Injection device with flexible dosage options

Abstract

An injection device incorporating a dose setting mechanism is proposed, where the dose setting mechanism comprises a dose selector having one or more dose stop points corresponding to a limited set of predetermined fixed doses, where the limited set of predetermined fixed doses comprises a lowest fixed dose and one or more higher fixed doses, and where at least one of the one or more higher fixed doses is equal to the lowest fixed dose plus a fraction of the lowest fixed dose. The dose setting mechanism may further comprise a coupling assembly rotatably engaged with a snap element such that the snap element is rotatable relative to the coupling assembly during both dose setting and dose delivery.

Description

[0001] This application is a divisional application of PCT patent application PCT / EP2017 / 001140 (international application date is September 25, 2017, priority date is July 13, 2017, Chinese patent application number is 201780093080.1, and the name of the invention is “Injection device with flexible dosage selection”) which entered the Chinese national phase on January 10, 2020. Technical Field

[0002] The present disclosure relates to an injection device, and in particular to a dose setting mechanism of the injection device. Background Art

[0003] There are many drug delivery devices on the market that are capable of delivering a dose of a drug automatically, semi-automatically or manually. Among the known types of delivery devices, "pen-type" injectors are becoming increasingly popular and are available in both reusable and disposable designs. Such devices are constructed with a dose setting mechanism that includes various interacting components for achieving the desired functions (such as setting a dose and then delivering the set dose). In most cases, these drug delivery devices have only one or two single fixed dose settings or variable dose settings, where each possible set dose must be a multiple of the lowest possible set dose. In other words, these existing variable dose injection devices do not allow the dose to be set as a fraction of the lowest possible dose.

[0004] A type of pen-type injector design has a dose setting mechanism located at the distal end of the device and a drug container, such as a cartridge, located at the proximal end. Known injector designs are typically multiple (variable) dose devices, meaning that the user can select (dial) a dose between 0 and the maximum allowed settable dose. The dose dial sleeve is printed with a range of possible dose settings, which typically corresponds to each possible incremental dose setting. For example, if the injector is designed and manufactured to have a maximum dose setting of 80 international units (IU), each settable incremental dose differs by one IU. In other words, to set a dose of 60 IU, the user will rotate the dose setting knob through the 60 possible dose settings until it displays 60 IU while viewing the dose dial sleeve markings indicating each incremental dose. Of course, there is nothing to prevent the user from accidentally setting an underdose of 59 IU or an overdose of 61 IU, especially if the user has a physical impairment, such as reduced vision or severe arthritis.

[0005] As mentioned above, some injection devices are manufactured and designed as so-called fixed dose designs, where the dose dial sleeve contains printing indicating only one or two doses. The design idea behind these devices is that it is for the user to rotate the dose setting knob until one of the fixed dose settings is observed, usually in a window in the syringe housing. However, in such syringe designs, the user is still required to step through each equal incremental dose setting until the marking of the fixed dose setting is observed in the window. Because the dose setting mechanism requires the user to physically step through each incremental dose setting, there is nothing to prevent the user from stopping at a dose that is less than or greater than the fixed dose setting. In addition, the user will experience a tactile or audible notification as the dose setting mechanism is dialed through each incremental dose to reach the final dose setting.

[0006] Another disadvantage of existing syringe designs is the inability to have fixed doses that are not multiples of a single incremental value. In other words, if a syringe is designed to have a maximum settable dose of 80 IU, then typically each incremental dose will be 1 IU. Therefore, it is not possible to set a dose of 2.3 IU. Using doses that can only be set to 2 or 3 IU. In other words, fractional doses cannot be set using such a dose setting mechanism. The ability to set fractional doses is important, especially during studies attempting to determine the optimal dose for a newly developed drug and / or for a new patient using an existing drug for the first time.

[0007] Although there are many drug delivery devices available for patients, there is a clear need to have a syringe capable of delivering one or more predetermined fixed doses, where at least one of the predetermined fixed doses is a fractional amount of a second predetermined fixed dose. The availability of pen-type injectors where the user cannot set and / or deliver a dose that is not one of several predetermined fixed doses is also an important goal. Moreover, it is highly desirable to have a syringe design where only a single mechanical component of the dose setting mechanism needs to be redesigned and manufactured to change or vary the predetermined fixed dose. This would allow for cost-effective manufacture of an injection device that can be easily customized to a patient to allow injection of one or more effective drug doses specifically customized for a particular user.

[0008] In summary, the problem to be solved consists in providing an injection device which prevents dose delivery as long as the rotational position of the dose knob does not correspond to a well-defined dose position.

[0009] This problem is solved by providing an injection device according to the present disclosure. Summary of the invention

[0010] The present disclosure proposes several dose setting mechanism designs which allow setting an injection device with one or more fractional predetermined fixed dose settings. The design can also prevent the setting of unintended doses, i.e. doses other than one of the predetermined fixed dose settings. The dose setting design provides a cost-effective way of manufacturing an injection device, since only a single component needs to be redesigned and manufactured in order to provide a complete injection device with one or more different predetermined fixed doses.

[0011] According to at least one embodiment of the present disclosure, a dose setting mechanism includes a coupling assembly, a dose knob, a dose selector, and a snap element. The coupling assembly is rotationally engaged with the snap element, which has a fixed set of snap coupling elements. During dose setting and dose delivery, the coupling assembly engages with a corresponding set of dose selector coupling elements. The coupling assembly is advantageously a floating spline assembly. The floating spline assembly advantageously may include a plurality of longitudinally extending splines that engage with splines on the dose knob during dose delivery, but not during dose setting. The floating spline assembly may also be axially fixed relative to the snap element. Other forms of coupling assemblies that can provide rotational engagement may also be advantageous.

[0012] In an advantageous embodiment, during dose setting and dose delivery, the snap element rotates relative to the coupling assembly and the dose selector. This is in particular due to the coupling assembly being rotatably fixed to the dose selector by corresponding coupling elements, preferably splines, on the inner surface of the dose selector. Advantageously, the dose selector is rotatably fixed to the housing by a spline connection. Since the dose selector is rotatably fixed to the housing by a spline connection, the engagement and meshing of the coupling assembly with the splines on the inner surface of the dose selector during dose setting and dose delivery prevents the floating spline assembly from rotating relative to the body. The snap element advantageously comprises a protrusion that engages a plurality of dose stop points located on the inner surface of the dose selector. In particular, the snap element is configured with a flexible arm having a radially extending protrusion that preferably protrudes outwards to engage a plurality of dose stop points located on the inner surface of the dose selector.

[0013] Advantageously, these dose stop points are preferably designed and manufactured by a molding process to be radially spaced from each other so that they define a limited set of predetermined fixed doses. During setting one of the predetermined doses, the snap element is advantageously rotated relative to the dose selector so that the protrusion on the snap element engages with and travels over one of the dose stop points. Once the protrusion travels over the dose stop point and stops rotating, this position of the snap element defines a single fixed drug dose for delivery. The limited set of predetermined fixed doses includes a minimum fixed dose and one or more higher fixed doses.

[0014] The distance between the dose stop points on the inner surface of the dose selector may be designed and manufactured such that one or more higher fixed doses are not equal to an even multiple of the lowest fixed dose. This results in a fixed dose setting comprising a fractional amount of the lowest fixed dose. In other words, the distance between the dose stop points may be manufactured, i.e. predetermined, such that at least one of the one or more higher fixed doses is equal to the lowest fixed dose plus a fractional amount of the lowest fixed dose. This is not possible with currently known dose setting mechanisms.

[0015] Advantageously, because the limited set of predetermined fixed doses is defined only by the number of and the relative spacing between dose stop points, and those dose stop points are uniquely located on a single component of the dose setting mechanism, i.e. the dose selector, this presents an efficient and cost-effective method to change the limited set of predetermined fixed doses without manufacturing any other components of the dose setting mechanism. In other words, only the design of the dose selector needs to be changed to result in the manufacture of a second dose selector, which can then replace the original dose selector during assembly of the injection device. Other components of the dose setting mechanism do not need to be replaced. In some cases, the printing appearing on the dose sleeve may be changed, but the design and manufacture of the dose sleeve remains unchanged. Replacing the original dose selector with a second dose selector having a different arrangement of dose stop points results in the dose setting mechanism having a different set of limited predetermined fixed doses.

[0016] The spatial relationship between the dose selector and the snap element advantageously changes between dose setting and dose delivery. In particular, there is a first fixed relative axial position between the snap element and the dose selector, which occurs during dose setting, and a second fixed axial relative position that occurs during dose delivery. In the first fixed position, the protrusion can engage the dose stop point. However, in the second fixed position, the protrusion cannot engage the dose stop point, wherein the first fixed relative position is achieved during dose setting and the second fixed relative position is achieved during dose delivery. When dose delivery is completed, the protrusion can engage with and travel over the end of the injection bump to provide a tactile and / or audible notification to the user that delivery is complete.

[0017] As mentioned above, the dose setting mechanism of the present disclosure may include functional and structural features that prevent the user from setting a dose other than one of the predetermined fixed doses, i.e., the so-called unintended dose. This failsafe feature of the present disclosure prevents setting a dose other than one of a limited set of predetermined fixed doses by using a biasing member that applies a reverse rotational force on the snap element during the dose setting process. The biasing member may be a torsion spring that is operably connected to the snap element by connection with the dose sleeve. When the torsion spring is incorporated into the dose setting mechanism, it is biased to a predetermined torque during assembly. The torque applies a force on the snap element so that during the dose setting by the user dialing or rotating the dose knob, the snap element is pushed to resist the rotational force applied by the user. Although the user easily overcomes the reverse rotational torque during the rotation of the dose knob, if the user releases the dose knob for some reason, the torque will cause the knob and the snap element to rotate in the opposite direction. In this case, the torque is preferably sufficient to reversely rotate the snap element so that the protrusion will return to engage with the previous dose stop point. In some cases, it may be desirable to use a biasing member that will reverse the rotation of the catch element so that the protrusion will return to the zero dose hard stop (sometimes also referred to as a stop). The failsafe feature will only come into play if the user does not rotate the dose knob and catch element far enough to cause the protrusion to engage and advance past the next dose stop (which corresponds to a higher fixed dose than the previous dose stop). As the dose knob is rotated during dose setting and the catch element engages successive dose stops, the torque applied by the torsion spring increases.

[0018] In some cases, it may be desirable to select a biasing member that applies only enough torque to reverse-rotate the snap element to the next lowest dose stop. In this case, the biasing member will not add any mechanical assistance to the user during the dose delivery process. There may also be situations where it is desirable to select and use a biasing member that generates enough torque during dose setting to achieve mechanical assistance through reverse rotational forces during dose delivery, so that the user needs to apply less axial force than if a biasing member with inherently less torque was used.

[0019] The dose knob is operably connected to the snap element by a set of knob coupling elements, advantageously knob splines, located on the inner surface of the dose knob. These knob coupling elements engage and mesh with a fixed set of snap coupling elements, in particular snap element splines, on the outer surface of the snap element during dose setting. In a preferred embodiment, the dose knob is rotated during dose setting. The rotation of the dose knob during dose setting advantageously causes rotation and axial movement of the snap element and only axial distal movement of the dose selector. The snap element translates axially in the distal direction relative to the housing because the snap element is rotatably fixed to the dose sleeve, which in turn is threadedly connected to the inner surface of the housing. The dose selector does not rotate relative to the housing because it is fixed to the housing by splines so that it can only move axially relative to the housing. The dose knob is axially fixed to the dose selector, but can be rotated relative to the dose selector so that during both dose setting and dose delivery, the dose knob, the dose selector, the dose sleeve and the snap element all move axially relative to the housing.

[0020] The snap element advantageously has a second set of coupling elements, advantageously splines, attached to the outer surface of the snap element. The second set of splines or floating spline assembly is a separate component of the dose setting mechanism and is not an integral part of the snap element, i.e., they are not rotationally fixed to the snap element. The coupling assembly is advantageously a floating spline assembly. The coupling assembly is preferably positioned circumferentially around the outer surface of the snap element in a free rolling manner so that when the coupling assembly is rotationally fixed relative to the housing, the snap element will rotate within or relative to the coupling assembly, advantageously the floating spline. The coupling assembly, in particular the floating spline assembly, is advantageously configured to have a plurality of radially protruding longitudinal coupling elements, in particular splines, spaced equidistantly from each other. This is in contrast to the dose stop points on the inner surface of the dose selector, where the intervals between the dose stop points do not have to be equal. However, the space between each dose stop point is a multiple of the space between each radially protruding longitudinal coupling element of the coupling assembly member.

[0021] In order to deliver the set dose, the user will apply an axial force on the dose knob relative to the housing in the proximal direction. If this axial force stops, a stopped dose delivery situation may occur. The dose setting mechanism of the present disclosure advantageously includes a second failsafe feature to prevent possible problems associated with a stopped dose delivery situation. As will be explained in more detail below, in a preferred embodiment, the start of the dose delivery process first involves an axial movement of the dose knob and the dose selector, which is axially fixed to the dose knob. This axial movement of the dose knob also causes the splines on the dose knob to disengage from the fixed splines on the snap element. This disengagement eliminates the rotationally fixed relationship between the dose knob and the snap element that exists during the dose setting process. The proximal axial movement of the dose knob and the dose selector that occurs during the start of the dose delivery process is relative to the housing, and at least initially relative to the snap element. The axial proximal movement of the dose selector causes the dose stop point to move out of radial alignment with the protrusion on the snap element. The dose knob and the dose selector are biased in the distal direction relative to the snap element by a second biasing member, which is preferably a compression spring. During dose setting, the second biasing member ensures that the coupling element, in particular the spline, on the dose knob engages with the fixed coupling element, in particular the fixed spline, on the snap element. However, during dose delivery, the distal biasing force applied by the second biasing member is overcome by the proximal axial force of the user on the dose knob, thus allowing disengagement of the coupling element.

[0022] As described above, during dose delivery, the user advantageously applies a counter-axial force in the proximal direction to move the dose knob and the dose selector axially relative to the snap element. If the injection is stopped and the axial force in the proximal direction is removed or fully reduced, the second biasing member will push the dose selector back in the distal direction to cause the projection and the dose stop point to realign, and cause the coupling element on the dose knob, preferably the spline to reengage the fixed coupling element on the snap element, advantageously the fixed spline. Because the snap element is subjected to the reverse rotation force from the first biasing member, this will tend to cause both the snap element and the dose knob to rotate in the direction of reducing the set dose to an unexpected and possibly unknown lower amount. In other words, the reverse rotation of the snap element will cause the projection to rotate to engage the next lower predetermined dose stop point. As will be explained in more detail below, the rotation of the snap element also advantageously causes the rotation of the nut (nut, sometimes also referred to as a screw sleeve) engaged with the piston rod, where the position of the nut relative to the piston rod is proportional to the amount of medicine to be delivered. The effect of allowing reverse rotation of the snap element in the event of a stopped injection is to reduce the pre-set intended dose by an amount which may not be determined by the user, thus resulting in a potential hazard in a dosing situation.

[0023] The second fail-safe feature of the dose setting mechanism of the present disclosure is advantageously achieved by using a radially protruding circumferential rib that engages with a second protrusion on the snap element so that the dose selector can only be pressed and moved in the proximal direction to start dose delivery when the second protrusion is aligned with the cutout in the radially protruding rib. This axial proximal movement of the dose selector at the start of dose delivery moves the radially protruding rib from a first position where the second protrusion is located on the proximal side of the rib to a second position. When moving to the second position, the rib moves relative to the second protrusion so that the cutout moves over the second protrusion so that it is then positioned on the distal side of the rib. Preferably, the radially protruding rib has a plurality of cutouts corresponding to each dose stop point. Once in the second position, if the user releases the proximal force on the dose knob, as the dose delivery continues, when the snap element begins to rotate in the opposite direction, the rib can now block the distal axial movement of the dose selector. The axial blocking feature occurs because the second biasing member pushes the dose selector in the distal direction, thereby causing the second protrusion to abut against the distal surface of the rib. This abutment prevents further movement of the dose selector and therefore prevents the fixed splines from re-engaging with the splines on the inside of the dose knob.

[0024] Thus, the second failsafe feature allows the dose selector to move in the distal direction only during dose delivery when the second protrusion is aligned with the cutout in the radially protruding rib. If the injection is stopped when the cutout in the rib corresponds to or is aligned with the position of the dose stop point, a distal axial movement of the dose selector will occur, but this movement will realign the first protrusion with the corresponding dose stop point and will reengage the fixed spline with the dose knob. Since the first protrusion is now reengaged with the dose stop point, the snap element and the dose knob will not rotate in the opposite direction relative to the housing, and therefore the nut will not rotate relative to the piston. As a result, the set dose is not reduced. Another benefit of this second failsafe feature is that the dose knob can only move axially relative to the snap element when the protrusion on the snap element is engaged with one of the dose stop points of the dose selector. This will prevent unintended dose delivery if the user rotates the dose knob while applying an axial drive force in the proximal direction.

[0025] The snap element may also include a catch arm that engages with a radially protruding longitudinal coupling element (advantageously spline) on the inner surface of the dose selector during dose delivery, so that rotation of the snap element produces audible feedback when the catch arm travels on the radially protruding longitudinal spline. During dose setting, the engagement between the first protrusion on the flexible arm of the snap element and the dose stop point produces a first number of tactile and / or audible notifications. During dose delivery, a second number of tactile and / or audible notifications are generated, at which the second number of notifications is greater than the first number. In some cases, the second number of notifications is equal to the total number of coupling elements (advantageously splines) corresponding to the set predetermined fixed dose. The degree of tactile notification and / or the level of audible notification can be changed by changing the shape and / or type of component material used to manufacture the coupling element or the catch arm. Similarly, the dose stop point and the first protrusion on the flexible arm can be configured to have a variety of shapes or materials to produce different tactile and / or audible notifications, so that the user will easily distinguish the difference between dose setting / dose cancellation and dose delivery.

[0026] The dose setting mechanism of the present disclosure may also include a sleeve (clutch) that is operably connected to the dose knob at the distal end of the sleeve. In one embodiment, the proximal end of the sleeve is rotatably fixed to the nut and can slide axially relative to the nut. The nut can be threadedly engaged with a piston rod configured to move axially only in the proximal direction, so that during dose delivery, the piston rod applies an axial force, causing the plunger in the drug container to move proximally to pressurize the drug so that it is discharged through the proximal opening in the drug container. The preferred shape of the piston rod includes a piston rod having a non-circular cross-section and having threads on the outer surface. The pitch of these threads is directly proportional to each predetermined fixed drug dose. A piston guide having a non-circular central opening can be included in the dose setting mechanism, where the piston guide receives the non-circular cross-section of the piston rod, so that during both dose setting and dose delivery, the piston guide can prevent the piston rod from rotating.

[0027] In a preferred embodiment, the dose setting knob and the sleeve are operably connected so that they are rotationally fixed to each other, so that during dose setting, rotation of the dose knob rotates the sleeve, which in turn rotates the nut. Rotation of the nut advantageously causes the nut to translate axially in the distal direction along the thread on the outer surface of the piston rod during dose setting and to translate in the proximal direction during dose cancellation. During dose delivery, the dose knob is advantageously prevented from rotating due to the engagement with the coupling assembly that is rotationally fixed to the housing. Since the sleeve is rotationally and axially fixed to the dose knob, the sleeve also does not rotate and can only move axially in the proximal direction during dose delivery. In this way, the nut also does not rotate during dose delivery and only moves axially with the piston rod in the proximal direction by a certain distance. This distance is directly proportional to the set dose. Due to the threaded engagement with the nut, this only axial movement of the nut necessarily causes an axial movement of the piston rod. As mentioned, during dose setting, advantageously the axial translational movement of the nut in the distal direction is directly proportional to the amount of drug that would be delivered if the piston rod were then moved proximally without rotating the nut relative to the piston rod.

[0028] The dose setting knob may also include an anti-roll feature, which prevents the injection device from rolling when the user places the unattended device on a flat surface such as a tabletop. In order to prevent the device from rolling and falling from a surface that could damage the device, the dose knob may include a radially protruding rib. The rib prevents the injection device from rolling more than 180 degrees when the device is placed on a flat surface. The radially protruding rib does not point or align with a corresponding marking on the body of the device. In other words, when the dose knob is turned to set a dose, the relative circumferential position of the rib does not correlate with any of a limited set of predetermined fixed doses. To set a dose, the knob is always turned in one direction, for example: clockwise. The knob is not turned during injection. Therefore, with each injection, the knob and therefore the radially protruding rib is turned further clockwise. Therefore, the radial position of the rib cannot be related to any part of the pen body, in particular, the predetermined dose.

[0029] The present disclosure relates to an injection device, and in particular to a dose setting mechanism of the injection device, where a user can select one or more predetermined fixed dose settings as a direct result of the design and manufacture of a single component of the dose setting mechanism. Changing the design of the single component of the dose setting mechanism allows for efficient manufacture of an injection device that can be customized for a specific dosing regimen and / or for dose range evaluation.

[0030] The present disclosure is also directed to a complete injection device. A possible embodiment of such an injection device includes a body having an attachment mechanism at a proximal end, the attachment mechanism being configured to be connected to a holder for a container, preferably a cartridge, the container containing a drug delivered to a patient in a series of set doses. A dose setting mechanism as described above can be used in the injection device, where a dose selector is configured to allow only a limited set of predetermined fixed doses to be set by the user of the device, wherein the limited set of predetermined fixed doses includes a minimum fixed dose and one or more higher fixed doses, and wherein at least one of the one or more higher fixed doses is equal to the minimum fixed dose plus a fractional amount of the minimum fixed dose. The dose stop points are circumferentially located on the inner surface of the dose selector, and the circumferential distance between each dose stop point and the zero dose hard stop point is directly proportional to each fixed dose.

[0031] In another embodiment of the injection device of the present disclosure, the device has a body having an attachment mechanism at a proximal end, the attachment mechanism being configured to connect a cartridge holder, the cartridge holder holding a cartridge containing a certain amount of drug, where the amount of drug is measured in doses. The device also includes a dose setting mechanism, the dose setting mechanism having a dose selector rotatably fixed to the body, where the dose selector includes a dose stop point, the dose stop point being configured to allow only a limited set of predetermined fixed doses that can be set using the dose setting mechanism. There is also a snap element rotatable relative to the dose selector. The snap element has a fixed set of snap coupling elements, advantageously snap element splines, which are integral with the outer surface and arranged circumferentially around the outer surface. The dose setting mechanism also includes a fail-safe component, the fail-safe component being configured to prevent a user of the injection device from setting a dose other than one of a limited set of predetermined fixed unit doses. During both dose setting and dose delivery, a coupling assembly axially fixed to the snap element allows the snap element to rotate relative to the coupling assembly. The dose knob has a first position during dose setting and a second position during dose delivery, allowing a user to select one of predetermined fixed doses, wherein in the first position the dose knob is splined to a fixed set of coupling elements, advantageously a fixed set of splines, but not splined to the coupling assembly, and in the second position the dose knob is splined to the coupling assembly but not to the fixed set of coupling elements.

[0032] The present disclosure is also directed to a method for designing and manufacturing an injection device based on performing a dose range assessment. Due to the unique design of the dose setting mechanism, this is possible, where only a single component (i.e., a dose selector) needs to be replaced with a different dose selector so that the injection device has a new limited set of predetermined fixed doses or only a single predetermined effective fixed dose. One such method includes providing a first injection device having a first dose setting mechanism, the first dose setting mechanism comprising a floating spline, a dose knob, a dose selector, and a snap element as described above. During dose setting and dose delivery, the floating spline assembly engages with a fixed set of splines on the dose selector. In addition, during dose delivery, the floating spline assembly engages with the splines on the dose knob, but does not engage during dose setting. The first injection device is then used in a dose range assessment test, where a plurality of first injection devices containing a drug are distributed to a plurality of test patients.

[0033] The subject is instructed to perform an injection of a predetermined drug dose using a first injection device. Physiological data may be collected from the subject after the injection is performed so as to analyze the collected physiological data to determine an effective single drug dose. Alternatively, the subject may simply report the effect of the injection of the predetermined dose. Based on the results of the analysis or report, a second injection device that has been manufactured with a second dose setting mechanism may be provided, where the manufacturing process involves redesigning the dose selector so that the second injection device can be set to a new limited set of predetermined doses or a single effective fixed dose. The floating splines, dose knobs, and snap elements in the second dose setting mechanism remain unchanged in design from those used in the first dose setting mechanism. In other words, only the dose selector must be redesigned and remanufactured. All other components used to assemble the second dose setting mechanism remain the same as those used in the first dose setting mechanism. In some cases, the marking print on the outer surface of the dose sleeve may be changed to reflect one or more new predetermined dose settings of the redesigned and newly manufactured dose selector. However, the design, manufacture, and functionality of the dose sleeve remain unchanged.

[0034] Another advantage of the dose setting mechanism of the present disclosure is related to the fact that only a single component needs to be changed to affect a new limited set of predetermined dose settings, so that the equipment and assembly method for assembling the entire injection device remain the same. Keeping the same assembly equipment and method is directly related to the fact that only the number and position of dose stop points in the dose selector need to be changed to obtain a new injection device.

[0035] The above advantages are directly related to the inherent flexibility of the design of the dose selector to achieve any possible number of predetermined fixed dose settings between zero dose and maximum dose, including fractional doses of the lowest set dose. This becomes important for pharmaceutical companies that want to evaluate new drugs or evaluate how existing drugs will affect different disease states. It is particularly advantageous to be able to easily and efficiently design different dose selectors, each with a different limited set of predetermined doses, including having fractional fixed predetermined doses, rather than making each fixed dose a multiple of the lowest fixed dose.

[0036] In injection devices of the type disclosed in the present disclosure, the manufacture of those devices may introduce unavoidable tolerances and functional gaps between individual components of the drug delivery device, in particular components of the dose setting mechanism. As a result, even after the drug delivery device has been assembled, gaps such as gaps between those components (such as between the piston rod foot and the sliding piston) may occur, so that the piston may not be in contact with the distal end of the foot. It is therefore important to eliminate any such gaps or manufacturing tolerance anomalies so that the dose setting mechanism is in a prestressed state before the first setting of one of the limited predetermined set doses. If this is not achieved, it may not be possible to correctly dispense the dialed predetermined set dose from the device. The initial manufacturing gaps may have tampered with the dose setting. In order to adjust the drug delivery device for use, a priming action is performed to ensure that the drive mechanism is correctly adjusted, for example, the piston rod and the attached foot are in contact with the sliding piston, so that the correct amount of drug can be expelled from the device. These adjustment actions can be achieved either during the manufacture / assembly process of the device or by the user who assembles the device shortly before the first use of the device. In the latter scenario, the user will need to dispense a small amount of drug, which will visually indicate that the drug delivery device is ready for use, but will also result in drug waste. The present disclosure describes a priming process that covers both possibilities.

[0037] These and other aspects of the present disclosure and advantages associated therewith will become apparent from the following detailed description of the disclosure and the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] In the following detailed description of examples of the present disclosure, reference will be made to the accompanying drawings, in which:

[0039] Figure 1 is a perspective view of a possible complete drug delivery device incorporating the structural member of the present invention;

[0040] Figure 2 Shows Figure 1 a perspective view of the device of where the cap is removed to allow the pen needle to be attached to the cartridge holder;

[0041] Figure 3 yes Figure 1 An exploded view of the device;

[0042] Figure 4 showing a perspective view of a snap element, with and without a coupling assembly rotationally connected thereto;

[0043] Figure 5 shows a perspective view of the coupling assembly in both an assembled state and a pre-assembled state;

[0044] Figure 6 shows a perspective view of the dose selector from both the distal and proximal ends;

[0045] Figure 7 is a perspective view of the piston guide;

[0046] Figure 8 is a perspective view of the piston rod;

[0047] Fig. 9 It is a perspective view of the drive;

[0048] Fig.10 It is an exploded perspective view of the nut and the sleeve;

[0049] Fig.11 is a perspective view of a housing of a dose setting mechanism;

[0050] Fig.12 is a perspective view of the dosage knob;

[0051] Fig.13 A possible force-priming feature of the dose setting mechanism is shown; and

[0052] Figures 14A-14E Various positions of the snap element relative to the dose selector are shown. DETAILED DESCRIPTION

[0053] In the present application, the term "distal portion / end" refers to the portion / end of the device, or the portion / end of its component or part, which is located farthest from the delivery / injection site of the patient according to the use of the device. Correspondingly, the term "proximal portion / end" refers to the portion / end of the device, or the portion / end of its component, which is located closest to the delivery / injection site of the patient according to the use of the device.

[0054] The dose setting mechanism 30 of the present disclosure (see Figure 3 ) can be used in a number of complete injection devices of various designs. One such embodiment of the complete injection device 10 is Figure 1 , which is shown in a zero dose state, as indicated by the marking 40 showing zero through the window 3 a of the housing 3 . Figure 2 Shows Figure 1The present invention provides a device in which the cap 1 is removed to expose the cartridge holder 2 and the proximal needle connector 7. The pen needle 4 is attached to the needle connector 7 by snap fit, thread, Luer-Lok or other secure attachment to the needle hub 5 so that the double ended needle cannula 6 can be in fluid communication with the drug contained in the cartridge 8. The cartridge 8 is sealed at the proximal end by a septum 8a and at the opposite distal end with a sliding piston 9.

[0055] As explained above, the dose setting mechanism 30 of the present disclosure is unique compared to other known pen-type injection devices in that only a single component of the dose setting mechanism 30, namely the dose selector 35, is primarily responsible for determining a limited set of predetermined fixed doses within the maximum permissible dose range. In addition, the limited set of predetermined fixed doses may contain fractional doses, which means that each fixed dose does not necessarily equal an equal multiple of other fixed doses. For example, one fixed dose setting may be equal to an equal multiple of a lower fixed dose plus a fraction of that equal multiple.

[0056] Dose selector 35 Figure 6 The outer surface of the dose selector 35 has a plurality of longitudinal grooves 35a, which always engage with the longitudinal splines 3b on the inner surface 3d of the housing 3 (see FIG. Fig.11 ). This engagement prevents relative rotation between the dose selector 35 and the housing 3, but allows the dose selector 35 to move axially relative to the housing 3. Other means for preventing relative rotation between the dose selector 35 and the housing 3, but allowing axial movement of the dose selector 35 relative to the housing 3 may also be advantageous. The outer surface of the dose selector 35 also has a connecting cutout 59, which is connected to the dose knob 31 (see Fig.12) are permanently engaged and locked so that the dose knob is axially fixed to the dose selector 35. These permanent snap fittings 31c allow the dose knob 31 to rotate relative to the dose selector 35 during both dose setting and dose cancellation. At the distal end of the inner surface 35b of the dose selector 35, there is a fixed set of dose selector coupling elements. In this example, a dose selector spline 54 is shown. Other dose selector coupling elements may also be advantageous. The dose knob 31 includes a knob coupling element. In this example, the knob coupling element is a knob spline 31a. Other knob coupling elements may be advantageous. The number and relative spacing between a set of fixed dose selector splines 54 are equal to the number and relative spacing between the fixed knob splines 31a located on the inner proximal surface of the dose knob 31. As explained more fully below, the reason for this equivalence is to ensure a smooth transition between the start of the dose setting process and the dose delivery process when the dose knob disengages a set of splines 44 and engages another set of splines 52. The space between each dose stop point 55a, 55 is a multiple of the space between each radially projecting longitudinal spline 52 on the floating spline assembly 34. The floating spline assembly 34 is a coupling assembly for establishing a rotationally fixed connection between parts of the dose setting mechanism 30. Other coupling assemblies including other coupling elements besides splines may also be advantageous.

[0057] The floating spline assembly 34 includes a longitudinal spline 52. The longitudinal spline 52 is a coupling element. For the coupling assembly, other coupling elements may also be advantageous. In one embodiment of the dose setting mechanism 30 of the present disclosure, the number of radially protruding longitudinal splines 52 that are equally spaced is selected to allow eighty radial positions between the knob 31 and the snap element 33. However, for ergonomic and other reasons, the zero dose hard stop point 55d and the selected maximum dose hard stop point 55c limit the available relative rotation of the dose setting knob to 270°. Therefore, this limited rotation means that there are actually only 60 (sixty) available radial positions (80 splines x 270° / 360°). In one example, a customer may only want an injection device with a maximum dose of 0.60ml. Then, this means that 60 radial positions will result in a grid (or increment) of 0.01ml. The user can select a fixed dose of, for example, 0.20ml or 0.21ml, instead of a dose of 0.205ml. In most applications a 0.01ml grid is sufficient for any practical use.

[0058] In another possible embodiment, if the maximum dose is selected to be 0.30ml using 80 equally spaced radially protruding longitudinal splines 52, this will be a grid of 0.005ml. This grid is usually finer than required, and an alternative approach for this selected maximum dose will be to have 40 equally spaced radially protruding longitudinal splines 52, rather than 80. When the knob splines 31a on the dose knob 31 engage with the fixed snap-fit ​​element splines 44 of the floating spline assembly 34 and the snap-fit ​​element 33, the finer the grid, the higher the possibility of binding / blocking problems. When using 80 radially protruding longitudinal splines 52, the preferred acceptable radial mismatch should be below 4.5°. The fixed snap-fit ​​element spline 44 is a snap-fit ​​coupling element. Instead of the fixed snap-fit ​​spline 44, other forms of coupling elements for the snap-fit ​​element 33 may also be advantageous. Advantageously, the forms of the coupling element, the snap coupling element, the knob coupling element and the dosage selector coupling element of the coupling assembly are adapted to each other to allow engagement between the various coupling elements as described above.

[0059] like Figure 6 As shown in , there is also a discontinuous radially protruding circumferential rib 56 on the inner surface 35b of the dose selector 35, which is selectively interrupted by a number of cutouts 56a at circumferential positions corresponding to the dose stop point 55 and the filling stop point 55a. As the term is used in the present disclosure, the filling stop point 55a is not considered to be a dose stop point because the drug discharged from the injection device corresponding to the filling stop point 55a is not a dose injected into the patient or injection device user. The function of the rib 56 and the cutout 56a will be explained in more detail below. The dose stop point 55 directly corresponds to a limited number of predetermined fixed doses that the dose setting mechanism can set, including a predetermined fixed filling dose in some cases. One or more dose stop points 55 may be included on the inner surface of the dose selector 35. Preferably, the dose stop point 55 is formed as an integral part with the inner surface 35b of the dose selector 35, which can be manufactured as a single molded component. The single molded dose selector facilitates an important attribute of the dose setting mechanism 30 of the present disclosure, which is the ability to change a single component of the injection device 10 to obtain different sets of limited predetermined doses. This is achieved by changing the number and / or relative circumferential spacing of the dose stop points 55 on the inner side of the dose selector 35.

[0060] The inner surface 35b also has a zero dose hard stop 55d. The circumferential spacing between each dose stop 55 and the zero dose hard stop 55d is proportional to one of a limited set of predetermined fixed doses. As mentioned, in some cases, it is desirable to include a filling stop 55a corresponding to a fixed filling dose, which allows the user to initially position the foot 42a of the piston rod 42 to abut against the distal surface of the piston 9 before attempting the first injection. This filling step ensures that the first injection accurately dispenses a dose of the drug corresponding to one of the predetermined fixed dose settings. The dose stop 55 and the filling stop 55a are configured to facilitate the shape of dose setting and dose cancellation, as will be explained in more detail below. Figure 6 A dose stop point is shown having inclined surfaces 55e and 55f. This is in contrast to the zero dose hard stop point 55d which is configured as a hard stop point.

[0061] Figure 6 Also shown in FIG. 3 is an optional end of an injection projection 55b on the inner surface of the dose selector 35. During the dose delivery process, when the projection 45 moves with the snap element 33 ( Figure 4 ) is rotated relative to the dose selector 35, when the snap element 33 returns to the zero dose setting, the protrusion 45 will eventually reach the end of the injection bump 55b. The protrusion 45 will climb up the bump 55b and pass over the bump 55b to generate a notification signal to the user that the injection device 10 has returned to the initial zero dose starting state. This notification does not necessarily indicate that the discharge of the set dose of drug has been achieved, but rather signals the user to start the recommended 10 second needle insertion holding time to ensure that the dose is fully delivered.

[0062] The setting of one or more predetermined fixed doses is achieved by the interaction of the snap element 33 with the dose selector 35 . Figure 4The snap element 33 is shown with and without a floating spline assembly 34 rotatably connected to the outer surface 33a of the snap element 33. The snap element 33 can be rotatably and axially connected to the dose sleeve 38 by an internal spline 48 and a snap element 48a. The projection 45 is arranged on a flexible arm 45a, where the projection 45 engages the dose stop point 55 and the filling stop point 55a only during dose setting and dose cancellation. In other words, for reasons explained below, during dose delivery, when the snap element rotates in the reverse rotational direction relative to the dose selector, the projection 45 does not engage with the dose stop point during dose delivery. A second or blocking projection 46 is located on the outer surface 33d at the proximal end of the snap element 33. The position of the blocking projection is selected so that in the event of a dose delivery interruption, the blocking projection can abut against the distally facing surface of the radially protruding rib 56. As explained below, if the user ceases to apply a proximal axial force on the dose knob 31 during dose delivery when the dose setting mechanism is between two predetermined fixed dose settings, this abutment will prevent the dose knob from moving axially in the distal direction.

[0063] FIG. 14A to FIG. 14E The relative positions of the blocking protrusion 46, the protrusion 45, the protruding rib 56 and the zero dose hard stop point 55d and the maximum dose hard stop point 55c are shown. Fig.14A The dose setting mechanism 30 is shown in an initial zero set dose position, where no axial force is applied to the dose knob 31, i.e. the so-called released state. Here, the blocking protrusion 46 abuts the zero dose hard stop 55d, preventing a dose less than zero from being dialed, i.e. causing the snap element 33 to rotate in a clockwise direction. The protrusion 45 is on the rear side of the filling stop 55a. Fig. 14B The dose setting mechanism 30 is shown set at one of a limited set of predetermined set doses (0.1 ml) before the dose knob 31 is depressed to initiate a dose delivery procedure. The protrusion 45 is located on the front side of the dose stop point 55, while the blocking protrusion 46 is located on the proximal side of the protruding rib 56, but axially aligned with the cutout 56a.

[0064] Fig. 14C It shows that before the snap element 33 starts to rotate Fig. 14B The dose delivery of the set 0.10 ml dose is started. Here, the dose selector 35 has now moved proximally relative to the snap element 33, causing the blocking protrusion 46 to be located at the distal end of the protruding rib 56. This relative position change is only possible due to the alignment of the cutout 56a with the blocking protrusion 46. The dose stop point 55 has now been disengaged from the radial alignment with the protrusion 45, thus allowing the snap element 33 to rotate counterclockwise relative to the dose selector 35 when the dose delivery process continues.

[0065] Fig.14DThe relative positions of the blocking protrusion 46 and the protruding rib 56 are shown in the case where the user releases (removes) the proximal axial force on the dose knob 31 during the dose delivery process. The protruding rib 56 abuts against the blocking protrusion 46, thus preventing the dose selector 35 from moving axially distally. This also prevents the knob splines 31a on the dose knob 31 from reengaging with the fixed snap element splines 44 on the snap element 33. Fig.14E The interaction of the maximum dose hard stop point 55c and the blocking protrusion 46 is shown in the case where the user dials out beyond the maximum predetermined fixed dose setting. As shown, the protrusion 45 has moved upward and exceeded the maximum predetermined fixed dose stop point 55, and the blocking protrusion 46 abuts the maximum dose hard stop point 55c, thereby preventing any further rotation of the snap element 33.

[0066] The snap element 33 also has a fixed set of snap element splines 44, which are preferably formed integrally with the snap element 33 during the manufacture of the snap element 33, for example during a molding process. These fixed snap element splines 44 do not rotate or move axially relative to the snap element 33. The number and spacing of these fixed snap element splines 44 are equal to the dose selector splines 54 on the inner surface 35b of the dose selector 35 and the knob splines 31a on the inner side of the dose knob 31. The function of the fixed snap element splines 44 will be explained below. The snap element 33 may also have a clicker 47, such as Figure 4 , the catch is shown as a flexible arm with a radially facing tip. The catch is configured to engage the knob splines 31a on the dose knob only during dose delivery, so that when the catch tip travels on the knob splines 31a of the dose knob 31, the rotation of the snap element 33 produces an audible and / or tactile feedback. During dose setting, the engagement of the protrusion 45 with the dose stop point 55 and the filling stop point 55a also produces a tactile and / or audible notification, but only when each predetermined dose setting is reached. The number of notifications during dose setting is less than the number of notifications generated by the catch 47 during dose delivery. This is because the catch 47 engages each of the equally spaced knob splines 31a on the inner surface of the dose knob 31.

[0067] The snap element 33 also has an outer surface 33a that receives and axially accommodates the floating spline assembly 34. The floating spline assembly 43 is axially accommodated to limit the axial movement of the floating spline assembly 34 relative to the snap element 33. Figure 4 As shown in FIG, axial accommodation of the floating spline assembly 34 to prevent distal and proximal movement is achieved by radial ribs 33b, 33c defining the outer surface 33a. Figure 533a, where the preferred construction is two halves 34a, 34b that can be connected to each other after being assembled on the surface 33a. The connection of the two halves 34a, 34b can be achieved by a snap fit, which is shown as a combination of arms 49, 51 that engage with the pawls 50a, 50b, respectively. Regardless of the type of connection, it is important that the engagement with the snap element 33 allows the floating spline assembly and the snap element to rotate relative to each other. The number and spacing of the knob splines 52 on the floating spline assembly 34 are equal to the number and spacing of the fixed snap element splines 44, the number and spacing of the dose selector splines 54 on the inner surface 35b of the dose selector 35, and the number and spacing of the knob splines 31a on the inner surface of the dose knob 31. This is necessary because the floating spline assembly 34 acts as a connector during dose delivery, as explained in more detail below, where the dose knob 31 is prevented from rotating relative to the dose selector 35. When the dose setting mechanism is assembled, the dose selector splines 54 on the inner surface of the dose selector 35 are fully engaged or meshed with the radially protruding longitudinal splines 52. This meshing of the radially protruding longitudinal splines 52 and the dose selector splines 54 rotationally fixes the floating spline assembly 34 to the dose selector 35. Since the dose selector 35 is splined to the housing 3 to prevent rotation, this results in the floating spline assembly 34 also being rotationally fixed to the housing 3.

[0068] like Figure 5 As shown in the figure, the distal proximal end 52a and the distal end 52b of each spline 52 are chamfered to help smoothly engage with the knob spline 31a on the dose knob 3 during the start of dose delivery. When the dose setting mechanism 30 is assembled, the dose knob 31 is spline-fixed to the snap element 33 by engagement of only the fixed fixed snap spline 44 and the knob spline 31a on the dose knob 31. Because the fixed snap element spline 44 is rotationally fixed to the snap element 33, rotation of the dose knob 31 necessarily causes the snap element 33 to rotate, so that the surface 33a rotates relative to the rotationally fixed inner surface 53 of the floating spline assembly 34. This rotation of the dose knob 31 and the snap element 33 occurs during dose setting and relative to the housing 3. During the start of the dose delivery process, the dose knob 31 is pressed in the proximal direction, causing it to move axially relative to the snap element 33. This initial movement disengages the knob splines 31a from the fixed snap element splines 44 and causes the knob splines 31a to subsequently engage the floating spline assembly 34. This new engagement of the knob splines 31a and the floating spline assembly 34 then prevents the dose knob from rotating relative to the housing 3 during dose delivery.

[0069] Details of the dose knob 31 are shown in Fig.12During assembly of the dose setting mechanism, the dose knob 31 may be axially fixed and attached to the dose selector 35 by means of a snap element 31c engaging with a corresponding cutout 59 (see Figure 6 ). This connection allows the dose knob 31 to rotate relative to the dose selector 35. The dose knob 31 also has a gripping surface 31d on the outer surface and includes radially protruding ribs 31b which act as an anti-roll feature, as well as a lever feature to help the user set or cancel a dose.

[0070] Fig.10 The nut 36 and the sleeve 32 are shown, which are permanently splined to each other by a spline connection during assembly of the dose setting mechanism 30. The spline connection is established by the connecting element 37 of the nut 36 and the connecting element 71 of the sleeve 32. The spline connection ensures that the sleeve 32 and the nut 36 are always rotationally fixed to each other during both dose setting and dose delivery. The spline connection also allows the sleeve and the nut to move axially relative to each other. In order to compensate for the thread 60 on the piston rod 42 (see Figure 8 ), the external thread 39 on the dosage sleeve 38 (see Figure 3 ) and the thread 67 on the driver 41 (see Fig. 9 ). A sliding connection is necessary to compensate for the difference in thread pitch between the nut and the outer surface of the piston rod and between the dose sleeve and the body. The thread between the driver and the piston guide has substantially the same pitch as the thread between the piston rod and the nut.

[0071] The proximal end of the nut 36 has an internal thread 70 that matches the thread 60 of the piston rod 42. The distal end of the sleeve 32 is configured as a dose button 72 and is permanently attached to the distal end of the dose knob 31 by engagement of a connector 73, which may also include a snap lock, adhesive and / or sonic welding. This connection ensures that the sleeve 32 is both rotationally and axially fixed to the dose knob during both dose setting and dose delivery.

[0072] like Figure 8 In addition to the threads 60 on the outer surface of the piston rod 42, two longitudinal flat surfaces 61 are included, which give the piston rod 42 a non-circular cross-section. A connector 62 is at the distal proximal end, which is shown as a snap fit, which connects to the disc or foot 42a (see Figure 3). The last dose feature of the dose setting mechanism is at the distal end of the piston rod 42, shown as an enlarged section 63. The enlarged section 63 is designed to stop the rotation of the nut 36 about the thread 60 when the amount of drug remaining in the cartridge 8 is less than the next highest predetermined dose setting. In other words, if the user attempts to set one of the predetermined fixed dose settings, which exceeds the amount of drug remaining in the cartridge, the enlarged section 63 will act as a hard stop point, thereby preventing the nut from rotating further along the thread 60 when the user attempts to reach the desired predetermined fixed dose setting.

[0073] During both dose setting and dose delivery, the piston rod 42 remains in a non-rotated state relative to the housing 3, as it is arranged in a non-circular through hole 64 in the center of the piston rod guide 43 (see Figure 7 ). The piston rod guide 43 is both rotationally and axially fixed to the housing 3. This fixation can be achieved when the piston rod guide 43 is a separate component from the housing 3, as shown in the figure, or when the piston rod guide 43 can be integral with the housing 3. The piston rod guide 43 also has a connector 65 that is configured to engage with the proximal end of the rotational biasing member, which is Figure 3 Shown in the drawing is a torsion spring 90, the function of which will be explained below. This connection of the rotational biasing member to the piston rod guide 43 anchors one end in a rotationally fixed position relative to the housing 3.

[0074] The distal end of the rotational biasing member (eg, torsion spring 90) is connected to the connector 66 on the driver 41 (see Fig. 9 ). The driver 41 is connected and rotationally fixed to the inner surface of the dose sleeve 38 by a driver spline 69 on the distal outer surface of the driver 41. On the proximal end of the driver 41, a thread 67 is on the outer surface, which engages with a matching thread on the inner distal surface of the piston rod guide 43. The thread between the driver and the piston guide has a pitch that is significantly different from the pitch of the thread between the dose sleeve and the housing. The nut 36 and the driver 41 rotate together during dose setting and dose cancellation, and therefore, they perform essentially the same axial movement. However, the movement is independent of each other, i.e., the nut 36 is rotated by the sleeve 32 and performs an axial movement due to the threaded connection with the thread 60 of the piston rod 42, while the driver 41 is rotated by the dose sleeve 38 and performs an axial movement due to the threaded connection with the piston rod guide 43 via the thread 67. The driver 41 also rotates during injection, and therefore it actively moves in the proximal direction during injection. However, the nut 36 does not rotate during injection, and therefore does not perform an active axial movement. The nut 36 moves only in the proximal direction during injection, as it is pushed axially by the driver 41. The rotating driver 41 pushing the non-rotating nut 36 causes the injection, as the piston rod 42 is pushed forward due to the threaded engagement with the nut.

[0075] For example, if the thread 70 of the nut 36 has a higher pitch than the pitch of the thread 67 of the driver 41, the nut 36 cannot move freely in the distal direction during dose setting because it will be hindered by the slower moving driver 41. In this way, this will cause the drug to be discharged during dose setting. Alternatively, if the thread of the nut 36 has a significantly lower pitch than the pitch of the thread 67 of the driver 41, the driver will move away from the nut during dose setting, and the driver will not push the nut when the injection has started, but only do so after the gap is closed. Therefore, it is preferred that the pitch of the thread 67 on the driver 41 is equal to or slightly greater than the pitch of the thread 70 on the nut 36. And, the thread 39 between the dose sleeve 38 and the housing 3 has a higher pitch than the thread of the nut and the piston rod. This is desirable because it creates a mechanical advantage that makes the dose delivery process easier for the user. For example, when the knob 31 is pushed a distance of 15mm, the piston rod 42 only moves 4.1mm. This results in a transmission ratio of about 3.6:1. A lower gear ratio will result in an increase in the force required by the user to complete the injection.

[0076] As will be explained in more detail below, since the torsion spring 90 is attached to the driver 41 and the driver is rotationally fixed to the dose sleeve 38, rotation of the dose sleeve 38 in a first direction during dose setting will wind the torsion spring 90 such that it exerts a counter-rotational force in an opposite, second direction on the dose sleeve 38. This counter-rotational force biases the dose sleeve 38 to rotate in the dose cancelling direction and provides the required force for the first fail-safe feature mentioned earlier.

[0077] The function of the complete injection device 10 and the dose setting mechanism 30 according to the present disclosure will now be described. The injection device 10 is provided to the user with or without a cartridge 8 of a drug located in the cartridge holder 2. If the injection device 10 is configured as a reusable device, the cartridge holder 2 is connected to the housing 3 of the dose setting mechanism 30 in a releasable and reusable manner. This allows the user to replace the cartridge with a new full cartridge 8 when all the drug is discharged or injected from the cartridge 8. If the injection device is configured as a disposable injection device, the cartridge of the drug is not replaceable because the connection between the cartridge holder 2 and the housing 3 is permanent. The cartridge 8 can be removed from the injection device 10 only by disconnection or deformation of the connection. Such a disposable device is designed to be thrown away once the drug has been discharged from the cartridge 8.

[0078] The user first removes the cap 1 from the device and then mounts an appropriate pen needle 4 to the cartridge holder 2 using the connector 7. If the injection device 10 is not pre-primed during assembly of the device, or does not have an automatic or forced priming feature as described above, the user will need to manually prime the device as follows. The dose knob 31 is rotated so that the protrusion 45 engages a first dose stop, such as the priming stop 55a, which corresponds to a predetermined small fixed dose of the drug. Rotation of the dose knob 31 causes the protrusion 45 on the snap element 33 to rotate relative to the dose selector 35 as the fixed snap element splines 44 engage the knob splines 31a on the dose knob 31. During dose setting, the dose selector 35 is rotated as shown in FIG. 1 . Figure 3 An axial biasing member, shown as a compression spring 91 , located between the catch element 33 and the dose knob 31 , applies an axial force on the dose knob in the distal direction to ensure that the fixed catch element splines 44 and the knob splines 31a remain engaged during dose setting.

[0079] The injection device 10 of the present disclosure may also have a so-called forced or automatic priming feature, one embodiment of which is Fig.13 31 , in which the sleeve 32 is not initially rotatably fixed to the dose knob 31. The slide lock 80 is located between the distal end of the sleeve 32 and the inner surface of the dose knob 31. Before the dose setting mechanism 30 is used, i.e., before the user can dial one of the predetermined fixed dose settings, the slide lock 80 will necessarily need to be pushed in the proximal direction so as to move distally relative to the dose knob. This axial movement causes the snap finger 81 to engage with the proximally facing surface 32d of the sleeve to form an irreversible locking relationship between the dose knob and the distal end of the sleeve. This locking relationship also causes the teeth 32c of the sleeve 32 and the corresponding teeth 82 of the slide lock 80 to mesh and interlock, so that the dose knob and the sleeve are rotatably fixed to each other. Before the slide lock 80 engages with the sleeve, the sleeve can be rotated, which also causes the nut to rotate to cause the piston rod 42 to move axially relative to the housing. The sleeve is rotated until visual observation and / or tactile notification indicates that the foot 42a located on the piston rod 42 is firmly abutted against the distally facing surface of the sliding piston 9. This abutment between the foot and the sliding piston 9 will ensure that the correct dialed dose is delivered from the needle cannula 6. This rotation of the sleeve is preferably performed during assembly of the injection device, and again after ensuring that the foot 42a is abutted against the sliding piston 9, the manufacturing process will cause the sliding lock 80 to be pushed into the final locked position. One possible way to achieve rotation of the sleeve 32 would be to use a gripper with a vacuum suction cup to rotate the sleeve 32. Alternatively, a groove or other connector may be designed into the distal surface of the sleeve that cooperates with a matching tool to engage and rotate the sleeve 32. This optional connector is Fig.13 It is shown as slit 32f.

[0080] The rotation of the protrusion 45 and the subsequent contact with one side of the filling stop 55a, or for that matter, any predetermined dose stop on the dose selector 35, will cause the flexible arm 45a to bend radially inward to allow the protrusion 45 to climb up, over and down the opposite side of the filling stop 55a or the dose stop 55. This movement and contact of the protrusion 45 produces an audible and / or tactile notification that a dose stop has been reached during the dose setting process. The type or level of notification can be modified by changing the design of the protrusion 45, the flexible arm 45a and / or the configuration of the dose stop 55 or the filling stop 55a. In some cases, it may be desirable to have a different notification for each predetermined dose setting. Likewise, it may also be desirable to have the notification during dose setting be different from the notification generated by the catch 47 during dose delivery.

[0081] Returning to the filling process, once the filling stop point 55a is reached, the user may need to cancel the filling process, and can do so by using a dose cancellation process. This cancellation process also applies to any predetermined dose setting. Dose cancellation is achieved by turning the dose knob in the opposite direction, so that the protrusion 45 is caused to rotate in the opposite direction relative to the dose stop point 55 or the filling stop point 55a. This will again produce a notification that may be the same or different from the dose setting notification and / or the dose delivery notification. Because the snap element 33 is rotationally fixed to the dose sleeve 38, and the dose sleeve is threadedly engaged to the inner surface 3d of the housing 3, the rotation of the dose knob 31 during dose setting and dose cancellation causes relative rotation between the dose sleeve 38 and the housing 3. The threaded connection between the housing 3 and the dose sleeve 38 causes the dose sleeve 38, the snap element 33, the sleeve 32 and the dose knob 31 to translate axially as the dose knob 31 rotates. During dose cancellation, these components rotate in the opposite or proximal direction and translate axially.

[0082] Rotation of the dose knob 31 also causes the nut 36 to rotate around the threads 60 on the outer surface of the piston rod 42, which do not rotate and are axially fixed relative to the housing 3 due to the relative pitch differences in the threaded portions as explained above. Rotation of the nut 36 relative to the fixed piston rod 42 (which is supported by its contact with the sliding piston) causes the nut to translate or climb up the piston rod in the distal direction. Reverse rotation during dose cancellation causes the nut 36 to translate in the opposite direction relative to the piston rod 42. The distance traveled by the nut to reach the desired dose setting is directly proportional to the amount of drug that will be expelled if the dose delivery process is initiated and completed. Because the pitch of the threaded connection between the dose sleeve 38 and the housing 3 is greater than the pitch of the threads 60 on the nut, the dose sleeve 38, the snap element 33, the sleeve 32 and the dose knob 31 will travel a greater axial distance than the nut 36 when they climb up or down the piston rod 42. The difference in axial movement would normally bind the dose setting mechanism, but this does not happen because the difference in pitch is compensated by the sliding spline connection between the nut 36 and the sleeve 32, thus allowing the sleeve 32 to travel axially a greater longitudinal distance than the nut 36. During injection, the sleeve 32 pushes the snap element 33 and thus the dose sleeve 38. This axial force causes the dose sleeve 38 to rotate to the housing 3 due to the thread 39. If the pitch of the thread 39 is high enough, the dose sleeve 38 will only start to rotate when pushed. If the pitch is too low, pushing will not cause rotation, because the low pitch thread becomes a so-called "self-locking thread".

[0083] The rotation of the dose knob 31 also causes a rotation of the driver 41 due to the splined rotationally fixed connection to the dose sleeve 38. Since the torsion spring 90 is fixed at one end to the driver 41 and at the other end to the piston rod guide 43, which in turn is axially and rotationally fixed to the housing 3, the torsion spring 90 is wound up to increase tension during dose setting. As described above, the torque of the torsion spring exerts a counter-rotational force on the dose sleeve 38. Preferably, during assembly of the dose setting mechanism, the torsion spring 90 is pre-tensioned so that the torsion spring exerts a counter-rotational force on the dose sleeve 38 even in a zero dose condition. The counter-rotational force provides a first fail-safe feature of the dose setting mechanism. The first fail-safe mechanism prevents the user from setting a dose that is not one of a limited set of predetermined dose settings. In other words, if the user rotates the dose knob 31 and the protrusion 45 is located between two dose stop points, or between the zero dose hard stop point and the first dose stop point 55 or the filling stop point 55a, and the user releases the dose knob, the reverse rotational force of the torsion spring 90 will return the protrusion 45 to the last engaged dose stop point, or return the protrusion 46 to the zero dose hard stop point 55d. In addition, during the dose cancellation process, the reverse rotational force will help the user to rotate the dose knob 31 back down to the next lower fixed dose setting, or possibly all the way back to the zero dose setting.

[0084] During dose setting, the dose knob 31 translates and moves away from the distal end of the housing 3. As the dose sleeve 38 rotates and translates, the process of dose setting (or dose cancellation) is observed in the window 3a of the housing 3 as the printed mark 40 on the dose sleeve 38 moves through the open window 3a. When the desired predetermined dose setting is reached, the mark for that dose will appear in the window 3a. Because the dose stop point 55 or the filling stop point 55a engages with the protrusion 45, the torsion spring will not have enough force to reverse the set dose to the next lower fixed dose setting. At this point, the injection device 10 is ready for the filling process, or if it has been filled, it is ready to deliver the drug to the injection site. In either case, the user will push the dose knob 31 in the proximal direction until the zero dose hard stop point 55d is reached and the zero dose mark is observed in the window 3a. During the filling step, the user will observe whether the drug is discharged from the cannula 6 of the pen needle 4. If no drug is discharged, this means that the piston foot 42a is not in abutment with the distal surface of the sliding piston 9. The priming step is then repeated until drug is observed to leave the cannula 6 .

[0085] The dose setting mechanism of the present disclosure may also have a maximum dose hard stop feature that prevents the user from setting a dose greater than the highest predetermined dose setting. This is achieved by using a maximum dose hard stop 55c that engages the second protrusion 46 if the user dials (i.e. rotates the dose knob 31) beyond the dose stop 55 corresponding to the highest predetermined dose setting (see Figure 4 and 6 ). The engagement of the second protrusion with the maximum dose hard stop 55c will prevent further rotation of the snap element. The maximum dose hard stop 55c is configured to have a certain shape so that the second protrusion 46 cannot rotate beyond the hard stop without deforming or damaging one or more components of the dose setting mechanism. In the event that the user dials beyond the last dose stop 55 and engages the maximum dose hard stop 55c with the second protrusion 46, releasing the dose knob 31 will allow the torsion spring 90 to reversely rotate the dose sleeve 38, the snap element 33 and the dose knob 31 back to the last dose stop 55.

[0086] The dose setting mechanism 30 may also have an anti-tamper or anti-disassembly feature that generally corresponds to the maximum dose hard stop point. The anti-tamper feature is formed between a hard stop point or hook 36b located on the outer surface of the nut 36 and the distally facing end wall 32b of the cutout 32a of the sleeve 32 (see Fig.10). As mentioned, the difference in pitch between the thread 60 of the piston rod 42 and the outer thread 39 of the dose sleeve 38 requires that the sleeve translates further distally than the nut 36 as it climbs onto the piston rod 42 during dose setting. The cutout 32a and / or hard stop 36b may be positioned so that axial translation of the sleeve 32 relative to the piston rod 42 stops at a predetermined position that generally corresponds to the engagement of the second protrusion 46 with the maximum dose hard stop 55c. The interaction of the hard stop 36b with the distally facing wall 32b will prevent further distal movement of the sleeve 32 relative to the nut 36, and may therefore prevent disassembly of the dose setting mechanism. Typically, attempts to disassemble an injection device are intended to replace an emptied cartridge with a counterfeit cartridge to allow the injection device 10 to be sold and reused as a fake new device. If someone were to pull the dose knob 31, pull the sleeve 32, and then pull the snap element 33 and the dose sleeve 38, the anti-counterfeiting feature would prevent disassembly. Although the threaded connection 39 of the dose sleeve 38 and the interior of the housing 3 serves as a primary disassembly feature, it may not be sufficient to prevent disassembly when the device is dialed to the maximum dose setting. As described above, a secondary disassembly feature at which the hard stop point 36b engages with the facing wall 32b can make up for this deficiency.

[0087] Once the dose setting mechanism 30 is primed, the user selects and sets the desired fixed dose by repeating the same steps for priming, except that the dose knob 31 will be rotated past the filling stop 55a until the appropriate dose stop is engaged by the protrusion 45 and the desired dose value appears in the window 3a. In some cases, it is preferred that no indicia is displayed in the window 3a when dialing between predetermined dose settings, while in other cases it is desirable to display an indication in the window 3a indicating a non-settable dose position between fixed dose settings.

[0088] Once one of the predetermined dose settings is dialed on the dose setting mechanism, the user may then apply an axial force in the proximal direction to initiate a dose delivery procedure. The axial force applied by the user overcomes the distal force applied by the second biasing member 91, causing the dose knob 31, the sleeve 32 and the dose selector 35 to move axially in the proximal direction relative to the snap element 33 and the housing 3. This initial movement disengages the knob splines 31a from the fixed snap element splines 44 and causes the knob splines 31a to engage with the floating spline assembly 34, thereby rotationally fixing the sleeve 32 and the dose knob 31 to the housing via the spline connection between the floating spline assembly 34 and the dose selector splines 54. Even though the dose selector 35 moves axially with the dose knob 31 and relative to the floating spline assembly 34, the dose selector splines 54 and the floating spline assembly 34 remain engaged during dose setting and during dose delivery.

[0089] The initial axial movement of the dose selector 35 relative to the snap element 33 causes the dose stop 55 to disengage from radial alignment with the protrusion 45, such that rotation of the snap element 33 relative to the dose selector 35 will not allow the protrusion 45 to engage either the dose stop 55 or the filling stop 55a, except of course the end of the injection bump 55b, which provides an audible and / or tactile notification to the user, a so-called end-of-injection notification, that the mechanical dose delivery process of the device has been completed. As mentioned, this notification also informs the user to maintain the cannula at the injection site for the recommended time, typically 10 seconds. Likewise, the initial axial movement of the dose selector relative to the snap element 33 also causes the radially protruding rib 56 to move proximally relative to the second protrusion 46, such that when rotation of the snap element 33 relative to the dose selector 35 occurs during the remainder of the dose delivery process, the protrusion 46 faces the distal side of the protruding rib 56. Due to the cutouts 56a in the protruding rib 56 at positions coinciding with each dose stop point 55a, 55, the protruding rib is able to move axially past the second protrusion 46. At the end of the injection, further rotation of the catch element 33 will cause the second protrusion to abut the zero dose hard stop point 55d, which will prevent any further rotation of the catch element 33.

[0090] In addition to the above-described end-of-injection feature, another end-of-injection notification feature may be incorporated as part of the driver 41. This alternative or additional end-of-injection feature also provides a tactile and / or audible notification to the user when the mechanical dose delivery process is complete. One configuration of this end-of-injection feature is Fig. 9 68a, 68b. The flexible arm 68b is loaded by the geometry of the interior of the dose sleeve 38 during dose setting. This holds the arm 68b inside the dose sleeve 38 because the flexible arm 68b bends to the right and inwards (see Fig. 9 ), and is held in place by flexible arm 68a. When zero is reached after dose delivery, flexible arm 68a bends by the geometry of the dose sleeve to release flexible arm 68b. This is possible because the driver 41 is turned by the dose sleeve 38 so that the two members have a purely linear movement relative to each other due to the difference in the pitch of the two corresponding threads 39 and 67.

[0091] When the user maintains an axial force on both the dose knob 31 and the dose button 72 during the continued dose delivery process, the sleeve 32 will abut the distal end of the catch element, causing it to move axially in the proximal direction. The sleeve 32 pushes the catch element 33. The catch element is fixed to the dose sleeve, so the sleeve pushes the dose sleeve 38. Since the dose sleeve 38 has a thread with a sufficiently high pitch relative to the body, the axial force on the dose sleeve 38 will cause the dose sleeve and therefore the catch element 33 to rotate relative to the housing 3, and by rotating relative to the housing 3, it moves in the proximal direction. The dose selector 35 slides into the housing, but does not rotate relative to the housing 3 due to the spline engagement between the housing splines 3b and the grooves 35a. The rotation of the dose sleeve 38 also causes the driver 41 to rotate into a threaded connection with the piston rod guide 43, which drives the piston rod proximally and causes the torsion spring 90 to be released at the same time. The driver 41 does not directly drive the piston rod 42. When the driver 41 rotates, the driver moves in the proximal direction and pushes the nut 36 forward. Since the nut 36 does not rotate, the driver 41 pushes the nut and the piston rod 42 forward.

[0092] The nut 36 does not rotate during dose delivery due to its rotationally fixed relationship with the sleeve 32 which is rotationally fixed to the housing by the rotationally fixed relationship of the dose knob 31, the floating spline assembly 34 and the housing 3. Therefore, the nut 36 can only move axially with it to carry the piston rod 42 because the piston rod is prevented from rotating by the non-circular opening 64 engaging the flat surface 61 on the piston rod 42. During dose setting, the piston rod moves axially the same distance as the nut initially translates relative to the piston rod. This axial movement without rotation is caused by the rotation and axial movement of the proximal end of the driver 41 abutting the flange 36a of the nut 36. The axial movement of the piston rod 42 causes the sliding piston 9 to also move axially relative to the inner wall of the stationary cartridge 8, forcing a certain amount of drug to flow out of the needle cannula 6, which is equal to the predetermined fixed dose set during the dose setting process.

[0093] If the user stops the dose delivery process by removing the axial force on the dose knob 31, the second fail-safe mechanism is activated. The removal of the axial force causes the compression spring 91 to bias the dose knob 31 in the distal direction. If the user stops the dose delivery between two predetermined fixed dose settings, both the dose knob and the axially fixed dose selector 35 will be prevented from moving proximally, as the second protrusion 46 will abut against the distally facing side of the protruding rib 56, which will stop the axial movement of the dose selector 35 and the dose knob 31. Without the abutment of the protrusion 46 with the protruding rib 56, the dose selector will then move distally, so that the knob splines 31a will re-engage with the snap element splines 44 on the snap element, thus placing the dose knob 31, the sleeve 32 and the nut 36 back into rotational engagement with the snap element 33. The torque applied by the driver 41 on the snap element 33 will then cause the nut 36 to rotate in the opposite direction, thus reducing the set dose by an unknown amount. This reverse rotation will continue until the next lowest predetermined fixed dose setting is reached, at which the corresponding dose stop point will stop the reverse rotation.

[0094] On the other hand, if dose delivery is stopped at one of the lower predetermined fixed dose settings, the cutout 56a in the protruding rib 56 will allow the dose selector 35 to move distally so that the second protrusion 46 is located on the proximal side of the rib 56. As described above, this will also re-engage the knob splines 31a of the dose knob 31 with the fixed set of snap element splines 44 to rotate the dose knob 31, sleeve 32 and nut 36 with the snap element 33 as described above. However, since the cutout 56a is only located at a circumferential position corresponding to the dose stop point 55, the snap element 33 and the nut 36 will not rotate back due to the engagement of the dose stop point 55 and the first protrusion 45. Because the nut 36 does not rotate back, there is no possibility of an unknown reduction in the set dose. Therefore, the resumption of the stopped dose delivery process will continue without any unknown reduction in the set dose, thereby allowing the originally set predetermined dose to be delivered.

[0095] It should be understood that the embodiments described above and shown in the drawings are to be regarded only as non-limiting examples of possible designs of the safety assembly.

Claims

1. A dose setting mechanism (30), comprising: Dosage knob (31); a dose selector (35) comprising one or more dose stop points (55) corresponding to a limited set of one or more predetermined fixed dose settings; as well as The snap-fit ​​element (33) The delivery of the set dose requires the application of an axial driving force to the dose knob (31) in the proximal direction. wherein the dose knob (31) and the dose selector (35) are configured to be axially moved in the proximal direction relative to the snap element (33) at the start of a dose delivery process, wherein the dosage selector (35) comprises a radially protruding circumferential rib (56), and the snap element comprises a blocking protrusion (46), wherein the radially protruding circumferential rib (56) has one or more cutouts (56a), wherein the dose selector (35) is configured to be pressed and moved only in the proximal direction to initiate dose delivery when the blocking protrusion (46) is aligned with one of the one or more cutouts (56a) in the radially protruding circumferential rib (56), allowing the radially protruding circumferential rib (56) to move axially past the blocking protrusion (46) to initiate dose delivery, wherein the blocking protrusion (46) is configured to engage the radially protruding circumferential rib (56) when the blocking protrusion (46) is not aligned with one of the one or more cutouts (56a) in the radially protruding circumferential rib (56).

2. The dose setting mechanism (30) according to claim 1, in, The radially protruding circumferential rib (56) is located on the inner surface (35b) of the dosage selector (35).

3. Dose setting mechanism (30) according to one of the preceding claims, in, The one or more cutouts (56a) correspond to each of the dose stop points (55).

4. The dose setting mechanism (30) according to claim 1 or 2, in, Axial movement of the dose selector (35) in the proximal direction moves the radially protruding circumferential rib (56) from a first position, in which the blocking protrusion (46) is located on a proximally facing side of the radially protruding circumferential rib (56), to a second position, in which the blocking protrusion (46) is located on a distally facing side of the radially protruding circumferential rib (56).

5. The dose setting mechanism (30) according to claim 1 or 2, in, The snap element (33) is configured to rotate relative to the dose selector (35) during dose setting and dose delivery.

6. The dose setting mechanism (30) according to claim 1 or 2, in, The proximal axial movement of the dose knob (31) causes the coupling element on the dose knob (31) to disengage from the coupling element on the snap element (33).

7. The dose setting mechanism (30) according to claim 1 or 2, in, Rotation of the snap element (33) during dose setting also causes rotation of a nut (36) engaged with a piston rod (42) of the dose setting mechanism (30), The position of the nut (36) relative to the piston rod (42) is proportional to the amount of drug to be delivered.

8. The dose setting mechanism (30) according to claim 1 or 2, in, The setting of the one or more predetermined fixed doses is achieved by the interaction of the snap element (33) with the dose selector (35).

9. The dose setting mechanism (30) according to claim 1 or 2, in, The dose knob (31) is configured to be rotated by a user during dose setting.

10. The dose setting mechanism (30) according to claim 9, in, Rotation of the dose knob (31) during dose setting causes rotation and axial movement of the snap element (33) and only axial movement of the dose selector (35).

11. The dose setting mechanism (30) according to claim 1 or 2, in, The one or more dose stop points (55) are circumferentially located on the inner surface (35b) of the dose selector (35), wherein the circumferential distance between each dose stop point (55) and a zero dose hard stop point (55d) is proportional to each fixed dose.

12. The dose setting mechanism (30) according to claim 1 or 2, in, The coupling assembly (34) is rotatably engaged with the snap element (33), wherein during dose setting and dose delivery, the coupling assembly (34) engages with a corresponding set of dose selector coupling elements on the dose selector (35), Wherein, the snap-fit ​​element (33) comprises a fixed set of snap-fit ​​connection elements, wherein the knob coupling element on the dose knob (31) engages and meshes with the fixed set of snap coupling elements of the snap element (33) during dose setting and does not engage and mesh during dose delivery, wherein the coupling assembly (34) comprises a plurality of radially protruding longitudinal splines (52) equally spaced from each other, wherein the coupling assembly (34) engages with the knob coupling element on the dose knob (31) via the radially protruding longitudinal splines (52) during dose delivery and does not engage during dose setting.

13. The dose setting mechanism (30) according to claim 12, in, The space between each of the dose stop points (55) is a multiple of the space between each of the radially projecting longitudinal splines (52).

14. The dose setting mechanism (30) according to claim 12, in, The coupling assembly (34) is axially fixed relative to the snap element (33).

15. An injection device comprising a dose setting mechanism (30) according to claim 1 or 2.

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