CN111295213A - Injection device with dose limiter - Google Patents

Abstract

The present disclosure relates to an injection device for setting and injecting a dose of a medicament, comprising: -an elongated housing (10) extending in an axial direction (z) and configured to house a dose setting mechanism (9), wherein the housing (10) comprises a side wall (43; 143) with at least a first fastening feature (41; 141); -a dose dial (12) rotatable relative to the housing (10) to set a dose; -a dose tracker (50) arranged inside the housing (10) and operatively connectable to the dose dial (12), the dose tracker (50) comprising at least one tracking stop feature (51), wherein the dose tracker (50) is one of translationally or rotationally displaceable relative to the housing (10) during setting of a dose, and wherein a positional state of the dose tracker (50) relative to the housing (10) indicates a specification of the dose; and-a limiter (70; 170) attachable to the side wall (43; 143) of the housing (10) from outside the housing (10) and engageable with the at least first fastening feature (41, 141), wherein the limiter (70; 170) comprises at least one limiter stop feature (71; 171) extending inwardly from the side wall (43; 143) when the limiter (70; 170) is attached to the side wall (43), wherein the limiter stop feature (71; 171) and the tracking stop feature (51) are configured to engage with each other and prevent displacement of the dose tracker (50) beyond a predefined maximum dose position state.

Description

Injection device with dose limiter

Description of the invention

In one aspect, the present disclosure relates to an injection device, such as a pen injector, for setting and dispensing a dose of a medicament. In particular, the present disclosure relates to an injection device providing a maximum dose mechanism, i.e. a dose setting and dispensing mechanism operable only for dispensing doses not exceeding a predefined maximum threshold.

Background

Injection devices for setting and dispensing single or multiple doses of liquid medicaments are well known per se in the art. Generally, such devices have a substantially similar purpose to a common syringe injector.

Injection devices, in particular pen-type injectors, have to meet a number of user-specific requirements. For example, in the case of a patient suffering from a chronic disease such as diabetes, the patient may be physically infirm and may also have impaired vision. Therefore, a suitable injection device, especially intended for home administration, needs to be robust in construction and should be easy to use. Moreover, the handling and general disposition of the device and its components should be understood and appreciated. Furthermore, the dose setting procedure as well as the dose dispensing procedure must be easy to operate and must be unambiguous.

Typically, such devices comprise a housing comprising a specific cartridge holder adapted to receive a cartridge at least partially filled with the medicament to be dispensed. Such devices further comprise a drive mechanism, typically having a displaceable piston rod adapted to be operably engaged with the piston of the cartridge. By means of the drive mechanism and its piston rod, the piston of the cartridge is displaceable in the distal or dispensing direction and thus a predefined amount of medicament can be expelled by means of the piercing assembly, which is releasably coupled with the distal section of the housing of the injection device.

A medicament to be dispensed by the injection device is provided and contained in a multi-dose cartridge. Such cartridges typically comprise a glass barrel sealed in the distal direction by a pierceable seal and further sealed in the proximal direction by a piston. For reusable injection devices, an empty cartridge may be replaced with a new one. Conversely, when the medicament in the cartridge has been dispensed or used up, the injection device of the disposable type will be discarded.

For some applications, it may be advantageous to limit the maximum dose specification that can be dispensed or expelled from the cartridge. Then, accidental overdose can be prevented.

Target

It is therefore an object of the present disclosure to provide an injection device that provides a maximum dose function or maximum dose limiter. The maximum dose function or maximum dose limiter should be easily adaptable to existing injection device designs. The maximum dose function or maximum dose limiter should also be configurable as required and should provide a simple and intuitive way to change the maximum dose specification that can be expelled by the injection device.

By modifying only a limited number of existing device components, the achievement of maximum dosing functionality should be achievable. A further object is to individually modify the maximum dose value or dose specification by changing only a single component or a few components of the device. Thus, the maximum dose function of the device or its drive mechanism should be configurable by changing only one or a few components of the device or its drive mechanism. The maximum dose function or maximum dose limiter should be universally applicable to various drive mechanisms and injection devices. In particular, the maximum dose function or maximum dose limiter should be equally applicable to disposable injection devices as well as to reusable injection devices.

Disclosure of Invention

In one aspect, an injection device for setting and dispensing to inject a dose of medicament is provided. The injection device comprises an elongated housing extending in an axial direction. The housing is configured and dimensioned to receive a dose setting mechanism. Typically, the housing is also sized and configured to receive a cartridge filled with a medicament. The housing includes a sidewall having at least a first fastening feature. Typically, the housing is cylindrical or tubular in shape. The cylinder long axis extends in the axial direction and the side wall is tubular or cylindrical in shape. The geometry of the side wall of the housing may thus define a radial direction and a circumferential direction.

The injection device further comprises a dose dial. The dose dial is rotatable relative to the housing to set a dose. The dose dial may be rotatably supported on or in the housing. For example, the dose dial may be rotatably supported at the proximal section of the housing. The dose dial is user actuatable. Thus, a user may grip and rotate the dose dial relative to the housing to set or select a variable gauge dose.

The injection device further comprises a dose tracker arranged inside the housing. The dose tracker is operably connectable to the dose dial. The dose tracker includes at least one tracking stop feature. The dose tracker is at least one of translationally or rotationally displaced relative to the housing during setting of a dose. The positional state of the dose tracker relative to the housing indicates the specification of the dose. In the present context, the "positional state" of a component (e.g., a dose tracker) includes the position of the component and the angular orientation of the component relative to another component (e.g., relative to the housing). The dose tracker may be rotatably supported inside the housing while being axially fixed. Alternatively, the dose tracker may be slidably supported inside the housing relative to the housing while being rotationally fixed to the housing. Furthermore, the dose tracker is translationally and rotationally displaceable relative to the housing. It can move along a helical path relative to the housing. It may be threadably engaged with the housing.

The dose tracker belongs to a dose setting mechanism. The state of the position of the dose tracker relative to the housing is unambiguously related to the actually set dose specification. Depending on the specific implementation of the dose tracker, the degree of rotation and/or the degree of longitudinal or axial translation of the dose tracker relative to the housing is indicative of the actually set dose specification.

The injection device further comprises a limiter attachable to a side wall of the housing. The limiter may be attached from outside the housing. Which is engageable with at least the first fastening feature. The limiter includes at least one limiter stop feature that extends inwardly from the sidewall when the limiter is attached to the sidewall. The limiter stop feature and the tracking stop feature are configured to engage each other and prevent displacement of the dose tracker beyond a predefined maximum dose position state.

The limiter and its at least one limiter stop feature may be attached and fixable to a specific portion of the housing sidewall that corresponds to a predefined maximum dose position state of the dose tracker's tracking stop feature. When the dose tracker reaches the maximum dose position state, the specific part of the housing to which the limiter and/or limiter stop feature is attached coincides with the position state of the tracking stop feature.

In other words, when the dose tracker reaches the maximum dose position state, its tracking stop feature engages (e.g., abuts) a limiter stop feature fixed to a corresponding portion of the sidewall. The limiter stop feature and the tracking stop feature may include mutually corresponding stop surfaces, e.g., extending in circumferential and radial directions for axial engagement. Alternatively, the limiter stop feature and the tracking stop feature comprise stop surfaces extending in the axial direction and the radial direction that correspond to each other for circumferential engagement. When configured for axial engagement, the interengagement of the limiter stop feature and the tracking stop feature provides an axial stop, blocking and preventing longitudinal or axial translation of the dose tracker beyond a predefined maximum axial dose position state.

When configured for circumferential or tangential engagement, the interengagement of the limiter stop feature and the tracking stop feature provides a rotational stop, blocking and preventing rotation of the dose tracker relative to the housing beyond a predefined maximum rotational dose position state.

The predefined maximum dose position state defines the maximum dose that can be selected and dispensed by the injection device. By placing the limiter stop feature at a predefined position on the housing sidewall corresponding to the position status of the dose tracker, in particular the tracking stop feature, the maximum dose dispensable by the injection device may be defined.

Typically, the limiter may be attached to the side wall of the housing by at least a first fastening feature. Here, the first fastening feature may provide a dual function. First, the first fastening feature may provide a fastening structure that attaches the limiter to a corresponding portion of the housing sidewall. Further, the location of the first fastening feature on the sidewall defines a maximum dose position state of the dose tracker.

The limiter may be attached to the side wall from outside the housing. This allows the maximum dose specification of the injection device to be modified even after delivery to the patient or medical staff. Attaching the limiter to the housing from outside the housing enables subsequent modification of the injection device without having to open the housing of the injection device.

In a further embodiment, the housing, in particular the side wall of the housing, comprises at least a second fastening feature, which is separate from the at least first fastening feature with respect to one of the axial direction and the circumferential direction of the housing. Here, the limiter is selectively engageable with at least one of the first and second fastening features. The second fastening feature may be shaped and configured identically to the first fastening feature. The second fastening feature is distinguished from the first fastening feature only by its position or location on the housing sidewall. A feature and a second fastening feature. The first and second fastening features are separated from each other with respect to one of an axial direction (z) and a circumferential or tangential direction (w) of the housing.

All features and effects described below and above in relation to the first fastening feature may equally be applied to the second fastening feature. Furthermore, the features and effects described below with respect to only one of the first and second fastening features or both the first and second fastening features are equally applicable to embodiments in which the injection device comprises only a single, i.e. first, fastening feature on the housing sidewall.

Typically, the limiter is in principle engageable with both the at least first and second fastening features. Only one of the first and second fastening features may be connected or engaged at a time. For example, the limiter may be engaged with the first fastening feature while the second fastening feature remains disengaged. In this configuration, the limiter and the attachment of the limiter to the sidewall at the first fastening feature define a first maximum dose gauge of the injection device. The limiter can be detached from the first fastening feature and can be attached to the second fastening feature, as and if desired. The limiter and its limiter stop feature are then located at a different position on the housing sidewall than the first fastening feature. In this second configuration, the limiter and its attachment to the side wall and the second fastening feature define a second maximum dose gauge of the injection device that is different from the first maximum dose gauge due to the spatial separation of the first and second fastening features.

In another embodiment, at least one of the first and second fastening features includes a through opening extending through a sidewall of the housing. Here, the limiter stop feature is shaped and configured to extend through the through opening. The provision of at least one through opening in the side wall of the housing provides the possibility of attaching the limiter to the outer surface of the housing and thus from the outside of the housing. Since the through opening and the limiter stop feature are complementary or correspondingly shaped, the limiter stop feature may be inserted from the outside through the through opening in the side wall so that the free end of the limiter stop feature protrudes from the inner surface of the side wall. There, the limiter stop feature may be operably engaged with a correspondingly shaped tracking stop feature to prevent and block rotational and/or translational displacement of the dose tracker beyond a predefined maximum dose position state.

Typically and according to another embodiment, each of the at least first and second fastening features includes a through opening extending through the sidewall. Further, the first and second fastening features may comprise the same or identical geometries. In this manner, the same limiter may be selectively attached to one of the first and second fastening features. This provides and enables the injection device to be reconfigured. When, for example, attached to a first fastening feature to define a first maximum dosage gauge, the limiter may be detached from the first fastening feature and may be attached to a second fastening feature to define a second maximum dosage gauge different from the first maximum dosage gauge.

In another embodiment, the limiter includes a base portion. The limiter stop feature protrudes from the base portion. When attached to the sidewall, the base portion may be located outside the sidewall or may be located inside the sidewall. The base portion may be configured as a handle providing a well-defined grip of the restraint. The base portion may also improve the fastening of the limiter to the side wall. The base portion may be permanently attached to the side wall, for example by means of an adhesive or by means of welding.

When the base portion is attached to one of the first and second fastening features, it may be shaped to cover the first and second fastening features. Thus, the base portion may include a cover having a dimension at least equal to or greater than the distance between the first and second fastening features on the housing sidewall. In this manner and when attached to the first fastening feature, for example by means of the first limiter stop feature, the base portion covers both the first fastening feature and the second fastening feature. In another configuration and when attached to the second fastening feature, for example by means of a limiter stop feature, the base portion also covers both the first and second fastening features.

For either configuration, it is also conceivable to attach the limiter to the outer surface of the housing by means of the base portion. In another embodiment, the cross-section of the at least one through opening of the first and second fastening features may be greater than the outer cross-section of the limiter stop feature of the limiter. This enables a relatively smooth and easy insertion of the limiter stop feature into and through the through opening of the first or second fastening feature. In order to reconfigure the injection device and its dose setting mechanism, the limiter stop feature may also be easily removed and extracted from the through opening of the first or second fastening feature.

In another embodiment, the base portion may be attached to the outer surface of the sidewall. The base portion may be located on the outside or outer surface of the sidewall as a result of the limiter stop feature protruding from the base portion, with the limiter stop feature extending through the sidewall and protruding from the inner surface of the sidewall to engage with the tracking stop feature of the dose tracker. The attachment to the outer surface of the base portion also facilitates permanent access to the base portion and thus the restraint. Since the base portion remains at the outer surface, it is accessible to the user or medical personnel, thereby enabling the limiter to be removed from the side wall to reconfigure the injection device when required.

In another embodiment, the limiter stop feature may be inserted through the at least one through opening of the first and second fastening features such that a free end of the limiter stop feature facing away from the base portion projects inwardly from the inner surface of the sidewall. Thus, the elongation (typically the radial elongation) of the limiter stop feature is greater than the thickness of the sidewall, and also greater than the thickness of the through opening extending through the sidewall. In this manner, attaching and abutting the base portion to the outer surface of the sidewall results in a configuration in which the free end of the limiter stop feature projects inwardly from the inner surface of the sidewall.

In another embodiment, at least one of the first and second fastening features includes a recessed portion on an outer surface of the sidewall. The recessed portion is disposed adjacent to the at least one through opening of the first and/or second fastening feature. Typically, the recessed portion is shaped and configured to receive the base portion of the restraint therein. In this way, the outwardly facing surface of the base portion may be flush with the outer surface of the side wall of the housing. Indeed, when the limiter is attached to one of the first and second fastening features, and when the limiter, in particular its base portion, covers at least both the first and second fastening features, the outer surface of the housing may comprise a rather uniform and smooth shape without protrusions or recesses.

In another embodiment, the depth of the recessed portion is equal to or greater than the thickness of the base portion. In this way, the base portion can be completely received inside the recessed portion. The base portion does not protrude from the outer surface of the sidewall when attached to and disposed in the recessed portion. This provides a rather uniform and smooth shape of the outer circumference of the housing.

In another embodiment, the first fastening feature and the second fastening feature each include a recessed portion. Here, the recessed portions of the first and second fastening features merge with one another and form an elongated recess on the outer surface of the sidewall. Typically, the elongate recess on the outer surface of the side wall provides a receptacle for the base portion of the restrictor. When the base portion of the limiter is inserted into the elongated recess, its limiter stop feature may extend into and through the through opening of the respective first or second fastening feature.

In another embodiment, the elongated recess extends in an axial direction and/or in a circumferential direction. The at least one through opening of one of the first and second fastening features is tangentially or circumferentially or axially arranged adjacent to the elongated recess. If the elongated recess extends in the axial direction, the through opening is arranged tangentially or circumferentially adjacent to the elongated recess. The at least one through opening of one of the first and second fastening features is axially arranged adjacent to the elongated recess when the elongated recess extends in a circumferential or tangential direction.

Typically, the first and second fastening features each comprise a through opening, wherein the through openings are axially separated from each other. Two through openings are circumferentially arranged adjacent to the elongated recess. Typically, the limiter is shaped to attach to a portion of the elongated recess and engage only one of the through openings of the first and second fastening features. The remaining part of the further through opening and the elongated recess may then remain uncovered. The remaining portion or the unoccupied through opening may be individually covered with a separate cover.

In another embodiment, a set of at least two differently shaped limiters may be provided. The at least two limiters may include equally sized base portions configured to completely fill the elongated recess. The two limiters may be distinguished from each other by the shape and position of their at least one limiter stop feature relative to the base portion. The first limiter may include a limiter stop feature configured to engage with the first fastening feature when the limiter is attached to the sidewall of the housing. The second limiter may include a limiter stop feature specifically configured to engage with the second fastening feature when the limiter is attached to the sidewall of the housing.

In this way, the first and second restrainers with identically shaped base portions may always completely fill and cover the elongated recesses on the outer surfaces of the side walls. Depending on the particular selection of one of the first and second limiters, only one of the first and second fastening features and only one of the respective first and second through-openings through the sidewall will be occupied by the limiter stop feature.

In another embodiment, only one limiter may be provided, the base portion of the limiter being symmetrical about the axis of symmetry. Here, the recessed portion on the outer surface of the side wall may comprise a respective symmetry such that the limiter is attachable and securable to the outer surface of the housing in a first configuration and a second configuration, wherein the second configuration is rotated, for example, by 180 ° compared to the first configuration. Typically, the axis of symmetry coincides with the center of the distance between the first and second fastening features. In this manner, the limiter stop feature of the limiter engages the first fastening feature when in the first configuration and the limiter stop feature engages the second fastening feature when in the second configuration, e.g., when the limiter is rotated about 180 °.

In another embodiment, the base portion is L-shaped and includes a first leg and a second leg. The first and second legs extend at 90 ° with respect to each other. When attached to the side wall of the housing, the first leg may extend in a circumferential direction of the side wall and the second leg may extend in an axial direction of the side wall. When the elongated recess extends in the axial direction, the second leg may extend along the elongated recess and the first leg may extend perpendicular thereto along the circumference of the sidewall.

The L-shaped base portion facilitates attachment of the limiter to the side wall. The second leg may be attached to and may be received in a recess or elongate recess on the outer surface of the side wall, thereby defining the radial position of the limiter relative to the housing. The first leg may support at least one limiter stop feature of the limiter that extends radially inward into the interior of the housing. Here, a first leg with at least one limiter stop feature attached thereto protrudes into the housing and engages with a tracking stop feature of the dose tracker, while a second leg provides a well-defined attachment of the limiter at a well-defined radial position of the housing.

In further embodiments, a limiter stop feature protrudes from an end of the first leg that faces away from the second leg. Here, the limiter stop feature may constitute a first leg, while the second leg may be considered a flange portion of the limiter extending along a side wall of the housing.

In a further embodiment, the injection device is equipped with a cap attachable to the outer surface of the sidewall. The cover is configured to cover at least the first fastening feature and the second fastening feature. The cover may also be configured to cover a recessed portion on an outer surface of the sidewall adjacent to the at least one through opening of the first and/or second fastening feature. When attached to the side wall of the housing, the cover effectively conceals and conceals the position and presence of the restraint.

The lid may comprise a flexible foil which is adhesively attachable to the outer surface of the housing side wall. The cover may be transparent. Alternatively, the cover may be opaque. The cover may include a printed surface. The cover may include a label attached to an outer surface of the housing. The label may contain instructions or information regarding the use of the medicament and/or regarding the use of the injection device.

Instead of a flexible foil, the lid may comprise a sleeve or a housing made of a plastic material or made of metal. The cover may be positively engaged with the elongated housing. The cover and housing may include mutually corresponding fastening features, such as protrusions and correspondingly shaped recesses. The side walls of the cover and housing may include interengaging clip or snap features that provide removable or non-removable fastening of the cover to the housing side walls.

For example, the cap may comprise a housing in the form of a sleeve or a portion of a cylinder, such as a half-shell. The cap may comprise radial projections or radial recesses on an inner surface portion to engage with correspondingly shaped recesses or projections provided on an outer surface of the housing side wall of the injection device. In this way, the cover may be clamped or secured to the side wall of the housing. When the cover comprises a plastic housing, the outer surface of the cover may comprise a label. The cap may also be fastened to the injection device by means of an adhesive or by means of an adhesive label. It is also conceivable to attach the cover to the housing by means of welding.

In another embodiment, the injection device further comprises a piston rod. The piston rod is typically a component of the drive mechanism and/or the dose setting mechanism. The piston rod may be axially displaceable to dispense a dose of medicament from the cartridge. When the injection device is in the dispensing mode, the drive mechanism and/or the dose setting mechanism thereof is/are configured to longitudinally drive and displace the piston rod in the axial distal direction.

Typically, injection devices are provided with a cartridge filled with a medicament (e.g. a liquid medicament). The cartridge is typically sealed in the proximal direction by means of a bung. The bung is axially displaceable inside the cartridge to expel the liquid medicament from its distal end. The distal end of the cartridge is typically sealed by a pierceable seal. The pierceable seal is pierceable by means of a double-tipped injection needle. The injection needle may typically be releasably attached to a distal end and/or a dispensing end of a housing of the injection device, typically to a distal end of a cartridge holder belonging to the housing of the injection device.

In a further embodiment, the injection device comprises a cartridge at least partially filled with a medicament. The cartridge comprises a barrel filled with a medicament. The cartridge and hence the barrel is sealed in an axially proximal direction by the bung. The bung is axially displaceable relative to the tub by means of the piston rod. When the piston rod is advanced in the distal direction during dose dispensing, it applies a driving pressure to the stopper. As the cartridge is secured inside the housing, the bung starts to move in a distal direction thereby increasing the internal pressure of the cartridge resulting in the medicament being expelled from the cartridge.

In another aspect, a method of modifying a maximum dose specification of an injection device is provided. The method comprises the step of providing an injection device. The injection device comprises an elongated housing extending in an axial direction and configured to accommodate a dose setting mechanism. Typically, the housing is also configured to receive and contain a cartridge filled with a medicament. The housing also includes a sidewall having at least a first fastening feature. Typically, the sidewall further comprises at least a second fastening feature. The injection device further comprises a dose tracker arranged inside the housing. The dose tracker includes at least one tracking stop feature. The dose tracker is at least one of translationally or rotationally displaced relative to the housing during setting of a dose. The state of the position of the dose tracker relative to the housing is unambiguously indicative of the actually set dose specification.

The method of modifying a maximum dose specification further comprises the step of attaching a limiter to the housing sidewall by means of at least one fastening feature. The limiter includes at least one limiter stop feature that extends inwardly from the sidewall when attached to the sidewall. The limiter stop feature and the tracking stop feature are configured to engage each other and prevent displacement of the dose tracker beyond a predefined maximum dose position state.

Typically, the method of modifying the maximum dose specification of an injection device is applicable to an injection device as described above. Thus, all of the features, benefits and effects described above in connection with the injection device are equally applicable to the method of modifying the maximum dose specification of an injection device.

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 furthest from the injection site of a human or animal.

As used herein, the term "drug" or "medicament" means a pharmaceutical formulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has a molecular weight of up to 1500Da and/or is a peptide, protein, polysaccharide, vaccine, DNA, RNA, enzyme, antibody or antibody fragment, hormone or oligonucleotide, or a mixture of the above pharmaceutically active compounds,

wherein in a further embodiment the pharmaceutically active compound is useful for the treatment and/or prophylaxis of diabetes or complications associated with diabetes (such as diabetic retinopathy), thromboembolic disorders (such as deep vein or pulmonary thromboembolism), Acute Coronary Syndrome (ACS), angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compound comprises at least one peptide for the treatment and/or prevention of diabetes or complications associated with diabetes, such as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compound comprises at least one human insulin or human insulin analogue or derivative, glucagon-like peptide (GLP-1) or an analogue or derivative thereof, or exendin (exendin) -3 or exendin-4, or an analogue or derivative of exendin-3 or exendin-4.

Insulin analogs are, for example, Gly (a21), Arg (B31), Arg (B32) human insulin; lys (B3), Glu (B29) human insulin; lys (B28), Pro (B29) human insulin; asp (B28) human insulin; human insulin wherein proline at position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein 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.

Insulin derivatives are for example B29-N-myristoyl-des (B30) human insulin; B29-N-palmitoyl-des (B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB 28ProB29 human insulin; B30-N-myristoyl-ThrB 29LysB30 human insulin; B30-N-palmitoyl-ThrB 29LysB30 human insulin; B29-N- (N-palmitoyl-glutamyl) -des (B30) human insulin; B29-N- (N-lithochol- γ -glutamyl) -des (B30) human insulin; B29-N- (. omega. -carboxyheptadecanoyl) -des (B30) human insulin and B29-N- (. omega. -carboxyheptadecanoyl) human insulin.

Exendin-4 means, for example, exendin-4 (1-39), a peptide having the following sequence: H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH 2.

Exendin-4 derivatives are for example selected from the following list of compounds:

h- (Lys)4-des Pro36, des Pro37 Exendin-4 (1-39) -NH2,

H- (Lys)5-des Pro36, des Pro37 Exendin-4 (1-39) -NH2,

des Pro36 Exendin-4 (1-39),

des Pro36[ Asp28] Exendin-4 (1-39),

des Pro36[ IsoAsp28] Exendin-4 (1-39) ],

des Pro36[ Met (O)14, Asp28] Exendin-4 (1-39),

des Pro36[ Met (O)14, IsoAsp28] Exendin-4 (1-39),

des Pro36[ Trp (O2)25, Asp28] Exendin-4 (1-39),

des Pro36[ Trp (O2)25, IsoAsp28] Exendin-4 (1-39) ],

des Pro36[ Met (O)14Trp (O2)25, Asp28] Exendin-4 (1-39),

des Pro36[ Met (O)14Trp (O2)25, IsoAsp28] Exendin-4 (1-39); or

des Pro36[ Asp28] Exendin-4 (1-39),

des Pro36[ IsoAsp28] Exendin-4 (1-39) ],

des Pro36[ Met (O)14, Asp28] Exendin-4 (1-39),

des Pro36[ Met (O)14, IsoAsp28] Exendin-4 (1-39),

des Pro36[ Trp (O2)25, Asp28] Exendin-4 (1-39),

des Pro36[ Trp (O2)25, IsoAsp28] Exendin-4 (1-39) ],

des Pro36[ Met (O)14Trp (O2)25, Asp28] Exendin-4 (1-39),

des Pro36[ Met (O)14Trp (O2)25, IsoAsp28] Exendin-4 (1-39),

Wherein the group-Lys 6-NH2 may be bound to the C-terminus of an exendin-4 derivative;

or an exendin-4 derivative having the sequence:

des Pro36 Exendin-4 (1-39) -Lys6-NH2(AVE0010),

H- (Lys)6-des Pro36[ Asp28] exendin-4 (1-39) -Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38 Exendin-4 (1-39) -NH2,

H- (Lys)6-des Pro36, Pro38[ Asp28] exendin-4 (1-39) -NH2,

H-Asn- (Glu)5des Pro36, Pro37, Pro38[ Asp28] exendin-4 (1-39) -NH2,

des Pro36, Pro37, Pro38[ Asp28] Exendin-4 (1-39) - (Lys)6-NH2,

H- (Lys)6-des Pro36, Pro37, Pro38[ Asp28] exendin-4 (1-39) - (Lys)6-NH2,

H-Asn- (Glu)5-des Pro36, Pro37, Pro38[ Asp28] Exendin-4 (1-39) - (Lys)6-NH2,

H- (Lys)6-des Pro36[ Trp (O2)25, Asp28] exendin-4 (1-39) -Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38[ Trp (O2)25] Exendin-4 (1-39) -NH2,

H- (Lys)6-des Pro36, Pro37, Pro38[ Trp (O2)25, Asp28] exendin-4 (1-39) -NH2,

H-Asn- (Glu)5-des Pro36, Pro37, Pro38[ Trp (O2)25, Asp28] Exendin-4 (1-39) -NH2,

des Pro36, Pro37, Pro38[ Trp (O2)25, Asp28] Exendin-4 (1-39) - (Lys)6-NH2,

H- (Lys)6-des Pro36, Pro37, Pro38[ Trp (O2)25, Asp28] exendin-4 (1-39) - (Lys)6-NH2,

H-Asn- (Glu)5-des Pro36, Pro37, Pro38[ Trp (O2)25, Asp28] Exendin-4 (1-39) - (Lys)6-NH2,

H- (Lys)6-des Pro36[ Met (O)14, Asp28] exendin-4 (1-39) -Lys6-NH2,

des Met (O)14Asp28 Pro36, Pro37, Pro38 Exendin-4 (1-39) -NH2,

H- (Lys)6-desPro36, Pro37, Pro38[ Met (O)14, Asp28] exendin-4 (1-39) -NH2,

H-Asn- (Glu)5-des Pro36, Pro37, Pro38[ Met (O)14, Asp28] Exendin-4 (1-39) -NH2,

des Pro36, Pro37, Pro38[ Met (O)14, Asp28] Exendin-4 (1-39) - (Lys)6-NH2,

H- (Lys)6-des Pro36, Pro37, Pro38[ Met (O)14, Asp28] exendin-4 (1-39) - (Lys)6-NH2,

H-Asn- (Glu)5des Pro36, Pro37, Pro38[ Met (O)14, Asp28] Exendin-4 (1-39) - (Lys)6-NH2,

H-Lys6-des Pro36[ Met (O)14, Trp (O2)25, Asp28] exendin-4 (1-39) -Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38[ Met (O)14, Trp (O2)25] exendin-4 (1-39) -NH2,

H- (Lys)6-des Pro36, Pro37, Pro38[ Met (O)14, Asp28] exendin-4 (1-39) -NH2,

H-Asn- (Glu)5-des Pro36, Pro37, Pro38[ Met (O)14, Trp (O2)25, Asp28] Exendin-4 (1-39) -NH2,

des Pro36, Pro37, Pro38[ Met (O)14, Trp (O2)25, Asp28] Exendin-4 (1-39) - (Lys)6-NH2,

H- (Lys)6-des Pro36, Pro37, Pro38[ Met (O)14, Trp (O2)25, Asp28] Exendin-4 (S1-39) - (Lys)6-NH2,

H-Asn- (Glu)5-des Pro36, Pro37, Pro38[ Met (O)14, Trp (O2)25, Asp28] Exendin-4 (1-39) - (Lys)6-NH 2;

or a pharmaceutically acceptable salt or solvate of any of the exendin-4 derivatives described above.

Hormones are, for example, pituitary hormones or hypothalamic hormones as listed in Rote list, chapter 50, 2008 edition, or regulatory active peptides and antagonists thereof, such as gonadotropin (gonadotropin) (follicle stimulating hormone (Follitropin), luteinizing hormone, chorionic gonadotropin (chlorinogonadotropin), gamete maturation hormone), growth hormone (Somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, goserelin.

The polysaccharide is, for example, a glycosaminoglycan, hyaluronic acid, heparin, low or ultra-low molecular weight heparin or derivatives thereof, or a sulfated form (e.g., polysulfated form) of the aforementioned polysaccharides, and/or pharmaceutically acceptable salts thereof. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (about 150kDa), also known as immunoglobulins that share a basic structure. They are glycoproteins because they have sugar chains added to their amino acid residues. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit); the secreted antibody may also be a dimer with two Ig units (e.g., IgA), a tetramer with four Ig units (e.g., teleost IgM), or a pentamer with five Ig units (e.g., mammalian IgM).

An Ig monomer is a "Y" shaped molecule composed of four polypeptide chains, two identical heavy chains and two identical light chains linked by disulfide bonds between cysteine residues, each heavy chain being about 440 amino acids long, each light chain being about 220 amino acids long, each heavy and light chain containing respective intrachain disulfide bonds that stabilize their folding, each chain being composed of domains named Ig domains, which contain about 70-110 amino acids and are divided into different categories by their size and function (e.g., variable or V regions and constant or C regions), which have unique immunoglobulin folds, with two of the β folded into a "sandwich" shape, held together by the interaction between conserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chains, represented by α, δ, ε, γ, and μ the types of heavy chains present define the isotype of the antibody, and these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively.

α and gamma comprise about 450 amino acids, and delta comprises about 500 amino acids, and mu and epsilon comprise about 550 amino acids, each heavy chain having a constant region (C)_H) And variable region (V)_H) Heavy chains gamma, α, and delta have constant regions composed of three tandem Ig domains, and hinge regions for increased flexibility, and heavy chains mu and epsilon have constant regions composed of four immunoglobulin domains.

In mammals, there are two types of immunoglobulin light chains, denoted by λ and κ. The light chain has two contiguous domains: one constant domain (CL) and one variable domain (VL). The approximate length of the light chain is 211 to 217 amino acids. Each antibody comprises two light chains that are always the same; only one type of light chain, κ or λ, is present per antibody in mammals.

Although the general structure of all antibodies is very similar, the unique properties of a given antibody are determined by the variable (V) regions as detailed above. More specifically, the variable loops (three per light chain (VL) and three on the heavy chain (VH)) are responsible for binding to the antigen, i.e. for its antigen specificity. These loops are called Complementarity Determining Regions (CDRs). Because the multiple CDRs from the VH and VL domains constitute the antigen binding site, it is the combination of the heavy and light chains (rather than each alone) that determines the final antigen-specific combination.

An "antibody fragment" contains at least one antigen-binding fragment as defined above and exhibits essentially the same function and specificity as the complete antibody from which it is derived. Limited proteolysis with papain cleaves the Ig prototype into three fragments. Two identical amino terminal fragments are antigen binding fragments (Fab), each of which comprises one complete L chain and about half of an H chain. The third fragment is a crystallizable fragment (Fc) that is similar in size but contains the carboxy-terminal half of the two heavy chains and their interchain disulfide bonds. The Fc comprises a carbohydrate, a complement binding site, and an FcR binding site. Limited pepsin digestion produces a single F (ab')2 fragment that contains both a Fab fragment and a hinge region, including the H-H interchain disulfide bond. F (ab')2 is bivalent for antigen binding. The disulfide bond of F (ab ')2 can be cleaved to obtain Fab'. In addition, the variable regions of the heavy and light chains may be fused together to form a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts. Acid addition salts are, for example, the HCl or HBr salts. Basic salts are, for example, salts with a cation selected from the cations of alkali metals or alkaline earth metals, such as Na + or K + or Ca2+, or the ammonium ion N + (R1) (R2) (R3) (R4), wherein R1 to R4 represent, independently of one another: hydrogen, an optionally substituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10-heteroaryl group. Other examples of pharmaceutically acceptable salts are described in the following documents: "Remington's Pharmaceutical Sciences" 17 th edition Alfonso R.Gennaro (eds.), Mark publishing Company, Easton, Pa., U.S.A.,1985 and Encyclopedia of Pharmaceutical technology.

Pharmaceutically acceptable solvates are for example hydrates.

It will also be apparent to those skilled in the art that various modifications and variations can be made in the injection device without departing from the spirit and scope of the disclosure herein. Furthermore, it should be noted that any reference signs used in the appended claims should not be construed as limiting the scope of the invention.

Drawings

In the following, embodiments of the drive mechanism and the injection device will be described in detail with reference to the accompanying drawings, wherein:

figure 1 schematically shows an embodiment of the injection device,

figure 2 shows an exploded view of the components of the injection device of figure 1,

figure 3 is a side view of one embodiment of an injection device with the limiter removed therefrom,

figure 4 is a side view of a limiter attachable to a side wall of an injection device,

figure 5 is a bottom view of the limiter according to figure 4,

fig. 6 is a side view of the injection device of fig. 3, with the limiter of fig. 4 and 5 attached thereto,

figure 7 is a side view of another embodiment of an injection device,

figure 8 is a further view of the injection device of figure 7 rotated slightly relative to the longitudinal axis,

figure 9 is an isolated perspective view of another embodiment of the limiter,

figure 10 shows the limiter of figure 9 from another angle,

fig. 11 indicates the limiter of fig. 9 in a first configuration, attached to a side wall of an injection device according to fig. 7 or 8,

fig. 12 shows the limiter of fig. 9 in a second configuration, attached to a side wall of an injection device,

figure 13 is a longitudinal section through a part of the injection device according to figure 7 or 8,

figure 14 is a cross section according to figure 13 with a limiter attached thereto,

figure 15 is a plan view of the section according to figure 14,

figure 16 shows a housing attachable to the housing of an injection device,

figure 17 shows the inside of the housing of figure 16,

fig. 18 shows the case of fig. 16 and 17 with the tag attached thereto, an

Fig. 19 shows the injection device of fig. 7 provided with the housing of fig. 16.

Detailed Description

The injection device 1 as shown in fig. 1 and 2 is a pre-filled disposable injection device comprising a housing 10 to which an injection needle 15 can be attached. The injection needle 15 is protected by an inner needle cap 16 and an outer needle cap 17 or a protective cap 18 configured to enclose and protect a distal section of the housing 10 of the injection device 1. The housing 10 may include and form a main housing portion configured to house the drive mechanism 8 as shown in fig. 2. The injection device 1 may further comprise a distal housing part, denoted 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 cartridge 6 filled with a liquid medicament. The cartridge 6 comprises a cylindrical or tubular barrel 25 sealed in the proximal direction 3 by means of a bung 7 located within the barrel 25. The bung 7 is displaceable in the distal direction 2 by means of the piston rod 20 relative to the barrel 25 of the cartridge 6. The distal end of the cartridge 6 is sealed by a pierceable seal 26, which is configured as a septum and pierceable by the proximally oriented tip of the injection needle 15. The cartridge holder 14 comprises a threaded socket 28 at its distal end for threaded engagement with a corresponding threaded part of the injection needle 15. By attaching the injection needle 15 to the distal end of the cartridge holder 14, the seal 26 of the cartridge 6 is penetrated, thereby establishing a fluid transfer path to the interior of the cartridge 6.

When the injection device 1 is configured to administer e.g. 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), wherein 1IU is the biological equivalent of about 45.5 μ g pure crystalline insulin (1/22 mg).

As further shown in fig. 1 and 2, the housing 10 includes a dosage window 13, which may be in the form of an aperture in the housing 10. The dose window 13 allows a user to view a limited portion of the number sleeve 80, which is configured to move when the dose dial 12 is rotated to provide a visual indication of the currently set dose. When turned during dose setting and/or dispensing or expelling, the dose dial 12 rotates in a helical path relative to the housing 10.

The injection device 1 may be configured such that turning the dose knob 12 causes a mechanical click to provide acoustic feedback to the user. The number sleeve 80 interacts mechanically with the piston in the insulin cartridge 6. When the needle 15 is penetrated into a skin portion of a patient and the trigger 11 or injection button is pushed, the insulin dose displayed in the display window 13 will be expelled from the injection device 1. When the needle 15 of the injection device 1 remains in the skin portion for a certain time after pushing the trigger 11, a higher percentage of said dose is actually injected into the patient. The expelling of the insulin dose may also cause a mechanical click, but it is different from the sound produced when using the dose dial 12.

In this embodiment, during insulin dose delivery, the dose dial 12 is turned to its initial position of axial movement, that is to say not rotated, while the number sleeve 80 is rotated to return to its initial position, for example displaying a dose of zero units.

The injection device 1 may be used for several injection procedures until the cartridge 6 is emptied or the medicament in the injection device 1 reaches an expiration date (e.g. 28 days after first use).

In addition, prior to the first use of the injection device 1, a so-called "prime shot" may need to be performed to remove air from the cartridge 6 and needle 15, for example by selecting two units of medicament and depressing the trigger 11 while holding the needle 15 of the injection device 1 up. For ease of presentation, it will be assumed hereinafter that the expelled amount substantially corresponds to the injected dose, such that for example the amount of medicament expelled from the injection device 1 equals the dose received by the user.

The expelling or drive mechanism 8, as illustrated in more detail in fig. 2, comprises a number of mechanically interacting components. The flange-like support of the housing 10 comprises a threaded axial through opening which is in threaded engagement with a first 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 proximally facing thrust receiving surface of the bung 7 of the cartridge 6. During a dispensing action, the piston rod 20 rotates relative to the housing 10, thereby undergoing a distally directed advancing movement relative to the housing 10, 30 and thus relative to the barrel 25 of the cartridge 6. As a result, the bung 7 of the cartridge 6 is displaced in the distal direction 2 by a well-defined distance due to the threaded engagement of the piston rod 20 with the housing 10.

The piston rod 20 is also provided with a second thread 24 at its proximal end. The distal thread 22 and the proximal thread 24 are oppositely threaded.

A drive sleeve 30 is also provided having a hollow interior to receive the piston rod 20. The drive sleeve 30 comprises an internal thread which is threadedly engaged with the proximal thread 24 of the piston rod 20. Furthermore, the drive sleeve 30 comprises an externally threaded section 31 at its distal end. The threaded section 31 is axially confined between the distal flange portion 32 and a further flange portion 33, which is located at a predetermined axial distance from the distal flange portion 32. Between these two flange portions 32, 33 a last dose limiter 35 is provided in the form of a semi-circular nut having an internal thread cooperating with the threaded section 31 of the drive sleeve 30.

The last dose limiter 35 further comprises a radial recess or radial protrusion at its outer circumference to engage with a complementary shaped recess or protrusion at the inside 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 incrementing direction 4 or clockwise during a continuous dose setting procedure results in a cumulative axial displacement of the last dose limiter 35 relative to the drive sleeve 30. An annular spring 40 is also provided in axial abutment with the proximally facing surface of the flange portion 33. Further, a tubular adapter (clutch)60 is provided. The adaptor 60 is provided with a series of circumferentially oriented serrations at a first end. A radially inwardly directed flange is positioned toward a second, opposite end of the adapter 60.

Furthermore, a dose dial sleeve is provided, also denoted as number sleeve 80. The number sleeve 80 is disposed outside the spring 40 and the adapter 60, and is located radially inside the housing 10. A helical groove 81 is provided around the outer surface of the number sleeve 80. The housing 10 is provided with a dosage window 13 through which a portion of the outer surface of the numeral 80 is visible. The housing 10 is also provided with helical ribs at the inner side wall portion of the insert 62 which will seat in the helical groove 81 of the number sleeve 80. A tubular insert 62 is inserted into the proximal end of the housing 10. It is rotationally and axially fixed to the housing 10. First and second stops are provided on the housing 10 to limit the dose setting process during which the number sleeve 80 rotates in a helical motion relative to the housing 10.

A dose dial 12 in the form of a dose dial grip is disposed about an outer surface of the proximal end of the number sleeve 80. 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 secured to the numerals 80 to prevent relative movement therebetween. The dose dial 12 is provided with a central opening.

The trigger 11 (also denoted as dose button) is substantially T-shaped. Which is disposed at the proximal end of the injection device 10. The stem 64 of the trigger 11 extends through an opening in the dose dial 12, through the inner diameter of an extension of the drive sleeve 30 and into a receiving recess at the proximal end of the piston rod 20. The rod 64 is held for limited axial movement in the drive sleeve 30 and resists rotation relative thereto. The head of the trigger 11 is generally circular. A trigger sidewall or skirt extends from the circumference of the head and is also adapted to seat in a proximally accessible annular recess of the dose dial 12.

The user rotates the dose dial 12 to dial a dose. In case the spring 40 also acts as a clicker and the adapter 60 is engaged, the drive sleeve 30, the spring or clicker 40, the adapter 60, and the number sleeve 80 rotate together with the dose dial 12. Audible and tactile feedback of the dialled dose is provided by the spring 40 and by the coupling 60. Torque is transmitted between the spring 40 and the clutch 60 by the serrations. The helical groove 81 on the number sleeve 80 and the helical groove in the drive sleeve 30 have the same lead. This allows the number sleeve 80 to extend from the housing 10 and the drive sleeve 30 to climb up the piston rod 20 at the same rate. At the limit of travel, a radial stop on the number sleeve 80 engages with a first stop or a second stop provided on the housing 10 to prevent further movement. Rotation of the piston rod 20 is prevented due to the opposite direction of the integral thread and the driven thread on the piston rod 20.

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

The injection device 1 configured as a pen injector allows dialling of a small dose without dispensing medicament from the cartridge 6 if the user inadvertently dials more than the desired dose. This is done by simply counter-rotating the dose dial 12. This causes the system to work in reverse. The flexible arm of the spring or clicker 40 then acts as a ratchet that prevents rotation of the spring 40. The torque transmitted through the adapter 60 presses the serrations against each other to produce a click sound corresponding to the reduction of the dialled dose. Typically, the serrations are arranged such that the circumferential extent of each serration corresponds to a unit dose.

When the desired dose has been dialled, the user may simply dispense the set dose by depressing the trigger 11. This axially displaces the adapter 60 relative to the number sleeve 80, disengaging its dog teeth. However, the adapter 60 remains rotationally keyed to the drive sleeve 30. The number sleeve 80 and the dose dial 12 are now free to rotate according to the helical groove 81.

The axial movement deforms the flexible arms of the spring 40 to ensure that the serrations are not tampered with 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 then serves to push back the spring 40 and the clutch 60 along the drive sleeve 30 to restore the connection between the clutch 60 and the number sleeve 80 when the distally directed dispensing pressure is removed from the trigger 11.

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 dialled dose has been dispensed, the number sleeve 80 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 80 with at least one or several corresponding stops of the housing 10.

The ejection mechanism or drive mechanism 8 as described above is merely an example of one of a number of different configurations of drive mechanisms that may typically be implemented in a disposable pen injector. The drive mechanism as described above is explained in more detail in, for example, WO 2004/078239 a1, WO2004/078240 a1 or WO 2004/078241 a1, the entire contents of which are incorporated herein by reference.

The dose setting mechanism 9 as illustrated in fig. 2 comprises at least a dose dial 12 and a number sleeve 80. When the dose dial 12 is rotated during setting of a dose and for setting of a dose, the number sleeve 80 starts to rotate relative to the housing along a helical path defined by the threaded engagement of the outer thread or helical groove 81 of the number sleeve with a correspondingly shaped threaded section on the inner surface of the housing.

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 with the number sleeve 80. The drive sleeve 30 is threadedly engaged with the piston rod 20, which is stationary relative to the housing 10 during dose setting. Thus, the drive sleeve 30 undergoes a helical or spiral movement during dose setting. When the dose dial is rotated in the dose incrementing direction 4 (e.g., clockwise), the drive sleeve 30 begins to travel in the proximal direction. To adjust or correct the gauge of a dose, the dose dial 12 may be rotated in the opposite direction, thus in the dose decrementing direction 5 (e.g. counter-clockwise).

At least one of the drive sleeve 30 and the number sleeve 80 serves as a dose tracker 50 that includes a tracking stop feature 51. In embodiments such as illustrated in fig. 13-15, one of the flanges 32 or 33 is provided and coincides with a tracking stop feature 51 of the dose tracker 50. A limiter 70 is also provided as a separate piece.

As illustrated in fig. 3, 7 or 8, the housing 10 includes tubular or cylindrical sidewalls 43, 143. The side walls 43, 143 include first and second fastening features 41, 141, 42, 142. As indicated, for example, in fig. 3, the first fastening feature 41 is axially separated from the second fastening feature 42. In the illustrated embodiment, the first and second fastening features 41, 42 each include a through opening 44 extending through a sidewall 43 of the housing 10.

The limiter 70 includes a flat shaped base portion 72 and a limiter stop feature 71 protruding from the base portion 72. The limiter stop feature 71 is configured and dimensioned to mate with the first fastening feature 41 and with the second fastening feature 42. The limiter stop feature 71 is configured and dimensioned to extend through the through opening 44 of one of the first and second fastening features 41, 42 at a time. The limiter stop feature 41 may be inserted through the through opening 44 of the first fastening feature 41 or the second fastening feature 42, respectively.

As shown for example in fig. 15, the limiter 170 is attached to the outer surface 145 of the sidewall 143 in a configuration that: a limiter stop feature 171 extends through second fastening feature 142, and limiter stop feature 171, or at least a free end thereof, projects radially inward from inner surface 146 of the sidewall. Since the limiter stop feature 71, 171 and the entire limiter 70, 170 are stationary fixed to the side wall 43, 143 of the housing 10, it provides an axial stop for the tracking stop feature 51 of the dose tracker 50 during setting of a dose. During dose setting, the axial path that the dose tracker 50 and its tracking stop feature 51 can travel in the proximal direction is limited by the position of the limiter 70, 170 and its limiter stop feature 71, 171.

Depending on the specific geometry of the inter-engaging stop features of the dose tracker 50 and the limiter 70, 170, it is also conceivable that the limiter stop features 71, 171 prevent rotation of the dose tracker 50 beyond a predefined maximum rotational position. In this way, the limiter stop feature 71, 171 may be arranged and attached to a predefined portion of the side wall 43, 143 of the housing 10 corresponding to a predefined angular position of the dose tracker 50 rotatably supported inside the housing 10. For example, the limiter stop features 71, 171 may form circumferential or radial stops for the tracking stop features 51 provided on the outer surface of the dose tracker 50 formed by the number sleeve 80, as shown in fig. 2.

Even though all of the presently illustrated embodiments include first and second fastening features 41, 141, 42, 142, embodiments are contemplated in which only a single, i.e., first fastening feature 41, 141 is provided in a sidewall 43, 143 of the housing 10. Here, the first fastening feature 41, 141 further includes a through opening 44, 144 to receive therethrough a correspondingly shaped limiter stop feature 71, 171. In addition to limiter stop features 71, 171 and tracking stop feature 51, drive mechanism 8 or dose setting mechanism 9 may also include an additional maximum dose limiter function. As illustrated in fig. 2, a tracking stop feature 51 may be provided on the outer surface of the number sleeve 80, which is configured to abut and engage with the stop feature 63 of the insert 62. The insert 62 is statically attached and fixed to the housing 10. Since a maximum dose of, for example, about 80i.u. has been set, the tracking stop feature 51 abuts the stop feature 63 of the insert 62, thereby preventing further rotation and/or translation of the number sleeve 80. In this embodiment, the digital sleeve 80 also serves as the dose tracker 50.

In addition to this maximum dose limiter function provided by the interaction of the number sleeve 80 and insert 62, it may be sufficient for the side walls 43, 143 of the housing 100 to include only the first fastening features 41, 141 for the limiters 70, 170. By attaching the limiter 70, 172 to the side wall 43, 143, an additional maximum dose stop is achieved and overrides the originally provided maximum dose limiter function. By attaching the limiter 70, 172 to the side wall 43, 143, the maximum dose limiter function of the drive mechanism 8 or of the dose setting mechanism 9 is modified from outside the injection device 1.

The dose limiter function provided by the interaction of the number sleeve 80 and the insert 62 may be replaced by the interaction of the dose tracker 50 and the limiter 70. For such embodiments, it is particularly beneficial for the housing 10 and the side walls 43, 143 to include at least first and second fastening features 41, 42, 141, 142. Then, in the first configuration, the limiter 70 is engaged or attached to the first fastening feature 41, and the limiter stop feature 71 protrudes from the first well-defined axial portion of the sidewall 43 of the housing 10. In the second configuration, the limiter 70 is engaged or attached to the second fastening feature 41. Then, the limiter stop feature 71 protrudes from a second well-defined axial portion of the sidewall 43 of the housing 10. In the present embodiment and as shown in fig. 3, the second fastening feature 42 is located proximal to the first fastening feature 41. In the second configuration and when the limiter stop feature 71 protrudes through the through opening 44 of the second fastening feature 42, the maximum dose gauge is increased compared to the first configuration in which the limiter stop feature 71 protrudes through the through opening 44 of the first fastening feature 41.

When attached to outer surface 45 of housing 43, flat-shaped base portion 72 of limiter 70 is substantially flush with outer surface 45, while limiter stop feature 71 projects radially inward and into the interior of housing 10. In the embodiment shown in fig. 4 and 5, limiter stop feature 71 comprises a pin extending perpendicularly from a flat shaped base portion 72. Limiter stop feature 71 includes a sloped section 73 at its free end to facilitate insertion and assembly of limiter stop feature 71 into through opening 44.

As illustrated in fig. 3-5, the base portion 72 of the limiter 70 includes an axial extension that is at least equal to or greater than the distance between the first and second fastening features 41, 42. Further, limiter stop feature 71 is disposed near an axial end of base portion 72. In this manner and when limiter stop feature 71 is attached to first fastening feature 41, the portion of base portion 72 facing away from limiter stop feature 71 covers second fastening feature 42. Vice versa, when limiter stop feature 71 is attached to second fastening feature 42, the distal portion of base portion 72 overlies first fastening feature 41. In this manner, base portion 72 includes a symmetrical shape that allows for securing and attaching restraint 70 in first and second configurations, wherein the first configuration is convertible to the second configuration by rotating restraint 70 by 180 °.

In another embodiment as illustrated in fig. 7-15, the first and second fastening features 141, 142 are also separated from each other in the axial direction (z) on the outer surface 145 of the sidewall 143 of the housing 10. Each of the fastening features 141, 142 includes a through opening 144 extending through the sidewall 143. Even a third fastening feature located proximal to the second fastening feature 142 is provided. These fastening features are arranged equidistantly on the housing 10. In the same manner as described above, the through openings 144 of the fastening features 141, 142 are configured to receive the limiter stop feature 171 of the limiter 170 as illustrated in fig. 9 and 10.

As shown in more detail in fig. 11, the first fastening feature 141 includes a recessed portion 147. In a similar manner, the second fastening feature also includes a recessed portion 147. The recessed portions are circumferentially adjacent to the through openings 144 of the first and second fastening features 141, 142, respectively. As further illustrated in fig. 11 and 12, the recessed portions 147 of the first and second fastening features 141 and 142 merge on the outer surface 145 of the sidewall 143 and form a common elongated recess 148. The elongated recess 148 includes a longitudinal recessed portion extending in a longitudinal or axial direction (z) of the elongated housing 10.

The elongated recess 148 includes a bottom 149 located at a radial distance from the outer surface 145 of the sidewall 143. The radial distance is at least equal to or greater than the thickness of the base portion 172 of the limiter 170. In this manner, the elongated recess 148 is configured to integrally receive the base portion 172 of the restraint 170. When attached to the sidewall 143, the limiter 170 and its base portion 172 do not radially protrude from the outer surface 145 of the sidewall 143.

As illustrated in fig. 9-12, the limiter 170 is L-shaped. The limiter 170 includes a first leg 173 and a second leg 174. The first leg 173 and the second leg 174 extend at an angle of about 90 °. When attached to the housing 10, the first leg 173 extends along the circumference (w) of the housing 10 and the second leg 174 extends along the axial elongation (z) of the housing 10. The first leg 174, and thus the base portion 172, is assembled inside the elongated recess 148, while the second leg 143 extends toward and into the through opening 144 of one of the first or second fastening features 141, 142. In fig. 11, the limiter stop feature 171, and thus the first leg 173, extends into the first fastening feature 141. In fig. 12, limiter stop feature 171, and thus first leg 173, extends into and engages second fastening feature 142.

When assembled to housing 10, base portion 172 of limiter 170 abuts bottom 149 of elongated recess 148. In this way, the radial position of the limiter 170 relative to the housing 10 is well defined.

As shown in fig. 11 and 12, a recessed section 150 is also provided circumferentially adjacent the elongated recess 148. The recessed section 150 is circumferentially opposite the through opening 144 of the first and second fastening features 141, 142. The recessed section 150 merges with the elongated recess 148. When attached to one of the first and second fastening features 141, 142, they provide access to the side edges of the base portion 172 of the limiter 170. In this manner, and with the aid of a pointed tool such as a screwdriver, for example, the base portion 172, and thus the entire limiter 170, may be lifted radially outward to detach the limiter 170 from the housing 10. The limiter 170 may then be attached to another fastening feature in order to modify the maximum dose specification of the injection device 1.

The limiter 70, 170 may be frictionally or adhesively attached to the side wall 43, 143 of the housing 10. The limiter 70, 170 may be fastened to the side wall 43, 143 by means of a separate component, for example by means of fasteners. Such fasteners may include an adhesive label or cover 90 that covers and secures the restraint 70, 170 to the sidewall 43, 143. In the embodiment of fig. 11 or 12, the limiter 170 may be press fit in one of the elongated recesses 148 or in one of the through openings 144 of one of the first or second fastening features 141, 142. It may also be permanently attached and fixed to the housing 10 by means of an adhesive or by means of welding. The limiter 70, 170 and housing 10 may comprise a moldable plastic material suitable for welding, such as laser welding or ultrasonic welding.

To temporarily or permanently secure the limiter 70, 172 to the housing 10, a label 100 may be provided that is adhesively attachable to the outer surface 45, 145 of the sidewall 43, 143. The label 100 may be provided with readable information printed thereon. The information may comprise instructions or general information about the medicament and/or about the handling or use of the injection device 1.

The label 100 may completely cover the limiter 70, 170 and the first and second fastening features 41, 42, 141, 142.

In addition and as illustrated in fig. 16-19, a separate cover 90 may be provided. The cover 90 may comprise a plastic material. The cover 90 may include a somewhat tubular shape cut in the longitudinal direction so as to include a semicircular cross section and include the shape of a half shell. Typically, the circumference of the cover 90 is greater than half of the outer circumference of the housing 10. In this way, the cover 90 may be clamped on the outer surfaces 45, 145 of the housing 10. The cover 90 is elastically deformable so as to at least temporarily enlarge the distance between its free ends and to allow a clamping attachment of the cover 90 in the radial direction of the housing 10. In one embodiment, the restrictor 70, 170 and the cover 90 may be integrally formed. Here, the restrainer 70 may protrude from an inner surface of the cover 90. The limiters 70, 170 and the cover 90 may be shaped and configured such that when the cover 90 is attached and secured to the housing 10, the limiters 70, 170 are located in one of the through openings 44, 144.

In order to stabilize and fix the cover 90 with respect to the axial and/or circumferential direction, mutually corresponding fastening elements 91, 151 may be provided on the inner surface of the cover 90 and the outer surface 145 of the housing 10. In the embodiment shown in fig. 7, 8, 17 and 19, the fastening elements 91 of the cover 90 comprise pins protruding radially inwards, and the fastening elements 151 of the housing 10 comprise correspondingly shaped recesses. When assembled correctly, the fastening element 91 is snapped into the fastening element 151. In this manner, the cover 90 is secured to the housing 10 for all three dimensions.

Additionally or alternatively, the tag 100 may be used to secure the cover 90 to the housing 10. As indicated in fig. 18, the label 100 may be adhesively attached to the cover 90 in such a manner: a portion of the label 100 also covers a portion of the outer surface 145 of the sidewall 143 of the injection device 1 that is not covered by the cover 90. Since the label 100 is adhesively attached to both the outer surface 145 of the housing 10 and the outer surface of the cover 90, the cover 90 can be secured to the housing 10 by means of the label 100.

Any of the features described above in connection with the first and second fastening features 41, 141, 42, 142 are equally valid for embodiments or implementations of the injection device having only one fastening feature 41, 141 on the side walls 43, 143 of the housing 10. By way of example only, the fastening feature 41, 141 may include a recessed portion 147 to receive the base portion 72, 172 of the restraint 70, 170. Further, only the first fastening feature 41, 141 may be covered by the cover 90 and/or the label 100.

List of reference numerals

1 injection device

2 distal direction

3 proximal direction

4 direction of dose escalation

5 direction of dose decrement

6 Cartridge

7 plug

8 driving mechanism

9 dose setting mechanism

10 outer casing

11 trigger

12 dose dial

13 dose window

14 Cartridge holder

15 injection needle

16 inner needle cap

17 outer needle cap

18 protective cap

20 piston rod

21 bearing

22 first thread

23 presser foot

24 second screw thread

25 barrels

26 seal

28 screw socket

30 drive sleeve

31 thread section

32 Flange

33 Flange

35 last dose limiter

36 shoulder

40 spring

41 fastening feature

42 fastening feature

43 side wall

44 through opening

45 outer surface

50 dose tracker

51 tracking stop feature

60 jointer

62 insert

63 stop feature

64 bar

70 limiter

71 restrictor stop feature

72 base part

73 inclined section

80 digital sleeve

81 groove

90 cover

91 fastening element

100 label

141 fastening feature

142 fastening feature

143 side wall

144 through opening

145 outer surface

146 inner surface

147 concave part

148 recess

149 push buttons

150 recess

151 fastening element

170 limiter

171 limiter stop feature

172 base part

173 supporting leg

174 support leg

Claims (17)

1. An injection device for setting and injecting a dose of a medicament, the injection device comprising:

an elongated housing (10) extending in an axial direction (z) and configured to house a dose setting mechanism (9), wherein the housing (10) comprises a side wall (43; 143) with at least a first fastening feature (41; 141),

a dose dial (12) rotatable relative to the housing (10) to set a dose,

-a dose tracker (50) arranged inside the housing (10) and operatively connectable to the dose dial (12), the dose tracker (50) comprising at least one tracking stop feature (51), wherein the dose tracker (50) is one of translationally or rotationally displaceable relative to the housing (10) during setting of a dose, and wherein a positional state of the dose tracker (50) relative to the housing (10) indicates a specification of the dose, and

-a limiter (70; 170) attachable to the side wall (43; 143) of the housing (10) from outside the housing (10) and engageable with the at least first fastening feature (41, 141), wherein the limiter (70; 170) comprises at least one limiter stop feature (71; 171) extending inwardly from the side wall (43; 143) when the limiter (70; 170) is attached to the side wall (43), wherein the limiter stop feature (71; 171) and the tracking stop feature (51) are configured to engage each other and prevent displacement of the dose tracker (50) beyond a predefined maximum dose position state.

2. The injection device according to claim 1, wherein the sidewall (43; 143) comprises at least a second fastening feature (42; 142) separate from the at least a first fastening feature (41; 141) with respect to one of an axial direction (z) and a circumferential direction (w) of the housing (10), and wherein the limiter (70; 170) is selectively engageable with one of the at least first and second fastening features (41, 42; 141, 142).

3. An injection device according to claim 2, wherein the limiter (70; 170) is connectable to or engageable with only one of the first and the second fastening features (41, 42; 141, 142) at a time.

4. An injection device according to claim 2 or 3, wherein a first maximum dose size of the injection device is defined when the limiter (70; 170) is attached to the side wall (43) at the first fastening feature (41; 141), and wherein a second maximum dose size of the injection device is defined when the limiter (70; 170) is attached to the side wall (43) at the second fastening feature (42; 142).

5. The injection device according to any one of the preceding claims, wherein at least one of the first and the second fastening features (41, 42; 141, 142) comprises a through opening (44; 144) extending through the side wall (43; 143), wherein the stop feature (71; 171) is shaped and configured to extend through the through opening (44; 144).

6. The injection device according to any one of the preceding claims, wherein the limiter (70; 170) comprises a base portion (72; 172) and the limiter stop feature (71; 171) protrudes from the base portion (72; 172).

7. An injection device according to claim 6, wherein the base portion (72; 172) is attachable to an outer surface (45; 145) of the side wall (43; 143).

8. An injection device according to any of claims 5 to 7, wherein the limiter stop feature (71; 171) is insertable through the through opening (44) such that a free end of the limiter stop feature (71; 171) projects inwardly from the inner surface (46) of the side wall (43).

9. The injection device according to any of the preceding claims 5 to 8, wherein at least one of the first and the second fastening features (141, 142) comprises a recessed portion (147) on the outer surface (145) of the side wall (143), and wherein the recessed portion (147) is arranged adjacent to the at least one through opening (144).

10. An injection device according to claim 9, wherein the depth of the recessed portion (47) is equal to or greater than the thickness of the base portion (72; 172).

11. The injection device of claim 9 or 10, wherein the first and second fastening features (141, 142) each comprise a recessed portion (147), and wherein the recessed portions (147) of the first and second fastening features (141, 142) merge with one another and form an elongated recess (148) on the outer surface (145) of the sidewall (143).

12. The injection device according to any one of claims 9 to 11, wherein the elongated recess (148) extends in the axial direction (z) and/or in a circumferential direction (w), and wherein the at least one through opening (144) of one of the first and second fastening features (141, 142) is arranged tangentially or circumferentially adjacent to the elongated recess (148).

13. The injection device according to claim 12, wherein the base portion (172) is L-shaped and comprises a first leg (173) and a second leg (174), wherein the first leg (173) extends in a circumferential direction (w), and wherein the second leg (174) extends along the elongated recess (148).

14. The injection device according to claim 13, wherein the limiter stop feature (171) protrudes from an end of the first leg (173) facing away from the second leg (174).

15. The injection device of any one of the preceding claims, further comprising a cap (90) attachable to the outer surface (145) of the sidewall (143) and configured to cover at least the first and second fastening features (141, 142).

16. The injection device according to any one of the preceding claims, further comprising a piston rod (20) and a cartridge (6), wherein the cartridge (6) comprises a barrel (25) filled with a medicament and sealed in the axial proximal direction (3) by a bung (7) which is axially displaceable relative to the barrel (25) by means of the piston rod (20).

17. A method of modifying a maximum dose specification of an injection device, the method comprising the steps of:

-providing an injection device (1) comprising:

a) an elongated housing (10) extending in an axial direction (z) and configured to accommodate a dose setting mechanism (9), wherein the housing (10) comprises a housing having at least a first fastening feature (41, 42; 141, 142) of the side wall (43; 143),

b) a dose tracker (50) arranged inside the housing (10) and comprising at least one tracking stop feature (51), wherein the dose tracker (50) is at least one of translationally or rotationally displaceable relative to the housing (10) during setting of a dose, wherein a positional state of the dose tracker (50) relative to the housing (10) is indicative of a specification of the dose,

-attaching a limiter (70; 170) to the side wall (43) of the housing (10) by means of the at least one fastening feature (41, 42; 141, 142), wherein the limiter (70; 170) comprises at least one limiter stop feature (71; 171) extending inwardly from the side wall (43; 143) when attached to the side wall (43; 143), wherein the limiter stop feature (71; 171) and the tracking stop feature (51) are configured to engage each other and prevent displacement of the dose tracker (50) beyond a predefined maximum dose position state.

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