is provided with a central opening.

[0122] The trigger 11 (also indicated as a dose button) is substantially T-shaped. It is provided at the proximal end of the injection device 10. The stem of the trigger 11 extends through an opening in the dose dial 12, through the inner diameter of an extension of the drive sleeve. The trigger 11 is retained for limited axial movement in the drive sleeve 30 and against rotation relative thereto. The head of the trigger 11 is generally circular. A trigger sidewall or skirt extends from the periphery of the head and is further adapted to be seated in a proximally accessible annular recess of the dose dial 12.

[0123] To dial a dose, the user rotates the dose dial 12. With the spring 40 also acting as a clicker and the clutch 44 engaged, the drive sleeve 30, the spring or clicker 40, the clutch 44 and the number sleeve 50 rotate with the dose dial 12. Audible and tactile feedback of the dialed dose is provided by the spring 40 and the clutch 44. Torque is transmitted through the saw teeth between the spring 40 and the clutch 44. The spiral groove 51 on the number sleeve 50 and the spiral groove in the drive sleeve 30 have the same lead. This allows the number sleeve 50 to extend from the housing 10 and the drive sleeve 30 so that the piston rod 20 climbs at the same rate. At the limit of travel, the radial stop on the number sleeve 50 engages with the first stop or the second stop provided on the housing 10 to prevent further movement in the dose increment direction 4. Due to the opposite direction of the integral thread and the driven thread on the piston rod 20, the rotation of the piston rod 20 is prevented.

[0124] The last dose limiter 35 keyed to the housing 10 is advanced along the threaded section 31 by rotation of the drive sleeve 30. When the final dose dispensing position is reached, a radial stop formed on the surface of the last dose limiter 35 abuts against a radial stop on the flange portion 33 of the drive sleeve 30, thereby preventing both the last dose limiter 35 and the drive sleeve 30 from further rotation.

[0125] If the user inadvertently dials more than the desired dose, the injection device 1 configured as a pen injector allows the dose to be dialed down without dispensing the medicament from the medicament container 6. To do this, the dose dial 12 is simply reversed. This causes the system to act in reverse. The flexible arm of the spring or clicker 40 then acts as a ratchet that prevents the spring 40 from rotating. The torque transmitted through the clutch 44 causes the saw teeth to ride on each other to produce a click corresponding to the dose reduction amount dialed. Typically, the saw teeth are arranged so that the circumferential extent of each saw tooth corresponds to a unit dose.

[0126] When the desired dose has been dialed, the user can dispense the set dose simply by pressing the trigger 11. This displaces the clutch 44 axially relative to the number sleeve 50, causing its dog teeth to disengage. However, the clutch 44 remains rotationally keyed to the drive sleeve 30. The number sleeve 50 and the dose dial 12 are now free to rotate according to the helical groove 51.

[0127] The axial movement deforms the flexible arms of the spring 40 to ensure that the serrations are not overhauled during dispensing. This prevents the drive sleeve 30 from rotating relative to the housing 10, although it is still free to move axially relative to the housing. The deformation is then used to push the spring 40 and the clutch 44 backward along the drive sleeve 30 to restore the connection between the clutch 44 and the number sleeve 50 when the distally directed dispensing pressure is removed from the trigger 11.

[0128] The longitudinal axial movement of the drive sleeve 30 causes the piston rod 20 to rotate through the through opening of the support of the housing 10, thereby advancing the bung 7 in the cartridge 6. Once the dialed dose has been dispensed, the number sleeve 50 is prevented from further rotation by contact of at least one stop extending from the dose dial 12 with at least one corresponding stop of the housing 10. The zero dose position may be determined by abutment of one of the axially extending edges or stops of the number sleeve 50 with at least one or several corresponding stops of the housing 10.

[0129] During dose setting and when the drive mechanism 8 or the dose setting mechanism 9 is in dose setting mode, the drive sleeve 30 rotates in unison with the dose dial 12 and the number sleeve 50. The drive sleeve 30 is threadedly engaged with the piston rod 20, which is stationary with respect to the housing 10 during dose setting. Thus, the drive sleeve 30 is subjected to a screwing or spiral motion during dose setting. When the dose dial is rotated in the dose incrementing direction 4 (e.g., in a clockwise direction), the drive sleeve 30 starts to travel in the proximal direction. In order to adjust or correct the size of the dose, the dose dial 12 can be rotated in the opposite direction, thus rotating in the dose decrementing direction 5 (e.g., counterclockwise).

[0130] The expelling mechanism or drive mechanism 8 as described above is only exemplary for one of a variety of drive mechanisms configured in different ways that can be implemented in disposable pen injectors in general. The drive mechanism as described above is explained in more detail in, for example, WO 2004 / 078239 A1, WO 2004 / 078240 A1 or WO 2004 / 078241 A1, the entire contents of which are incorporated herein by reference.

[0131] As from Figure 1 As will be further apparent, the distal end of the cartridge holder 14 comprises a proximally directed stop face 54, for example on the inner side of the end face of the cartridge holder 14. The end face of the cartridge holder 14 may be provided with a central aperture 55. In this way and when a needle assembly 15 having a double pointed injection needle 19 is attached, the proximal end 67 of the injection needle 19 may pass through the aperture 55 and may penetrate a seal 26 as provided at the outlet 61 of the medicament container 6.

[0132] For the example currently shown, the medicament container 6 is implemented as a cartridge. The medicament container 6 comprises a tubular barrel 25. The barrel 25 comprises a shoulder portion 66 that radially narrows towards the distal end 63, the shoulder portion extending into a head portion 69 arranged at the free distal end 63 of the barrel 25. The outlet 61 of the medicament container 6 is covered and / or sealed by a pierceable seal 26, which can be fixed to the head portion 69 by a fixing cap 60. The fixing cap 60 can include or form a crimping cap that provides a form fit of the fixing cap 60 and the seal 26 to the distal end 63 of the barrel 25. The fixing cap 60 comprises a central outlet orifice 62, through which the proximal end 67 of the injection needle 15 can be guided in order to pierce or penetrate the seal 26, as shown in FIG. Figure 3 As shown in .

[0133] like Figure 1The injection device 1 shown in the figure can be in a pre-use configuration as defined above. In the pre-use configuration, the piston rod 20 and / or the pressure foot 23 are in longitudinal and mechanically biased abutment with the bung 7 of the medicament container 6. The medicament container 6 is retained inside the cartridge holder 14 by the longitudinal abutment of the distal end 63 of the medicament container 6 with the proximal stop surface 54 of the cartridge holder 14. Additionally or alternatively, the shoulder portion 66 of the medicament container 6 is in longitudinal distal abutment with a proximal stop surface of a complementary shape as provided on the inner side of the cartridge holder 14.

[0134] Due to the longitudinal abutment between the pressure foot 23 and the proximal end of the bung 7 , the medicament container 6 is restrained and / or fixed inside the housing 10 or the cartridge holder 14 towards the proximal direction 3 .

[0135] When the final assembled configuration of the injection device 1 is reached, i.e. when the cartridge holder 14 and the medicament container 6 located therein are fixed or attached to the body 10 of the injection device 1, as shown in FIG. Figure 5 As schematically illustrated in , a mutual abutment configuration between the bung 7 and the piston rod 20 may have been obtained. However, when reaching the final assembly configuration and during assembly of the injection device, applying substantial and distally directed pressure to the bung 7 of the medicament container 6 is generally avoided.

[0136] Now and for the present injection device 1 , a dedicated step is provided for converting the injection device 1 into the pre-use configuration by moving the piston rod 20 in the distal direction 2 against the bung 7 until a well-defined mechanically biased abutment with the bung 7 is obtained.

[0137] When the pre-use configuration is reached, the piston rod 20 and / or if the pressure foot 23 applies a distally directed pre-use pressure to the bung 7, which is counteracted by the abutment of the distal end 63 or shoulder portion 66 with the complementary shaped proximally facing stop surface 54 of the cartridge holder 14. The pre-use pressure applied to the bung 7 is typically greater than or equal to the drive pressure that is normally required to move the bung in the distal direction when the injection needle 19 has unimpeded access to the interior of the medicament container 6 in order to inject the dose of medicament. In this way and when the pre-use configuration is reached, the drive train or drive mechanism 8 and the medicament container 6 are in a pre-tensioned or biased state.

[0138] In the pre-use configuration, the distal end 63 of the medicament container 6 and thus the outlet 61 is not connected to the needle assembly 15 and remains unconnected thereto. Due to the increased pressure level inside the medicament container, the elastomeric seal 26, in particular the central portion of the seal 26 located at or overlapping the outlet aperture 62 of the fixed cap 60, may undergo an outward bulge or deformation that projects distally, thus resulting in the formation of a corresponding outwardly and distally extending bulge 64 of the seal 26. Now and in order to convert the injection device 1 from the pre-use configuration to the ready-to-use configuration, it is intended to attach the needle assembly 15 to the distal end of the injection device 1.

[0139] During and after the needle assembly 15 is attached to the cartridge holder 14, the proximal end 67 of the injection needle 19 will penetrate the seal 26, as shown in FIG. Figure 3 As a result and due to the increase in fluid pressure inside the medicament container, there may be a pressure release in the medicament container 6 as soon as the proximal end 67 crosses the seal 26. The pressure release is accompanied by the discharge of a certain amount of medicament through the injection needle 19.

[0140] Therefore, during the needle assembly process, a few drops may be expelled from the distal end 68 of the injection needle 19. As a result and due to the pressure release, the raised portion 64 of the seal 26 may relax into the initial non-biased state 64', such as Figure 3 The elastic return movement of the seal 26 from the outwardly extended ridge 64 toward the non-biased or relaxed state 64' is accompanied by a slight reduction in the available storage space for liquid medicament inside the medicament container 6. This reduction in storage space may also help to expel a limited amount of medicament through the injection needle 19 when the needle is attached.

[0141] When the needle assembly is attached and secured to the injection device 1, the amount of medicament that may be expelled due to the pressure release during the attachment of the injection needle to the injection device may be captured in the inner needle cap 16 and / or the outer needle cap 17, which are attached to the needle assembly 15. In this way and due to the needle caps 16, 17, the end user or patient may not be aware of the pressure release action when the needle assembly is attached. The amount of medicament expelled during the attachment of the needle may be captured quite neatly in the inner needle cap 16 and / or the outer needle cap 17. In the final step of preparing the injection device for an injection procedure, the needle caps 16, 17 will have to be removed.

[0142] When the injection needle has penetrated the seal 26 during the assembly process of the injection needle 15, the conversion of the injection device from the pre-use configuration to the ready-to-use configuration has begun. Figure 3 , the final attachment position of the needle assembly 15 to the injection device 1 and / or the medicament container 6 is schematically shown. Figure 3As indicated in , and when reaching the final assembled position, the proximal end 67 of the injection needle 19 is located at a well-defined longitudinal distance from the inner surface of the seal 26 .

[0143] During the attachment process of the needle assembly 15 to the injection device 1, there will be sufficient time for the pressure release action as described above to take place. To some extent and immediately after the attachment of the injection needle 19 to the injection device 1 has been completed, the pressure release has effectively terminated and the end user may not even be aware of the pressure release action induced by the injection needle attachment.

[0144] exist Figure 6 In the flowchart of FIG. 1 , numerous steps of a method of preparing an injection device 1 are schematically shown. At a first step 100, an injection device 1 as described herein is provided. The injection device 1 may be implemented as a pen-type injector of a disposable or reusable type. The injection device 1 may be implemented entirely mechanically or even electromechanically. For some examples, the injection device 1 comprises a mechanical energy storage device, such as a spring, which is initially biased and / or biased by and / or during setting a dose.

[0145] For other examples, the dispensing force for advancing the piston rod 20 in the distal direction 2 for the purpose of injecting a dose is completely provided by the user of the device 1. For other examples, the mechanical energy storage device provides at least a part of the driving force during an injection procedure.

[0146] In a subsequent step 102, the injection device 1 is converted into a pre-use configuration. In step 102, the piston rod 20 of the drive mechanism 8 is advanced in the distal direction 2 so as to obtain a longitudinal and mechanically biased abutment with the bung 7 of the medicament container 6. For some examples, the piston rod 20 is advanced by a predefined distance relative to the housing 10 and / or relative to the medicament container 6 in a default manner.

[0147] For other examples, the advancement movement may be pressure controlled. Here, a pressure sensing arrangement may be provided, by which the abutment pressure between the stopper 7 and the piston rod 20 may be quantitatively determined. When a predefined pre-use pressure between the piston rod 20 and the stopper 7 is reached, the pre-use configuration has been reached, and the final ongoing distal advancement movement of the piston rod 20 is then terminated in response.

[0148] Insofar as the piston is moved a predefined distance in the distal direction 2, the predefined distance is selected such that final tolerances, mechanical play and final longitudinal gap dimensions between the piston rod and the bung may be closed and / or eliminated. For some examples, conversion of the injection device to the pre-use configuration may be obtained simply by setting or dialing a dose of a predefined size (e.g. a dose size of only a few units) and by carrying out a corresponding dispensing procedure (e.g. by pressing the trigger 11 of the drive mechanism 8, thereby advancing the piston rod 20 or plunger by a well-defined longitudinal distance relative to the housing 10 and / or relative to the medicament container 6).

[0149] The advancing movement of the piston rod 20 is accompanied by a pre-use pressure build-up onto the bung 17. When the pre-use configuration is reached, the distal end 63 of the medicament container 6 is sealed and remains sealed to prevent any uncontrolled expulsion of medicament therefrom. After step 102 and after the injection device 1 has been converted to the pre-use configuration, the injection device may be wrapped or packaged in a package that may be subjected to transportation and / or storage.

[0150] In a subsequent step 104 (typically performed by a consumer or end user of the injection device 1), the needle assembly 15 is suitably attached to the injection device 1. The attachment of the needle assembly 15 includes penetrating the seal 26 by the injection needle 19, thereby providing a pressure relief of the drive mechanism 8 and / or the medicament container 6. During the attachment of the needle assembly 15 to the injection device 1, a corresponding amount of medicament 27 may be expelled through the injection needle 19. Several drops may appear or gradually form at the distal end 68 of the injection needle, and this amount of medicament 27 may be captured inside the inner needle cap 16.

[0151] In a subsequent and final step 106 of preparing the injection device 1 , the end user may detach the outer needle cap 17 and the inner needle cap 16 in order to enable injection of the medicament into biological tissue.

[0152] exist Figure 7 In the embodiment, an injection system is further shown, which includes at least one injection device 1, 1' and a package 80, 80'. The package is implemented as a composite package and includes a receptacle 80 (a receptacle sized to receive or accommodate at least one injection device 1, 1'). In the example currently shown, the package 80 is a secondary package or outer package sized to receive two separate injection devices 1, 1'. The injection device 1' is even wrapped in an additional separate package 80'. Both injection devices 1, 1' are implemented as pen-type injectors. They are arranged in the package 80, 80' in the above-mentioned pre-use configuration. In order to use the injection device 1, 1', it is only necessary to attach and / or fix the needle assembly 15 to the outlet end of the respective injection device 1, 1'.

[0153] Due to the mechanically biased abutment between the bung 7 of the medicament container 6 located inside the injection device 1, 1' and the corresponding piston rod 20 or pressure foot 23, there will be a somewhat automatic procedure due to the pre-tensioned or biased configuration of the drive mechanism 8 or transmission train of the injection device 1, 1'.

[0154] Reference numerals

[0155] 1 Injection device

[0156] 2 Distal direction

[0157] 3 Proximal direction

[0158] 4 Dose escalation direction

[0159] 5 Dose reduction direction

[0160] 6 Medicine Containers

[0161] 7. Stopper

[0162] 8 Driving mechanism

[0163] 10 Housing

[0164] 11 Trigger

[0165] 12 Dose dial

[0166] 13 Dosage Window

[0167] 14 Cartridge holder

[0168] 15-pin assembly

[0169] 16 Inner needle cap

[0170] 17 Outer needle cap

[0171] 18 Protective cap

[0172] 19 Injection needle

[0173] 20 Piston rod

[0174] 21 Bearing

[0175] 22 First thread

[0176] 23 Pressure foot

[0177] 24 Second thread

[0178] 25 tubes

[0179] 26 Seals

[0180] 27 Pharmacy

[0181] 28 Threaded socket

[0182] 30 Drive sleeve

[0183] 31 Threaded section

[0184] 32 Flange

[0185] 33 Flange

[0186] 35 Last dose limiter

[0187] 40 Spring

[0188] 44 Clutch

[0189] 50 Number Sleeve

[0190] 51 Grooves

[0191] 55 Orifice

[0192] 60 Fixed cap

[0193] 61 Exit

[0194] 62 outlet opening

[0195] 63 Far End

[0196] 64 raised part

[0197] 65 punctureable part

[0198] 66 Shoulder section

[0199] 67 Proximal

[0200] 68 Far End

[0201] 69 Head

[0202] 70 Needle Seat

[0203] 80 Packaging

[0204] 81 Seats

Claims

1. An injection device (1) for setting and injecting a dose of a medicament, the injection device comprising: - a housing (10), a medicament container (6) containing an injectable medicament (27), the medicament container (6) being sealed in the proximal direction (3) by a removable stopper (7) and comprising an outlet (61) towards a distal end (63), a drive mechanism (8) arranged inside the housing (10) and comprising a piston rod (20) extending in a longitudinal direction and operable to apply a distally directed pressure to the bung (7) in order to expel the dose of medicament through the outlet (61), - Among them, In a pre-use configuration of the injection device (1), before expelling a first dose of medicament and / or before using the injection device (1) for the first time, the piston rod (20) is in longitudinal and mechanically biased abutment with the bung (7).

2. The injection device (1) according to claim 1, wherein: In the pre-use configuration, the piston rod (20) applies a distally directed pre-use pressure to the bung (7), which is greater than or equal to a drive pressure required to move the bung (7) in the distal direction (2) in order to inject the dose of the medicament.

3. An injection device (1) according to any one of the preceding claims, wherein: In the pre-use configuration of the injection device (1), the outlet (61) is sealed and impenetrable to the medicament.

4. An injection device (1) according to any one of the preceding claims, wherein: The seal (26) is secured to the distal end (63) by a securing cap (60) which includes an exit orifice (62) to provide access to a pierceable portion (65) of the seal (26).

5. The injection device (1) according to claim 4, wherein: In a pre-use configuration of the injection device (1), the pierceable portion (65) of the seal (26) comprises or forms a raised sealing portion (64) which at least partially protrudes distally through the outlet orifice (62).

6. An injection device (1) according to any one of the preceding claims, wherein: In the pre-use configuration of the injection device (1), the hydrostatic pressure inside the medicament container (6) is greater than the atmospheric pressure.

7. An injection device (1) according to any one of the preceding claims, wherein: In the pre-use configuration of the injection device (1), the piston rod (20) is in a starting position relative to the housing (10), which is distally offset compared to the initial position of the piston rod (20) when the injection device (1) is assembled.

8. An injection device (1) according to any one of the preceding claims, wherein: The injection device (1) is convertible from the pre-use configuration to a ready-to-use configuration by attaching a needle assembly (15) to the outlet (61), wherein the needle assembly (15) comprises an injection needle (19) for penetrating a seal (26) of the medicament container (6).

9. The injection device of claim 8, wherein: The injection needle (19) is a double-pointed injection needle which pierces the seal (26) of the outlet (61) of the medicament container (6) when the injection device is converted from the pre-use configuration to the ready-to-use configuration.

10. An injection device as claimed in any one of the preceding claims 8 or 9, wherein The needle assembly (15) comprises at least one of an outer needle cap (17) and an inner needle cap (16), which cover the distal end (68) of the injection needle (19) and are configured to receive or capture a portion of the medicament (27) discharged through the distal end (68) of the injection needle (19) during the process of attaching the needle assembly (15) to the injection device (1).

11. An injection system comprising: - a packaging (80) providing a receptacle (81) for the injection device (1), - An injection device (1) according to any one of the preceding claims, arranged inside the receptacle (81) in its pre-use configuration.

12. A method of preparing an injection device (1) for injecting a medicament, the method comprising the following steps: - providing an injection device (1) as claimed in any one of the preceding claims 1 to 10, - converting the injection device (1) into the pre-use configuration by moving the piston rod (20) in the distal direction against the bung (7) of the medicament container.

13. The method of claim 12, further comprising the steps of: After the injection device (1) is converted into the pre-use configuration, a needle assembly (15) is attached to the injection device (1), wherein the needle assembly (15) comprises a double-pointed injection needle (19) having a proximal end (67) and a distal end (68).

14. The method of claim 13, wherein: When the needle assembly (15) is attached to the injection device (1), the proximal end (67) penetrates the seal (26) of the medicament container (6).

15. A method as claimed in any one of claims 12 to 14, wherein: During attachment of the needle assembly (15) to the injection device (1), a portion of the medicament (27) is expelled through the injection needle (19) due to the distally directed pre-use pressure applied by the piston rod (20) to the bung (7) in the pre-use configuration.

16. The method of claim 15, wherein: The needle assembly (15) comprises at least one of an outer needle cap (17) and an inner needle cap (16), which covers the distal end (68) of the injection needle (19) and receives or captures the portion of the medicament (27) discharged through the distal end (68) of the injection needle (19) during the process of attaching the needle assembly (15) to the injection device (1).

17. A method as claimed in any one of claims 12 to 16, wherein: By attaching the needle assembly (15) to the injection device (1), the injection device (1) can be converted from the pre-use configuration to the ready-to-use configuration.

18. A method as claimed in any one of claims 12 to 17, wherein After being converted into the pre-use configuration, the injection device (1) is arranged inside a packaging (80) for transportation and / or storage.

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