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 accommodate a dose setting mechanism (9) ), wherein the housing (10) comprises a side wall (43; 143) having at least a first fastening feature (41; 141); a dose dial (12), which can be relative to the housing (10) rotates to set a dose; - a dose tracker (50) arranged inside the housing (10) and operably connectable to the dose dial (12), the dose tracker (50) comprising at least a 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 the dose a positional state of the tracker (50) relative to the housing (10) indicating the size of the dose; and a limiter (70; 170) attachable to the housing (10) from outside the housing (10) 10) of said side wall (43; 143) and engageable with said at least first fastening feature (41, 141), wherein said limiter (70; 170) comprises when said limiter (70) ; 170) at least one limiter stop feature (71; 171) extending inwardly from said side wall (43; 143) when attached to said side wall (43), wherein said limiter stop feature The member (71; 171) and the tracking stop feature (51) are configured to mutually engage and prevent displacement of the dose tracker (50) beyond a predefined maximum dose position state.

Description

Injection device with dose limiter

illustrate

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 that provides a maximum dose mechanism, ie a dose setting and dispensing mechanism that is only operable to dispense a dose that does not exceed a predefined maximum threshold.

background

Injection devices for setting and dispensing single or multiple doses of liquid medicaments are themselves well known in the art. Typically, such devices serve a substantially similar purpose to that of a common syringe.

Injection devices, especially pen injectors, have to meet many user-specific requirements. For example, where the patient suffers from a chronic disease such as diabetes, the patient may be frail and may also be visually impaired. Therefore, suitable injection devices especially intended for home use need to be robust in construction and should be easy to use. Moreover, the manipulation and general handling of the device and its components should be clear and easily understood. 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 also include a drive mechanism, typically having a displaceable piston rod adapted to operatively engage the piston of the cartridge. By means of the drive mechanism and its piston rod, the piston of the cartridge can be displaced in the distal direction or in the dispensing direction and thus can expel a predefined amount of medicament by means of the piercing assembly, which is in contact with the housing of the injection device The distal segment is releasably coupled.

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

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

Target

Accordingly, it is 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 on demand and should provide an easy and intuitive way to change the maximum dose specification that can be expelled through the injection device.

By modifying only a limited number of existing device components, it should be possible to achieve maximum dose functionality. A further aim is to individually modify the maximum dose value or dose specification by changing only a single component or a few components of the device. Therefore, it should be possible to configure the maximum dose function of the device or its drive mechanism by changing only one or a few components of the device or its drive mechanism. The maximum dose function or maximum dose limiter shall be universally applicable to various drive mechanisms and injection devices. In particular, the maximum dose function or maximum dose limiter should apply equally to single-use injection devices as well as reusable injection devices.

SUMMARY OF THE INVENTION

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

The injection device also includes a dose dial. The dose dial is rotatable relative to the housing to set the 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 end section of the housing. The dose dial is user actuatable. Thus, the user can grip and rotate the dose dial relative to the housing to set or select a variable gauge dose.

The injection device also includes a dose tracker disposed 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 status of the dose tracker relative to the housing indicates the specification of the dose. In the current context, a "positional state" of a component (eg, a dose tracker) includes the location of the component and the angular orientation of the component relative to another component (eg, 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. Additionally, the dose tracker is translationally and rotationally displaceable relative to the housing. It can move relative to the housing along a helical path. It can be threadedly engaged with the housing.

A dose tracker is a dose setting mechanism. The positional state of the dose tracker relative to the housing is unambiguously related to the actual 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 actual set dose specification.

The injection device also includes a restrictor attachable to the side wall of the housing. The limiter can be attached from the outside of the housing. It 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 interengage and prevent displacement of the dose tracker beyond a predefined maximum dose position state.

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

In other words, when the dose tracker reaches the maximum dose position state, its tracking stop feature engages (eg, abuts) a limiter stop feature secured to a corresponding portion of the sidewall. The limiter stop feature and the tracking stop feature may include mutually corresponding stop surfaces, eg, extending in circumferential and radial directions for axial engagement. Alternatively, the limiter stop feature and the tracking stop feature include mutually corresponding stop surfaces extending in the axial and radial directions for circumferential engagement. When configured for axial engagement, the interengagement of the limiter stop feature and the track stop feature provides an axial stop, thereby blocking and preventing longitudinal or axial translation of the dose tracker beyond a predefined maximum axial Dose position status.

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

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 side wall that corresponds to the positional state of the dose tracker, in particular the tracking stop feature, the maximum dose that can be dispensed by the injection device can be defined.

Typically, the restraint can be attached to the side wall of the housing by at least a first fastening feature. Here, the first fastening feature may serve a dual function. First, the first fastening feature may provide a fastening structure for attaching the restraint to a corresponding portion of the side wall of the housing. Furthermore, the location of the first securing feature on the sidewall defines the maximum dose position state of the dose tracker.

The restrictor can be attached to the side wall from the outside of the housing. This allows modification of the maximum dose specification of the injection device even after delivery to the patient or medical staff. Attaching the restrictor to the housing from outside the housing enables subsequent modification of the injection device without opening the housing of the injection device.

In further embodiments, the housing, in particular the sidewall of the housing, includes at least a second fastening feature that is connected to at least the first fastening with respect to one of an axial direction and a circumferential direction of the housing. Feature separation. 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 the same as the first fastening feature. The second fastening feature differs from the first fastening feature only by its location or positioning on the side wall of the housing. 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 with respect to the first fastening feature may equally apply 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 with respect to both the first and second fastening features are equally applicable where the injection device comprises only a Embodiment of a single or first fastening feature.

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

In another embodiment, at least one of the first and second fastening features includes a through opening extending through the sidewall of the housing. Here, the limiter stop feature is shaped and configured to extend through the through opening. Providing at least one through opening in the side wall of the housing provides the possibility to attach the restrictor 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 can be inserted from the outside through the through opening in the side wall so that the free end of the limiter stop feature is free from The inner surface of the side wall protrudes. There, the limiter stop feature may be operatively 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 at least the first and second fastening features includes a through opening extending through the side wall. Furthermore, the first and second fastening features may comprise the same or the same geometry. In this way, the same limiter can be selectively attached to one of the first and second fastening features. This provides and enables reconfiguration of the injection device. When, for example, attached to the first fastening feature to define a first maximum dose size, the limiter is detachable from the first fastening feature and attachable to the second fastening feature to define a different A second maximum dose strength of a maximum dose strength.

In another embodiment, the restrictor includes a base portion. A 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 that provides a well-defined grip on the limiter. The base portion may also improve the securing of the restrictor to the side wall. The base portion may be permanently attached to the side wall, eg by means of adhesive or by 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. Accordingly, the base portion may include a cover having dimensions at least equal to or greater than the distance between the first and second fastening features on the sidewall of the housing. In this manner and when attached to the first fastening feature, eg by means of the first limiter stop feature, the base portion covers both the first and second fastening features. In another configuration and when attached to the second fastening feature, eg 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 larger than the outer cross-section of the limiter stop feature of the limiter. This enables a fairly smooth and easy insertion of the limiter stop feature into and through the through opening of the first or second fastening feature. The limiter stop feature can also be easily removed and withdrawn from the through opening of the first or second fastening feature in order to reconfigure the injection device and its dose setting mechanism.

In another embodiment, the base portion may be attached to the outer surface of the sidewall. Since the limiter stop feature protrudes from the base portion, the base portion may be located on the outside or outer surface of the sidewall, while the limiter stop feature extends through the sidewall and protrudes from the inner surface of the sidewall to interface with the dose tracker of the tracking stop feature engages. The attachment to the outer surface of the base portion also facilitates permanent access to the base portion and thus the limiter. Since the base portion remains at the outer surface, it is accessible to the user or medical personnel, enabling the restrictor to be removed from the side wall in order to reconfigure the injection device if needed.

In another embodiment, the limiter stop feature is insertable through the at least one through opening of the first and second fastening features such that the free end of the limiter stop feature facing away from the base portion is from the side The inner surface of the wall protrudes inwardly. Accordingly, the extension (typically, radial extension) of the limiter stop feature is greater than the thickness of the sidewall, and is 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 protrudes 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 the outer surface of the sidewall. The recessed portion is arranged 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 restrictor 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 Comprising a fairly uniform and smooth shape with no 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 received completely inside the recessed portion. When attached to and disposed in the recessed portion, the base portion does not protrude from the outer surface of the side wall. This provides a fairly uniform and smooth shape of the outer circumference of the casing.

In another embodiment, the first fastening feature and the second fastening feature each include a recessed portion. Here, the recessed portions of the first fastening feature and the second fastening feature merge with each other and form an elongated recess on the outer surface of the side wall. Typically, the elongated recess on the outer surface of the side wall provides a kind of 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 can extend into and through the through opening of the corresponding first or second fastening feature.

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

Typically, the first and second fastening features each include through openings, wherein the through openings are axially separated from each other. Two through-openings are arranged circumferentially adjacent 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 remainder of the other through opening and the elongated recess can then remain uncovered. This residual portion or unoccupied through-opening can be covered separately with a separate cover.

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

In this way, the first and second restrictors with likewise shaped base portions can always completely fill and cover the elongated recesses on the outer surface of the side wall. Depending on the particular choice of one of the first and second restraints, only one of the first and second fastening features and only one of the corresponding first and second through openings through the sidewall will be restrained Stop feature occupancy.

In another embodiment, only one limiter may be provided, the base portion of which is symmetrical about the axis of symmetry. Here, the recessed portion on the outer surface of the side wall may include corresponding symmetry such that the restrictor is attachable and fastenable to the outer surface of the housing in a first configuration and a second configuration, wherein the second configuration Compared to the first configuration, it is for example rotated by 180°. 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 securing feature when in the first configuration, and the limiter stop feature when in the second configuration, such as when the limiter is rotated about 180° The piece engages the second fastening feature.

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° relative to each other. When attached to the side wall of the housing, the first leg may extend in the circumferential direction of the side wall and the second leg may extend in the 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 to the circumference of the side wall.

The L-shaped base portion facilitates attachment of the restrictor to the side wall. The second leg can be attached to and can be received in a recessed portion or elongated 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 inwardly to the interior of the housing. Here, a first leg having at least one limiter stop feature attached thereto protrudes into the housing and engages with the tracking stop feature of the dose tracker, while the second leg is well defined in the housing Provides a well-defined attachment of the limiter at the radial position of the .

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

In further embodiments, the injection device is equipped with a cap attachable to the outer surface of the side wall. 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 of the outer surface of the sidewall adjacent 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 hides and conceals the location and presence of the restrictor.

The cover may include a flexible foil that is adhesively attached to the outer surface of the sidewall of the housing. 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 the 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 cover may comprise a sleeve or housing made of plastic material or metal. The cover can 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 lid and the side walls of the housing may include interengaging clip or snap features that provide releasable or non-removable securing of the lid to the side walls of the housing.

For example, the cover may comprise a casing in the form of a sleeve or part of a cylinder, such as a half-shell. The cover may include radial projections or radial recesses on the inner surface portion for engagement with correspondingly shaped recesses or projections provided on the outer surface of the side wall of the injection device housing. In this way, the cover can be clamped or fixed to the side wall of the housing. When the cover includes a plastic housing, the outer surface of the cover may include a label. The cap can also be fastened to the injection device by means of 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 includes a piston rod. The piston rod is typically part of the drive mechanism and/or the dose setting mechanism. The piston rod is 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 its dose setting mechanism is configured to drive and displace the piston rod longitudinally in the axial distal direction.

Typically, an injection device is provided with a cartridge filled with a medicament (eg, a liquid medicament). The cartridge is typically sealed in the proximal direction by means of a stopper. The stopper 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 can be pierced by means of a double pointed injection needle. The injection needle is typically releasably attachable to the distal end and/or the dispensing end of the housing of the injection device, typically to the distal end of the cartridge holder belonging to the housing of the injection device.

In further embodiments, the injection device includes a cartridge at least partially filled with a medicament. Cartridges include barrels filled with medicament. The cartridge, and thus the barrel, is sealed by the plug in the axial proximal direction. The plug is axially displaceable relative to the barrel by means of the piston rod. When the piston rod is advanced in the distal direction during dose dispensing, it applies driving pressure to the bung. Since the cartridge is secured inside the housing, the stopper begins to move in a distal direction, thereby increasing the internal pressure of the cartridge, resulting in expulsion of the medicament from the cartridge.

In another aspect, a method of modifying a maximum dose specification of an injection device is provided. The method includes the step of providing an injection device. The injection device includes an elongated housing extending in an axial direction and configured to accommodate the dose setting mechanism. Typically, the housing is also configured to receive and house a cartridge filled with a medicament. The housing also includes a sidewall having at least a first fastening feature. Typically, the sidewall also includes at least a second fastening feature. The injection device also includes a dose tracker disposed 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 positional state of the dose tracker relative to the housing unambiguously indicates the actual dose specification set.

The method of modifying the maximum dose specification further includes the step of attaching the limiter to the side wall of the housing 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 interengage 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. Therefore, all the features, benefits and effects described above in connection with the injection device are equally applicable to the method of modifying the maximum dosage strength of the injection device.

In the present context, the term "distal" or "distal" refers to the end of the injection device facing the injection site of the human or animal. The term "proximal" or "proximal end" refers to the opposite end of the injection device that is furthest from the injection site in the human or animal.

As used herein, the term "drug" or "medicine" 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 1500 Da, and/or is a peptide, protein, polysaccharide, vaccine, DNA, RNA, enzyme, antibody or antibody fragment, hormone or oligonucleotide, or Mixtures of the above-mentioned pharmaceutically active compounds,

Wherein in additional embodiments, the pharmaceutically active compound is useful for the treatment and/or prevention of diabetes or complications associated with diabetes (eg, diabetic retinopathy), thromboembolism (eg, deep vein or pulmonary thromboembolism), Acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis,

wherein, in further embodiments, the pharmaceutically active compound comprises at least one peptide for the treatment and/or prevention of diabetes or diabetes-related complications such as diabetic retinopathy,

Wherein in further embodiments, the pharmaceutically active compound comprises at least one human insulin or a human insulin analog or derivative, glucagon-like peptide (GLP-1) or an analog or derivative thereof, or a toxic Exendin-3 or Exendin-4, or an analog or derivative of Exendin-3 or Exendin-4.

Insulin analogs are eg 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 in which the proline at position B28 is replaced by Asp, Lys, Leu, Val or Ala, and in which Lys at position B29 can 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 eg 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-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29- N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin; B29-N-(N-lithoyl-Y-glutamyl)-des(B30) human insulin; B29-N -(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-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-NH2.

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 -Lys6-NH2 can be combined with the C-terminus of the exendin-4 derivative;

or an exendin-4 derivative having the following 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,Pro38Exendin-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)5 des 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-NH2;

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

Hormones are, for example, pituitary or hypothalamic hormones as listed in chapter 50 of Rote Liste, 2008 edition or regulatory active peptides and antagonists thereof, such as Gonadotropine (Follitropin, Luteinizing Hormone) , Choriongonadotropin (Choriongonadotropin, Gamete Maturation Hormone), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonarelin, Triptorel Lin, leuprolide, buserelin, nafarelin, goserelin.

Polysaccharides are, for example, glycosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin or ultra low molecular weight heparin or derivatives thereof, or sulfated forms (eg, polysulfated forms) of the foregoing polysaccharides, and/or pharmaceutically acceptable of salt. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (about 150 kDa), also known as immunoglobulins that share a basic structure. Since they have sugar chains added to amino acid residues, they are glycoproteins. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit); secreted antibodies can also be dimers with two Ig units (eg IgA), four Ig units Tetramers (eg, teleost IgM), or pentamers (eg, mammalian IgM) with five Ig units.

Ig monomers are "Y" shaped molecules composed of four polypeptide chains; two identical heavy chains and two identical light chains are linked by disulfide bonds between cysteine residues. Each heavy chain is about 440 amino acids long; each light chain is about 220 amino acids long. The heavy and light chains each contain intrachain disulfide bonds that stabilize their folding. Each chain is made up of domains called Ig domains. These domains comprise approximately 70-110 amino acids and are grouped into different classes (eg, variable or V regions and constant or C regions) according to their size and function. These domains have a unique immunoglobulin fold in which two beta folds form a "sandwich" shape, held together by interactions between conserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chains, represented by alpha, delta, epsilon, gamma, and mu. The type of heavy chain present defines the antibody's isotype; these chains are found in IgA, IgD, IgE, IgG and IgM antibodies, respectively.

Different heavy chains differ in size and composition; alpha and gamma contain approximately 450 amino acids, delta approximately 500 amino acids, and mu and epsilon approximately 550 amino acids. Each heavy chain has two regions, a constant region ( _CH ) and a variable region (V _H ). Within a species, the constant regions are essentially the same in all antibodies of the same isotype, but differ in antibodies of different isotypes. Heavy chains gamma, alpha and delta have a constant region consisting of three tandem Ig domains, and a hinge region for increased flexibility; heavy chains mu and epsilon have a constant region consisting of four immunoglobulin domains. The variable region of the heavy chain differs in antibodies produced by different B cells, but is the same for all antibodies produced by a single B cell or B cell clone. The variable region of each heavy chain is approximately 110 amino acids long and consists of a single Ig domain.

In mammals, there are two types of immunoglobulin light chains, denoted by λ and κ. Light chains have two contiguous domains: a constant domain (CL) and a variable domain (VL). The approximate length of the light chain is 211 to 217 amino acids. Each antibody contains two light chains that are always the same; only one type of light chain, kappa or lambda, 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 on each light chain (VL) and three on the heavy chain (VH)) are responsible for antigen binding, ie for its antigenic specificity. These loops are called complementarity determining regions (CDRs). Because multiple CDRs from the VH and VL domains constitute the antigen-binding site, it is the combination of 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 substantially the same function and specificity as the complete antibody from which the antibody fragment is derived. Restriction proteolysis with papain cleaved the Ig prototype into three fragments. The two identical amino-terminal fragments are antigen-binding fragments (Fab), each containing a complete L chain and about half an H chain. The third fragment is a crystallizable fragment (Fc), which is similar in size but contains the carboxy-terminal half of the two heavy chains and their interchain disulfide bonds. Fc contains carbohydrate, complement binding site and FcR binding site. Limited pepsin digestion yields a single F(ab')2 fragment comprising both the Fab segment and the hinge region, including the H-H interchain disulfide bonds. 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 can 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, HCl or HBr salts. Basic salts are, for example, salts having cations selected from alkali or alkaline earth metal cations, such as Na+ or K+ or Ca2+, or ammonium ions N+(R1)(R2)(R3)(R4), wherein R1 to R4 independently of each other represent: hydrogen, optionally substituted C1-C6-alkyl group, optionally substituted C2-C6-alkenyl group, optionally substituted C6-C10-aryl group group, or an optionally substituted C6-C10-heteroaryl group. Additional examples of pharmaceutically acceptable salts are described in "Remington's Pharmaceutical Sciences" 17th Ed. Alfonso R. Gennaro (ed.), Mark Publishing Company, Easton, Pa., U.S.A., 1985 and the 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 disclosed herein. Furthermore, it should be noted that any reference signs used in the appended claims shall not be construed as limiting the scope of the invention.

Description of drawings

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

Figure 1 schematically shows an embodiment of an 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 from which the restrictor has been removed,

Figure 4 is a side view of a restrictor attachable to a side wall of an injection device,

Figure 5 is a bottom view of the restrictor according to Figure 4,

Figure 6 is a side view of the injection device of Figure 3 with the restrictor of Figures 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 restrictor,

Figure 10 shows the restrictor of Figure 9 from another angle,

Figure 11 indicates the restrictor of Figure 9 in a first configuration attached to the side wall of the injection device according to Figure 7 or Figure 8,

Figure 12 shows the restrictor of Figure 9 in a second configuration attached to the side wall of the injection device,

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

Fig. 14 is a section according to Fig. 13 with the restrictor attached thereto,

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

Figure 16 shows a housing attachable to an injection device housing,

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

Figure 18 shows the housing of Figures 16 and 17 with the label attached thereto, and

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

Detailed ways

The injection device 1 shown in Figures 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 surround and protect the distal section of the housing 10 of the injection device 1 . Housing 10 may include and form a main housing portion configured to accommodate drive mechanism 8 as shown in FIG. 2 . The injection device 1 may also comprise a distal housing part, denoted as a cartridge holder 14 . The cartridge holder 14 may be permanently or releasably connected to the main housing 10 . The cartridge holder 14 is typically configured to receive 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 stopper 7 located in the barrel 25 . The stopper 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 can be pierced by the proximally oriented tip of the injection needle 15 . The cartridge holder 14 includes a threaded socket 28 at its distal end for threaded engagement with a corresponding threaded portion 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 delivery pathway to the interior of the cartridge 6 .

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

As further shown in FIGS. 1 and 2 , the housing 10 includes a dose window 13 which may be in the form of an aperture in the housing 10 . The dose window 13 allows the user to view a limited portion of the digital sleeve 80, which is configured to move when the dose dial 12 is turned 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 induces a mechanical click to provide acoustic feedback to the user. The digital sleeve 80 interacts mechanically with the piston in the insulin cartridge 6 . The insulin dose displayed in the display window 13 will be expelled from the injection device 1 when the needle 15 is pierced into the patient's skin portion, and when the trigger 11 or injection button is pushed. When the needle 15 of the injection device 1 remains in the skin part for a certain time after the trigger 11 is pushed, a higher percentage of said dose is actually injected into the patient. The expulsion of the insulin dose can also cause a mechanical click, but it is different from the sound produced when the dose dial 12 is used.

In this embodiment, during insulin dose delivery, the dose dial 12 is rotated to its initial position of axial movement, that is, without rotation, while the digital sleeve 80 is rotated to return to its initial position, eg, to display zero units dose.

The injection device 1 can be used for several injection sessions until the cartridge 6 is emptied or the medicament in the injection device 1 has reached its expiry date (eg 28 days after the first use).

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

The ejection or drive mechanism 8, as illustrated in more detail in Figure 2, includes a number of mechanically interacting components. The flange-like support of the housing 10 includes a threaded axial through opening that threadedly engages the first or distal thread 22 of the piston rod 20 . The distal end of the piston rod 20 includes a bearing 21 on which the pressure foot 23 is free to rotate, with the longitudinal axis of the piston rod 20 as the axis of rotation. The pressure foot 23 is configured to axially abut against the proximally facing thrust receiving surface of the stopper 7 of the cartridge 6 . During the dispensing action, the piston rod 20 rotates relative to the housing 10 , thereby undergoing a distally directed advancing movement relative to the housings 10 , 30 and thus relative to the barrel 25 of the cartridge 6 . As a result, the stopper 7 of the cartridge 6 is displaced by a well-defined distance in the distal direction 2 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 threads 22 and the proximal threads 24 have opposite directions of rotation.

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

The last dose limiter 35 also includes radial recesses or radial protrusions at its outer circumference to engage with complementary shaped recesses or protrusions at the inner side of the side wall of the housing 10 . In this way, the last dose limiter 35 is splined to the housing 10 . Rotation of the drive sleeve 30 in the dose increment direction 4 or clockwise during successive dose setting procedures 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 which axially abuts the proximally facing surface of the flange portion 33 . Furthermore, a tubular clutch 60 is provided. The adapter 60 is provided at a first end with a series of circumferentially oriented serrations. A radially inwardly directed flange is positioned toward the second opposite end of the adapter 60 .

In addition, a dose dial sleeve, also denoted digital sleeve 80, is provided. The number sleeve 80 is provided outside the spring 40 and the adapter 60 and 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 dose window 13 through which a portion of the outer surface of the numeral 80 can be seen. The housing 10 is also provided with a helical rib at the inner sidewall portion of the insert 62 that will seat in the helical groove 81 of the digital sleeve 80 . The 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 digital sleeve 80 rotates relative to the housing 10 in a helical motion.

A dose dial 12 in the form of a dose dial grip is arranged around the outer surface of the proximal end of the digital 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 number 80 to prevent relative movement therebetween. The dose dial 12 is provided with a central opening.

The trigger 11 (also denoted as a dose button) is substantially T-shaped. It is provided at the proximal end of the injection device 10 . The rod 64 of the trigger 11 extends through the opening in the dose dial 12 , through the inner diameter of the extension of the drive sleeve 30 and into the 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 the dose. With spring 40 also serving as a clicker and adapter 60 engaged, drive sleeve 30 , spring or clicker 40 , adapter 60 , and digital sleeve 80 rotate with dose dial 12 . Audible and tactile feedback of the dialed dose is provided through the spring 40 and through the adapter 60 . Torque is transmitted between the spring 40 and the adapter 60 through the serrations. The helical grooves 81 on the digital sleeve 80 and the helical grooves 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 digital sleeve 80 engages 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 orientation of the integral threads on the piston rod 20 and the driven threads.

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

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

When the desired dose has been dialed, the user can simply dispense the set dose by depressing the trigger 11 . This displaces the adapter 60 axially relative to the number sleeve 80, disengaging its canine teeth. However, the adapter 60 remains in rotational engagement with the drive sleeve 30 . The digital sleeve 80 and dose dial 12 are now free to rotate according to the helical groove 81 .

Axial movement deforms the flexible arms of spring 40 to ensure that the serrations are not overhauled during dispensing. This prevents the drive sleeve 30 from rotating relative to the housing 10, although it is still free to move axially relative to the housing. The deformation is then used to push back the spring 40 and adapter 60 along the drive sleeve 30 to restore the connection between the adapter 60 and the digital 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 stopper 7 in the cartridge 6 . Once the dialed dose has been dispensed, further rotation of the digital sleeve 80 is prevented 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 the 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 expelling mechanism or drive mechanism 8 described above is only an example of one of many different configurations of drive mechanisms that can typically be implemented in disposable pen injectors. Drive mechanisms as described above are explained in more detail, for example, in WO 2004/078239 A1, WO 2004/078240 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 includes at least a dose dial 12 and a digital sleeve 80 . When the dose dial 12 is rotated during and for setting a dose, the digital sleeve 80 begins to rotate relative to the housing along a helical path defined by the external thread or helical groove 81 of the digital sleeve and the housing The threaded engagement of correspondingly shaped threaded segments on the inner surface of the .

During dose setting and when either the drive mechanism 8 or the dose setting mechanism 9 is in the dose setting mode, the drive sleeve 30 rotates in unison with the dose dial 12 and with the digital 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 helical motion during dose setting. When the dose dial is rotated in the dose increment direction 4 (eg clockwise), the drive cannula 30 begins to travel in the proximal direction. To adjust or correct the size of the dose, the dose dial 12 may be rotated in the opposite direction, thus in the dose decreasing direction 5 (eg counterclockwise).

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

As illustrated in FIGS. 3 , 7 or 8 , the housing 10 includes tubular or cylindrical side walls 43 , 143 . The side walls 43 , 143 include first fastening features 41 , 141 and second fastening features 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 fastening feature 41 and the second fastening feature 42 each include a through opening 44 extending through the side wall 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 can 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 side wall 143 in a configuration with the limiter stop feature 171 extending through the second fastening feature 142, the limiter stop feature 171 or at least its free end protrudes radially inwardly from the inner surface 146 of the side wall. Since the limiter stop feature 71 , 171 and the entire limiter 70 , 170 are stationary fixed to the side walls 43 , 143 of the housing 10 , it is the tracking stop feature 51 of the dose tracker 50 during setting of a dose Axial stop is provided. During dose setting, the axial path that the dose tracker 50 and its tracking stop features 51 can travel in the proximal direction is limited by the position of the limiters 70 , 170 and their limiter stop features 71 , 171 .

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

Even though all of the presently illustrated embodiments include first and second fastening features 41 , 141 , 42 , 142 , embodiments are conceivable in which only the side walls 43 , 143 of the housing 10 are provided A single or first fastening feature 41 , 141 . Here, the first fastening features 41 , 141 also include through openings 44 , 144 to receive correspondingly shaped limiter stop features 71 , 171 therethrough. In addition to the limiter stop features 71 , 171 and the tracking stop feature 51 , the drive mechanism 8 or dose setting mechanism 9 may also include an additional maximum dose limiter function. As illustrated in FIG. 2 , tracking stop features 51 , which are configured to abut and engage with stop features 63 of insert 62 , may be provided on the outer surface of digital sleeve 80 . The insert 62 is statically attached and secured to the housing 10 . Since a maximum dose of, eg, about 80 I.U. has been set, the tracking stop feature 51 abuts the stop feature 63 of the insert 62, preventing further rotation and/or translation of the digital sleeve 80. In this embodiment, the digital cannula 80 is also used as the dose tracker 50 .

In addition to this maximum dose limiter function provided by the interaction of the digital sleeve 80 and the insert 62 , the side walls 43 , 143 of the housing 100 only include the first fastening feature 41 for the limiter 70 , 170 , 141 may be sufficient. By attaching the limiters 70, 172 to the side walls 43, 143, an additional maximum dose stop is achieved and overrides the originally provided maximum dose limiter function. By attaching the limiters 70 , 172 to the side walls 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 digital cannula 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 the 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 , the limiter stop feature 71 protruding from the first well-defined axial portion of the side wall 43 of the housing 10 . In the second configuration, the limiter 70 is engaged or attached to the second fastening feature 41 . The limiter stop feature 71 then protrudes from a second well-defined axial portion of the side wall 43 of the housing 10 . In this embodiment and as shown in FIG. 3 , the second fastening feature 42 is located proximal of 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 specification is increased compared to the first configuration in which the limiter stop The stop feature 71 protrudes through the through opening 44 of the first fastening feature 41 .

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

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

In another embodiment as illustrated in FIGS. 7-15 , the first and second fastening features 141 , 142 are also in the axial direction (z) of each other on the outer surface 145 of the side wall 143 of the housing 10 separation. Each of the fastening features 141 , 142 includes a through opening 144 extending through the side wall 143 . There is even a third fastening feature located proximal to the second fastening feature 142 . 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 FIGS. 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 FIGS. 11 and 12 , the recessed portions 147 of the first fastening feature 141 and the second fastening feature 142 merge on the outer surface 145 of the side wall 143 and form a common elongated recess 148 . The elongated recess 148 includes a longitudinally recessed portion extending in the 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 side wall 143 . This radial distance is at least equal to or greater than the thickness of the base portion 172 of the restrictor 170 . In this manner, the elongated recess 148 is configured to receive the base portion 172 of the restrictor 170 as a whole. When attached to the sidewall 143 , the restraint 170 and its base portion 172 do not protrude radially from the outer surface 145 of the sidewall 143 .

As illustrated in FIGS. 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 approximately 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 towards 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 extend into the first fastening feature 141 . In FIG. 12 , the limiter stop feature 171 and thus the first leg 173 extend into and engage the second fastening feature 142 .

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

As shown in FIGS. 11 and 12 , a recessed section 150 circumferentially adjacent to the elongated recess 148 is also provided. The recessed section 150 is circumferentially opposite the through openings 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 restraint 170 can be raised radially outward to remove the restraint 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 restraints 70 , 170 may be frictionally or adhesively attached to the side walls 43 , 143 of the housing 10 . The restraints 70, 170 may be fastened to the side walls 43, 143 by means of separate components, for example by means of fasteners. Such fasteners may include adhesive labels or covers 90 that cover the restraints 70 , 170 and secure them to the side walls 43 , 143 . In the embodiment of FIG. 11 or FIG. 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 secured to the housing 10 by means of adhesives or by means of welding. The restraints 70, 170 and the housing 10 may comprise a moldable plastic material suitable for welding, such as laser welding or ultrasonic welding.

To temporarily or permanently secure the restraints 70 , 172 to the housing 10 , a label 100 may be provided that is adhesively attached to the outer surfaces 45 , 145 of the side walls 43 , 143 . Label 100 may be provided with readable information printed thereon. The information may include 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 restraints 70 , 170 and the first and second fastening features 41 , 42 , 141 , 142 .

Additionally and as illustrated in Figures 16-19, a separate cover 90 may be provided. Cover 90 may comprise a plastic material. The cover 90 may comprise a slightly tubular shape cut in the longitudinal direction so as to comprise a semicircular cross-section and to comprise 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 manner, 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 clamped attachment of the cover 90 in the radial direction of the housing 10 . In one embodiment, the restraints 70, 170 and the cover 90 may be integrally formed. Here, the restrictor 70 may protrude from the inner surface of the cover 90 . The restraints 70 , 170 and cover 90 may be shaped and configured such that when the cover 90 is attached and secured to the housing 10 , the restraints 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 Figures 7, 8, 17 and 19, the fastening elements 91 of the cover 90 comprise radially inwardly projecting pins 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 with respect to all three dimensions.

Additionally or alternatively, the label 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 way that a portion of the label 100 also covers a portion of the outer surface 145 of the side wall 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 for embodiments of the injection device having only one fastening feature 41 , 141 on the side wall 43 , 143 of the housing 10 or The implementation is equally valid. By way of example only, the fastening features 41 , 141 may include recessed portions 147 to receive the base portions 72 , 172 of the restraints 70 , 170 . Furthermore, the only first fastening features 41 , 141 may be covered by the cover 90 and/or the label 100 .

List of reference signs

1 Injection device

2 Distal direction

3 Proximal orientation

4 Direction of dose escalation

5 Direction of dose decrement

6 cartridges

7 stoppers

8 drive mechanism

9 Dose setting mechanism

10 shell

11 Triggers

12 dose dial

13 Dosage window

14 Cartridge holder

15 injection needles

16 inner needle cap

17 Outer needle cap

18 Protective caps

20 Piston Rod

21 Bearings

22 First thread

23 Presser foot

24 Second thread

25 barrels

26 Seals

28 threaded socket

30 Drive bushing

31 Thread section

32 flange

33 Flange

35 Last dose limiter

36 Shoulder

40 spring

41 Fastening Features

42 Fastening Features

43 Side walls

44 Through opening

45 outer surface

50 Dose Tracker

51 Tracking Stop Feature

60 adapter

62 Inserts

63 Stop features

64 bars

70 Limiter

71 Limiter Stop Feature

72 Base part

73 Inclined section

80 digital casing

81 groove

90 hood

91 Fastening elements

100 tags

141 Fastening Features

142 Fastening Features

143 Sidewall

144 Through opening

145 outer surface

146 inner surface

147 Recessed part

148 Recess

149 buttons

150 Recess

151 Fastening elements

170 Limiter

171 Limiter Stop Feature

172 Base part

173 Outriggers

174 Outriggers

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.

Images