Electronic system, user interface member, drug delivery device, and method for detecting whether a drug delivery device is or has been exposed to a fluid - Patents.com

Abstract

An electronic system, a user interface member, a drug delivery device, and a method for detecting whether a drug delivery device is or has been exposed to a fluid. In at least one embodiment, the electronic system is configured to compare a measurement result obtained by the measurement (21) unit with a reference and to determine the exposure of the drug delivery device to the fluid based on a result of the comparison. The measurement result is suitable for providing information about the drug delivery device.

Description

[Technical Field]

[0001] An electronic system for a drug delivery device is provided. Also provided are a user interface member for the drug delivery device, a drug delivery device, and a method for detecting whether the drug delivery device is or has been exposed to a fluid. [Background technology]

[0002] Administering an injection is a process that presents many risks and challenges, both mentally and physically, for users and medical professionals. Drug delivery devices may aim to make self-injection easier for patients. Drug delivery devices that use electronic devices are becoming increasingly popular both in the pharmaceutical industry and with users or patients. Stable operation of electronic components is desirable to ensure that drug delivery devices operate correctly. Summary of the Invention [Problem to be solved by the invention]

[0003] One object to be achieved is to provide an improved electronic system for a drug delivery device. Preferably, the electronic system may enable detection of exposure of electrical elements of the drug delivery device to a fluid. Further objects to be achieved are to provide an improved user interface member, an improved assembly, and an improved drug delivery device, as well as an improved method for detecting whether a drug delivery device is or has been exposed to a fluid. [Means for solving the problem]

[0004] These objects are achieved, inter alia, by the subject matter of the independent claims. Advantageous embodiments and further developments are the subject matter of the dependent claims and are also presented in the following description and in the drawings.

[0005] First, an electronic system for the drug delivery device is specified.

[0006] According to at least one embodiment, the electronic system is configured to compare the measurement results obtained by the measurement unit with a reference. The measurement unit may be part of the electronic system. In particular, the electronic system may be configured to determine the deviation of the measurement results obtained by the measurement unit from the reference. Each measurement value may be associated with a measurement value or reading of the measurement unit, respectively. The measurement values ​​may be in the form of an analog signal of the measurement unit or a digitized signal of the measurement unit. For example, the analog measurement value is converted to a digital signal using an analog-to-digital converter (ADC). The reference may be a reference value, a distribution of reference values, or a curve of reference values, respectively.

[0007] Here and below, comparing a measurement result with a standard may mean, in particular, comparing each measurement value with a standard value, for example by determining the difference between the measurement value and the standard value and / or by determining whether the measurement value is above or below the standard value.

[0008] According to at least one embodiment, comparing the measurement to a reference includes comparing an amplitude of the measurement to an amplitude of the reference.

[0009] According to at least one embodiment, comparing the measurement to a standard includes comparing a dynamic range of the measurement to a dynamic range of the standard.

[0010] According to at least one embodiment, comparing the measurement result to a reference includes comparing the curve shape of the measurement result to the curve shape of the reference. This comparison may be performed to determine the correlation between the curve of the measurement result and the curve of the reference. 2 Determining a power value.

[0011] The measurement unit may be or may include a sensor, in particular an electric or electronic measurement unit that provides a measurement result in the form of an electric or electronic signal and / or requires electrical power to operate.

[0012] According to at least one embodiment, the measurement results are suitable for providing information about the drug delivery device. In other words, information about the drug delivery device can be extracted from the measurement results. The information can be, for example, information about the state of the drug delivery device or information about an operating process performed by or with the drug delivery device. The information about the state of the device can be information different from information about whether the drug delivery device or an element thereof is or has been exposed to a fluid. Nevertheless, in the present disclosure, the measurement results can be evaluated to ascertain whether the drug delivery device or an element thereof is or has been exposed to a fluid.

[0013] For example, the measuring unit is configured to measure or detect, respectively, an operating process of the drug delivery device. The operating process may be a drug delivery process, a dose setting process, or an activation process of the drug delivery device. The measurement result or measured value, respectively, may be indicative of the operating process. For example, the measuring unit may be configured to detect a movement of an element of the drug delivery device relative to the measuring unit, and the measurement result may be indicative of such movement.

[0014] According to at least one embodiment, the electronic system is configured to determine exposure of the drug delivery device or the electronic system to a fluid based on the result of the comparison. In particular, this means that the electronic system can determine whether the drug delivery device, e.g., the interior of the drug delivery device, or a part of the interior, in particular the electrical elements of the drug delivery device, is or has been exposed to a fluid. The determination of whether such exposure has occurred is made based on the result of the comparison. The fluid may be a gaseous fluid or a liquid fluid, e.g., water or moisture.

[0015] For example, if the amplitude and / or dynamic range and / or curve shape of the measurement result deviates from the reference amplitude and / or dynamic range and / or curve shape by, for example, more than a predetermined threshold, it may be determined that the drug delivery device is or has been exposed to the fluid. Otherwise, it may be determined that the drug delivery device has not yet been exposed to the fluid.

[0016] For example, if the measured value, or the maximum, minimum, or average measured value of the measured values, is above or below the reference value, or the maximum, minimum, or average reference value, for example, by a predetermined threshold, it is determined that the drug delivery device is or has been exposed to the fluid. Otherwise, it may be determined that the drug delivery device has not yet been exposed to the fluid.

[0017] In at least one embodiment, the electronic system for the drug delivery device is configured to compare a measurement result obtained by the measurement unit with a reference and determine exposure of the drug delivery device to the fluid based on a result of the comparison, the measurement result being suitable for providing information about the drug delivery device.

[0018] The present invention is based on the recognition that moisture or water or other fluids, among other things, can have several effects on a drug delivery device, for example on the system of the drug delivery device that detects dial setting and / or dose ejection. For example, if the drug delivery device utilizes an optical encoder system, the readings or measurements from a measurement unit in the form of an optical sensor may be affected by the presence of moisture, water or other fluids due to a number of factors.

[0019] Water droplets can obstruct the passage of light to and from an optical sensor, causing refraction or broadening of the intended optical path. Water droplets near an optical sensor can contact the electrical lines that power the active emitter side of the optical sensor or detect voltage / current on the receiver side of the optical sensor, resulting in changes in resistance, capacitance, or inductance between the individual lines. Such disruptions to the optical path or moisture contacting the electrical lines leading to the optical sensor can be detected by monitoring sensor readings. In fact, the inventors observed that empirical data collected during the development and construction phase indicated that sensor readings or measurements can be affected by the presence of water. Water can increase sensor readings or measurements toward saturation levels that are not typically reached during standard operation. Therefore, deviations of sensor readings from expected values ​​(norms) can be used to determine the presence or presence of moisture affecting sensor function.

[0020] Using the electrical systems specified herein, it may be possible to detect the presence of fluid before the fluid has any adverse effect on the use or robustness of the drug delivery device, and in such cases, the user can be alerted to the presence of fluid, for example, to the possibility that device performance may be compromised.

[0021] According to at least one embodiment, the measuring unit is configured to be placed in or is located in the drug delivery device, in particular the measuring unit is configured to be placed inside the drug delivery device or inside a member of the drug delivery device.

[0022] According to at least one embodiment, the measurement results used for comparison with the reference are measurements obtained during a measurement period. The measurement period can be a predetermined period, e.g., several seconds. For example, the measurement period can be at least 0.1 seconds, at least 0.5 seconds, at least 1 second, or at least 10 seconds. Additionally or alternatively, the measurement period can be up to 50 seconds, up to 20 seconds, or up to 15 seconds. During the measurement period, the measurement unit may obtain multiple measurements, e.g., at least 10 measurements, at least 100 measurements, at least 1000 measurements, and / or up to 10,000 measurements. The measurements can be obtained periodically during the measurement period, e.g., at a frequency of at least 100 Hz, at least 1,000 Hz, and / or up to 5,000 Hz. For example, the frequency can be between 500 Hz and 4,000 Hz. Outside of the measurement period, the measurement unit does not perform measurements. For example, the measurement unit can be powered off.

[0023] When comparing the measurement results to a reference, only the measurement results from one measurement period may be considered, for example, the maximum measurement value of at least some or all of the measurement results from the measurement period, or the average measurement value of at least some or all of the measurement results from the measurement period may be compared to the reference.

[0024] According to at least one embodiment, the electronic system is configured to repeatedly, e.g., periodically, compare the measurement results with the reference and repeatedly determine the exposure of the drug delivery device to the fluid based on the results of the comparison, e.g., the electronic system is configured to compare the measurement results of a measurement period with the reference after the end of the measurement period and before the start of the next measurement period.

[0025] According to at least one embodiment, the measurements are from a measurement period that is repeated periodically, for example, the measurement period is repeated at least every minute, at least every hour, or at least every day, for example, regardless of whether a drug delivery device is used or not.

[0026] According to at least one embodiment, the electronic system is configured to adjust the reference to changes in the operating voltage of the measurement unit, for example, changes in the operating voltage in the form of a voltage drop that appears as the drug delivery device ages or results from wear effects due to use. The electronic system can be configured to adjust the reference to this voltage drop.

[0027] The measuring unit may be powered by a power source, such as a battery. Such a power source may show aging or wear effects in the form of a decrease in the voltage provided by the power source (operating voltage). The decrease in operating voltage then affects the measurement results of the measuring unit. For example, the maximum reading of the measuring unit decreases with the decrease in voltage. Such a decrease in voltage can be taken into account by adjusting the reference, for example, by making the reference time-dependent. For example, the reference is set to decrease with increasing time. The adjustment of the reference can be predetermined, for example, by manually setting different references for different time points after the first use of the device. This setting can be done during manufacturing of the drug delivery device and / or during programming of the electronic system.

[0028] According to at least one embodiment, the electronic system is configured to adjust the reference based on voltage data, the voltage data being indicative of an operating voltage of the measurement unit, in which case the electronic system is in particular configured to adjust the reference dynamically, i.e. based on the voltage data.

[0029] According to at least one embodiment, the electronic system is configured to adjust the criteria based on previous measurements of the measurement unit obtained during a preceding period, in particular, the electronic system is configured to dynamically adjust the criteria based on previous measurements.

[0030] For example, the criterion may be adjusted to follow trends in previous measurements of the measurement unit. For example, if previous measurements, such as amplitude or maximum measurement, have increased or decreased over time during the preceding period, the criterion may also be increased or decreased. The criterion may be selected to be a previous measurement or an average of the previous measurements.

[0031] According to at least one embodiment, the criteria are fixed criteria, i.e., they do not change over time, e.g., they are determined based on empirical data collected during development of the drug delivery device.

[0032] According to at least one embodiment, the drug delivery device is configured to perform several drug delivery processes sequentially. For example, during each such drug delivery process, a dialed-in dose is delivered to the user. The drug delivery device may be configured to perform at least 10 drug delivery processes, at least 100 drug delivery processes, or at least 1000 drug delivery processes. To perform a large number of drug delivery processes, the drug container storing the drug may need to be changed.

[0033] According to at least one embodiment, the electronic system is configured to adjust the criterion based on measurement results of the measurement unit associated with the last n drug delivery processes, where n is greater than or equal to 1. For example, n is at least 5 or at least 10. Additionally or alternatively, n is at most 50 or at most 20.

[0034] Measurement results associated with a drug delivery process are in particular measurement results obtained during the drug delivery process or immediately before or after the drug delivery process, for example, within a time window of up to 1 minute before and / or after the start or end of the drug delivery process, respectively.

[0035] For example, the maximum or average measurements associated with the various drug delivery processes are determined for each drug delivery process, and then the reference value is adjusted based on the last n maximum or average measurements, e.g., the reference value is set to the average of the last n maximum or average measurements.

[0036] According to at least one embodiment, the measurements are measurements obtained during use of the drug delivery device, in particular during the drug delivery process, i.e. during the period when the drug is actually delivered, e.g., the measurement period is the duration of the drug delivery process.

[0037] According to at least one embodiment, the measurement is obtained during a period when the drug delivery device is not in use, for example, during the period between two subsequent drug delivery processes. In particular, the measurement may be obtained immediately before or after a drug delivery process. The measurement period may then be the period between two subsequent drug delivery processes.

[0038] According to at least one embodiment, measurements at the beginning of the measurement period are not used (e.g., ignored or discarded) in the comparison with the reference. For example, at least the first five, at least the first ten, or at least the first fifteen measurements of the measurement period are not used. Alternatively or additionally, the electronic system may be configured such that one or more measurements from an early stage of the measurement period are not compared with the reference. That is, these measurements may be ignored in the comparison operation. The early stage may include the first two measurements obtained, e.g., five or more, ten or more, or fifteen or more measurements, and / or may have a duration greater than 2 ms. Only measurements obtained after the early stage has ended, e.g., from the 16th or 17th measurement, may be considered for the comparison.

[0039] The operating voltage of the measurement unit at the beginning of the measurement period, e.g., at the beginning of the delivery process, may drop, e.g., during the first measurement. This drop results in a rapid decrease in the associated measurement value. After the first measurement, the voltage may stabilize to a constant operating voltage for the remainder of the measurement period. Therefore, it is advantageous to ignore the early measurement results for comparison, since if these results are taken into account, they may falsely indicate fluid inflow into the system.

[0040] According to at least one embodiment, the measuring unit is a sensor, e.g. of the electronic system or of the drug delivery device. The sensor may be configured to measure the amount of the delivered dose during the drug delivery process. The sensor may in particular be configured to detect a relative movement, in particular a relative rotation, between the sensor and a further element, e.g. a movable member of the drug delivery device.

[0041] In other words, the measurement results may be suitable to provide information regarding the amount of the dose set during the dose setting process or indicate the amount of the delivered dose during the dose delivery process.

[0042] According to at least one embodiment, the measurement unit is an optical sensor. The optical sensor may be configured to emit radiation and detect a portion of the radiation reflected by a movable member of the drug delivery device. The optical sensor may include an LED, e.g., an infrared LED, and a sensor element configured to detect a reflected portion of the radiation emitted by the LED, e.g., reflected from the movable member. The movable member may include alternating regions of different reflectivity with respect to the radiation emitted by the optical sensor. That is, the movable member may include an encoder structure. The movable member may be an encoder member or an encoder component. The regions of different reflectivity may be regions of different colors, e.g., black and white regions.

[0043] According to at least one embodiment, the electronic system is configured to generate an output signal to communicate to a user when exposure of the drug delivery device to a fluid is confirmed, and in particular, the output signal is generated only when exposure of the drug delivery device to a fluid is confirmed.

[0044] According to at least one embodiment, the electronic system includes or is a processor. In particular, the processor may be configured to receive a measurement result of the measurement unit and / or to compare the measurement result with a reference and / or to determine whether exposure of the drug delivery device to the fluid has occurred or occurred based on the result of the comparison. The processor may also be configured to generate an output signal.

[0045] According to at least one embodiment, the electronic system further comprises a measurement unit for obtaining measurements.

[0046] According to at least one embodiment, the electronic system includes a communication unit that can be configured to communicate to a user when exposure of the drug delivery device to a fluid is confirmed, for example, by operating the communication unit based on an output signal when exposure of the drug delivery device to a fluid is confirmed.

[0047] The communication unit may be an LED configured to emit light, for example white light, and the drug delivery device may be configured such that the light emitted by the LED is visible to a user using the drug delivery device.

[0048] Additionally or alternatively, the drug delivery device may include a communication unit in the form of an acoustic sound generator, for example a loudspeaker, configured to provide an acoustic signal to communicate confirmed exposure to the fluid.

[0049] By communicating possible fluid exposure to the user, the user may be indicated that the drug delivery device may provide erroneous results or that the drug delivery device should no longer be used.

[0050] According to at least one embodiment, the electronic system includes a circuit board, for example a PCB, such as a flexible-rigid PCB (Printed Circuit Board), and the measurement unit and / or the processor and / or the communication unit may be disposed on and / or electrically connected to the circuit board.

[0051] The electronic system may further include a battery for powering the processor and / or the measuring unit and / or the communication unit. The electronic system may also include a wireless communication unit, e.g., a Bluetooth unit, for communicating information obtained using the measuring unit to an external device, such as a smartphone or computer. For example, the delivered dose measured using the measuring unit is communicated to the external device.

[0052] The electronic system may also include, for example, an analog-to-digital converter for converting analog signals from the measurement unit to digital signals. The electronic system may also include, for example, electromechanical switches for enabling and / or disabling the power supply of the measurement unit.

[0053] According to at least one embodiment, the electronic system is configured to determine the exposure of the drug delivery device to the fluid based on the measurement results of the measuring unit and the further measuring unit. In particular, the drug delivery device and / or the electronic system may include the further measuring unit. All features disclosed in relation to the measuring unit are also disclosed in relation to the further measuring unit, and vice versa. In particular, the further measuring unit may be a sensor, such as an optical sensor, for measuring the amount of the delivered dose, in particular during the delivery process. The sensors of the measuring unit and the further measuring unit may be out of phase with respect to an encoder structure provided by the movable member (see further above). The sensor and encoder structure may be adapted such that the sensor outputs (i.e., electrical signals) are combined to provide a multi-bit Gray code, e.g., a 2-bit Gray code, during relative movement (e.g., relative rotation) between the sensor and the encoder structure. The combination of sensor outputs may be unique for many different relative positions between the movable member and the sensor. The 2-bit Gray code uniquely characterizes, for example, four relative positions.

[0054] For example, the electronic system is configured to confirm exposure of the drug delivery device to the fluid only if the measurement result of each measurement unit indicates exposure to the fluid. For example, exposure of the drug delivery device to the fluid is confirmed only if comparison of the measurement results of both measurement units with their respective standards individually indicates exposure to the fluid. Determining whether the further measurement units indicate exposure of the drug delivery device to the fluid can be done in the same way as for the measurement units, for example if the measurement value of the further measurement unit is above the standard value.

[0055] Next, a user interface member is designated, which may be a knob or button permanently connected or connectable to the container holder of the drug delivery device or removably connectable to the container holder of the drug delivery device.

[0056] According to at least one embodiment, the user interface member includes an electronic system as specified above, and therefore all features disclosed in relation to the electronic system are also disclosed in relation to the user interface member.

[0057] The electronic system may be disposed within the user interface member. For example, the electronic system may be circumferentially surrounded by a housing element of the user interface member. The electronic system may be disposed inside the user interface member such that the electronic system is protected from fluids.

[0058] According to at least one embodiment, the user interface member is configured to be touched by a user to operate the user interface member to perform the dose dialing and / or drug delivery process. Thus, the user interface member may be configured to perform the dose dialing and / or drug delivery process when connected to the container holder and operated by a user.

[0059] For example, the user interface member may include a side surface that forms an outer surface of the component and is configured to be grasped by a user. The side surface may radially outwardly define the boundary of the user interface member. In particular, the side surface may extend parallel to or at an acute angle to the longitudinal axis of the user interface member or drug delivery device.

[0060] The side surface may be configured to be grasped by a user with two fingers to rotate the user interface member about the longitudinal axis, e.g., relative to the container holder. Additionally or alternatively, the user interface member may include a proximal surface facing proximally. The proximal surface may extend perpendicular or oblique to the longitudinal axis and / or the side surface. The proximal surface may be configured to be touched by a user with, e.g., only one finger, particularly to push the user interface member distally.

[0061] According to at least one embodiment, the side surface may include a gripping feature, such as a groove, which may extend parallel to the longitudinal axis or at an acute angle to the longitudinal axis. The gripping feature may facilitate a user's grip of the user interface member.

[0062] According to at least one embodiment, the user interface member includes a measurement unit, for example, the measurement unit is disposed inside the user interface member.

[0063] Next, an assembly is specified. The assembly may be an assembly for a drug delivery device. The assembly may be attachable to a drug delivery device. Alternatively, the assembly may be part of or the drug delivery device.

[0064] The assembly may include a movable member and a measurement unit as described above in relation to the electronic system. Alternatively or additionally, the assembly may include an electronic system as described above.

[0065] In one embodiment, the assembly may include an electronic system with an optical sensor and an encoder structure, e.g., a Gray code encoder ring. The electronic system, e.g., the optical sensor, may be configured to detect and / or quantify movement of the encoder structure. Movement of the encoder structure may indicate a dialed-in dose on the drug delivery device and / or an ejected dose from the drug delivery device, e.g., the size of the dialed-in dose or the ejected dose. In one embodiment, the electronic system of the assembly may be configured to detect fluid inflow into the assembly or drug delivery device through detection of optical properties, e.g., reflective and / or refractive properties, of a fluid droplet present between the optical sensor and the encoder structure, e.g., a Gray code encoder ring. If fluid is present, the fluid causes a change in the output signal of the sensor, e.g., a higher or lower output signal compared to a situation without exposure to fluid. In other words, the optical sensor may be configured to detect the presence of fluid in an optical path between the sensor and the encoder structure by detecting an amount or portion of radiation reaching the sensor. In one embodiment, radiation may be emitted by the optical sensor or a component thereof, e.g., an LED. A portion of this radiation may be refracted by the fluid in the optical path before being reflected by the encoder structure. Alternatively or additionally, the reflected portion may be refracted again by a fluid in the optical path before reaching the sensor. The sensor may be configured to detect the reaching portion of the radiation. By comparison with the reference, the assembly, e.g., its electronic system, may determine the presence of a fluid in the optical path. In other words, the assembly, e.g., its electronic system, may determine the exposure of an element, e.g., an electrical element of the drug delivery device, to the fluid based on the result of the comparison.

[0066] The assembly may in particular include the electronic system specified above, and therefore all features disclosed in relation to the electronic system are also disclosed in relation to the assembly and vice versa.

[0067] Next, a drug delivery device is specified. The drug delivery device may be an injection device and / or a pen-type device, such as a dial-extension pen. The drug delivery device may be a variable dose device that allows the dose of drug delivered to the user to be variably set. For example, the drug delivery device may be a reusable device.

[0068] According to at least one embodiment, the drug delivery device includes an electronic system or a user interface member as specified above, and therefore all features disclosed with respect to the electronic system and / or with respect to the user interface member are also disclosed with respect to the drug delivery device.

[0069] The electronic system may in particular be located inside the drug delivery device. The electronic system may be located so as to be protected from fluids reaching the drug delivery device. Similarly, the measurement unit may be located inside the drug delivery device and protected from fluids.

[0070] According to at least one embodiment, the drug delivery device includes a container holder for holding the drug container. The container holder may be a housing of the drug delivery device or may be a separate element connected to or connectable to the housing. The container holder may be configured to hold the drug container in an axially and / or rotationally fixed state relative to the housing of the drug delivery device. In particular, the container holder may hold the drug container so that the drug container does not move axially and / or rotationally during the drug delivery process.

[0071] According to at least one embodiment, the medication container is filled with a medication.

[0072] Drug delivery devices and / or user interface members as specified herein may be elongate and / or include a longitudinal axis, e.g., a main axis of extension. Additionally or alternatively, the drug delivery device and / or user interface member may have rotational symmetry about the longitudinal axis. A direction parallel to the longitudinal axis is referred to herein as the axial direction. As an example, the drug delivery device and / or user interface member may be cylindrical.

[0073] Furthermore, the drug delivery device may include an end, e.g., a longitudinal end, that may be configured to face or be pressed against a skin area of ​​the human body. This end is referred to herein as the distal end. A drug or agent may be delivered via the distal end. The opposite end is referred to herein as the proximal end. In use, the proximal end is away from the skin area. The axial direction from the proximal end to the distal end is referred to herein as the distal direction. The axial direction from the distal end to the proximal end is referred to herein as the proximal direction. The distal end of a member or element or feature of a drug delivery device is understood herein to be the end of the member / element / feature that is most distal. Thus, the proximal end of a member or element or feature is understood herein to be the end of the element / member / feature that is most proximal.

[0074] In other words, "distally" is used herein to designate a direction, end, or surface that is or will be positioned to face or point toward the discharge end of a drug delivery device or a component thereof, and / or that points away from the proximal end, will be positioned to face away from the proximal end, or faces away from the proximal end. On the other hand, "proximally" is used herein to designate a direction, end, or surface that is or will be positioned to face or point away from the discharge end and / or distal end of a drug delivery device or a component thereof. The distal end may be the end closest to the discharge end and / or farthest from the proximal end, and the proximal end may be the end farthest from the discharge end. The proximal face may face away from the distal end and / or face toward the proximal end, and the distal face may face toward the distal end and / or face away from the proximal end. The discharge end may be, for example, the needle end at which a needle unit is or will be attached to the device.

[0075] As used herein, directions perpendicular to and / or intersecting the longitudinal axis are referred to as radial. Radially inward is a radial direction pointing toward the longitudinal axis. Radially outward is a radial direction pointing away from the longitudinal axis. As used herein, the terms "angular," "azimuthal," or "rotational" are used synonymously. Such directions are those perpendicular to the longitudinal axis and perpendicular to the radial direction.

[0076] A method of operating the drug delivery device may be as follows: A user interface member in the form of a knob connected to a container holder and including an electronic system is grasped and rotated by a user, e.g., by a side of the user interface member, thereby dialing in the dose to be injected into the user. The knob may be rotated on a helical path relative to the drug container holder, thereby moving, e.g., in a proximal direction. After dialing in the desired dose, the knob may be pushed axially, e.g., distally, to inject the dose of drug. For this purpose, the user may press on the proximal face of the knob. During the distal knob movement, the knob itself does not rotate, but a movable element of the drug delivery device may rotate. This allows the dialed dose to be expelled, e.g., injected, into the patient. A sensor in the knob may measure the rotation of the movable element. The sensor's measurement may be transmitted to a processor of the electronic system. The processor may determine the delivered dose based on the measurement. This information may be transmitted to an external device, e.g., by means of a wireless communication unit. The processor may also compare the measurement results with a standard and then, based on the results of this comparison, determine whether the interior of the drug delivery device, in particular the sensor or at least one other electrical element, is or has been exposed to the fluid.

[0077] Next, a method for detecting whether a drug delivery device is or has been exposed to a fluid is specified. The method may be particularly implemented using the electronic system, assembly, or drug delivery device specified above. Hence, all features disclosed in relation to the electronic system, assembly, or drug delivery device are also disclosed in relation to the method, and vice versa.

[0078] According to at least one embodiment, the measuring unit is located within the drug delivery device.

[0079] According to at least one embodiment, the method comprises receiving a measurement result obtained by the measuring unit, the measurement result being suitable for providing information about the drug delivery device, in other words the measurement result being suitable for providing information about the amount of the dose set during a dose setting process or indicating the amount of the delivered dose during a dose delivery process.

[0080] According to at least one embodiment, the method includes comparing the measurement results to a standard.

[0081] According to at least one embodiment, the method includes determining exposure of the drug delivery device or its electrical elements to the fluid based on the results of the comparison.

[0082] Further provided are a computer program and a computer readable medium, the computer program including instructions that, when executed by a computer, cause the computer to perform a method for detecting whether a drug delivery device is or has been exposed to a fluid, and the computer readable medium having the computer program stored thereon.

[0083] The electronic system, user interface member, drug delivery device, and method described herein will be described in more detail below based on exemplary embodiments with reference to the drawings. In the individual figures, the same reference numerals indicate the same elements. However, the size ratios involved are not necessarily to scale, and individual elements may be shown in exaggerated size for better understanding. [Brief explanation of the drawings]

[0084] [Figure 1] 1 illustrates an exemplary embodiment of a drug delivery device in an exploded view. [Figure 2] 1A-1C show the proximal portion of an exemplary embodiment of a drug delivery device in different views. [Figure 3] 1A-1C show the proximal portion of an exemplary embodiment of a drug delivery device in different views. [Figure 4] 1 shows measurement results from an exemplary embodiment of a drug delivery device. [Figure 5] 1 shows measurement results from an exemplary embodiment of a drug delivery device. [Figure 6] 1 shows measurement results from an exemplary embodiment of a drug delivery device. [Figure 7] 1 shows measurement results from an exemplary embodiment of a drug delivery device. [Figure 8] 1 shows measurement results from an exemplary embodiment of a drug delivery device. DETAILED DESCRIPTION OF THE INVENTION

[0085] Illustrative Embodiments In the following, exemplary embodiments are described with reference to an insulin injection device, however, the present disclosure is not limited to such applications and may be equally well positioned with injection devices configured to deliver other medications, or with drug delivery devices in general, preferably pen devices and / or injection devices.

[0086] Certain exemplary embodiments in this document are described with respect to a drug delivery device in the form of an injection device including a user interface member in the form of a knob that simultaneously embodies an injection button and a dose setting (dial setting) member, similar to the devices disclosed in, for example, WO 2014 / 033195 A1 or WO 2014 / 033197 A1. Thus, the knob can be used to initiate and / or perform a dose delivery operation of the drug delivery device, and can also be used to initiate and / or perform a dose setting operation. The device can be of the dial-extending type, i.e., the length of these devices increases during dose setting. Other injection devices with the same kinematic behavior of dial extension during dose setting and dose ejection operating modes are also known, for example, the Kwikpen® or Savvio® devices marketed by Eli Lilly and the FlexPen®, FlexTouch®, or Novopen® devices marketed by Novo Nordisk. Therefore, the application of the general principles to these devices is considered straightforward and will not be further described. However, the general principles of this disclosure are not limited to that kinematic behavior.

[0087] Certain other embodiments can be devised for application to injection devices in which there is a separate injection button and grip component / dose setting member, such as the device disclosed in WO 2004 / 078239 A1. The present disclosure therefore also relates to a system with two separate user interface members, for example one for the dose setting operation and one for the dose delivery operation. To switch the device between the dose setting and dose delivery configurations, the user interface member for dose delivery can be moved relative to the user interface member for dose setting.

[0088] If one user interface member is provided, it may be moved distally relative to the housing. During each movement, a clutch between two elements of the device's dose setting mechanism and drive mechanism may change state, for example, from an engaged state to a disengaged state, or vice versa. When the clutch, formed, for example, by sets of interlocking teeth on the two elements, is engaged, the two elements may be locked against rotation relative to one another; when the clutch is disengaged or released, one of the elements may be allowed to rotate relative to the other. One of the elements may be a drive element or drive sleeve that engages with the plunger rod of the dose setting and drive mechanism. The drive sleeve may be designed to rotate relative to the housing during dose setting and may be locked against rotation relative to the housing during dose delivery. The engagement between the drive sleeve and the plunger rod may be threaded. Thus, because the drive sleeve cannot rotate during dose delivery, axial movement of the drive sleeve relative to the housing rotates the plunger rod. This rotation may be translated into axial displacement of the plunger rod during the delivery operation due to the threaded engagement between the plunger rod and the housing.

[0089] 1 is an exploded view of an exemplary embodiment of a drug delivery device 100. In this exemplary embodiment, the drug delivery device 100 is an injection device, such as a pen-type injector.

[0090] The injection device 100 of FIG. 1 is an injection pen including a housing 10 that holds a medication container 14, e.g., an insulin container, or a container holder for such a container 14. The container 14 may contain a medication, e.g., insulin. The container 14 may be a cartridge or a receptacle for a cartridge that may contain or be configured to accept a cartridge. A needle 15 may be secured to the container 14 or the receptacle. The container 14 may be a cartridge, and the receptacle may be a cartridge holder. The needle 15 is protected by an inner needle cap 16 and either an outer needle cap 17 or another cap 18. The insulin dose to be dispensed from the injection device 100 can be set, programmed, or "dialed" by turning a user interface member 2 in the form of a knob 2; the currently programmed or set dose is then displayed, e.g., in multiple units, via a dose window 13. The units may be determined by a dose setting mechanism that may allow rotation of the knob 2 relative to the housing 10 only in integer multiples of one-unit setting increments that may define one dose increment. This can be achieved, for example, by a suitable ratchet system. The indicia displayed in window 13 can be provided on a number sleeve or dial sleeve 70. For example, if injection device 100 is configured to administer human insulin, the dose is displayed in so-called international units (IU), with 1 IU being the bioequivalent of approximately 45.5 micrograms (1 / 22 mg) of pure crystalline insulin. Other units can also be used in injection devices for delivering analog insulin or other medications. It should be noted that the selected dose can equally well be displayed differently than that shown in dose window 13 of FIG. 1.

[0091] Dose window 13 may be in the form of an opening in housing 10 that allows the user to view a limited portion of dial sleeve 70 that is configured to move when knob 2 is turned to provide a visual indication of the currently programmed dose. As knob 2 is turned during programming, it is caused to rotate a helical path relative to housing 10.

[0092] In this exemplary embodiment, the knob 2 includes one or more features 71a, 71b, 71c in the form of formations to facilitate gripping and / or attachment of a data collection device or electronic system.

[0093] The injection device 100 may be configured so that turning the knob 2 produces a mechanical click sound to provide acoustic feedback to the user. In this embodiment, the knob 2 also functions as an injection button. When the needle 15 is inserted into a patient's skin area and the knob 2 is then pressed axially, the insulin dose displayed in the display window 13 is expelled from the injection device 100. If the needle 15 of the injection device 100 remains within the skin area for a certain period of time after the knob 2 is pushed back, the dose is injected into the patient's body. The expulsion of the insulin dose may also produce a mechanical click sound, but this click sound is different from the sound produced when the knob 2 is rotated while dialing the dose.

[0094] In this exemplary embodiment, during delivery of an insulin dose, knob 2 is returned to its initial position in an axial movement without rotation, while dial sleeve 70 or number sleeve 70 is rotated back to its initial position, e.g., to indicate a dose of zero units. As already mentioned, the present disclosure is not limited to insulin, but should encompass all drugs in drug container 14, particularly liquid drugs or drug formulations.

[0095] The injection device 100 can be used for several injection processes until the insulin container 14 is empty or the expiration date of the medication in the injection device 100 is reached (eg, 28 days after first use).

[0096] Furthermore, before using the injection device 100 for the first time, it may be necessary to perform a so-called "prime shot" to ensure accurate fluid flow from the insulin container 14 and needle 15, for example by selecting 2 units of insulin and pressing the knob 2 while holding the injection device 100 with the needle 15 facing upwards. For simplicity of presentation, it is assumed below that the ejected volume substantially corresponds to the dose to be injected, e.g. the amount of medication ejected from the injection device 100 is equal to the dose the user will receive.

[0097] As explained above, the knob 2 also functions as an injection button, such that the same component is used for dialing / setting the dose and ejecting / delivering the dose. Again, it should be noted that a configuration with two different user interface members, preferably movable relative to one another only in a limited way, is also possible. However, the following discussion focuses on a single user interface member providing dose setting and dose delivery functions. In other words, the setting surface of the member touched by the user for the dose setting operation and the dose delivery surface touched by the user for the dose delivery operation are immovably connected. Alternatively, they may be movable relative to one another if different user interface members are used. During each operation, the user interface member preferably moves relative to the device's body or housing. During dose setting, the user interface member moves proximally and / or rotates relative to the housing. During dose delivery, the user interface member preferably moves axially, e.g., distally, without rotating relative to the housing or body.

[0098] 1 also shows the coordinate system used herein to designate the positions of members or elements or features. The distal direction D and the proximal direction P extend parallel to the longitudinal axis L. The longitudinal axis L is the main axis of extension of the device 100. The radial direction R is a direction perpendicular to and intersecting the longitudinal axis L. The azimuthal direction C, also referred to as the angular or rotational direction, is a direction perpendicular to the radial direction R and the longitudinal axis L. To improve the clarity of the figures, not all of the following figures show the different directions and axes.

[0099] Figure 2 shows in cross section the proximal portion of the drug delivery device 100 of Figure 1. Figure 3 shows the same proximal portion but in a different cross section. As can be seen, a user interface member 2 in the form of a knob 2 is connected to the housing 10. The knob 2 can be permanently or removably connected to the housing 10.

[0100] The drug delivery device 100 also includes a plunger rod 11a, a drive sleeve 11b, and a dial sleeve 11c. These elements are operatively coupled for dose dialing and dose injection. During dose injection, the dial sleeve 11c rotates, for example, together with the number sleeve 70. This rotation is detected by a measurement unit 21 in the form of an optical sensor 21 located inside the knob 2, which does not rotate during dose injection. For example, the dial sleeve 11c and / or the number sleeve 70 may include alternating black and white regions with different reflectivities to radiation, e.g., radiation emitted by the optical sensor 21. These regions may form an encoder structure. The encoder structure may also have a surface profile with alternating depressions and protrusions on the dial or number sleeve. In particular, the optical sensor 21 may be sensitive to fluids and / or its measurements may be affected by the presence of fluids. Although the optical sensor 21 is surrounded by housing elements 20, 27 in the form of a grip element 20 and a proximal cover element 27 permanently connected by a snap connection 26, it may still happen that fluid reaches the optical sensor 21. In this case, the measurement results of the optical sensor 21 may no longer be reliable. It is useful to know whether the measurement results can be trusted or not.

[0101] In this exemplary embodiment, the user interface member 2 includes an electronic system having a processor 28. The electronic system is configured to compare the measurement results of the optical sensor 21 with a reference and, based on the result of this comparison, determine whether the interior of the user interface member 2, in particular the optical sensor 21, is or has been exposed to a fluid such as water or moisture. The electronic system may also be configured to adjust the reference for changes in the operating voltage of the optical sensor 21 and / or adjust the reference based on previous measurement results of the optical sensor 21 obtained during a preceding period. For example, the electronic system is configured to adjust the reference based on measurement results of the optical sensor 21 associated with the last five or last ten drug delivery processes, where n≧1. All of these steps may be performed by the processor 28.

[0102] The optical sensor 21 can also be part of an electronic system. The optical sensor 21 and the processor 28 are mounted on a common circuit board 22, e.g., on the same side or different sides, e.g., opposite sides, of the circuit board 22. Measurements by the optical sensor 21 can be transmitted to the processor 28 via the circuit board 22. The optical sensor can detect radiation reflected from a dial sleeve or number sleeve (which can function as a moving, e.g., rotating, encoder component) onto the sensor. Therefore, the sensor conveniently includes a radiation-sensing element, e.g., an optoelectronic detector chip. Radiation, e.g., infrared radiation, can be generated by a radiation source, e.g., the sensor's radiation source, and emitted toward the encoder component. The radiation can be reflected by the encoder component toward the sensor, exciting the radiation-sensing element and generating a signal. Due to the encoder structure provided by the encoder component, e.g., a surface shape with alternating areas of different reflectivity, such as alternating bumps or black and white areas, the amount (intensity) of radiation reaching the sensor varies, and this amount of radiation can be detected using a signal obtained from the sensor. This allows the system to quantify how much the encoder component has rotated relative to the sensor 21. The encoder component may rotate relative to the sensor only during dose delivery (dose injection), and therefore the amount of relative rotation allows calculation of the dose of drug delivered during the dose delivery operation.

[0103] In addition to the optical sensor 21, the knob 2 includes an electromechanical switch 23, a battery 24, and an LED 25. The circuit board 22 may be electrically connected to the optical sensor 21 to receive measurements from the sensor 21 and / or to provide power to the sensor 21. The battery 24 may be used to provide power to additional electrical or electronic elements on the circuit board 22, such as the sensor 21, the LED 25, the processor 28, and / or a communication unit (not shown). The mechanical switch 23 may be operated by the drive sleeve 11b when the knob 2 is moved axially, e.g., distally, relative to the drive sleeve 11b. By operating the mechanical switch 23, the sensor 21 and / or the LED 25 and / or the processor 28 may be powered on.

[0104] The LED 25 may be configured to inform the user of the operation or operating status of the drug delivery device 100. To this end, the cover element 27 forming the proximal face of the knob 2 may include a transparent area through which light from the LED 25 can exit the knob 2. The transparent area may be formed, for example, between a side surface of the knob 2 and the proximal face of the knob 2.

[0105] The processor 28 may be configured to generate an output signal upon determining exposure of the drug delivery device 100 to a fluid. This output signal may be used to operate the LED 25 to communicate to a user the exposure of the drug delivery device 100 to a fluid. Alternatively or additionally, an error code may be generated, which may be stored in a memory of the system and / or transmitted to another device.

[0106] The knob 2, or electronic system in general, of Figures 2 and 3 may include two optical sensors 21. Only one of these optical sensors 21 is shown in Figure 2, with the other optical sensor 21 being hidden, for example, behind other elements. The sensor 21 is conveniently out of phase with respect to the encoder structure on the rotary encoder component, for example, the dial sleeve or number sleeve. However, systems using only one sensor are also possible. The sensor and encoder structure may be adjusted so that the combined sensor output provides, for example, a two-bit Gray code that characterizes four unique relative positions of the encoder structure and the sensor.

[0107] 4 shows the measurement results of the optical sensor 21 during normal operation of the sensor 21, i.e., when no fluid is flowing inside the knob 2 and does not alter the function of the sensor 21. The y-axis on the left represents the measurement value in arbitrary units after conversion from an analog signal to a digital signal (the ADC may also be part of the electronic system and may be implemented on the circuit board 22). The x-axis represents time in milliseconds. Curve C1 shows the measurement results of the first optical sensor 21, and curve C2 shows the measurement results of the second optical sensor 21. Curve C3 shows the operating voltage at the sensor 21 provided by the battery 24, with the y-axis on the right as a reference for the operating voltage, here in units of, for example, volts.

[0108] 4 shows the measurement results of one drug delivery process. Curves C1 and C2 each have peaks and valleys associated with the white and black regions (and / or protrusions and recesses) on the dial sleeve and / or number sleeve. For example, peaks are associated with high reflectivity (white) regions on the encoder component (dial sleeve and / or number sleeve), and valleys are associated with low reflectivity (black) regions. For high reflectivity (white) regions, the sensor 21 reading is greater than 3000. For low reflectivity (black) regions, the reading is approximately 0.

[0109] The readings or measurements at the (each) sensor may be taken or obtained at a sampling frequency or rate, for example under the control of processor 28. That is, the measurements may be taken at different times. The sensors may be operated at sampling frequencies or rates of 500 Hz, 1000 Hz, 2000 Hz, 3000 Hz, 4000 Hz (see further below) or more, preferably in cases where at least the movement of the encoder components is to be monitored, for example during dose delivery operation.

[0110] It is also visible in Figure 4 that the operating voltage drops as time decreases. This voltage drop results in a decrease in the measured value over time, which can already be observed by the difference in peak height.

[0111] 4, it can also be seen that initially the operating voltage may have irregularities, for example, on the X-axis, ranging from 0 to about 25. This irregularity may be due to actuating the sensor near the beginning of the drug delivery process or operation, for example, by triggering switch 23.

[0112] 5 shows the maximum measurement values ​​of each of the two sensors 21 for 390 drug delivery processes. The x-axis represents the maximum measurement value of the first optical sensor 21, and the y-axis represents the maximum measurement value of the second optical sensor 21. As can be seen, the maximum measurement values ​​of the first optical sensor 21 are all less than 3600, and the maximum measurement values ​​of the second optical sensor 21 are all less than 3450. These values ​​can be used as the reference values ​​(dashed lines) mentioned above.

[0113] 6 shows the measurement results of the optical sensor 21 during the drug delivery process as a function of the time the sensor 21 is exposed to a fluid such as water. As can be seen, also between the peaks, i.e., when the sensor 21 faces the black area, the measurement result is no longer 0, which is a result of exposure to the fluid. Furthermore, the measurement value of the first sensor (curve C1) is significantly higher than the measurement value of the first sensor in FIG. 4.

[0114] In Figure 6, the horizontal dashed lines indicate reference values ​​that can be used to determine whether exposure to fluid has occurred, for example, because sensor readings (measurements) above them are abnormal and indicate the inflow of liquid into the system. The measurements of the first sensor 21 are above these reference values ​​only in Figure 6, but are well below these reference values ​​in Figure 4. By comparing the measurements to the reference values, for example, by determining that the measurements during the delivery process (measurement period) or at least the maximum measurement exceeds the reference values, it can be determined that the sensor has been exposed to fluid.

[0115] During operation of the system, for example, during ongoing drug delivery operation, it may not be possible to determine whether the respective sensor output or measurement result should be within the peak or valley region or on the rising or falling edge or side of the respective curve. In this case, only the higher reference value can be used, i.e., the reference value that indicates that the sensor output or measurement result should be within the peak region (in the illustrated case, these are the values ​​shown by the first and third dashed lines from the left side of Figure 6). Therefore, other values ​​(see the values ​​shown by the second and fourth dashed lines) may not be suitable as reference values ​​in this case.

[0116] It can also be seen in Figure 6 that the reference value (horizontal dashed line) decreases with increasing time, taking into account the voltage drop that appears over time, as can be seen in curve C3.

[0117] Similar to FIG. 5, FIG. 7 shows the maximum readings of two sensors 21. However, this time, both sensors 21 have been exposed to fluid. It can be seen that some of the maximum readings exceed the reference values ​​of 3600 and 3450, respectively. Measurements with these maximum readings may indicate that a sensor 21 has been exposed to fluid. It can also be seen that in some measurements, both sensors 21 produce maximum readings that exceed their respective reference values. To be more certain that actual exposure to fluid has occurred, only such readings can be used as an indicator of exposure.

[0118] FIG. 8 shows the measurement results of one of the optical sensors, e.g., the first optical sensor 21, during the drug delivery process (see curve C1). Curve C3 shows the operating voltage applied to the first sensor 21. It can be seen that at the beginning of the drug delivery process, the voltage, for example, drops relatively quickly (see also the irregularity in FIG. 4 at the beginning of the delivery process, which may be the region shown in FIG. 8), and the measurement value of sensor 21 also decreases accordingly. After a while, the voltage stabilizes, and so does the measurement value of sensor 21. Therefore, to determine whether exposure to fluid has occurred, the first measurement value at the beginning of the measurement period (or delivery process) can be omitted. For example, an initial number of measurements (samples) or measurements taken at a predetermined initial time interval from the start of the dose delivery process or operation may be ignored and / or not compared to a reference value. For example, a number N or more of measurements may be ignored, where N is equal to one of the following: 5, 10, 15, 16, 17, 18, 19, or 20. Alternatively or additionally, N may be 30, 25, 20, 19, 18, 17, 16, or less. For example, the initial predetermined time interval may be 1 ms, 2 ms, 3 ms, 4 ms, or more. Alternatively or additionally, the initial predetermined time interval may be 10 ms, 9 ms, 8 ms, 7 ms, 6 ms, 5 ms, 4 ms, or less. Measurements during the dose delivery operation or process may be obtained at a (preferably constant) frequency or sampling rate of one of the following values: 1000 Hz, 1500 Hz, 2000 Hz, 2500 Hz, 3000 Hz, 3500 Hz, 4000 Hz, or more. For example, if the rate is 4000 Hz, the first 16 values ​​(or measurements for the first 4 ms after the start of the dose delivery process) may be ignored, and only subsequent measurements may be used for comparison with the reference. The start of the dose delivery process may be characterized by the triggering of switch 23, for example, to generate a switch signal. The switch signal may indicate that the user has pressed the knob 2 to deliver a preset dose. In response to the switch signal, the sensor 21 may be turned on or switched from a slower response rate to a faster response rate.

[0119] During the dose delivery process, the maximum sensor reading may be determined and / or stored. During or after the process, the determined and / or stored value may be compared to a reference value, for example, 3450. If the maximum reading is higher, an error code may be generated indicating fluid influx into the system and / or the error may be signaled to the user via an LED or another device.

[0120] It should be noted that the dynamic range of the measurements and / or the shape of the curve determined by the measurements can also be used as criteria for determining fluid inflow or exposure of the system.

[0121] The terms "drug" or "medicament" are used synonymously herein to refer to a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally, a pharmaceutically acceptable carrier. An active pharmaceutical ingredient ("API"), in the broadest sense, is a chemical structure that has a biological effect on humans or animals. In pharmacology, drugs or agents are used to treat, cure, prevent, or diagnose disease, or otherwise improve physical or mental well-being. Drugs or agents may be used for a limited duration or periodically for chronic conditions.

[0122] As described below, drugs or pharmaceutical agents 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, as well as 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.

[0123] The drug or agent may be contained within a primary package or "drug container" adapted for use in a drug delivery device. The drug container may be, for example, a cartridge, syringe, reservoir, or other solid or flexible container configured to provide a chamber suitable for storage (e.g., short-term or long-term storage) of one or more drugs. For example, in some cases, the chamber may be designed to store the drug for at least one day (e.g., from one day to at least 30 days). In some cases, the chamber may be designed to store the drug for about one month to about two years. Storage may occur at room temperature (e.g., about 20°C) or at refrigerated temperatures (e.g., from about -4°C to about 4°C). In some cases, the drug container may be or include a dual-chamber cartridge configured to separately store two or more components of a pharmaceutical formulation to be administered (e.g., an API and a diluent, or two different drugs), one in each chamber. In such cases, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components prior to and / or during administration to the human or animal body. For example, the two chambers may be configured to be in fluid communication with each other (e.g., via a conduit between the two chambers) and to allow mixing of the two components by a user, if desired, prior to administration. Alternatively, or in addition, the two chambers may be configured to allow mixing upon administration of the components to the human or animal body.

[0124] The drugs or agents contained 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, and thromboembolic disorders, such as deep vein thromboembolism or pulmonary thromboembolism. Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis, and / or rheumatoid arthritis. Examples of APIs and drugs are those listed in handbooks such as the Rote Liste 2014, e.g., but not limited to, Main Group 12 (antidiabetic agents) or 86 (oncology agents), and the Merck Index, 15th edition.

[0125] 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, e.g., human insulin, or a human insulin analog or derivative; glucagon-like peptide (GLP-1), a GLP-1 analog or GLP-1 receptor agonist, or an analog or derivative thereof; a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms "analog" and "derivative" refer to a polypeptide having a molecular structure that is formally derivable from the structure of a naturally occurring peptide, e.g., the structure of human insulin, by deletion and / or replacement 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 replaced amino acid residue may be either a codable amino acid residue or another naturally occurring residue, or a purely synthetic amino acid residue. 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 that of a naturally occurring peptide, such as the structure of human insulin, in which one or more organic substituents (e.g., fatty acids) are attached to one or more of the amino acids. In some cases, one or more amino acids present in the naturally occurring peptide may be deleted and / or replaced by other amino acids, including non-codable amino acids, or amino acids, including non-codable amino acids, may be added to the naturally occurring peptide.

[0126] Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin in which the proline in position B28 can be replaced by Asp, Lys, Leu, Val or Ala and in position B29 Lys can be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0127] 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-myristoylLysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin. B29-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.

[0128] Examples of GLP-1, GLP-1 analogues and GLP-1 receptor agonists are e.g. lixisenatide (Lyxumia®), exenatide (exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide produced by the salivary glands of the Gila monster), liraglutide (Victoza®), semaglutide, taspoglutide, albiglutide (Syncria®), dulaglutide (Trulicity®), rexendin-4, CJC-1134-PC, PB-1023, TTP-054, langrenatide / HM-11260C (efpegrenatide), HM-15211, CM-3, GLP-1 eligen, ORMD-0901, NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexene, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, ZP-DI-70, T T-401 (Pegapamodtide), BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Tirzepatide (LY3298176), Bamadutide (SAR425899), Exenatide-XTEN, and Glucagon-Xten.

[0129] Examples of oligonucleotides are eg mipomersen sodium (Kynamro®), a cholesterol-lowering antisense therapeutic for the treatment of familial hypercholesterolemia or RG012 for the treatment of Alport syndrome.

[0130] Examples of DPP4 inhibitors are linagliptin, vildagliptin, sitagliptin, denagliptin, saxagliptin, and berberine.

[0131] Examples of hormones include pituitary or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follitropin, lutropin, chorion gonadotropin, menotropin), somatropine (somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0132] Examples of polysaccharides include glycosaminoglycans, hyaluronic acid, heparin, low-molecular-weight heparin, ultra-low-molecular-weight heparin, or derivatives thereof, or sulfated polysaccharides, such as the polysulfated forms of the above-mentioned polysaccharides, and / or pharmaceutically acceptable salts thereof. An example of a pharmaceutically acceptable salt of polysulfated low-molecular-weight heparin is enoxaparin sodium. Examples of hyaluronic acid derivatives include Hylan GF 20 (Synvisc®), sodium hyaluronate.

[0133] 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 antigen-binding ability. An antibody can be a polyclonal antibody, a monoclonal antibody, a recombinant antibody, a chimeric antibody, a deimmunized or humanized antibody, a fully human antibody, a non-human (e.g., murine) antibody, or a single-chain antibody. In some embodiments, an antibody has effector function and is capable of fixing complement. In some embodiments, an antibody has reduced or no binding ability to Fc receptors. For example, an antibody can be an isotype or subtype, antibody fragment, or mutant that does not support binding to Fc receptors, e.g., an antibody has a mutated or deleted Fc receptor binding region. The term antibody also includes antigen-binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTIs) and / or dual variable region antibody-like binding proteins with a crossover binding region orientation (CODV).

[0134] The term "fragment" or "antibody fragment" refers to a polypeptide (e.g., an antibody heavy and / or light chain polypeptide) derived from an antibody polypeptide molecule that does not include the full-length antibody polypeptide but comprises at least a portion of the full-length antibody polypeptide that is still capable of binding to antigen. Antibody fragments can include truncated portions of a full-length antibody polypeptide, but the term is not limited to such truncated fragments. Antibody fragments useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments, such as bispecific, trispecific, tetraspecific, and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments, such as bivalent, trivalent, tetravalent, and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and VHH-containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

[0135] The term "complementarity determining region" or "CDR" refers to short polypeptide sequences within the variable regions of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term "framework region" refers to amino acid sequences within the variable regions of both heavy and light chain polypeptides that are not CDR sequences and that are primarily responsible for maintaining the proper orientation of the CDR sequences to enable antigen binding. Although the framework regions themselves are typically not directly involved in antigen binding, as is known in the art, certain residues within the framework regions of a particular antibody may be directly involved in antigen binding or may affect the ability of one or more amino acids within the CDRs to interact with the antigen.

[0136] Exemplary antibodies are anti-PCSK-9 mAbs (e.g., alirocumab), anti-IL-6 mAbs (e.g., sarilumab), and anti-IL-4 mAbs (e.g., dupilumab).

[0137] Pharmaceutically acceptable salts of any of the APIs described herein are contemplated for use as drugs or medicaments in drug delivery devices. Pharmaceutically acceptable salts include, for example, acid addition salts and base salts.

[0138] It will be understood by those skilled in the art that modifications (addition and / or deletion) of various components of the APIs, formulations, devices, methods, systems, and embodiments described herein may be made without departing from the full scope and spirit of the invention, and that the invention encompasses such modifications and all equivalents thereof.

[0139] Exemplary drug delivery devices may include needle-based injection systems as described in Table 1 of Chapter 5.2 of ISO 11608-1:2014(E). As described in ISO 11608-1:2014(E), needle-based injection systems may be broadly distinguished into multi-dose container systems and single-dose (partial or full discharge) container systems. The container may be a replaceable container or a non-replaceable one-piece container.

[0140] As further described in ISO 11608-1:2014(E), a multi-dose container system may include a needle-based injection device with replaceable containers. In such a system, each container holds multiple doses and may be fixed or variable in size (pre-set by the user). Another multi-dose container system may include a needle-based injection device with a non-replaceable, one-piece container. In such a system, each container holds multiple doses and may be fixed or variable in size (pre-set by the user).

[0141] As further described in ISO 11608-1:2014(E), a single-dose container system may include a needle-based injection device with replaceable containers. In one example of such a system, each container holds a single dose and, in doing so, expels the entire deliverable volume (full expulsion). In a further example, each container holds a single dose and, in doing so, expels a portion of the deliverable volume (partial expulsion). Also as described in ISO 11608-1:2014(E), a single-dose container system may include a needle-based injection device with a non-replaceable, one-piece container. In one example of such a system, each container holds a single dose and, in doing so, expels the entire deliverable volume (full expulsion). In a further example, each container holds a single dose and, in doing so, expels a portion of the deliverable volume (partial expulsion).

[0142] The invention described herein is not limited by the description in connection with the exemplary embodiments, but rather includes any novel feature and any combination of features, and in particular any combination of features in the claims, even if that feature or combination itself is not explicitly recited in the claims or exemplary embodiments. [Explanation of symbols]

[0143] 10 Medication container holder / housing 11a Plunger rod 11b Drive sleeve 11c dial sleeve 13 Dose window 14 Drug containers 15 needles 16 Inner needle cap 17 Outer needle cap 18 Cap 20 Grip Elements 21 Measuring unit / optical sensor 22 Circuit Board 23 Electromechanical Switch 24 Battery 25 LED 26 Snap Connection 27 Cover Elements 28 processors 70 Dial Sleeve 71a…71c Formations 100 Drug delivery device D. Distal direction P proximal direction L Longitudinal axis R Radial direction C. Azimuth direction / Rotation direction / Angle direction

Claims

1. An electronic system for a drug delivery device (100), comprising: comparing the measurement results obtained by the measurement unit (21) with a standard, said measurement results being suitable for providing information about said drug delivery device (100); determining exposure of the drug delivery device to a fluid based on the results of the comparison; An electronic system for a drug delivery device (100) configured to:

2. The electronic system of claim 1 , configured to determine exposure of electrical elements of the drug delivery device to fluid based on the result of the comparison.

3. the electronic system is configured to adjust the reference to changes in the operating voltage of the measuring unit (21); and / or the electronic system is configured to adjust the reference based on previous measurements of the measuring unit (21) obtained during a preceding period; and / or Comparing the measurement result to the standard comparing the amplitude of the measurement result with the reference amplitude; comparing the dynamic range of the measurement result with the dynamic range of the reference; Comparing the curve shape of the measurement result with the reference curve shape. at least one of:

3. An electronic system according to claim 1 or 2.

4. The drug delivery device (100) is configured to perform several drug delivery processes sequentially, the electronic system is configured to adjust the criterion based on measurement results of the measurement unit (21) associated with the last n drug delivery processes, where n≧1; and / or the measurements are measurements obtained during use of the drug delivery device (100); and / or The measurements are taken during periods when the drug delivery device (100) is not in use. The result is The electronic device according to any one of claims 1 to 3.

5. said measuring unit (21) being a sensor for measuring the amount of the delivered dose during the drug delivery process; and / or The measuring unit (21) is an optical sensor. The electronic system according to any one of claims 1 to 4.

6. the electronic system is configured to compare the measurement results obtained by the measurement unit (21) with the reference during a measurement period in which the measurement unit (21) obtains a measurement result, the electronic system being configured so that one or more measurement results at an early stage of the measurement period are not compared with the reference; and / or The electronic system is configured to generate an output signal to communicate to a user when exposure of the drug delivery device to a fluid is confirmed. The electronic system according to any one of claims 1 to 5.

7. a processor (27) for receiving the measurement results, comparing the measurement results with the standard, and determining exposure of the drug delivery device (100) to a fluid based on the result of the comparison; the measuring unit (21) for obtaining the measurement results; a communication unit (25) for communicating to a user if exposure of said drug delivery device (100) to a fluid is confirmed; The electronic system according to any one of claims 1 to 6, comprising:

8. The electronic system of any one of claims 1 to 7, wherein the electronic system is configured to determine exposure of the drug delivery device (100) to a fluid based on the measurement results of the measuring unit (21) and the measurement results of a further measuring unit (21).

9. A user interface member (2) for a drug delivery device (100), comprising: An electronic system according to any one of claims 1 to 8, the user interface member (2) is configured to be touched by a user to operate the user interface member for performing a dose dialing and / or drug delivery process; User interface member (2).

10. A drug delivery device (100), comprising: An electronic system according to any one of claims 1 to 8 or a user interface member (2) according to claim 9; a container holder (10) for holding a medication container; and optionally a drug container (14) filled with a drug; A drug delivery device (100) comprising:

11. 1. A method for detecting exposure of a drug delivery device (100) to a fluid, comprising: A measuring unit (21) is disposed in the drug delivery device (100), and the method comprises: receiving the measurement results obtained by the measurement unit (21); comparing the measurement results to a standard; determining exposure of the drug delivery device to a fluid based on the results of the comparison; and Including, method.

12. The measurement results obtained by the measurement unit (21) are suitable for providing information about the drug delivery device (100), and / or the method comprises: determining exposure of an electrical element of the drug delivery device to a fluid based on the result of the comparison. The method of claim 11.

13. The method according to claim 11 or 12, wherein the method is implemented by an electronic system according to any one of claims 1 to 8.

14. An electronic system for a drug delivery device (100), said electronic system comprising: comparing the measurement results obtained by the measurement unit (21), which are suitable for providing information about the drug delivery device (100), with a standard; determining exposure of an electrical element of the drug delivery device to a fluid based on the results of the comparison; The electronic system is configured to:

15. The electronic system of any one of claims 1 to 8 or 14, wherein the measurement unit (21) is an optical sensor (21) configured to emit radiation and detect a portion of the radiation reflected by a movable member of the drug delivery device (100).

Images