Patent Application
20230285673
The present disclosure relates to an arrangement for a drug delivery device.
Drug delivery devices, such as auto-injectors, are known in the art for dispensing a medicament to the injection site of a patient.
In EP 2 583 708 A1 a medicament delivery device is proposed which includes a tubular operation member, a tubular extension part and a tubular activation member which are assembled in a housing.
Certain aspects provide an improved arrangement for a drug delivery device.
One aspect of the present disclosure relates to an arrangement for a drug delivery device. Another aspect of the present disclosure relates to a drug delivery device, which preferably includes the arrangement. A further aspect relates to a method for assembling an arrangement. Therefore, features which relate to the arrangement do also apply for the drug delivery device and the method and vice versa. As opposed to the arrangement, the drug delivery device may have a reservoir retainer configured to retain a reservoir within a housing and/or a reservoir, which, preferably, includes a medicament. The reservoir may be arranged in the reservoir retainer. The reservoir may be syringe, e.g., a syringe with a staked needle. The device may be an auto-injector. The arrangement may be a drive arrangement, i.e., an arrangement having components which operate during a dose deliver operation for which the arrangement is designed. It should be noted that the present disclosure is not restricted to the embodiments which are claimed and that the disclosure may contain other innovative concepts than the claimed ones. Specifically, features can be extracted from the specific context they are disclosed in and may be combined with other features. It goes without saying that features disclosed in conjunction with different embodiments may be combined with one another.
In an embodiment, there is provided a drive arrangement for a drug delivery device. The drive arrangement includes:
“Distal” is used herein to specify directions, ends or surfaces which are directed or face towards the dispensing end of the drug delivery device or away from a proximal end. For example, the dispensing end of the device may be the distal end. On the other hand, “proximal” is used to specify directions, ends or surfaces which are directed or face away from the dispensing end of the drug delivery device. For example, the proximal end of the device may be the end furthest away from the dispensing or distal end.
In the configuration of the embodiment described further above, the plunger rod may be locked to a plunger rod release member which may be a collar. Accordingly, all further disclosures and features relating to the collar do apply to the plunger rod release member as well and vice versa. The plunger rod release feature may be a collar beam, e.g., movably and/or resiliently connected to a sleeve-like main body portion of the collar. The collar and the collar beam are movable relative to the housing, i.e., they are not fixed to the housing, which is also termed case in the following. The retention feature may be a notch in the plunger rod. The collar beam may be configured to engage the notch, for example by means of a collar prong which may be arranged at the end of the collar beam. The end may be a free end. There can be also two or more collar beams, collar prongs and/or notches accordingly. The prong may protrude radially, e.g., inwardly, from an axially extending portion of the collar beam. The configuration in the first position discussed further above may ensure that the plunger rod cannot move independently from or relative to the collar, unless the engagement of the collar beam to the plunger rod has been released as is the case in the second position. The second position may be an end position for the collar, i.e., a position in which the axial and/or rotational movement of the collar is stopped, e.g., by the collar abutting an axial and/or rotational end stop. If the engagement of the collar beam to the plunger rod is released the plunger rod can move in the distal direction, relative to the housing and the collar, for an injection or delivery operation under the force of the drive unit. In the first position, the engagement between the plunger rod and the plunger rod release member may react the force of the, e.g., pre-loaded, drive unit, if applicable with the aid of a support. When the plunger rod release member is in the second position, the drive unit may be released and the plunger rod may move for the delivery operation. The drive unit may include a drive spring, a gas powered drive means or other means to provide energy for a delivery operation of the arrangement. The movement of the plunger rod may be used to drive the delivery of the medicament, e.g., from a reservoir of the drug delivery device. Therefore, it should only occur if a delivery operation is wanted. Therefore, the release of the plunger rod should be reliable and safe. The release of the plunger rod may be subject to a movement of the collar which releases a collar beam from the plunger rod. Without the pre-determined movement(s) of the collar the plunger rod is not released. The movement of the collar may be initiated by the user of the drug delivery device. Therefore, an accidental release of the plunger rod, which would lead to an unwanted delivery operation may be avoided. In particular, when the plunger rod and the plunger rod release member are secured to one another in the first position, they may both move relative to the housing when the plunger rod release member is moved from the first position to the second position. Therefore, the plunger rod and the release member may have a reliable relative position in the first position and during the movement from the first position into the second position.
Moreover, providing a plunger rod release member in addition to the plunger rod avoids having drive features such as protrusions or bosses on the plunger rod which are provided to control the release of the plunger rod. Such features are often provided at the proximal end of the plunger rod and, if those features are dispensed with, the axial extension of a reservoir may be increased, for example, without having to increase the length of the device.
In an embodiment, the movement of the plunger rod release member from the first position to the second position includes axial movement and/or rotational movement. The first position and the second position may be axially and/or angularly offset from one another.
In an embodiment in the first position, the plunger rod release feature is radially supported. The radial support may prevent a disengagement of plunger rod release feature and plunger rod as a radial, e.g., radial outward movement, of the plunger rod release feature relative to the plunger rod may be prevented. In the second position, the radial support may be removed, e.g., on account of the movement of the plunger rod release member relative to the housing, to allow a radial movement of the plunger rod release feature relative to the retention feature such that the plunger rod release feature may disengage the retention feature. The radial movement of the plunger rod release feature, which, as has been discussed above already, may be a collar beam, can be prevented by a drive unit holder ring of a drive unit holder which acts as a radial support. The safety for avoiding an accidental release of the plunger rod is improved as the release of the plunger rod release feature requires additionally that a radial support is removed. The support may be provided by a component fixed axially and rotationally relative to the housing or by the housing itself. The support may also assist in reacting the drive unit force, e.g., a part of the force, preferably not the entire drive unit force.
In an embodiment the plunger rod is
It is advantageous for avoiding an accidental release to rotationally secure the plunger rod release member to the plunger rod, so that the movement for releasing the plunger rod is of a different kind than the movement of the plunger rod after release which is axially. It is also advantageous alternatively or cumulatively to axially secure the plunger rod release member to the plunger rod, so that prior to the axial movement after release the plunger rod undergoes another axial movement during the releasing process.
In an embodiment the movement of the plunger rod release member and/or the plunger rod from the first position to the second position is or includes a helical movement relative to the housing. This is advantageous because a combined rotational and axial movement is required in order to a release the plunger rod to the second position. In particular, if the second position is axially and rotationally (angularly) offset from the first position, which may require a helical movement form the first position into the second position, the risk of an accidental release of the plunger rod may be reduced over systems which involve only rotational and/or only axial movement.
In an embodiment the plunger rod release member is mechanically coupled to an interface member, e.g., having a hollow body. The interface member may be secured to the housing axially and rotationally. The interface member may be secured to the housing axially and rotationally. Having a separate interface member may have advantages in the manufacturing process. However, in terms of the function it has during operation of the drive arrangement, the interface member could also be integral with the housing. The interface member may be a sleeve. One of the plunger rod release member and the interface member may include a helical interface feature, e.g., a protrusion, which is configured to convert an axial movement of the plunger rod release member, preferably relative to the housing and/or driven by the drive unit, and/or an axial force acting on the plunger rod release member, e.g., by the drive unit and/or in the distal direction, into an axial and rotational movement of the plunger rod release member. The other one of the plunger rod release member and the interface member may include a feature, e.g., a collar tongue, engaging the helical interface feature to guide the helical movement. The force required for the movement of the plunger rod release member from the first position into the second position may be provided by the drive unit. The interface member may be a drive unit holder. The interface feature may be a drive unit holder sawtooth boss. It may interact with the collar, for example with the collar tongue which is arranged at the collar. The drive unit holder sawtooth boss may be configured as a ramp such that, when the collar tongue is pushed axially onto the ramp, the ramp forces the rotational movement of the collar or the drive unit holder. The ramp may be inclined into the distal direction in a portion which guides the movement of the plunger rod release feature relative to the housing. This embodiment is particularly advantageous because the drive unit which drives the delivery or injection in a drug delivery device may apply its force axially along the longitudinal axis. This force may be used for generating the rotational movement of the plunger rod release member. The application of the drive unit force in the axial direction to the collar causes the collar to move in the distal direction towards the drive unit holder in a combined axial and rotational movement of the collar.
The plunger rod release member may be mounted on the interface member and movable relative to the interface member. One section of the plunger rod release member may be arranged on the exterior of the interface member. Alternatively or additionally, a section of the plunger rod release member, e.g., a section including the plunger rod release feature, may be arranged in the interior of the interface member. The interface member may provide an axial end stop for the plunger rod release member such that the axial movement of the plunger rod release member is stopped by the interface member in the second position.
In an embodiment a deepening is provided in the housing, wherein, in the first position, the plunger rod release feature is angularly and/or axially offset from the deepening, and wherein, in the second position, the plunger rod release feature is received within the deepening, preferably to disengage the retention feature of the plunger rod. Particularly, when in the second position, the plunger rod release feature may be moved or movable into the deepening, preferably by a force provided by the drive unit. The deepening may be a recess extending radially and/or axially. The deepening may be provided in the interface member, such as a drive unit holder ring of the drive unit holder. The deepening may be a groove, into which the collar beam can flex, e.g., outwardly. When the collar beam faces this deepening and flexes outwardly the collar beam may be at the second position. The deepening can be offset axially and/or angularly in the first position relative to the collar beam. If the deepening is offset axially relative to the collar beam a relative axial movement of the collar to housing or the drive unit holder is required to reach the second position in which the collar beam can flex outwardly into the deepening. If the deepening is offset relative to the collar beam angularly in the first position a relative rotational movement of the collar to housing or the drive unit holder is required to align the collar beam and the deepening such that the collar beam (release feature) can flex into the deepening. The collar may include two or more collar beams. Accordingly, the housing or the drive unit holder ring can include two or more deepenings which are adjusted such that the two or more collar beams can flex into a deepening. The deepening may define the second position of the collar or plunger rod release member relative to the housing. This configuration may assist in ensuring that the plunger rod is only released from the collar, when the collar has been rotated into the second position. This rotation may be concurrent with the axial movement of the collar relative to the housing.
In an embodiment, in the first position, the engagement between the plunger rod release feature and the retention feature reacts the force of the drive unit, which may be pre-stressed. This has the advantageous consequence that as soon as the plunger rod is released it will be pushed in the distal direction, due to the force of the drive unit, for initiating the injection process. Moreover, the force of the drive unit may be used to drive axial movement of the plunger rod release member or collar relative to the housing. Also, the force of the drive unit may be used to disengage the plunger rod and the plunger rod release member, e.g., to move the release feature, e.g. radially and/or outwardly, relative to the plunger rod.
In an embodiment, in the first position, a rotational movement of the plunger rod release member is blocked by a blocking interface established between the plunger rod release member and a moveable trigger member, e.g., by blocking interface features on the members which engage one another to prevent the rotation. The rotation which is prevented may be rotation in the same direction as the rotation which may be necessary to move the plunger rod release member into the second position. The trigger member may be moveable, preferably relative to the housing, to release the blocking, e.g., axially movable, such as proximally. The trigger member may be rotationally locked relative to the housing. For example, it may be rotationally locked to the interface member, e.g., by engaging axial guide slots provided in the interface member such as on an outer surface thereof. The interface member may, in turn, be rotationally locked to the housing, e.g., by snap features or other suitable means of securing two parts to one another. The trigger member may react a part of the drive unit force in the first position which may be transferred to the trigger member via the plunger rod release member. The trigger member may provide the interface to the user which is contacted by the user to trigger or initiate a dispensing operation. The moveable trigger member may be a needle cover which is movable axially along the longitudinal axis. Features disclosed in the following for the needle cover apply for the trigger member as well. The needle cover may include a blocking interface feature which may be a needle cover leg rib. The needle cover is movable relative to the housing. In a first position the needle cover leg rib may block a rotation of the collar, e.g., by angularly abutting a feature on the collar. In a second position, the needle cover leg rib does not block the rotation of the collar. The collar may include a collar firing boss which interacts with the needle cover leg rib such that if they overlap axially in their position and/or abut a blocking of the rotation occurs and if they do not overlap or no longer abut a rotation of the collar is allowed. In the first position of the needle cover the needle cover blocks rotation of the collar. It is also possible that the needle cover includes two needle cover leg ribs and/or that the collar includes two collar firing bosses which act in the same manner. The rotation of the collar takes care that the collar beam is facing the deepening of the drive unit holder ring in the second position, so that it can flex outwards and release the plunger rod.
In an embodiment the interface member includes a guiding portion for guiding the moveable trigger member axially along the longitudinal axis. This reduces possibly occurring torques acting on the moveable trigger member as the lever arm or leverage may be reduced as compared to a situation without a guiding portion. The trigger member may extend from the distal end up to the plunger rod release member and have one or more arms extending proximally. The guiding portion may be arranged closer to the plunger rod release member, especially closer to the blocking interface feature on this member, than to the distal end of the trigger member. This configuration is particularly advantageous, if the trigger member has a certain length. For example, the trigger member may protrude distally from the housing and the plunger rod release member may be proximally offset from the distal end of the housing. The trigger member may have a sleeve-like portion which protrudes distally from the housing in the first position of the plunger rod release member. One or more arms of the trigger member may extend axially towards the proximal end. The respective arm may be connected to the sleeve-like portion. The respective arm may be guided by the guiding portion in a region between the distal end of the housing and the blocking interface of the trigger member with the plunger rod release feature. The blocking feature of the trigger member may be provided proximally offset from the guiding portion, preferably by a distance which is smaller than the proximal offset of the guiding portion or the interface member from the distal end of the housing.
In an embodiment, the interface member has a portion which is received in the interior of the plunger rod release member. The interface member may have another or second portion, e.g., axially offset from the portion, which is not received in the interior. The second portion may overlap radially with the plunger rod release member, e.g., a sleeve-like portion thereof.
In an embodiment the interface member includes a radial outward step or flange, wherein
In an embodiment, the interface member which may be a drive unit holder may include, e.g., at the end a distal portion a drive unit holder ring. The drive unit holder ring may include the deepening. The plunger rod release feature, i.e., the collar beam extends into the interior of the ring, such that if the ring is adjusted appropriately relative to the collar, the collar beam can flex into the deepening provided in the ring. The drive unit holder includes a fixing portion for fixing the drive unit holder to the housing. Therefore, the drive unit holder is not moveable relative to the housing. The plunger rod release feature, i.e., the collar beam, may extend into the opening of the drive unit holder which is a part of the drive unit holder ring. At its inside of the drive unit holder ring the deepening is arranged into which the collar beam can flex outwardly for releasing the plunger rod. Therefore, also at least a part of the plunger rod is arranged at the inside of the drive unit holder ring. In this configuration the positionally fixed part, i.e., the drive unit holder ring, is also the starting position of the plunger rod at its release position. This gives the overall device additional stability. Alternatively or cumulatively the positionally fixed part, i.e., the drive unit holder and its radial outward step or flange, defines an end stop for the collar. This is also advantageous as the end stop is at a mechanically fixed part. An end stop for the collar means a defined status for its axial and rotational state relative to the drive unit holder, e.g., as an initial position for a priming operation or as an end position to release the plunger rod.
In an embodiment the interface between the plunger rod release feature and the retention feature which is established in the first position includes at least one surface which is inclined relative to the longitudinal axis, i.e., oblique to the longitudinal axis and non-perpendicular. The interface can include a collar prong with an inclined surface. An inclined surface is advantageous as the force of the drive unit applies a force in the axial direction to the plunger rod. Via the inclined surface, this force can be used to generate a radial movement to release the engagement between plunger rod release member and plunger rod. When the collar prong is locked into the plunger rod via a notch the force is applied to the collar prong as well resulting in a force towards its inclined surface such that the collar beam flexes radially outward. As a result, once the collar beam is at a position, axially and/or rotationally, facing the deepening, the release of the plunger rod is achieved by a transfer of the force of the drive unit to the inclined surface of the prong, without any additional adjustment.
Consequently, the drive unit force may be used to move the plunger rod release feature out of engagement with the retention feature. The inclined surface, e.g., on the plunger rod release feature, when subjected to an axial load such as the drive unit force, generates a radial force acting on the plunger rod release feature which, if not reacted, such as by the support, e.g., in the interface member, or the housing, causes a radial movement of the plunger rod release feature, e.g., in the outward direction, to disengage the plunger rod release feature and the retention feature.
In an embodiment, the plunger rod release member includes a, preferably rigid main body or main body portion, and the plunger rod release feature is movably connected to the main body, e.g., finger-like. The main body may provide mechanical stability where the engagement/disengagement functionality may be provided by the flexible plunger rod release feature connected to the main body. The main body may be sleeve-like.
In an embodiment, the plunger rod release feature is elastically deflectable, e.g., relative to the main body.
In an embodiment, the interface member is a member separate from the housing but axially and rotationally secured to the housing. The interface member, e.g., the drive unit holder, is separately manufactured but is fixed to the housing when the drive arrangement is assembled. Therefore, the drive unit holder along with the collar, the plunger rod, and the drive unit can be assembled as a separate unit and then fixed to the housing. This provides advantageous flexibility in manufacturing and assembling of the drive arrangement.
In another aspect a drug delivery device is provided which includes a drive arrangement and a reservoir, e.g., a syringe, and may includes a medicament for injection. The reservoir, e.g., the syringe, may include a volume equal to or greater than 2.5 ml, in particular a volume of 3 ml.
In an embodiment the drug delivery device is a needle-based injection device with integrated non-replaceable container, where each container holds a single dose, whereby the entire deliverable volume is expelled when the device is operated for delivering the single dose. The drug delivery device may fulfil the requirements of ISO 11608-1, 3rd ed. 2014 Dec. 15.
Embodiments will now be described, by way of example only, with reference to the accompanying drawings, in which:
The same reference numbers apply to the same features throughout the figures and the following explanations.
An embodiment of a drug delivery device is described in the following with reference to
The case 201 is adapted to hold a medicament container, such as a syringe 109. The syringe 109 may be a pre-filled syringe and includes a needle for injecting a medicament. The reservoir, e.g., the syringe, may receive a medicament having a volume equal to or greater than 2.5 ml. The needle may be covered by a protective needle shield 125, which is why the needle is not visible in
The device includes a needle cover 105 which may be movably retained within the case 201, e.g., telescopically. The needle cover 105 may be arranged to cover the needle, preferably when the needle shield has been removed and/or when the delivery operation has been completed. The needle may be the one included by the syringe or one provided in the case when a cartridge without a pre-mounted needle is used as container or reservoir. The needle cover may function as a trigger member, which, when moved relative to the case from an initial position, e.g., in the proximal direction, triggers the dose delivery operation which may be spring-driven. Alternatively, another member, such as a button, may be provided as trigger member (not illustrated).
The device further includes a needle cover spring 119, which may be arranged to cooperate with the needle cover 105 in the drug delivery device. The needle cover spring may be arranged to bias the needle cover, e.g., distally. Accordingly, when the needle cover is moved proximally relative to the housing the needle cover spring may be loaded and the force of the loaded spring may be used to drive the needle cover distally, e.g., once an element reacting the spring force, such as the skin of the user, is removed from the needle cover 105.
A plunger rod 111 of the device is arranged to be driven by a drive spring 113 of the device, e.g., a compression spring and/or a helical spring. When the plunger rod 111 moves distally relative to the syringe, the medicament in the syringe is dispensed from the device. The plunger rod may move distally relative to syringe and case under the force of the drive spring during the delivery operation. The drive spring may be pre-loaded. The entire force required to move the plunger rod may be provided by the pre-load in the drive spring. No loading or setting operation may be required. The container may contain an amount of medicament, which is sufficient for only one delivery operation. Thus, the device may be a, e.g., disposable, device for administering a single dose of medicament. The drive spring force, e.g., the force with which the drive spring is pre-loaded, may be greater than or equal to any one of the following values: 20 N, 25 N, 30 N, 45 N or even higher.
The device 100 further includes a collar 117. The collar is arranged to be operatively connected to a drive spring holder 115 of the device 100 as will become apparent from the further explanations below. The drive spring holder 113 provides a cavity in which the drive spring 113 is received. The cavity may be provided by a sleeve-like portion of the drive spring holder. The drive spring is at least partly received in the drive spring holder. A proximal surface of the drive spring may abut a distal surface of the drive spring holder. The drive spring holder may react the force of the pre-loaded drive spring.
The plunger rod 111 serves for transferring the force of the drive spring 113 to the syringe 109, particularly the stopper 129. The drive spring may be retained between a proximal facing surface of the plunger rod 111, e.g., an inner surface, and a distally facing surface of the drive spring holder 113. The syringe barrel and the needle may be axially secured in the case, e.g., by means of an appropriate bearing surface provided in the interior of the case or by means of an additional syringe holder. The drive spring 113 is arranged within the plunger rod 111 biasing the plunger rod 111 in the distal direction. In another exemplary embodiment, the plunger rod 111 may be solid and the drive spring 113 may engage the plunger rod at a proximal end of the plunger rod 111. Likewise, the drive spring 113 could be wrapped around the outer diameter of the plunger rod 111 and extend within the syringe 109. The needle cover spring 119 may be operatively coupled between the needle cover 105 and the collar 117.
When the drug delivery device 100 is assembled all components shown in
When the needle cover is moved proximally, the needle will protrude from the device and can be introduced into the target tissue.
Further, this figure shows a part of the drive spring holder 115 connected with a needle cover leg 131 and collar tube 123. The collar tube 123 is surrounded along the axis X by the needle cover spring 119. It further shows the drive spring holder 115, the needle cover spring 119 and the collar tube 123.
Before the device is prepared to be in the primed position or state, the device 100 is in a so-called un-primed position or state. In this un-primed state one or more locking mechanisms are in place which ensure that an accidental release of the plunger rod is avoided. A sub-assembly including plunger rod, drive spring, collar and/or drive spring holder may be in this position or state already when it is connected with other parts of the device during the assembling process.
Therefore, the drive spring may be kept reliably in a tensioned state until the device is brought into the primed state, which is the condition ready to release the plunger rod. Accordingly, the un-primed state may be maintained until the device 100 is completely assembled and the primed position is established for sale and use.
In the presently proposed mechanism, the needle cover may be used for switching from the un-primed state to the primed state. The needle cover 105 is movable axially relative to the case 201 along the longitudinal axis X, in particular in the proximal direction. The collar 117 is axially and rotationally movable relative to the case 201. The drive spring holder 115 is fixed with the fixing portion 171 to the case 201 and is a member separate from the case 201 but axially and rotationally secured to the case 201. The needle cover leg ribs 135 of the needle cover 105 are in mechanical contact with the ramped collar priming bosses 147 or can be brought into contact with the ramped collar priming bosses 147 when the needle cover 105 is moved proximally when the device is switched from the unprimed state to the primed state, i.e. when the priming operation is performed. In
The unprimed state is illustrated very schematically by way of
When the needle cover 105 is moved in the proximal direction along the axis X, for priming the device, the collar 117 and the plunger rod 111 (not shown), which is slaved or immovably coupled to the collar as will be explained below, until the plunger rod is released from the collar, are also pushed in the proximal direction along the axis X on account of the engagement of the needle cover with the priming bosses 147, which transfers an axial force and a rotational force to the collar 117 due to the ramps are oblique surfaces of the priming bosses. It should be noted, that, instead of having a plurality of priming bosses, one priming boss 147 may be sufficient. If the collar tongue 145 already angular abuts the drive spring holder sawtooth boss 139 when the axial and rotational force is imparted to the collar, the movement of the needle cover causes, on account of the block rotational movement, and axial movement of the collar 117 in the proximal direction relative to the case and/or the drive spring holder 115. If there is not yet an angular abutment between, the collar and the drive spring holder, the collar may be moved axially and rotationally relative to the drive spring holder 115 on account of the forces transferred to it via the needle cover and the priming boss. However, independent of whether there is an abutment already when the needle cover in cooperation with the priming boss starts to transfer axial and rotational forces to the collar, after the collar 117 and, particularly, the collar tongue 145 has cleared axially the drive spring holder sawtooth boss 139, rotation of the collar relative to the drive spring holder is no longer blocked and a rotational movement of the collar 117 relative to the case and the drive spring holder 115 occurs. The axial and rotational movements of the collar are symbolized in
The needle cover legs 131 are guided by the drive spring holder rails 157, which are arranged at the outside of the drive spring holder ring portion 167, along the axis X. The drive spring holder 115 is fixed to the front case 121 by the fixing portion. The collar 117 and the plunger rod 111 are held together by the collar beams 141 and its collar prongs 143 which are locked into the notches 151 of the plunger rod 111. When the drive spring holder sawtooth boss 139 is axially overlapping with the collar tongue 145 (see
The rotation of the collar 117 is stopped or blocked when the collar firing boss 159 of the collar gets in contact with the needle cover leg rib 135 which overlap in their positions at least partially axially. The collar firing boss 159 of the collar 117 then prevents the collar 117 from rotating further around the longitudinal axis X as the needle cover leg is locked rotationally relative to the housing or case 201 and the collar firing boss 159 abuts the needle cover leg rib 135. Thus, the collar cannot rotate in that direction which it would have to rotate for the delivery operation—in
The needle cover leg rib 135 may provide an angularly oriented surface which abuts the collar firing boss 159 in the primed position. Thus, the leg rib 135 blocks rotation of the collar 117 to avoid an accidental release of the plunger rod. The needle cover leg rib(s) may have a distally oriented surface which in the primed position abuts a proximally facing surface of the collar. In this way a distal movement of the needle cover relative to the case and the collar may be prevented. The distally facing surface may be a surface of the leg rib 135. The angularly facing surface and the distally facing surface may be implemented by an L-shaped geometry of the leg needle cover leg rib 135 as depicted in
Alternatively or additionally, an axial end stop may be provided which stops the collar 117, e.g., the drive spring holder ring 161. The movement of the collar beams 141 radially outward is caused by the force of the drive spring 113. The collar prongs 143 which are locked into the notches have an oblique surface which is oriented in the proximal direction such that the edge of the notches 151 are pushed under the force of the drive spring 113 towards this oblique surface. The edge of the notches 151 glides in the distal direction along the collar prongs which causes the collar prongs 143 to move radially outward so that the collar beams 141 flex radially outward, preferably elastically. In another embodiment the collar beams 141 during mounting are bent elastically inwardly towards the axis X and covered by the drive spring holder ring 167. The collar beams 141 then continuously apply a force towards the drive spring holder ring 167. Once the collar beams 141 face the drive spring holder grooves 149 they flex outwards into the drive spring holder grooves 149 due to the lack of radial support in this region.
The drive spring holder 115 may react a part of the drive spring force which is transferred to it via the collar beams 141 or an elastic restoring force which tends to disengage the collar beam 141 from the plunger rod 111, e.g., by radially supporting the collar beam. When the collar beam has reached the position of the groove 149 by axial and rotational movement of the collar relative to the drive spring holder, the radial support is removed and the collar beams will disengage the plunger rod. After the collar beams have disengaged the plunger rod, the beams may be biased radially inwardly. That is to say they tend to move inwardly (again). The collar beams, in particular the prongs, may abut an exterior surface of the plunger rod after the disengagement, e.g., on account of an elastic restoring force which tends to move the collar beams inwardly.
In order to lock the needle cover 105 against proximal movement relative to the housing or the case, particularly in the end position after the delivery operation has been performed, the needle cover has one or a plurality of needle cover lock arms 163. In the depicted embodiment, two arms are provided. However, more than two arms may be provided as well. In case there are a plurality of arms 163 they are preferably evenly distributed in the angular direction. The needle cover lock arms are expediently oriented axially, particularly proximally. A free end of the needle cover lock arms 163 may face in the proximal direction. The needle cover lock arms 163 may be arranged to abut or abut a distally facing surface of the case or housing or a component which is at least axially, but preferably axially and rotationally, secured relative to the housing or case. In the position depicted in
The inner portion 600 may be radially spaced apart from an inner wall of a portion of the case which delimits the interior of the device from the exterior. Accordingly, a channel, e.g., an axially extending channel, which may be continuous in the circumferential direction, may be formed between the portion 600 and an inner wall of the case or housing. The channel may be configured to receive a section of the needle cover, e.g., when the needle cover is arranged in the initial position and/or moved proximally to trigger the delivery operation.
Laterally, in an outer surface of the inner portion 600, one or a plurality of guide slots 602 may be formed. The guide slots may be arranged and configured to guide the lock arms 163 axially, e.g., by receiving the needle cover lock features 165. The lock features 165 may be received in the guide slots 602 when the needle cover is in its initial position, e.g., that position from which the delivery operation may be triggered by moving the needle cover proximally. As is depicted in
The respective needle cover lock arm 163, which expediently has a proximally facing free end, may be flexibly, e.g., elastically, connected to the remainder of the needle cover. The arm 163 may be resiliently displaceable relative to the longitudinal axis, e.g., outwardly. The resilient bias generated by the elastic displacement of the arm may move the arm 163 and the needle cover lock feature 165 inwardly again after the feature has cleared the inner portion. The needle cover lock arm may be pivotable relative to the needle cover. The ability to pivot may be provided by way of a hinge portion 175 in the needle cover which has a reduced thickness which is located in a region of the arm 163 remote from the free end. The hinge portion may be a film hinge portion. However, already the presence of distinct arms may provide for enough resiliency or flexibility for the present purposes and the hinge portion 175, though advantageous, may be dispensed with.
The needle cover lock arm 163 may be axially oriented, e.g., parallel to the axis X. Preferably, the needle cover lock arm is axially oriented in both positions, the initial position and the end position. The same may hold for an intermediate position, i.e., a position, where the needle cover is proximally displaced relative to the initial position for triggering the delivery operation. The respective needle cover lock arm 163 is connected to the remainder of the needle cover 105 via a connecting portion 177. The connecting portion 177 may extend circumferentially and, particularly, may have the shape of a sleeve. The connecting portion 177 may be radially inwardly offset from an inner wall of the front section 133 of the needle cover 105. In this way, there may be a radial clearance between the connecting portion 177 and inner surface. Alternatively or additionally, a distance may be present in the radial direction between the lock arm 163 and an inner surface of the front section 133 of the needle cover. This distance allows radial flexibility for radial deflection of the arm 163 in the outward direction during the movement of the needle cover into the end position and/or radially inward movement, e.g., due to its intrinsic resiliency, back into a radial position where the arm is arranged to abut the distally facing surface of the inner portion such as a surface of wall 601. The connecting portion 177 may be axially oriented. The connecting portion 177 may be connected to the front section 133 of the needle cover which defines the outer lateral surface of the needle cover via a further connecting portion 179, which preferably extends in the radial direction, e.g., outwardly. Connecting portion 179 may be provided at the end of the axial connecting portion 177 remote from the needle cover lock arms 163. The needle cover lock arm 163 may be restricted to the interior of the needle cover, especially its front section 133. The connecting portion 179 may provide a bearing surface for the needle cover with which the needle cover is configured to bear against the skin of a user of the drug delivery device during the delivery operation.
As compared to needle covers which use obliquely oriented fingers on an outer surface of the needle cover which interact with an inner surface of the housing for locking the needle cover in the end position after the delivery operation, the present construction with the needle cover lock arms 163 which are arranged on the interior and not on the exterior facilitates the provision of a syringe with a shorter needle. This is, because the axial extension of the slanted needle cover lock arms does not have to be taken into account when designing the needle cover. Moreover, as the needle cover lock arms are provided in the interior, they are hidden and cannot be manipulated in an attempt to reuse the device or uncover the needle again. Providing syringes with shorter needles may facilitate modifying an existing device architecture to accommodate syringes of higher volumes such as a volume greater than or equal to 2 mL, or greater than or equal to 2.5 mL or greater than or equal to 3 mL without having to extend the length of the device and/or its diameter considerably.
Aside from the shorter needle cover, the collar may assist in avoiding a considerable increase in the dimension, especially lengthwise, due to use of a higher volume syringe. Drive features, e.g., bosses, which may be required on the plunger rod, e.g., its proximal end, can be dispensed with as the collar 117 governs the rotational and axial movement of the plunger rod until the plunger rod is released from the collar. Thus, there is no need to provide the plunger rod with profiled surface structures which guide the plunger rod rotationally. The axial space which is saved by using the collar for the plunger rod release can be accommodated by a portion of the syringe.
As discussed above, the internally arranged needle cover lock arms 163 prevent proximal movement of the needle cover 105. Distal movement of the needle cover is prevented by a proximal surface which is axially secured to the housing abutting a distal surface of the needle cover such as a distal surface delimiting the needle cover cut out 137 as depicted in
The different positions of the needle cover with respect to the housing or case are explained in more detail below.
The arrangement in
From the unprimed position in
A needle shield grabber (not shown in this representation, see 103 in
The needle cover 105 may be moved axially in the proximal direction until its proximal movement is blocked, e.g., by the arms 163 or the features 165 hitting the distal surface of the inner portion. Now, further axial movement of the needle cover in the proximal direction is prevented. As the cap is moved further in the proximal direction towards its end position relative to the case, on account of the obliqueness of the distally facing surface of the needle cover lock feature 165, the feature 165 and the associated arm 163 may be deflected radially outwardly, such as towards an inner wall of the needle cover 105. Thereafter, the needle cover 105 may be moved proximally relative to the case or housing. Then, the features 165 may engage the guide slots 602. This movement of the needle cover may be effected by way of an assembly tool which can be introduced through apertures in the cap through which the needle cover 105 can be contacted. However, it is also conceivable that the axial movement of the needle cover into its initial position in which the needle cover lock features 165 engage the guide slots 602 occurs on account of the movement of the cap 101 relative to the case into its end position. In this case, the radial movement of the needle cover lock features may be effected by the portion of the cap being introduced into the interior of the needle cover. In this case, an axial support is not required to radially displace the needle cover lock arms. Whether or not the support is advisable or used for the radial displacement of the arms 163 may depend on the force required to displace the arms radially.
As is depicted in
After the injection operation or delivery operation has been performed, the needle cover 105 may be moved towards the end position and into the imposition by way of the needle cover spring as has already been discussed previously.
As has been discussed previously the collar or plunger rod release member 117 is moved proximally after the plunger rod has been released from the collar. Then the drive spring force is no longer transferred to the collar 117. When moving proximally, the collar 117 moves towards an inner surface of the case or housing. The proximal movement of the collar 117 is driven by the needle cover spring 119, which is operatively coupled between the needle cover 105 and the collar, e.g. by abutting the distal surface of flange 161. In the previously described embodiment, the collar may move purely axially in the proximal direction. It is, however, possible to use force of the needle cover spring to rotate the collar 117, e.g., to establish a needle cover lock by means of the collar in order to lock the needle cover 105 against proximal movement in the end position. The end position may be distally offset from the initial position.
Due to the rotation, a feature on the collar such as a needle cover lock feature 302 provided on the collar may be rotated into a position where it angularly and radially overlaps with a proximally facing surface associated with the needle cover, e.g. a proximal surface of the needle cover legs 131. In this position, the lock feature 302 may abut or be arranged to abut the needle cover 105. As the collar, in its proximal end position cannot be moved proximally anymore, e.g. as it abuts a distally facing surface of the case, the abutment between the needle cover and the needle cover lock feature 302 on the collar prevents proximal movement of the needle cover and, accordingly, provides a needle cover lockout suitable to lock the needle cover in its end position against proximal movement relative to the case or housing.
The terms “drug” or “medicament” are used synonymously herein and describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient (“API”), in the broadest terms, is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders.
As described below, a drug or medicament can include at least one API, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Examples of API may include small molecules having a molecular weight of 500 Da or less; polypeptides, peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double or single stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.
The drug or medicament may be contained in a primary package or “drug container” adapted for use with a drug delivery device. The drug container may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more drugs. For example, in some instances, the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days). In some instances, the chamber may be designed to store a drug for about 1 month to about 2 years. Storage may occur at room temperature (e.g., about 20° C.), or refrigerated temperatures (e.g., from about −4° C. to about 4° C.). In some instances, the drug container may be or may include a dual-chamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered (e.g., an API and a diluent, or two different drugs) separately, one in each chamber. In such instances, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components prior to and/or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing. Alternatively or in addition, the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body.
The drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and/or prophylaxis Y of many different types of medical disorders. Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis. Examples of APIs and drugs are those as described in handbooks such as Rote Liste 2014, for example, without limitation, main groups 12 (anti-diabetic drugs) or 86 (oncology drugs), and Merck Index, 15th edition.
Examples of APIs for the treatment and/or prophylaxis Y of type 1 or type 2 diabetes mellitus or complications associated with type 1 or type 2 diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptor agonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms “analogue” and “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, by deleting and/or exchanging at least one amino acid residue occurring in the naturally occurring peptide and/or by adding at least one amino acid residue. The added and/or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogues are also referred to as “insulin receptor ligands”. In particular, the term “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may have been deleted and/or replaced by other amino acids, including non-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide.
Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.
Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29) (N-tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-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-gamma-glutamyl)-des(B30) human insulin, B29-N-omega-carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); B29-N—(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.
Examples of GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, for example, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide/HM-11260C, CM-3, GLP-1 Eligen, ORMD-0901, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034. MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN and Glucagon-Xten.
An examples of an oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia.
Examples of DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.
Examples of hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.
Examples of polysaccharides include a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra-low molecular weight heparin or a derivative thereof, or a sulphated polysaccharide, e.g. a poly-sulphated form of the above-mentioned polysaccharides, and/or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a poly-sulphated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate.
The term “antibody”, as used herein, refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab′)2 fragments, which retain the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has reduced or no ability to bind an Fc receptor. For example, the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region. The term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and/or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV).
The terms “fragment” or “antibody fragment” refer to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and/or light chain polypeptide) that does not include a full-length antibody polypeptide, but that still includes at least a portion of a full-length antibody polypeptide that is capable of binding to an antigen. Antibody fragments can include a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments. Antibody fragments that are useful in the present disclosure include, for example, Fab fragments, F(ab′)2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and VHH containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.
The terms “Complementarity-determining region” or “CDR” refer to short polypeptide sequences within the variable region of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term “framework region” refers to amino acid sequences within the variable region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining correct positioning of the CDR sequences to permit antigen binding. Although the framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen.
Examples of antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6 mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).
Pharmaceutically acceptable salts of any API described herein are also contemplated for use in a drug or medicament in a drug delivery device. Pharmaceutically acceptable salts are for example acid addition salts and basic salts.
Those of skill in the art will understand that modifications (additions and/or removals) of various components of the APIs, formulations, apparatuses, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the present concepts, which encompass such modifications and any and all equivalents thereof.
| Number | Date | Country | Kind |
|---|---|---|---|
| 20315380.4 | Aug 2020 | EP | regional |
The present application is the national stage entry of International Patent Application No. PCT/EP2021/071606, filed on Aug. 3, 2021, and claims priority to Application No. EP 20315380.4, filed on Aug. 7, 2020, the disclosures of which are incorporated herein by reference.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2021/071606 | 8/3/2021 | WO |
