Medication delivery device

[0001] The present invention relates to a drug delivery device and a method of producing or assembling such a device. The invention relates in particular to dosage mechanisms suitable for use in drug delivery devices, in particular pen-type injectors, preferably having dose setting devices and a guide device enabling dispensing of a medicinal product from a cartridge containing one or more doses of a drug. In particular, the present invention relates to such drug delivery devices in which a user can set the dose of drug to be administered from a multi-dose cartridge. Most preferably, the drug delivery device comprises a cartridge containing one or multiple doses of drug that can be replaced when the drug supply is completely depleted.

[0002] The present invention further relates to a reset mechanism for a drug delivery device, and in particular to a reset mechanism comprising a reset element which is coupled to the piston rod of the drug delivery device. Most preferably, the reset mechanism of the present invention is turned on and off by, respectively, attaching and detaching the drug reservoir to and from the housing of the drug delivery device.

[0003] Such drug delivery devices find application where systematic injection is required by persons who have not received adequate medical training, i.e. patients. This is becoming increasingly common among people with diabetes for whom self-medication can effectively control diabetes.

[0004] Such circumstances place a number of requirements on such drug delivery devices. Such a device must have a solid construction, and at the same time be easy to use in terms of handling its parts, the user's understanding of how it works, and administering the required dose of medicine. The dose setting must be easy and unambiguous. For diabetic patients, many users will be physically ailing and may also have impaired vision, requiring the dosing mechanism to have a low release force guiding device and the drug delivery device to have an easy to read dose setting indicator.

[0005] For environmental and economic reasons, this type of drug delivery device has been developed to allow rejection of only part of the device after all the medicine has been depleted, usually only the drug cartridge itself. This puts an additional requirement on such a drug delivery device that the re-setting of the drive mechanism when a new cartridge is attached or inserted to the drug delivery device must be easy and unambiguous, without the user having to directly touch any component of the drive mechanism , thereby reducing the risk of damage to the drive mechanism through, for example, its contamination.

[0006] Another requirement for such reusable devices is that when a new cartridge is attached, there should be no displacement of the pin in the cartridge, and therefore the content of the cartridge does not

272 274 029 BI should be compressed before setting the dose and administering it. If this happened, it could affect the accuracy of the device.

[0007] In the medical field, user-operated drug delivery devices are well known.

[0008] WO 2004/078239 A1 discloses a drive mechanism for a drug delivery device with a housing having a screw thread, a dose dial sleeve having a screw thread coupled to a screw thread of the housing, a guide sleeve releasably connected to the dose dial sleeve and a clutch means located between the dose dial sleeve and the guide sleeve. When the dose dial knob sleeve and the guide sleeve are engaged by a clutch means, both can rotate relative to the housing. When the dose dial sleeve and the guide sleeve are disengaged, the dose dial sleeve can rotate relative to the housing while the guide sleeve cannot rotate relative to the housing, whereby the guide sleeve can be axially displaced so that the longitudinal direction of the piston rod is transmitted on the piston rod force to release the drug. This document does not describe how to replace the cartridge or how to reset the drive mechanism.

[0009] The following documents describing the prior art relate to the issue of the re-use of such devices using a disposable and replaceable drug cartridge that are connected to / detachable from a reusable (re-adjustable) drive mechanism.

[0010] Document EP 0 554 996 B1 discloses an injection device comprising a housing and an element for attaching a fluid-containing cartridge and an internal piston to the housing. A lead screw is movably mounted inside the housing, and a dose setting device is provided for selecting the amount of fluid to be dispensed by the device. This device provides a solution to the issue of cartridge replacement and resetting the dose mechanism of the reusable injection device. The new cartridge is inserted into the housing, which is then screwed into place, while the piston of the cartridge pushes the lead screw into the device, which can have the disadvantage of being pressurized at the end of the screw.

[0011] Document US 5 827 232 speaks of a drug delivery pen comprising a drug-containing disposable cartridge assembly. The cartridge assembly includes a cartridge with a sealed pierceable distal end and, inside it, a plunger in a fluid-tight sliding engagement for releasing the drug from the cartridge as the plunger moves toward the distal end. Furthermore, the drug delivery pen includes a reusable pen body assembly that has a housing, a lead screw located in the housing, and a driving means for moving the lead screw toward the distal end by sections selected on the pen body. Although this device provides a solution to the issue of re-setting the pen drive mechanism for drug delivery, it requires the user to align the applicator with the slots at the distal end of the piston rod, which may prove difficult for users with impaired vision and / or dexterity.

[0012] WO 1997/010864 A1 describes a drug delivery pen comprising an applicator assembly for retaining a cartridge having a plunger, the applicator assembly having a series of threads of thread at the proximal end. The pen body assembly includes a series of threads at the distal end for winding

ΕΡ 2 274 029 BI for a series of threads in the applicator assembly. The lead screw extends from the distal end to engage the piston in the cartridge. A means for moving the lead screw towards the distal end is provided for introducing the lead screw into the cartridge. Furthermore, to allow automatic and easy retraction of the lead screw to the pen body as the pen body assembly approaches and is bolted to the applicator assembly, a means for decoupling the lead from the lead screw is present. However, the disclosed solution to attaching the new applicator assembly to the reusable pen body assembly may have the disadvantage that pressure is applied to the piston at the end of assembly.

[0013] The object of the invention is to avoid the disadvantages of known drug delivery devices, and in particular to provide a flexible re-setting mechanism suitable for use in a drug delivery device by which the drug delivery device can be re-set for reuse after replacing the drug cartridge .

[0014] The drug delivery device of the present invention is a valuable alternative in the art to known drug delivery devices. For example, the drug delivery device of the present invention has the advantage that the piston rod is inserted back into the body of the device when a new cartridge is attached, without the user having to touch any part of the dosage mechanism and without any displacement of the cartridge plug. The drug delivery device of the present invention furthermore has the advantage of easily replacing the drug cartridge almost without applying pressure to the cartridge plug during re-positioning of the device and thus without compressing the drug contained within the cartridge before the first dose setting and release.

[0015] According to the invention, a drug delivery device has been developed comprising:

• a housing having proximal and distal ends, • a medicine container intended for attachment to the housing, • the piston rod is moved towards the distal end for dispensing of the drug, and • a guide device for rotating the piston rod in the first rotational direction, thereby moving the piston rod in the direction distal end for drug administration.

[0016] The piston rod comprises two threaded sections, the first of which is provided for threading with the resetting means and the second is provided for threading with the guide device, the threads of the first and second threaded sections being opposite. In the operating state, rotation of the re-adjusting element relative to the housing is prevented and thus the piston rod cannot move towards the proximal end. In the re-positioning state, the re-positioning element is free to rotate relative to the housing, so the drug delivery device can be re-positioned by rotating the piston rod together with the re-adjusting member in the second rotation direction and displacing the piston rod towards the proximal end.

[0017] The drug delivery device of the present invention is designed so that in the operating condition the piston rod can be moved axially towards the distal

Końca 2 274 029 BI and rotated in one direction (first rotational direction) relative to the housing by the guide device for drug delivery, while axial movement of the piston rod towards the proximal end relative to the housing is prevented.

[0018] According to the present invention, the drug delivery device is designed such that, in the operating condition, rotation of the re-positioning element relative to the housing is prevented. Preferably, in the operating state, any movement (both transiational and rotational) of the re-positioning element relative to the housing is prevented. Preferably, the resetting element is secured inside the housing so that its axial movement relative to the housing in any condition is prevented, and in addition its rotation is only prevented in the operational state. Alternatively, the re-setting element may be fixed inside the housing so that it is held so that it can rotate and, to a limited extent, axially with respect to the housing in the re-setting state, while in operating condition its axial and rotational movement with respect to the housing is prevented. .

[0019] Furthermore, the drug delivery device is designed such that in the re-positioning state, the piston rod is free to axially move in the direction proximal end relative to the housing (while rotating in the other direction - the second rotational direction). Preferably, the drug delivery device is designed such that, in the re-positioning state, the piston rod is free to be reciprocated back toward the proximal end relative to the housing, e.g. to re-position the piston rod when a new drug reservoir ( e.g. a new cartridge or applicator with a new cartridge) is bonded at the distal end of the device housing.

[0020] According to a preferred embodiment of the present invention, the drug delivery device is designed such that • when the drug dispenser is attached at the distal end of the housing, the re-setting element is in operative condition, and • when the drug dispenser is detached from the distal end housing, then the reset item is in a reset condition.

[0021] According to such an embodiment, the movement leading to attachment of the medicament reservoir to the housing results in the displacement element being moved to such a position or bringing it into a state in which it is pivotally locked with respect to the housing. This can be achieved, for example, by moving the reset device to a position where it engages with objects (e.g., teeth or projections) of the housing or other non-rotatable component of the drug delivery device, or, e.g., by moving another non-rotatable component to position in which it engages the resetting element and prevents it from rotating.

[0022] The present invention therefore further relates to a drug delivery device comprising:

• a housing having a proximal end and a distal end, • a drug reservoir intended to be attached to the distal end of the housing • a piston rod moved towards the distal end for drug delivery, and • a guide device for rotating the piston rod in the first rotational direction and thereby moving the piston rod towards the distal end for drug delivery.

272 274 029 BI [0023] The piston rod is threaded to a reset element. Preferably, the piston rod comprises two threaded sections, the first of which is provided for threading with the resetting means and the second is provided for threading with the guide device, the threads of the first and second threaded sections being opposite.

[0024] When the drug reservoir is attached to the housing, rotation of the re-positioning element relative to the housing is prevented, and thus the piston rod cannot move towards the proximal end. When the drug dispenser is detached from the housing, the re-setting element is free to rotate relative to the housing, so the drug delivery device can be re-positioned by rotating the piston rod together with the re-setting element in the second rotation direction, thereby displacing the piston rod in the direction of near the end. The device is therefore in an operational state when the drug reservoir is attached to the housing and in a reset state when the drug reservoir is detached from the housing.

[0025] According to a preferred embodiment of the present invention, the medicament reservoir is intended to be attached to the distal end of the housing by coupling the first coupling agent to the second coupling agent. The first engaging means and the second engaging means are movable to engage, e.g., by a drug dispenser movement that includes rotational movement without axial displacement of the drug dispenser (e.g., motion that ends in a rotational movement without axial displacement of the drug dispenser) relative to the housing (or vice versa, through the movement of the housing, which includes rotational movement without axial movement of the housing (e.g., which ends in a rotational movement without axial displacement of the housing) relative to the drug dispenser). The re-positioning element can thus advantageously be put into operating state during the rotational movement of the drug reservoir during which the drug reservoir does not move axially with respect to the housing or during the rotational movement of the housing during which the housing does not move axially with respect to the drug reservoir.

[0026] However, the drug reservoir can be coupled to the housing by any coupling means known to those skilled in the art.

[0027] The medicament dispenser of the drug delivery device may comprise an activating means for putting the resetting means into operative condition (and also preferably for holding it therein) in which the resetting means preferably directs the piston rod for drug delivery. The housing and the drug reservoir can be movable to engage, for example, through a movement that includes and preferably ends in a rotational movement without axial displacement of the actuating means relative to the housing, whereby the activating means brings the resetting element into an operational state. [0028] The drug delivery device may be designed such that, by displacing, e.g. rotatable, the actuating means, the activating means directly or indirectly interacts with the resetting element to bring it into working condition and thereby bring the device into administering the drug to the working state for dispensing the drug, in which rotation of the re-positioning element relative to the housing is prevented and in which movement of the piston rod towards the proximal end is prevented.

272 274 029 BI [0029] In a preferred embodiment of the present invention, the first and second coupling means of the housing and the drug reservoir are designed such that when the drug reservoir and the housing are moved to engage with each other, the switching means is first rotated and axially displaced relative to the housing, and then rotated without axial displacement, thereby bringing the dose setting member back into working condition. When the first and second coupling means are disengaged (i.e. when the drug reservoir is detached from the housing), the reset device preferably leaves the operating state or is moved out of it into a different position (reset state) in which it no longer steers or drives maintains the piston rod.

[0030] According to a preferred embodiment of the present invention, the drug dispenser or drug dispenser insert comprises a first coupling means, and the housing or housing insert includes a second coupling means.

[0031] The first coupling means may for example be a drug reservoir thread (preferably external thread) and the second coupling means may be a housing coupling member or housing insert for engaging with the drug reservoir thread, the distal end of the drug reservoir thread becoming an annular the groove so that the drug reservoir is attached to the housing by first rotating and moving towards the proximal end relative to the housing, and then only rotating relative to the housing. Only the rotation at the end of the coupling movement is caused by the movement of the coupling element along an annular groove that has no scale (i.e. whose pitch is zero). Preferably, the annular groove is only an arcuate annular groove that extends around a portion (e.g., 1/6) of the circumference of the substantially tubular end of the drug reservoir. Optionally, the thread / annular groove may be part of the housing and the drug reservoir may include a coupling element. [0032] Alternatively, the distal end of the housing may, for example, be provided with an insert comprising a second coupling means and intended to engage with the first coupling means at the proximal end of the drug dispenser, the insert being secured against rotation but free to move axially with respect to the housing (limited axial movement), except that the axial movement of the insert towards the distal end is limited by the holding means. In particular, the housing insert may include an internal thread as a second engaging means for engaging the first engaging means which is an external thread at the proximal end of the drug reservoir, wherein the drug reservoir includes an engaging means and is rotated and displaced axially with respect to the insert and housing in the first stage of coupling the drug reservoir with the housing, and in the second stage of coupling the drug reservoir with the housing, the drug reservoir is rotated, while axial movement of the storage container relative to the housing is prevented, the insert being displaced towards the distal end by rotation of the drug storage in the second stage. The insert can be moved toward the distal end, for example, until the insert rests against the retaining means or when the internal thread of the insert is over.

[0033] According to a preferred embodiment of the present invention, the insert is a movable sleeve with an internal thread and the holding element is a holding ring which limits the axial movement of the sleeve towards the distal end. The retaining ring is attached to the distal end of the housing in such a way that its rotation and axial movement relative to the housing are prevented. Moreover, for pressing the bushing against the axial stop means (e.g. annular ribs) inside

Obudowy 2 274 029 BI of the housing is provided with a spring member when the drug reservoir is not coupled to the device housing. The spring member preferably abuts one side against the proximal side of the holding ring and the other side against the distal side of the movable sleeve. The sleeve is coupled to the housing so that it can move linearly, but is prevented from turning. When the housing and the drug reservoir are moved to engage with each other, the outer thread at the proximal end of the drug reservoir engages with the inner thread of the sleeve. Thus, the drug dispenser is screwed to the distal end of the housing until the proximal edge or bead of the drug dispenser rests on the distal side of the retaining ring. Such a support prevents further linear movement of the drug reservoir towards the proximal end. However, further rotation of the drug reservoir is possible, which causes the sleeve to move linearly towards the distal end, against the force exerted by the elastic center, until the sleeve rests on the proximal side of the holding ring. Such a support completes the engaging movement of the housing and the drug reservoir. Only the rotation of the drug reservoir at the end of the coupling movement is used to bring the re-setting element into its operating state in which it directs the piston rod to dispense the drug.

[0034] In all embodiments of the present invention, the resetting means is preferably a nut that is threadedly engaged with a piston rod, preferably an external thread of the piston rod. According to a preferred embodiment of the present invention, the re-adjusting element is a nut which is threadedly engaged with the piston rod and which is engaged with the locking means in the operating state and in the re-setting state it is detached from the locking means.

[0035] According to a preferred embodiment of the present invention, the guiding device comprises a guiding sleeve and a second threaded section of a piston rod is provided for engaging the thread with the guiding sleeve.

[0036] In such an embodiment, the drug delivery device may be designed such that the guide sleeve is threadedly coupled to the piston rod (its second threaded section) and when the guide sleeve guides the piston rod towards the distal end for drug delivery, then the guide sleeve is displaced axially, but its rotation relative to the housing is prevented, thus causing axial displacement towards the distal end and rotation of the piston rod. The sliding of the guide sleeve towards the distal end (without rotating it) relative to the housing during drug delivery results in the guide sleeve moving towards the distal end relative to the piston rod. This movement causes the piston rod to rotate in the first rotational direction due to the fact that the guide sleeve is threaded to the second threaded section of the piston rod. This rotational movement of the piston rod displaces the piston rod torsionally towards the distal end due to the threaded engagement of the alignment element with the first threaded section of the piston rod. The piston rod therefore pushes the piston inside the drug reservoir towards the distal end, thereby releasing the drug from the drug reservoir. [0037] A mechanical gearing can be obtained, for example, if the thread of the second threaded section (on which the guide device is mounted, preferably the guide sleeve) has a larger pitch of the thread of the first threaded section (on which the re-setting element is screwed). Thus, according to a preferred embodiment of the present invention, the piston rod has a first section

ΕΡ 2 274 029 BI thread with a first pitch, and on the second threaded thread a thread with a second pitch, whereby the first pitch is smaller than the second pitch (the thread pitch on the first threaded section is smaller than the thread pitch on the second threaded section).

[0038] Preferably, the screening device of the present invention further comprises a stop means, which stop means is designed such that • during dose setting, the guide sleeve cannot move axially without rotating relative to the housing, and when dispensing a dose, it is impossible to turn the guide funnel here relative to the housing, axial displacement of the guide track relative to the housing towards the distal end is possible.

[0039] The stop means may, for example, comprise a clutch means that is non-rotatably coupled to the guide sleeve. Preferably, the clutch means is located between the dose dial knob sleeve and the guide sleeve and is provided for engaging and disengaging the dose dial knob and guide sleeve.

[0040] The device for administering the screen of the present invention preferably comprises a dosing mechanism that includes a piston rod and a guide device. The dosage mechanism may further include:

• a dose dial sleeve having a screw thread engaged with the screw thread of the housing, the guide sleeve being releasably coupled to the dose dial sleeve, and

a) the clutch means between the dose dial sleeve and the guide sleeve, whereby the dose dial sleeve and the guide sleeve are engaged (by means of the clutch means), both can rotate relative to the housing, and

b) when the dose dial sleeve and the guide sleeve are disengaged, the dose dial sleeve can rotate relative to the housing, while rotation of the guide sleeve relative to the housing is not possible, although the guide sleeve can move axially towards the distal end, thereby moving force towards the distal end on the piston rod.

[0041] Preferably, when the dose dial sleeve and the guide sleeve are engaged (by means of a clutch means), both can rotate and move axially relative to the housing, but both cannot move axially without rotating relative to the housing (on the example because the sleeve of the dose knob is coupled to the housing by means of a screw thread). According to a preferred embodiment of the present invention, the dose dial knob sleeve and the guide sleeve are engaged during dose setting and disengaged during dose delivery.

[0042] The dose dial knob sleeve and the guide sleeve are preferably engaged during re-setting of the dose delivery device (in the re-setting state). Preferably, in the reset state, the guide sleeve cannot move axially. Optionally and most preferably, in the reset state, the guide sleeve can move axially only in conjunction with a rotary movement (e.g., the guide sleeve is indirectly connected to the housing thread via clutch means and the dose dial sleeve) and cannot move axially without turning. IN

Therefore, in the reset state, when a force is applied (e.g. by the user) to push the distal end of the piston rod (e.g. presser foot) towards the proximal end, then the piston rod rotates together with the element to resetting in the second direction of rotation. The piston rod is thus reciprocally displaced towards the proximal end due to the threaded engagement between the guide sleeve and the second threaded section, while the guide sleeve does not move axially.

[0043] According to a preferred embodiment of the present invention, the pitch (and pitch) of the screw thread of the dose dial sleeve, which is engaged with the screw thread of the housing, is the same as the pitch (and pitch) of the thread on the second threaded section of the piston rod. In this case, the offset of the dose dial knob sleeve relative to the housing is identical to the offset of the guide sleeve relative to the piston rod during dose setting.

[0044] In all the above-mentioned embodiments, the dose delivery device may include a blocking means that is non-rotatable with respect to the housing and which can engage the reset device, thereby blocking the reset device to prevent its rotation with respect to the housing in working condition. Preferably, the locking means is spline-connected to the housing or to the housing insert, whereby it can move axially, but its rotation relative to the housing is prevented. Preferably, the locking means can move axially only to a limited extent relative to the housing. Optionally, the blocking means may be attached to the housing or even be part of the housing, and therefore any movement thereof relative to the housing may be prevented.

[0045] When the re-setting element is engaged with the locking means in operative condition, rotation of the piston rod is preferably prevented in one rotational direction and its axial movement is prevented towards the proximal end relative to the housing, but it can rotate in the remaining direction and pivot axially toward the distal end relative to the housing for drug delivery.

[0046] The resetting means or locking means of the drug delivery device of the present invention may have a shape that cooperates with the shape of the engaging means to engage the locking means and the positioning means by rotating (preferably without axial movement) of the activating means relative to the housing.

[0047] In particular, at least one sloping surface may be located on the actuation means and at least one suitably sloping surface may be positioned on the resetting means or on the blocking means, the sloping surfaces being formed such that for cooperation of the activating means and the resetting means or the engaging means and the blocking means, the sloping surfaces may slide on each other.

Preferably, the engaging means comprises at least one protrusion with an inclined surface positioned fixed or movably on the engaging means or comprises at least one hump with the inclined surface to cooperate with the resetting element or the locking means, e.g. by rotation of the engaging means in in one direction relative to the housing and thus for engaging the alignment element with the locking means.

Blok2 274 029 BI [0049] The blocking means and the re-setting element may, for example, comprise teeth of the work surface that are mutually engaged when the blocking means and the dose delivery element are engaged in the operating state. In the reset state, the working surface teeth are uncoupled, and thus the locking means and the re-setting means are uncoupled.

[0050] Furthermore, the dose delivery device is preferably designed such that the locking means decouples from the resetting element under the force exerted by the setting means, for example when the drug reservoir is detached from the housing. The setting means is preferably a spring that pushes the resetting element and the locking means away from each other when the drug reservoir is separated from the housing of the drug delivery device. Most preferably, the adjusting means pushes the locking means axially away from the reset element when the drug dispenser is detached from the distal end of the housing, thereby disengaging the locking means from the reset element.

[0051] Additionally or alternatively, the drug delivery device may be designed such that when the drug reservoir is detached from the housing, the locking means decouples from the resetting element, after which the resetting element is free to rotate relative to the housing. When the locking means and the resetting element are uncoupled in this embodiment, then the resetting element is already in the operating state, but in the resetting state. According to a preferred embodiment, the piston rod is free to move toward the proximal end when the locking means is disengaged from the reset element.

[0052] Preferably, the drug reservoir is an applicator that is intended to receive a drug-filled cartridge. The applicator is intended to be attached to the distal end of the housing. Optionally, the drug reservoir may, for example, be a cartridge having a first coupling means for engaging the second housing coupling means. The drug-filled cartridge is preferably a drug-containing tubular body closed on one side by a piston and on the other by a septum. When the plunger is moved toward the proximal end of the cartridge, then the drug is released, for example, through a needle that extends beyond the septum and which is in communication with the drug (e.g., insulin).

[0053] According to a preferred embodiment of the present invention, the drug reservoir (or insert or attachment of the drug reservoir) and housing (or insert or attachment of the housing) can be additionally provided with latch objects by which the drug reservoir and the housing are kept engaged during normal operation. use of the device for administering the medicine, especially during dose setting and drug delivery. Furthermore, the snap objects can provide the user with an audible and tactile feedback when the drug dispenser is securely attached to the housing.

[0054] The drug delivery device may be a pen device and / or an injector device. The drug delivery device may include a needle or may be needle-free.

[0055] The term "drug delivery device" according to the present invention will mean a single or multi dose, single use or multiple use device intended for dispensing a dose of the medicinal product and preferably multiple selected doses, e.g. insulin, growth hormones, low molecular weight heparins and their analogues and / or derivatives etc. Such a device

EP 2 274 029 B1 may have any shape, e.g. compact or pen-like. Dosing can be accomplished by using a mechanical (optionally manual) dosing mechanism or electronic dosing mechanism or electromechanical dosing mechanism or dosing mechanism based on stored energy, such as a spring, etc. The dose can be selected by using a manual or electronic mechanism, or electromechanical. In addition, this device may contain components designed to monitor physiological properties, such as blood glucose, etc. Furthermore, such device may include a needle or may be needle-free. Preferably, the term "drug delivery device" will mean a multi-dose pen reusable device having mechanical and manual dose delivery and dose selection mechanisms that is intended for regular use by persons without formal medical training, such as patients. Preferably, the drug delivery device is of the injector type. Most preferably, the drug delivery device is for administering the drug in liquid form.

[0056] The term "drug reservoir" will preferably mean, in the context of the present invention, a drug-containing cartridge or cartridge assembly, and most preferably an dispenser for receiving a drug-containing cartridge. Furthermore, the terms "drug cartridge" and "cartridge" and "cartridge assembly" are used interchangeably in the context of the present invention. This means that the use of the term "drug cartridge" includes each meaning of the terms "cartridge" or "cartridge assembly" and retreat.

[0057] The term "applicator" according to the present invention will mean any component and / or components intended to hold a drug cartridge containing a drug to be dispensed by a drug delivery device. The applicator can have any shape, e.g. cylindrical and / or tubular. As a rule, the applicator may be uniform or it may be a complex tubular or non-tubular cylindrical component. It can be made of any suitable material known to those skilled in the art, e.g. transparent material. In addition, the applicator or applicator liner is preferably provided with a coupling agent, e.g. a screw thread or partial thread, or a bayonet or the like, on the outer and / or inner surface of the distal end and / or the proximal end of the applicator or insert, intended to engage with the corresponding coupling means located on the outer and / or inner surface of the housing, housing inserts and / or needle assembly. In a preferred embodiment, the applicator is a uniform tubular structure having an external thread at its proximal end.

[0058] The term "housing" according to the present invention will preferably mean any external housing ("housing", "body", "shield") or also an internal housing ("insert", "internal body") having a coupling means such as a thread helical, projection or any other suitable means known to those skilled in the art. The housing may be designed to allow the safe, correct and convenient operation of the drug delivery device or any mechanism thereof. Usually, it is intended to engage with any of the internal components of the drug delivery device (e.g., dosing mechanism, cartridge, plunger, piston rod) to cover, attach and direct and / or protect, by limiting exposure to such contaminants. like liquids, dirt, dust etc. As a rule, the housing can be uniform or it can be

272 274 029 BI as a complex tubular or non-tubular component. The outer casing can also be used to contain a cartridge from which multiple doses of the medicinal product can be dispensed. [0059] The term "reset device" according to the present invention will preferably mean any component intended to prevent the re-setting of the drug delivery device when the reset device and thus the drug delivery devices are in operational condition and intended for allowing re-setting of the drug delivery device when the re-setting element, and thus the drug delivery devices are in a reset state. The reset item may therefore take the reset status and the operational state. The re-adjusting element preferably also has the function of directing the piston rod in operational condition during drug delivery. To perform such a steering function, the resetting element preferably includes a shape to cooperate with the corresponding shape of the piston rod, e.g. an internal thread for twisting the outer thread of the piston rod after it, or a non-round hole for holding a piston rod with a corresponding non-round shape, or a piston rod with a segment having a corresponding non-round shape.

[0060] The term "operating condition" according to the present invention will preferably mean such a position or condition of the reset device in which the reset device prevents the drug delivery device from being re-positioned, i.e. directly or indirectly prevents the piston rod from moving closer. end. Preferably, the operating condition is further such a position or state of the re-adjusting element in which the re-adjusting element directs and / or holds the piston rod. The resetting means and thus the drug delivery devices are preferably in an operational state when the drug delivery device is used for dose setting and drug delivery.

[0061] The term "resetting condition" according to the present invention will preferably mean such a position or state of the resetting element in which the resetting element allows the drug delivery device to be re-positioned, i.e. directly or indirectly allowing the piston rod to move in the direction near the end. The reset device is preferably in an operational state when the drug delivery device is dismantled (i.e. the drug reservoir is detached from the housing) to replace the empty refill with a new refill filled with medicine.

[0062] The term "nut" according to the present invention will preferably mean any component intended for threaded engagement with a piston rod, preferably to function as a guide for the piston rod. Furthermore, the term "nut" according to the present invention will preferably mean any component with a threaded round hole that may be uniform or may be a complex component. According to a preferred embodiment of the present invention, the resetting means is a nut. In a further, more specific embodiment, the cap is free to rotate relative to the housing when it is not engaged with the locking means of the dose delivery device. According to one embodiment of the present invention, the nut is free to rotate and is secured against linear axial movement relative to the housing when it is not engaged with the locking means but is secured against rotation and linear axial movement relative to the housing when engaged with the locking means. Most preferably, the cap

272 274 029 BI is free to rotate and is held so that it can be limited to linearly axial displacement relative to the housing when it is not engaged with the drug delivery device locking means, but is secured against rotation and linear axial movement relative to the housing when it is coupled with blocking agent. In an even more specific embodiment, the nut has a textured surface, e.g., a set of working surface teeth (saw teeth, claw teeth, disc teeth or the like) or any other suitable friction surface preferably to engage with the textured surface of another component of the device, most preferably a blocking agent.

[0063] The term "blocking means" according to the present invention will preferably mean any component that is part of the housing, attached to the housing or engaged with the housing or insert so that its rotation relative to the housing is prevented, and most preferably so that it can move longitudinally, but its rotation relative to the housing is prevented. In a preferred embodiment, the locking means has a textured surface, e.g., a set of working surface teeth (saw teeth, claw teeth, disc teeth or the like) or any other suitable friction surface. In a more preferred embodiment, the non-rotatable locking means is intended for coupling with the resetting element, thereby preventing the resetting element from rotating relative to the housing. In a more specific preferred embodiment of the present invention, the textured surface of the non-rotatable locking means engages with the textured surface of the reset member (preferably the nut) in operative condition to prevent the reset member from rotating as long as the drug reservoir (preferably the applicator) is engaged with housing.

[0064] The term "inclusion agent" according to the present invention will preferably mean any component of the drug delivery device, and / or a component of the drug delivery device intended to engage any other component (s) of the drug delivery device from, and / or uncoupling from another component of the drug delivery device and / or components of the drug delivery device and / or for holding any component (or components) of the drug delivery device in engagement. Preferably, the activation means is a means for activating the blocking means to engage the blocking means with the resetting means. Optionally, the activation means may be a means for activating the reset means to engage the reset means with the locking means. In a preferred embodiment of the present invention, the inclusion means will form an integral part of the proximal end of the syringe container, e.g. the apiikator of the drug delivery device.

[0065] The term "restrictive means" according to the present invention will mean any object (or objects) and / or component (s) of the drug delivery device intended to prevent the axial and / or rotational movement of any component ί / fub components in at least one direction. In a preferred embodiment of the present invention, the term "restricting means" will mean any object perpendicular to the proximal-distal end of the medicament delivery device (in particular any planar surface object perpendicular to the proximal-distal end of the medicament delivery device)

272 274 029 BI designed to prevent axial movement of a component in one direction when the component is based on a perpendicular object. According to another preferred embodiment of the present invention, the term "stop means" will mean any object that provides a radial or rotational restriction intended to prevent rotation of a component in one rotational direction when the component stop is against a radial or rotatable stop.

[0066] In yet a further embodiment of the present invention, the term "restrictor" will mean a component ("end stop") of the dosing mechanism that prevents dose setting that exceeds the amount of drug remaining in the tray. Preferably, the end stop is a component that is secured against rotation but which can move axially relative to the housing and which will prevent the at least one component from rotating and / or axially displacing after setting the final dose, thereby preventing the setting of a dose that exceeds the amount of medicine remaining in the cartridge. Furthermore, the "end stop" will preferably have a helical thread on the outer surface designed to engage with the inner helical thread of the dose knob of the dose mechanism or the sleeve insert of the dose knob. Preferably, the pitch of the outer screw thread of said dose knob sleeve for threaded engagement with the housing will be greater than the pitch of the inner screw thread of the dose knob sleeve for threaded engagement with said end stop.

[0067] The term "coupling" according to the present invention will mean the mutual coupling of two or more components of the dosing mechanism / drug delivery device with each other by means of, e.g., a spline, thread, or overlapping teeth, preferably the mutual engagement of threads of the elements components ("threaded coupling").

[0068] The term "coupling means" according to the present invention will preferably mean any means known to those of skill in the art that can be used to couple two or more components of a device for administering a window, e.g. partial or complete threads, grooves, coupling elements that they engage with threads and / or grooves or centers that form a bayonet lock.

[0069] The term "uncoupling" according to the present invention will mean unlocking two or more components of the dosing mechanism / drug delivery device. According to one example, the term "uncoupling" according to the present invention will mean unlocking two or more dosing mechanism / drug delivery device by the force exerted by the setting means. The two components can also be decoupled under the influence of the force exerted by the user of the device, e.g. a patient unscrewing the drug container from the housing.

[0070] The term "adjusting means" according to the present invention will preferably mean any component intended to act with force on the component and / or components to ensure that the component and / or components (e.g. to engage) or distance (e.g. to disengage). Preferably, the adjusting means can be made of any flexible material known to those skilled in the art

EP 2 274 029 B1 suitable for storing energy (e.g. metal, rubber or plastics) and may take any suitable form, e.g. springs. In a more preferred embodiment, the adjusting means is a spring-loaded component located e.g. between the reset element and the locking means. In another preferred embodiment, the setting means is a spring component located between the nut and the locking means and disposed in the housing.

[0071] The term "distal end" according to the present invention will mean that end of the device or device component that is closest to the dispensing end of the device. Preferably, a needle assembly is present at the distal end of the drug delivery device of the present invention, the needle of which can be inserted into the patient's skin for drug delivery.

[0072] The term "proximal end" according to the present invention will mean that end of the device or component of the device that is furthest from the dispensing end of the device. Preferably, a button is present at the proximal end of the drug delivery device of the present invention that is pressed to dispense the dose.

[0073] The term "dosage mechanism" according to the present invention will mean any component and / or component and / or assembly intended to allow the user to select ί / or set the dose to be dispensed and / or for delivery and / or for delivery the force required to deliver a dose of medicine. Such a dosing mechanism may consist of mechanical and / or electromechanical components or electronic components. In addition, the dosing mechanism may be in and / or coupled to the device housing or may be an independent assembly. The dosing mechanism of the present invention comprises a piston rod and a guide device for moving the piston rod towards the distal end for drug delivery. Preferably, the dosing mechanism of the present invention comprises a guide bushing and a dose dial knob sleeve. More preferably, the dosing mechanism of the present invention comprises a guide bushing, a dose dial knob sleeve, a clutch means, a dose dial knob handle, and a push button means.

[0074] The term "piston rod" according to the present invention will mean a component adapted to operate through / within the housing, intended to convey axial displacement (preferably towards the distal end) through / within the drug delivery device, preferably from the guide sleeve to a plunger to withdraw / dispense from the drug cartridge, preferably being an injectable product. Such a piston rod may be flexible or not. It may be a straight stem, lead screw, part of a rack system, part of a worm gear system, or the like. 'Piston rod' will also mean a component with a circular or non-circular cross-section. It may be made of any suitable material known to those skilled in the art.

[0075] In a preferred embodiment, the piston rod comprises at least two, and more preferably two external and / or internal helical threads (threaded sections). In another preferred embodiment of the piston rod according to the present invention, the first helical thread (first threaded section) is at the distal end and the second helical thread (second threaded section) is at the proximal end of the piston rod, whereby said threaded section threads

ΕΡ 2 274 029 BI have opposite locations. In a further preferred embodiment, the piston rod according to the present invention comprises at least two threaded sections with threads having the same pitch and the same pitch at the distal and proximal ends. In yet another preferred embodiment of the present invention, the pitch and pitch of the second helical thread of the piston rod will be greater than the pitch and pitch of the first helical thread. More preferably, the pitch ratio of the screw threads of said first and second screw threads is in the range 1: 1.01 to 1:20, even more preferably in the range 1: 1.1 to 1:10, and most preferably 1: 2.3. Preferably, one of these threads (the thread of the other threaded section) is intended to engage with the guide sleeve. Preferably, the remaining of these threads (the thread of the first threaded section) is intended to engage with the nut. According to the most preferred embodiment of the present invention, the first externally threaded piston rod section with a thread having a smaller pitch is intended to engage with the internal thread of the nut, and the second externally threaded piston rod section with a thread having a larger pitch is intended to engage with the internal thread of the guide sleeve . In a further preferred embodiment of the present invention, the piston rod is provided with a stop means for limiting the axial movement of the end stop towards the proximal end. The stop means may be e.g. a coil of one of the external threads of the piston rod.

[0076] The term "dose dial knob sleeve" according to the present invention will preferably mean a component of a drug delivery device that is directly or indirectly used to dial / unscrew the dose of drug to be dispensed. Additionally or alternatively, the dose dial knob sleeve is intended to indicate the selected dose of the disposable product (drug). This can be achieved by using markings, symbols, numerals, etc., e.g., printed on the outside of the sleeve of the dose dial or odometer or the like. Most preferably, the dose dial knob sleeve is marked using laser printing. In a preferred embodiment of the present invention, the dose dial knob sleeve is essentially a tubular component with a substantially circular cross section having alternatively:

• both internal and external threads, or • internal and external threads • external threads.

[0077] Preferably, the dose dial knob sleeve includes an external thread for engaging the internal thread of the housing or housing liner. Preferably, the dose dial knob sleeve of the present invention includes an external screw thread with a pitch that is similar and preferably the same as the pitch of the internal screw thread of the guide sleeve. In a more specific embodiment of the present invention, the dose dial knob sleeve is provided with a series of radially extending members adapted to abut against a corresponding series of radial stops located within the housing and the housing insert. Such radial stop means are preferably provided to inhibit further reciprocating displacement of the dose dial knob sleeve outside the housing when the dose has been set and / or to

272 274 029 BI to suppress further reciprocating movement of the dose dial sleeve inside the housing when the dose is dispensed.

[0078] The term "guiding device" according to the present invention will preferably mean any component and / or components and / or assembly intended to transmit force to the piston rod for dispensing a dose of drug. Such a guide device may consist of mechanical and / or electromechanical and / or electronic components. The device may fit in and / or be coupled to the housing, or it may be an independent assembly. Preferably, the guide device according to the present invention comprises a guide sleeve. More preferably, the guide device of the present invention comprises a clutch guide guide sleeve and a push button means.

[0079] The term "guide sleeve" according to the present invention will preferably mean any component for direct or indirect guidance of the piston rod towards the distal end for drug delivery, and most preferably for guiding the piston rod directly. According to a preferred embodiment of the present invention, the guide sleeve is essentially a tubular component with a substantially circular cross-section. In a preferred embodiment, the guide sleeve is coupled to the piston rod. Preferably, the guide sleeve includes an internal thread for screwing onto the external thread of the piston rod. The guide sleeve is further preferably detachably connected to the dose dial knob sleeve, most preferably by a clutch means.

[0080] The term "thread" or "helical thread" according to the present invention will preferably mean a full or partial thread, e.g. a cylindrical spiral fin / groove located on the inner and / or outer surface of the drug delivery device component and also having a substantially triangular or rectangular or round cross section designed to allow continuous, free, rotatable and / or axial movement of each other components. Optionally, the thread may also be designed to prevent rotational or axial movement of certain components in one direction by being unable to disengage from it.

[0081] The term "pitch" according to the present invention will preferably mean the axial distance over which the nut would move by making one complete turn; preferably, "pitch" will mean the axial distance of the component having the screw thread, ie, the dose dial knob sleeve, guide bushing, piston rod, etc., of the dosing mechanism by one rotation. Thus, the pitch is a function of the thread pitch of the component.

[0082] The term "pitch" according to the present invention will preferably mean the distance between successive crests of the screw thread, measured parallel to the axis of the screw thread.

[0083] The present invention provides, in one aspect thereof, a drug delivery device according to the present invention for dispensing a medicinal product and preferably for dispensing a pharmaceutical composition (e.g. a solution, suspension) containing an active ingredient selected from the group consisting of insulin, hormone growth, low molecular weight heparin and their analogues and derivatives.

[0084] The invention further relates to a method of producing or assembling a medicament delivery device according to one of the above-mentioned embodiments. The method preferably comprises a step

272 274 029 BI for connecting the storage hopper to the distal end of the device housing by coupling the first coupling means to the second coupling means. The coupling action, when the drug reservoir is attached to the housing, results in bringing the re-setting element into a working condition in which the re-setting element is prevented from rotating relative to the housing and in which the re-setting element thus prevents the piston rod from moving towards the proximal end, and therefore re-setting the drug delivery device.

[0085] Without limiting it in any way, the present invention will be explained in more detail below with reference to the drawings in which:

Figures 1a to 1c show a cross-sectional view of one embodiment of the drug delivery device according to the invention in three different conditions;

- figures 2a to 2c schematically show an embodiment of an activating means cooperating with a blocking means in three different states according to one embodiment of the present invention;

- figure 3 is an enlarged cross-sectional view of the central part of the embodiment according to figures 1a to 1c showing the element for resetting the drug delivery device in operative condition;

- figure 4 schematically shows another embodiment of a medicament delivery device according to the present invention with a different arrangement of the activating means, the blocking means and the resetting means; and • figure 5 shows a further embodiment of the drug delivery device according to the invention. [0086] Referring first to Figures 1a to 1c, there is shown a device for administering the window of the present invention in three different positions.

[0087] The drug delivery device 1 comprises an applicator 2 and an (outer) housing 3. The housing 3 is preferably varnished. The distal end of the housing 3 is provided with an insert 3A, which is fixedly attached to the housing. The insert 3A is provided with a second coupling means 4 for engaging the first coupling means 5 of the applicator 2. In the embodiment illustrated here, the housing insert 3A is provided with a series of partial threads formed on the inner surface of the insert 3A. The proximal end of the applicator 2 is provided with a first coupling means 5 for engaging the second coupling means 4 of the insert 3A. In the embodiment illustrated here, the applicator 2 is provided with a thread whose distal end becomes a (partial) annular groove (not shown) formed on the outer surface of the applicator 2. The applicator 2 is secured inside the distal end of the housing 3 by engaging the second coupling means 4 of the insert 3A of the housing 3 with the first coupling means 5 of the applicator 2. In the illustrated preferred embodiment of the present invention, the proximal end of the applicator 2 is further provided with an engagement means 70 intended to engage and lock the reset means (nuts 11) in the operating state (described below and shown in Fig. 3).

[0088] In applicator 2 there is a cartridge 6 from which multiple doses of the medicinal product can be administered. The piston 7 is held in the cartridge 6.

272 274 029 BI [0089] The removable cap (not shown) can be detachably attached to the distal end of the applicator 2. Preferably, the cap includes a clip that is latched onto the cap. The attachment can also be varnished.

[0090] The distal end of the applicator 2 is provided with a suitable coupling means 8, such as a screw thread, bayonet or the like, to engage with a suitable needle assembly (not shown) to allow release of the drug from the cartridge 6 and its injection.

[0091] The drug delivery device 1 according to figures 1a to 1c comprises a dosing mechanism that includes a piston rod 17. The piston rod 17 has a generally circular cross section. The presser foot 18 is located at the distal end of the piston rod 17. The presser foot 18 is preferably made of two separate parts that are snap-connected together around the distal end portion of the piston rod 17. The presser foot 18 is positioned so that it rests against the proximal surface of the stem 7. The piston rod 17 is moved towards the far end by means of a guide device, thereby pushing the piston 7 so that it moves axially within the cartridge 6 towards the distal end for dispensing the drug. A first thread 15 is formed at the distal end of the piston rod 17 (first threaded section 15). A second thread 16 is formed at the proximal end of the piston rod 17 (second threaded section 16). The first thread 15 and the second thread 16 are arranged opposite to each other. Preferably, at least one of the first and second threads 16 is a multiple thread, and most preferably both are double threads.

[0092] The guide device comprises a guide sleeve 19 that extends around the piston rod 17. The guide sleeve is generally cylindrical. The guide sleeve 19 is provided, at its distal end, with a radially extending flange 20. The helical groove (thread) 21 extends along the inner surface of the guide sleeve 19. The second thread 16 of the piston rod 17 is adapted to work inside the helical groove 21 of the guide sleeve 19.

[0093] The bead 22A and the protrusion 22B are formed at the proximal end of the guide sleeve 19. The protrusion 22B has a reduced inner and outer diameter compared to the rest of the guide sleeve 19. The proximal end of the protrusion 22B is provided with a radially outwardly facing flange 23.

[0094] The clutch 24 is located around the guide sleeve 19, between the guide sleeve 19 and the end stop 28 (described below). The clutch 24 is adjacent the proximal end of the guide sleeve 19. The clutch 24 is generally cylindrical and is provided, at the distal end, with a series of circumferentially directed saw teeth 29. Each saw tooth has a longitudinally directed surface and an inclined surface. At the proximal end of the clutch 24 is a radially inwardly directed flange 30. The flange 30 of the clutch 24 is located between the bead 22A of the guide sleeve 19 and the radially outwardly flange 23 of the projection 22B. The proximal end of the clutch 24 is provided with a series of saw teeth 31. The clutch 24 is attached to the guide sleeve 19 by means of tabs (not shown) to prevent rotation between the clutch 24 and the guide sleeve 19. The clutch 24 is provided with a series of flexible arms 32 (not shown) which engage with a series of projections on the inner surface of the sleeve 27 of the dose selector knob (described below).

[0095] The clutch plate 25 and the adjusting means 26 are located between the distal end of the clutch 24 and the proximal surface of the radially outgoing flange 20 of the guide sleeve 19. In the illustrated embodiment, the adjusting means 26 is a spring. The proximal surface of the clutch plate 25 is provided

ΕΡ2 274 029 BI into a series of peripherally directed teeth of 33 saws. The clutch plate 25 is secured against rotation relative to the housing 3. Saw teeth 33 of the clutch plate 25 interact with the teeth 29 of the saw at the distal end of the clutch 24 during dose setting (as described below).

[0096] The end stop 28 is located around the guide sleeve 19, between the guide sleeve 19 and the sleeve 27 of the dose selector. The end stop 28 is secured against rotation with respect to the housing 3 and is free to move axially with respect to the housing 3. At the distal end of the end stop 28 there is a radially extending flange 34 intended to engage spline objects (not shown) on the inner surface of the housing 3. In the illustrated embodiment, the outer surface of the end stop 28 is provided with a helical groove (thread) that extends over the entire length of the end stop 28. The helical groove (thread) is coupled to the threaded insert 53 of the sleeve 27 of the dose dial. The inner surface of the end stop 28 is provided with a plurality of spline objects (not shown). The clutch plate 25 is engaged and thus secured against rotation relative to housing 3.

[0097] The dose dial sleeve 27 is located between the clutch 24 and the housing 3. A screw groove (41) is present around the outer surface of the dose dial sleeve 27. The housing 3 is provided with a helical rib (thread) 42 adapted to be embedded in a helical groove (thread) 41 of the sleeve 27 of the dose selector. In the illustrated embodiment, the helical rib (thread) 42 is formed on the inner surface of the insert 43. The threaded insert 43 is secured against rotation and axial movement relative to the housing 3. The screw rib 42 extends through one circulation of the inner surface of the insert 43. The proximal end of the dose dial sleeve 27 is provided with an inwardly directed flange in the form of a plurality of radially extending members 45.

[0098] The housing 3 is further provided with a window 40 (not shown) through which part of the outer surface of the sleeve 27 of the dose dial can be seen. A visual indication of the dose that can be unscrewed is located on the outer surface of the sleeve 27 of the dose selector. The window 40 conveniently only allows visual perception of the currently wrung out dose. The window may be designed to allow viewing of the visual indication of the currently dialed dose enlarged by acting as a magnifying glass. Preferably, the window 40 is filled with a transparent polymer. Most preferably, the window 40 is part of the housing insert 3, which is made by two-component injection molding, in which the dark polymer section surrounds the transparent polymer section. The insert is fixed to the housing, e.g. with adhesive tape.

[0099] The threaded insert 43 of the housing 3 is provided with a series of radial stop objects 55, 56 (not shown). The distal end of the dose dial sleeve 27 is provided with a series of stop objects 44 (not shown) against which the stop objects 56 of the insert 43 resist to prevent further sliding of the dose dial sleeve 27 from the housing 3 after the maximum dose has been set.

[0100] The dose dial knob 46 is disposed around the outer surface of the proximal end of the dose dial knob 27. The outer diameter of the dose selector handle 46 preferably corresponds to the outer diameter of the housing 3. The dose selector handle 46 is attached to the sleeve 27 of the dose selector to prevent movement between these parts. Knob handle 46

Dawki 2 274 029 BI is provided with a central opening 47. An annular recess 48, made at the proximal end of the dose dial handle 46, extends around the opening 47.

[0101] The button 49 is located at the proximal end of the drug delivery device 1. In the illustrated embodiment of the present invention, the button 49 has a substantially T-shaped cross section with the shank 50. The button 49 preferably has freedom of rotation relative to the housing 3. Preferably, the button 49 comprises a washer (not shown) made of friction reducing material (e.g. modified polymer material thorns) to reduce friction between the button and the dose dial handle 46 during dispensing. The stem 50 of the button 49 passes through the central hole 47 in the dose dial knob holder 46 and extends through the inner diameter of the projection 22B of the guide sleeve 19. The stem 50 of the button 49 is stopped for limited axial displacement in the guide sleeve 19 and the coupling 24. In the illustrated embodiment, the head 51 of the button 59 is substantially circular. The shield 52 depends on the circumference of the head 51. The shield 52 is adapted to be embedded in the annular recess 48 of the dose dial handle 46.

[0102] The inner surface at the distal end of the dose dial sleeve 27 is provided with a helical thread (not shown). In the illustrated embodiment, the screw thread of the dose dial sleeve 27 is on the inner surface of the threaded insert 53. The insert 53 is held inside the dose dial sleeve 27 with the end cap 54 attached to the distal end of the dose dial sleeve 27. The end cap 54 is secured against both rotation and axial movement relative to the sleeve 27 of the dose dial. The screw groove (thread) of the end stop 28 is engaged with the threaded insert 53 of the sleeve 27 of the dose dial.

[0103] The drug delivery device 1 further comprises a nut 11, which is a re-setting element and which has a series of teeth 12 of the work surface on the distal surface and a threaded round hole 13. The first thread 15 of the piston rod 17 passes through the threaded round hole 13 of the nut 11 and threaded with it. The axial displacement of the nut 11 towards the distal and / or proximal end relative to the housing 3, e.g. towards the proximal end, the plate 57 inside the housing 3 prevents. The plate 57 can be a separate component or it can be formed as part of the housing 3. In the devices shown in figures 1a to 1c, the nut 11 is in the operating condition in which the rotation of this nut is prevented from the housing 3 by the locking means 9, which thus prevents the piston rod 17 from moving towards the proximal end during dose setting and dispensing.

[0104] In the illustrated embodiment, the drug delivery device 1 is further provided with a locking means 9. The locking means 9 is secured against rotation against the housing 3, but this locking means 9 has the freedom of limited axial movement relative to the housing 3 when the housing 3 is coupled to the applicator 2 or disengaged from it. The locking means 9 is provided, on the proximal surface, with a series of teeth 10 of the working surface for engaging with the teeth 12 of the working surface of the nut 11. The adjusting means 14, in the form of a spring, is located between the proximal surface of the locking means 9 and the plate 57 inside the housing.

[0105] In the illustrated embodiments of figures 1a to 1c, the applicator 2 (drug reservoir) comprises an engaging means 70 with humps 71, the sloping humps 71 interacting with the sloping surfaces 72 of the blocking agent 9 when the applicator 2 is connected to the housing 3 (as described

ΕΡ 2 274 029 BI hereinafter with reference to figures 2a to 2c and 3). This interaction causes the locking means 9 to engage the nut 11. The engagement means 70 thus puts the nut 11 into operating condition. This interaction will be described in detail below.

[0106] Therefore, when the applicator 2 (drug dispenser) is attached to the distal end of the housing 3, then the re-positioning element 11 is in operating condition, and when the applicator 2 (drug dispenser) is detached from the distal end of the housing 3, then the reset item 11 is in the reset state.

[0107] In the operational state, rotation of the re-positioning element 11 relative to the housing 3 is prevented, and thus the piston rod 17 is prevented from moving towards the proximal end, while in the re-setting state, the re-setting element 11 can rotate relative to the housing 3, so the drug delivery device can be re-positioned by rotating the piston rod 17 together with the re-adjusting element in the second rotational direction, and thus the displacement of the piston rod 17 towards the proximal end.

[0108] The method of operating the drug delivery device 1 of the present invention will now be described.

[0109] To set the dose amount, the user turns the dose dial knob 46, thus rotating the dose dial knob 27. When unscrewing the dose, the clutch 24 is coupled to the sleeve 27 of the dose dial by means of saw teeth 31 at the proximal end of the clutch 24. Since the clutch 24 is coupled to the rotatable sleeve 27 of the dose knob, the clutch 24 and the guide sleeve 19 rotate with the sleeve 27 of the dose knob due to the latching engagement of the clutch 24 with the guide sleeve 19.

[0110] Audible and tactile feedback for dose rate dialing is provided by the clutch plate 25 and clutch 24. This feedback signal is provided by the teeth 29 of the clutch saw 24 sliding on the teeth 33 of the clutch plate saw 25 when the clutch 24 rotates relative to housing 3. When unscrewing the dose, the clutch plate 25 is pushed axially towards the proximal end of the device by the setting means 26, which ensures that the saw teeth 29 and 33 of the clutch plate 25 and clutch 24 remain in contact. Since the clutch plate 25 is secured against rotation by spline objects on the inner surface of the end stop 28, which is secured against rotation relative to the housing 3, the clutch 24 rotates relative to the clutch plate 25 during dose setting. Due to the profile of the saw teeth 29 and 33, preferably triangular, the saw teeth 29 of the clutch 24 are able to slide on the saw teeth 33 of the clutch plate 25 when the clutch 24 rotates. Preferably, the ratio of the angular spacing of the clutch saw teeth 29 and clutch plate saw teeth 33 is such that each tooth pitch corresponds to a conventional unit dose, or the like.

[0111] The dose dial sleeve 27 is reciprocatingly slid out of the housing 3 (rotation and axial displacement towards the proximal end) when the dose to be released is increased due to its engagement with the housing 3 (its insert 43) through threads 41, 42. The screw groove 41 of the sleeve 27, the dose selector knobs and the internal thread 21 of the guide sleeve 19 have the same pitch. This allows the sleeve 27 of the dose selector to exit the housing 3 and the guide sleeve 19 to enter along the second thread 16 of the piston rod 17 towards the proximal end at the same speed (movement

272 274 029 BI with axial displacement towards the proximal end relative to the housing 3 and relative to the piston rod 17).

[0112] At the end of this displacement, the radial stop (not shown) on the dose dial sleeve 27 engages with the stop object 56 located on the insert 43 of the housing 2 to prevent further displacement. During dose setting, rotation of the piston rod 17 is prevented due to opposite directions of the first and second threads 16 on the piston rod 17, the first thread 15 being engaged with the nut 11 and the second thread 16 being engaged with the guide sleeve 19.

[0113] The end stop 28, which rotation against the housing 3 is prevented, preferably due to spline objects (not shown), moves axially towards the proximal end of the housing 3 when the sleeve 27 rotates and moves towards the proximal end during dose setting. When the maximum dose that can be dispensed from the cartridge 6 is set, the radially extending flange 34 rests on the radial stop means 60 formed on the piston rod 17, preventing further axial displacement of the end stop 28 towards the proximal end and further rotation of both the tape 27 the dose selector and the guide sleeve 19 to set a larger dose.

[0114] If the user accidentally dialed a larger than desired dose, then the drug delivery device allows the dose to be reduced by turning, without having to release the medicinal product from the cartridge 6. The dose dial knob 46 is rotated in the opposite direction for this purpose. This causes the system to work the other way around. Rotating the clutch 24 in the reverse direction causes the teeth 29 and 33 of the clutch saw 24 and clutch plates 25 to slide over each other, making click sounds corresponding to the reduction of the screwed out dose. Preferably, the saw teeth 29 and 33 are arranged such that the circumferential extent of each saw tooth corresponds to a unit dose.

[0115] Figure 1a shows the drug delivery device in a state prior to setting the first dose. Figure 1b shows the drug delivery device 1 according to figure 1a in a state in which the dose has been set. The dose knob sleeve 27 extends from the housing 3 towards the proximal end.

[0116] Once the desired dose has been set, the user can dispense this dose by pressing the button 49. This causes the clutch to move 24 axially towards the distal end of the device relative to the dose dial sleeve 27, thereby disengaging the clutch 24 from the dose dial sleeve 27. However, the clutch 24 remains locked in rotation with the guide sleeve 19. Thus, uncoupling the clutch 24 results in the disengagement of the sleeve 27 of the dose dial from the guide sleeve 19. The sleeve 27 of the dose selector and the associated handle 46 of the dose selector can now rotate freely, driven by the screw rib 42 of the insert 43 located in the screw groove 41 of the sleeve 27 dose dials. When dispensing the dose, the sleeve 27 of the dose selector is slid and retracted back into the housing 3 towards the distal end.

[0117] The pressure exerted by the user on the button 49 further results in axial movement of the clutch 24 towards the distal end, without rotation relative to the housing 3. The axial movement of the clutch 24 moves the clutch plate 25 towards the distal end against the force exerted by the setting means 26 until the clutch plate 25 rests against the bead on the guide sleeve 19 and the clutch 24 and plate 25 engage so that the clutch rotation 24 and clutch plates relative to each other is prevented,

272 274 029 BI, thus preventing the clutch 24 and guide sleeve 19 from rotating relative to housing 3 during dose release. When the clutch plate 25 is spline-connected to the end stop 28 to prevent the clutch plate 25 from rotating relative to the housing 3, the clutch plate 25, the clutch 24 and the guide bushing 19 slide together towards the distal end but do not rotate.

[0118] The axial movement of the clutch 24 causes the guide sleeve 19 to move axially toward the distal end. The longitudinal axial displacement of the guide sleeve 19 towards the distal end further (by means of the internal thread 21 of the guide sleeve 19 and the second thread 16 of the piston rod 17) the rotation of the piston rod 17 (first thread section 15) and thus its reciprocating torsion through the hole 13 in the nut 11 to thereby move the piston 17 in the cartridge 6.

[0119] After the unscrewed dose is released, the dose dial knob 27 further prevents rotation by engaging a series of rotatable stop objects (not shown) extending from the dose dial handle 46 with the stop objects 55 on the housing insert 3. In the illustrated embodiment, the rotatable stop objects run axially from the dose dial handle 46 and have an inclined end surface. The position of the zero dose is determined by abutting one of the axially extending edges of the rotational stop objects (not shown) against the respective stop 55 on the insert 43.

[0120] The rotational movement of the dose selection knob 27 during dose release causes the end stop 28 to move axially towards the distal end back to its initial position within the housing 3.

[0121] Figure 1c shows the drug delivery device according to figures 1a and 1b after dose release. The piston rod 17 and piston 7 in the cartridge 6 have been displaced towards the distal end. The dose dial sleeve 27 and end stop 28 are in their original positions relative to housing 3.

[0122] After the last dose has been released, the used cartridge 6 can be removed and disposed of. To remove the cartridge 6, detach the applicator 2 from the housing 3 by unhooking the coupling means of the first and second 4. After detaching the applicator 2 from the housing 3, the used cartridge 6 can be removed from the applicator 2 and a new cartridge 6 can be placed in the applicator 2.

[0123] To re-use the drug delivery device 1, it must be re-positioned by moving the piston rod 17 towards the proximal end to its initial position. As long as the nut 11 is in working condition, the movement of the piston rod 17 towards the proximal end is prevented • due to the opposite directions of the first 15 and second threads 16 on the piston rod 17, the first thread 15 being engaged with the non-rotating nut 11 and the second the thread 16 is coupled to the guide sleeve 19, and ♦ because of the clutch 24 that engages the guide sleeve 19 with the sleeve 27 of the dose dial and thus indirectly with the housing thread 42, whereby the clutch 24 forms part of the stop means that prevents the piston rod 17 from moving towards the proximal end in the operating state.

ΕΡ 2 274 029 BI [0124] Therefore, the nut 11 should be put into a reset state in which it can rotate relative to the housing 3 so that the piston rod 17 can be moved towards the proximal end. [0125] Detaching the applicator 2 from the housing 3 causes the locking means 9 to disengage, due to the force exerted by the setting means, from the nut 11. The locking means 9 then ceases to prevent the nut 11 from turning. In this way, the nut 11 is no longer in the operating state, but in the reset state. This allows the nut 11 to rotate freely and thus reciprocates to move the piston rod back towards the proximal end.

[0126] To attach the applicator 2 containing the new cartridge 6 to the housing 3, the piston rod 17 must be displaced axially towards the proximal end. Such displacement towards the proximal end can be caused by the piston 7 of the cartridge 6, abutting against the end of the piston rod 17 and moved towards the proximal end relative to the housing 3 when the applicator 2 with the cartridge 6 is moved towards the housing 3 by the user. Alternatively, the user may push the piston rod 17 towards the proximal end e.g. with a finger, and then attach the applicator 2 with the insert 6 to the housing 3. Because the nut 11 (which is threadedly engaged with the piston rod 17) is free to rotate relative to the housing 3 in the re-condition positioning, the piston rod 17 is free to rotate and move towards the proximal end until the locking means 9 and the nut 11 engage. Pushing the piston rod 17 back with the piston 7 of the new cartridge 6, which is pressed against the pressure foot 18 of the piston rod 17, has the advantage that the pressure foot 18 of the piston rod 17 is already resting on the piston 7 of the cartridge 6 when the device is re-adjusted . Thus, the preparatory displacement of the piston rod 17 (to remove air from the cartridge 6) can be very small, and thus loss of drug due to preparation can be minimal.

[0127] The applicator 2 containing the new cartridge 6 is coupled to the housing 3 by engaging the first and second coupling means 4. When the applicator 2 is moved so as to engage with the housing 3, the applicator 2 first rotates and moves axially towards the proximal end because the second coupling means 4 of the insert 3A of the housing 3 moves along the threaded section of the first coupling means 5 of the applicator 2 until when the second coupling means 4 reaches the annular groove section of the first coupling means 5. The further movement of the second coupling means 4 in this annular groove causes the applicator 2 to rotate without its axial movement relative to the housing 3. The first and second coupling means 4 can therefore be coupled by the movement of the applicator 2, which ends in a rotational movement without axial movement of the center. switching 70 relative to housing 3. Such further rotation of the applicator 2 (without axial movement) causes the humps 71 of the switching means 70 to slide along the sloping surfaces 72 of the locking means 9. The locking means 9 is thus displaced axially towards the proximal end against the force exerted by the setting means 14 until the teeth 10 of the working surface of the locking means 9 engage with the teeth 12 of the working surface of the nut 11, thereby introducing the nut 11 (the element for reuse In this position, the nut 11 is secured against axial movement and rotation. In this operating condition, rotation of the piston rod 17 in one rotational direction and its axial displacement towards the proximal end relative to the housing 3 is prevented, but it can rotate in the remaining rotational direction and move axially towards the distal end relative to the housing 3 for drug delivery.

ΕΡ 2 274 029 BI [0128] The only rotational movement of the applicator 2 and the engagement means 70, which engages the locking means 9 with the nut 11, ends when the latching objects (not shown) of the applicator 2 and the housing insert 3A engage. In this position, the engagement means 70 keeps the nut 11 in operating condition.

[0129] The rotational movement (without axial displacement) of the applicator 2 relative to the housing 3, which engages the locking means 9 with the nut 11 has the advantage that it does not increase the pressure on the piston 7 of the cartridge 6 before the drug delivery device 1 is used.

[0130] In this way, the dosing mechanism of the drug delivery device 1 of the present invention is set to a zero dose position (in which no dose is released), as shown in Figure 1a.

[0131] Figures 2a to 2c schematically show an embodiment of an engaging means cooperating with a blocking agent in three different states according to one embodiment of the present invention.

[0132] Figure 2a shows the blocking means 9 and the activating means 70 before any interaction occurs between them. In the embodiment shown, the switching means 70 is e.g. part of a drug reservoir (e.g. apiikator 2) of the drug delivery device. In the embodiment shown, the drug delivery device component comprising the inclusion means 70 further includes first coupling means 5 for engaging the second coupling means 4, which are preferably part of the housing of the drug delivery device or housing liner. The first and second coupling means 4 are designed so that to engage the two components that comprise these coupling means 5, 4 (preferably the housing and the drug reservoir), the two components are first rotated and moved axially relative to each other (first stage), and then only rotated, without moving them axially relative to each other (second stage). The interaction between the activating means 70 and the blocking means 9 takes place only at this second stage, when the two components (e.g. the drug reservoir and the housing), thus the activating means 70 and the blocking means 9, only rotate relative to each other. The blocking means 9 is preferably non-rotatable with respect to the housing of the drug delivery device.

[0133] Figure 2a shows the engaging means 70 and the locking means 9 in a first step when both rotation (arrow 35) and axial movement (arrow 36) occur between them. At this stage, the second coupling means 4 moves along the first section of the first coupling means 5, which is the thread 37. The distal end of the thread 37 changes into the second section of the first coupling means 5, which is a partial annular groove 38. In a schematic drawing, such an annular groove 38 looks like a straight section, since the drawing shows a view of the outer surface of the substantially cylindrical components.

[0134] The second coupling means 4 is at least one coupling element which engages with the thread 37 and the annular groove 38. The illustrated coupling element has the shape of a parallelogram. [0135] In the embodiment shown, the locking means 9 and the activating means 70 have a special shape for cooperation. The engagement means comprises humps 71 with inclined surfaces to interact with the correspondingly inclined surfaces 39 of the locking means 9, which form triangular recesses 58.

[0136] In Figure 2a, the combined axial movement 36 and rotation of the activation means 70 relative to the locking means 9 results in the activation means 70 approaching the locking means 9 until the activation means 70 rests on the locking means 9 in position wherein the humps 71 are connected to the triangular recesses 58 of the blocking means 9, as shown in figure 2b. In this position, the second coupling means 4 has reached the point where the thread 37 of the first coupling means 5 passes into the annular groove 38 of the first coupling means 5. Combined axial movement 36 and rotation of the engaging means 70 relative to the locking means 9 (first coupling stage) passes now in only the rotational movement of the activation means 70 relative to the locking means 9 (second coupling step).

[0137] During this rotation, the sloping surfaces of the humps 71 and the depressions 58 slide along each other. This interaction of the engagement means 70 and the locking means 9 during rotation without axial displacement leads the locking means 9 (which is non-rotational relative to the housing (not shown) axially towards the proximal end (arrow 59) as shown in figure 2c. Such axial displacement of the blocking means 9 (preferably against the force exerted by the setting means not shown) engages the blocking means 9 with the (not shown) re-setting element (e.g. nut), thereby bringing the re-setting element into working condition, wherein it prevents the piston rod 17 from moving towards the proximal end during dose setting and dispensing of the drug delivery device. The coupling of the locking means 9 and the resetting element can be established e.g. by mutual engagement (not shown) of the teeth of the working surface of the locking means 9 and the resetting element.

[0138] Figure 3 is an enlarged cross-sectional view of the middle part of the embodiment of Figures 1a to 1c showing an element for resetting the drug delivery device in an operative condition.

[0139] The applicator 2 of the drug delivery device is attached to the housing 3 of the drug delivery device by coupling the first coupling agent 5 to the second coupling agent 4 (not shown). The applicator 2 comprises a first coupling means 5 and the housing insert 3A contains a second coupling means 4. The two-part pressure foot 18 is attached at the distal end of the piston rod 17 and rests on the piston 7 of the drug cartridge 6.

[0140] According to such an embodiment, the applicator 2 comprises an engaging means 70 that includes humps 71 with sloping surfaces for interacting with the correspondingly sloping surfaces 72 of the blocking means 9. The blocking means 9 is engaged with the nut 11, which is a re-setting element operational condition serving to prevent the piston rod 17 from moving towards the proximal end. The tips of the humping means 71 of the actuating means 70 are pressed against the distal surface of the locking means 9, thus keeping the nut 11 in working condition. The teeth 10 of the working surface of the locking means 9 are engaged with the teeth 12 of the working surface of the nut 11. This coupling of the nut 11 with the locking means 9 prevents the nut 11 from rotating relative to the housing 3. The nut 11 is threaded with the first thread 15 of the piston rod 17. Due to this threaded engagement and engagement (opposite) of the second thread 16 of the piston rod 17 with the guide sleeve (not shown), the piston rod 17 is prevented from moving towards the proximal end as long as the nut 11 is in working condition. Center

ΕΡ 2 274 029 BI adjustment 14 is present to push the nut 11 and the locking means 9 away from each other when the applicator 2 is disconnected from the housing 3 (not shown).

[0141] Figure 4 schematically shows another embodiment of the drug delivery device according to the present invention with a different arrangement of the switching agent and the resetting element.

[0142] The activating means 70 comprises humps 71, and the drug reservoir 2 comprises a first engaging means 5 with threaded sections 37 and an annular groove 38. The resetting means 11 has sloping surfaces 39 for cooperation with the humps 71 of the activating means 70. When the sloping surfaces of the humps 71 and the reset element 11 abut against each other and slide along each other during the rotational movement of the actuating means 70 relative to the housing 3 in the second coupling step, then the reset element 11 is pressed against the locking means 9, whereby the teeth 12 of the working surface of the resetting element 11 engage the teeth 10 of the working surface of the locking means 9. The locking means 9 is not necessarily a separate component in this embodiment. It can also be part of the housing 3.

[0143] Figure 5 shows another embodiment of a drug delivery device according to the invention. [0144] The drug delivery device 1 according to figure 5 comprises an apiikator 2 and a (outer) housing 3. The distal end of the housing 3 is provided with an insert 3B intended to engage with the proximal end of the applicator 2. The insert 3B is secured against rotation with respect to the housing 3, but is free to move axially relative to housing 3. The range of axial movement of the insert 3B is limited by a retaining means 63 which is engaged with the housing and secured against both axial and rotational movement relative to the housing 3.

[0145] The inner surface of the insert 3B is provided with a second coupling means 4. The second coupling means 4 can be any suitable means known to those skilled in the art, such as a bayonet, screw thread and the like. Preferably, the second coupling means 4 is a helical thread and corresponds to the first coupling means 5 at the proximal end of the applicator 2, which is preferably also a helical thread.

[0146] In the illustrated embodiment of the present invention, the proximal end of the applicator 2 is further provided with an activation means (not shown) intended to activate and lock the resetting element (not shown) in the operating condition.

[0147] The adjusting means 64 is between the proximal surface of the holding means 63 and the distal surface of the insert 3B. The adjusting means 64 may be made of any suitable flexible material known to those skilled in the art, such as stainless steel, rubber or the like, and may take any suitable form, such as a spring, spacer or the like. In the illustrated embodiment of the present invention, the setting means 64 is a wave spring. The adjusting means 64 is designed to ensure that the insert 3B does not rest on the holding means 63 when the applicator 2 is not attached to the housing 3.

[0148] Further components of this drug delivery device will not be described in detail, but are preferably similar to the components described with reference to figures 1a to 1c.

[0149] The method of operating the drug delivery device of the present invention will now be described.

ΕΡ 2 274 029 BI [0150] Dose setting and dose release may eg occur in a similar manner to that described with reference to figures 1a to 1c.

[0151] After reaching the position after dispensing the last dose, the used cartridge can be removed and discarded. To remove the cartridge, the applicator 2 must be detached from the housing 3, preferably the applicator 2 is unscrewed from the housing

3. After detaching the applicator 2 from the housing 3, the used cartridge can be removed from the applicator 2 and a new cartridge inserted into the applicator 2.

[0152] Detaching the applicator 2 from the housing 3 results in (not shown) the resetting element from its operating condition, e.g. by uncoupling the locking means from the resetting element under the force exerted by the setting means. This, for example, allows the re-adjusting element to freely rotate and thus move the piston rod towards the proximal end to re-position the device.

[0153] With the removal of the applicator 2, the insert 3B is axially displaced towards the proximal end, away from the distal end of the housing 3 (away from the retaining means 63), for a limited distance due to the force exerted by the setting means 64.

[0154] To attach the applicator 2 to the housing 3, the piston rod is moved axially towards the proximal end relative to the housing 3. This displacement towards the proximal end is caused by the piston of the new cartridge resting on the end of the piston rod and moving it towards the proximal end relative to the housing 3 when the applicator 2 with the cartridge is approaching the housing 3. Because the reset element is not yet in the operating state, the piston rod is therefore free to move towards the proximal end until the reset element has entered the operating state, e.g. when the locking means engage the reset element . Pushing the piston rod with the piston of a new cartridge that is pressed against the piston rod presser foot has the advantage that the piston rod foot already rests on the piston of the cartridge when the device is reset. Thus, the preparatory displacement of the piston rod (to remove air from the cartridge) can be very small, and thus the loss of drug due to preparation will be minimal.

[0155] The applicator 2 containing the new cartridge is then coupled to the housing, preferably threaded. As the applicator 2 is moved to engage the housing 3, the first coupling means 5 located at the proximal end of the applicator 2 engages with the second coupling means of the 3ES insert. The applicator 2 can rotate and move axially towards the proximal end (first coupling step) until the stop means 65 (e.g. the annular outer rim) on the applicator 2 will rest against the holding means 63. The stop means 65 prevents further axial movement of the applicator 2, but allows the applicator 2 to rotate (second coupling step). As the applicator 2 continues to rotate, the insert 3B is moved axially, against the force exerted by the adjusting means 64, towards the distal end of the housing 3 and thus towards the holding means 63.

[0156] Such only rotation of the applicator 2 further causes the re-setting element to be in the operating state (not shown) by the engagement means, e.g. by axially displacing the locking means towards the proximal end against the force exerted by the setting means until,

ΕΡ 2 274 029 BI when the teeth of the working surface of the locking means engage with the teeth of the working surface of the resetting element.

[0157] In this way the guiding mechanism is set to the zero dose position (or in which no dose is released).

[0158] The rotary motion (without axial displacement) of the applicator 2, which brings the re-setting element into working condition, has the advantage of not causing any increase in pressure on the plunger of the cartridge before the first use of the drug delivery device after the insertion of a new cartridge.

Numerical references drug delivery device applicator housing

3A housing insert

3B housing insert second coupling means first coupling means piston coupling coupling agent blocking agent working surface teeth locking agent re-adjusting element / nut working surface teeth nuts nut hole adjusting means first piston stem thread second piston stem thread piston stem presser foot guide sleeve sleeve flange guide thread of the guide sleeve

22A swelling

B projection flange clutch clutch plate adjusting medium sleeve of the dose selector knob end stop

EP 2 274 029 BI saw teeth at the distal end of the clutch saw flanges saw teeth at the proximal end of the coupling flexible arms saw teeth clutch plates flange at the distal end of the end stop direction of rotation axial movement direction ring thread groove sloping surfaces external window screw thread sleeve dose dial knob housing inserts, stop objects on the sleeve of the dose selector knob, radially diverging members dose knob handle central hole of the dose selector handle annular recess of the dose selector handle button button stem button head button cover threaded insert of the dose selector sleeve end cap stop objects on the insert 43 stop objects on the insert 43 cavity plate direction of the proximal end radial stop on the piston rod retainer adjusting means stopping means humping devices