Infusion device and method for preparing an infusion device for injection - Patents.com

Abstract

The present disclosure relates to an injection device (1) for setting and injecting a dose of a medication, the injection device comprising: a housing (10); a medication container (6) containing an injectable medication (27), the medication container (6) being sealed by a movable stopper (7) towards a proximal direction (3) and including an outlet (61) towards a distal end (63); a drive mechanism (8) disposed within the housing (10) and including a piston rod (20) extending along a longitudinal direction and operable to apply distally directed pressure to the stopper (7) to expel the dose of medication through the outlet (61), wherein in a pre-use configuration of the injection device (1), prior to expulsion of a first dose of medication and / or prior to a first use of the injection device (1), the piston rod (20) abuts the stopper (7) in a longitudinal and mechanically biased manner.

Description

[Technical Field]

[0001] The present disclosure relates to the field of injection devices, and in particular to the field of pen injectors for setting and injecting single or multiple doses of medication. In another aspect, the present disclosure relates to a method of preparing an injection device for injecting medication. [Background technology]

[0002] Drug delivery devices for setting and dispensing single or multiple doses of liquid medication are well known in the art. Generally, such devices serve substantially the same purpose as a conventional syringe.

[0003] Drug delivery devices, such as pen injectors, must meet several user-specific requirements. For example, in the case of patients with chronic diseases such as diabetes, patients may be physically weak and have impaired eyesight. Therefore, drug delivery devices, particularly those suitable for home care, must be robust in construction and easy to use. Furthermore, the operation and general handling of the device and its components must be clear and easy to understand. Such injection devices must provide for the setting and subsequent dispensing of uniformly or variably sized doses of medication. Furthermore, the dose setting and dose dispensing procedures must be easy to operate and clear.

[0004] Patients suffering from certain illnesses may need to inject a fixed amount of medication via a pen injection syringe.

[0005] Some drug delivery or infusion devices offer the selection of variable-sized doses of medication and the infusion of preset doses, while other infusion devices offer the setting and dispensing of fixed doses, where the amount of medication to be infused according to a given prescription schedule is always the same and is fixed or unalterable over time.

[0006] Some injection devices are implemented as reusable devices, where the user can replace the medication container, such as a cartridge. Other injection devices are implemented as disposable devices, where the entire injection device is intended to be discarded once the contents, i.e., medication, have been used up.

[0007] Here, for example, a cartridge form commonly used in handheld injection devices includes a tubular barrel sealed proximally by a movable stopper, piston, or bung. The piston rod of the drive mechanism of such an injection device is configured to advance distally, thereby urging the stopper in this direction as well to increase fluid pressure within the medication container, thereby resulting in dispensing or injection of the medication via a distally located outlet (typically in fluid communication with an injection needle).

[0008] Due to unavoidable manufacturing and / or assembly tolerances, for example, an axial gap may occur between such a piston or stopper of the medication container and the piston rod. Typically, before the first use of the device, the end user must perform a so-called priming of the drive mechanism to ensure that the initial dose setting and subsequent dose dispensing steps will deposit the correct amount of medication in a predetermined manner. For this purpose, the user is typically instructed to dial in a limited dose size to perform an initial priming shot or blank shot, which will then expel a limited amount of medication through the injection needle. After performing such a priming step or procedure, the device is ready for use.

[0009] In some devices, such a priming procedure must only be performed before the first use of the device with the drug container assembled therein. Once the priming procedure has been performed, the infusion device can be used repeatedly without such supplemental priming procedures between individual dose injection procedures.

[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 involve waste of medication. Finally, a large number of unnecessarily performed priming procedures may result in an insufficient amount of medication remaining in the medication container for setting and administering the final dose. Incorrect or unintended use of such injection devices can pose a significant risk of insufficient dosage. Summary of the Invention [Problem to be solved by the invention]

[0011] It is therefore desirable to provide an improved infusion device that allows for improved and simplified use thereof, particularly for preparing the device before performing dose setting and injection procedures. In particular, the process of priming the infusion device should be simplified for the end consumer or patient. [Means for solving the problem]

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

[0013] The injection device further includes a drive mechanism including a piston rod disposed within the housing and extending longitudinally therethrough, the piston rod and / or the drive mechanism operable to apply distally directed pressure to the stopper to expel a dose of the medicament through the outlet of the medicament container.

[0014] The injection device is transferable to a pre-use configuration. When in the pre-use configuration, the piston rod is in longitudinal and mechanically biased abutment with the stopper. Thus, in the pre-use configuration, the drive mechanism is biased or pre-tensioned. Here, the piston rod is biased against the stopper of the drug container and therefore in pre-tensioned abutment therewith. In fact, when in the pre-use configuration, any longitudinal tolerance and / or any longitudinal mechanical play of the drive mechanism is eliminated so as to consistently translate the initial and distally directed displacement of the piston rod into a respective distally directed movement of the stopper of the drug container.

[0015] Typically, the injection device is in a pre-use configuration before expelling the first dose of medication and / or before the first use of the injection device.

[0016] In some examples, the injection device is subject to transportation and / or storage when and as long as it is in the pre-use configuration; in other words, the injection device is in 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 longitudinal abutment of the drive mechanism and the stopper of the drug container, is longitudinally biased or longitudinally pre-tensioned without dispensing or expelling a portion of the injectable drug through the outlet of the drug container. Thus, in the pre-use configuration, the drug container is in a fully filled configuration, and the entire drug initially filled or disposed in the drug container is still disposed or contained within the drug container.

[0017] In some examples, the medicament container includes a tubular barrel sealed by a stopper toward the proximal longitudinal end of the barrel. An outlet is provided at the distal longitudinal end of the medicament container, which may be sealed by a seal, for example, in the form of an elastomeric sealing disk. Here, the medicament container may be implemented as a cartridge, with the outlet sealed by the elastomeric seal and configured to be punctured or penetrated by a double-tip injection needle.

[0018] Typically, as long as the injection device is in the pre-use configuration, the seal of the outlet of the medication container is not punctured or penetrated: the seal is fully intact and has not yet been penetrated by any injection needle or similar piercing structure.

[0019] In the present injection device, by transitioning the injection device to a pre-use configuration before using the injection device, a priming step of the drive mechanism and / or medication container is not or no longer required 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 may simply be required to attach the needle assembly to the outlet of the medication container. Subsequently, the eventual elevated pressure level within the medication container, which may result from the longitudinally biasing abutment between the piston rod and the stopper, may be relieved, resulting in the final ejection of a small amount, e.g., a few drops, of liquid medication through the outlet and thus through the injection needle of the needle assembly. Nevertheless, when in the pre-use configuration, a separate user-induced execution of the priming procedure or blank shot is no longer required.

[0020] When the injection device is provided to the patient or user in a pre-use configuration, and when the user or patient properly attaches the injection needle to the outlet of the drug container, an increase in fluid pressure within the drug container can induce the ejection of a small amount of liquid drug, e.g., a few drops.

[0021] In either case, due to the longitudinal and mechanically biasing abutment between the piston rod and the stopper, the drive mechanism or injection device does not have any longitudinal tolerances in the drive train of the drive mechanism, so that the set dose can be fully dispensed or injected by performing a subsequent first or initial setting and injection procedure on the drive mechanism.

[0022] Therefore, in the currently proposed injection device, priming, mechanical biasing, or pretensioning of the drive mechanism, thereby longitudinally and mechanically biasing the piston rod into abutment with the stopper of the cartridge, can be performed at the end of manufacturing or assembly of the injection device, for example, by a pharmaceutical company. The injection device can remain in the pre-use configuration during transportation and storage to the patient or customer. Therefore, when a 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 carry out a separate priming procedure. The end user or patient simply needs to correctly assemble the needle assembly to the housing and / or the outlet of the drug container to move the injection device from the pre-use configuration to the ready-to-use configuration.

[0023] According to a further example, when in the pre-use configuration, the piston rod exerts a distally directed pre-use pressure on the stopper, the pre-use pressure being greater than or equal to the driving pressure required to move the stopper distally to inject a dose of the drug.

[0024] When a pre-use pressure is applied to the stopper, the stopper may not move distally despite the fact that the pre-use pressure is greater than the driving pressure required to move the stopper distally, and the outlet of the drug container may then be sealed and remain sealed as long as the injection device is in the pre-use configuration.

[0025] For example, because the liquid drug contained in the drug container is substantially incompressible, applying a relatively large pre-use pressure in the distal direction to the stopper may have no substantial effect other than longitudinal compression of the stopper controlled by the resilient material of the stopper, which leads to the creation of elevated pressure within the drug container.

[0026] It may only be when a needle, for example a double-tipped needle, is attached to the outlet of the medication container that the pre-use pressure exerted by the piston rod on the stopper of the medication container results in dispensing a relatively small amount of medication through the outlet.

[0027] According to a further example, the distal end of the medication container longitudinally abuts a stop surface of the housing. Typically, the stop surface of the housing is provided at or near the distal end of the housing. The housing of the injection device may comprise a single or multiple housing components. In a multiple housing component case, the housing may include a main housing component, also referred to as the body of the injection device, which forms the proximal housing component. A further housing component of the injection device may provide a cartridge holder or cartridge retainer, which may form or constitute the distal housing component of the injection device.

[0028] The cartridge holder or cartridge retainer portion of the housing of the injection device may include a mechanical connector at its distal end that is complementary in shape to the counter-connector of a standardized needle assembly. The cartridge holder is sized and configured to receive a drug container, for example in the form of a cartridge. The body of the housing is configured and sized to receive a drive mechanism. The proximal end of the cartridge holder may be removably or non-removably connectable or fastenable to the distal end of the body of the housing. Typically, in the final stages of assembly of the injection device, the cartridge or drug container is inserted distally through the proximal end of the cartridge holder, and then the cartridge holder with the cartridge or drug container assembled therein is connected and secured to the distal end of the body. The inevitable geometric metrology or assembly tolerances of the numerous components of the injection device may result in a fairly loose fit between the piston rod and the stopper and / or a longitudinal gap between the proximal face of the drug container or cartridge stopper and the distal end of the piston rod. The cartridge holder can then be mechanically secured to the body of the injection device, and then the drive mechanism can be used to advance the piston rod distally until it reaches mechanically biasing abutment with the stopper, thereby transitioning the injection device to a pre-use configuration.

[0029] In some instances, a distally directed stop surface on the drug container, e.g., a distally facing shoulder portion of the drug container, may longitudinally abut a complementary shaped, proximally directed stop surface on the housing or cartridge holder. In this manner, the drug container or cartridge is distally confined relative to the housing or cartridge holder. Due to the longitudinally biasing abutment between the cartridge stopper and the piston rod, the drug container is also longitudinally confined relative to the housing of the injection device in a proximal direction.

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

[0031] The pre-use configuration can be terminated, or the injection device can be transitioned from the pre-use configuration to the ready-to-use configuration, simply by attaching a needle assembly to the distally located outlet, thereby piercing the seal of the drug container, for example, with an injection needle.

[0032] By way of further example, when the injection device is in the pre-use configuration, the outlet of the medication container is not punctured and remains unpunctured. Here, the outlet may be covered or closed by a pierceable seal, such as an elastomeric sealing disc, also referred to as or including a rubber septum. As long as the injection device is in the pre-use configuration, the seal remains intact and unpunctured.

[0033] Transitioning the injection device from a pre-use configuration to a ready-to-use configuration may involve piercing the outlet seal with, for example, a double-tipped syringe needle.

[0034] According to a further example, the drug container includes a barrel, e.g., of tubular shape. The outlet of the drug container is sealed by a needle-penetrable elastomeric seal. Here, the outlet of the drug container is provided by the outlet of the barrel. Thus, the needle-penetrable elastomeric seal seals and closes the outlet of the barrel of the drug container. The barrel may be substantially tubular in shape. It may include a neck portion that narrows or is radially stepped down toward its distal end and thus toward the outlet. For example, the outlet provided at the distal end of the barrel may include a bead cap. Here, the elastomeric seal, e.g., in the form of a pierceable sealing disk, is held and fixed in a head portion provided at the distal end of the drug container barrel.

[0035] According to a further example, the drug container includes a seal that closes or seals the outlet of the drug container. The seal is secured to the distal end of the drug container by a locking cap. The locking cap includes an outlet aperture for providing access to the pierceable portion of the seal. Typically, the pierceable portion of the seal is a radially central portion of the seal. The locking cap may be a crimped cap or a beaded cap that covers or surrounds the distal free end of the barrel of the drug container. The locking cap may be made of a flexible material such as a flexible sheet metal material, e.g., aluminum.

[0036] The fixation cap provides a liquid-proof and durable fixation of the pierceable seal to the outlet of the medication container. In the same way, the pierceable portion of the seal is uncovered and remains uncovered, and thus accessible, through the outlet aperture of the fixation cap, providing direct access for, for example, a double-tipped syringe needle to pierce the seal and thereby gain fluid transfer access to the interior of the medication container. The seal as provided and / or fixed to the outlet of the medication container may be elastically deformable.

[0037] According to a further example, when in the pre-use configuration, the pierceable portion of the seal includes or forms a bulged seal portion that protrudes at least partially distally through the exit aperture of the fixation cap. This bulged seal portion may result from the application of pre-use pressure to the stopper, where the stopper may be subjected to longitudinal compression. As the piston rod applies pre-use pressure to the stopper, the stopper itself may also tend to move distally relative to the sidewall of the drug container, e.g., relative to the barrel of the container, thereby increasing fluid pressure and thereby inducing an outwardly bulging deformation of the seal, which causes the pierceable portion of the seal to begin protruding distally through the exit opening.

[0038] The creation of such an outwardly extending or outwardly protruding pierceable portion of the seal provides the user with visual or tactile feedback that the injection device is in a pre-use configuration. In some examples, the distal end of the housing of the injection device, for example the distal end of the cartridge holder, includes an aperture for receiving an injection needle therethrough. If the outwardly protruding seal portion is not palpable at the aperture of the cartridge holder or housing, it may at least be visible through this aperture.

[0039] The inflated sealing portion that protrudes at least partially and distally from the drug container allows a patient or user of the injection device to visually or tactilely check whether the injection device is in its intended pre-use configuration before attaching the respective injection needle to the distal end of the injection device.

[0040] According to another example, when in the pre-use configuration, the hydrostatic pressure within the drug container is greater than atmospheric pressure, and therefore, when in the pre-use configuration, the interior of the drug container is prone to elevated pressure compared to atmospheric pressure.

[0041] This elevated pressure level can result in the formation or creation of a bulging seal portion in the pierceable portion of the seal of the medication container or cartridge.

[0042] According to a further example of the injection device, when in the pre-use configuration, the hydrostatic pressure within the drug container exceeds atmospheric pressure by a factor p, where 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. Such a pressure increase can provide a well-defined level of pretension, sufficient to eliminate longitudinal tolerances and / or mechanical play in the injection device and drive mechanism. On the other hand, the pressure increase is well below the upper threshold level at which the mechanical structures of the injection device, drive mechanism, or drug container may be mechanically damaged.

[0043] According to another example, when in the pre-use configuration, the piston rod of the drive mechanism longitudinally abuts the movable stopper and the medication container and exerts a longitudinally directed pressure on the stopper in the range of 10 kPa to 130 kPa. Thus, there can be a well-defined longitudinal or axial abutment between the piston rod and the stopper at a contact pressure in the range of 10 kPa to 130 kPa.

[0044] In some examples, the contact pressure is in the range of 20 kPa to 100 kPa. In some examples, the contact pressure is in the range of 40 kPa to 80 kPa. In some examples, the contact pressure is in the range of 50 kPa to 70 kPa.

[0045] In 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 contact pressure between the piston and the piston rod can be adjusted according to the type of medicament, in particular according to the viscosity of the medicament, and / or with respect to the geometric dimensions or material properties of the medicament container or stopper.

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

[0048] Here, a dose of a predetermined size, e.g., 1 to 5 units, can be set by the drive mechanism, and each dose can be substantially injected only by performing the respective injection or dispensing procedure, resulting in a respective distal displacement of the piston rod according to the predetermined size dose. In this manner, a relatively small dose size, such as 1, 2, or up to 5 international units of medication, can be set, and the drive mechanism can then be triggered to inject such a dose, thereby moving the piston rod from the initial position toward and to the priming or pre-use position, where the piston rod abuts the stopper in the longitudinal direction and mechanically biased manner described above. During this virtual injection procedure, the outlet of the medication container is sealed and remains sealed, effectively preventing the liquid medication from being expelled.

[0049] In another aspect, the present disclosure relates to an infusion system. The infusion system includes a package providing a receptacle for an infusion device. The infusion system further includes an infusion device, as described above, disposed within the receptacle in a pre-use configuration. The infusion system, i.e., the package with the infusion device disposed therein, may be intended for transport and / or storage of the infusion device.

[0050] By keeping the injection device in its pre-use configuration within the package, the user does not need to perform a separate priming procedure on the injection device before first use. Rather, to transition the injection device from the pre-use configuration to the ready-to-use configuration, the user simply attaches or assembles an appropriate needle assembly to the injection device. During or after attaching the needle assembly to the injection device, the proximal end of a dual-tipped injection needle may be provided to extend through an aperture in the distal end of the injection device and pierce the seal of the medication container.

[0051] A relatively small amount of medication can be initially dispensed during the needle attachment step due to the increased pre-use pressure within the medication container. Because the piston rod of the drive mechanism abuts and remains in longitudinal abutment with the stopper, the injection device is in a ready-to-use configuration immediately after attachment of the needle assembly.

[0052] The injection system includes an injection device as described above, and to that extent all of the features, effects and advantages described above in connection with the injection device apply equally to the injection system.

[0053] The package may include one of a blister package, a foil-type package, or a cardboard package. The package may include a single or multiple injection devices. In some examples, the package is opaque. In other examples, the package, or portions thereof, are translucent. Packages that are opaque to electromagnetic radiation, particularly in either the visible spectral range and / or the infrared or UV spectral range, may effectively protect the medication contained in the medication container from such radiation, thereby enabling an extended storage or shelf life of the medication disposed within the medication container.

[0054] In a further example, the packaging may be liquid- and / or gas-resistant, and therefore impermeable to liquid, gas or gaseous substances. In this way, the injection device may 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 of preparing an injection device for injecting a medication, the method typically including the steps of providing an injection device as described above, followed by the step of transitioning the injection device to the pre-use configuration described above by moving a piston rod distally relative to a stopper of a medication container.

[0056] Typically, the forward movement of the piston rod is such that the piston rod exerts a well-defined pressure on the piston rod's stopper. In some examples, the distal advancement of the piston rod continues or is continued until a predefined pressure level is reached between the piston rod and the stopper. In some examples, the forward movement of the piston rod is pressure controlled. In other examples, the piston rod is advanced distally a predefined distance, the predefined distance being greater than the longitudinal tolerance margin between the distal end of the piston rod and the proximal end of the stopper upon final assembly of the injection device.

[0057] In this way, after final assembly of the injection device, advancing the piston rod distally a predetermined distance can somehow ensure that not only will the piston rod abut longitudinally against the stopper, but that the piston rod also exerts a clearly defined pressure on the stopper that exceeds a predetermined threshold.

[0058] The pressure threshold may be in a range higher than the driving pressure normally required to move the stopper distally to inject a dose of medication when the needle is attached to the injection device and the medication can be expelled through the needle and out the outlet of the medication container.

[0059] As mentioned above, in the pre-use configuration, the drug container is sealed and remains sealed at its outlet to prevent uncontrolled dispensing or expulsion of drug from the drug 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, and insofar as all of the effects, features and advantages as described above in relation to 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 company, where conversion of the injection device can be performed as a final step after final assembly of the injection device on-site by the pharmaceutical company. The injection device in its pre-use configuration can be stored and shipped or transported to the consumer and / or patient. As such, the consumer or patient no longer needs to perform a separate priming procedure. Rather, they simply need to attach the needle assembly to the injection device in its pre-use configuration, which automatically converts the injection device to the ready-to-use configuration.

[0062] Transitioning the injection device to a pre-use configuration prior to packaging and shipping the injection device to a consumer or patient has the added advantage of securely securing the drug container within the housing of the injection device. In this way, the drug container can be kept slack-free within the housing of the injection device during transport and / or shipping. Furthermore, the mechanically biased abutment between the piston rod and the stopper can keep the entire drive mechanism somewhat pre-tensioned or pre-biased, thereby inhibiting any movement of loosely attached components of the drive mechanism that might otherwise be subject to vibration or similar small movements during transport or shipping.

[0063] According to a further example, the method of preparing an injection device further includes attaching a needle assembly to the injection device after transitioning the injection device to a pre-use configuration. Typically, the needle assembly includes a double-tipped injection needle having a proximal end and a distal end. The injection needle is beveled at both its distal end and its proximal end. When the needle is attached to the injection device, the proximal end of the needle pierces a seal provided on an outlet of the medication container.

[0064] According to a further example, the proximal end of the injection needle pierces the seal of the medication container when the needle assembly is attached to the injection device.

[0065] Typically, the needle assembly includes a needle hub or needle holder, which may be somewhat tubular in shape. The needle hub typically includes a counter-connector that is complementary in shape to a connector at the distal end of the injection device. The connector and counter-connector may be implemented as male and mating female threads, respectively. In other examples, the connector and counter-connector may form a snap-fit ​​or bayonet connection.

[0066] The injection needle is typically removably fastened to a needle holder. By attaching the needle, particularly the needle hub, to the distal end of the injection device, a fluid transfer connection is established between the injection needle and the interior of the medication container. In this manner, attachment of the injection needle to the injection device can transition the injection device to a ready-to-use configuration. Due to the mechanically biasing abutment between the piston rod and the stopper, hydrostatic pressure can build up within the medication container prior to attachment of the needle assembly. Once the needle assembly is attached to the injection device, a type of pressure release can occur, resulting in a limited amount of medication being expelled through the injection needle.

[0067] In a further example of the method, during attachment of the needle assembly to the injection device, a portion of the medication is expelled through the injection needle by a distally directed pre-use pressure exerted on the stopper by the piston rod in the pre-use configuration.

[0068] Applying pre-use pressure to the stopper can result in increased hydrostatic pressure within the drug container unless an injection needle is attached to the drug container or injection device. Applying distally directed pre-use pressure to the stopper can also result in longitudinal compression of the stopper due to the stopper's elastic properties. Because the liquid drug contained within the drug container is substantially incompressible, increased pressure applied to the stopper can result in radial expansion of the stopper, thereby increasing the sealing function of the stopper's sealing ability. Therefore, longitudinal compression of the stopper can result in radial expansion of the stopper, causing the stopper to apply increased radially outward pressure against the sidewall of the tubular barrel of the drug container.

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

[0070] According to another example, the needle assembly includes at least one of an outer needle cap and an inner needle cap that covers the distal end of the injection needle. The outer needle cap or the inner needle cap is further configured to receive or capture a 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. The portion of the medicament that is expelled, for example automatically, upon attachment of the needle assembly to the injection device may then be captured inside the outer needle cap or the inner needle cap, and the patient may not even be aware of the expulsion of the medicament.

[0071] Furthermore, during the needle assembly process, the pressure release that leads to the expulsion of a small amount of medication through the needle may occur during needle attachment and before the needle assembly is fully attached to the injection device, so that when the final mutually assembled configuration of the needle assembly and injection device is reached, the process of expelling a small amount of medication from the medication container may already be complete.

[0072] According to a further example, the injection device can be or is transferred from a pre-use configuration to a ready-to-use configuration by attaching a needle assembly to the injection device to transition the injection device to the ready-to-use configuration, and it is no longer necessary for the user to perform a separate priming procedure, for example by dialing or setting a dose of a predefined size and then injecting that dose of medication. It is simply necessary to attach the needle assembly to the injection device and capture a specific amount of medication that will ultimately be expelled through the injection needle.

[0073] When the user subsequently uses the injection device and attempts to remove the inner and / or outer needle cap, no more drops will form 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 procedure or prime has been performed somewhat automatically 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 a further example, the injection device may be placed in a package for transport and / or storage after being converted to a pre-use configuration. Thus, the method for preparing the injection device may be performed on-site at a pharmaceutical company. After final assembly of the injection device, it may be converted to its pre-use configuration. The injection device may then be packaged or wrapped, thereby forming an injection system.

[0075] The method of preparing the injection device may be continued by the end user or patient, where the injection device may be unpacked or removed from its packaging and the needle assembly may be properly attached to the injection device. As a further optional method step, after the needle assembly has been attached and secured to the injection device, at least one of the outer needle cap and the inner needle cap may be removed from the needle assembly. The injection device is then in a ready-to-use configuration, and the user may thereafter set and inject single or multiple doses of medication.

[0076] The injection device is not intended to implement a user-controlled priming procedure, and the user is not instructed in any way to set a dose and then trigger an injection procedure for the purpose of priming such extra, potentially drug-wasting, medication procedures between repeated dose injection procedures, thereby effectively avoiding potential misuse of the injection device.

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

[0078] In this context, the term "distal" or "distal end" refers to the end of the injection device facing the injection site of a human or animal, and the term "proximal" or "proximal end" refers to the opposite end of the injection device that is furthest from the injection site of a human or animal.

[0079] The terms "drug" or "medicament" are used synonymously herein to refer to a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient ("API"), in the broadest sense, is a chemical structure that has a biological effect on humans or animals. In pharmacology, drugs or agents are used to treat, cure, prevent, or diagnose disease, or otherwise improve physical or mental well-being. Drugs or agents may be used for a limited duration, or periodically for chronic conditions.

[0080] As described below, drugs or pharmaceutical agents may contain at least one API or a combination thereof in various types of formulations to treat one or more diseases. Examples of APIs include small molecules with 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, as well as nucleic acids, double-stranded or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.

[0081] The drug or agent may be contained within a primary package or "drug container" adapted for use with the drug delivery device. The drug container may be, for example, a cartridge, syringe, reservoir, or other rigid or flexible container configured to provide suitable chambers for storage (e.g., short-term or long-term storage) of one or more drugs. For example, in some cases, the chambers may be designed to store the drug for at least one day (e.g., from one day to at least 30 days). In some cases, the chambers may be designed to store the drug for about one month to about two years. Storage may occur at room temperature (e.g., about 20°C) or at refrigerated temperatures (e.g., from about -4°C to about 4°C). In some cases, the drug container may be or include a dual-chamber cartridge configured to separately store two or more components of a pharmaceutical formulation to be administered (e.g., an API and a diluent, or two different drugs), one in each chamber. In such cases, the two chambers of the dual-chamber cartridge may be configured to allow mixing of two or more components prior to and / or during administration into the human or animal body. For example, the two chambers may be configured to be in fluid communication with each other (e.g., by a conduit between the two chambers) to allow mixing of the two components if desired by a user prior to administration. Alternatively or additionally, the two chambers may be configured to allow mixing of the components as they are administered into the human or animal body.

[0082] Drugs or agents contained in drug delivery devices such as those described herein can be used to treat and / or prevent many different types of medical disorders. Examples of disorders include, for example, diabetes or complications associated with diabetes, such as diabetic retinopathy, and thromboembolic disorders, such as deep vein or pulmonary embolism. Further examples of disorders include acute coronary syndrome (ACS), angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis, and / or rheumatoid arthritis. Examples of APIs and drugs include those listed in handbooks such as the Rote Liste 2014, including, but not limited to, Main Group 12 (antidiabetic drugs) or 86 (oncology drugs), and the 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 a human insulin analog or derivative; glucagon-like peptide (GLP-1), a GLP-1 analog or GLP-1 receptor agonist, or an analog or derivative thereof; a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms "analog" and "derivative" refer to a polypeptide having a molecular structure that is formally derivable from the structure of a naturally occurring peptide, e.g., the structure of human insulin, by deleting and / or replacing at least one amino acid residue occurring in the naturally occurring peptide and / or by adding at least one amino acid residue. The added and / or replaced amino acid residue may be either a codable amino acid residue or another naturally occurring residue, or a purely synthetic amino acid residue. Insulin analogs are also referred to as "insulin receptor ligands." In particular, the term "derivative" refers to a polypeptide having a molecular structure formally derivable from the structure of a naturally occurring peptide, e.g., the structure of human insulin, in which one or more organic substituents (e.g., fatty acids) are attached to one or more amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may be deleted and / or substituted with other amino acids, including non-encodeable amino acids, or amino acids, including non-encodeable amino acids added to the naturally occurring peptide.

[0084] Examples of insulin analogues include 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 in which the proline at position B28 may be replaced by Asp, Lys, Leu, Val or Ala and the Lys at position B29 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 include B29-N-myristoyl-des(B30) human insulin, Lys(B29)(N-tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®), 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, and B30-N-myristoyl-ThrB29LysB30 human insulin. , B30-N-palmitoyl-ThrB29LysB30 human insulin, B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin, B29-N-omega-carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®), B29-N-(N-lithocholyl-gamma-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 analogues and GLP-1 receptor agonists include, for example, lixisenatide (Lyxumia®), exenatide (exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide produced by the salivary glands of the flathead monster), liraglutide (Victoza®), semaglutide, taspoglutide, albiglutide (Syncria®), dulaglutide (Trulicity®), rexendin-4, CJC-1134-P C, PB-1023, TTP-054, langrenatide / HM-11260C (efpegrenatide), HM-15211, CM-3, GLP-1 Erigen, 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, MAR-701, MAR709, ZP-2929, ZP-3022, ZP-DI-70, TT-401 (pegapamoditide), BHM-034. These include MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, tirzepatide (LY3298176), bamadutide (SAR425899), exenatide-XTEN, and glucagon-Xten.

[0087] Examples of oligonucleotides include, for example, mipomersen sodium (Kynamro®), a cholesterol-lowering antisense therapeutic agent for the treatment of familial hypercholesterolemia, or RG012 for the treatment of Alport syndrome. Examples of DPP4 inhibitors include linagliptin, vildagliptin, sitagliptin, denagliptin, saxagliptin, and berberine.

[0088] Examples of hormones include pituitary hormones or hypothalamic hormones or regulatory active peptides such as gonadotropins (follitropin, lutropin, chorion gonadotropin, menotropin), somatropine (somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin and goserelin, and their antagonists.

[0089] Examples of polysaccharides include glycosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin, or ultra-low molecular weight heparin, or derivatives thereof, or sulfated forms of the above polysaccharides, such as polysulfated forms, 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 (Synvisc®), sodium hyaluronate.

[0090] As used herein, the term "antibody" refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments that retain antigen-binding ability. An antibody can be a polyclonal antibody, a monoclonal antibody, a recombinant antibody, a chimeric antibody, a deimmunized or humanized antibody, a fully human antibody, a non-human (e.g., murine) antibody, or a single-chain antibody. In some embodiments, an antibody has effector function and can fix complement. In some embodiments, an antibody has reduced or no Fc receptor binding ability. For example, an antibody can be an isotype or subtype, antibody fragment, or mutant that does not support Fc receptor binding, e.g., in which the Fc receptor binding region has been mutated or deleted. The term "antibody" also includes antigen-binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTIs) and / or dual variable region antibody-like binding proteins with a crossover 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 and / or light chain polypeptide) that does not contain the full-length antibody polypeptide but still contains at least a portion of the full-length antibody polypeptide that is capable of binding to an antigen. Antibody fragments can include truncated portions of the full-length antibody polypeptide, although the term is not limited to such truncated 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, such as bispecific, trispecific, tetraspecific, and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments, such as bivalent, trivalent, tetravalent, and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and VHH-containing antibodies. 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 regions 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 regions of both heavy and light chain polypeptides that are not CDR sequences but are primarily responsible for maintaining the correct arrangement of the CDR sequences to permit antigen binding. Although the framework regions themselves are typically not directly involved in antigen binding, as is known in the art, certain residues within the framework regions of a particular antibody can be directly involved in antigen binding or can influence the ability of one or more amino acids within the CDRs to interact with the antigen.

[0093] Examples of antibodies are anti-PCSK-9 mAb (e.g., alirocumab), anti-IL-6 mAb (e.g., sarilumab), and anti-IL-4 mAb (e.g., dupilumab).

[0094] Pharmaceutically acceptable salts of any API described herein are also contemplated for use with the drug or agent in the drug delivery device. Pharmaceutically acceptable salts include, for example, acid addition salts and base salts.

[0095] Those skilled in the art will understand that modifications (addition and / or deletion) of the various components of the APIs, formulations, devices, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the invention, including such modifications and all equivalents thereof.

[0096] An exemplary drug delivery device may include a needle-based injection system as described in Table 1 of Section 5.2 of ISO 11608-1:2014(E). As described in ISO 11608-1:2014(E), needle-based injection systems can be broadly categorized into multi-dose container systems and single-dose (partial or full discharge) 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 include a needle-based injection device with replaceable containers. In such a system, each container holds multiple doses and may be fixed or variable in size (pre-set by the user). Another multi-dose container system may include a needle-based injection device integrated with a non-replaceable container. In such a system, each container holds multiple doses and may be fixed or variable in size (pre-set by the user).

[0098] As further described in ISO 11608-1:2014(E), a single-dose container system may include a needle-based injection device with replaceable containers. In one example of such a system, each container holds a single dose, thereby dispensing the entire deliverable amount (full discharge). In a further example, each container holds a single dose, thereby dispensing a portion of the deliverable amount (partial discharge). Also as described in ISO 11608-1:2014(E), a single-dose container system may include a needle-based injection device integrated with non-replaceable containers. In one example of such a system, each container holds a single dose, thereby dispensing the entire deliverable amount (full discharge). In a further example, each container holds a single dose, thereby dispensing a portion of the deliverable amount (partial discharge).

[0099] In the following, examples of injection devices and methods for preparing them for injection will be described in more detail with reference to the drawings. [Brief explanation of the drawings]

[0100] [Figure 1] 1 shows a schematic longitudinal cross-sectional view of an example of an injection device. [Figure 2] 1 shows the distal end of the medication container when the injection device is in a pre-use configuration. [Figure 3] 3 shows the drug container according to FIG. 2 after attachment of the needle assembly to the injection device. [Figure 4] 1 shows an injection device and needle assembly. [Figure 5] 10 further shows the injection device with the cartridge holder removed from the body of the injection device. [Figure 6] 1 is a flow chart of a method for preparing an infusion device for injecting a medication. [Figure 7] 1 shows the injection device placed in a package. DETAILED DESCRIPTION OF THE INVENTION

[0101] The injection device 1, as shown in Figures 1, 4, and 5, is a pre-filled, disposable injection device that includes a housing 10 to which a needle assembly 15 can be attached. The needle assembly 15 includes a double-tipped injection needle 19. The needle 19 is protected by an inner needle cap 16 and either an outer needle cap 17 or a protective cap 18 configured to surround and protect the distal section of the housing 10 of the injection device 1. The housing 10 may include or form a main housing part configured to house a drive mechanism 8. The injection device 1 may further include a distal housing component shown as a cartridge holder 14. The cartridge holder 14 may be permanently or removably connected to the main housing 10. The cartridge holder 14 is typically configured to house a medication container 6, implemented as a so-called cartridge that is filled with, for example, a liquid medication.

[0102] The cartridge or drug container 6 includes a cylindrical or tubular barrel 25 that is sealed in a proximal direction 3 by a stopper 7 disposed within the barrel 25. The stopper 7 is displaceable in a distal direction 2 relative to the barrel 25 of the drug container 6 by a piston rod 20. The distal end of the drug container 6 is sealed by a pierceable seal 26 configured as a septum and pierceable by a proximally directed tip 67 of an injection needle 19.

[0103] The needle assembly 15 includes a needle hub 70 that includes a counter-connector that is complementary in shape to the connector 28 provided at the distal end of the housing 10 or cartridge holder 14. In the presently shown example, the connector 28 includes a threaded socket with external threads that are complementary in shape to the internal threads provided in the side wall of the needle hub 70. In this way, the needle assembly 15 can be attached and detached to the distal end of the injection device 1 by screwing or unscrewing.

[0104] By attaching the needle assembly 15 to the distal end of the cartridge holder 14 , the seal 26 of the medication container 6 is penetrated by the injection needle 19 , thereby establishing fluid transfer access to the interior of the medication container 6 .

[0105] When the infusion device 1 is configured to administer, for example, human insulin, the dosage set by the dose dial 12 at the proximal end of the infusion device 1 may be displayed in so-called international units (IU, where 1 IU is bioequivalent to approximately 45.5 μg of pure crystalline insulin (1 / 22 mg)).

[0106] 1 and 4, the housing 10 includes a dosage window 13, which may be in the form of an aperture in the housing 10. The dosage window 13 allows a user to view a limited portion of the number sleeve 50, which is configured to move to provide a visual indication of the currently set dose as the dose dial 12 is turned. The dose dial 12 rotates in a helical path relative to the housing 10 when turned during setting and / or when dispensing or expelling a dose.

[0107] The injection device 1 may be configured such that turning the dosage knob 12 produces a mechanical click to provide audible feedback to the user. The numeric sleeve 50 mechanically interacts with a piston within the medication container 6. When the needle 19 is inserted into the patient's skin and the trigger 11 or injection button is pressed, the dose displayed in the display window 13 is expelled from the injection device 1. If the needle 19 of the injection device 1 remains in the skin for a period of time after pressing the trigger 11, a high percentage of the dose is actually injected into the patient's body. The expulsion of a dose of medication 27 may also produce a mechanical click, but this is different from the sound produced when using the dose dial 12.

[0108] In this embodiment, during delivery of a dose of medication, the dose dial 12 moves axially, i.e., is turned to its initial position without rotation, while the number sleeve 50 rotates back to its initial position, e.g., to display a dose of zero units.

[0109] The injection device 1 can be used for several injection processes until the drug container 6 is empty or the expiry date of the drug in the injection device 1 is reached (eg 28 days after first use).

[0110] The ejection mechanism or drive mechanism 8, as shown in more detail in FIG. 1 , includes a number of mechanically interacting components. A support, such as a flange, of the housing 10 includes a threaded axial through-opening that is threadedly engaged with a first or distal thread 22 of the piston rod 20. The distal end of the piston rod 20 includes a bearing 21 in which a foot 23 is free to rotate about its axis of rotation with the longitudinal axis of the piston rod 20. The foot 23 is configured to axially abut a proximally facing thrust bearing surface of the stopper 7 of the medication container 6. During a dispensing operation, the piston rod 20 rotates relative to the housing 10, thereby experiencing a distally directed forward movement relative to the housing 10 and, therefore, relative to the barrel 25 of the medication container 6. As a result, the stopper 7 of the medication container 6 is displaced distally 2 a well-defined distance due to the threaded engagement between the piston rod 20 and the housing 10.

[0111] The piston rod 20 is further provided at its proximal end with a second screw 24. The distal screw 22 and the proximal screw 24 are crossed on opposite sides.

[0112] A drive sleeve 30 is further provided having a hollow interior for receiving the piston rod 20. The drive sleeve 30 includes an internal thread that is threadably engaged with the proximal thread 24 of the piston rod 20. The drive sleeve 30 further includes an external thread 31 at its distal end. The thread 31 is axially confined between a distal flange portion 32 and another flange portion 33 that is positioned a predetermined axial distance from the distal flange portion 32. A final dose limiter 35 in the form of a semicircular nut is provided between the two flange portions 32, 33 and has internal threads that mate with the thread 31 of the drive sleeve 30.

[0113] The final dose limiter 35 further includes a radial recess or protrusion on its outer periphery for engaging a complementary recess or protrusion on the inside of the side wall of the housing 10. In this manner, the final dose limiter 35 is splined to the housing 10. Rotating the drive sleeve 30 in the dose increment direction 4, or clockwise, during successive dose setting procedures causes a cumulative axial displacement of the final dose limiter 35 relative to the drive sleeve 30. An annular spring 40 is further provided for axially abutting the proximally facing surface of the flange portion 33. A tubular clutch 44 is also provided. At a first end, the clutch 44 is provided with a series of circumferentially oriented sawtooth teeth. Towards a second, opposite end of the clutch 44 is disposed a radially inwardly oriented flange.

[0114] Further provided is a dose dial sleeve, also shown as a number sleeve 50. The number sleeve 50 is provided outside the spring 40 and clutch 44 and is positioned radially inward of 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 dosage window 13 through which a portion of the outer surface of the number 50 is visible. The housing 10 is further provided with a spiral rib on its inner sidewall portion, the spiral rib being located in the spiral groove 51 of the number sleeve 50. The housing 10 is provided with first and second stops to limit the dose setting procedure in which the number sleeve 50 is rotated in a spiral motion relative to the housing 10.

[0115] A dose dial 12 in the form of a dose dial grip is disposed around the outer surface of the proximal end of the numeral 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 numeral 50 to prevent relative movement therebetween. The dose dial 12 includes a central opening.

[0116] The trigger 11, also referred to as the 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 and through the inner diameter of the extension of the drive sleeve 30. The trigger 11 is retained for limited axial movement within and against rotation relative to the drive sleeve 30. The head of the trigger 11 is generally circular. A sidewall or skirt of the trigger extends from the periphery of the head and is further adapted to be seated in a proximally accessible annular recess in the dose dial 12.

[0117] To dial in a dose, the user rotates the dose dial 12. With the spring 40 also functioning as a clicker and the clutch 44 engaged, the drive sleeve 30, spring or clicker 40, clutch 44, and numeric sleeve 50 rotate with the dose dial 12. Audible and tactile feedback of the dialed-in dose is provided by the spring 40 and clutch 44. Torque is transmitted through the sawtooth between the spring 40 and clutch 44. The spiral grooves 51 of the numeric sleeve 50 and the spiral grooves of the drive sleeve 30 have the same lead. This allows the numeric sleeve 50 to extend from the housing 10 and the drive sleeve 30 to move up the piston rod 20 at the same rate. At the limit of travel, the radial stop of the numeric sleeve 50 engages either a first stop or a second stop on the housing 10 to prevent further movement in the dose-increment direction 4. Rotation of the piston rod 20 is prevented by the entire driven thread on the piston rod 20 being in the opposite direction.

[0118] A final dose limiter 35, which is coupled to the housing 10, advances along the threads 31 due to rotation of the drive sleeve 30. Upon reaching the final dose dispensing position, a radial stop formed on the surface of the final dose limiter 35 abuts a radial stop on the flange portion 33 of the drive sleeve 30, preventing both the final dose limiter 35 and the drive sleeve 30 from further rotation.

[0119] If a user unintentionally dials in a dose greater than the desired dose, the injection device 1, configured as a pen injector, allows the dose to be dialed lower without dispensing medication from the medication container 6. To do this, the dose dial 12 is simply rotated backwards, causing the system to operate in reverse. The flexible arm of the spring or clicker 40 then acts as a ratchet, preventing the spring 40 from rotating. Torque transmitted through the clutch 44 causes the sawtooth teeth to overlap each other, producing a clicking sound corresponding to the dialed-in dose reduction. Typically, the sawtooth teeth are arranged so that the circumferential extent of each tooth corresponds to a unit dose.

[0120] Once the desired dose has been dialed in, the user may dispense the set dose by simply depressing the trigger 11. This causes the clutch 44 to be displaced axially relative to the number sleeve 50, disengaging its dog teeth. However, the clutch 44 remains rotationally engaged relative to the drive sleeve 30. The number sleeve 50 and dose dial 12 are now free to rotate in accordance with the spiral grooves 51.

[0121] The axial movement deforms the flexible arm of spring 40 to ensure the sawtooth cannot overhaul during dispensing. This prevents drive sleeve 30 from rotating relative to housing 10, but still allows free axial movement relative to the housing. The deformation is then used to urge spring 40 and clutch 44 back along drive sleeve 30, restoring the connection between clutch 44 and trigger sleeve 50 once distally directed dosing pressure is removed from trigger 11.

[0122] Longitudinal axial movement of the drive sleeve 30 rotates the piston rod 20 through a through opening in the support of the housing 10, thereby advancing the stopper 7 in the cartridge 6. Once the dialed dose has been dispensed, the numeric sleeve 50 is prevented from further rotation by at least one stop extending from the dose dial 12 contacting at least one corresponding stop on the housing 10. The zero dose position may be determined by abutment of one of the axially extending edges or stops of the numeric sleeve 50 with at least one or several corresponding stops on the housing 10.

[0123] During dose setting and when the drive mechanism 8 or dose setting mechanism 9 is in dose setting mode, the drive sleeve 30 rotates simultaneously with the dose dial 12 and the numeric sleeve 50. The drive sleeve 30 is threadably engaged with the piston rod 20, which is stationary relative to the housing 10 during dose setting. The drive sleeve 30 therefore tends to a screwing or helical movement during dose setting. The drive sleeve 30 begins to move proximally as the dose dial is rotated in the dose increase direction 4, e.g., clockwise. To adjust or modify the dose size, the dose dial 12 is rotatable in the opposite direction, and therefore in the dose decrease direction 5, e.g., counterclockwise.

[0124] The above-described discharge or drive mechanism 8 is merely illustrative of one of several differently configured drive mechanisms that may generally be implemented in a disposable pen-type injector. Such drive mechanisms are described in more detail in WO 2004 / 078239 A1, WO 2004 / 078240 A1, or WO 2004 / 078241 A1, each of which is incorporated herein by reference in its entirety.

[0125] 1, the distal end of the cartridge holder 14 includes a proximally oriented stop surface 54, for example, on the inside 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 manner, when the needle assembly 15 including the double-tipped injection needle 19 is attached, the proximal end 67 of the injection needle 19 may pass through the aperture 55 to reach and penetrate the seal 26 provided at the outlet 61 of the medication container 6.

[0126] In the currently shown example, the drug container 6 is implemented as a cartridge. The drug container 6 includes a tubular barrel 25. The barrel 25 includes a radially narrowing shoulder portion 66 that extends toward the distal end 63 into a head portion 69 provided at the distal free end 63 of the barrel 25. The outlet 61 of the drug container 6 is covered and / or sealed by a pierceable seal 26 that can be secured to the head portion 69 by a locking cap 60. The locking cap 60 can include or form a beaded cap that provides a form-fit of the locking cap 60 and the seal 26 to the distal end 63 of the barrel 25. The locking cap 60 includes a central outlet aperture 62 through which the proximal end 67 of the injection needle 15 can be guided to pierce or penetrate the seal 26, as shown in FIG. 3 .

[0127] The injection device 1 as shown in Figure 1 may be in a pre-use configuration as defined above. In the pre-use configuration, the piston rod 20 and / or the presser foot 23 are in longitudinal and mechanically biased abutment with the stopper 7 of the medicament container 6. The medicament container 6 is held inside the cartridge holder 14 by 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, a shoulder portion 66 of the medicament container 6 is in longitudinal distal abutment with a complementary shaped proximal stop surface provided on the inside of the cartridge holder 14.

[0128] Towards the proximal direction 3 , the medicament container 6 is trapped and / or secured inside the housing 10 or cartridge holder 14 by longitudinal abutment between the retainer 23 and the proximal end of the stopper 7 .

[0129] 5, once the final assembled configuration of the injection device 1 is reached, i.e. once the cartridge holder 14 with the drug container 6 disposed therein is fixed or attached to the body 10 of the injection device 1, a mutual abutment configuration between the stopper 7 and the piston rod 20 may already be obtained. However, once the final assembled configuration is reached and during assembly of the injection device, the application of substantial distally directed pressure on the stopper 7 of the drug container 6 is generally avoided.

[0130] Here, the injection device 1 provides a dedicated step for transferring the injection device 1 into a pre-use configuration, i.e., by moving the piston rod 20 in the distal direction 2 relative to the stopper 7 until a clearly defined mechanically biased abutment with the stopper 7 is obtained.

[0131] Upon reaching the pre-use configuration, the piston rod 20 and / or presser foot 23 exert a distally directed pre-use pressure on the stopper 7 that is counteracted by abutment of the distal end 63 or shoulder portion 66 with a complementary shaped, proximally facing stop surface 54 on the cartridge holder 14. The pre-use pressure exerted on the stopper 7 is typically equal to or greater than the drive pressure normally required to move the stopper distally to inject a dose of medication when the injection needle 19 has unobstructed access to the interior of the medication container 6. Thus, upon reaching the pre-use configuration, the drive train or drive mechanism 8 and medication container 6 are in a pre-tensioned or biased state.

[0132] In the pre-use configuration, the distal end 63, and therefore the outlet 61 of the medication container 6, is not and remains unconnected to the needle assembly 15. As a result of an increase in pressure level within the medication container, the elastomeric seal 26, and in particular the central portion of the seal 26 that is located at or overlaps the outlet aperture 62 of the fixation cap 60, may be prone to protrude distally and bulge outward or deform, resulting in the formation of a respective outwardly extending bulge portion 64 of the seal 26. It is now intended to attach the needle assembly 15 to the distal end of the injection device 1 in order to transition the injection device 1 from the pre-use configuration to the ready-to-use configuration.

[0133] During and upon installation of the needle assembly 15 in the cartridge holder 14, the proximal end 67 of the injection needle 19 pierces the seal 26, as shown in FIG. 3. As a result, due to an increase in fluid pressure within the drug container, there may be a pressure release within the drug container 6 as soon as the proximal end 67 crosses the seal 26. The pressure release is accompanied by the expulsion of a specific amount of drug through the injection needle 19.

[0134] As a result, a few drops may be expelled from the distal end 68 of the injection needle 19 during the needle assembly process. As a result, pressure release may cause the bulge portion 64 of the seal 26 to relax to an initial, unbiased state 64', as shown in FIG. 3. The resilient return movement of the seal 26 from the outwardly stretched bulge portion 64 toward the unbiased or relaxed state 64' is accompanied by a slight reduction in the available storage space for the liquid medicament within the medicament container 6. This reduction in storage space may also contribute to expelling a limited amount of medicament through the injection needle 19 upon needle installation.

[0135] The amount of medication that may be expelled due to pressure release during attachment of the needle to the injection device may be trapped in the inner needle cap 16 and / or outer needle cap 17 that are attached to the needle assembly 15 when the needle assembly is attached and secured to the injection device 1. In this manner, the needle caps 16, 17 may prevent the end user or patient from noticing the pressure release action during attachment of the needle assembly. The amount of medication that is expelled during attachment of the needle may be fairly accurately trapped in the inner and / or outer needle caps 16, 17. The final step in preparing the injection device for performing an injection procedure requires removal of the needle caps 16, 17.

[0136] The transition of the injection device from the pre-use configuration to the ready-to-use configuration has already begun when the needle 15 pierces the seal 26 during the assembly process of the injection device. The final attachment position of the needle assembly 15 to the injection device 1 and / or medication container 6 is shown schematically in Figure 3. As shown in Figure 3, once the final assembly position is reached, the proximal end 67 of the needle 19 is located at a well-defined longitudinal distance from the inner surface of the seal 26.

[0137] There is sufficient time for the pressure release action described above during the process of attaching the needle assembly 15 to the injection device 1. To that extent, the pressure release essentially ends immediately after the needle 19 is attached to the injection device 1, and the end user may not even notice the pressure release action caused by the needle attachment.

[0138] The flowchart in Figure 6 shows a number of steps in a method for preparing an injection device 1. In a first step 100, an injection device 1 as described herein is provided. The injection device 1 may be implemented as a disposable or reusable pen-type injector. The injection device 1 may be implemented entirely mechanically or even electromechanically. In some examples, the injection device 1 includes a mechanical energy storage device, such as a spring, that is initially energized and / or that is energized by and / or during dose setting.

[0139] In other examples, the dosing force for advancing the piston rod 20 in the distal direction 2 to inject the dose is provided solely by a user of the device 1. In other examples, a mechanical energy storage device provides at least a portion of the driving force during the injection procedure.

[0140] In a subsequent step 102, the injection device 1 is transitioned to a pre-use configuration by advancing the piston rod 20 of the drive mechanism 8 in the distal direction 2 to longitudinally and mechanically biased abutment with the stopper 7 of the drug container 6. In some examples, the piston rod 20 is advanced by default a predefined distance relative to the housing 10 and / or relative to the drug container 6.

[0141] In another example, the forward movement may be pressure controlled, whereby a pressure sensing arrangement may be provided, whereby 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 is reached, after which any final ongoing distally forward movement of the piston rod 20 is responsively stopped.

[0142] The predefined distance is selected such that by moving the piston a predefined distance in the distal direction 2, the final tolerances, mechanical play, and final longitudinal gap size between the piston rod and the stopper can be reduced and / or eliminated. In some examples, transition of the injection device to the pre-use configuration is achieved simply by setting or dialing a predefined size dose, for example a dose size of only a few units, and performing the respective dosing procedure, for example by pressing the trigger 11 of the drive mechanism 8, thereby advancing the piston rod 20 or plunger a well-defined longitudinal distance relative to the housing 10 and / or to the medication container 6.

[0143] The forward movement of the piston rod 20 is accompanied by a build-up of pre-use pressure on the stopper 17. Once the pre-use configuration is reached, the distal end 63 of the drug container 6 is sealed, and remains sealed, to prevent any uncontrolled expulsion of drug therefrom. After step 102, and after the injection device 1 has been moved to the pre-use configuration, it may be wrapped or packed in a package for transport and / or storage.

[0144] In a subsequent step 104, typically performed by the consumer or end user of the injection device 1, the needle assembly 15 is properly attached to the injection device 1. Attachment of the needle assembly 15 involves piercing the seal 26 with the injection needle 19, thereby providing pressure relief for the drive mechanism 8 and / or medication container 6. In the process of attaching the needle assembly 15 to the injection device 1, a respective amount of medication 27 may be expelled through the injection needle 19. A few drops may form or be ejected at the distal end 68 of the injection needle, and that amount of medication 27 may be trapped inside the inner needle cap 16.

[0145] In a subsequent final step 106 of preparing the injection device 1, the end user may remove the outer needle cap 17 and the inner needle cap 16 to allow injection of the agent into the biological tissue.

[0146] FIG. 7 further illustrates an injection system including 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 sized to receive or accommodate at least one injection device 1, 1′. In the currently shown example, the package 80 is a secondary or outer package sized to receive two individual injection devices 1, 1′. The injection device 1′ is also enclosed in a further package 80′. Both injection devices 1, 1′ are implemented as pen-type injectors. They are placed within the package 80, 80′ in the pre-use configuration described above. To use the injection devices 1, 1′, it is only necessary to attach and / or secure a needle assembly 15 to the outlet end of each injection device 1, 1′.

[0147] The mechanically biased abutment between the stopper 7 of the drug container 6 placed in the injection device 1, 1' and the respective piston rod 20 or presser foot 23 causes the procedure to be carried out somewhat automatically due to the pretensioned or biased configuration of the drive mechanism 8 or drive train of the injection device 1, 1'. [Explanation of symbols]

[0148] 1 Injection device 2 Distal direction 3 Proximal direction 4 Dose escalation 5 Direction of dose reduction 6. Medicine containers 7 Stopper 8 Drive mechanism 10. Housing 11 Triggers 12 Dose Dial 13 Dosage window 14 Cartridge holder 15 Needle Assembly 16 Inner needle cap 17 Outer needle cap 18 Protective cap 19 Syringe needle 20 Piston rod 21 Bearings 22 First screw 23 Press 24 Second screw 25 barrels 26 stickers 27 Drugs 28 threaded socket 30 Drive sleeve 31 Threaded section 32 flange 33 flange 35 Final Dose Limiter 40 Spring 44 Clutch 50 Numeric Sleeve 51 Groove 54 Stopping surface 55 aperture 60 Fixed Cap 61 Exit 62 Exit Aperture 63 Distal end 64 Bulging part 65 Pierceable part 66 Shoulder 67 Proximal end 68 Distal end 69 Head part 70 needle hub 80 packages 81 Receptacle

Claims

1. An injection device (1) for setting and injecting a dose of a drug, said injection device comprising: a housing (10), a drug container (6) containing an injectable drug (27), said drug container (6) being sealed by a movable stopper (7) towards the proximal direction (3) and comprising an outlet (61) towards the distal end (63); a drive mechanism (8) disposed within said housing (10) and including a longitudinally extending piston rod (20), said drive mechanism (8) operable to apply distally directed pressure to said stopper (7) to expel said dose of said medicament through said outlet (61); Including, In the pre-use configuration of the injection device (1), the piston rod (20) abuts the stopper (7) longitudinally and mechanically biased before expelling the first dose of the medication and / or before the first use of the injection device (1).

2. 2. The injection device (1) of claim 1, wherein in the pre-use configuration, the piston rod (20) applies a pre-use pressure directed distally to the stopper (7), the pre-use pressure being equal to or greater than the driving pressure required to move the stopper (7) distally (2) to inject the dose of the medicament.

3. 3. An injection device (1) according to claim 1 or 2, 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 claims 1 to 3, wherein the seal (26) is secured to the distal end (63) by a securing cap (60) including an exit aperture (62) to provide access to a pierceable portion (65) of the seal (26).

5. 5. The injection device (1) of claim 4, wherein in the pre-use configuration of the injection device (1), the pierceable portion (65) of the seal (26) includes or forms a bulged seal portion (64) that protrudes at least partially distally through the exit aperture (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 within the drug container (6) is greater than atmospheric pressure.

7. An injection device (1) as described in any one of claims 1 to 6, wherein in the pre-use configuration of the injection device (1), the piston rod (20) is in a priming position relative to the housing (10), and the priming position is offset distally 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 claims 1 to 7, wherein the injection device (1) is transferable from the pre-use configuration to the ready-to-use configuration by attaching a needle assembly (15) to the outlet (61), the needle assembly (15) comprising an injection needle (19) for piercing a seal (26) of the drug container (6).

9. 9. The injection device of claim 8, wherein the injection needle (19) is a double-tipped needle that pierces the seal (26) of the outlet (61) of the drug container (6) when the injection device is transferred from the pre-use configuration to the ready-to-use configuration.

10. 10. The injection device of claim 8, wherein the needle assembly (15) includes at least one of an outer needle cap (17) and an inner needle cap (16) configured to cover the distal end (68) of the injection needle (19) and to receive or capture a portion of the medicament (27) that is expelled 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. 1. An injection system comprising: - a package (80) providing a receptacle (81) for the injection device (1); An injection device (1) according to any one of claims 1 to 10, arranged in its pre-use configuration in said receptacle (81). an injection system including:

12. A method for preparing an infusion device (1) for injecting a drug, comprising the steps of: - providing an infusion device (1) according to any one of claims 1 to 10, - moving the injection device (1) into the pre-use configuration by moving the piston rod (20) distally relative to the stopper (7) of the drug container. A method comprising:

13. 13. The method of claim 12, further comprising the step of attaching a needle assembly (15) to the injection device (1) after transitioning the injection device (1) to the pre-use configuration, the needle assembly (15) comprising a double-tipped injection needle (19) having a proximal end (67) and a distal end (68).

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

15. 15. The method according to any one of claims 12 to 14, wherein during the process of attaching the needle assembly (15) to the injection device (1), in the pre-use configuration, a portion of the medicament (27) is expelled through the injection needle (19) by a pre-use pressure exerted by the piston rod (20) in a distal direction against the stopper (7).

16. 16. The method of claim 15, wherein the needle assembly (15) includes at least one of an outer needle cap (17) and an inner needle cap (16) that cover the distal end (68) of the injection needle (19) and receive or capture the portion of the medicament (27) expelled 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. The method of any one of claims 12 to 16, wherein the injection device (1) is transferable from the pre-use configuration to the ready-to-use configuration by attaching the needle assembly (15) to the injection device (1).

18. The method according to any one of claims 12 to 17, wherein the injection device (1) is placed in a package (80) for transport and / or storage after being transferred to the pre-use configuration.

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