Drug delivery device for reducing measurement error of dosage

Abstract

A drug delivery device (100) comprising: a housing (102, 104) including one or more bridging contacts (304); a movable dial (108) at least partially located within the housing and arranged to move relative to the one or more bridging contacts (304), the dial including a series of conductive strips (306, 310, 314) on an outer surface of the dial (108), the one or more bridging contacts (304) selectively connecting and disconnecting conductive strips (306, 310, 314) of the series of conductive strips (306, 310, 314) as the movable dial (108) moves to provide alternating electrical signals; and at least one electronic component (202, 218) configured to: detect the alternating electrical signals; determine whether the electrical signals indicate contact between the conductive strips and the bridging contacts; and determine a drug dosage programmed into the drug delivery device based on the electrical signals.

Description

Technical Field

[0001] The present invention relates to a drug delivery device, particularly an injection device, for reducing dosing errors caused by the connection of a user's body to an electrical sensor contact.

Background Art

[0002] Pen-type drug delivery devices are applied when regular injections are performed by persons who have not received formal medical training. This is becoming increasingly common among diabetic patients, and through self-treatment, such patients can effectively manage their diabetes on their own.

[0003] For good or complete blood glucose management, the dose of insulin or insulin glargine must be adjusted for each individual according to the blood glucose value to be achieved. The present invention relates to syringes, such as hand-held syringes, particularly pen-type syringes; that is, the present invention relates to syringes of a type that enable the administration of a pharmaceutical product by injection from a multi-dose cartridge. In particular, the present invention relates to such syringes in which the user can set the dose. The dose to be injected can be manually selected, for example, in the syringe, by turning the dose knob and observing the actual dose from the dose window or display of the injection device.

Summary of the Invention

Problems to be Solved by the Invention

[0004] Users who self-administer insulin typically need to administer from 1 to 80 international units. For example, in order to prevent incorrect handling of the device or to track the dose already applied, and in order to be able to monitor the dose, it is desirable to measure information related to the state and / or use of a drug delivery device, such as an injection device, such as information regarding the dose injected.

Means for Solving the Problems

[0005] A drug delivery device comprising: a housing including one or more bridging contacts; a movable dial at least partially located within the housing and arranged to move relative to the one or more bridging contacts, the dial including a series of conductive strips on the outer surface of the dial, and the one or more bridging contacts selectively connect and disconnect conductive strips of the series of conductive strips as the movable dial moves to provide an alternating electrical signal; and at least one electronic component configured to: detect the alternating electrical signal; determine whether the electrical signal indicates contact between the conductive strip and the bridging contact; and determine a programmed drug dosage within the drug delivery device, particularly an injection device, based on the electrical signal. A drug delivery device is provided.

[0006] In one or more embodiments of the drug delivery device, one or more of the following configurations can be utilized: - The signal is a digital signal; - The dial is arranged to rotate relative to the housing and the one or more bridging contacts during a dosage programming event, and / or the dial is arranged to move helically out of the housing during a dosage programming event; - The at least one electronic component includes at least one of a microcontroller, a comparator, and an analog-to-digital converter; - Detecting the alternating electrical signal by the at least one electronic component includes detecting a voltage at at least one of the series of conductive strips; - The at least one electronic component is applied to compare a voltage detected at at least one of the series of conductive strips with a threshold voltage; - The at least one electronic component is applied to compare an analog voltage detected at at least one of the series of conductive strips with a threshold voltage; - At least one electronic component is adapted to increase a dosage count when a detected voltage exceeds a threshold voltage; - At least one electronic component is adapted not to increase a dosage count when a detected voltage is less than a threshold voltage; - A series of conductive strips includes at least one power strip connected to a battery and at least one sensor strip connected to at least one electronic component; - The device includes a microcontroller, the microcontroller having a low power mode and being configured to wake up from the low power mode when an electrical signal is received; - The microcontroller is configured to wake up from the low power mode when receiving an electrical signal from an electrical connection to the conductive strip; - The device further includes a resistive element and a switch, the switch selectively connecting a resistance to at least one of the series of conductive strips based on whether the microcontroller is in the low power mode; - The resistance is selectively connected to one sensor strip or a plurality of sensor strips; - The series of conductive strips includes at least two sensor strips (306) and at least two power strips; - Programming a dosage includes dialing in a dosage; - The series of conductive strips includes at least one power strip (310) connected to a battery and at least one sensor strip (306) connected to at least one electronic component; - One or more bridging contacts (304) are not connected to an electronic component, and the bridging contacts (304) selectively connect and disconnect the power strip (310) to the sensor strip (306) as the movable dial (108) moves to provide an alternating electrical signal.

[0007] In another aspect, a method of operating a drug delivery device is provided, the method comprising: detecting an alternating electrical signal; determining whether the electrical signal indicates contact between a conductive strip and a bridging contact; and determining a programmed drug dosage within the drug delivery device, particularly an injection device, based on the electrical signal.

[0008] The method can further comprise: detecting a voltage at at least one of a series of conductive strips; and comparing the detected voltage at the at least one conductive strip with a threshold voltage.

[0009] The method can further comprise increasing a dosage count in response to determining that the detected voltage exceeds the threshold voltage.

[0010] The method can further comprise not increasing the dosage count if it is determined that the detected voltage is less than the threshold voltage, in response to determining that the detected voltage is less than the threshold voltage.

[0011] The method can further comprise entering a low power mode by a microcontroller; and activating the microcontroller from the low power mode when an electrical signal is received.

[0012] The method can further comprise connecting a resistor to at least one of a series of conductive strips in response to determining that the microcontroller is in the low power mode; and disconnecting a resistive element from at least one of a series of conductive strips in response to determining that the microcontroller has been activated from the low power mode.

[0013] In some embodiments of the present invention, one or more of the following configurations can be implemented: - The dial is arranged to rotate relative to the housing and one or more bridging contacts during a dosage programming event; - The dial is arranged to move in a helical manner so as to emerge from the housing during a dosing programming event; - The conductive strip is arranged to make electrical contact with one or more bridging contacts in a first group of relative orientations of the dial and the one or more bridging contacts, and to interrupt electrical contact with the one or more bridging contacts in a second group of relative orientations of the dial and the one or more bridging contacts, the first group being different from the second group; - The conductive strip is printed, plated, or etched on the outer surface; - The conductive strip is arranged to include a power strip connected to a potential and a sensor strip including an input to a processor; - The power strip and the sensor strip are arranged alternately around the dial; - The bridging contacts alternately couple the power strip to the sensor strip to provide a conductive path between the strips and decouple the electrical contacts; - The power strip, the sensor strip, and the bridging contacts are arranged to be able to implement a Gray code for registering the dial-set dosage; - The Gray code is a 2-bit Gray code or a 3-bit Gray code; - The dial includes a 0U detection strip located adjacent to the dosage delivery button; - The microcontroller enters a low-power mode; it is configured to start from the low-power mode when an electrical signal is received.

[0014] In one embodiment, the drug delivery device includes an electronic component that detects a voltage detected in at least one of a series of conductive strips, compares the voltage detected in the at least one conductive strip with a threshold voltage, and increases the dosage count if the detected voltage exceeds the threshold; or does not increase the dosage count if the detected voltage is less than the threshold.

[0015] The following description refers to the following figures:

Brief Description of the Drawings

[0016]

Figure 1

Figure 2

Figure 3A

Figure 3B

Figure 4A

Figure 4B

Figure 5A

Figure 5B

Figure 6A

Figure 6B

Figure 7A

Figure 7B

Figure 8

Figure 9

Figure 10

Embodiments for Carrying Out the Invention

[0017] Referring initially to FIG. 1, an external view of a drug delivery device 100 according to an embodiment of the present invention is shown. The device 100 shown in FIG. 1 is a pen-type injection device having an elongated cylindrical shape for setting and delivering a drug such as insulin. The device 100 includes a housing 102 having a first housing member 104 and a second housing member 106. A rotary dial 108 is located at a first (or proximal) end of the first housing member 104. The rotary dial 108 has substantially the same outer diameter as the first housing 104. The second housing member 106 can be removably coupled to a second end of the first housing member 104. The second housing member 106 is configured such that a needle (not shown) or a similar drug delivery device can be attached thereto. To achieve this, the second (or distal) end of the second housing member 106 can have a threaded portion 110. The threaded portion 110 can have a diameter smaller than the remaining portion of the second housing member 106.

[0018] A display mount 112 is located on the first housing member 104. A display can be supported on the display mount 112. The display can be an LCD display, a segment display, or any other suitable type of display. The display mount 112 can cover a recess (not shown) in the first housing member 104. A number of electronic components, which will be described in more detail with respect to FIG. 2, can be disposed directly below the display mount 112.

[0019] The first housing member 104 houses the drug dosage setting and delivery mechanism. The second housing member 106 houses a drug cartridge (not shown). The drug housed in the drug cartridge may be any type of medicament and preferably may be in liquid form. The drug delivery mechanism of the first housing member 104 can be configured to engage with the drug cartridge of the second housing member 106 to facilitate drug expulsion. The second housing member 106 can be removed from the first housing member 104 for inserting the drug cartridge or removing a used cartridge. The first and second housing members 104, 106 can be connected to each other in any suitable manner, for example, by a screw or bayonet connection. The first and second housing members 104, 106 can be irreversibly connected to each other such that the drug cartridge is permanently housed within the drug delivery device 100. Further, the first and second housing members 104, 106 may form part of a single housing member.

[0020] The rotary dial 108 is configured to be manually rotated by a user of the drug delivery device 100 to set the drug dosage to be delivered. (Shown in detail in FIGS. 3A, 3B, 4A, 4B) The dial 108 includes a screw thread system (not shown), whereby the dial 108 is axially displaced from the housing 102 when rotated in a first direction. The dial 108 may be rotatable in both directions or only in the first direction. Preferably, the dial 108 is rotatable in both directions and can increase (by rotating in the first direction) and decrease (by rotating in the second direction) the required dosage.

[0021] Device 100 is configured to deliver a set drug dose when the set drug dose is set by rotation of the rotary dial 108. The set drug dose is delivered, for example, when the user applies an axial force to the proximal end of the device. The rotary dial 108 can support a dose delivery button 308 that is depressed to deliver the set drug dose. In one embodiment, when the dose delivery button 308 is depressed, the dial 108 does not rotate. When the dose delivery button 308 is depressed, the dial 108 moves toward the body 104 of the device 100 and thus administers the drug.

[0022] The display 112 can be configured to display information regarding the set and / or delivered drug dose. The display 112 can further display additional information such as the actual time, the time of the last use / injection, the remaining battery capacity, one or more warning signs indicating that the dose set on the dial has not been fully administered, and / or the like.

[0023] Referring now to FIG. 2, a schematic diagram of an electrical circuit example 200 forming part of the drug delivery device 100 is shown. The circuit 200 includes a microcontroller 202, a non-volatile memory such as ROM 204, a writable non-volatile memory such as flash memory 205, a volatile memory such as RAM 206, a display 210, contacts 212 (e.g., conductive strips 306, 310 described later), and a bus 208 connecting each of these components. The circuit 200 also includes a battery 214 or some other suitable power source for providing power to each of the components, and a switch 216, which will be described in more detail later. The circuit 200 also includes additional components 218. In one embodiment, the additional component 218 is a comparator. In one embodiment, the additional component 218 is an analog-to-digital converter (hereinafter referred to as an AD converter).

[0024] Circuit 200 can be integral with device 100. Alternatively, circuit 200 can be housed within an electronic module that can be attached to device 100. Additionally, circuit 200 can include additional sensors, such as optical or acoustic sensors. Circuit 200 can include an audible alarm (not shown) that can be controlled by processor 202 to sound an alarm when a dial-set dosage is not fully dispensed.

[0025] ROM 204 can be configured to store software and / or firmware. This software / firmware can control the operation of processor 202. Processor 202 utilizes RAM 206 to execute the software / firmware stored in the ROM to control the operation of display 210. Thus, processor 202 can also include a display driver. Processor 202 utilizes flash memory 205 to store the dial-set amount of dosage and / or the amount of dosage dispensed, as will be described in more detail later. Processor 202 can be a microcontroller or a microcontroller unit.

[0026] The battery 214 can provide power to each of the components including the contact 212. The supply of power to the contact 212 can be controlled by the processor 202. The processor 202 can receive signals from the contact 212. The processor 202 can determine when the contact 212 is energized and can be configured to interpret these signals. Information can be provided to the display 210 at an appropriate time by software / firmware and the operation of the processor 202. This information can include measured values determined from signals received by the processor 202 from the contact 212. The electronic module including the circuit 200 can be embedded within the dial 108. For example, the electronic module can be embedded within the button 308, thereby eliminating the need to remove and reuse the electronic module when used with a disposable pen-type syringe or other disposable drug delivery device. The embedded electronic module can enable recording of the dosage set on the dial and delivered from the pen. This function can be valuable to a wide variety of device users as a memory aid or to support detailed logging of dosage history. It is envisioned that the electronic module can be connectable to a mobile device or the like and can be configured to enable the dosage history to be periodically downloaded from the module.

[0027] Here, with reference to FIGS. 3 to 10, an operating example of the dial 108 will be described.

[0028] FIGS. 3A and 3B show perspective views of a part of the dial 108 of the drug delivery device 100 suitable for use in the present invention. FIG. 3A shows the dial 108 with the button 308 removed. FIG. 3B shows the dial 108 together with the components around the main body 104 of the device 100 with the button 308 in place. FIGS. 4A and 4B show plan views of a part of the dial 108 of the drug delivery device 100 suitable for use in the present invention.

[0029] Dial 108 includes sleeve 302. In one embodiment, sleeve 302 is cylindrical and is arranged to rotate relative to the first member of housing 104 during dosing programming (however, it does not rotate relative to housing 104 during delivery of the dose).

[0030] In one embodiment, sleeve 302 includes conductive strips 306, 310, 314. The conductive strips can be printed, plated, or etched onto the outer surface of the movable dosing programming component 302 (this outer surface can be housed within housing 104 as in the arrangement shown in FIG. 1 when the dose is not set). For example, conductive strips 306, 310, 314 can be formed from conductive ink. For example, conductive strips 306, 310, 314 can be formed by electroplating. The resistance of conductive strips 306, 310, 314 when printed with conductive ink can be in the range of 100 Ω to 1 kΩ (depending on the ink selected). When conductive strips 306, 310, 314 are electroplated, their resistance can be in the range of 0 to 10 Ω.

[0031] Some of conductive strips 306, 310 are energizing power strips 310 that are electrically connected to a voltage source to provide a potential. The energizing power strip 310 can be electrically connected to the voltage source via a series resistor to limit the current that can flow through this circuit. The other of conductive strips 306, 310 are sensor strips 306 that are electrically connected to the input terminals of processor 202.

[0032] The sleeve 302 can include at least one power strip 310 and at least one sensor strip 306. In one embodiment, the sleeve 302 includes two or more of each of the power strip 310 and the sensor strip 306. For example, the sleeve 302 can include two power strips 310 and two sensor strips 306. In principle, the sleeve 302 can include any suitable number of conductive strips 306, 310, such as three, four, five, six, etc. each. The sleeve 302 can include the same number of each type of conductive strip 306, 310. The power strip 310 can be formed as a continuous strip. The continuous strip can be, for example, in a W shape (or a plurality of U-shaped shapes connected to each other), and the sensor strip 306 is located within the gap formed in the W shape.

[0033] The strips 306, 310 can be positioned such that a sensor strip 306 is located between each two power strips 310, and vice versa. Preferably, the conductive strips 306, 310 are separated by a non-conductive gap 316. Preferably, there is a non-conductive gap between each pair of the sensor strip 306 and the conductive strip 310. The gap 316 can be made of the same material as the sleeve 302, such as a non-conductive plastic. Alternatively, the gap 316 can be made of a suitable electrical insulating material.

[0034] In one embodiment, the sensor strip is electrically connected to the processor 202 embedded in the button 308 by the conductive contact 312. The contact 312 is located within the sleeve 302. The contact 312 is formed of a conductive material, such as metal. In one embodiment, one contact 312 is provided for each power conductive strip 310, and one contact 312 is provided for each sensor conductive strip 306. Accordingly, the number of contacts 312 can correspond to the total number of all conductive strips 306, 310. As described above, when the power strip is provided with a U-shape, a W-shape, or a continuous W-shape, the number of contacts 312 may be less than the total number of all conductive strips 306, 310. The contact 312 can be fixed to the sleeve 302 so as to be in permanent contact with each adjacent conductive strip 306, 310.

[0035] The body 104 of the device 100 includes a bridging contact 304. The bridging contact 304 is formed of a conductive material, such as metal. The bridging contact 304 is located within the body 104 adjacent to the first (proximal) end of the housing 104. The bridging contact 304 is fixed within the body 104 and is configured to enable contact between the sensor strip 306 and the power strip 310, between the sensor strip 306 and the gap 316, or between the power strip 310 and the gap 316 in response to rotation of the dial 108 and thus also the sleeve 302. The bridging contact 304 is not electrically connected to the processor 202.

[0036] Preferably, each bridging contact 304 has a contact point 304a that is narrower than the gap 316 to ensure that no signal is transmitted from the surrounding conductive strips 306, 310 when the contact point 304a contacts any non-conductive gap 316.

[0037] In one embodiment, the bridging contact 304 is formed using a metal press (e.g., using stainless steel), and three contact points 304a are formed as bumps. This manufacturing method can facilitate the provision of low-cost bridging contacts. The bump contacts 304a are formed at the ends of the cantilevered members to achieve a preload and ensure good radial contact pressure with the conductive strips 306, 310 even under worst-case tolerance conditions. The bridging contact 304 can be aligned in the rotational and axial directions within the cylindrical housing 104.

[0038] Rotation of the dial 108 selectively connects and disconnects the contacts 212 (conductive strips 306, 310) on the dosage programming component, thereby encoding the electrical signals received by the processor 202 by alternating them. The processor 202 can be implemented within any suitable electronic module including the electrical circuit 200. By turning the dial 108, and thus the sleeve 302, the bridging contact comes into contact with the conductive strips 306, 310. Contact between the sensor strip 306 and the power strip 310 via the bridging contact 304 closes the circuit between the sensor strip 306 and the power strip 310, the bridging contact 304, and the contacts 312 associated with the respective conductive strips 306, 310. Thus, a voltage is detected. This can be registered as "1" (logical high). Contact between the power strip 310 or the sensor strip 306 and the gap 316 via the bridging contact 304 opens the circuit. This can be detected as "0" (logical low).

[0039] In this way, by using the known positioning of the conductive strips 306, 310 and the gap 316, the rotation of the dial 108 and the sleeve 302 relative to the body 104 and the bridging contact 304 can be detected. Then, the known movement of the dial 108 and the sleeve 302 is converted into a dial-set dosage, which can then be stored in memory, and / or displayed, and / or transmitted to an external device as appropriate. Various methods can be used to encode the information; for example, Gray code can be used. For example, considering the number of conductive strips 306, 310, the width of each conductive strip 306, 310 and the gap 316, and the configuration of the bridging contact, etc., a periodic Gray code can be generated during operation.

[0040] Figures 3A, 3B and 4A, 4B and 5A show one embodiment including four vertical conductive strips 306, 310 (two energized power strips 310 and two sensor strips 306 arranged alternately), which is suitable for encoding a dosage of 24 units. Alternatively, or in addition to a code (e.g., numbers) printed on the sleeve 302, embodiments of the present invention use the electrical state of the conductive strips 306, 310 themselves to form an input to the microcontroller 202. The rotation of the dial 108 can be electronically encoded to identify the selected dosage value before the dosage is delivered. The simplest Gray code that can be used to count the dosage and detect the direction of rotation is a 2-bit Gray code. The embodiment shown above uses three bridging contacts 304 arranged equidistantly around the circumference of the sleeve 302. In this embodiment, the contact points 304a of the bridging contact 304 extend between two points on the cylinder body that are each 60° apart.

[0041] As shown in 2D of FIG. 5B, other arrangements are possible. For example, the conductive pattern can have a variable strip width and gap ratio and, together with the three equally spaced bridging contacts 304 as described above, form a 2-bit orthogonal signal during rotation. The black areas represent regions of conductive material (conductive strips 306, 310), and the white areas represent regions where no conductive material is deposited (gaps 316). However, there are numerous configurations of conductive strips 306, 310 and bridging contacts 304 that can generate a periodic Gray code during rotation and can thus be used to encode a desired dosage setting.

[0042] Generally, all sensor strips 306 may be of the same width or may have different widths. Alternatively or additionally, the power strips 310 can be of the same width or can have different widths. As is apparent from FIG. 5A, one of the gaps 316 may be wider than the remaining gaps. FIG. 5B shows a pattern that can be used to generate a 3-bit Gray code.

[0043] The sleeve 302 can further include a 0U detection strip 314. The 0U detection strip 314 can be located on the sleeve 302 adjacent to the dosage delivery button 308. During dosing of the dial-set dosage, the 0U detection strip is typically the last portion of the contact 212 that contacts the bridging contact 304. Thus, the 0U detection strip 314 can be provided to ensure that when the button 308 is pushed down towards the body 104 and the dial-set dosage is dispensed, this fact is registered as a separate signal. In other words, the 0U detection strip 314 is configured to not be engaged by the bridging contact 314 when the dosage has not been dispensed or has not been fully dispensed.

[0044] Figures 6A and 6B show two embodiments of the electronic circuit to be used. In both embodiments, as described above, the power strip 310 is connected to a given potential. In both embodiments, the potential of the sensor strip 306 is measured and used as an input to the microcontroller 202.

[0045] In the embodiment of Figure 6A, the sensor strip 306 is at a low voltage (with respect to the battery 214) when not connected to the power strip 310 by the bridge contact 304. When the sensor strip 306 is connected to the power strip 310 by the bridge contact 304, the sensor strip 306 reaches a potential closer to the battery 214. This higher potential is used as an input to the microcontroller 202. In the embodiment of Figure 6B, the sensor strip is at a high voltage (i.e., a potential close to the battery potential) when not connected to the power strip 310. When the sensor strip 306 is connected to the power strip 310 by the bridge contact 304, the potential in the sensor strip 306 decreases. And this lower potential is used as an input to the microcontroller 202.

[0046] Hereinafter, the present invention will be described with respect to the embodiment of Figure 6A. It will be apparent to those skilled in the art that the present invention is applicable to the embodiment of Figure 6B.

[0047] The resistor R1 (see Figure 6A) ensures that the sensor strip 306 is at a stable potential until it is connected to the power strip 310 by the bridge contact 304. Preferably, in order to limit the current drawn from the battery, the resistor R1 is as high as possible. For example, the resistor R1 can be approximately 1 MΩ. The resistor R1 can be, for example, 0.5 MΩ to 1.5 MΩ, 0.8 MΩ to 1.2 MΩ, 0.9 MΩ to 1.1 MΩ, or 1 MΩ. A relatively high value of R1, for example a value of approximately 1 MΩ, can help limit the current flowing to a user who accidentally touches the strips 306, 310, 314.

[0048] The resistance of the bridging contact 304 is preferably low, for example approximately 1 Ω. The resistance of the bridging contact 304 can be, for example, 0.5 Ω to 1.5 Ω, 0.8 Ω to 1.2 Ω, 0.9 Ω to 1.1 Ω, 1 MΩ. Thus, the resistance R1 is high compared to the resistance of the bridging contact 304. Thus, the microcontroller 202 can read the voltage in the sensor strip. Such a configuration is advantageous for reducing power consumption and thus limiting the required battery size. Preferably, the microcontroller 202 is in a low-power mode whenever the device 100 is not in use (i.e., ideally most of the time) to further conserve the battery. The microcontroller 202 preferably uses a digital signal generated by a change in potential in the sensor strip 306 to activate the microcontroller 202 from the low-power mode without consuming additional power.

[0049] When the dial 108 rotates, as described above, the sleeve 302 extends axially (spirally) outward from the body 104 of the device 100. Thereby, the conductive strips 306, 310 are exposed. Thus, the conductive strips 306, 310 may accidentally connect to each other by means other than the bridging contact 304. For example, when the user accidentally touches the sleeve 302 and the conductive strips 306, 310, the user's finger may connect the conductive strips 306, 310. If such an accidental connection occurs in the order of valid contact (i.e., the order that may be made by the bridging contact 304 when the dial 108 is rotated and thus the dose is set), such contact may cause an error in the recording of the dialed and / or dosed dose.

[0050] This situation is shown in FIGS. 7A and 7B. Preferably, the microcontroller 202 is configured to detect a value range as "1" (i.e., high potential) and to detect a value range as "0" (i.e., low potential). This is schematically shown by lines 702 and 706. Any signal exceeding the high potential value 706 is detected as high potential, i.e., "1". Any signal less than the low potential value 702 is detected as low potential, i.e., "0". The area between line 702 and line 706 is undefined.

[0051] FIG. 7A shows the read values in a situation where the dial 108 is rotated and there is no contact between the conductive strips 306, 310 and the user's finger. As described above, the resistance of the bridge contact 304 is low. Therefore, the potential at the sensor strip 306 when there is no contact between the sensor strip 306 and the power supply strip 310 through the bridge contact 304 is close to 0V (i.e., less than the low potential line 702). Therefore, the potential at the sensor strip 306 when there is contact between the sensor strip 306 and the power supply strip 310 through the bridge contact 304 is close to the battery voltage 708 (i.e., exceeding the high potential line 706).

[0052] FIG. 7B shows the reading values in a situation where the dial 108 is rotated and contact occurs between the conductive strips 306 and 310 and the user's finger. The contact between the conductive strips 306 and 310 and the user's finger may occur in addition to any circuit formed by the bridging contact. The resistance of the user's finger is higher than the resistance of the bridging contact 304. The influence on the sensor strip 306 when the bridging contact 304 connects the sensor strip 306 and the power strip 310 is negligible. However, the influence on the potential of the sensor strip 306 when the bridging contact 304 does not connect the sensor strip 306 and the power strip 310 is so large that it cannot be ignored, and the potential between point 712 and point 714 enters the undefined region between line 702 and line 706. This may introduce a measurement error if the undefined value is interpreted as not being less than the low potential line 702 (logical low, "0") and thus being a high potential value (logical high, "1").

[0053] To mitigate the above-described problem, the circuit 200 is configured to detect the potential change caused by the conductive strips 306 and 310 connected by the bridging contact 304 and reject any potential change caused by the conductive strips 306 and 310 connected by the user's finger.

[0054] In the embodiment shown in FIG. 8, a comparator 218 is provided. The comparator has two analog inputs (shown as + and - in FIG. 8) and one digital output. The sensor strip 306 is connected to the first input of the comparator. The second input of the comparator is connected to a constant reference voltage 220. This reference voltage can be set to a value close to the high potential value 706. The digital output of the comparator becomes logical high ("1") only when the potential in the sensor strip 306 is higher than the reference value (for example, exceeds the reference value set to be close to the high potential value 706). Otherwise, the output of the comparator is logical low ("0").

[0055] This makes it possible to distinguish the situations shown in FIGS. 7A and 7B. In the situation of FIG. 7A, the output of the comparator is "1" every time. However, in FIG. 7B, the output of the comparator becomes "1" only outside points 712 and 713, that is, only when the signal 704 from the sensor strip 306 rises beyond not only the low potential value 702 but also the high potential value 706. Generally, the tolerance of the comparator may be much smaller than the width of the undefined region between line 702 and line 706. In addition, since a reference value can be set, the comparator enables high flexibility (for example, compared to an embodiment where the low / high potential values 702, 706 are characteristics of a specific microcontroller used).

[0056] In the case of a 2-bit rotary encoder (i.e., the sleeve 302 having two sensor strips 306, two power strips 310 and a 0U strip 314 as described above), it is preferable to use one of three comparators for each input to the microcontroller 202. The first and second comparators are associated with two encoder lines (the sensor strip 306 and the power strip 310), and the third comparator is associated with the 0U strip 314. This arrangement is beneficial for reducing the risk of connecting each of the respective sensor strip 306, power strip 310 or 0U strip 314 with a user's finger.

[0057] A further advantage of the comparator as described is its digital output, which can be used as a digital input and wake-up signal to the microcontroller 202 when the microcontroller 202 is in a low power mode.

[0058] In one embodiment, an AD converter (not shown) can be used instead of the comparator. The AD converter can be used to convert the voltage of the sensor strip 306 from an analog signal to a digital signal. Then, the digital signal can be compared with a software-set threshold value. In this way, the AD converter reproduces the behavior of an external electronic comparator in software. Since many microcontrollers include a built-in AD converter, this arrangement eliminates the need for additional components such as an additional integrated circuit to implement the comparator of the above-described embodiment. Therefore, this solution is particularly suitable for devices where cost is a concern.

[0059] In order to reduce the power consumption of the continuously operating (reading) AD converter and thus reduce the required battery size, the following method can be implemented. FIG. 10 shows an example of an implementation aspect of this method.

[0060] By reconfiguring the pins of the microcontroller 202, the signal (voltage) from the sensor strip 306 can be configured as a digital input for waking up the microcontroller from the low-power mode. Contact between the power strip 310, the sensor strip 306, and the user's finger may detect a transition that wakes up the microcontroller from the low-power mode. Thereafter, the signal is read by the AD converter, and it can be determined whether the voltage exceeds a threshold value (for example, the high potential value 706), and thus whether the signal corresponds to the connection of the power strip 310 and the sensor strip 306 by the bridge contact 304 or the connection by the user's finger.

[0061] In particular, before entering the low-power mode, the microcontroller 202 (preferably including a built-in AD converter) can configure the input pins connected to each of the two sensor strips 306 and the 0U strip 314 (not shown) as digital inputs including interrupts that activate the microcontroller upon a logic level transition (step S1). Then, the microcontroller can enter the low-power mode (step S2). Thus, when a transition is detected at the input pins of the sensor strip 306 and / or the 0U strip 314, the microcontroller 202 wakes up from the low-power mode (step S3). And the microcontroller 202 can reconfigure the input pins connected to each of the three sensor strips 306 as analog inputs (step S4). The voltage at the input pins corresponding to the sensor strip 306 and / or the 0U strip 314 can be read using the AD converter (step S5). The obtained voltage can be compared with the software-set threshold (step S6). Thus, the microcontroller 202 can determine whether the transition was caused by the power strip 310 and the sensor strip 306 and / or the 0U strip 314 being connected by the bridging contact 304 (step S8). If it is determined that the transition was not caused by the power strip 310 and the sensor strip 306 and / or the 0U strip 314 being connected by the bridging contact 304, the microcontroller 202 waits for a suitable delay time and returns to configuring the input pins connected to each of the two sensor strips 306 and the 0U strip 314 (not shown) as digital inputs including interrupts that activate the microcontroller upon a logic level transition, and can continue the sequence of steps described above (step S9’). If it is determined that the transition was caused by the power strip 310 and the sensor strip 306 and / or the 0U strip 314 being connected by the bridging contact 304, the microcontroller 202 can increment or decrement the current count of the selected dosage (step S9).Then, as long as the microcontroller 202 does not detect any operation over a suitable delay time, it can keep polling the analog voltage at the input pins corresponding to the sensor strip 306 and / or the 0U strip 314 and continue to record the dial-set dosage until the microcontroller returns to the first step of this sequence, i.e., step S1 (step S10).

[0062] As described above, it is advantageous from the perspective of battery life that the value of the resistor R is as high as possible, and in particular, significantly higher compared to the resistance of the bridge contact 304. However, the lower the value of the resistor R1, the lower the value of the resistor bridging the power strip and the sensor strip that causes the measurement error.

[0063] To address this issue, in one embodiment (which can be combined with any of the above-described embodiments), the arrangement of FIG. 9 can be adopted. The circuit shown in FIG. 9 includes an additional resistive element S8. This resistive element can be, for example, a resistor. The resistance value of the resistive element R8 is lower compared to the resistor R1. For example, the value of the resistor R8 can be approximately 100 kΩ. For example, the value of the resistor R8 can be less than 200 kΩ, less than 180 kΩ, or less than 170 kΩ. For example, the value of the resistor R8 can be 164 kΩ. Generally, the value of R8 is selected to be sufficiently low compared to the resistor R1 (described above), but high enough to meet any given safety limit that restricts the current that could flow through the user's finger if the user accidentally touches the contact.

[0064] Resistor R8 is provided in parallel with resistor R1. Q1 is a switch operated by microcontroller 202. The switch Q1 can be, for example, a transistor. When the microcontroller 202 is in the low-power mode, the switch Q1 is open. Thus, the resistance connected to the sensor strip 306 is high (e.g., approximately 1 MΩ; possible values of R1 have been described above). When the microcontroller 202 starts up from the low-power mode, it closes the switch Q1. The effective value of the resistance decreases from R1 to the parallel combination of R1 and R8, and thus the circuit becomes resistant to a finger with lower resistance bridging the power strip and the sensor strip.

[0065] Providing the arrangement of FIG. 9 can help save battery life. Since the microcontroller 202 is expected to be in a low-power state for most of its life, the switching of the resistance between R1 and the parallel combination of R1 and R8 may have only a minor impact on battery life.

[0066] The terms "drug" or "agent" are used synonymously herein and describe a pharmaceutical formulation comprising 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 humans or animals. In pharmacology, a drug or medicine is used for the treatment, cure, prevention, or diagnosis of a disease or, alternatively, to improve physical or mental well-being. A drug or agent can be used for a limited duration or, in the case of a chronic disorder, periodically.

[0067] As described below, a drug or agent can contain 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 with 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.

[0068] 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 a 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 a 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 a 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.

[0069] The drugs or agents included in the drug delivery devices described herein 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.

[0070] 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 human insulin analogs or derivatives, glucagon-like peptide (GLP-1), GLP-1 analogs or GLP-1 receptor agonists, and their analogs or derivatives, dipeptidyl peptidase-4 (DPP4) inhibitors, or pharmaceutically acceptable salts or solvates thereof, or mixtures of any of them. As used herein, the terms "analog" and "derivative" refer to 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, such as the 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.

[0071] 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.

[0072] 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.

[0073] 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 eligens, 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.

[0074] Examples of oligonucleotides include, for example, the cholesterol-lowering antisense therapeutic agent mipomersen sodium (Kynamro®) for the treatment of familial hypercholesterolemia.

[0075] Examples of DPP4 inhibitors include vildagliptin, sitagliptin, denagliptin, saxagliptin, and berberine.

[0076] Examples of hormones include pituitary hormones or hypothalamic hormones or regulatory active peptides and their antagonists, for example, gonadotropins (folitropin, lutropin, chorionic gonadotropin, menotropin), somatropin (Somatropine) (Somatropin), desmopressin, terlipressin, gonadorelin, tryptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0077] 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 hylan G-F20 (Synvisc (registered trademark)), sodium hyaluronate.

[0078] 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 functions and is capable of fixing complement. In some embodiments, the antibody has reduced or no binding ability to Fc receptors. For example, the antibody can be an isotype or subtype, antibody fragment or mutant that does not assist in binding to Fc receptors, for example, having a mutation or deletion in the Fc receptor-binding region. The term antibody also includes antigen-binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTIs) and / or dual variable domain antibody-like binding proteins (CODVs) having a crossover binding region orientation.

[0079] 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 may 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 invention include, for example, Fab fragments, F(ab’)2 fragments, scFv (single-chain Fv) fragments, linear antibodies, single-specific or multispecific antibody fragments, e.g., bispecific, trispecific, tetra-specific, and multispecific antibodies (e.g., diabodies, tribodies, tetrabodies), monovalent or polyvalent antibody fragments, e.g., bivalent, trivalent, tetravalent, and polyvalent 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.

[0080] The term "complementary determining region" or "CDR" refers to short polypeptide sequences within the variable regions of both 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 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 may directly participate in antigen binding or may affect the ability of one or more amino acids within the CDR to interact with the antigen.

[0081] Examples of antibodies are anti-PCSK-9 mAbs (e.g., alirocumab), anti-IL-6 mAbs (e.g., sarilumab), and anti-IL-4 mAbs (e.g., dupilumab).

[0082] 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 include, for example, acid addition salts and basic salts.

[0083] Without departing from the scope and spirit of the present invention, various modifications (additions and / or deletions) of the various components of the APIs, formulations, devices, methods, systems, and embodiments described herein can be made, and it will be understood by those skilled in the art that the present invention encompasses such modifications and all equivalents thereof.

Claims

1. A drug delivery device (100), comprising: A housing (102, 104) including one or more bridging contacts (304); A movable dial (108) at least partially located within the housing and arranged to move relative to one or more bridging contacts (304), the dial including a sleeve (302) having a series of conductive strips (306, 310, 314) on an outer surface of the sleeve, The series of conductive strips includes at least one power strip (310) connected to a battery and at least one sensor strip (306) connected to at least one electronic component, One or more bridging contacts (304) selectively connect and disconnect the power strip to the sensor strip as the movable dial (108) moves, providing an alternating electrical signal, One or more bridging contacts (304) are not connected to at least one electronic component except when connected via a sensor strip, At least one electronic component (202, 218) Detects the alternating electrical signal; Determines whether the electrical signal indicates contact between the conductive strip and the bridging contact; And at least one electronic component configured to determine a dosage of a drug programmed within the drug delivery device based on the electrical signal. The bridging contacts (304) are equally spaced around the circumference of the sleeve (302). The drug delivery device.

2. The drug delivery device according to claim 1, wherein the signal is a digital signal.

3. The dial is arranged to rotate relative to the housing and one or more bridging contacts during a dosing programming event, and / or the dial is arranged to move helically out of the housing during a dosing programming event, the drug delivery device according to claim 1 or 2.

4. At least one electronic component (202, 218) comprises at least one of a microcontroller (202), a comparator (218), an analog-to-digital converter (218) The drug delivery device according to any one of claims 1 to 3.

5. Detecting an alternating electrical signal by at least one electronic component (202, 218) comprises detecting a voltage at at least one of a series of conductive strips (306, 310, 314), the drug delivery device according to any one of claims 1 to 4.

6. At least one electronic component (202, 218) is applied to compare a voltage detected at at least one of a series of conductive strips (306, 310) with a threshold voltage, the drug delivery device according to claim 5.

7. At least one electronic component (202, 218) is applied to compare an analog voltage detected at at least one of a series of conductive strips (306, 310) with a threshold voltage, the drug delivery device according to claim 5.

8. At least one electronic component (202, 218) is applied to increase a dose count when a detected voltage exceeds a threshold voltage, the drug delivery device according to claim 6 or 7.

9. At least one electronic component (202, 218) is applied not to increase a dose count when a detected voltage is less than a threshold voltage, the drug delivery device according to any one of claims 5 to 8.

10. A drug delivery device according to any one of claims 1 to 9, comprising a microcontroller (208), wherein the microcontroller has a low power mode and is configured to start from the low power mode when an electrical signal is received.

11. The drug delivery device according to claim 10, wherein the microcontroller is configured to start from the low power mode when receiving an electrical signal from an electrical connection to a conductive strip.

12. The drug delivery device according to claim 10 or 11, further comprising a resistive element and a switch, wherein the switch selectively connects a resistance to at least one of a series of conductive strips based on whether the microcontroller is in the low power mode.

13. The drug delivery device according to claim 12, wherein the resistance is selectively connected to one sensor strip (306) or a plurality of sensor strips (306).

14. The drug delivery device according to any one of claims 1 to 13, wherein the series of conductive strips includes at least two sensor strips (306) and at least two power strips (310).

15. Programming a dosage includes dialing a dosage, for the drug delivery device according to any one of claims 1 to 14.

16. A method of operating a drug delivery device according to any one of claims 1 to 15, comprising: detecting an alternating electrical signal; determining whether the electrical signal indicates contact between a conductive strip and a bridging contact; determining a dosage of a drug programmed into the drug delivery device based on the electrical signal and the method as described above.

17. Detecting a voltage in at least one of a series of conductive strips; comparing the voltage detected in at least one conductive strip with a threshold voltage; The method according to claim 16, further comprising. **Claim 18** Increasing a dosage count in response to determining that the detected voltage exceeds the threshold voltage; The method according to claim 17, further comprising. **Claim 19** Not increasing the dosage count if it is determined that the detected voltage is less than the threshold voltage in response to determining that the detected voltage is less than the threshold voltage; The method according to claim 17 or 18, further comprising. **Claim 20** Entering a low power mode by a microcontroller; Activating the microcontroller from the low power mode when an electrical signal is received; The method according to any one of claims 16 to 19, further comprising. **Claim 21** Connecting a resistor to at least one of a series of conductive strips in response to determining that the microcontroller is in the low power mode; Disconnecting a resistive element from at least one of a series of conductive strips in response to determining that the microcontroller has been activated from the low power mode; The method according to claim 20, further comprising.

Images