Device for attachment to an injection device

Abstract

An auxiliary device configured to be attached to a drug delivery device, the auxiliary device comprising: first means adapted to mechanically couple the auxiliary device to a dose selector of the drug delivery device; second means adapted to select a dose to be delivered by the drug delivery device; third means adapted to mechanically couple the second means to the first means, such that a dose selection made using the second means generates a torque that is transmitted to the first means via the third means; a sensor configured to output a signal indicative of the generated torque; and electronic circuitry configured to receive the signal output from the sensor and determine the selected dose based on the signal. [Selected figure] Figure 3

Description

Technical Field

[0001] The present disclosure relates to a device configured to hold an injection device or syringe and capable of detecting a selected dosage for injection.

Background Art

[0002] There are various diseases that require regular treatment by injection of drugs. Such injections can be performed by using an injection device, which can be done by medical staff or by the patient themselves.

[0003] Injection devices (i.e., devices capable of delivering a drug from a pharmaceutical container) are typically classified into two types: manual devices and auto-injectors.

[0004] In a manual device, the user has to apply mechanical energy to push the liquid through the needle. This is usually done by some form of button / plunger that the user has to continuously press during the injection. There are numerous disadvantages for the user from this approach. If the user stops pressing the button / plunger, the injection will also stop. This means that if the device is not used properly (e.g., the plunger is not fully pressed to its final position), the user may risk delivering an insufficient dose. Especially when the patient is elderly or has problems with their hands, the force required to inject may be too high for the user.

[0005] The extension of the button / plunger may be too large. Thus, it is inconvenient for the user to reach the fully extended button. The combination of the injection force and the button extension may cause hand tremors / shaking, which in turn increases discomfort when the inserted needle moves.

[0006] Automated injection devices are intended to make it easier for patients to self-administer injection treatments. Current treatments delivered by self-administered injections include drugs for diabetes (both insulin and the new class of GLP-1 drugs), migraine, allergies, hormone therapy, drugs for anticoagulation, etc. Automated injection devices can be used to deliver a single dose of a specific life-saving drug. For example, they are often prescribed to people at risk of anaphylaxis. They are also often used in the military to protect personnel from chemical warfare agents. Alternatively, autoinjectors are used, for example, to administer drugs to people suffering from multiple sclerosis, rheumatoid arthritis, anemia, according to a prescribed treatment schedule.

[0007] An autoinjector is a device that fully or partially replaces the actions involved in parenteral drug delivery from a standard syringe. These actions can include removal of the protective syringe cap, insertion of the needle into the patient's skin, injection of the drug, removal of the needle, needle shielding, and prevention of reuse of the device. This overcomes many of the disadvantages of manual devices. The force required by the user / button extension, hand tremors, and the likelihood of delivering an incomplete dose are reduced. Triggering can be accomplished by a number of means, such as a trigger button, or the action of the needle reaching its injection depth. In some devices, the energy to deliver the liquid is provided by a spring.

[0008] An autoinjector can be a disposable or single-use device that is used only to deliver a single dose of a drug and must be discarded after use. Other types of autoinjectors can be reusable. Usually, they are arranged so that the user can load and remove a standard syringe. Reusable autoinjectors can be used to perform multiple parenteral drug deliveries, but the syringe is disposed of after being consumed and removed from the autoinjector. The syringe can be packaged with additional components to provide additional functionality.

[0009] In a typical scenario, the disease can be treated by the patient himself, for example, by injecting the drug dosage daily, weekly, bi - weekly, or monthly using an auto - injector.

[0010] The correct administration and termination of the drug are important for the safety and efficacy of the drug (pharmaceutical safety monitoring). Failures in user - administered dosages can be minimized by monitoring the injection device and the application time. Typical patient failures are as follows: 1. The user may forget the correct due date of his next injection. This is especially true for drug treatment intervals longer than one day, for example, twice a week, every other day, bi - weekly, etc., or for intervals specific to the treatment, such as twice in the first week, every other day in the second week, and then intervals of 2, 2, 3 in the third week, etc. 2. The user may take too much time between removing the auto - injector cap and performing the injection, which may cause the needle to clog and / or the device to stop working. 3. The user does not perform the holding time (also known as the "dwell time") after the injection is completed. SUMMARY OF THE INVENTION PROBLEM TO BE SOLVED BY THE INVENTION

[0011] The present disclosure describes a reusable add - on device suitable for use with a single - use auto - injector, which can record the injection history, monitor the dosage administration, and assist the patient in performing the injection correctly and on time. MEANS FOR SOLVING THE PROBLEM

[0012] The first aspect provides a supplementary device configured to be attached to a drug delivery device, the supplementary device comprising: a first means adapted to mechanically couple the supplementary device to the dosage selector of the drug delivery device; a second means adapted to select a dosage to be delivered by a drug delivery device; a third means adapted to mechanically couple the second means to the first means such that a dosage selection made using the second means generates a torque that is transmitted to the first means via the third means; a sensor configured to output a signal indicative of the generated torque; an electronic circuit configured to receive the signal output from the sensor and determine a selected dosage based on the signal comprising.

[0013] The electronic determination of the selected dosage has the advantage of being further processed, for example, by an external electronic device such as a smartphone or computer, in particular a mobile computer such as a tablet PC or laptop PC, or an electronic drug injection assistance device. Further processing can include, for example, displaying the selected dosage on an external device for information, or comparing the determined selected dosage with a prescribed dosage and notifying the user of a deviation of the selected dosage from the prescribed dosage. Furthermore, the determined and selected dosage can be stored for later processing or evaluation. The auxiliary device can be implemented with fewer components, reducing technical complexity and thus production costs. Another advantage is reusability, which means that the auxiliary device can be designed to be used with several drug delivery devices. The first means can also be designed to be used with different drug delivery devices. For example, the first means can be made applicable to the type of drug delivery device for which the auxiliary device is to be used. The only requirement is that the drug delivery device needs to be designed for dosage selection and have a dosage selector to which the first means can be mechanically coupled.

[0014] The second means is further applied to trigger the release button of the drug delivery device in order to inject the selected dosage, and the third means is further applied to transmit the compressive force applied to the second means for injection to the release button. For example, the second means can include a button for activating the release button of the drug delivery device. When the user presses this button, it triggers the release button of the drug delivery device because the compressive force applied by the user to the button is transmitted to the release button by the third means.

[0015] The auxiliary device can further include a spring that forces the second means to its initial position, in which case no compressive force is applied on the release button of the drug delivery device. Forcing the second means to its initial position can be processed, for example, by an electronic circuit for detecting the end of injection.

[0016] In an implementation form, the third means can include at least one spring for torque transmission. One end of at least one spring can be fixedly connected to the second means, and the other end can be arranged to apply a force to the sensor when torque is generated by the second means. The electronic circuit can receive the measurement of the force as a signal output from the sensor and be configured to determine the selected dosage based on the measurement of the force.

[0017] In another implementation form, the third means can include one spring for torque transmission, both ends of the spring can be fixedly connected to the second means, and the spring can be formed to apply a force to the sensor when torque is generated by the second means. The electronic circuit can receive the measurement of the force as a signal output from the sensor and be configured to determine the selected dosage based on the measurement of the force.

[0018] In yet another implementation form, the third means can include a sensor, and the sensor can include at least one element made of a quantum tunneling composite material. A change in torque generated when a dosage selection is made can then cause a change in the resistance of at least one element made of the quantum tunneling composite material. The electronic circuit can be configured to receive the change in resistance as a signal output from the sensor and determine the selected dosage based on the received change in resistance.

[0019] In yet another implementation form, the third means can include a connecting plate, a sensor wheel, and a pin that is fixedly connected to the second means and extends through a bearing portion in the wheel to the release button of the drug delivery device, so that the pressure applied to the second means is transmitted to the release button by the pin. The bearing portion can include an anti-rotation lock so that the rotation of the pin is transmitted to the wheel. The wheel can be further connected to the connecting plate so that the rotation of the second means is transmitted to the wheel. The wheel can be connected to the connecting plate so that the rotation of the wheel is restricted, and the wheel can include at least two bendable spokes, and at least one of the spokes includes a sensor element applied to measure the bending of at least one spoke. The electronic circuit can be configured to receive the measured bending as a signal output from one or more sensor elements and determine the selected dosage based on the received bending measurement. The sensor element can be made of one of the following sensor materials in combination with the wheel material: a quantum tunneling composite material combined with a rubber wheel; a force-sensing resistance material combined with a plastic wheel; a strain gauge sensor material combined with a plastic or metal wheel.

[0020] The electronic circuit of the auxiliary device can be configured to process the received signal output from the sensor by performing a peak measurement of the signal output indicating the operation of the second means and counting the measured peaks in order to determine the selected dosage. The peak can be generated particularly during the selection of the dosage, for example, when the user dials in the desired dosage. The electronic circuit can then "count the clicks" via the peak measurement and derive the selected dosage from the counted peaks.

[0021] The second means can include a printed circuit board with an electronic circuit and a battery for supplying the electronic circuit of the printed circuit board and the sensor. The printed circuit board and the battery can be formed, for example, so as to be arranged together as a batch within the second means, and the second means can be designed as a knob or cap that covers the printed circuit board, the battery, the third means, and at least partially the first means.

[0022] The electronic circuit can include a communication circuit configured to communicate with an external electronic device. The communication circuit can include, for example, a wireless unit for transmitting data to and / or receiving data from one or more external devices.

[0023] The electronic circuit can be configured to transmit the determined and selected dosage and / or receive data via the communication circuit. For example, the determined and selected dosage can be transmitted wirelessly, via, for example, a Bluetooth® connection, to the user's computer or smartphone.

[0024] The auxiliary device can be applied to detect a mechanical connection to a dosage selector of a drug delivery device and, when detected, supply electrical energy to an electronic circuit. For example, the first means can include a switch that can be activated when the first means is connected to the dosage selector of the drug delivery device, particularly when the first means is clipped onto the dosage selector. Activation of the switch then connects the battery and the electronic circuit, thus enabling power to be supplied to the electronic circuit and allowing it to operate.

[0025] The auxiliary device can further include a display unit, such as an LCD (liquid crystal display) or an electronic ink display. The electronic circuit can be configured to control the display unit such that the selected dosage is displayed on the display unit.

[0026] The electronic circuit can include a processor and at least one memory. The processor can be configured to store information regarding the selected dosage and / or the last injection operation performed in the memory when it is determined that an injection has been performed using the drug delivery device. The information can include at least a time stamp associated with the last injection operation performed.

[0027] A second aspect provides a system including the auxiliary device of the first aspect and a drug delivery device. The drug delivery device can be a powered auto-injector. The dosing mechanism of the powered auto-injector uses a pre-compressed spring as a power source.

Brief Description of the Drawings

[0028]

Figure 1

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DETAILED DESCRIPTION OF THE INVENTION

[0029] In the following, embodiments of the present disclosure will be described with reference to an autoinjector. However, the present disclosure is not limited to such applications, and can be similarly well implemented using an injection device that releases other drugs, or using other types of drug delivery devices such as syringes, pre-filled syringes, needleless injectors, and inhalers.

[0030] The injection device 10 according to the embodiments will next be described with reference to FIGS. 1A and 1B. In some embodiments, the injection device 10 is a single-use autoinjector 10. The autoinjector 10 has a proximal end P and a distal end D. The proximal end P is oriented towards the patient's injection site during injection, while the distal end D is oriented away from the injection site.

[0031] The autoinjector 10 includes a body 9 and a cap 12 (also referred to herein as an outer needle cap or ONC 12). The body 9 includes an outer housing 11. The outer housing 11 is an elongated tube. The outer housing 11 includes a cartridge holder, or syringe holder (not shown), which supports a cartridge or syringe 18 containing a liquid drug 16. This description will hereinafter refer to the cartridge 18 supported by a cartridge holder (not shown). The cartridge 18 is shown in FIG. 1B by a dashed line.

[0032] The outer housing 11 also houses a dosing mechanism (not shown) for dosing the drug 16 during injection.

[0033] The hollow needle 17 is in communication with the internal volume of the cartridge 18 and serves as a conduit for the liquid drug 16 during injection. The needle 17 and the cartridge 18 are in fixed positions relative to each other and to the body 9. A stopper, plunger, piston, or plug 14 is movable within the cartridge 18 to expel the drug contained within the cartridge 18 through the needle 17 under the operation of the dosing mechanism.

[0034] The dosing mechanism is mechanically coupled to the piston 14 of the cartridge 18. The dosing mechanism is configured to axially move the piston proximally along the cartridge 18 to dose the medicament 16 through the needle 17. The dosing mechanism includes components that cooperate to apply a force to the piston 14 in response to an actuation input made by the user. Here, the actuation input that triggers the application of force to the piston 14 is received by the dose dispensing button 13 located at the distal end of the auto-injector 10. The dosing mechanism is mechanically coupled to the dosing button 13.

[0035] The body 9 further includes a dose selector 23 at the distal end of the outer housing 11. The dose selector 23 allows the user to manually select the dose to be injected by rotating it in the clockwise direction. An internal mechanism (not shown) is mechanically coupled to the dosing mechanism to adjust to inject the selected dose.

[0036] The body 9 also includes a cap support 19 at the proximal end of the outer housing 11. The cap support is concentric with the outer housing 11 and can have a smaller diameter. The cap support 19 extends from the proximal end of the housing 11. The ONC 12 is received on the cap support 19 to close the proximal end of the body 9 and cover the needle 17. The ONC 12 includes a cylindrical wall 21 and an end wall 22. As shown in Figure 1A, when using the ONC 12 located on the body 9, the inner surface of the cylindrical wall 21 is in firm adjacent contact with the outer surface of the cap support 19 so as to be held in the attached position.

[0037] Before injecting the medicament 16, the user selects the dosage to be injected via the dosage selector 23. To inject the medicament 16, the ONC12 is removed from the device 10 by the user and placed in the configuration shown in FIG. 1B. Next, the proximal end of the auto-injector 10 is placed against the injection site of the patient, who may be the user or another person. The user then activates the dosing button 13. This causes the dosing mechanism to force the piston 14 to eject the medicament from the cartridge 18 through the needle 17 into the patient's injection site.

[0038] The cartridge 18 is transparent, and a window 15 is provided in the housing 11 in alignment with the cartridge 18 so that the medicament 16 contained within the cartridge 18 is visible. The user of the auto-injector can determine by inspection whether the entire amount of the medicament 16 has been discharged from the cartridge 18 during the injection.

[0039] A label is provided on the housing 11. The label contains information 100 regarding the medicament contained within the injection device 10, including information that identifies the medicament. The information 100 that identifies the medicament can be in text form. The information 100 that identifies the medicament can also be in color form. The information 100 that identifies the medicament can also be encoded into a barcode, QR code, or the like. The information 100 that identifies the medicament can also be in the form of a black and white pattern, a color pattern, or shading.

[0040] FIG. 2 is a schematic view of an embodiment of an auxiliary device 50 releasably attached to the injection device 10 of FIG. 1. The auxiliary device 50 includes a carrier interface 51 configured to be clamped onto the dosage selector 23 of the injection device 10 of FIG. 1 so as to be mechanically coupled to the dosage selector 23 such that rotation of the interface 51 is transmitted to the dosage selector 23. The auxiliary device 50 further includes a dial knob 52 for dosage selection. The dial knob 52 at least partially overlaps the carrier interface 51.

[0041] Figure 3 is a cutaway view of a first embodiment of an auxiliary device 50 showing the internal mechanism for dose selection. The carrier interface 51 is clamped onto the dose selector 23 of the injection device. The metal spring 53 is mounted on a printed circuit board (PCB) 54 that includes an electronic circuit and sensors to effect torque transmission of the dial knob 52 and to define its reset position. A battery 55 for supplying the electronic circuit of the PCB 54 is disposed between the PCB 54 and the inside of the dial knob 52. Two guides 56, 57 are included outside the interface 51 as can be seen in Figure A. The guides 56, 57 are provided for the dial knob 52, which provides two functions, namely dose selection by rotation about the axis of the body 9 and injection by depressing to the release button 13 of the injection device. The guide 57 prevents damage to the sensor and / or the spring 53 when the device end stop is reached and defines the reset position of the dial knob 52. The guide 56 prevents overwinding of the dial knob 52. A further spring 58 is disposed between the carrier interface 51 and the dial knob 52 to bias the dial knob 52 to the reset position.

[0042] Figure 4 shows a perspective view of an implementation form including two springs 53, 53' and arranged on the PCB 54. Both springs 53, 53' are welded to the PCB 54 at one end 53''. The other ends of the springs 53, 53' are arranged on the sensor element 59 on the PCB 54 and are freely movable. The end stops 53''' limit the movement of the freely movable spring ends in their respective directions. When the user rotates the dial knob 52 to select a dosage (clockwise), or cancel the selection, or correct the selected dosage (counterclockwise), the force for setting the dial is applied to the springs 53, 53' via cams 51', 51'' provided in the dial knob 52 (Figure 5), which causes the movement of the freely movable spring ends on the sensor element 59. The rotation of the PCB 54 is prevented by the anti-rotation lock 54'. The movement of the spring ends is limited by the end stops 53''' arranged on the sensor element 59. The movement of the spring ends on the sensor element 59 can generate a sensor signal, which is detected and processed by the electronic circuit of the PCB 54 to determine the selected dosage, which will be described later with reference to Figure 16.

[0043] Figure 6 is a perspective view of another implementation form including one spring 53'''' and arranged on the PCB 54. The two ends of the spring 53'''' are both welded near the opposite edges of the PCB 54. The spring 53'''' contacts two sensor elements 59' welded to the PCB 54 on one of its sides. One sensor element is provided to detect the counterclockwise rotation of the dial knob 52 (for example, when canceling the selection of the dosage, etc.), and the other sensor is provided to detect the clockwise rotation of the dial knob 52 (for example, when selecting the dosage, etc.). Both sensor elements 59' are arranged on different sides of the spring 53''''.

[0044] FIG. 7 shows two cutaway views of the first embodiment where the dosage selection, or dial knob 52, is in two different states. The upper figure shows the unused state, or the state of setting or selecting the dosage, and no pressure is applied to the dial knob 52. The lower figure shows the injection state when the dial knob 52 is pushed down.

[0045] Before continuing with the description of further embodiments, the determination of the selected dosage and injection by the electronic circuit of the PCB 55 will be described with respect to the figure of FIG. 16, which shows an exemplary progression of sensor signals generated during dial setting or selection of the dosage using the auxiliary device 50 and during injection of the selected dosage. Using the auxiliary device 50 together with the injection device 10 is initiated by attaching the auxiliary device 50 onto the injection device button 23 provided for dosage selection. The auxiliary device 50 can automatically detect the attachment, for example, by a microswitch arranged within and activated when attached to the carrier interface 51. This detection can trigger the power supply 55 of the electronic circuit of the PCB 54. The user can then check the initial unit position to set the absolute value, especially the "0" dosage selection. The auxiliary device 50 can then be used at any time thereafter. The user can then select or dial set the desired dosage to be injected by the injection device 10, for example, by rotating the dial knob 52, such as in the clockwise direction. A clockwise rotation generates a sensor signal corresponding to the sensor measurement of the movement of the free ends of the springs 53, 53' of the auxiliary device 50, as described above. The measurement usually includes peaks, such as voltage peaks of the measured voltage, corresponding to the clicks generated by the user's dosage selection, as shown in the figure of FIG. 16. By counting these peak measurements, the electronic circuit can determine the selected dosage. When the user presses down the dial knob 52, the springs 53, 53' then move forward towards the release button 13 and are pressed onto the release button 13, which activates the injection. At the same time, the freely movable end portions of the springs 53, 53' are pressurized by pressing the dial knob 52 onto the sensor element 59, and the sensor element 59 can detect this pressure and generate a strong signal greater than the peak, and this signal is further detected by the electronic circuit as the start of the injection. The correct end of the injection position or time can be detected by the reset force (progress of reset) measurable by the sensor element 59.

[0046] Figure 8 is a perspective view of a second embodiment of the auxiliary device 60 releasably attached to the injection device 10 of FIG. 1. The auxiliary device 60 includes a carrier interface 61 configured to be mechanically coupled to the dose selector 23 of the injection device 10 of FIG. 1, in particular clamped onto the dose selector 23 such that rotation of the interface 61 is transmitted to the dose selector 23. The auxiliary device 60 further includes a dial knob 62 for dose selection and an injection button 63. Inside the device 60, a PCB 64 and a battery 65 as a power source for the electronic circuit of the PCB 64 are arranged (dashed lines in FIG. 8). The sensor 66 is made of a quantum tunneling composite (QTC) material.

[0047] Figure 9 is a perspective view of the PCB 64 with the QTC component used as the sensor 66. The QTC component 66 includes two blades 66''' arranged opposite to each other. The blades 66''' can include electrical connection points 66', 66'' for connection to the electronic circuit of the PCB 64. The surface resistance of the QTC component between the connection points 66', 66'' is affected by the pressure applied to the blades 66'''. The pressure is applied by the dial knob 62 rotated by the user for dose selection. The knob 62 transmits a torque change to the sensor 66, in particular to the blades 66'''. The change in resistance between the connection points 66', 66'' can be processed and detected, for example, by the circuit shown in FIG. 10 to determine the selected dose: The microcontroller can be configured to detect the reference resistance Rref between the points 66', 66'' and the voltage U divided by a voltage divider circuit including the QTC component resistance.

[0048] FIG. 11 is a perspective view of an alternative implementation of the second embodiment, and the PCB with the electronic circuit can be arranged at an angle of approximately 90° with respect to the direction of the forcer 67. The dial knob 62', shown partially transparent, is formed to directly apply pressure to the QTC sensor 66 when rotated as the user selects or dials a dosage to indicate the distal end of the injection device with the release button 13 and the dosage selector 23. The forcer 67 transmits the pressure applied on the release button 13 at the axis of the body 9 to initiate the injection. The QTC sensor 66 can include several surface resistances represented by a plurality of electrical connection points. All the resistances can be connected in parallel, for example, by the electronic circuit of the PCB, such that the lowest surface resistance has a relatively large influence on the total resistance of the parallel connection.

[0049] FIG. 12 shows two cutaway views of the embodiment from FIG. 8 with the injection button 63 in two different positions. The upper figure shows the unused state, or the state of dialing or selecting a dosage, with no pressure applied to the injection button 63. The lower figure shows the injection state when the injection button 63 is depressed. In this state, the pressure applied to the injection button 63 is transmitted to the release button 13 of the injection device via the battery 65, the PCB 64, the QTC sensor 66, and the forcer 67.

[0050] Figure 13 is a cutaway view of a third embodiment of an auxiliary device 70 detachably attached to the injection device 10 of Figure 1. The auxiliary device 70 includes a carrier interface 77 configured to be mechanically coupled to the dose selector 23 of the injection device 10 of Figure 1, and in particular to be clamped onto the dose selector 23, such that rotation of the interface 77 is transmitted to the dose selector 23. The auxiliary device 70 further includes a dial knob 71 for dose selection. Within the device 70, a PCB 72 and a battery 73 as a power source for the electronic circuitry of the PCB 72 are disposed. An injection torque pin 74 is provided to transmit the pressure applied onto the dial knob 71 along the shaft 76 to the injection release button 13. The injection torque pin 74 extends through a clutch coupling plate that is part of the carrier interface 77 and a sensor wheel 75 disposed within the clutch coupling plate.

[0051] The sensor wheel 75 and the clutch coupling plate of the carrier interface 77 are shown in more detail in Figure 14. The wheel 75 has at least two spokes 79 and a central bearing portion 78 through which the injection torque pin 74 can extend. The central bearing portion 78 includes an anti-rotation lock 78' that prevents rotation of the pin 74 within the bearing portion and ensures that the torque applied to the pin 74 by the dial knob 71 is transmitted to the spokes 79 and the wheel 75. The outer contour of the wheel 75 includes teeth 75' that mate with corresponding teeth on the inside of the carrier interface 77. The teeth can be implemented for a permanent freely operating interface to the dose selector 23 (the teeth are more or less necessary).

[0052] At least one of the spokes 79 can be used to implement a sensor element. The implemented sensor element detects the bending of the spoke 79. The sensor element can be implemented in various combinations of different sensor techniques and different sensor wheel materials. The combinations can be, for example, a QTC material combined with a rubber wheel; a force sensing resistor material combined with a plastic wheel; a strain gauge sensor material combined with a plastic or metal wheel.

[0053] Depending on the combination of the sensor technique and the sensor wheel material, the design of the wheel with the implemented sensor element may vary. The spokes of the wheel 75 are flexible and bend when torque is applied to the wheel 75 when the rotation of the wheel 75 is prevented. A wheel 75 with specially designed spokes 79' is shown in FIG. 15. The spoke 79' includes a recess in which the sensor elements R1, R2 are disposed.

[0054] The tapering of the spoke 79' caused by the recess allows for greater bending of the spoke 79', as seen in the left figure of FIG. 15. When the dosage is dialed, for example, when the user selects the dosage by rotating the dial knob 71 clockwise, or when the user corrects the selected dosage by rotating the dial knob 71 counterclockwise, torque is transmitted from the dial knob 71 to the wheel 75 via the injection torque pin 74, which causes the bending of the spoke 79', as shown in the left and right figures of FIG. 15. When no torque is applied to the wheel 75, it is in a free state, as shown in the central left figure, and the spoke 79' does not bend. The bending of the spoke 79' activates the sensor elements R1, R2, which can be measured by the electronic circuit of the PCB 72. The reset force (return to the free state) of the wheel 75 depends on several parameters, such as the wheel material, design, and reaction force of the spoke 79' in particular.

[0055] The injection device can be at least partially held within the auxiliary device as disclosed herein, but nevertheless can be removed from the auxiliary device, for example, when the injection device becomes empty and needs to be replaced. The injection device and the auxiliary device can include an alignment configuration that cooperates such that the auxiliary device is reliably and correctly oriented and positioned relative to the injection device. For example, the injection device and the auxiliary device can be releasably fixed together using a bayonet fitting, in which case the injection device has a protrusion on the housing and the auxiliary device has a corresponding groove for receiving the protrusion.

[0056] Figure 17 is a block diagram of the electronic circuit 100 of the auxiliary device. The electronic circuit 100 includes a processor 101, a memory 102 that stores an operating system for the processor 101, and software 104 that processes sensor signals and determines a selected dosage from the processed sensor signals, as well as data transmission and reception. The processor 101 controls a communication circuit 106, which is a wireless unit in particular, configured to transmit and / or receive information wirelessly with another device. Such transmission can be based on, for example, wireless transmission or optical transmission. In some embodiments, the wireless unit is a Bluetooth transceiver. Alternatively, the wireless unit can be replaced or supplemented by a wired unit configured to transmit and / or receive information in a wired connection with another device, for example, via a cable or fiber connection. When data is transmitted, the unit (value) of the data transmitted can be defined explicitly or implicitly. For example, in the case of an insulin dosage, international units (IU) can always be used, and in other cases, the units used can be transmitted explicitly, for example, in a coded form. The data transmitted can also include a time stamp associated with the injection.

[0057] The battery 105 supplies power to the processor 101 and other components by the power supply 103. The attachment of the auxiliary device to the injection device can be detected by a sensor or a microswitch that is automatically activated, which can be used as a wake-up or switch when triggered. Therefore, the auxiliary device can automatically turn on and start operating when attached to the injection device. Similarly, when the auxiliary device is removed from the injection device, the power can be automatically turned off to save the battery power.

[0058] In operation, the processor 101 is configured by software 104 to receive and process signals output by one or more sensors 108 of an auxiliary device, such as those shown in FIG. 16. The processor 101 can count the peaks of the sensor signals and derive the dosage selected by the user from the counted peaks. For example, when the user rotates the dial knob of the auxiliary device, the processor 101 can multiply the number of counted peaks corresponding to one click by the dosage unit. The processor 101 can also be configured to detect the start and end of an injection from the sensor signal. As described above with reference to FIG. 16, when the injection button is pressed, the output sensor signal can clearly indicate the start of the injection, for example, by a large peak measurement. When the processor 101 detects such a signal, it can generate a timestamp and store it in the memory 102 together with the determined and selected dosage. Further, the end of the injection can be detected by the processor 101, and the timestamp can be stored in the memory 102. After the injection, the processor 101 can be configured to transmit the stored information regarding the selected dosage of the drug and / or the use of the injection device via the communication circuit 106 to an external electronic device, such as a smartphone or a computer. This information can also be displayed on the display 107 used by the user of the injection device. The information can be processed by the auxiliary device itself or at least partially provided to another device (e.g., a blood glucose monitoring system or a computing device).

[0059] Processor 101 can be further configured to record the user's injection history. The injection device can be a single-use auto-injector, while the auxiliary device is reusable and can be configured to be removed from the used syringe and attached to a new syringe. The processor 101 of the auxiliary device can have an internal clock to generate a timestamp associated with the injection event. The clock can be a relative clock or an absolute clock. The auxiliary device is configured to communicate with an external device via a wireless unit 106, and the external device can provide absolute time.

[0060] The terms "drug" or "medication" are used synonymously herein and describe a pharmaceutical formulation that includes one or more active pharmaceutical ingredients or their pharmaceutically acceptable salts or solvates, optionally together with a pharmaceutically acceptable carrier. An active pharmaceutical ingredient ("API") is, in the broadest sense, a chemical structure that has a biological effect on a human or animal. In pharmacology, a drug or medication is used to treat, cure, prevent, or diagnose a disease or otherwise to improve physical or mental well-being. A drug or medication can be used for a limited duration or, in the case of a chronic disorder, periodically.

[0061] As described below, a drug or agent can include at least one API or a combination thereof in various types of formulations for the treatment of one or more diseases. Examples of APIs include small molecules having a molecular weight of 500 Da or less, polypeptides, peptides, and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes), carbohydrates and polysaccharides, and nucleic acids, double-stranded or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids can be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.

[0062] A drug or medicament can be contained in a primary package or “drug container” adapted for use in a drug delivery device. The drug container can be, for example, a cartridge, syringe, reservoir, or other rigid or flexible vessel configured to provide a chamber suitable for containing one or more drugs (e.g., short-term or long-term containment). For example, in some cases, the chamber can be designed to contain the drug for at least one day (e.g., from one day to at least 30 days). In some cases, the chamber can be designed to contain the drug for about one month to about two years. The containment can be carried out at room temperature (e.g., about 20 °C) or refrigerated temperature (e.g., about -4 °C to about 4 °C). In some cases, the drug container can be or include a dual-chamber cartridge configured to separately contain in each chamber two or more components of the pharmaceutical formulation to be administered (e.g., an API and a diluent, or two different drugs). In such cases, the two chambers of the dual-chamber cartridge can be configured to allow mixing between the two or more components before and / or during dosing into a human or animal body. For example, the two chambers can be configured to be in fluid communication with each other (e.g., via a conduit between the two chambers) and, optionally, allow mixing of the two components by the user before dosing. Alternatively or additionally, the two chambers can be configured to allow mixing upon dosing of the components into a human or animal body.

[0063] The drugs or agents included in the drug delivery devices described in this specification can be used for the treatment and / or prevention of many different types of medical disorders. Examples of disorders include, for example, diabetes or complications associated with diabetes such as diabetic retinopathy, thromboembolic disorders such as deep vein thrombosis or pulmonary embolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis. Examples of APIs and drugs are those described in handbooks such as the Rote Liste 2014 (for example, but not limited to, main group 12 (antidiabetic agents) or 86 (oncological agents)) or the Merck Index, 15th edition.

[0064] Examples of APIs for the treatment and / or prevention of type 1 or type 2 diabetes or complications associated with type 1 or type 2 diabetes include insulin, such as human insulin, or a human insulin analog or derivative, glucagon-like peptide (GLP-1), a GLP-1 analog or GLP-1 receptor agonist, and its analog or derivative, dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or a mixture of any of them. As used herein, the terms "analog" and "derivative" refer to a polypeptide having a molecular structure formally derivable from the structure of a naturally occurring peptide, such as the structure of human insulin, by deletion and / or exchange of at least one amino acid residue present in the naturally occurring peptide and / or by addition of at least one amino acid residue. The added and / or exchanged amino acid residues can be any of the codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogs are also referred to as "insulin receptor ligands". In particular, the term "derivative" refers to a polypeptide having a molecular structure formally derivable from the structure of a naturally occurring peptide, for example, a molecular structure of human insulin in which one or more organic substituents (such as fatty acids) are attached to one or more of the amino acids. Optionally, one or more amino acids present in the naturally occurring peptide are deleted and / or replaced by other amino acids including non-codable amino acids, or amino acids are added including those non-codable for the naturally occurring peptide.

[0065] Examples of insulin analogs are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin in which the proline at position B28 may be replaced by Asp, Lys, Leu, Val or Ala and the Lys at position B29 may be replaced by Pro; Ala(B26) human insulin; Des(B28 - B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0066] Examples of insulin derivatives are, for example, B29 - N - myristoyl - des(B30) human insulin, Lys(B29)(N - tetradecanoyl) - des(B30) human insulin (insulin detemir, Levemir®); B29 - N - palmitoyl - des(B30) human insulin; B29 - N - myristoyl human insulin; B29 - N - palmitoyl human insulin; B28 - N - myristoyl LysB28ProB29 human insulin; B28 - N - palmitoyl - LysB28ProB29 human insulin; B30 - N - myristoyl - ThrB29LysB30 human insulin; B30 - N - palmitoyl - ThrB29LysB30 human insulin; B29 - N - (N - palmitoyl - gamma - glutamyl) - des(B30) human insulin, B29 - N - omega - carboxypentadecanoyl - gamma - L - glutamyl - des(B30) human insulin (insulin degludec, Tresiba®); B29 - N - (N - lithocholyl - gamma - glutamyl) - des(B30) human insulin; B29 - N - (ω - carboxyheptadecanoyl) - des(B30) human insulin and B29 - N - (ω - carboxyheptadecanoyl) human insulin.

[0067] Examples of GLP-1, GLP-1 analogs, and GLP-1 receptor agonists include, for example, lixisenatide (Lyxumia®), exenatide (exendin-4, Byetta®, Bydureon®, a 39-amino acid peptide produced by the salivary gland of the Gila monster), liraglutide (Victoza®), semaglutide, taspoglutide, albiglutide (Syncria®), dulaglutide (Trulicity®), r exendin-4, CJC-1134-PC, PB-1023, TTP-054, langlenatide / HM-11260C, CM-3, GLP-1 eligine, ORMD-0901, NN-9924, NN-9926, NN-9927, nodexen, viadorl-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, exenatide-XTEN, and glucagon-Xten.

[0068] Examples of oligonucleotides include, for example, mipomersen sodium (Kynamro®), a cholesterol-lowering antisense therapeutic agent for the treatment of familial hypercholesterolemia.

[0069] Examples of DPP4 inhibitors include vildagliptin, sitagliptin, denagliptin, saxagliptin, and berberine.

[0070] Examples of hormones include pituitary hormones or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (folitropin, lutropin, chorionic gonadotropin, menotropin), somatropine (Somatropin), desmopressin, terlipressin, gonadorelin, tryptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0071] Examples of polysaccharides include glucosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin or ultra-low molecular weight heparin or their derivatives, or sulfated polysaccharides such as the above-mentioned polysaccharides in poly-sulfated form, and / or their pharmaceutically acceptable salts. An example of a pharmaceutically acceptable salt of poly-sulfated low molecular weight heparin is enoxaparin sodium. Examples of hyaluronic acid derivatives are hyaluron G-F20 (Synvisc (registered trademark)), sodium hyaluronate.

[0072] As used herein, the term "antibody" refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments that retain the ability to bind to an antigen. Antibodies can be polyclonal antibodies, monoclonal antibodies, recombinant antibodies, chimeric antibodies, deimmunized or humanized antibodies, fully human antibodies, non-human (e.g., murine) antibodies, or single-chain antibodies. In some embodiments, the antibody has effector function and is capable of fixing complement. In some embodiments, the antibody has a reduced or no ability to bind to an Fc receptor. For example, the antibody can be an isotype or subtype, an antibody fragment or a mutant having a mutation or deletion in the Fc receptor binding region that does not assist in binding to the Fc receptor. The term antibody also includes antigen-binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or dual variable domain antibody-like binding proteins (CODV) having a crossover binding region orientation.

[0073] The term "fragment" or "antibody fragment" refers to a polypeptide (e.g., an antibody heavy chain and / or light chain polypeptide) derived from an antibody polypeptide molecule that does not include a full-length antibody polypeptide but still includes at least a portion of the full-length antibody polypeptide capable of binding to an antigen. An antibody fragment can include a cleaved portion of a full-length antibody polypeptide, but the term is not limited to such cleaved fragments. Antibody fragments useful in the present disclosure include, for example, Fab fragments, F(ab’)2 fragments, scFv (single-chain Fv) fragments, linear antibodies, single-specific or multispecific antibody fragments, such as bispecific, trispecific, tetra-specific, and multispecific antibodies (e.g., diabodies, tribodies, tetrabodies), monovalent or multivalent antibody fragments, such as divalent, trivalent, tetravalent, and multivalent antibodies, minibodies, chelated recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and VHH-containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

[0074] The term "complementary determining region" or "CDR" refers to short polypeptide sequences within the variable regions of both the heavy and light chain polypeptides that primarily play a role in mediating specific antigen recognition. The term "framework region" refers to the amino acid sequences within the variable regions of both the heavy and light chain polypeptides that are not CDR sequences and primarily play a role in maintaining the proper arrangement of the CDR sequences to enable antigen binding. The framework region itself typically does not directly participate in antigen binding, but as is known in the art, certain residues within the framework region of a particular antibody can directly participate in antigen binding or can affect the ability of one or more amino acids within the CDR to interact with the antigen.

[0075] Examples of antibodies are anti-PCSK-9 mAb (e.g., alirocumab), anti-IL-6 mAb (e.g., sarilumab), and anti-IL-4 mAb (e.g., dupilumab).

[0076] Any pharmaceutically acceptable salts of the APIs described herein are contemplated for use in a drug or agent in a drug delivery device. Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts.

[0077] Those skilled in the art will understand that modifications (additions and / or removals) of the various components of the APIs, formulations, devices, methods, systems, and embodiments described herein can be made without departing from the full scope and spirit of the disclosure, which is understood to encompass such modifications and any and all equivalent forms thereof.

Claims

1. An auxiliary device configured to be attached to a drug delivery device, comprising: a first means adapted to mechanically couple the auxiliary device to a dosage selector of the drug delivery device; a second means adapted to select a dosage to be delivered by the drug delivery device; a third means adapted to mechanically couple the second means to the first means such that a dosage selection made using the second means generates a torque transmitted to the first means via the third means; a sensor configured to output a signal indicative of the generated torque; an electronic circuit configured to receive a signal output from the sensor and, based on the signal, determine a selected dosage, the electronic circuit including a communication circuit configured to communicate with an external electronic device, and via the communication circuit, transmit the determined and selected dosage to the external electronic device The auxiliary device including the above.

2. The second means is further adapted to trigger a release button of the drug delivery device to inject a selected dosage, and the third means is further adapted to transmit a compressive force applied to the second means for injection to the release button. The auxiliary device according to claim 1.

3. The auxiliary device according to claim 2, further including a spring that forces the second means to an initial position where no compressive force is applied to the release button of the drug delivery device.

4. The third means includes at least one spring for torque transmission, one end of the at least one spring being fixedly connected to the second means, and the other end being arranged to apply a force to the sensor when torque is generated by the second means. The electronic circuit is configured to receive a force measurement as a signal output from the sensor and, based on the force measurement, determine a selected dosage. The auxiliary device according to claim 1, 2, or 3.

5. The third means includes one spring for torque transmission, both ends of the spring being fixedly connected to the second means, and the spring being formed to apply a force to the sensor when torque is generated by the second means. The electronic circuit is configured to receive a force measurement as a signal output from the sensor and, based on the force measurement, determine a selected dosage. The auxiliary device according to claim 1, 2, or 3. **Claim 6** The third means includes a sensor, the sensor includes at least one element made of a quantum tunneling composite material, a change in torque generated when a dosage is selected causes a change in resistance of at least one element made of the quantum tunneling composite material, and an electronic circuit is configured to receive the change in resistance as a signal output from the sensor and determine the selected dosage based on the received change in resistance. The auxiliary device according to claim 1, 2, or 3. **Claim 7** The third means includes a connecting plate, a sensor wheel, and a pin fixed to and connected to the second means and extending through a bearing portion in the wheel to the release button of the drug delivery device. Thus, the pressure applied to the second means is transmitted to the release button by the pin. The bearing portion includes an anti-rotation lock so that the rotation of the pin is transmitted to the wheel. The wheel is further connected to the connecting plate so that the rotation of the second means is transmitted to the wheel. The wheel is connected to the connecting plate so that the rotation of the wheel is restricted. The wheel includes at least two bendable spokes, and at least one of the spokes includes a sensor element of a sensor applied to measure the bending of at least one spoke. Further, the electronic circuit is configured to receive the measured bending as a signal output from the sensor element of one or more sensors and determine the selected dosage based on the received bending measurement. The auxiliary device according to claim 1, 2, or 3. **Claim 8** The sensor element of the sensor is made of one of the following sensor materials combined with the wheel material, namely: a quantum tunneling composite material combined with a rubber wheel; a force sensing resistor material combined with a plastic wheel; a strain gauge sensor material combined with a plastic or metal wheel. The auxiliary device according to claim 7. **Claim 9** The electronic circuit is configured to process the signal output from and received by the sensor by performing a peak measurement of the signal output indicating the operation of the second means and counting the measured peak to determine the selected dosage. The auxiliary device according to any one of claims 1 to 8. **Claim 10** The second means is the auxiliary device according to any one of claims 1 to 9, including a printed circuit board having an electronic circuit, a battery for supplying the electronic circuit of the printed circuit board, and a sensor. **Claim 11** The auxiliary device according to any one of claims 1 to 10, which is applied to detect mechanical connection to a dosage selector of a drug delivery device and supply electrical energy to the electronic circuit when detected. **Claim 12** The auxiliary device according to any one of claims 1 to 11, further including a display unit, wherein the electronic circuit is configured to control the display unit so that the selected dosage is displayed on the display unit. **Claim 13** The electronic circuit includes a processor and at least one memory. The processor is configured to store, in the memory, the selected dosage and / or information regarding the last injection operation when it is determined that an injection has been performed using the drug delivery device. The information includes at least a time stamp associated with the last injection operation. The auxiliary device according to any one of claims 1 to 12. **Claim 14** A system including the auxiliary device according to any one of claims 1 to 13 and a drug delivery device.

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